Kerala Gynaecology

Vaginal Discharge

Posted On April 25, 2018 by Dr.Shobhana Mohandas

Physiological causes of leucorrhoea: The term leucorrhoea is used to denote a simple increase in normal vaginal secretions, but currently it is used to describe every white discharge of a non-purulent nature. The physiological causes of leucorrhoea are

• Ovulation: when the high peak of estrogen provokes the endocervical glands into excessive secretions.
• As a result of sexual stimulation.
• Premenstrual congestion.
• During pregnancy.

Leucorrhoea in the premenarchal age group: Any foreign body should be looked for and removed. In infective leucorrhoea, a course of anti-infective agents could be given. A proper cleaning of the vulval region followed by application of estrogen cream helps to increase the thickness of the vaginal epithelium and reduces the vulnerability of the vulval region to infection. Low dose estrogen tablets of Estriol (Evalon)1mg for 10 days or estradiol (Lynoral) 0.01mg daily for 3-4 days is also helpful.

Causes of leucorrhoea in the reproductive age group:

Broadly, the causes of vaginal discharge could be classified into

• Infectious causes: These include bacterial vaginosis, vulvovaginal candidiasis, trichomonas vaginitis, mucopurulent cervicitis, gonorrhea, condyloma accuminata, herpes type2 virus and cytolytic vaginosis.
• Normal discharge secondary to hormonal changes: These could occur due to physiologic leukorrhea (midcycle cervical mucus/postintercourse) or atrophic vaginitis.
• Other causes: There may be chemical/allergic vaginitis, foreign body, desquamative inflammatory vaginitis, chronic cervicitis, cervical ectropion, cervical polyps, cervical and endometrial cancer and collagen disorders.

Vaginal discharge in a postmenopausal woman: :

A: In women who are not on estrogen replacement therapy, there is relative lack of estrogen effect in postmenopausal women. Hence in postmenopausal women, most cases of vulvo- vaginitis are due to atrophic vaginitis. This is changing with an increasing trend to use estrogens in postmenopausal women for the prevention of osteoporosis and general sexual well being. In senile vaginitis, or atrophic vaginitis, a purulent and often slightly bloodstained discharge is evident. The vagina is inflamed and oedematous. Vulva is inflamed, tender and excoriated. The raw inflamed areas may become adherent and produce an obliteration of the canal, causing the infection to spread upwards into the cervix and endometrium, leading to pyometra. Senile vaginitis can mask a hidden cancer of the endocervix or endometrium. Hence it must be investigated by doing a diagnostic curettage.Mainstay of treatment in senile vaginitis is to improve the resistance of the vaginal epithelium by giving estrogen. Estrogen also raises the glycogen content of the vagina and lowers the vaginal pH, making it more acidic and inhibits the growth of organisms. Estrogen creams applied locally twice is effective in these cases.

Bacterial vaginosis:

Bacterial vaginosis is the most common cause of vaginal discharge. In this condition, there is bacterial overgrowth, primarily anaerobes, without signs of inflammation. Presentaion: The patient may present with a fishy-smelling increased vaginal discharge not accompanied by leukorrhea, vulvar burning, or pruritis. Aetiology:Its presence represents a change in the vaginal ecosystem, specifically a decrease in lactobacilli, which is part of the normalflora; a proliferation of pathogenic inhabitants of the vagina; and an elevation of pH (>4.5). Sexual transmission:Whether BV is sexually transmitted remains unsettled. The majority of observations, suggests that BV is probably not sexually transmitted. Diagnosis: The diagnosis of BV requires the presence of at least 3 of the following 4 criteria: 1.A homogenous noninflammatory discharge (not many WBCs).

Treatment: The various modalities are:

• .Metronidazole 2g PO as single dose or 500mg PO twice daily for 7 days.
• Cindamycin 300mg PO b.i.d for 7 days.
• 2% clindamycin cream b.i.d for 7 days.
• Metronidazole gel given as suppository b.i. d for 7 days.
• Ampicillin had been suggested in the past for bacterial vaginosis, but is not effective.
• In pregnancy, the recommended regimen is metrondazole in the dose of 250mg three times daily for 7 days.It is contraindicated in first trimester. Alternative regimens in pregnancy are with 2g single dose orally, or local cream.

Trichomonial vaginitis:

A: Trichomonal vaginitis is caused by the protozoan Trichomonas vaginalis, a motile organism with four flagella,It accounts for 10 to 25 percent of vaginal infections.It is sexually transmitted and may be identified in 30 to 80 percent of the male sexual partners of infected women. Trichomoniasis is associated with and may act as a vector for other venereal diseases. Studies indicate that this infection increases the transmission rate of the human immunodeficiency (AIDs) virus.

Presentation: There is copious, malodorous, yellow-green (or discolored) discharge,pruritus and vaginal irritation. There may be no symptoms in 20 to 50 percent of affected women. On examination there may be vulvar and vaginal edema and erythema. The cervix may have a strawberry appearance in 25% of women. The vaginal pH is elevated (>4.5) Microscopic examination will show many trichomonads and many polymorphonuclear cells.

Treatment:

• Metronidazole 2g orally in a single dose. Metronidazole could be given in the the dose of 500mg twice daily for 7 daily as an alternative.
• Clotrimazole, another nitro-imidazole compound similar to metronidazole, has been reported to attain nearly a 50% cure rate when given as an intravaginal cream.
• Sexual partners should be treated simultaneously even if they are asymptomatic.
• Sexual partners should be treated simultaneously even if they are asymptomatic.

Vaginal candidiasis: Vulvovaginal candidiasis is a common cause of vaginitis in women. In 80-90% of cases, the causative organism is Candida albicans.

Predisposing factors: Risk of this infection is increased in women who use oral contraceptive pills, a diaphragm and spermicide, or an IUD. Other risk factors include young age at first intercourse, intercourse more than four times per month and receptive oral sex. The risk of vulvovaginal candidiasis is also increased in some women who have diabetes, are pregnant or are taking antibiotics.

Presentation: Women with vulvovaginal candidiasis frequently complain of pruritus, vaginal irritation and dysuria. In vulvovaginal candidiasis, the discharge is usually white and thick, with no odor and a normal pH. Women with candidiasis can have vulvar and vaginal erythema and, occasionally, scaling and fissures of vulvar tissue.

Diagnosis: Microscopy of the discharge with 10% KOH will often reveal hyphae or budding yeast in 50%-70% of cases C albicans organisms are easiest to identify, as they have long hyphae with blastospores along their length and a terminal cluster of chlamydia spores.

Treatment:Vulvovaginal candidiasis could be treated with intravaginal creams or pessaries or oral drugs. Recommended intravaginal agents are:

• Butoconazole 2% cream, 5 g intravaginally for 3 days.
• Clotrimazole 1% cream, 5 g intravaginally for 7 to 14 days.
• Clotrimazole 100 mg vaginal tablet daily for 7-10 days.
• Clotrimazole 100 mg vaginal tablet, two tablets daily for 3 days.
• Clotrimazole 500 mg vaginal tablet, one tablet in a single application.
• Miconazole 2% cream, 5 g intravaginally for 7 days
• Miconazole 200-mg vaginal suppository, one daily for 3 days.
• Miconazole 100-mg vaginal suppository, one daily for 7 days.
• Nystatin 100,000-unit vaginal tablet, one daily for 14 days
• Tioconazole 6.5% ointment, 5 g intravaginally in a single application.
• Terconazole (Terazole) 0.4% cream, 5 g intravaginally for 7 days
• Terconazole 0.8% cream, 5 g intravaginally for 3 days
• Terconazole 80-mg vaginal suppository, one daily for 3 days.

Recurrent candidal vaginitis:

Recurrent infections may be treated with a weekly administration of fluconazole 150mg for up to 12 consecutive weeks. An alternative topical maintenance regimen consists of clotrimazole vaginal suppositories 500 mg weekly. When infection is related to menstruation, 100-mg clotrimazole vaginal suppositories nightly for several days preceding menstruation may be effective. But it must be remembered that 15% of women harbour yeast organisms in their GI tract and for these women, local treatments may not be effective and oral preparations may be the only solution. It is important to avoid douching and wearing tight underclothings to prevent recurrences. Tight undergarments tend to retain moisture in the vaginal secretions.Immunosuppressive factors like diabetes should be looked for and treated.

Cytolytic vaginitis: A: Cytolytic Vaginosis is a condition thought to be caused by an overgrowth of lactobacilli and possibly other bacteria, which causes cytolysis of vaginal epithelium and a frothy white discharge. Symptoms, which usually increase during the second half of the menstrual cycle, include dyspareunia, vulvar pruritus, and dysuria. Physical examination is remarkable for the presence of white frothy discharge and a pH level between 3.5 and 4.5.

Patients with cytolytic vaginosis are frequently misdiagnosed as having chronic yeast infections and treated unsuccessfully with various antifungal medications, especially when the health care provider relies on the patient’s symptoms and not on a thorough examination of the wet mount. This is treated with sodium bicarbonate douches two to three times a week and then once or twice a week as needed to increase the pH of the vagina and decrease the amount of lactobacilli. The recommended douching solution should include 30 to 60 g of sodium bicarbonate to 1 L of warm water.

Cervical ectropion: Cervical ectropion is the new terminology for what was previously known as erosion of the cervix. It indicates migration of endocervical epithelium over the surface of the cervix. This lesion is usually symmetric about the os and is not particularly friable. It is accompanied by a mucoid cervical discharge. Ectropion is more common in women taking oral contraceptives, and the increased amount of exposed columnar epithelium may contribute to the greater risk of chlamydial infection among women taking oral contraceptives. It is often impossible on clinical grounds alone to differentiate ectropion from true infection. Levofloxacin once-a-day therapy can be useful for uterine cervicitis.

Q: What are the causes, presentation and treatment of mucopurulent cervicitis?

A: Normal cervical discharge is clear and mucoid. Purulent or mucopurulent discharge is associated with gonococcal or chlamydial infection. Chlamydial infection of the cervix is usually associated with hypertrophic cervicitis. On examination the cervix may appear normal or exhibit edema, erythema, and hypertrophy with a mucopurulent discharge from the os . Mucopurulent cervicitis caused by Chlamydia trachomatis is characterized by a thick yellow-white discharge coming from the cervical os in conjunction with 10 or more leukocytes per microscopic field (high-power oil immersion) on Gram’s stain examination. Because the diagnostic tests and treatments for cervicitis are different from those for vaginitis, it is important to differentiate these conditions. Several clues can help to rule out cervical infection as the cause of a vaginal discharge. Almost 90 percent of symptomatic or asymptomatic women with chlamydial cervicitis meet at least two of the following criteria: (1) younger than 24 years, (2) sexual intercourse with a new partner in the previous two months, (3) presence of mucopurulent cervicitis, (4) cervical bleeding induced by swabbing the endocervical mucosa and (5) no form of contraception.

Treatment:

• Doxycycline (100 mg twice a day for 7 days)
• Erythromycin (500 mg four times a day for 7 days), with treatment of the partner and follow-up culture 1 week after completed treatment.
• Azithromycin 1gm as a single dose is as effective as Doxycycline 100mg /day for seven days, but is more expensive.
• Azithromycin 1gm as a single dose is as effective as Doxycycline 100mg /day for seven days, but is more expensive.

Gonococcal cervicitis: In typical cases of gonococcal cervicitis the cervical os is reddened and produces a purulent discharge. Laboratory detection: Polymorphonuclear cells are normally present in the endocervix, but abnormally increased numbers are suggestive of gonococcal cervicitis. This can be detected crudely on a Gram stain of the endocervical material. After the endocervixhas been cleaned off, a swab is inserted into the cervix and gently rotated, and therecovered material is applied to a microscope slide by rolling the swab over an areaabout 1 × 2 cm. The specimen is then Gram stained. Observation of 10 to 30 PMNs per oil-immersion field in the densest portion of the slide correlates statistically with the presence of gonococci or chlamydiae.

Treatment: One of four initial regimens-are recommended as initial therapy:

• Ceftriaxone, 125 mg IM.(this drug probably aborts incubating syphilis also)
• Cefixime, 400 mg orally.
• Ciprofloxacin, 500 mg orally.
• Ofloxacin, 400 mg orally.

The major drawback of Ceftriaxone is the necessity for intramuscular administration. Ciprofloxacin and Ofloxacin should be avoided in pregnant women, and because they lack activity against Treponema pallidum, these drugs will not abort incubating syphilis. The efficacy of cefixime against incubating syphilis is uncertain. Although cross-reactions between penicillin and the cephalosporins appear to be uncommon in persons treated for gonorrhea and although many clinics routinely use ceftriaxone, cefixime, or other cephalosporins to treat gonorrhea in patients with histories of penicillin allergy, the safest approach in such circumstances would be to use an oral fluoroquinolone. Regardless of the single-dose regimen chosen, the initial treatment should be followed by a regimen active against C. trachomatis. In addition to treating chlamydial infection, along with an attendant reduction in the risk of postgonococcal urethritis and salpingitis, giving a second drug may reduce the potential for selection of gonococci with increased antimicrobial resistance. The recommended regimens are doxycycline, 100 mg orally twice daily for 7 days, or a single oral dose of azithromycin 1.0-g. The latter is highly effective against genital chlamydial infection. A single dose of 2.0 g azithromycin is effective against both gonorrhea and chlamydial infection, but cost and gastrointestinal intolerance limit its utility. Erythromycin, in a divided-dose regimen totaling 2.0 g/day orally, is acceptable as follow-up therapy if neither azithromycin nor a tetracycline can be given.

Infectious vaginal discharge: Treatment: A: In most centers in India, gynaecology health providers do not take endocervical swabs for gram staining or do tests to detect chlamydia. Treatment is essentially empirical. In this scenario it is useful to remember that all fluoroquinolones are active against N. gonorrhoeae, and ofloxacin (but not ciprofloxacin) is active against C. trachomatis. Neither ciprofloxacin nor ofloxacin is highly active against anaerobic bacteria. A regimen consisting of 14 days of treatment with oral ofloxacin plus metronidazole provides comprehensive coverage for all likely pathogens. Several studies have demonstrated good short-term outcomes in women with mild to moderate PID treated with ofloxacin alone, and some investigators believe that most outpatients with acute PID can be safely treated without providing coverage for anaerobic bacteria(i.e, there is no need to add metronidazole to the regiment). However, most authorities agree that it is prudent to routinely add metronidazole (or clindamycin) to improve coverage for anaerobic pathogens.

Herpetic cervicitis: Herpetic cervicitis may be present without external lesions. Cervicitis is seen on physical examination in about 90% of women whose cervical cultures are positive for herpes simplex virus. The cervix usually displays diffuse friability and, less frequently,frank ulcers or necrosis. Cervical discharge is usually mucoid, but it is occasionally mucopurulent, and in one series herpetic cervical infection caused 8% of cases of mucopurulent cervicitis. Affected patients may have lower abdominal pain, but inguinal adenopathy is rare unless the disease is accompanied by lesions of the external genitalia because lymphatic drainage of the cervix involves the external iliac rather than the inguinofemoral nodes. First-episode primary genital herpes is characterized by fever, headache, malaise, and myalgias. Pain, itching, dysuria, vaginal and urethral discharge, and tender inguinal lymphadenopathy are the predominant local symptoms. Widely spaced bilateral lesions of the external genitalia are characteristic Lesions may be present in varying stages, including vesicles, pustules, or painful erythematous ulcers. The cervix and urethra are involved in more than 80% of women with first-episode infection.

Treatment of genital herpes: A: Acyclovir, Famcyclovir and Valacyclovir are useful in the treatment of genital herpes The dosage schedule for Acyclovir is given below:
First episode: Acyclovir: PO 200 mg 5 times daily for 7 days or 400mg tid for 10 days.
Recurrence: Acyclovir: PO 200 mg 5 times daily or 400 mg tid for 5 d.
Suppression: Acyclovir: PO 400-mg bid or 200 mg tid for up to 5 y.

Cervicitis: Aetiology: Human papillomavirus, particularly certain subtypes, frequently infects the cervix. It has been observed since 1837 that cancer of the cervix behaves epidemiologically as if it were a sexually transmitted disease. The strongest infectious association with cancer of the cervix has been established for some types of human papillomavirus. Other organisms occasionally considered causes of cervicitis include adenovirus, measles virus, cytomegalovirus, Enterobius vermicularis, amoebae,M. tuberculosis, group B streptococci, N. meningitidis, and actinomycetes, the last usually in association with the use of intrauterine contraceptive devices. The chancre of syphilis sometimes manifests as a cervical lesion.

Herpes in pregnancy: In general, the clinical manifestations of recurrent genital herpes, including the frequency of subclinical versus clinical infection and the duration of lesions, pain, and constitutional symptoms are similar in pregnant and nonpregnant women. Recurrences appear to increase in frequency over the course of pregnancy. Among women who are HSV-2 seropositive entering pregnancy, several clinical series and a recent study indicates that there is no effect of recurrent clinical infection on neonatal outcome, including birth weight and gestational age. First-episode infections in pregnancy have more severe consequences to mother and infant. Visceral dissemination during the third trimester occasionally occurs and prematurity or intrauterine growth retardation, or both, may be seen. The acquisition of primary disease in pregnancy carries the risk of potential transplacental transmission of virus to the neonate.Primary

Chronic cervicitis: Treatment: Chronic cervicitis is one of the common disorders encountered in daily practice. To overcome this problem,the first step should be antibiotic therapy in the acute phase. If this fails, the infection becomes chronic and may spread to internal genital organs leading to pelvic inflammatory disease and eventually to infertility. Chronic form of infection may lead to the development of dysplasia and neoplasm. Hence if the patient does not improve after 2-3 months, minor surgical therapy is indicated. Various methods such as electrocautery, loop diathermy, cryotherapy or laser are used to destroy the inflamed area if the chronic cervicitis is accompanied by ectropion.

• The procedure should be done in the first half of the cycle, as there is the danger of ascending infection and postoperative infection in the premenstrual period. But puncture biopsy of nabothian cysts may be done at any time during the cycle.
• A vaginal cytology, and if possible a colposcopy should be done to know if there is cervical intraepithelial neoplasia. Carcinoma of the cervix or endometrium is a contraindication.
• Pregnacy should be ruled out.
• Any acute inflammation of the cervix should be treated, as doing the procedure on the cervix in the acutely inflammed state would produce spread of infection into the parametrial tissues.

Electocoagulation: Electocauterisation is done with either a thermal or a spark-type electrocautery n a radial strip fashion. Because there are very few nerve endings carrying pain sensation from the cervix, this can be done in the office without anesthesia. After the procedure, the patient should be administered local creams or vaginal suppositories to aid healing.

Cryosurgery: Cryosurgery destroys tissue by freezing. The refrigerants (carbondioxide, Freon,nitrous oxide, or nitrogen- all in liquid state) are passed through a hollow probe placed in the cervical canal and against the external os. The advantages are the ease of administration and lack of discomfort as compared with thermal or electrocauterization. This tratment method has the disadvantage of causing a profuse vaginal discharge for 2-3 weeks following its application.

Laser: In laser (light amplification by stimulated emission of radiation) therapy, a high-energy beam of light in the infrared spectrum is directed to the cervix, resulting in complete vaporization of cells. As a result, there is no necrotic tissue slough and no resulting leukorrhea. Disadvantages are the relatively large size and high cost of the equipment as well as the special training required.

Aim: The aim of these methods is destruction of infected tissues with subsequent healing by fibroblastic proliferation and reepithelialization. Complete healing may take up to 6 weeks. The cervix should be inspected again at the end of this time to be certain that healing is satisfactory. If cauterization must be repeated, it should be done 1-2 months after the initial tratment to encourage healing.

Complications: Reactivation of salpingitis may occur if treatment is done in the presence of acute cervicitis. Cervical stricture may follow deep cauterization carried high into the endocervical canal. Cauterization or freezing of a cervix that contains an unrecognized malignant tumour will mask the neoplastic process, resulting in further delay in its recognition and perhaps serious consequences.

Cervical intraepithelial neoplasia: Cervical intraepithelial neoplasia is a premalignant lesion of the cervix.There is abnormality of cervical epithelium displaying proliferation of parabasal cells with disordered polarity, loss of cellular junctions, coarse nuclear chromatin clumping, abnormal nuclear cytoplasmic ratio, and high mitotic index. Reported as grades I (low grade) to Ill (high grade, including carcinoma in situ) dysplasia It remains asymptomatic and can be diagnosed only on routine screening. McIndoe (1984) concluded that women with cytological evidence of continuing neoplasia afer initial diagnosis of carcinoma in situ of the cervix had an 18% chance of developing invasive cancer of the cervix or vaginal vault at 10 years and a 36% chance at 20 years. Routinely screening women with vaginal cytology and coloposcopy can pick up these women and prevent them from progressing to carcinoma cervix.

Pap smear:

A: Pap smear is vaginal cytology, where exfoliated cells from the vagina are examined for various purposes. It was introduced by Papanicolou and can be used to screen women for premalignant lesions of the cervix. It is important to remember that it is only a screening procedure and not a diagnostic procedure. Suspicious cases found on Pap smear need further evaluation with colposcopy, simple biopsy or cone biopsy. The physician cannot rely on the Pap smear alone to be diagnostic for that particular lesion. Pre-procedure precautions: The Pap smear is best performed during midcycle. The patient should avoid douching, vaginal medications, and intercourse for 24 hours prior to the procedure. Reschedule the examination if the patient is actively menstruating.

Procedure :

• Clarify the patient’s risk factors for cervical dysplasia by history.
• Label the end of a glass slide with the patient’s name and other identifying data as necessary.
• Insert speculum and adjust it to obtain adequate visualization of the cervix.
• Determine whether the vagina or cervix appears inflamed or infected. Avoid rubbing or otherwise traumatizing the cervix.
• Identify cervical landmarks, including the transformation zone with its squamocolumnar junction. Note the nature of the cervical mucus. Excess mucus or discharge may be gently blotted, not rubbed, from view. Note any gross cervical lesions such as erosions, leukoplakia, nabothian cysts, or condylomata
• Obtain the Pap smear by using an endocervical sampling device(Cytobrush,Papette,or Cervexbrush). If the two-sample method of obtaining cells is used,first insert the Cytobrush into the canal and rotate 90 to 180 degrees. Follow this by a gentle smear of the entire transformation zone with a spatula device, fitting the contour of the patient’s remaining transformation zone.Sampling the vaginal pool has little advantage during Pap smear screening unless the patient has had a hysterectomy. In this instance, be sure to sample the vaginal cuff. If vaginal abnormalities are seen, another Pap smear of these areas (using a spatula) may be submitted on a separate slide. Areas that appear abnormal on visualization will
• The preparation is evenly applied to its appropriate slide immediately after sampling and then the slide is sprayed or dipped in preservative within 5 seconds and sent to the histopathologylaboratory.
• Make sure the Pap smear requisition form includes all pertinent data regarding the patient. Be sure to include clinical findings, patient risk factors, or yourconcerns as part of this “referral”.

Interpretation and further management: All Pap smears reported as abnormal require some form of intervention. A report of dysplasia warrants colposcopy. Many clinicians recommend colposcopy for reports of atypia also, especially in patients with numerous risk factors.

• Class I: normal smear; no abnormal cells (CIN Class- normal)
• Class II: atypical cells; no neoplasia (CIN class-reparative or atypical)
• Class III: smear contains abnormal cells consistent with dysplasia
• (CIN class- CIN I or II mild,moderate dysplasia)
• Class IV: smear contains abnormal cells consistent with carcinoma in situ (CIN class- CIN III, CIS)
• Class V: smear contains abnormal cells consistent with carcinoma of squamous origin

CIN class- carcinoma

• * CIN = cervical intraepithelial neoplasia.
• CIS = carcinoma in situ.

The American College of Obstetricians and Gynecologists (ACOG) recommends that all women who have been sexually active or are at least 18 years old undergo an annual Papanicolaou test (vaginal cytology) and pelvic examination. The ACOG and the US PreventativeService Task Force agree that if three annual Papanicolaou screens are normal,screening may be performed less frequently than yearly at the discretion of the physician based on the woman’s risk factors. Some clinicians will screen a subset of women with low risk factors every 3 years providing that there are three negative yearly Pap smears and the risk factors do not change.

• Any visible or palpable lesion of the cervix. Follow precaution that Pap smear is not diagnostic and further assessment may be necessary.
• Any abnormal vaginal bleeding or discharge.
• Posthysterectomy (hysterectomy for benign disease): Every 3 years if patient’s risk for cancer remains low.
• Posthysterectomy (hysterectomy for dysplasia, carcinoma): annually after three to four normal Pap smears at 4- to 6-month intervals.
• Posttreatment for cervical dysplasia, malignancy: Every 4 months for three visits; every 6 months for two visits; annually thereafter.
• Victims of rape, incest, abuse: As part of initial work-up. Repeat in 6 to 12 months.
• Currently it is not considered necessary to continue screening beyond the age of 64 years, provided that: the woman has had three consecutive negative smears,the most recent one was done no more than three years previously.

contraindications include clinical circumstances where sample collection is difficult to obtain or difficult to interpret (e.g., active vaginitis or cervicitis, pelvic inflammatory disease [PID], or menses). The clinician must weigh the benefits versus the risk of obtaining the screening Pap smear under these circumstances. For instance, if a woman presents with abnormal vaginal bleeding, a Pap smear is advised, despite the presence of blood. This contrasts with a patient who comes in for a routine Pap smear screening and has begun to menstruate. In the later instance, the Pap smear can be deferred to a

Atypical/ premalignant lesions of the cervix: Management:

The following treatment modalities are useful in patients with CI N.

• Chemical :Topical concentrated trichloroacetic acid (TCA 50% to 85%) or bichloracetic acids are desiccant acids that have been used to treat CIN.
• Cold Coagulation: Cold coagulation is also a highly effective ablative treatment for CIS. The name iscounterintuitive: that is, this method involves heat destruction of tissue, although the amount of heat is less than that used with other coagulation methods. A 100°C Teflon probe is applied directly to the cervical tissue.
• Cryotherapy: Cryotherapy is a relatively safe, easy, and inexpensive ablative treatment for CIN. As is true in any method of treatment for cervical dysplasia, the goal is destruction of the lesion, including the abnormal transformation zone.
• Electrocoagulation: Cervical lesions have been treated with monopolar electrocoagulation for years with good success reported. With this method, there is a continuous flow of electrons from the generator to the handpiece tip back to the generator via the grounding pad and the patient. The electron flow is highly “channeled” through the small surface area of the handpiece tip and spread over a large-area grounding pad as the electrons make the circuit. The result is a concentrated thermal effect at the handpiece tip and no thermal effect at the grounding pad. At 45°C, irreversible tissue damage occurs that is notusually visible to the naked eye. At 100°C, desiccation occurs. At greater than 100°C, vaporization and carbonization occur. The most efficient way to obtain deep thermal damage at the tissue level is a low continuous current (e.g., cutting current) with a large-surface-area handpiece tip (e.g., a ball electrode). The ball should be used in contact mode (placed directly on the tissue) and held in place long enough to obtain deep penetration into the cervical glands. Firm pressure on the tip against the surface is essential to achieve the broad surface contact.
• Laser Vaporization :Carbon dioxide laser vaporization continues to be used widely, with excellent success rates for treating CIN.
• Total Hysterectomy :Historically, hysterectomy was a mainstay of excisional therapy for CIS. With theadvent of more sensitive outpatient diagnostic modalities and less invasive treatmentmodalities, hysterectomy is now rarely indicated for CIN. Hysterectomy might beconsidered for (1) patients who have high-grade lesions who have failed conservativetreatments, (2) patients who have high-grade lesions who desire sterilization, (3) patientswho have high-grade lesions who cannot be treated adequately with local therapies, and(4) patients who have high-grade lesions who have no access for follow-up diagnosticprocedures after a conservative therapy. Disadvantages of hysterectomy are the

(LLETZ) are relatively simple outpatient treatments for CIN. Indications for LLETZ are as follows: Unsatisfactory colposcopic examination

Treatment of biopsy-proven CIN 2, CIN 3, and CIS

Suspicion of squamous microinvasive disease or adenocarcinoma in situ

Persistent CIN 1 for 1 year or noncompliant patient.

Two-grade discrepancy between the cytologic, colposcopic, or histologic diagnos

Symptomatic cervical ectropion

Menopause

Posted On April 25, 2018 by Dr.Shobhana Mohandas

Menopause is a term used to describe the permanent cessation of the primary functions of the human ovary. The ovary functions by releasing ova and hormones, both of which are stopped with menopause. Hormones produced by the ovary are oestrogen and progesterone. Both these hormones normally cause menstruation by their effect on the uterine lining, called the endometrium. Thus, when ovary sort of shuts down, with menopause, the effect of both these hormones cease.

Natural menopause occurs anywhere between ages of 45 and 55. Better nutrition may delay the onset of menopause. Menopause can be artificially induced if both ovaries are surgically removed. Rarely, menopause may occur at a young age, prematurely. It is surgically induced if both ovaries are removed for some reason.

Natural menopause is associated with lack of functioning of ovaries, which are two hormone producing organs situated near the womb or the uterus. Normally, these ovaries produce 3 hormones,viz: oestrogen, progesterone and androgens. When they stop functioning, a woman faces many physical and mental changes

Irregular heavy bleeding: Before the actual cessation of periods, the periods may get delayed by 7 days or longer. Gradually a cycle may sometimes be missed and these periods of absence will finally lead to stoppage of menstruation. In some women, these changes may be accompanied by heavy bleeding. This requires medical help if it is very heavy, otherwise, she may become anaemic. Heavy bleeding also requires medical evaluation to rule out pathological causes of bleeding.

Hot flashes: The sudden sensation of extreme heat in the upper body, particularly the face, neck, and chest is referred to as a “hot flash.” Perspiration, flushing, chills, clamminess, anxiety, and occasionally palpitations can occur. They last anywhere between 1-5 minutes.

Osteoporosis: Osteoporosis literally means porous bones. Many years after menopause, the process of bone formation is not as fast as the process bone loss and this leads to less strong bones. In women, this is partly attributed to lack of the hormone oestrogen.

Loss of cardioprotection : It is known that women who have not undergone menopause have less chance of getting a heart attack as compared to men of the same age. However, once her ovaries stop functioning, the odds that a woman may get a heart attack are the same as for men of comparable age. The protection provided by oestrogen is no longer there.

Hypothyroidism as a consequence of menopause. There is reduced production of a hormone called thyroxine, normally produced by the thyroid gland , situated in the neck. The woman as a consequence, may tire easily, may get water logging in her body, and in extreme cases may not be able to tolerate cold.

Depression : Women in their menopausal period may suddenly develop depressive symptoms, like easy crying, easy irritability, or sleeplessness. These symptoms are caused in some women due to fluctuating oestrogen levels, which has secondary effects in the brain. Usually at this time, the woman also faces an “Empty nest syndrome”. This means, till about 40 years, her house was filled with echoes of her children asking her for something or screaming for something not done. But suddenly they leave her and fly away to be on their own. She suddenly feels unwanted and this negative feeling adds to her symptoms of depression. If it is severe, along with medicines to replace deficient hormones, she may need antidepressant medications.

Vaginal symptoms: Due to lack of the hormone oestrogen in late menopausal years, there is dryness in the vagina. There also can be itching and burning sensation. There may be small breaks in the vaginal skin in extreme cases. This can be treated with local oestrogen creams or tablets.

Hot flashes: Hot flushes are sudden or mild waves of heat on the upper part of the body that last from 30 seconds to a few minutes, caused by a decreased estrogen production during menopause. Hot flushes are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may last from two to ten minutes for each occurrence. The sensation of heat usually begins in the face or face and chest, although it may appear elsewhere such as the back of the neck, and it can spread throughout the whole body. In addition to being an internal sensation, the surface of the skin, especially on the face, becomes hot to the touch. The sensation of heat is often accompanied by visible reddening of the face.

• Estrogen only for women without uterus
• Estrogen with progesterone for women with uterus to prevent endometrial hyperplasia
• Tibolone for women with contraindication to estrogen or progesterone
• SERMS
• Phytoestrogens
• Clonidine, and other miscellaneous treatment options.

Oral oestrogen preparations:

Conjugated equine estrogen;strength: tablets of 0.625mg and 1.25mg.

Estradiol valerate strength: tablets of 1mg and 2mg.

Estriol strength: 2mg tablet.

Conjugated equine estrogen has been the most studied estrogen preparation. It is the gold standard against which all other preparations are studied. Micronised estradiol valerate is a single estrogen preparation, as opposed to conjugated equine estrogen, which is a conjugate of different types of estrogen. Estriol has been found to have less effect in causing breast cancer and has less uterine stimulatory effect,as it is a weaker estrogen.But estriol affords less cardioprotection compared to other estrogen preparations .It is required in very high doses(12mg) to effect prevention of osteoporosis by increasing bone mineral density and at such doses the side effects may be intolerable.

For treatment of hot flushes usually double dose of estrogen (1.25mg of conjugated estrogen or 2mg of estradiol) may be needed. Treatment should be given on all days of the month as giving it for only 25 days has no added advantage and some women may develop symptoms during this week off. For the treatment of hot flushes treatment may be given for a year and stopped for a week to see if symptoms recur. If they do not recur treatment may be stopped. If they do recur, treatment may be continued for another year after which the patient may be re-evaluated.

Estrogen in HRT can cause Nausea,dyspepsia,leg cramps,breast tenderness,vaginal discharge and withdrawal bleeds that may be unacceptable to the patient. The breast tenderness and nausea may disappear in a few months. If the other side effects bother the patient, switching over to another estrogen preparation, reducing the dose, switching over to continuous combined therapy are other alternatives.

The only indication for adding progestin suppliments to oestrogen replacement is to avoid the complication of endometrial hyperplasia which might occur with oestrogen therapy alone. Hence progestin supplimentation need be given only to women with intact uterus. Supplimentation with progestins has to be given at least 10 days per month to prevent endometrial hyperplasia.

There are two methods of supplimenting oestrogen therapy with progestins.

• Cyclical therapy: Here the progestin therapy is given for 10-12 days every month.
• Continuous therapy: Progestins in lower dose is given every single day of the month.

The progestins that are available are:

Norethisterone. Medroxy progesterone. Dydrogesterone. Natural micronised progesterone.

• Norethisterone: 1.25mg/ day in cyclical therapy and 0.3-1.25mg /day for combined therapy.
• Medroxy progesterone 10mg/day for cyclical therapy and 2.5-5mg/day for combined therapy.
• Dydrogesterone: 10-20mg/day for cyclical therapy and 10mg /day for combined therapy.
• Micronised progesterone: 200mg/day for cyclical therapy and 100mg/day for combined therapy.

Dydrogesterone and micronised progesterone which have lesser side effects have equivalent effects on the endometrium and provide useful alternatives for women who experience side effects with medroxyprogesterone. Side effects of progestins include mood symptoms such as irritability and depression, breast tenderness, and bloating. Oestrogen increases the level of High density lipoproprotein cholesterol, but this effect is nullified to some extent by synthetic progestins which are added to prevent endometrial hyperplasia. Dydrogesterone which has a structure closest to progesterone and Micronised progesterone do not nullify this effect that much, thus maintaining the cardioprotective effect of oestrogen. However the price of both these compounds is much higher than medroxyprogesterone acetate and for the middle income group it may be prudent to start on a less costly preparation and to switch over to costlier drugs only in case side effects tend to bother the patient enough to stop Hormone replacement therapy.

Tibolone: Tibolone is a synthetic steroid with estrogenic, and to a lesser extent,progestogenic and androgenic properties . In postmenopausal women, administration of tibolone reduces gonadotropin secretion , improves climacteric complaints , and prevents the decline (and even increases) bone mineral density without inducing the recurrence of menstrual bleedings.It is known as a “bleed free” HRT and is thus expected to have better compliance. The cost of therapy is, however ,very high and thus its use may be limited to the affluent population only .The dose is 2.5mg once daily.

SERMs : SERMs are selective oestrogen receptor modulators. They are estrogen look alikes and act as agonists on some sites and antagonists on others. The idea is to have the beneficial effects of HRT like prevention of osteoporosis, hot flushes etc without troublesome effects like endometrial hyperplasia.

Phytooestrogens : Phytoestrogens are weak estrogens of plant origin. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids) and whole-grain cereals, seeds, and nuts (mainly ligands). High dietary intake of plant estrogens not only reduces the risk for breast cancer but has been linked to fewer menopausal symptoms

Non estrogen treatments for menopausal symptoms: Nonestrogen treatments include Steroids(Progestins,androgens),SERMs, Phytoestrogens,Nonsteroidal medications(Clonidine,lofexidine,antidopaminergic ompounds, Bellergal, Propranolol,Natural remedies( Gensing,Vitamin E, Cohash, Bee pollen) and Life style/environmental modifications( avoidance of caffeine,layered clothing, exercise).

Natural nutritional supplements to alleviate menopausal symptoms: Vitamin E,d alpha-tocopherol 100-400 IU two times per day, citrus bioflavenoids with ascorbic acid 200 mg four to six times daily could help. The patient should reduce refined carbohydrate, caffeine, and alcohol intake. Soy protein, 50mg per day has been shown to decrease the intensity of hot flashes. Significant amounts of phytoestrogens also are found in cashews, peanuts,oats, corn, wheat, apples and almonds.

Osteoporosis (FAQ’s)

What is osteoporosis? Osteoporosis is the thinning of bone tissue and loss of bone density over time. In osteoporosis the bone mineral density (BMD) is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered. Osteoporosis occurs when there is an imbalance between new bone formation and old bone resorption. Two essential minerals for normal bone formation are calcium and phosphate. After menopause sets in, oestrogen levels fall , and this leads to osteoporosis. Decreased dietary intake of calcium lack of weight bearing exercise, also contribute to the setting in of osteoporosis.

What are the symptoms of osteoporosis? Osteoporosis is a silent disease. It may not cause any symptoms till there are minute fractures called fragility fractures, which commonly occur in vertebra, rib, wrist, and hip. Multiple vertebral fractures lead to a stooped posture, loss of height, and chronic pain with resultant reduction in mobility in the elderly. If there is loss of more than 1.5 inches then it means already there are micro-fractures in the spine. This hump is because of weak extensor muscles of the back along with very small fractures of the upper backbone which go unnoticed most of the time and are not diagnosed in more than one-third cases. This interferes with the quality of women’s life by causing chronic backache, decreased chest space resulting in respiratory problems and decreased abdominal space leading to poor digestion.

How can one prevent osteoporosis? Doing weight bearing exercises for about half an hour per day after theage of 35 is a good way of keeping osteoporosis away. Taking calcium rich food like milk or milk products, green leafy vegetables, and legumes,can aslo prevent osteoporosis. Calcium excretion is enhanced with intake of tea or coffee and one should cut down on their consumption.

How is Osteoporosis diagnosed? One need not wait till one gets physical symptoms to know if the bones are weak. Periodic testing of the bones with special tests like DEXA or ultrasound of the heel bone can detect if the bones are osteoporotic. This exam is used to measure bone mineral density (BMD). It is most commonly performed using dual-energy x-ray absorptiometry (DXA or DEXA) or bone densitometry. The amount of x-rays absorbed by tissues and bone is measured by the DXA machine and correlates with bone mineral density.

The DXA machine converts raw density information to a patient’s T score and Z score. The T score measures the amount of bone in comparison to a normal population of younger people and is used to estimate the risk of developing a fracture. Z score measures the amount of bone a patient has in comparison to those in the same age group. This number can help indicate whether there is a need for further medical tests.

What are the indications to treat osteoporosis with drugs?

• In women presenting with fragility fractures.
• Radiological diagnosis of incidental vertebral fracture or osteopenia.
• T score of <-2.5 at hip or spine on Dexa.
• with secondary causes of osteoporosis and high risk of fractures.
• In absence of DEXA, intervention is individualised understanding a cost benefit ratio..

What are the drugs available for treatement of osteoporosis? There are two groups of drugs, drugs that prevent bone resorption, and drugs that help bone formation. Drugs that prevent bone resorption: Bisphosphonates: Alendronate(10mg once daiy orally or 70mg orally once weekly), Ibandronate (2.5mg orally daily or 150mg orally once a month)

Chronic Pelvic Pian

Posted On April 25, 2018 by Dr.Shobhana Mohandas

Chronic pelvic pain may be defined as noncyclic abdominal and pelvic pain of at least 6 months duration.

Aetiology: Chronic pelvic pain could be due to pelvic,abdominal,musculoskeletal,or urogenital problems.Pelvic causes are commonly due to endometriosis, chronic pelvic inflammatory disease or due to adhesions.(12,34,38) Pelvic venous congestion, a condition where the pelvic veins remain dilated could also give rise to pelvic pain. The most common gastrointestinal problem associated with pelvic pain is irritable bowel syndrome, which is usually accompanied by altered stool passing. Abdominal neural trigger points could be another cause of pelvic pain. These are discrete (usually 1-2cm diameter) hyperpathic foci, the cause of which remains obscure. It could be due to subcutaneous sensory nerves being trapped in fibrotic or retracted surgical incisions. They could occur in nonsurgical conditions also. Urogenital causes of chronic pelvic pain include urinary tract infections, cystitis, or even interstitial cystitis of autoimmune etiology. In a few cases it becomes difficult to identify any cause for the pain.

Some of the gynaecologic causes of pelvic pain could be pelvic inflammatory disease, pelvic adhesions, pelvic venous congestion, endometriosis, ectopic pregnancy, fibroids, ovarian cysts, or neoplasms.

Diagnosis:

Pelvic inflammatory disease: BPelvic inflammatory disease (PID) is a difficult disease to diagnose because it may present with a wide range of nonspecific symptoms ranging from minimal discomfort to septic shock.(16) It may range from subclinical endometritis to frank salpingitis, pyosalpinx, tubo-ovarian abscess, pelvic peritonitis, and perihepatitis Bilateral lower abdominal pain is the most common presenting symptom. Perihepatitis causes right quadrant upper abdominal pain mimicking acute cholecystitis. Other common symptoms are abnormal vaginal discharge, metrorrhagia, postcoital bleeding, abnormal uterine bleeding (endometritis), dysuria, fever, and nausea or vomiting; The centre for disease control (CDC) have laid down criteria for diagnosis and grading of pelvic inflammatory disease. Diagnosis of pelvic inflammatory disease requires the presence of all 3 major plus one or more minor criteria. Major Criteria are, Lower abdominal pain with or without rebound adnexal tenderness/mass,Adnexal tenderness and Cervical motion tenderness. Minor criteria are, Temperature .380 C,White blood count> 10,000/mm3,Pus or bacteria on Gram stain from culdocentesis, Inflammatory pelvic mass or complex by ultrasound or bimanual examination,Elevated sedimentation rate and Cervical Gram stain with intracellular Gram-negative diplococci. However,Peipert et al have in one study found that if one uses the CDC criteria for diagnosis of PID, >15% of cases will be missed.They have concluded that a clinician should consider empiric treatment of at-risk women with adnexal tenderness if there is no other obvious diagnosis to explain the clinical signs and symptoms(17). Overdiagnosis of PID may be less deleterious than underdiagnosis.It is useful to remember that women who have acute PID present during the first half of the menstrual cycle. Presentation later in the cycle indicates an infection of longer duration and increases the likelihood that a tuboovarian abscess has organized.(19)

Pelvic adhesions: Not all patients with adhesions have pain and it has been found in one study that the incidence of pelvic adhesions in patients with chronic pelvic pain was not statistically different from the overall patient population. Kresch et al theorized that adhesions could restrict the mobility of the pelvic organs and that those involving the parietal peritoneum or bowel would cause pain(9). It has been proved that peritoneal adhesions contain sensory nerve endings and that they may cause pain when appropriately stimulated(30).Adhesions overlying the ovary may result in pain at ovulation by restricting the proper growth of the follicular cyst and discharge of the oocyte. Adhesions resulting from infection or endometriosis are sources of noxious stimulation which accompanies the adhesions formation process. Adhesions which have formed or are forming in the cul-de-sac create the opportunity for pain with movement of the uterus and hold of the uterus in retroversion which can then result in increased dysmenorrhea, pelvic congestion, and collision dyspareunia.However, when a patient comes with pelvic pain after pelvic inflammatory disease, the clinician should be cautious and rule out all other possible causes of pelvic pain before subjecting the patient to surgery for adhesiolysis.

Pelvic venous congestion: Varicosities in the pelvic veins could cause pelvic pain. The uterus, the ovaries and the vulva could be affected by this condition. The patients could present with pain during and after intercourse (lasting up to 24 hours), tender ovaries, backache,dysmenorrhoea,varicosities on one or both sides of the vulva and buttocks or even the whole leg,irritable bladder,abnormal menstrual bleeding or vaginal discharge. The pain is typically described as dull and aching pain that periodically gets worse premenstrually and during periods, when tired, when standing (It may get worse as the day wears on), during or after intercourse, and during pregnancy. After flaring up, the pain typically takes anywhere from several hours to a full day to resolve. Pelvic congestion syndrome is usually diagnosed after a thorough pelvic exam reveals no inflammation or other abnormalities. (5) A specific diagnoses is made by examining the pelvic veins by means of Pelvic ultrasound or Laparoscopy. Venography is also useful in diagnosing the condition, but is not used in India to diagnose this condition.

Endometriosis: Women reporting two or more of dysmenorrhea, pelvic pain or deep dyspareunia symptoms could be having endometriosis. Local tenderness on pelvic examination could be associated with uterosacral and cul-de-sac implants of endometriosis. For details of this condition, refer to the chapter on endometriosis(Q11,15

Evaluation: A: A proper history should be taken, keeping in mind the various causes of pelvic pain. As mentioned before, the diagnosis of ovarian cyst, ectopic pregnancy or fibroid could be made from history, examination and ultrasonography. If no obvious cause is found, the following guidelines should be followed.

• A gentle palpation of the introitus can diagnose vestibulitis
• While palpating the relaxed pelvic muscles posteriorly any muscular spasm could be noted.
• Any nodularity near the uterosacrals suggests endometriosis.
• Tenderness on bimanual examination could suggest PID.

Abdominal wall causes of pain:

• Iatrogenic peripheral nerve injuries (entrapment of a cutaneous nerve in the suture or scar of an abdominal incision),
• Nerve entrapment without prior history of surgery: Usually found along lateral margin of rectus muscle
• Impalpable interparietal hernias. Small hernias in obese women are usually not easily identifiable.
• Myofascial pain syndromes
• Rib tip syndrome:There is pain along the costal margin generated by the hypermobility of the 8th,9th and 10th ribs.
• Abdominal pain of spinal origin: When normal anatomy of the spine is disturbed in such a way that the roots of the intercostals nerves are irritated, abdominal pain may result.
• Rectus sheath haematoma arising from spontaneous rupture of epigastric vessels .

To differntiate abdominal pain arising from the viscera and pain arisng from the musculofascial structures, Carnetti’s test may be useful. The examiner’s hand is placed over the tender spot in the abdomen. The patient is asked to slowly raise her head up with the examining hand still placed over the abdomen. When the abdominal muscle is tensed, the pressure is reapplied and the patient is asked if the pain has altered. If the cause of the symptom is intra-abdominal, the tense muscles now protect the viscera and the tenderness should be diminished. If the source of pain is in the abdominal wall, the pain remains the same or is increased.

Treatment of pelvic inflammatory disease: In view of the lack of sensitivity of some currently used laboratory tests for C.trachomatis and N.gonorrhoeae among asymptomatic men, the Study Group endorses the recommendation contained in the CDC Sexually Transmitted Diseases Treatment Guidelines that sex partners should be treated empirically with regimens effective against both of these infections. (34) . Pavoneen.J has, mentioned that in most situations, combination treatment with doxycycline plus metronidazole is an effective treatment for inpatient and outpatient PID (17). In cases where N.gonorrhea is suspected, it is recommended that a single-dose therapy for gonorrhea should be provided (e.g., ciprofloxacin 500mg, or cefixime,1-g oral single dose).

Single dose Azithromycin has been shown to be effective in the treatment of chlamydial cervicitis, but its role in the treatment of PID remains controversial (19).Patients should demonstrate clinical improvement (ie, defervescence and decreased pain) within 72 hours of the initiation of treatment. Outpatients who do not improve within 72 hours require hospitalization, and inpatients who do not improve within 3 to 5 days require further diagnostic evaluation and/or surgical intervention.

Tubo-ovarian abscess: (10)Patients suspected of having a tubo-ovarian abscess should be hospitalized and given broad-spectrum antimicrobial drugs that include adequate coverage for gram-negative anaerobes. Failure of response to medical therapy is suggested by lack of improvement within 72 hours or increase in the size of the mass. Eighty-five percent of abscesses with a diameter of 4 to 6 cm respond to antibiotics alone, but only 40% of those 10 cm or larger respond. Surgical intervention for a tubo-ovarian abscesses that does not respond to antimicrobial therapy can be carried out laparoscopically, percutaneously, transvaginally, or by laparotomy. Patients with a suspected leaking or ruptured abscess should undergo immediate laparotomy after rapid stabilization and institution of broad-spectrum antibiotics.Hysterectomy with bilateral salpingo-oophorectomy as the sole treatment for tubo-ovarian abscess is now outmoded. , unilateraladnexectomy with continued medical management is an accepted surgical treatment of unilateral TOA. Some advocate simple drainage of abscess collections with aggressive medical therapy as the best way to maximize ovarian conservation for future reproduction. Laparoscopic and pelviscopic drainage of abscess collections and of pyosalpinxes is increasingly used. Ultrasound-guided transvaginal aspiration of abscesses may also be effective .After cure of acute PID complicated by TOA, there is justification for fertility surgery and for treatment with procedures aimed at optimizing either natural or in vitro fertilization techniques.

B.Complicated salpingitis- (tuboovarian abscess or inflammatory complex Clindamycin 900 mg IV q 8 hr plus Gentamicin loading dose of 2 mg/kg IV or IM followed by a maintenance dose of 1.5 mg/kg q 8 hr . Notification, evaluation, and treatment of symptomatic and asymptomatic sexual partners is an integral part of PID therapy to prevent reinfection. Assessment of male partners should take into account the reservoir of asymptomatic males who harbor gonorrhea and chlamydia, regardless of the organisms isolated from their female partners with PID. At a minimum, all sexual partners should be assessed for the presence of these organisms. Some authorities advocate presumptive therapy for all sexual partners of women with newly diagnosed PID.

Genital Tuberculosis:

Genital tract tuberculosis is an extremely indolent infection. Disease may not become manifest for more than 10 years after the initial seeding of the genital tract. Presenting symptoms may be unusual vaginal bleeding patterns, including altered menses, amenorrhea, and postmenopausal bleeding. Approximately 25% to 35% of women with pelvic tuberculosis have vague, chronic lower abdominal or pelvic pain. The chief symptom of young women with genital tract tuberculosis is infertility. Occasionally, women with the disease have tuberculous peritonitis and ascites, although these more commonly are secondary to direct hematogenous seeding of the peritoneum. Treatment options for a patient with chronic pelvic pain: The patient with chronic pelvic pain should be evaluated thoroughly regarding the cause of pelvic pain whether the cause is abdominal or pelvic. If the pelvic examination shows any abnormality, it should be treated accordingly. A course of NSAID’s is usually given as first line of treatment. Next, a course of tricyclic antidepressants may be given. They are thought to act by the blockage of the uptake of serotonin and norepinephrine in the central nervous system. If medical treatment is not effective, surgical modalities may have to be thought of. A laparoscopy may aid in further diagnosis and any surgical therapies like adhesiolysis, fulgration of endometriotic implants, etc. If the pelvic examination is normal, any neuropathies should be identified and treated with injections.

Surgical intervnentions for the treatment of chronic pelvic pain:

A: The possible surgical interventions for the treatment of chronic pelvic pain are:(34)

• Resection or vaporization of vulvar/vestibular tissue for HPV induced or chronic vulvodynia/vestibulitis;
• cervical dilation for cervix stenosis;
• hysteroscopic resection for intracavitary or submucous myomas or intracavitary polyps;
• myomectomy or myolysis for symptomatic intramural, subserosal or pedunculated myomas;
• Adhesiolysis for peritubular and periovarian adhesions, and enterolysis for bowel adhesions, adhesiolysis for all thick adhesions in areas of pain as well as thin adhesions affecting critical structures such as ovaries and tubes;
• salpingectomy or neosalpingostomy for symptomatic hydrosalpinx;
• hysterectomy if relief has not been achieved by organ preserving surgery such as resection of all endometriosis and presacral neurectomy, or the central pain continues to be disabling. Before such a radical step is taken, MRI of the uterus to confirm presence of adenomyosis may be helpful;
• uterine suspension for symptoms of collision dyspareunia, pelvic congestion, severe dysmenorrhea, cul-de-sac endometriosis;
• resection of endometriosis from all surfaces including removal from bladder and bowel as well as from the rectovaginal septal space. Complete resection of all disease in a debulking operation is essential;
• repair of all hernia defects whether inguinal, femoral, spigelian, ventral or incisional;

Role for laparoscopy in the evaluation and treatment of chronic pelvic pain:

Conjugated equine estrogen;strength: tablets of 0.625mg and 1.25mg.

Estradiol valerate strength: tablets of 1mg and 2mg.

Estriol strength: 2mg tablet.

Laparoscopy serves three important diagnostic functions: diagnostic confirmation, histological documentation, and patient reassurance. Laparoscopy should be done only after thorough medical and psychologicl evaluation and failure of all medical therapies. This will reduce the number of negative laparascopies. However, it has been shown that in patients where medical treatment has failed, laparoscopy does have a positive effect in curing the disease in some patients,by reassuring the patient that she is not suffering from any serious ailment. Laparoscopy could be done under local anaesthesia with the patient conciously pointing out the areas where she gets pain while the surgeon probes the various parts of the pelvis. By this technique of laparosocpic pain mapping, it was found that thin filmy adhesions cause more pain than thick adhesions. Although the role of laparoscopic adhesiolysis has been questioned by a few workers as they found a lot of patients with extensive pelvic adhesionswho did not have pain, various studies have shown that laparoscopic adhesiolysis in patients with chronic pelvic pain effects a cure in 64-84% of patients.(34) Laparoscopic release of intestinal adhesions, ovarian adhesions, fulgration of endometriotic implants, etc could result in curing many cases of chronic pelvic pain.(13)

Uterine nerve ablation:

In patients with central uterine pain and dysmenorrhoea, uterine nerves in the uterosacral ligaments are ablated laparoscopically. This is called laparoscopic uterine nerve ablation or LUNA. In some of these patients, there are endometriotic implants in the uterosacral ligaments. In these patients, LUNA has to be combined with resection of endometriotic implants. Resection and treatment of the uterosacral nerves may be more effective if accompanied by treatment of the connective fiber tissues bridging the posterior aspect of the cervix and lower isthmic region where the nerve fibers coalesce. This creates an arch of ablated nerve tissue from left uterosacral ligament across the posterior cervical attachment and progressing down along the right uterosacral ligament The LUNA, in skilled hands, is a safe procedure. In less experienced hands it can result in perforation of uterine vessels and injury to the ureter. It is not as efficacious as presacral neurectomy for central pain.

Pelvic venous congestion:

Pelvic venous congestion is a poorly understood disorder and a myriad of treatment modalities have been suggested but the final answer is yet to be found. Laparoscopy remains the main mode of diagnosing the disorder. The following treatment modalities have been tried for the disorder.

• Medroxy progesterone acetate (MPA) 30mg/day for 6 months. The pain is found to recur after stopping treatment. (27)
• Suprefact 3.6mg monthly for 6 months has been found superior to MPA but is a very costly treatment. (27)
• Ovarian artery embolization has been tried but long term results are awaited.
• Hysterectomy with bilateral oophorectomy is the last resort, but patients should be warned that pain might persist in a small subset of patients even after surgery.

The only indication for adding progestin suppliments to oestrogen replacement is to avoid the complication of endometrial hyperplasia which might occur with oestrogen therapy alone. Hence progestin supplimentation need be given only to women with intact uterus. Supplimentation with progestins has to be given at least 10 days per month to prevent endometrial hyperplasia.

There are two methods of supplimenting oestrogen therapy with progestins.

• Cyclical therapy: Here the progestin therapy is given for 10-12 days every month.
• Continuous therapy: Progestins in lower dose is given every single day of the month.

Trigger point injections:

A: Trigger point inections involve injection of local anaesthetics into specific sites. It is useful in patients with chronic pelvic pain of myofascial origin. This can be diagnosed when there is tenderness or twitch of the muscle on palpating a particular area .Sometimes a thickened band like structure can be felt in the muscle. In cases of deep dyspareunia, trigger points should be sought in the levator ani, obturator internus, piriformis and iliacus-psoas muscle groups. For pelvic pain expressing itself in the right and left lower quadrants, trigger points are sought in the rectus abdominus, external and internal obliques, iliacus, psoas, and quadratus lumbaricus. For central low pelvic pain, trigger points are sought in the rectus abdominus and pyramidalis. (1)Once an area of abdominal wall pain tenderness has been identified, its position is localized as accurately as possible with a single fingertip. The tender spot is injected with a mixture of 1ml 1% lignocaine and 25 mg hydrocortisone acetate using a 21 guage needle. To start with, a small bleb is raised in the skin overlying the tender spot. The needle is then inserted, and its point is moved around the tissues until the patient complains of pain similar to the original symptom. The injection is made into that point and into the immediately surrounding area. 80% of correctly diagnosed patients are completely or partially relieved of their pain by this treatment. 56% of patients with parietal pain treated with local injections of 5% aqueous phenol are pain-free or improved at follow-up 3.5 years after treatment. In one study, treatment of abdominal wall trigger points was performed by placing a 22-guage, 1.5 in. needle through the trigger point and slowly penetrating the fat pad until the needle tip reproduced the same sharp pain. The abdominal wall trigger points were found in fatty tissues above the fascia or along the margins of the abdominal wall scar tissue. Injection of 3 to 5 ml of 0.25% bupivacaine stimulated sharp and times severe pain followed by relief. Additional trigger points of the vulva, vagina and cervix and paracervical tissues were injected. Using these techniques a total of 89% of patients with abdominal-pelvic pain syndrome reported relief or improvement in pain such that no further therapy was required. The efficacy of injecting the parietes to relieve chronic abdominal symptoms has been well documented.

• Mechanical disruption of the abnormal contractile elements, which may result in the relief of muscle tautness and hyperirritability
• Fluid injections, which may dilute nerve-sensitized substances that may be present
• Muscle fiber damage, which may release intracellular potassium, causing a depolarization block of nerve fibers
• Focal necrosis caused by the anesthetic agent, which could contribute to the destruction of the trigger point.

Primary dysmenorrhoea:

A: Primary dysmenorrhoea is defined as cramping pain in the lower abdomen occurring just before or during menstruation, in the absence of other diseases such as endometriosis. . Systemic symptoms of nausea, vomiting, diarrhea, fatigue, fever, headache or lightheadedness are fairly common. Pain usually develops within hours of the start of menstruation and peaks as the flow becomes heaviest during the first day or two of the cycle. Secondary causes of dysmenorrhoea, like Adenomyosis, Endometriosis, Pelvic inflammatory disease, Inflammation and scarring (adhesions), Cervical stenosis and polyps, Functional ovarian cysts, Fibroids (intracavitary or intramural), Benign or malignant tumors of ovary, bowel or bladder, or other site, Intrauterine contraceptive devices or Inflammatory bowel disease must be ruled out.

NSAID’s like Ibubprofen, Naproxene, Mefenamic acid and Rofecoxib could be effective in providing pain relief. If pain relief is not obtained, OC-pills could be tried.

Lack of response to NSAID’s and OC-pills calls for further investigations like laparoscopy to rule out causes of secondary dysmenorrhoea like endometriosis.

Transdermal Nitroglycerine, 0.1-0.2 mg given per hour during first few days of the menstrual cycle,

Thiamine {vitamin B6) 100mg given each day for 90 days, and giving magnesium supplements.

Transcutaneous electric nerve stimulation (TENS) is another modality that is being tried out.

Acupunture and Laparoscopic presacral neurectomy have also been found useful. (3)

Contraception

Dysfunctional Uterine Bledding

Posted On April 24, 2018 by Dr.Shobhana Mohandas

Dysfunctional uterine bleeding (DUB) is an old terminology for abnormal uterine bleeding occurring in the absence of any obvious pelvic pathology.

Management strategies are discussed below:

Acute episode of DUB in the perimenopausal period: In the perimenopausal period the patient is most likely to be suffering from anovulatory bleeding.However it is mandatory to rule out pregnancy and pelvic infection as possible causes of bleeding. Hypothyroidism is common in this age group, and should be ruled out by history and clinical examination.It is not necessary to do endocrinological tests for hypothyroidism in all patients with abnormal uterine bleeding(27). A careful medical history should be taken to rule out diseases of the liver,adrenals. She should be questioned regarding the use of anticonvulsants. When all functional causes of abnormal bleeding are ruled out a diagnosis of DUB is made. In this age group it is mandatory to do an endometrial sampling to rule out carcinoma(26).

Scenario Abroad:In some countries,endometrial sampling is done using 3mm plastic suction cannulas, the names of some of them being ,Pipelle, Explora,vabra aspirator, Z-Sampler,&Endosampler(2). Studies have found office endometrial sampling superior to D & C(28).

An alternative is to do a transvaginal ultrasonography on day 4,5,or 6(17). An endometrial thickness of 5mm rules out endometrial hyperplasia.

Since polymenorrhoea is usually due to local inflammatory reaction, NSAIDs in the dose usually used for ovulatory bleeding may be enough to cure it. This will also take care of uterine cramps if they are the source of lower abdominal pain. Bioflanoids (Gynae CVP) could be added. Iron should be added to prevent anaemia.

In cases where it is more than 5mm or when the image is not clear, a procedure called saline infusion sonohysterography could be performed. In this procedure, the uterine cavity is slightly distended with saline and then,TVS done. This delineates the endometrium better, and allows for better diagnosis of endometrial polyps and small submucous myomas sonographically.

Dilatation and curettage is done only when medical treatment fails .Whenever curettage is done it is best done hysteroscopically as a blind D& C has proved to miss out lesions quite often(28).

Indian scene: In our country, endometrial sampling devices are not common. Thus in cases as the one mentioned above,wherever vaginal sonograpy is available it could be done and if the endometrial lining is 5mm on day 4,5 or 6 of the period,one could reasonably rule out hyperplasia and go in for medical treatment. In centres where vaginal sonography is not possible, and in cases where the endometrium is 5mm on day 4,5 or 6,a dilatation and curettage is mandatory to rule out malignancy. A hysteroscopic biopsy as a primary diagnostic modality for DUB may not be practical in our setup. In cases where a vaginal sonogram picks up an endometrial polyp, in well informed and willing patients, a hysteroscopic polypectomy would be ideal. After a D&C, quite often, the bleeding abates, but it is better to put the patient on maintenance medical therapy to avoid recurrence.

Majority of doctors in the survey were using Norethisterone in the dose of 15mg /day to stop acute bleeding. But if a dose of 15mg of Norethisterone/Norethindrone does not stop bleeding, one should step up the dose before calling it a failure of therapy. Norethisterone could be given in doses of upto 30mg/day. 16% of doctors in the survey were found to be using Norethisterone in this dose. Once the bleeding has stopped, the dose could be tapered to 15mg daily and this dose continued for 21 days. Medroxy progesterone could be given in a dose of 60-120mg on the first day and 20 mg daily in the subsequent days.

Monophasic OC pills could also be used to control acute uterine bleeding. To stop an acute episode of bleeding, OC-pills should be given in the dose of 1 tablet four times a day (25,26,28). Even if the bleeding stops, the treatment should be continued for 7 days. In such a high dose, the patient may experience severe nausea or vomiting and antiemetics should be given simultaneously. After 7 days, the dose should be reduced to one/day and continued for 21 days.(28) . Another regimen is to give Regular oral contraceptives containing 35mug of ethinylestradiol in a regimen of 4 tablets for the first day, 3 for the second day, 2 for the third day, and then 1 per day until the pill pack is finished.(12)

Maintenance therapy: Progestins are commonly used in North America and the UK. (28)This is also true in India. Oral medroxyprogesterone acetate 10 mg a day from days 16 through 25 each cycle may be given. Alternatively, Norethindrone/Norethisterone 5 to 10 mg one to three times a day may also be used to manage recurrent anovulatory dysfunctional uterine bleeding. Progestins are generally administered for 7 days (minimum duration for the prevention of hyperplasia) to 12days of each cycle.(26) For anovulatory patients who are difficult to treat, the course of progestin therapy can be extended for 14 to 21 days each month. Prolonged use of high-dose progestins is associated with side effects, which include fatigue, mood changes, weight gain, and atherogenic changes in the lipid profile.(13) Dydrogesterone,a progesterone that has a structure very similar to progesterone and micronised progesterone, which is natural progesterone in the micronised form has also been studied for the treatment of DUB. Both agents are costly (Dydrogesterone-Around Rs.10 for a 5mg tabletµnised progesterone Rs 18 for a 100mg tablet).

Dydrogesterone may be given in the dose of 10mg b.i.d (together with estrogen) for 5-7 days to arrest bleeding & in the dose of 10mg b.i.d (together with estrogen) from 11th- 25th day of the cycle to prevent bleeding. In a study comparing the effects of micronized progesterone (300 mg per day) and the progestin norethisterone (15 mg per day) in premenopausal women, menstrual cycles were well controlled with either agent, but cessation of dysfunctional uterine bleeding was achieved more frequently in the women who took micronised progesterone(26) Another alternative is to use Combined oral contraceptive pills which have been shown to effectively reduce menstrual bleeding by up to 60% in normal uteri. OC pills given for 2-3 months result in a stable, atrophic endometrium. The most common side effects include weight gain, abdominal discomfort, and midcycle breakthrough bleeding.

DUB in the reproductive age group: In women in the reproductive age group, pelvic infection and pregnancy should be ruled out by pelvic examination, urine pregnancy test, and if necessary vaginal ultrasonography. Any abnormality detected should be treated accordingly. A routine haemogram should be done. If there are no abnormalities detected, a diagnosis of dysfunctional uterine bleeding should be made. Dysfunctional uterine bleeding in this age group could be ovulatory in nature,although typically the history of regular menstruation on a monthly basis indicates ovulatory cycles. In practice, a specific diagnosis often is not sought if the patient is not immediately desirous of pregnancy. Instead empirical medical therapy is begun.(30) Women with ovulatory dysfunctional bleeding are usually not lacking in progestin, but have underlying imbalances in prostanglandins.

Nonsteroidal antiinflammatory drugs like Mefenamic acid 500mg , Ibuprofen 400mg three times a day,Diclofenac sodium could correct the prostaglandin imbalance.(13) NSAID�s are known to reduce flow by 20%. NSAIDs need not be used through out the cycle. Tranexamic acid in the dose of 2g/day could be used as an antifibrinolytic agent. Ethamsylate was used as a plasminogen activator inhibitor, but controlled studies show conflicting results about it�s efficacy. . It is used extensively in India. 20% of doctors in our survey have mentioned the use of drugs like Ethamsylate,NSAIDs,etc for the control of bleeding in the reproductive age group .Preparations containing vitaminK,,Vitamin C ,and flavonoids (e.g:GynaeCVP,Styptovit,Styptomet) have been found useful for the treatment of menorrhagia, though the last study on the use of Vitamin K (Menadione) was done 57 years ago. If the above measures do not reduce bleeding, hormonal therapy with progestogens or oestrogen could be tried.T he long-term treatment for women with ovulatory dysfunctional uterine bleeding is the most difficult type of dysfunctional uterine bleeding to manage and a combination of one or more of the agents mentioned above may be required along with hormonal treatment.

Heavy DUB in the very young girl in the menarchal age group:

At the outset, any pelvic abnormality should be ruled out. A pelvic examination may be embarassing for the patient and may not yield much information in an unwilling patient. An abdominal ultrasound examination can rule out most of the pelvic pathologies. Once uterine or ovarian pathologies are excluded, a bleeding diathesis should be ruled out. Recent studies have shown that as much as 20% of patients with menorrhagia may have a bleeding diathesis(29).History of easy bruisability, bleeding from minor trauma should be taken. A detailed physical examination must be done to look for pallor, bleeding spots and hepatosplenomegaly. A total count, haemoglobin value, bleeding time, clotting time, prothrombin time and Activated partial thromboplastin time should be done. A correct diagnosis of coagulopathy made at this time will have important implications for the management of future pregnancies, as APH and PPH can be anticipated and treated(28).

Medical therapy: Any anaemia should be treated with haematinics or blood transfusion according to severity. Acute bleeding can be controlled with hormone therapy even in the patient with coagulation disorders. Thus while the results of the blood tests are awaited, hormone therapy could be started. a) Oral contraceptive pills with 35micrograms of estrogen and a progestin 6-8hourly could be tried along with antiemetics if necessary for 24-48 hours(26). If the bleeding continues the dose should be increased by using pills containing 50micrograms of oestrogen every 6 hours. When the bleeding stops, the dose should be tapered over a week to 1 pill daily. When the initial packet is empty, she should immediately begin a new 28 day packet of 35microgram pills. The menstrual period immediately following the treatment may be heavy due to the estrogenic content of OC �pills.

Progestins: Norethisterone/Norethindrone could be tried in the dose of 30 mg/day in divided doses for 3 days . The dose could be tapered to 15mg /day once the bleeding abates and continued for a total of 21 days. Medroxy progesterone acetate in the dose of 60-120 mg during the first day of admission and 20 mg/day for the following 10 days was found effective in one study(16).

Maintenance therapy could be given with either Norethisterone(5-10mg one to three times/day) or Medroxyprogesterone 10mg a day on days 16 through 25 each cycle(13) . For anovulatory patients who are difficult to treat, the course of progestin therapy can beextended for 14 to 21 days each month. Cyclic administration of combination oral contraceptives is effective in reducing the risk of recurrent bleeding episodes.

Answer: women aged >=35 years with no other risk factors who have stopped smoking more than a year ago may consider using combined hormonal contraception. The excess risk of MI associated with smoking falls significantly 1 year after stopping and is gone 3-4 years later, regardless of the amount smoked

Minimal but irregular bleeding in the adolescent:

If the adolescent girl can tolerate the bleeding emotionally and physically, she can be followed without hormonal intervention. NSAIDs could decrease the flow and a multivitamin with iron could be given prophylactically. Although convincing studies are not there, Ethamsylate, preparations like Gynae CVP,Styptovit, etc could also be tried. But if the girl is anemic (History of being too tired to study is often given), or is bothered that the bleeding affects her day to day life, a combined oral contraceptive containing 30-35 microgram of estrogen can be prescribed along with iron. All patients taking oral contraceptives should be seen at 1,3,and 6 months. If the adolescent has done well and does not wish to continue the oral contraceptive, it may be stopped at that time.

Minimal irregular bleeding in the perimenopausal woman: A cervical polyp should be ruled out. A transvaginal sonogram should be done to rule out endometrial polyps. If no obvious cause is found, the intermittent vaginal spotting is probably associated with minimal(low) estrogen stimulation(estrogen breakthrough bleeding). (3) In this circumstance, where minimal endometrium exists, the beneficial effect of progestin treatment is not achieved, because there is insufficient tissue on which the progestin can exert action. 1.25mg Conjugated estrogen or 2mg estradiol daily can be prescribed for 7-10 days. All estrogen therapy should be followed by progestin withdrawal or continued OCP.

Post-menopausal bleeding :

The golden dictum was that a woman with postmenopausal bleeding should be diagnosed to have endometrial carcinoma unless proved otherwise. But in the changed scenario of today a lot of other factors have to be taken into consideration. Awareness of hormone replacement therapy having increased, a lot of general practitioners have also started using hormone replacement therapy. Patient should be directly questioned on the use of hormone replacement therapy. If she is on estrogens, the dose should be adjusted or alternate therapy advocated. Other wise the management is the same as for the perimenopausal woman.

Q:If a 48 year old woman comes with intermenstrual bleeding with occasional menorrhagia presents to the OPD, and pelvic examination shows a normal uterus with non tender pelvis and a normal looking cervix, what should be the line of management?

A:This is a case of dysfunctional uterine bleeding, as no obvious cause for bleeding can be found. Intermenstrual bleeding is generally the hallmark of oestrogen deficiency in the perimenopausal lady, like the one mentioned here. In this case, since there are occasional bouts of menorrhagia, there is a possibility of endometrial polyps. However, in the perimenopausal period the patients may present with episodes of ovulatory bleeding (which are predictable, because they are regular), interspersed with episodes of anovulatory bleeding which is erratic. This becomes confusing to the patient and the physician. This happens due to decreased inhibin levels, and variable estradiol levels with normal FSH levels.

If no abnormality is seen, then put her on conventional Combined oral contraceptive pills (COCs) with 30mcg EthinylEstradiol, as her intermenstrual bleed may be because of estrogen breakthrough. This will also correct her Menorrhagia. Continue for at least six cycles and then stop the COCs. Intermittent anovulation during the perimenopause may be associated with physical complaints like hot flashes, and night sweats. Oral contraceptive pills regulate menstrual cycles, decrease vasomotor symptoms, improve bone mineral density, and decreases the need for surgical intervention for DUB1. Additionally, endometrial and ovarian cancer rates are reduced in women using oral contraceptive therapy. Generally, oral contraceptives are well tolerated and enhance menstrual health and quality of life for the perimenopausal woman.

Answer: women who have the intrauterine progesterone-only system inserted at age >=45 years for contraception or for the management of menorrhagia can be counseled about retaining the device for up to 7 years, safely without the risk of pregnancy.

Q: What should be looked for in Transvaginal ultrasound(TVUS) in a patient with peri menopausal bleeding PV with normal pelvis on per vaginal examination?

Q: What is Endometrial sampling? Should Endometrial sampling be done for all women with increased thickness of endometrium? A: Endometrial sampling is a technique of taking a biopsy of the endometrium to rule out malignancy. Generally, this was done by dilatation and curettage in the past, but now, it is has been found that sampling the endometrium using special devices like an endometrial pipelle can also rule out malignancy. It is necessary to rule out malignancy this way for women in the reproductive and perimenopausal age group, ie: >45 years with abnormal uterine bleeding. It is also deemed necessary when high risk factors for malignancy, are present,viz;Age > 45, history of infertility, family history of colonic carcinoma, and nulliparity4,5.. All post menopausal women presenting with uterine bleeding, and women on Tamoxifen/Letrozole post-CA Breast should also undergo endometrial sampling.

Q: What is sonohysterogram? When does the gynaecologist order this investigation?

A: Sonohysterogram or SIS ( Saline Infusion Sonography ) infuses saline into the endometrial cavity during Trans vaginal ultrasonography (TVUS) to enhance the image. Many alternate terms have been used to describe this technique: echohysteroscopy, hydrosonography, sonohysterography, sonohysterogram, sonohysterosalpingography, and sonoendovaginal ultrasound. SIS allows the clinician to evaluate the uterus for intracavitary lesions more accurately than TVUS. The indications for SIS are3,6:

• Abnormal bleeding in premenopausal or postmenopausal patients
• Evaluation of an endometrium that is thickened, irregular, immeasurable or poorly defined by conventional transvaginal ultrasound (TVUS).
• Irregular endometrial appearance by TVUS in women using tamoxifen.
• The need to differentiate between sessile and pedunculated masses of the endometrium.
• Presurgical evaluation of intracavitary fibroids.

Q: If endometrial sampling is normal, what should be the first line of management?

A: In the perimenopausal age, anovulatory bleeding is more likely to be the cause of DUB. This has to be tackled with progestogens or oral contraceptive pills as first line of management. In hypertensive and diabetic patients, oral contraceptives with high dose oestrogen may be harmful. Some patients cannot tolerate hormones. Some patients may not respond to hormone treatment or may take treatment irregularly leading to more irregularities in bleeding. Alternative medical treatment methods or conservative surgical measures have to be resorted to in such patients.

Derangements in the local haemostatic mechanism may cause ovulatory bleeding . Antiprostaglandins like Mefenamic acid and antifibrinolytic agents like Tranexamic acid may be useful in the management of such patients. Patients with ovulatory DUB must be evaluated for intracavitary uterine pathology (with SIS or hysteroscopy), since hormonal dysfunction is not the likely cause of bleeding. Intracavitatory causes like endometrial polyps or submucous fibroids have to be ruled out. If such pathology is diagnosed, there is an option of hysteroscopic resection in centres with facilities for such procedures.

Q: Should hysteroscopy be done for all patients with dysfunctional uterine bleeding?

A:All patients with DUB need not undergo Hysteroscopy. However, all patients of ovulatory DUB are best evaluated with a hysteroscope, because patients with ovulatory DUB are more likely to have intracavitary uterine pathology, since hormonal dysfunction is not the likely cause of bleeding. In these patients, if on TVS, the endometrial thickness is irregular, the endo-myometrial interface is ill defined, then hysteroscopy offers a better chance of diagnosis. Patients with anovulatory DUB, where concomitant intra -cavitary lesions are suspected, may also be offered hysteroscopy2,6.

Q: What is Tranexamic acid? What is the dose and how long in an index month can it be given?

A: Tranexamic acid is an Antifibrinolytic Agent and is a synthetic lysine derivative which blocks lysine- binding sites on plasminogen. It prevents plasmin from binding to fibrin, thus inhibiting fibrinolysis . Tranexamic acid has been shown to reduce menstrual bleeding by approximately 50% 7,8. In most studies tranxemic acid was administered from days 1 to 4 or 5 of menses in a dose of 4 g/day1,7,8. Maximum of 4 gms can be given per day in divided doses. It has been studied in the dose of 1.95gm daily was also found to be effective in one study9.

Q; What is ormeloxifene? For how many months can treatment with ormeloxifene be given?

A:Ormeloxifene (also known as centchroman) is one of the selective estrogen receptor modulators, or SERMs, a class of medication which acts on the estrogen receptor. It is best known as a non-hormonal, non-steroidal oral contraceptive which is taken once per week. Ormeloxifene may be effective for dysfunctional uterine bleeding and advanced breast cancer. It can be used for the treatment of DUB at any age. However, it is not suitable for women desiring pregnancy, due to it�s contraceptive effects. Doses: Dysfunctional uterine bleeding: 60 mg twice a week for the 1st 12 weeks and then 60 mg once a week for up to next 12 weeks10

Q: Is there any difference in medical treatment if there is metabolic syndrome?

A: Women with metabolic syndrome tend to be diabetic and hypertensive in the perimenopausal age. Giving high dose oral contraceptive pills may be harmful in these patients. Such patients can be treated by giving them withdrawal bleeds without allowing them to go into prolonged periods of amenorrhoea. If she has PCOS, metformin may be helpful. Progestogens or antifibrinolytic agents will have to be chosen instead of COC�s. Ormiloxefene is a new option. The LNG-IUD, is another option.

Q: What is LNG-IUD? What are the effects and side effects?

A: The LNG-IUS is an intrauterine delivery system, which delivers levonorgestrel @ 20mcg per day. The IUS has a similar shape to the Nova-T 380 copper IUD with the vertical stem containing a mixture of 52 mg levonorgestrel and polydimethyl siloxane (PDMS), surrounded by a rate-controlling PDMS capsule11. The total length of the system is 32 mm, and the T-shaped plastic frame is impregnated with barium sulphate, making the device radio-opaque. Two threads are attached to the loop at the base of the IUS to aid removal. This system allows a steady, local release of 20 mg levonorgestrel per day initially, and has few systemic side-effects (approximately the equivalent of taking two progestogen- only pills/week). Following insertion of an IUS, women frequently complain of menstrual disturbance. Approximately 17% of women will complain of prolonged bleeding (>8 days) in the first month of use, with this falling to 3% at 3 months. Some complaints include mood changes, nausea, headache, bloating, breast tenderness, fluid retention and skin problems.

Q: In a woman with cystic glandular hyperplasia, in the perimenopausal age, is there any need for hysterectomy?

A: WHO classifies hyperplasia into two varieties, simple or complex types, each with atypical or non �atypical pathology. Studies have found high concentrations of progesterone receptors in hyperplasia without atypia whereas lower levels were found in atypical hyperplasia12,13. Hyperplasia without atypia may disappear completely with progesterone therapy. Progesterone therapy has to be given for 6 months. LNG IUD is another option. However, studies have shown discrepancies between endometrial pipelle specimens of endometrium /D&C samplings and hysterectomy specimens of endometrium12. So ideally, if a pipelle sample shows hyperplasia, a hysteroscopic directed biopsy should be taken to rule out atypical hyperplasia. If a hysteroscopic directed biopsy is negative for atypia, progesterone treatment may be tried. In women who show atypia, either on hysteroscopy or on pipelle sampling, the clinician must be worried that the patient may be harbouring endometrial carcinoma. A hysterectomy may be prudent in these women. Ablative procedures are not currently recommended for such patients.

Q:What are the other options beside hysterectomy for a woman who cannot tolerate medical treatment due to side effects or if she has a failure of medical treatment?

Hysteroscopic resection was the first efficacious ablation therapy for DUB . It was introduced in 1976 by Neuwirth et al. and offered a surgical alternative to hysterectomy. Subsequently, laser ablation, radio-frequency monopolar resection, and rollerball ablation were developed. These are commonly called First Generation Techniques.Later the second generation techniques followed, Second-generation techniques mostly involve tissueheating as the method of endometrial destruction. They are blind in nature, not being performed under direct hysteroscopic vision with the exception of the HydroTherm AblatorTM. They therefore, avoid the risks of fluid distension media. Some techniques may be performed under local anaesthesia. For all methods, the woman should have no desire to retain her fertility. The uterus should be of 12 week size or less. Cryoablation, Free fluid thermal ablation, Impedance-controlled bipolar radiofrequency,ELITT, Photodynamic endometrial ablation, Thermal balloon endometrial ablation are some of the second generation ablation techniques14.15,16. Thermal balloon endometrial ablation is the most popular among these in India.

Q: What is the role of D&C in the management of DUB?

A: Dilatation and curettage (D&C) causes a temporary reduction of menstrual blood loss for the first month, but at following cycles, the amount of blood loss tends to increase as compared to blood loss before the D&C . Therefore, D&C must be considered obsolete in the treatment of dysfunctional uterine bleeding, but unfortunately it is still performed on a large scale in women suffering from dysfunctional uterine bleeding1,2,3.

References :

• Linda Bradley: Menstrual dysfunction: 1247-1245: Cleveland Clinic: Current Clinical Medicine, 2nd ed. Copyright 2010.Saunders.
• 2.Marles .Y.B et al: Current treatment of dysfunctional uterine bleeding: Maturitas 47 (2004) 159�174.
• H. Marret et al: Clinical practice guidelines on menorrhagia: management of abnormal uterine bleeding before menopause: Euro.J. Ob & Gynand ReprBiology .152 (2010) 133�137.
• Thomas.E.S., Perimenopause, chapter 61,Section 8: Clinical Gynecology (1stEd) � 2006 Elsevier Inc. Ed: Eric J. Bieber.
• Freeman EW, Lukes A, VanDrie D, et al. A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding. Am J Obstet Gynecol 2011;205:319.e1-7.
• .Diana Mansour: Modern management of abnormal uterine bleeding � the levonorgestrel intra-uterine System: Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 21, No. 6, pp. 1007�1021, 2007.
• Adolf Gallinat et al: NovaSure Impedance-Controlled System for Endometrial Ablation: The Journal of the American Association of Gynecologic Laparoscopists: August 2002, Vol. 9, No. 3.

.Aksu F; Madazli R,et al., High-dose medroxyprogesterone acetate for the treatment of dysfunctional uterine bleeding in 24 adolescents: Aust N Z J Obstet Gynaecol 1997 May;37.

• Apgar.B.S: Treatment of Dysfunctional Uterine Bleeding: Primary Care; Clinics in Office Practice :Volume 24 � Number 1 � March 1997.
• Bonduelle M,|Walker JJ: A comparative study of Danazol and Norethisterone in dysfuntional uterine bleeding presenting as menorrhagia. Postgrad Med J 1991 Sep: 67(791) : 833-6.
• Bonnar.J: Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid: BMJ – 1996 Sep 7; 313(7057): 579-82.
• Chomczyk I; Sipowicz M; Dydrogesterone in the regulation of cycle disturbances in adolescence: Ginekol Pol 1999 May;70(5):343-7.
• Hickey M, Higham J,et al., Progestogens versus oestrogens and progestogens for irregular uterine bleeding associated with anovulation (Cochrane Review) Synopsis in Issue 3 of The Cochrane Library for 2000.
• Hidlebaugh.D.A: Cost and quality-of life issues asssociated with different surgical therapies for the treatment of abnormal uterine bleeding: Obstetrics and Gynecology Clinics Vol 27 . NO 2 . June 2000.
• Stabinsky.S.A,EinsteinM. Et al: Modern treatments of Menorrhagia Attributable to Dysfunctional Uterine bleeding: Obstetrics &Gynecological Survey pp61-72.Vol.54.NO1 : January1999.
• Vilos.G.A., – Hysterectomy: Outdated as a Treatment of Menorrhagia?: Editorial, New Eng J Med.July 1996
• Shah.A.A, Grainger.D.A., Contemporary Concepts in managing menorrhagia : CME in medscape 1996.
• Oriel.K.A. Schrager.S., Abnormal Uterine Bleeding : American family physician,October 1,1999 60:1371-82.
• Long.C.A: Evaluation of patients with abnormal uterine bleeding: American Journal of Obstetrics and Gynecology:Volume 175 � Number 3 � September 1996.

Infertility

Posted On April 24, 2018 by Dr.Shobhana Mohandas

Infertility is defined as a state in which a couple, desirous of a child cannot conceive after 12 months of unprotected intercourse. But, if a couple approaches a doctor for infertility, they should be evaluated to see that they do not have any major problems.

Initial evaluation of the female:

Infertility, the inability to conceive after 1 year of unprotected intercourse, is estimated to affect one in six couples at some point in their life. Investigations should be normally be instigated as soon as the couple seeks help, as gross irregularities that one could come across during history taking or examination can be corrected immediately. There are many situations unique to the Indian set up, like couples staying separately, or working for long hours with no time for intimacies, interference from overbearing family members, being just some of them. Social stigma attached to infertility is also peculiar to the subcontinent.

It is important to try and start counselling in the presence of only the husband and wife, without interference from relatives or friends. . In India, the male partner quite often refuses to be involved in discussions. If the male partner refuses to meet the gynaecologist, it would be better to talk to the female partner alone, confidentially, as this would bring out many points in the history, which may be masked, in the presence of parents or friends. For example, H/O medical termination of pregnancy before marriage, or the presence of children by another marriage, are quite often suppressed unless the woman is interrogated separately.

Initial evaluation of a patient:

• Whether the couple are staying together, and the frequency of intercourse.
• There is pain during intercourse
• Regularity of menstruation
• H/O abortions/deliveries
• Associated History of any medical disorders

Physical Examination:

General Examination:

BMI:Determination of body mass index(BMI) is important, as both obesity as well as being too underweight can be causes of disorders of ovulation and pregnancy wastage. Determination of BMI is made from the height and weight (Kg/m2). The normal range is 20-25kg/m2. BMI of >30 falls in the obesity range.

A cursory examination can reveal stigmata of hyperandrogenism, like acne, hirsuitism, and male pattern of balding , which are suggestive of Poycystic ovarian syndrome(PCOS). Hirsuitism can be graded and given a “Ferriman Gallway” score.

Virilisation is a higher grade of androgenism with very high circulating androgen levels and causes deepening of the voice, increase in muscle bulk,cliteromegaly and breast atrophy beside the other signs of hyperandrogenism. Other than severe PCOS,it could also be seen in congenital adrenal hyperplasia(CAH) , androgen secreting tumors and Cushing’s syndrome.

Breasts should be examined to look for galactorrhoea. It is important to know that examination of breasts, vagina, or even stress can elevate prolactin levels and therefore, blood tests should never immediately follow examination of the patient.

Local examination: It is mandatory to do a per vaginal (PV) and per speculum examination as it can give a lot of valuable information. The advent of Utrasonography has led to a reluctance to do vaginal examination. However, a PV has, quite often led to the discovery that the couple are not even aware of the need for proper penile insertion into the vagina for completion of intercourse. Some such couple who have not even consummated their marriage have been known to undergo expensive investigations for infertility. Acute retroversion and retroflexion of the uterus with the cervix lying almost close to the urethra will need proper counselling. The average gynaecologist asks the patient to lie for half an hour in the supine position with a pillow under her buttocks so that the cervix dips into the pool of semen in the vagina. However, in the retroflexed uterus, the supine position may not serve that purpose. Irregularities in the fornices , specially the posterior fornix is suggestive of either endometriosis or post infective adhesions, and such findings on initial evaluation should prompt the clinician to start evaluating and treating the patient straight away. Acute pelvic infection is another finding which can be missed if one solely relies on ultrasound reports. These “misses” are more likely in the patient who comes with reports from many doctors and more so when some investigative reports show gross abnormalities like resistant PCOD or Azoospermia in the male, just to name a few. The doctor who sees the patient with many reports, may just omit Per vaginal examination, thus missing out a recent infection or polyp or endometriosis. A per speculum examination can sometimes reveal cervicitis or endometrial polyps, or even simple trichomonal infection and if they are detected and treated after proper examination it can improve results in a fertility clinic.

Endocervical swabs and tests for Chlamydia detection: Chlamydia trachomatis can cause cervicitis , salpingitis and endometritis in women, although symptoms can be mild and non-specific1. Antibodies can be tested in serum and antigens in endocervical swabs. Some clinics routinely test serum for anti chlamydial antibodies. The presence of chlamydial antibodies predicts tubal damage in 90% of cases. Chlamydial antigen can be detected by enzyme linked immunosorbent assy in (ELISA) of endocervical swabs. A sensitive urinary assay also has been developed for the screening of past chlamydial infection. However, Chlamydia detection tests may be negative in the presence of upper genital infection.

Bacterial vaginosis causes up to 50% of vaginal infections. It is associated with infective complications following gynaecological surgery, first and second trimester miscarriage and premature labor/delivery. There is also an increased risk of miscarriage after IVF in women found to have bacterial vaginosis. Screening for bacterial vaginosis can be useful in the investigation of infertility.

Investigating the female further, should be target oriented, to determine if the woman has ovulatory disorder, tubal factor, cervical factor or immulogical cause for infertility. As against semen analysis for the male, which is a simple test, most of the investigations for dertermining female factor of infertility are cumbersome and some invasive, so one has to be careful in deciding which patient should undergo the investigation, and the frequency with which she has to undergo the tests.

Ovulatory disorders: Oligo ovulation or anovulation is the commonest female factor of infertility. Empirical treatment for infertility is most often targeted at correcting ovulatory disorders. Documenting ovulation before starting therapy for oligo/Anovulation would be ideal instead of empirical treatment, which can have draw backs, like reduced cervical mucus with the use of prolonged clomiphene therapy. The following investigations can help ascertain if a woman is ovulating.

Basal body temperature chart: The temperature of the woman is taken every day before rising from bed and noted. Just after ovulation the temperature rises by 0.2-0.50 C due to a rise in progesterone levels and remains higher than the preovulatory phase. It is a retrospective diagnosis and can strain the patient, though it is a fairly good method of documenting ovulation. However, a flat BBT chart does not necessarily mean anovulation, as 10-75% of ovulatory cycles fail to show a rise in BBT.

Serum progesterone measurements:A serum progesterone value greater than 30nmol/L in the luteal phase suggests ovulation. However, in a woman with an erratic cycle, it is difficult to know when to do a progesterone measurement. In such patients, if the progesterone level is 15-30, it need not mean anovulation as it may be in the proliferative phase of menstruation. Thus the progesterone value has to be co-related with the onset of menstruation. Progesterone levels combined with USG is more useful.

Urinary LH kits: Urinary LH is measured using reagent strips by the patient herself . In response to a preovulatory surge in estradiol, LH levels surge in the bloodstream and spill into the urine. The kit measures the LH as it accumulates in the urine and a midcycle surge predicts ovulation.

Ovulation induction kits can help couples to time intercourse. The testing should be carried out at the same time every day starting two to three days before expected ovulation. 3 drops of urine is put on the kit. A colour change predicts ovulation in 12-24 hours. The true window of fertilization is actually short (usually 24 hours), but the sperm can remain in the cervical mucus for 72 hours. Thus even if the monitor predicts several days of LH surge, the sperm in the mucus can still reach the ovum in case of ovulation, on any one of these days.

However, this is a prospective test and ovulation cannot be confirmed , as increase in LH levels may not always end in ovulation. In patients with elevated LH levels, like in PCOD, the LH levels may remain high, the kits showing positive surge every day of the month.

Ultrasound: Ultrasonography as an investigative tool is basically used for detecting ovulation and timing ovulation. By and large, transvaginal sonography is preferred over the older method of transabdominal sonography. Rarely, wives with vaginismus, or whose husbands have erectile dysfunction or premature ejaculation may find transvaginal sonography painful. In such patients, abdominal sonography may be needed to monitor ovulation.

Assessment of follicles: A baseline scan should be done on day 3-5 of the cycle, to rule out ovarian cysts or persisting corpus luteal cysts from the previous cycle. If a cyst is detected, it would be apt to commence ovarian stimulation only after the patient has had another spontaneous menstrual bleed, which indicates that the endogenous secretion of ovarian hormones has returned to baseline levels. This can be corroborated by the finding of a thin endometrial lining (less 5mm). A baseline scan also can rule out the presence of hydrosalpinges,or submucous fibroids.

The preovulatory follicle grows at a rate of 2-3 mm per day and is 17-25mm at the time of ovulation. Inner diameter of the follicle is measured, in 2 dimensions,Anteroposterior and longitudinal, and the mean taken.

Pregnancy is associated with follicles of larger size at the time of ovulation are usually those greater than 20mm. Largest diameter of the preovulatory follicle is 16-18mm in normal or clomiphene stimulated cycles.

Ultrasound features of ovulation are:

• Reduction in size of the follicle.
• Loss of definition of the folllicular wall.
• Presence of fluid in the pouch of Douglas .
• Multiple echoes in the follicle.
• Change in texture of endometrium.

AEvaluation of endometrium: The sonographic appearance of the endometrium may reflect an adequately receptive tissue and may be related to the success or failure to achieve pregnancy. Endometrial thickness, measured in the plane through the central longitudinal axis of the uterus between the interfaces of the endometrium and myometrium represents the estrogenic activity of the uterus. In the normal cycle, the endometrial thickness ranges from 6-12mm in the late follicular phase and is usually 10-12mm at around the time of ovulation. Periovulatory endometrium has a characteristically three line pattern. The middle layer represents the lumen of the endometrial cavity. The mucus in the lumen makes the cavity echogenic, represented as the middle line. A thin or homogenous endometrium in the pre-ovulatory phase may be associated with poor fertility outcome. Endometrium becomes hyperechoic in the luteal phase.

Colour Doppler sonography in infertility: Poor uterine flow is a cause for infertility7. Measuring uterine bloodflow using resistance index and pulsatility index In the uterine artery has been useful in predicting success in IVF cycles. Sustained diastolic flow in the uterine artery during early and midsecretory phase is associated with a high chance of success in IVF cycles8. Women with poor uterine perfusion could have their embryos preserved for transfer at a later date, when their endometrial receptivity is better.

Endocrine profile:

Endocrine profile is optimally performed during the first 3 days of the cycle. The initial workup should include measurement of thyroid stimulating hormone, prolactin, and cycle day 3 FSH and estradiol levels.
Thyroid disease is found very commonly in reproductive age women and should be assessed by doing a Thyroid Stimulation test,(TSH) which is the most sensitive test of thyroid function- an elevation suggesting hypothyroidism. Hypothyroidism can also elevate prolactin levels.
Women with hyperandrogenism should in addition undergo determination of testosterone, dehydroepiandrosterone sulphate (DHEAS), and 17- hydroxyprogesterone (17OHP) levels. Women with PCOS should have a fasting glucose or 2-hour glucose tolerance test. Some workers use glucose to insulin ratio or simply insulin level to gauge the degree of insulin resistance.

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Tests for Ovarian reserve:

In every woman, there is a resting follicle pool, which represents the ovarian reserve, from which follicles will be recruit ed for maturation. The term “ovarian reserve” refers to a woman’s current supply of oocytes and is associated with reproductive potential. A diminished ovarian reserve greatly decreases a patient’s chances for conception. Abnormal results may predict a lower pregnancy rate, but the possibility of pregnancy cannot be totally ruled out. Ovarian reserve can be assessed by Biochemical tests, Dynamic tests, Sonography and Ovarian biopsy4.

Biochemical tests: FSH: Basal (Day 3) FSH levels indicate ovarian responsiveness. An FSH level>15IU/ml indicates that ovarian activity is minimal. Estradiol: In older women, a more advanced follicular recruitment by cycle day 3 results in high serum estradiol concentrations in the early follicular phase. Basal levels of Estradiol >80pg/ml is associated with higher cancellation rates in IVF. Inhibin: Inhibin is a polypeptide produced by granulose cells of the ovary. Inhibin levels below 45pg/ml demonstrated a poorer response to ovulation induction in ART cycles. Serum Mullerian hormone (AMH): AMH is produced by granulosa cells and it regulates the transition from resting primordial follicles into growing follicles. Levels decline with advancing female age. The advantage is that levels do not fluctuate with menstrual cycle.

Dynamic tests for ovarian reserve:

Clomiphene challenge test: Clomiphene is administered at the oral dose of 100mg between days 5 and 9 and FSH levels measured twice, once on the 2ND and 3rd day and again on the 9-11th day. A total FSH level >26IU indicates poor ovarian reserve. However, basal FSH levels have been found to correlate better than clomiphene challenge test to know ovarian reserve.
Exogenous FSH Ovarian Reserve test (EFORT): In this test, following the measurement of basal FSH and estradiol levels, estradiol respose 24 hours following a 300IU FSH injection on day 3 is determined. However, it is a costly test and therefore, not routinely used.

Ultrasonographic markers:

Colour Doppler sonography in ART: Ovarian blood flow, Endometrial blood flow, etc can be assessed with colour Doppler. Good flow indicates good endometrial receptivity. If endometrium is non receptive as per Doppler studies, in ART cycles, precious embryos can be stored till another cycle, where the endometrium has been made receptive.

Tests to assess tubal patency: All patients who seek evaluation of fertility need to have their tubes evaluated at some point of time. Even patients with obvious anovulation or azoospermia, will need tubal evaluation, if pregnancy is not achieved after treatment for a few cycles. Patients with prior pelvic inflammatory disease, sexually transmitted diseases such as gonorrhoea or Chlamydia trachomatis, or a history of septic abortions are most likely to have tubal disease. Patients with positive antichlamydial antibodies are likely candidates for tubal infertility.

Hysterosalpingography :

Hysterosalpingography involves the X-ray imaging of the pelvis while a contrast medium is injected into the uterus through a cannula positioned in the cervical canal. The uterine cavity and tubes can be imaged in real time and the spill of the radioactive medium into the pelvis noted. X-rays are taken while the dye passes through the uterus and after it spills into the pelvis . Cannulas used: In India, either metal cannulae that can be screwed into the cervical canal, or balloon catheters that are passed into the uterine cavity itself are used. Contrast medium:A water soluble medium is usually used and will be absorbed after an hour. Sometimes the cause of an apparent blockage is a mucus plug, which might be flushed through the tube by the contrast medium. Thus there are reports of an increased chance of pregnancy in the 2 or 3 months that follow either an HSG.

Q: If endometrial sampling is normal, what should be the first line of management?

A: In the perimenopausal age, anovulatory bleeding is more likely to be the cause of DUB. This has to be tackled with progestogens or oral contraceptive pills as first line of management. In hypertensive and diabetic patients, oral contraceptives with high dose oestrogen may be harmful. Some patients cannot tolerate hormones. Some patients may not respond to hormone treatment or may take treatment irregularly leading to more irregularities in bleeding. Alternative medical treatment methods or conservative surgical measures have to be resorted to in such patients.

Derangements in the local haemostatic mechanism may cause ovulatory bleeding . Antiprostaglandins like Mefenamic acid and antifibrinolytic agents like Tranexamic acid may be useful in the management of such patients. Patients with ovulatory DUB must be evaluated for intracavitary uterine pathology (with SIS or hysteroscopy), since hormonal dysfunction is not the likely cause of bleeding. Intracavitatory causes like endometrial polyps or submucous fibroids have to be ruled out. If such pathology is diagnosed, there is an option of hysteroscopic resection in centres with facilities for such procedures.

Timing: An HSG should be performed optimally within 10 days of a menstrual period when there should be no risk of a pregnancy. The HSG can be uncomfortable, especially if there is either tubal spasm or a tubal obstruction. Tubal spasm can occur and antispasmodics have been employed. A slow injection of dye can prevent tubal spasm.

Antibiotic prophylaxis: Routine antibiotic prophylaxis is recommended with a 3-5 day course of doxycyclin to treat silent pelvic infection, particularly, chlamydia.

Characteristic findings: The cavity of the body of the uterus is usually triangular, sometimes with a concave or convex fundus.

• Filling defects that are in the uterine cavity can sometimes be due to air bubbles. These defects have to be distinguished from endometrial polyps.
• Irregular filling defects could be caused by intrauterine adhesions, which could be a cause of recurrent abortions.
• Submucous fibroids can show as filling defects.
• Partial or complete septum can be diagnosed on HSG by seeing the contrast free longitudinal filling defect in the centre.
• Partial or complete septum can be diagnosed on HSG by seeing the contrast free longitudinal filling defect in the centre.
• Pelvic tuberculous may lead to calcification, which can be seen on an X-ray.

Sonosalpingography2

An 8f foley’s urinary catheter is inserted into the uterine cavity and 2.5-3.0ml saline is injected into the bulb to stabilise it. While concentrating on scanning the space between the cornu and the ovary on either side, 20ml saline along with air is pushed through the Foleys catheter . Patent tubes distend with the mixture of agitated saline and air-bubbles gush past the ovary. As an extension,in a procedure called hydrogynecography, after giving Atropine and antispasmodics orally half an hour before, 300 ml of normal saline is injected to flood the pelvis, delineating all sorts of adhesions, flimsy and dense. However, one has to be sure there is no active pelvic infection before doing the procedure. Ultrasound contrast hysterosalpingography : It is now possible to perform an HSG using ultrasonography and an ultrasound contrast medium which contains galactose microparicles(“Echovist”) and is therefore free of the possible risks of radiation. Caution: Both Sonosalpingogram and hysterosalpingography should not be performed in the presence of active pelvic infection. These investigations are contraindicated in the presence of adnexal masses.

Advanntages of hysterosalpingography:

• It gives a permanent pictorial record of the findings.
• Tubal pathologies like hydrosalpinx and beaded tubes can be seen more specifically
• Uterine pathologies like unicornuate uterus, septate uterus/bicornuate uterus,T-shaped uterus, etc, are better delineated on hysterosalpingogram.

Disadvantages:

• In the presence of air bubbles, intrauterine adhesions cannot be diagnosed conclusively.

Advantages of Sonosalpingogram:

Since most infertility clinics have an ultrasound machine in their clinic, with just an addition of facilities to detect tubal patency, tubal patency test can be done immediately with the evaluation of infertility. Additional findings like fibroids, uterine polyps,etc can be diagnosed more accurately on sonosalpingogram.

Disadvantage:

• In hydrosalpinx, tubal flow may give a false impression of tubal patency.
• Expertise in ultrasonography has a higher learning curve compared to HSG
• Spill of fluid has to be detected immediately, while the liquid flows out. However, the site of the block cannot be pinpointed, as cornual, fimbrial, etc. This can affect planning of management. Cornual blocks are better managed hysteroscopically, while fimbrial blocks or midtubal blocks due to external adhesions need laparoscopic management.

Laparoscopy and hysteroscopy:

Laparoscopy is not done as an initial investigative tool, unless there are obvious stigmata of endometriosis clinically. Hysteroscopy should always accompany laparoscopy for infertility, as many findings like incidental polyps can be detected on hysteroscopy. Laparoscopy can ascertain tubal patency, presence of adhesions or endometriosis which can alter the tubo-ovarian anatomy. Peri-hepatic adhesions, pathognomonic of chlamydial infection, should be looked for in all laparoscopies for infertility. Laparoscopy is usually resorted to after many failed cycles of treatment of infertility. Laparoscopy should always be done in centres where operative corrections are possible in cases where there are detrimental anatomical factors for infertility.

Cervical factor of infertility and Immune factor of infertility :

Cervical receptivity was tested by doing the post coital test, where live sperms were quantified in the cervical mucus after intercourse. However, this test is no longer performed. Presence of antisperm antibodies in the serum of the infertile couple and in the cervical mucus also used to be looked for, but the utility of this test is currently being questioned.

Initial evaluation of the male: The simplest evaluation in male infertility is the semen evaluation. Semen should be collected after two days abstinence into a wide bore container and preferably examined within half an hour of collection. If the semen parameters are abnormal, the male should be examined to see if the testes are of normal size and for the presence of varicocoele. Grossly big varicocoeles should undergo surgical correction. If the count is very low and if the hair growth on the face is low there could be Klinefelter-s syndrome. Estimation of serum FSH and Testosterone could be helpful in planning treatment in patients with very low counts.

Volume: The mean normal volume suggests incomplete sample collection. But if repeated semen analyses shows low volume, it is abnormal. If it is less than 0.5ml,and there are no sperms in the ejaculate, one must think in terms of retrograde ejaculation and examine the urine for sperms immediately after ejaculation. If the volume is low and the ejaculate contains sperms, a post coital test should be done to see if adequate sperms reach the cervical mucus. If not, the couple may benefit from intrauterine insemination with husband-s sperms.

Sperm density: Sperm density should be 20 million or more sperm per milliliter. Normally 40% or more sperms are motile. Azoospermia is defined as absence of spermatozoa in the ejaculate. The ananlysis should be repeated twice to confirm the diagnosis. Motility is a more important parameter of sperm function compared to count.

Treatment of male infertility:

General advice: Men with oligospermia should be advised to abstain from alcohol and smoking as both have deleterious effects on spermatogenesis. Heat can have a detrimental effect and sitting hot baths and wearing tight-fitting underpants and trousers should be avoided. Diabetes, chronic renal failure or thyrotoxicosis should be looked for and treated. As simple an acute illness as a streptococcal sore throat requiring penicillin can result in a temporary azoospermia. It is therefore important to note any such illness in the past 3 months when reviewing the results of semen analyses.

Frequency of intercourse: The concentration of motile sperm in sequential ejaculates decreases in normospermic men. But men with oligozoospermia or asthenozoospermia appear to benefit from sequential ejaculations and they should be advised to have intercourse at least daily, if not twice daily, around the time of ovulation rather than follow the usual advice given to normospermic men of alternate day intercourse.

Medical therapy: Pus-cells in the semen should be treated with doxycyclin(100mg/day)_ or ciprofloxacin (500mg/day) for 4-6 weeks. If the condition recurs in 3 months-s time,long-term antibiotic therapy may be tried until a pregnancy has been achieved.

Low motility: Low doses of oral androgens,e.g. fluoxymesterone,10mg twice a week for at least 6 weeks, may be helpful in some cases. The improvement usually last for several months and treatment may be repeated. Injections of hCG(5000IU once or twice a week) have also been used to enhance motility.

Low count: In men with hypogonadotropic hypogonadism as proved by low or low normal range of FSH LH and Testosterone values will benefit from gonadotropin therapy. Treatment with either hCG alone(In the dose mentioned above) or hMG one amp.IM on alternate days for 45 injections combined with hCG will benefit the patient. The effect of Clomiphene citrate (in the dose of 25mg day for 3 months) in idiopathic oligoasthenospermia is controversial. A Cochrane review has mentioned that the endocrine parameters may be improved with Clomiphene,but the reviewers are not convinced about it-s effect in improving pregnancy rates. Other studies have found it to be quite useful. Testosterone administration may be ineffective and may be contraceptive.

Use of anti-oxidants: Reactive oxygen species are highly reactive oxidising agents belonging to the class of free radicals. Excessive production of ROS in semen can overwhelm the antioxidant defense mechanisms of spermatozoa and seminal plasma causing oxidative stress. Antioxidants are a broad group of compounds that destroy free radicals in the body, thereby protecting against oxidative damage to cells.

• Zinc in the dose of 66 mg along with folic acid 5mg per day, was shown to increase sperm count in a randomised controlled study. Biological zinc administratio was shown to improve sperm count in patients with chronic prostatitis in another study.
• Scott et al concluded in a double blind placebo controlled study that men with placebo controlled study that men with low sperm motility could improve their sperm motility with selenium in the dose of 100umg/day or selenium with vitaminA 1mg, with vitamin C 10mg with vitamin D 15mg for 3 months.
• Carnitine: :L-Carnitine and acetyl-L carnitine are highly concentrated in the epididymis and play a crucial role in sperm metabolism and maturation. They are related to sperm motility and have antioxidant properties. Carnitine enhances sperm energy production and therefore, motility. In a multicentre study of 100 patients treated with 3 gma carnitine for 4 months significant improvement in sperm motility was reported by Lewin et al, particularly in patients with idiopathic asthenospermis.
• Con-enzyme Q10: Balercia et al used Co-enzyme Q10 in the dose of 200mg twice daily for 6 months in patients with sperm count >20mill/ml with forward motility less than 50% with good results. Other than this, there are not many clinical reports on this antioxidant. In India, many pharmaceutical companies market this drug in the dose of 30-50 mg/day for asthenospermia. We still do not know if it is of any use, especially in this dose.
• Glutathione: Injectable Glutathione 600mg IM on alternate days for a period of 2 months in a study by Lenzi et al resulted in significant improvements in overall motility, progressive motility , velocity, linearity and amplitude of lateral head displacement. Oral Glutathione is of limited value in male infertility.
• Lycopene: Gupta and Kumar treated 30 infertile men with 4 mg lycopene for 3 months and found a significant improvement in sperm counts and motility with no significant changes in sperm morphology. A 20% pregnancy rate was seen during the course of the study.

Surgical treatment:

If a varicocoele is present, it may be ligated. The effect of varicocoel ligation on fertility has been controversial. But if the semen parametres are abnormal and the female factors are either not there or corrected, it is reasonable to get this abnormality corrected, as the presence of varicocele is often associated with a decline in spermatogenesis and testosterone production and elevation in serum FSH concentration.

Treatment of female infertility

The five cardinal causes of female infertility, viz: ovulatory dysfunction, tubal blocks, cervical factors , endometriosis and immunological infertility should be evaluated and treated. Usually, a patient comes with multiple causes and each cause should be evaluated and treated. Quite often, the clinician falls into the pitfall of trying to treat one cause of infertility, and forgetting other factors which may be co-existing. For example, if a woman has irregular periods, caused by ovulatory dysfunction, the onus of treatment my be in trying to treat anovulation and co-existing vaginal infections or tubal blocks may get overlooked. Thus, it is necessary to try and look at each factor every time the patient visits the doctor.

Evaluation and treatment of tubal infertility:

The old method of diagnosing tubal block was to do a tube testing where air is injected into the uterine cavity. Patency is confirmed by hearing a gurgling sound in the lower abdomen as heard through a stethescope.This has been found to be an inaccurate method, but is still practised in many centres in India, where patients cannot afford any costlier methods.

Hysterosalpingogram; A radio opaque dye is injected into the uterus and an X-ray taken.The uterus,tube and spillage of dye into the abdomen can be seen. Anatomical abnormalities of the uterus can be evaluated along with any blocks in the tubes. The procedure can be painful. The author sometimes does it under I-V Ketamine in the operation theatre under C-Arm control, but the films are not as clear as the routine HSG. Sonosalpingogram: Under sonographic control, saline is forced into the uterus through a foley-s bulb and the spillage of fluid in the pouch of Douglas evaluated. Additional information like fibroid uterus can be picked up, but the tube cannot be delineated properly.

Laparoscopy: Ringer lactate with or without the dye methylene blue is injected into the uterus and the spillage of dye into the abdomen noted. There is the added advantage of the chance for evaluating the entire pelvis and correcting any adhesions or endometriotic patches. The disadvantage is the necessity for anaesthesia and the increased cost in private set up. Many types of intrauterine catheters have come iin the market for the release of proximal tubal obstruction. Using cannulae and guide wires, proximal tubal block can be negotiated under sonographic control, fluoroscopic control or through the hysteroscope. The patient should be aggressively managed to achieve a pregnancy soon after as many of the blocks removed in this fashion tends to recur after some time.

Laparoscopy in infertility: Indications: In the 1980-s there was a tendency to post all infertile patients for routine laparoscopy. However, considering the low yield of positive findings when such an approach is taken, and the morbidity involved in anesthesia, we do not routinely advocate laparoscopy for all infertile patients. If the patient gives history of congestive dysmenorrhoea and there is nodularity in the pouch of Douglas, she probable is suffering from external endometriosis. In such cases, laparoscopic evaluation should not be delayed and should be done as soon as the patient presents herself to the clinician. For patients in whom uterus appears normal on pelvic examination, laparoscopy could be delayed for a few cycles. For patients with polycystic ovarian disease, where treatment with clomiphene citrate has failed, before going in for treatment with gonadotropins, laparoscopic ovarian drilling would be a better option. It is not only cost effective, but also gives an opportunity to evaluate the rest of the pelvis. If medical treatment of infertility does not yield results after five or six months laparoscopic evaluation should be done as it will detect asymptotic adhesions and endometriotic patches. In patients undergoing artificial insemination with donor-s semen (AID) if there is no pregnancy after 3-4 attempts a laparoscopic assessment should be done before trying further inseminations.

Cervical factor of infertility: Cervical factors account for about 10% of the cases of female infertility. Cervical factor can be detected by a post-coital test. Postcoital test or PCT should be done in the preovulatory phase of the cycle. The couple should abstain from intercourse for 2 days prior to the test, since it takes 48 hours to replete sperm reserves. It could be done between 1-12 hours after intercourse. A normal PCT is defined as good quality cervical mucus and 10 or more progressively motile sperm per hpf. The mucus component should also be evaluated. Cervical mucus acts like a ladder on which the sperm climbs up to reach the uterus It is usually clear, mucoid and copious in midcycle . Lack of adequate cervical mucus or hostility in the cervical mucus can lead to infertility.

When the quality of mucus is poor, the cause could be infection. Infection with Chlamydia trachomatis can be detected with cervical mucus cultures. In India, where health care is not insured, the usual practice is to give empiric therapy with Doxycyclin 100mg daily for 7 days in suspected cases. Besides chlamydia other agents, which could cause vaginitis and secondary cervicitis, should be sought for and treated. There could be vagainal mycosis, Trichomoniasis, or gardnerella vaginitis.These should be treated apporopriately as mentioned in the chapter on leucorrhoea. If the culture is negative, or if empiric therapy with antibiotics fail, there could be either estrogen deficiency or to failure of endocervical cells to respond to normal levels of estrogen. Empiric therapy with Estrogen (Ethinyl estradiol, 0.01mg per day on days 6 to 9,increased to 0.02mg per day on days 10-13 of a 28 day cycle), gonadotropins or cryosurgery for cervicitis

An abnormal postcoital test with scant cervical mucus, a poor cervical score, cervical stenosis or an endocervix that is friable and bleeds in response to gentle manipulation may indicate cervical factor with an anatomical basis. When cervical stenosis is suspected, one can try passing a 2-4mm dilator through the cervical os. If it does not pass or passes with difficulty, a true stenosis should be dagnosed. Application of estrogen vaginal cream (Refer to chapter on menopause) twice daily for 3-4 weeks may soften the stenotic cervix and allow the small dilator to pass. Such patients are difficult to treat and may need intrauterine insemination. When the cervix appears friable and causes bleeding on passing a dilator. Cervical varicosities should be suspected. Cryosurgery of the cervix may help.

Intrauterine insemination: Intra Uterine Insemination is one of the simplest procedures among the procedures called the Artificial reproductive technologies or ART. Semen is washed with special media and centrifuged. The motile sperms from the sample is separated and introduced into the uterine cavity along with a little (0.3-0.6ml) media using special intrauterine cannulae. The common indications are cervical factor infertility & male infertility. But it can be performed in any woman with patent tubes, where all other factors of infertility have been treated and she has what can be termed intractable infertility. The ovaries are usually hyperstimulated with clomiphene citrate and gonadotropins to produce a lot of follicles. The ovulation is monitored using ultrasonography on alternate days and insemination is done on the day previous to the day of expected ovulation. Ovulation is timed by giving HCG injections on the day the follicle reaches the size of 18mm on ultrasonography.Ovulation is expected to occur 36 hors later. Pregnancy rates can vary from 16% to 25% and varies from centre to centre. It is high in cervical factor infertility (50%) and low in male factor infertility where husband-s sperms are used for infertility. Patients expect a lot, almost 100% result, when they come for IUI as it is very stressful having to come for serial ultrasonography and to collect semen in an alien atmosphere. Patients should be told that even a newly married couple who are fertile take 3 or 4 months to conceive and even though one makes sure that ovulation, tubal factor, and cervical factor have been taken care of , there still may be failures at the point where the sperm enters the ovum or at implantation.

IVF-ET: IVF-ET is In Vitro Fertilisation and Embryo Transfer. The gametes (ovum and sperm) are taken out of the body and fertilisation done outside the body in vitro. The fertilised embryo is transferred into the uterus. The chance of pregnancy is about 30% in larger units. This procedure was started for patients with blocked tubes, but now the indications have widened to almost all cases of infertility where conventional treatments have failed. The cost of therapy is about Rs.50, 000 to Rs.75, 000 per cycle.

ICSI: Intracytoplasmic sperm injection: In IVF-ET the sperms and ova are incubated together in a petridish and the sperms are expected to penetrate the ova by themselves. As against this, in ICSI, a single sperm is taken into a micropipette and injected directly into the ovum. With this procedure fertilisation rates are higher. It has another advantage that not only men with profound oligospermia(low count) or asthenoteratospermia (low motility with increased number of abnormal forms), but also those with obstructive azoospermia, after microsurgical or direct aspiration of sperm from either the epididymis or testis can be benefitted. Sperms need to be alive, but need not be motile for this procedure.

TESA: Testicular Sperm Aspiration:Sperms are directly taken from the seminiferous tubules and ICSI performed.

PESA: Per Epididymal Sperm Aspiration. Sperms are aspirated from the epididymis and ISCI performed.

Ovum donation: Oocyte donation can be used to treat women with premature ovarian failure of whatever cause and those who do not wish to use their oocytes for genetic reasons. The ovum from a donor is inseminated with the sperm of the patient-s husband and the resultant embryo introduced into the uterus of the infertile woman. As the embryo might genetically be the donor mother-s recently another procedure has been developed. Here the ovum of the infertile woman is taken and the cytoplasm replaced with that of the donor ovum.

Preimplantation diagnosis: In women with repeated pregnancy losses, the embryo is developed in vitro. One of the cells is aspirated and chromosomal study performed to see if the embryo is genetically normal. Embryo transfer is done only if the embryo is normal.

Fibroids

Posted On April 24, 2018 by Dr.Shobhana Mohandas

What are fibroids?

Fibroids are innocuous estrogen dependent benign tumours occurring in the uterus.

What are the symptoms caused by fibroids?

In a large majority of patients, fibroids are asymptomatic, being diagnosed incidentally on ultrasonography, done for some other purpose.Only 20% to 50% of women with myoma are symptomatic (1) .

Menorrhagia. When fibroids are situated in any location near the endometrial cavity, it may increase the surface area of endometrium shed, leading to menorrhagia. It is not the size of the tumour, but its proximity to the endometrium that is important in causing menorrhagia. Dysregulation of local growth factors could also cause vascular abnormalities which could cause abnormal uterine bleeding. (2) Although menorrhagia is the most common manifestation of abnormal uterine bleeding in fibroids, there could be other presentations, like intermenstrual spotting or post coital bleeding, also. Hypermenorrhea may also be enhanced by the presence of an endometritis, which is a frequent histologic finding within the endometrium.

Pelvic pressure: Large tumours could lead to pelvic discomfort, Myomas in the broad ligament may cause unilateral lower abdominal pain, or may cause sciatic nerve pain.

Bladder symptoms: Myomas that compress the bladder can cause urinary symptoms of urgency or increased frequency. There could be other features like,outflow obstruction, and ureteral obstruction with hydronephrosis

How are fibroids diagnosed? Fibroids can be diagnosed by clinical examination, but it is at best, a presumptive diagnosis. An enlarged uterus, irregular in multiple fibroids, firm on palpation, is suggestive. Any mass in the pelvis that moves with the uterus, is suggestive of fibroids, as a differential diagnosis of ovarian masses, which generally do not move with the uterus.

Sonohysterogram may be useful in diagnosing submucosal fibroids. In this procedure, the uterine cavity is filled with saline, before doing sonography. This s delineates small masses near the endometrium, which may otherwise have been missed on ordinary ultrasonogram.

Hysteroscopy is useful in diagnosing submucous myomas, but it is invasive and is probably useful only if a concomitant surgical procedure of hysteroscopic myomectomy is planned on diagnosis.

Myomectomy in infertile women: The impact of leiomyomata on reproduction is not clear due to the paucity of well controlled studies.(15). Intracavitary and large submucosal leiomyomata are most likely causally related to infertility. . Removal of submucosal and large intramural leiomyomata has been associated with improved outcome in infertile women undergoing assisted reproductive technologies such as in vitro fertilization(8). If the clinical problem is repeated miscarriage,preterm labor, or intrauterine growth restriction or the leiomyomata are large,preconceptional removal of intramural leiomyomata may be appropriate. All patients with myomas should be educated about specific risks during pregnancy, including miscarriage, pelvic pain,premature labor, and postpartum hemorrhage. In the absence of other causes of infertility or after the unsuccessful treatment of other infertility factors, it is reasonable to suggest myomectomy as an option. Most patients can be treated without surgery. There is ultrasonographic evidence of recurrence in 25% to 51% of patients, and as many as 10% require a second major operative procedure (9). According to one study(29), most recurrences occur10-30 months following original surgery. Myomectomy removes only the fibroids, the genetic predisposition for the formation of fibroids remaining intact.

Asymptomatic fibroids: Fibroids regress after menopause and should be left alone if asymptomatic. Hormone replacement therapy with estrogen can be given in indicated cases even if fibroids are present as the estrogen content in hormone replacement therapy is too small to cause any change in the size of fibroids(17). However there are a lot of options like Alendronate phytoestrogens, etc which could also be considered in place of estrogen in menopausal women requiring estrogen replacement therapy.

Fibroids in pregnancy: A fibroid diagnosed during pregnancy should be managed expectantly. There is an increased chance of red degeneration of fibroid which may lead to pain and tenderness on palpation. These symptoms should be managed symptomatically with rest and analgesics. During second and third trimester the fibroid flattens out along the walls of the uterus and are usually less symptomatic. The patient should be given a warning of increased chance of abortion or premature delivery. During labour, unless there is obstruction to the passages, there is no indication for LSCS. In case an LSCS has to be done,the classical teaching is not to touch a fibroid during the surgery, but a few workers have tried myomectomy succesfully at LSCS using a tourniquet around the uterine arteries to reduce blood loss

How can you diagnose if the fibroid like lesion on imaging modalities is a fibrosarcoma? Rapid growth of the tumour is indicative of a malignant lesion. Any enlarged uterus in a postmenopausal woman not known previously to have fibroids should alert one to the possibility of fibrosarcoma. MRI can show irregular margins in fibrosarcoma, instead of regular margins in ultrasonography. There is evidence that combining dynamic MRI (i.e., MRI enhanced by gadopentetate dimeglumine) and measurement of serum lactate dehydrogenase levels is useful in distinguishing leiomyosarcoma from benign fibroid tumors.

What happens to fibroids after menopause? Myomas commonly regress after menopause, which is accompanied with an atrophic endometrium and cessation of uterine bleeding. Postmenopausal women on hormone therapy, however, may experience persistence of abnormal uterine bleeding. It has been reported that postmenopausal women with submucosal myomas using hormone therapy experience a twofold increase in the incidence of abnormal bleeding as compared with the women with no submucosal myomas.

Which are the fibroids that need be treated? Only fibroids which cause symptoms need positive treatment. Asymptomatic fibroids seen incidentally on ultrasound need not be treated if they are small in size. Studies of myoma treatments

have found no significant change in uterine size or myoma volume over 6–12 months of follow-up in placebo arms . A nonrandomized study of women who had uterine size of R8 weeks and who chose hysterectomy or watchful waiting found that 77% of women choosing observation

develop new symptoms and, after menopause, bleeding stops and myomas decrease in size (3) When the size of the uterus is more than 12 weeks, even asymptomatic fibroids are usually tackled, as they interfere with imaging of ovaries due to the size of the tumour and thus early ovarian lesions may be missed. Similarly, fibroids, which due to their proximity to the ureter cause hydronephrosis need be tackled.

What are the medical options available in a patient with fibroid? Gonadotropin releasing hormone agonists(GnRH agonists) are agents which increase the production of gonadotropins(FSH & LH) . This inhibits production of estrogen, creating a state of pseudomenopause. The fibroids shrink while on treatment and come back to the original size once the administration is stopped. The analogues can thus temporarily reduce the size of the fibroids.

Daily subcutaneous (SC) injections of GnRH-a have been found to decrease uterine size from 13.8 weeks to 9.5 weeks after 8 weeks of treatment . Monthly GnRH-a, given for 6 months, reduces myoma volume by 30%, non-myoma volume by 43%, and total uterine volume by 35% (15). Reduction

to pretreatment levels within 4–6 months . However, 64% of women in one study remained asymptomatic 8–12 months after treatment. Dose: Inj Goserline acetate 3.5mg subcut. Every month.After 3 months the size of the fibroid will reduce by 40-50%. Inj.triptorelin 3.73mg every 4 weeks. Indication: To buy time till the actual surgery is undertaken, meanwhile treating anaemia, or some medical condition. It can also be used to reduce the size of the fibroids so that an abdominal surgery could be converted to a vaginal,laparoscopic or hysteroscopic procedure(19). The size and symptoms recur on stopping treatment. Thus treatment with this group of drugs is reserved for reducing the size of the tumour to facilitate surgery, or to temporarily prolong the date of surgery while keeping the patient symptom free from fibroids.

The drug Mifepristone or RU486, initially developed for Medical termination of pregnancy has also shown to shrink fibroids. However, Because of the P-blocking action of RU-486, endometrial hyperplasia may result from unopposed exposure of the endometriumto estrogen. There are no large studies on the use of the drug in fibroids and it is not known how long it will be before the fibroids recur. Symptoms of fibroid, viz: Menorrhagia can be controlled with progesterone containing intrauterine devices. Other haemostatic drugs can be used to control menorrhagia, but the size of the fibroids will remain same. Medical therapy in a perimenopausal woman may be instituted, in the hope that the woman may attain menopause soon and that the disease can be kept quiet till then. However, the age of onset of menopause being uncertain, this indefinite period of medical treatment may be bothersome to some patients.

Can a woman with a fibroid take oral contraceptive pills? Studies have found no evidence that low-dose contraceptives cause the growth of uterine fibroid tumors; thus, these tumors are not a contraindication to the use of these contraceptives(2)

Can a woman with asymptomatic fibroids take hormone replacement therapy if she is bothered too much by hot flashes? Fibroids regress after menopause and should be left alone if asymptomatic. Hormone replacement therapy with estrogen can be given in indicated cases even if fibroids are present as the estrogen content in hormone replacement therapy is too small to cause any change in the size of fibroids(4). However, as discussed earlier, the incidence of abnormal uterine bleeding is higher in these women and other options like Alendronate phytoestrogens, etc which could also be considered in place of estrogen in menopausal women requiring estrogen replacement therapy.

What is the role of progesterone releasing IUD’s in the treatment of fibroids? Levonorgestrel-releasing intrauterine system (LNG IUS) are popularly used in women with menorrhagia needing contraception, as they locally release the progestogen Levonorgestrel, reducing menorrhagia, without the systemic side effects of progesterone therapy. Patients with LNG IUS must expect occasional irregular spotting in the first 6 months of insertion and learn not to bother about it.

In a study, women with uterine size less than 12 weeks size were treated with LNG IUS. They found that the LNG IUS diminishes menstrual blood loss, improves iron deficiency anemia, and reduces uterine and leiomyoma size during the first year of use.(5). A profound decrease in blood loss was seen to occur in the first 3 months of use. Women with distorsion of the uterine cavity are not good candidates for this treatment. The mechanism of shrinkage of a uterus, enlarged by either adenomyosis or leiomyoma treated with intrauterine levonorgestrel, is unknown. It could be due to increased impedence in uterine arteries caused by progesterone, or by inhibition of IGF-I by IGF-binding protein-1 following long term exposure to Levonorgestrel. Insulin-like endometrial growth factor-I (IGF-I) is believed to act as a mediator of E2 action in the growth of uterine myoma and therefore, inhibiting it reduces E2 action.

What is uterine artery embolisation? Uterine artery embolisation is a nonsurgical treatment for the treatment of fibroids. It can be done only in centres with facilities for angiographic studies. The uterine artery is cannulated via the right femoral artery under fluoroscopic control and obstructive particles, usually polyvinyl alcohol are injected into the uterine artery. Then the cannula is steered into the aorta and from there into the left uterine artery which is also cannulated and obstructive particles injected. The blood supply to the fibroids is thus curtailed. They undergo degeneration. The advantage is that all the fibroids can be treated simultaneously and the procedure can be completed under sedation.

Postprocedural pain, the result of hypoxia, anaerobic metabolism, and formation of lactic acid, usually requires 1 night of pain management in the hospital. Most women are discharged the next day and may need to take nonsteroidal anti-inflammatory medications for 1–2 weeks. Many women can return to normal activity within 1–3 weeks, although about 5%–10% of women have pain for >2 weeks. About

10% of women will require readmission to the hospital for postembolization syndrome, which may be characterized by diffuse abdominal pain, nausea, vomiting, low-grade fever,malaise, anorexia, and leucocytosis and pelvic sepsis have been reported in some cases after this procedure. Tropeano et al found found no evidence for fibroid embolization advancing the timing of menopause in women before the age of 45 years. Premature ovarian failure and vaginal discharge are also known after effects in some patients.

pedunculated myomas, recent GnRH-a treatment or previous iliac or uterine artery occlusion, or postmenopausal status. Women with very large multiple fibroids are not good candidates for this modality of treatment. Although very rare, complications of UAE may necessitate life-saving hysterectomy. Therefore, women who would not accept hysterectomy under any circumstance should not undergo UAE.

What is MRI guided ultrasound treatment of fibroids? MRI-guided focused ultrasound (MRgFUS) is a noninvasive method of thermal ablation, which, through MRI guidance, allows for 3D treatment planning and feedback of temperature deposition in the area to be treated.This is a non-invasive treatment option for patients suffering from symptomatic fibroids. It does not require anaesthesia and Women undergoing this treatment do not require a hospital stay, and can usually return to work and full resumption of normal activities within a day or two of the procedure. Fibroid shrinkage can be seen by 6 months. Most patients benefit from it and symptomatic relief is sustained for two plus years. Up to 16-20% of patient will require an additional treatment.

What are the surgical options available for fibroids?

Surgical treatment options currently include abdominal myomectomy; laparoscopic myomectomy; hysteroscopic myomectomy; endometrial ablation; and abdominal, vaginal, and laparoscopic hysterectomy. Serious medical conditions, such as severe anemia or ureteral obstruction, often need to be addressed surgically. Surgical intervention may also be indicated in women who have myomas that are associated with menorrhagia, pelvic pain or pressure, or urinary frequency or incontinence that compromises quality of life. Women with large symptomatic myomas who have completed childbearing are most often recommended to have a hysterectomy.

When is myomectomy offered to a perimenopausal woman with fibroids? What are the ways in which it can be done? In a woman with fibroids, who wants to preserve her uterus,myomectomy is the only option.. Case–controlled studies suggest that there may be less risk of intraoperative injury with myomectomy when compared with hysterectomy. Myomectomy through a laparotomy incision is the preferred route for the ordinary surgeon. However, a large scar on the abdomen may necessitate long periods of absence from work, as the woman cannot lift heavy objects, due to fear of developing a hernia.

Laparoscopic Myomectomy with endosuturing is safe in the hands of an experienced endoscopic surgeons. When the number of fibroids are many, laparoscopic route of tackling them, may lead to missing deep seated fibroids, since the tactile sensation is not permissible in the laparoscopic route. Otherwise, laparoscopic myomectomy may be the preferred route if the surgeon is experienced.

What is the role of hysterectomy in fibroids? Women who have completed their families, with intractable symptoms that affect their lives and who have not been helped by other therapies may benefit from hysterectomy. Laparoscopic assisted vaginal hysterectomy or vaginal hysterectomy offer less morbidity for the patient post-operatively.

References:

• BukulmezO et al: Clinical features of Myomas: Obstet Gynecol Clin N Am 33 (2006) 69– 84.
• EvansP.et al: Uterine fibroid tumours: diagnosis and treatment: American Family Physician Web site at www.aafp.org/afp. Copyright© 2007 American Academy of Family Physicians.
• KothariS et al; Risk assessment of the menopausal patient. Medical Clinics of North America Volume 83 Number 6 November 1999.
• Sankaran S, Medical management of fibrods: Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 22, No. 4, pp. 655–676, 2008.
• EisingerS H et al: Open-label study of ultra low-dose mifepristone for the treatment of uterineLeiomyomata: European Journal of Obstetrics & Gynecology and Reproductive Biology 146 (2009) 215–218.
• Stewart .EA et al: Clinical outcomes of focused ultrasound energy for the treatment of uterine fibroids: Fertility and Sterility_ Vol. 85, No. 1, January 2006.
• Morita Y et al; Non-invasive magnetic resonance imaging-guided focused ultrasound treatment for uterine fibroids – early experience: European Journal of Obstetrics & Gynecology and Reproductive Biology 139 (2008) 199–203.
• Feng C et al: Improved quality of life is partly explained by fewer symptoms after treatment of fibroids with mifepristone.

Ovarain Cyst

Posted On April 6, 2018 by Dr.Shobhana Mohandas

Ovarian cysts are quite often functional cystic spaces in the ovary. But sometimes they could be endometriomas or if there are solid areas present, may harbour malignancy. Current management principles of ovarian cysts are outlined below:

Asymptomatic unilateral cysts in the adolescent:

Unilateral ovarian cysts in the adolesent with pain: If the patient has persistent pain accompanied by autonomic symptoms like vomiting, one has to think in terms of a twist in the ovarian cyst. Identification of the twisted vascular pedicle through ultrasonography is suggestive of ovarian torsion, and color Doppler sonography could be helpful in predicting the viability of adnexal structures by depicting blood flow within the twisted vascular pedicle. A diagnosis of twisted ovarian cyst warrants surgery. During surgery, a bluish colour in the cyst on initial inspection is not confirmatory of gangrene in the ovary. In some cases, untwisting of the cyst may bring back vascularity to the ovary, which may then regain its original colour (8). A cystectomy may now be done. In case the ovary has undergone gangrene, adnexectomy is the only option. Laparoscopic techniques if available are kindest to the patient in these circumstances. If the patient has symptoms of endometriosis like congestive dysmenorrhoea, an endometrioma has to be suspected. In India, Ultrasonography in this age group is usually done with transabdominal probes, which may be inadequate to distinguish a simple cyst from an endometrioma. Endometriomas should be managed by laparoscopic ovarian cystectomy and coagulation of any other endometriotic implants.

Unilateral unilocular simple ovarian cyst in the reproductive age group: In this age group, a vaginal sonography is possible, and in expert hands, a differentiation can be be made between a simple cyst and an endometrioma, the latter showing internal echoes. A simple cyst could be observed for 3 months. If it does not disappear, the diagnosis of a benign ovarian neoplasm like serous or mucinous cystadenoma should be made. If the patient has completed her family, salpingo-oophorectomy could be done on the affected side, instead of cystectomy. Hysterectomy is a much more complicated procedure compared to ovarian cystectomy and is not warranted for treatment of benign neoplastic cysts. Endometriomas in this age group should be tackled taking in to consideration the findings in the rest of the abdomen. If there is extensive endometriosis in the pelvis, it may be prudent to do a hysterectomy with bilateral oophorectomy if the patient has completed her family. She should subsequently be put on hormone replacement therapy to prevent symptoms of oestrogen deficiency.

Ovarian cysts with solid areas in the adolescent age group: The presence of solid areas in the cyst makes the mass a complex mass. Complex masses should alert one to the possibility of neoplasms, benign or malignant. However, the mere presence of solid areas is not diagnostic of neoplasm. Complex cysts could be corpus luteum cyst, hemorrhagic cyst, ectopic pregnancy, ovarian torsion, tubo-ovarian abscess or appendiceal abscess,

endometrioma, or either benign or malignant neoplasm. Assuming that pregnancy, torsion, and infectious causes are excluded, a repeat sonogram should be performed after the next menses. Patients with pain may need to be scanned at a shorter interval. Hemorrhagic cysts can have a variable sonographic appearance that commonly changes over a period of days. If the mass decreases in size on ultrasound follow-up, it can continued to be followed. If the cyst persists for longer than two or three cycles, then neoplasm is more likely, and surgical evaluation is indicated. As with simple cysts, increase in size, pain, or mass effect should prompt earlier surgical intervention. Malignancy should be suspected on ultrasonography in some cases by observing the thickness of the capsule, shadowing, echogenecity, etc. Even if the ovarian cyst is palpable over the umbilicus, In the author’s experience, if an ovarian cyst is palpable above the umbilicus, unilocular and filled with clear fluid as shown on Ultrasound, it is possible to select a site on the abdomen where the cyst is looking tense and adjacent to the abdominal wall and put a needle in and aspirate the fluid through suction. Now it becomes easier to put in the laparoscope and salpingooophorectomy/cystectomy becomes possible. In a large cyst, the thinner portion of the cyst is first excised. This makes it easier to delineate the ovarian wall from the cyst wall. A cystectomy can now be performed. However, in a huge ovarian cyst, the functional ovarian tissue left behind after such a procedure is very less.

Unilateral cysts in the menopausal woman: If the cyst is only 3-5cm, she should have a serum CA-125 level done and a color doppler sonography done. If CA–125 levels are less than 65IU and colour doppler is suggestive of a nonmalignant lesion, she could be followed up at 2,3,6,9, and 12 months and annually there after. In cysts larger than this a unilateral salpingo-oophorectomy should be done, provided the CA125 levels and color doppler is suggestive of a nonmalignant lesion. An international multicenter study found that postmenopausal patients with an asymptomatic simple ovarian cyst 3-5 cm in diameter and a normal CA125 had a 0% risk of malignancy (6). CA125 is an antigenic determinant that is elevated in 80% of all patients with serous cystadenocarcinoma of the ovary but in only 50% of the patients with stage I disease. As a diagnostic aid, measurement of CA125 is most useful in postmenopausal patients with an ultrasonographically suspicious mass. In this setting, a level greater than 65 U/mL has been shown to have a positive predictive value of 97%. Color flow Doppler has been reported to be helpful in identifying malignancy. Computerized tomography (CT) does not have as good resolution of ovarian masses as ultrasound but does tell you a lot about the rest of the abdomen. Magnetic resonance imaging (MRI) is a little better at describing ovarian masses and, like CT, gives a good view of the entire abdomen; however, MRI is more costly. In summary, simple unilocular cysts are likely to be benign but should always be followed up with Ca- 125 levels. If it is greater than 65 U/ml, to be on the safe side the patient should be treated as ovarian malignancy. When CA125 levels are normal, the patients should be followed up.

Multilocular cysts: Multilocular cysts as opposed to simple cysts need careful evaluation. Cysts >6cm should alert one to the possibility of malignancy. The differential diagnosis of such a cyst in this age group should include an inflammatory tubo-ovarian mass, an endometrioma, a benign Teratoma (Dermoid) or even a hemorrhagic corpus luteum cyst.. In all these conditions a laparoscopic cystectomy/salpingo-oophorectomy is all that is needed. Here, it is useful to remember that CA-125 is elevated (>35mIU) in endometriomas, Pelvic infections, pregnancy and assossiated liver disease. A markedly elevated Ca-125 (>200mIU) may make one strongly suspect malignancy and take a decision straight away in favour of a hysterectomy with bilateral salpingo-oophorectomy. A normal CA-125 level alone is not enough to rule out malignancy. Quite often the diagnosis of borderline malignant ovarian tumour is made presumptively at the time of surgery on seeing the excrescences on the tumour, adhesions etc, confirmation being made only after histopathology. Thus in a patient with multilocular cysts, a colour doppler scanning and testing of serum for tumour markers might help in preoperatively detecting malignancy, but even if preoperative evaluation does not indicate malignancy a careful histopathology is mandatory postoperatively.

Ovarian cyst in pregnancy: Traditionally, asymptomatic ovarian cysts >8cm should be removed only after 16 weeks as till then there is a possibility that the cyst is a corpus luteum cyst. Asymptomatic corpus luteal cysts disappear in second trimester. But symptomatic cysts (Torsion, haemmorrhage, rupture) should be removed even in first trimester.Ultrasonographic cyst aspiration could be tried in selected cases.(20) In cases where cystectomy is done before 10 weeks, progesterone support should be given as the corpus luteum may have been removed.Progesterone suppositories are available in strengths of 100mg and 200mg. These could be given twice daily orally or vaginally. Vaginal route is known to give better absorption rates. One study has reported 6 cases of laparoscopic cystectomy for adnexal torsion without miscarriages, proving that in skilled hands laparoscopy is safe in 1sttrimester(17). The author also has done 2 laparoscopic ovarian cystectomies in first trimester of pregnancy with good maternal and fetal outcome. Ovarian cysts getting impacted in the pouch of Douglas causing obstruction to labour in second stage could also be aspirated.

Myomectomy in infertile women: The impact of leiomyomata on reproduction is not clear due to the paucity of well controlled studies.(15). Intracavitary and large submucosal leiomyomata are most likely causally related to infertility. . Removal of submucosal and large intramural leiomyomata has been associated with improved outcome in infertile women undergoing assisted reproductive technologies such as in vitro fertilization(8). If the clinical problem is repeated miscarriage,preterm labor, or intrauterine growth restriction or the leiomyomata are large,preconceptional removal of intramural leiomyomata may be appropriate. All patients with myomas should be educated about specific risks during pregnancy, including miscarriage, pelvic pain,premature labor, and postpartum hemorrhage. In the absence of other causes of infertility or after the unsuccessful treatment of other infertility factors, it is reasonable to suggest myomectomy as an option. Most patients can be treated without surgery. There is ultrasonographic evidence of recurrence in 25% to 51% of patients, and as many as 10% require a second major operative procedure (9). According to one study(29), most recurrences occur10-30 months following original surgery. Myomectomy removes only the fibroids, the genetic predisposition for the formation of fibroids remaining intact.

Q: What should be management of a unilocular simple 3-5 cm cyst in a menopausal woman? A: The possibility of malignancy has to be kept in mind, more in the postmenopausal woman. The protocol of management should be the same. An international multicenter study found that postmenopausal patients with an asymptomatic simple ovarian cyst 3-5 cm in diameter and a normal CA125 had a 0% risk of malignancy3. CA125 is an antigenic determinant that is elevated in 80% of all patients with serous cystadenocarcinoma of the ovary but in only 50% of the patients with stage I disease. As a diagnostic aid, measurement of CA125 is most useful in postmenopausal patients with an ultrasonographically suspicious mass. In this setting, a level greater than 65 U/mL has been shown to have a positive predictive value of 97%. In RCOG guidelines2, It is recommended that ovarian cysts in postmenopausal women should be assessed using CA125 and transvaginal grey scale sonography. There is no routine role yet for Doppler, MRI, CT or PET.

Q: What should be the management of a multilocular cyst in the post menopausal woman” A: Multilocular cysts as opposed to simple cysts need careful evaluation. Cysts >6cm should alert one to the possibility of malignancy. The differential diagnosis of such a cyst in this age group should include an inflammatory tubo-ovarian mass, an endometrioma, a benign Teratoma (Dermoid) or even a hemorrhagic corpus luteum cyst.. In all these conditions a laparoscopic cystectomy/salpingo-oophorectomy is all that is needed. Here, it is useful to remember that CA-125 is elevated (>35mIU) in endometriomas, Pelvic infections, pregnancy and assossiated liver disease. A markedly elevated Ca-125 (>200mIU) may make one strongly suspect malignancy and take a decision straight away in favour of a hysterectomy with bilateral salpingo-oophorectomy. A normal CA-125 level alone is not enough to rule out malignancy. Quite often the diagnosis of borderline malignant ovarian tumour is made presumptively at the time of surgery on seeing the excrescences on the tumour, adhesions etc, confirmation being made only after histopathology. Thus in a patient with multilocular cysts, a colour doppler scanning and testing of serum for tumour markers might help in preoperatively detecting malignancy, but even if preoperative evaluation does not indicate malignancy a careful histopathology is mandatory postoperatively.

Q. What should be the management of a menopausal woman with an simple ovarian cyst of larger than 6cm? A:In a woman with an ovarian cyst larger than 5 cm differentiation should be made between organic and functional cysts. Normally formed follicles or corpus luteum in the ovary may sometimes undergo cystic transformation, leading to formation of follicular cysts or corpus leuteal cysts, which are functional cysts. . The majority of follicular cysts disappear spontaneously by either reabsorption of the cyst fluid or silent rupture within 4 to 8 weeks of initial diagnosis 4. Unless ultrasound features definitely indicate organic cyst, a presumptive diagnosis of functional ovarian cyst could be made and the patient watched over for 6 months. However, persistence of the cyst over 6 months means there is likelihood that the cyst is not functional, and that it needs surgical intervention. If the patient has acute or chronic pelvic pain, which could be attributable to the cyst, surgical treatment is warranted, even if the cyst appears to be functional.

In younger women, if there is no suspicion of malignancy, ovarian cystectomy with conservation of ovary could have been done. But in a post menopausal woman, unilateral salpingooophorectomy with removal of the tissue without possible spillage into the abdomen would be the ideal treatment of choice. Laparoscopic surgery being a less morbid procedure, for the patient, should be preferred if the centre has facilities for laparoscopy. In case of suspected malignancy, although there are many reports of laparoscopic surgery in advanced centres, by and large, laparotomy is considered to be the gold standard.

A point scale (0 to 4) was developed within each category, with the total points per evaluation varying from 0 to 12.

An ultrasound morphology index score less than 5 in a pre-menopausal woman is in keeping with a benign aetiology.

have found no significant change in uterine size or myoma volume over 6–12 months of follow-up in placebo arms . A nonrandomized study of women who had uterine size of R8 weeks and who chose hysterectomy or watchful waiting found that 77% of women choosing observation

In post-menopausal patients, a morphology index score ≥5 has a positive predictive value for malignancy of 0.45.

Malignancy indexing can also be helpful in diagnosing malignancy in a post menopausal woman.
Risk of Malignancy Index(RMI) = U ×M ×CA 125.
U=Ultrasound score.
M=3, a constant for menopausal women.
CA 125=value of CA 125.

• Moderate-risk RMI = 25 to 250; Risk of cancer is 20%;
• High-risk RMI = >250 Risk of cancer is 75%;
• Low-risk RMI = less than 25; Risk of cancer is less 3%

Q: What are the risk factors for ovarian cancer? A: Family history of ovarian cancer is associated with increased risk of ovarian cancer. Family history of epithelial cancers are specially associated with increased risk of ovarian cancer. There are genetic markers, which can predict whether such an individual is at an increased risk of developing ovarian cancer. The most studied gene associated with ovarian cancer is the BRCA1 gene. If relatives of patients who develop ovarian cancer are found to have this gene, they could undergo frequent surveillance for development of ovarian cancer. If such individuals have to undergo hysterectomy, they should undergo a prophylactic bilateral oophorectomy as well. Similarly there are quite a few other genes also which have been found to be present in increased frequency in women with ovarian cancer. But, without further studies to confirm their usefuleness, it has not been found necessary to genetically screen the population as a whole to see who is at increased risk of ovarian cancer. These studies are available in India,but are prohibitively costly.

Post-menopausal women with suspicious pelvic mass and:

• Elevated CA-125 level (>35 U/mL)
• Ascites
• A nodular or fixed pelvic mass
• Evidence of abdominal or distant metastasis
• A family history of 1 or more first-degree relatives with ovarian or breast cancer.

Pre-menopausal women with a suspicious pelvic mass and:

• Greatly elevated CA-125 level (> 200 U/mL)
• Evidence of abdominal or distant metastasis
• Ascites
• A family history of 1 or more first-degree relatives with ovarian or breast cancer.

Risk factors for ovarian cancer: Family history of ovarian cancer is associated with increased risk of ovarian cancer.Family history of epithelial cancers are specially associated with increased risk of ovarian cancer. There are genetic markers, which can predict whether such an individual is at an increased risk of developing ovarian cancer. The most studied gene associated with ovarian cancer is the BRCA1 gene. If relatives of patients who develop ovarian cancer are found to have this gene, they could undergo frequent surveillance for development of ovarian cancer. If such individuals have to undergo hysterectomy, they should undergo a prophylactic bilateral oophorectomy as well. Similarly there are quite a few other genes also which have been found to be present in increased frequency in women with ovarian cancer. But, without further studies to confirm their usefuleness, it has not been found necessary to genetically screen the population as a whole to see who is at increased risk of ovarian cancer. These studies are as yet not available in India.
Infertility and nulliparity is associated with increased risk of ovarian cancer. The use of infertility drugs was suspected to increase the risk, but it has been found that it is infertility per se and not the use of ovulation inducing drugs that increases the risk of ovarian cancer.

Stage I Growth limited to the ovaries

• Stage IA Growth limited to one ovary; no ascites,No tumor on the external surfaces;capsules intact.
• Stage IB Growth limited to both ovaries; noascites. No tumor on the external surfaces;capsules intact.
• Stage IC Tumor either stage IA or IB, but with tumor on surface of one or both ovaries;or with capsule ruptured; or with ascitescontaining malignant cells; or with positive peritoneal washings.
• Stage II Growth involving one or both ovaries,with pelvic extension.
• Stage IIA Extension or metastases to the uterus or tubes.
• Stage IIB Extension to other pelvic tissues.
• Stage IIC * Tumor either IIA or IIB but on thesurface of one or both ovaries; or with capsule(s) ruptured;
• Or with ascitescontaining malignant cells; or withpositive peritoneal washings.
• Stage III Tumor involving one or both ovaries with peritoneal implants outside the pelvis or Positive retroperitoneal or inguinal nodes;
  superficial liver metastasis equals stageIII;
  tumor is limited to the true pelvis, but there is histologically proven malignant extension to small bowel or omentum
• Stage IIIA Tumor grossly limited to the true pelviswith negative nodes but with Histologically confirmed microscopicseeding of abdominal peritoneal surfaces.
• Stage IIIB Tumor involving one or both ovaries with histologically confined implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes are negative
• Stage IV Growth involving one or both ovaries with distant metastases; if pleural effusion is present, there must be positive cytology to categorize as stage IV.

Benign tumours in adolescents: Breen and Maxson combined four series to demonstrate the shifting distribution of ovarian neoplasms by patient age. In young adolescents 10 to 14 years old, 72% of ovarian neoplasms were germ cell; 8%, sex cord stromal; and 16%,epithelial tumours. Among the older adolescents 15 to 17 years old, 49% were germ cell; 16%,sex cord stromal, and 28%, epithelial.

Cystic teratomas: Cystic teratomas (Dermoids) are the most common benign tumour in this age group. Dermoids are benign germ cell tumours. They usually contain skin, teeth, bones, hair, and extremities. . On sonography, dermoid cysts often appear as complex cystic masses that contain solid elements that cause shadowing. Laparoscopy or laparotomy can be used to remove dermoids by cystectomy in most patients or by oophorectomy when necessary. If the dermoid is larger than 6 cm or the patient has undergone multiple surgical procedures with adhesions, laparotomy is the preferred treatment approach.. Careful attention should be given to the other ovary because of the 12% rate for bilateral occurrence. There is a 1-2% chance of malignant change in Dermoids, but this is unusual in this age group, being an occurence seen usually in the post-menopausal age group.

Dysgerminoma: It is the commonest germcell malignancy.In early cases unilateral salingo-oophorectomy followed by surveillance is all that is necessary. In advanced cases, combination chemotherapy has to be added.

Other germ cell tumours: Other germ cell malignancies found in adolescents include immature teratoma, embryonal carcinoma, endodermal sinus tumor, gonadoblastoma, choriocarcinoma, and mixed germ cell tumors. Many of these tumors produce markers, as previously discussed, that may be useful for following response to therapy. Most patients should receive postoperative chemotherapy with bleomycin, etoposide, and cisplatin, with the exception of those with stage I, grade I immature teratoma, who can be followed with surveillance. The survival rate for these patients is not as good as those with dysgerminoma but is still excellent, especially for those with early stage disease with appropriate adjuvant chemotherapy.

Tumour markers in ovarian Ca in adolescent age group: Whenever a patient is suspected to have an ovarian malignancy, she should have the levels of tumour markers checked, both for diagnostic purposes and for following up the patient after surgery. The tumor marker, Cancer antigen 125(CA-125) is not as useful in adolescents as in menopausal patients. Elevation can be caused by a variety of processes that result in peritoneal irritation, such as endometriosis or PID, making the test nonspecific in this age group. Germ cell tumours are more common in this age group and the tumour markers specific to these tumours will be more useful in this age group.

Alpha-Fetoprotein can be made by endodermal sinus tumors, embryonal cell cancer, mixed germ cell malignancies, and rarely by immature teratomas. Serum beta-hCG can be found in nonpregnant patients with embryonal cell carcinoma and choriocarcinoma. Patients with dysgerminoma may have elevated lactate dehydrogenase levels. Tumor markers are most useful for following treatment response in patients diagnosed with ovarian malignancies.

Ovarian caner in the adult woman:

Epithelial tumours: Benign epithelial tumors: Conservative surgery with the preservation of some ovarian tissue is enough in young women with benign epithelial tumors. This usually includes ovarian cystectomy or oophorectomy. In postmenopausal women a TAH/BSO can be considered to avoid future cancer risk.
Malignant epithelial tumours: Almost 85% of all ovarian malignancies are derived from ovarian epithelium, making epithelial malignancies the most commonly encountered ovarian cancer. It could be borderline, or frankly malignant. They include, Serous, mucinous, endometrioid, clear cell, Brenner-transitional cell, mixed mesodermal, and undifferentiated tumors.

excrescences,rupturedcapsule,ascites,peritoneal implants,haemmorrhage and necrosis,solid areas or intracystic papillations. These tumours have to beremoved by cytoreductive surgery. Cytoreductive surgery is the removal of as much of the tumor and its metastases as possible. It includes TAH, BSO, and complete omentectomy with resection of any metastatic lesions. In some patients, bowel resection and retroperitoneal lymphadenopathy are necessary to

obtain optimal cytoreduction. Optimal cytoreduction is achieved when the largest residual tumor mass measures less than 1.5 cm. This has to be followed up with chemotherapy. Sometimes the tumour appears inoperable at first laparotomy. These patients are first given chemotherapy and when the tumour is more amenable to surgery, cytoreductive surgery should be attempted.

Germ cell tumours: Germ cell tumours include: dysgerminoma, endodermal sinus tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, teratoma, mixed forms, and gonadoblastoma.

Benign germcell tumours: These are Gonadoblastoma, Mature teratoma (Dermoid), & Struma ovarii.

Malignant Germcell tumours: These include dysgerminoma, endodermal sinus tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, teratoma, mixed forms, and gonadoblastoma.

Nondysgerminomatous malignancies: Unilateral tumors are the rule in nondysgerminomatous germ cell malignancies. Because of this, unilateral oophorectomy should be performed. This would preserve the contralateral ovary, as long as it appears normal, for hormone production and future childbearing potential. . Cytoreductive surgery for advanced disease should be undertaken when possible. In patients needing to preserve childbearing function, unilateral salpingo-oophorectomy should be done followed by chemotherapy. Normal menstruation is known to resume on stopping chemotherapy. There is hardly any role for second look laparotomy for follow up of germcell tumours. Measuring tumour markers may be enough for follow up.

Stage IB onwards: If the patient has completed child bearing, TAH with BSO may be done. Data are limited on treating patients with advanced or recurrent stromal tumors because of the rarity, multihistologic patterns, and indolent behavior of these tumors. Even less information is available regarding which patients should receive adjuvant therapy. However, use of chemotherapy and even radiotherapy has been described in a few studies for recurrent tumours.

Unilateral salpingo-oophorectomy may be enough for patients with with the following tumours:

• Grade I, stage 1A Invasive epithelial tumors.
• Borderline tumors.
• Germ cell tumors.
• Stromal cell tumors.

References:

• Holzer.RA,Persons.RK.,Evaluation of ovarian cysts: American family physician: Volume 84, Number 3 ◆ August 1, 2011.
• Drake J. Diagnosis and management of the adnexal mass. Am Fam Physician. 1998;57:2471-2475.
• Joshi.M,et al, Sonography of adnexal masses: Ultrasound Clin 2 (2007) 133–153.
• Beretta P; Franchi M et al. Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation. Fertil Steril 1998 Dec;70(6):1176-80.
• Busacca M; Marana R Recurrence of ovarian endometrioma after laparoscopic excision. Am J Obstet Gynecol 1999 Mar;180(3 Pt 1):519-23
• Flynn MK; Niloff JM Outpatient minilaparotomy for ovarian cysts. J Reprod Med 1999 May;44(5):399-404
• Gabriel oeslner,MD et al., Long term follow up of the twisted ischaemic adnexa managed by detorsion:Fertility and Sterility Vol.60 No6 December,1993.
• Goldstein SR. Conservative management of small postmenopausal cystic masses. Clin Obstet Gynecol.1993;35:395-401.
• Guerriero S; Mallarini G. et al. Transvaginal ultrasound and computed tomography combined with clinical parameters and CA-125 determinations in the differential diagnosis of persistent ovarian cysts in premenopausal women. Ultrasound Obstet Gynecol 1997 May;9(5):339-43.
• Lee EJ; Kwon HC. Diagnosis of ovarian torsion with color Doppler sonography: depiction of twisted vascular pedicle. J Ultrasound Med 1998 Feb;17(2):83-9
• Lee EJ; Kwon HC,et al: Diagnosis of ovarian torsion with color Doppler sonography: depiction of twisted vascular pedicle.J Ultrasound Med 1998 Feb;17(2):83-9.
• Linda Van Lee,“Clinical presentation of adnexal masses” at 48th annual meeting of American College of Obstetricians and Gynecologists, San Fransisco,May 2000.
• Schutter EM, Kenemans P, Sohn C, et al. Diagnostic value of pelvic examination, ultrasound, and serum CA125 in postmenopausal women with a pelvic mass. An international multicenter study. Cancer. 1994;74:1398-1406.
• Stark JE; Siegel MJ Ovarian torsion in prepubertal and pubertal girls: sonographic findings. Am J Roentgenol 1994 Dec;163(6):1479-82.
• Troiano RN; Taylor KJ . Sonographically guided therapeutic aspiration of benign-appearing ovarian cysts and endometriomas. Am J Roentgenol 1998 Dec;171(6):1601-5.Volume 46 • Number 3 • June 1999
• Zanetta G; Lissoni A. et al., Role of puncture and aspiration in expectant management of simple ovarian cysts: a randomised study. BMJ 1996 Nov 2;313(7065):1110-3.

Endometeriosis

Posted On March 9, 2018 by Dr.Shobhana Mohandas

Endometriosis may be defined as the presence of functioning endometrial tissue outside the uterus. It is usually confined to the pelvis in the region of the ovaries, uterosacral ligaments, cul-de-sac, and uterovesical peritoneum. The development and extension of endometrial tissue into the myometrium is termed adenomyosis. An endometrioma may be defined as an area of endometriosis, usually in the ovary, that has enlarged sufficiently to be classified as a tumor. When an endometrioma is filled with old blood, resembling tar or chocolate syrup, it is commonly known as a chocolate cyst.

Clinical features & diagnosis of Endometriosis: Endometriosis classically presents with pelvic pain,dyspareunia,congestive dysmenorrhoea or as infertility. Pain,is usually bilateral, varies from mild to severe discomfort in the lower abdomen and is often associated with rectal pressure. Many affected women complain of lower back and leg pain. A constant soreness in the lower abdomen or pelvis throughout the cycle, which is aggravated just before the menses or during coitus, may be the only complaint. Since many of these symptoms mimic many other illnesses, diagnosing endometriosis can be difficult. Endometriosis can manifest as nodularity in the pouch of Douglas, decreased mobility of uterus due to pelvic adhesions, masses in the pelvis due to ovarian endometriosis,etc. The best time to examine a patient with suspected endometriosis is postmenstrually. At this time the nodularities found on pelvic examination increase in size, confirming the suspicion of endometriosis.

Besides the usual sites like ovaries, uterosacral ligaments, cul-de-sac and uterovesical peritoneum, endometriosis can present at unusual sites like lungs, liver, rectovaginal septum, scar tissue, etc. These implants could present as haemoptyis (lungs), cyclic right subcostal pain (liver), painful defaecation or bleeding per rectum during periods (rectovaginal septum), or as pain with defaecation and malena(Colon).

For confirmatory diagnosis,currently, the “gold standard” is direct visualization of endometrial lesions using laparoscopy, often with confirmation by biopsy of excised endometriotic tissue.(8).Ultrasound scanning ,a diagnostic modality used widely for the detection of a wide arrayof pathologies is not very much useful in confirming the diagnosis of endometriosis. Ovarian endometriomas can be detected on ultrasound scanning, but external endometriotic implants, for example,the ones on uterosacrals and pelvic peritoneum cannot be picked up on sonography. Presumptive diagnosis of adhesions can be made from the fixity of ovaries, and uterus on ultrasound, but a definitive diagnosis requires a laparoscope. CT scanning and MRI may be useful in diagnosing endometriosis at extrapelvic sites of endometriosis like lungs and liver, but are not of much use in pelvic endometriosis.

Medical treatment of endometriosis: The medical therapy of endometriosis is done with agents like OC-pills, progestins,NSAID’s,Danazol and GnRh analogues. The objective is to produce a state of amenorrhoea which may be akin to a pseudopregnancy(OC-Pills,progestins) or pseudomenopause(Danazol,GnRh analogues). This inhibits or delays progression of the disease.

OC-pills: Initial management in a patient suspected of having endometriosis and not desiring pregnancy is to start on OC-pills and NSAID’s for 3 months. If there is no response, there is no point in switching over to another brand of OC-pills or NSAID. A more aggressive approach is needed.

Progestins: Oral administration of medroxyprogesterone acetate, 50 mg daily,can improve symptoms in 80% of patients with moderate to severe endometriosis. Minor bleeding, weight gain and edema, are some of the side effects that are usually well tolerated. Subjective improvement in symptoms has been noted by some workers with 30 mg of medroxyprogesterone acetate. Unfortunately, recurrence rates have been reported to reach 42% after 2 years of therapy. As an alternative to medroxyprogesterone acetate, one may choose to administer norethindrone acetate, 5 mg daily for 6 months. A similar response can also be achieved with 40 mg of megestrol acetate daily. Parenteral medroxyprogesterone acetate depot may also be given at a dose of 100 mg every 2 weeks for 3 months followed by 200 mg monthly for 3 to 6 months.

Danazol: Danazol is a weakly androgenic preparation. In doses of 200mg/day it can reduce pelvic pain but for effectively reducing endometriosis doses that can produce amenorrhoea is required. 400-800mg/day may be needed to produce amenorrhoea. Danazol is teratogenic and patients at risk of getting pregnant should be asked to use contraception. It may be given for 8-12 weeks preoperatively before repeat surgery. For patients who refuse surgery, 52-78weeks course may be necessary. More than 75% of patients receiving danazol have one or more side effects. Major side effects seen with danazol therapy are weight gain, edema, decreased breast size, acne, oily skin, hirsutism,deepening of the voice, headache, hot flashes, changes in libido, and muscle cramps.Significant weight gain (2 to 10 kg) is not uncommon. All these side effects are reversible with the exception of voice changes. The time course for the resolution of androgenic symptoms may be long; 6 months or more is usual.

Gonadotropin-Releasing Hormone Agonist Therapy: GnRH is a hypothalamic decapeptide that stimulates pituitary LH and FSH secretion. Chemicals similar in structure to the native gonadotropin releasing hormone is used to induce amenorrhoea. Depot preparations of these compounds are usually used to produce amenorrhoea. The effects are comparable to Danazol without the androgenic side effects of Danazol. Dose: Goserlin and leuprolide are 2 depot preparations available in India. The dosage of leuprolide is a single monthly 3.75-mg depot injection given intramuscularly every month. Gosarelin, in a dosage of 3.6 mg, is administered subcutaneously every 28 days. Treatment should be continued for at least 3months. Each injection may cost upto Rs.7000-8000. There may be estrogenic side effects like dry vagina, hot flashes,etc. These can be prevented by giving estrogens and progestogens .For e.g:Conjugated estrogens in the dose of 1.25mg with Medroxyprogesterone acetate 2.5 mg daily.

Surgical treatment of endometriosis: Laparoscopic adhesiolysis, and fulgration of implants form the main stay of surgical treatment. Endometriomas are drained and the cyst lining either peeled off or fulgrated using cautery or laser.In women who have completed their family hysterectomy with salpingo-oophorectomy is the definitive mode of therapy.

References:

• Bergqvist A; Bergh Tet al., Hughes E, Fedorkow D et al., Ovulation suppression for endometriosis: Cochrane review last updated on15.02.1996.
• Busacca.M,Marana.R., Recurrence of ovarian endometrioma after laparoscopic excision
• Catalano GF; Marana R ., Laparoscopy versus microsurgery by laparotomy for excision of ovarian cysts in patients with moderate or severe endometriosis. J Am Assoc Gynecol Laparosc 1996 Feb;3(2):267-70.
• Harrison RF, Barry-Kinsella C., Efficacy of medroxyprogesterone treatment in infertile women with endometriosis: a prospective, randomized, placebo-controlled study. Fertil Steril 2000; 74:24-30.
• Fedele.L. Bianchi.s. et al., Gonadotropin-releasing hormone agonist treatment for endometriosis of the rectovaginal septumAm. J. Obstetrics and Gynecology Vol 183 • NO 6 • December 2000.
• Giorlandino.C,Taramanni.C,Ultrasound-Guided Aspiration of Ovarian Endometriotic Cysts: Int.J.Gynecol Obstet 1993;43:41-44.
• Hornstein.M.D,Barbieri.R.L., – Endometriosis: Ryan: Kistner’s Gynecology & Women’s Health, 7th ed., Copyright © 1999 Mosby, Inc.
• Kamran S. Moghissi., A Clinician’s Guide to the Use of Gonadotropin-Releasing Hormone Analogues in Women: Medscape Women’s Health5(1), 2000. © 2000 Medscape, Inc.
• Lapp.T., ACOG Issues Recommendations for the Management of Endometriosis: American Family PhysicianVolume 62 • Number 6 • September 15, 2000.
• MacDonald .S.R,Klock.SC., Long-term outcome of nonconservative surgery (hysterectomy) for
• Minjarez .D.A,Schlaff.W.D.,Update on the medical treatment of endometriosis: Obstetrics and Gynecology Clinics Vol 27 • NO 3 • September 2000.
• contraceptives after laparoscopic treatment of ovarian endometriomas: A prospective, randomized trial : American Journal of Obstetrics and Gynecology Volume 183 • Number 3 • September 2000.
• Muzii L, Marana R., The impact of preoperative gonadotropin-releasing hormone agonist treatment on laparoscopic excision of ovarian endometriotic cysts: Fertil Steril 1996 Jun;65(6):1235-7.
• Prentice A, Deary AJ,et al., Progestagens and anti-progestagens for pain associated with endometriosis:Cochrane review last updated on 17.01.2000.
• Rana N; Thomas S; Decrease in the size of ovarian endometriomas during ovarian suppression in stage IV endometriosis. Role of preoperative medical treatment. J Reprod Med 1996 Jun;41(6):384.
• Selak V, Farquhar C,et al., Danazol for pelvic pain associated with endometriosis: Cochrane Review Abstracts, last updated on 27.02.1997.
• Vercellini.P,Olga de Giorgi., Depot medroxyprogesterone acetate versus an oral contraceptive combined with very-low-dose danazol for long-term treatment ofpelvic pain associated with endometriosis:Am J Obs & Gyn. Vol 175 • NO2 • August1996.

Anovulation

Posted On April 6, 2018 by Dr.Shobhana Mohandas

Anovulation is one of the commonest factors treated in infertility. It is known that women ovulate infrequently and modern life requires the couple to stay separately quite often. Therefore ovulation inducing drugs are given commonly to women when they come for infertility evaluataion, more so , because it is easily prescribed.

Evaluation of ovulation:

History: Irregular periods are suggestive of anovulation. Women who are having regular menstrual cycles (frequency of 23-35days, with no more than 2-3 days variation each month) have a greater than 95% chance that they are ovulating.
Basal body temperature chart: The temperature of the woman is taken everyday before rising from bed and noted. Just after ovulation the temperature rises by 0.2-0.50 C and remains higher than the preovulatory phase. It is a retrospective diagnosis and very strainful to the patient, but in patients who cannot are not willing for serial vaginal USG, this could be used as a fairly good method of documenting ovulation.
Urinary LH kits: Urinary LH is measured using reagent strips by the patient herself . The testing should be carried out at the same time every day starting two to three days before expected ovulation. A colour change predicts ovulation in 12-24 hours. This is a prospective test and ovulation cannot be confirmed , as increase in LH levels may not always end in ovulation.
Ultrasound: The preovulatory follicle grows at a rate of 2-3 mm per day and is 17-25mm at the time of ovulation.Pregnancy is associated with follicles of larger size at the time of ovulation and usually those greater than 20mm. Ultrasound features of ovulation include a reduction in size of the follicle associated with loss of definition of the folllicular wall, together with the presence of fluid in the pouch of Douglas and even multiple echoes in the follicle. Ultrasound assessment is usually carried out one or two days before expected ovulation and repeated one or two days after ovulation. The pre-ovulatory endometrium changes its texture after ovulation and is another indicator of ovulation on ultrasonography.

Clinical examination:A proper clinical examination could give clues regarding the etiology of the ovulatory disorder.

Bodymass: Obesity is usually associated with anovulation, being more of a central obesity.
Hirsuitism: The raised androgen levels in PCOD patients is associated with hirsuitism. Acanthosis Nigricans:These are hyperpigmented patches on the dorsal surfaces of the body.
Breasts: The breasts should always be examined in all infertile patients. Expression of the nipples may reveal galactorrhoea, which may be a sign of subtle hyperprolactinaemia. This should be differentiated from the pathological nipple discharges.

Diagnosis of anovulation:

Urinary LH kits or serial ultrasonography could be used to make a presumptive diagnosis of ovulation and to time ovulation. Vaginal sonography has an edge over abdominal sonography for follicular study as the follicles and the endometrium are depicted much more clearly by the vaginal probe.

Hormone profile:

• Serum prolactin levels- to determine hyperprolactinaemia.
• Serum FSH levels on day3- To determine premature ovarian failure(FSH>40IU),
• diminished ovarian resereve(FSH-15-20IU), hypogonadotropism,etc.
• Serum LH levels – (>10IU in midfollicular phase suggestive of PCOD).
• Serum DHEAS (Dehydroepiandrosterone)levels –(>10micromole /L suggestive of adrenal involvement)
• Serum T3,T4,TSH levels- To diagnose hypothyroidism.
• Insulin levels->30mu/L fasting suggestive of hyperinsulinaemia which may lead to PCOD.
• GTT- To diagnose insulin resistance in PCOD.

Candidates for ovulation induction:

Ovulation induction should be considered only in patients who have ovulatory disorders. The administration of Clomiphene citrate(The first line of therapy in anovulation) to normally ovulating women does not increase the pregnancy rate in infertile women (5) as shown in controlled studies. This principle may have to be waived in patients undergoing treatment with Artificial Reproductive Technology. In patients undergoing intrauterine insemination, results are improved when their ovaries are stimulated artificially. In patients undergoing IVF ET/ICSI, the cycles are planned so that a certain number of patients can have their ovum pickups done on the same day simultaneously.

Ovulatory disorders:
Ovulation can be presumed to occur when menstrual cycles occur regularly at intervals of 28 to 35 days.
Ovulatory disorders could be:

• Oligoovulation where ovulation occurs in lesser frequency as compared to normal population,
• Anovulation where ovulation does not take place at all
• Luteal phase defects, where ovulation takes place, but there is defective formation and growth of the corpus luteum, which normally forms after ovulation.

Some of the ovulatory disorders are described below. Polycystic ovarian syndrome:This is a common condition among anovulatory patients and affects 6-10% of all women(13). The finding of polycystic ovaries may appear in many an ultrasonography report and to the uninitiated doctor, it may sound like a cystic disease of the ovary. Polycystic ovarian syndrome is in fact a disease where there is hormonal imbalance, leading to the development of multiple follicles in the ovary.
Pathology: In the normally ovulating ovary there may be multiple follicles seen on USG before day 7 of the menstrual period. One of them become dominant and ovulates. In polycystic ovaries, the ovarian size is increased,the multicystic appearance of the ovaries persist, and there is no dominance of any one follicle and consequently there is no ovulation.
Clinical findings:Polycystic ovarian syndrome has a gradual onset in young women with mild hirsuitism which gradually increases and comes to medical attention 1 year after onset. The onset of symptoms is typically in the decade between 15 and 25 years. Some women have acne in addition to hirsuitism. Some women with PCOS have Acanthosis nigracans. Women with PCOS tend to be obese. Amenorrhoea or an irregular menstrual pattern may be the presenting symptom. They may come with infertility. Sometimes in addition to reduced conception, pregnancy outcome may also be adversely affected with miscarriage rates as high as 65% being reported.

Clomiphene citrate: Action: It mimics the appearance of estrogen and tricks the body, mainly the hypothalamus to believe that oestrogen levels are higher than what it actually is. It occupies estrogen receptors leading to the production of gonadotropin releasing hormones from the hypothalamus and gonadotropins from the pituitary, resulting in formation of a dominant follicle,subsequently followed by ovulation.
Indication: Clomiphene citrate is most effective and should be considered the initial treatment of choice for women with anovulation or oligo-ovulation associated with normal endogenous estrogen production and normal levels of FSH (WHO group 2). Clinically, this represents the large and heterogeneous group of women with polycystic ovary disease.

Dose:The initial recommended dosage is 50 mg once daily for 5days; therapy can be initiated on cycle days 3, 4, or 5. In the absence of documented ovulation, the clomiphene citrate dosage should be increased to 100 mg daily for 5 days. An additional 25% of patients will ovulate if the dosage of Clomiphene citrate is increased to 100 mg daily for 5 days. Gysler et al reported that 26% of patients who eventually ovulated required a daily dosage of 150 mg or more. Once the minimal effective dose to induce ovulation has been determined, there is no advantage to increasing the dosage in subsequent cycles, even in the absence of pregnancy. Treatment with clomiphene citrate should be continued for three to six ovulatory cycles. Approximately 90% of clomiphene-induced pregnancies occur within four to six ovulatory cycles. Detection of ovulation should be sought during each cycle. In most patients, ovulation takes place approximately 5 to 12 days after the last treatment dose.

Monitoring cycles:Different strategies may optimize the timing of intercourse or intrauterine inseminations. These include frequent intercourse after cycle day 10, BBT charting, measurement of urinary or serum LH, or serial ultrasound monitoring. Contraindications; Clomiphene is contraindicated in moderate to large ovarian cysts, pregnancy, organic intracranial lesions, pituitary macroadenomas, liver disease, uncontrolled thyroid or adrenal dysfunction, visual disturbances and undiagnosed abnormal uterine bleeding.

Insulin lowering agents: Recent literature has shown that one of the major biochemical features of polycystic ovary syndrome is insulin resistance accompanied by compensatory hyperinsulinemia (elevated fasting blood insulin levels). Hyperinsulinemia produces the hyperandrogenism of polycystic ovary syndrome, interfering with the pituitary ovarian axis, leading to increased LH levels, anovulation, amenorrhea, and infertility. It has been shown that lowering serum insulin concentrations with metformin (Glyciphage 1500 mg a day) or troglitazone (Rezulin 400 mg a day) ameliorates hyperandrogenism, by reduction of ovarian enzyme activity that results in male hormone production. Out of these, Metformin is available in India as 500mg and 850mg tablets. The dose is 500-850mg three times daily. It has been shown to reverse the endocrine abnormalities seen with PCOD in 2-3 months time. The therapy reduces hirsutism, obesity, blood pressure, triglyceride levels, and facilitates reestablishment of the normal pituitary_ovarian cycle, thus often allowing resumption of normal ovulatory cycles and pregnancy. , When given to non_diabetic patients, neither metformin nor troglitazone lowers blood sugar while both appear to be very safe. In the first week of taking the medication, people will often experience upset stomach or diarrhea, which usually resolves after the first week. For those on metformin, starting with one pill daily the first week and increasing to twice a day during the second week can minimize this side effect. Patients with reduced renal function (creatinine >1.5 or creatinine clearance less 60%) are at a higher risk for a rare side effect of metformin therapy called lactic acidosis, and the drug should be given cautiously, if at all, to such patients. Metformin given during pregnancy has not shown increased incidence of congenital anomalies in the fetus. Recurrent abortions caused due to PCOD can benefit from Metformin therapy.

Treatment with Gonadotropins: HMG or FSH are given singly or in adjunct to Clomiphene citrate with ultrasound monitoring. A dose of 75IU or 150IU is started on day 2 or 3 and given daily or alternate days , with doses being adjusted according to the growth of follicle seen on Ultrasonography and serum estrogen levels, if same day results are available. Gonadotropin injections are costly, between Rs2500-Rs10,000 per cycle depending on the drug used and the response.In case of failures, the whole treatment has to be repeated in subsequent months.

Laparoscopic drilling: A few holes are made into the surface of the ovary, draining the subcapsular cysts, and reducing the intraovarian androgen levels, thus facilitating ovulation. Spontaneous ovulation rates ranges from 55-92% and overall pregnancy rates ranges from 56-76%. The mean duration of ovulation ranged from 20-40 days postoperatively in one particular study. Thus if the husband is staying away from the wife, the procedure is ideally performed 1 month before he comes home. Usually the effect of drilling in producing ovulation lasts for more than a year. Gjonnaess followed a large cohort of women and his data suggest that of the women who ovulate in response to ovarian drilling, only 3-4% stop ovulating in the subsequent year. This is where laparoscopic drilling scores over gonadotropin administration. The patient has to spend only once for the surgery, while in gonadotropin administration, the patient has to repeatedly spend huge amounts month after month in case of failures.

Polycystic ovarian syndrome affects 5-10% of all reproductive age women1 The basic pathological findings in PCOS include, elevated LH levels, and subsequently elevated androgen levels, like testosterone and dehydroepiandrostenedione. There is increased resistance to insulin, which can be aggravated by obesity. All these factors need to be addressed while treating a patient with PCOS.

Raloxifene Clomiphene citrate (CC), the traditionally used ovulogen, is a selective estrogen-receptor modulator (SERM), and it presumably works to induce ovulation by inhibiting negative endogenous estrogen feedback on the hypothalamicpituitary axis, resulting in an increase in follicle-stimulating hormone (FSH) secretion, follicular growth, and ovulation. However, endometrial receptivity decreases and miscarriage rates are high with the use of this agent. Raloxifene is a SERM approved for the treatment of osteoporosis in postmenopausal women , with antiestrogenic effects at the

Pioglitazone Hyperinsulinemia caused by insulin resistance in PCOD causes hyperandrogenemia. Metformin is traditionally used to improve this resistance and lower the blood glucose levels. However, many patients cannot tolerate the side effects of Metformin and some are resistnant to it . Pioglitazone is another insulin sensitizing agent which can be used to improve ovulation in PCOS. Its action is different from Metformin. It acts after insulin binding by insulin receptors to improve the action of insulin, reduces its resistance to hormones, and inhibits glucose production in the liver3. pioglitazone may be

Atrovastatin and Simvastatin4,5: The cholesterol lowering Statins, Atorvastatin in the dose of 20 mg or Simvastatin 20 mg per day has been found to be effective in reducing inflammation, biochemical hyperandrogenemia, and metabolic parameters in patients with PCOS after a 12-wk period. Homocysteine levels have also been found to be lower with the use of Statins in PCOS patients.

Insositol : The inositol phosphoglycans (IPGs) are putative mediators in a nonclassic insulin signaling cascade for glucose uptake and use.Insulin-resistant women with PCOS display decreased insulin stimulated release of d-chiro-inositol (DCI)-containing IPGs(DCI-IPGs) during an oral glucose tolerance test (OGTT), which was related to impaired coupling between insulin action and the release of the DCI-IPG. Oral nutritional supplementation with inositol, part of the vitamin B complex (B8) and an intracellular second messenger, was demonstrated to enhance insulin sensitivity and improve the clinical and hormonal characteristics of patients with PCOS In addition, inositol supplementation was shown to restore spontaneous ovulation with the consequent increase in conception, either alone or when combined with gonadotropin.6

Multivitamins Jorge et al,7 in a prospective study concluded that consuming multivitamin supplements at least three times per week was associated with a reduced risk of ovulatory infertility. This association appeared to be mediated in part by folic acid.

Vitamin D3: Selimoglu et al have, using a single dose of 300,000 units of 25-hydroxyvitamin vitamin D3 orally, in PCOS women in a study, concluded that PCOS women are mostly deficient in vitamin D3 and supplementing them with vitamin D3, can have a beneficial effect in improving insulin resistance in obese women with PCOS12 .

N-Acetyle cysteine: N- acetyle cysteine as an adjunct to clomiphene citrate or Metformin could improve insulin sensitivity in PCOS subjects8,9,10. 1.8gm/day in normal weight women (600mg three times a day)and 3 gm/day in extremely obese women for 5 to 6 weeks are the dosages recommended.

Arginine Nitric oxide (NO) has a positive role in oocyte maturation and ovulation. L-Arginine is a positive NO enhancer. In one study, Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/day) plus L-arginine (ARG) (1600 mg/day) for 6 months. It concluded that prolonged treatment with NAC+ARG might restore gonadal function in PCOS11. This effect seemed associated to an improvement in insulin sensitivity
When faced with a patient with severe PCOS, and achieving pregnancy with standard treatment seems difficult, it would be helpful to supplement the patient with adjuvants that may help reduce insulin sensitivity, and help oocyte maturation and ovulation, with positive effects on the endometrium. Replacing Clomiphene and Metformin with Raloxifene or Pioglitazone are options worth trying in selected cases.

Luteal phase defect: Pathology: Luteal phase defect (LPD) refers to a relative deficiency in the secretion of progesterone by the corpus luteum.The defective functioning of the corpus luteum leads to inadequate development of the endometrium,poor implantation and pregnancy wastage. The most accurate diagnosis of luteal phase defect can be done by dating the endometrium on the 23rd to 24th day of the cycle and it is seen to lag behind by 2 days. It is not always practical.

Clinical picture: Luteal phase defects manifests as unexplained infertility and pregnancy wastage. Thinning of the endometrium found on transvaginal sonography may be suggestive. In early pregnancy recurrent losses (3 abortions in succession) the incidence of LPD could be 20-40%. The incidence among subjects with unexplained infertility, employing endometrial biopsy as diagnostic measure, is in the range of 10-20%.

Associated pathologies:Luteal phase dysfunction may be associated with several clinical entities, including mild or intermittent hyperprolactinemia (of any cause), strenuous physical exercise,inadequately treated 21-hydroxylase deficiency, and habitual abortion.

Treatment

• In patients with abnormal ovulation, Clomiphene citrate should be administered.
• In patients with normal ovulation, progesterone supplemetation should be given in the second half of the cycle. Micronised progesterone could be given in the dose of 100mg twice daily. Vaginal administration of this drug has better absorption compared to the oral route.
• In cases of LPD associated with mild hyperprolactinaemia, Bromocriptine should be added to treatment.
• Administration of additional HCG injections in the latter half of the cycle.
• As a last resort, gonadotropin supplimentation could be tried.

Hyperprolactinaemia:

• Aetiology:Numerous clinical conditions may cause elevated.
• prolactin levels, among them pituitary tumors, certain medications, chest wall trauma.
• Chronic renal insufficiency, hypothyroidism, empty sella syndrome, pituitary stalk.
• transection, and occasionally nonpituitary tumors.

Presentation: Hyperprolactinaemia presents with hypoestrogenism,menstrual irregularities(Oligomenorrhoea or secondary amenorrhoea),anovulation and galactorrhea. Galactorrhea is not present always. Subtle ovulatory dysfunctions such as follicular dysfunction and luteal phase deficiency are the other well-recognised manifestations of this endocrinopathy, which present as ‘Unexplained infertility’. Hence prolactin determinations are essential in all patients with these disturbances.

Bromocryptine: Bromocryptine is a dopamine agonist and inhibits the production of prolactin. Hyperprolactinaemia with infertility has extremely high pregnancy rates when treated with Bromocryptine. Bromocryptine could be admininistered to patients with galactorrhoea, specially when infertile, even if prolactin levels are normal.Treatment with Bromocryptin could be useful in some cases of corpus leuteum insufficiency presenting as unexplained infertility. In cases of failed induction of ovulation with Clomiphene citrate, one of the ways of improving results could be by adding Bromocryptine.

Dose: The optimal dose of Bromocryptine is 2.5mg twice daily. It could be either taken orally or placed in the vagina, from where it is absorbed. Oral administration could result in side effects like severe nausea, vomiting,giddiness,constipaton, abdominal bloating, etc. Starting the drug at a low dose, once a day, could reduce the severity of side effects. The drug could be started in a dose of 1.25 mg once daily after food, and gradually increased to 1.25 mg twice daily over 2 days and finally reach the dose of 2.5mg twice daily.

Dose: Often the dosage range required to restore ovulation is between 2.5mg to 7.5mg daily. Serum prolactin level should be redetermined after 3-4 weeks of treatment. Usually 2.5mg twice daily is needed to normalise prolactin levels, but some patients can be maintained on dosages as low as 1.25 mg at bedtime.

Duration of treatment: Although B romocriptine therapy usually restores ovulatory cycles after approximately 2 months, with or without the normalization of serum prolactin levels, alternative ovulation induction agents such as clomiphene citrate or gonadotropin therapy should be added if it does not. Alternate treatment options should also be considered after 4-6 months of ovulatory cycles without conception. Bromocryptin therapy could be stopped once the patient becomes pregnant, but continuation should be strongly considered for patients with macroadenomas to minimize pregnancy-associated complications. Administration does not cause increased risks for miscarriage,adverse obstetric outcomes, or congenital anomalies.(Kistner)

Premature ovarian failure:

Pathology: When premature menopause occurs before the age of 35,it is due to premature ovarian failure.

Clinical picture: The patients present with secondary amenorrhoea. On testing the FSH and LH levels in the serum they are found to be raised and in the menopausal range

Etiology:It may be caused by genetic defects,infectious and iatrogenic destruction of primordial follicles as a result of mumps oophoritis,irradiation or chemotherapy. It has also been hypothesized that it may be an autoimmune disease. There could be other autoimmmune disorders assossiated with it like Addison disease,thyroiditis, hypoparathyroidism, diabetes, pernicious anemia, myasthenia gravis, and vitiligo. Associated diseases:Because of the associated polyendocrine autoimmune syndromes, patients should be screened for diabetes, anemia, thyroid, adrenal, and parathyroid insufficiency.

Treatment: Accepting an ovum from a donor and going in for IVF-ET is the only option out in patients suffering from infertility. Any other diseases which may be associated with POF should be meticulously looked for and treated.

Diminished Ovarian Reserve

• Recently, a subgroup of patients with unexplained infertility has been described as
• having incipient ovarian failure or diminished ovarian reserve (Toner et al, 1991). These
• patients have elevated FSH levels on day 3 that are greater than 15 to 20 mIU/mL.
• They often have normal ovulation and menstrual cycles, but they respond poorly to
• human menopausal gonadotropins. As do patients with POF, these patients have an
• extremely poor chance for future fertility in the absence of IVF with donor oocytes.

F Hypothalamic Amenorrhea

Pathology:There is reduced production of Gonadotropin releasing hormones from the hypothalamus and consequently reduced production of gonadotropins, leading to reduced follicular development,anovulation and amenorrhoea.

Endocrinology&diagnosis: In contrast to polycystic ovarian syndrome (PCOS), hypothalamic amenorrhea is associated with a hypoestrogenic state. Normal or low gonadotropin levels and the absence of progestin-induced bleeding confirm the diagnosis.

Aetiology:Common causes of hypothalamic amenorrhea include exercise, weight loss, and stress. It has a better prognosis compared to premature ovarian failure.

G Thyroid Disease

Euthyroid:Many practitioners give tablets of thyroxine empirically to infertile women even though they are euthyroid. This sort of treatment remains unsubstantiated.

Subclinical hypothyroidism: The role of thyroid hormone therapy for patients with subclinical hypothyroidism (i.e. elevated TSH level and normal thyroxine and triiodothyronine levels) remains unclear and warrants further investigation.

Clinical hypothyroidism:Patients with clinical hypothyroidism may benefit from thytoid hormone replacement with a resumption of normal ovulatory function.

H Adrenal Disease: Certain disorders of adrenal gland like Addison disease, Cushing syndrome,etc can be associated with ovulatory disorders.

Clomiphene failures:

The following alternatives may be tried.

• When standard doses of Clomiphene does not result in ovulation, extending the course to 14 days has been shown to be effective in some patients.
• Clomiphene may be combined with a single dose of hCG (5000-10,000IU).Serial ultrasound examination should be done and hCG given on he day the follicular diameter exceeds 18mm.
• Serum Dehydro epiandrostenedione levels(DHEAS is an adrenal androgen) should be estimated. If it is >2umg/ml, an adrenal involvement could be presumed. In such cases, adding Dexamethasone 0.5mg daily should be considered
• If the tri-iodo-thyronine levels are below 80ng/ml, combining Clomiphene with throxine, 0.1mg/day will help.
• Clomiphene can be combined with Gonadotropins. The required dose of gonadotropins is reduced when clomiphene is combined.
• Combining Bromocriptine with clomiphene in patients with normal prolactin levels is not supported by current literature.

References :

• Serdar.E.B, Physiology and pathology of the female reproductive axis: Melmed: Williams Textbook of endocrinoloty, 12th ed. Copyright 2011 Saunders,, An imprint of Elsevier.
• Ernesto de Paula Guedes Neto et al: Prospective, randomized comparison between raloxifene and clomiphene citrate for ovulation induction in polycystic ovary syndrome.Fertility and Sterility:Vol. 96, No. 3, September 2011 .7.6333333333
• Hirotaka Ota et al, Successful pregnancies treated with pioglitazone in infertile patients with polycystic ovary syndrome : Fertil Steril_ 2008;90:709–13.
• Fulghesu AM : N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome – Fertil Steril – 01-JUN-2002;
• Rizk AY: N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome. Fertil Steril – 01-FEB-2005; 83(2): 367-70.
• Badawy A : N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand – 01-JAN-2007; 86(2): 218-22.
• Masha A : acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome. J Endocrinol Invest – 01-DEC-2009; 32(11): 870-2.