CURRENT CONCEPTS IN TREATING ENDOMETRIOSIS IN INFERTILE PATIENTS

 

Endometriosis is one of the most enigmatic diseases in gynecology. Though the cause effect relationship between fecundity and endometriosis is controversial and a definite link has yet to be established.

Treatment modalities for endometriosis include no treatment, medical/surgical, and a combination of both. Treatment has to be individualized taking into consideration the clinical features, laparoscopic findings, age of the patient and duration of infertility.

MEDICAL THERAPY OF ENDOMETRIOSIS :

Numerous drugs/combinations have been described in the treatment of endometriosis with varying degrees of efficacy.

The main advantage of drug therapy is that it manages lesions that are not detected by the surgeon. It avoids the risk of surgery, anesthesia, and more importantly that of post-operative adhesion formation, which may further compromise fertility. Disadvantages include the side effects and cost of the drugs as well as a longer duration of treatment. Usually 3-6 months are required before there is any evidence of improvement. Medical therapy for endometriosis can be used either pre-operatively or post-operatively. Pre-operative treatment will reduce the inflammation and vascularity, thus reducing the risk of post-operative adhesion formation. It will also reduce the risk of formation of functional ovarian cysts, thus preventing unnecessary surgical manipulation of the ovaries. Usually three months of drug therapy is advocated before attempting any form of surgery.

The rationale behind post-operative treatment is that it will eradicate the residual implants - both visible and invisible.

Progestogens :

Progesterone acts by causing decidualization and atrophy of the estrogen dependant endometriotic foci. The action not only depends upon the dose and duration of therapy, but also upon the activity of the individual agent. Common progestogens used include medroxy progesterone acetate, norethisterone, and dydrogesterone. Side effects include irregular, bleeding, weight gain, fluid retention, breast tenderness, mood changes, depression, headache etc.

Danazol

Danazol, a derivative of 17-ethinyl testosterone, was considered to be the standard treatment for endometriosis.

This acts directly on the intracellular steroid receptors, inhibits ovarian steriodogensis and also reduces the GnRH pulse frequency as well as secretion of gonadotrophins. The cumulative effects are anti estrogenic, anti progestogenic and androgenic actions. It also has an immuno suppressive effect.

As the half-life of danazol is approximately 4.5 hours, ideally the drug should be administered at least every 8 hours. A minimum starting dose of 400 mg/day is adequate for most women. This is increased if necessary to suppress ovulation and relieve symptoms.

Side effects are androgenic (weight gain, acne, oily skin, hirsuitism) and hypoestrogenic (hot flashes, decreased libido, breast atrophy, depression). If administered during pregnancy, it may cause masculinization of a female fetus. Another important adverse action is its effect on the lipid profile. Increase in LDL and decrease in HDL necessitate caution while treating woman at risk for ischaemic heart disease.

GnRH analogs :

GnRH analogs act by down regulating the pituitary gland, resulting in a pseudomenopausal state.

Today, this forms the backbone of medical therapy of endometriosis. Various doses and formulations are in use, but long acting implants produce the best results in terms of pituitary desensitization, laparoscopic scoring and histological regression.

Side effects are consistent with the hypoestrogenic state and include hot flushes, breast atrophy, dry skin, mood swings, decreased libido etc. The most important of these is the trabecular bone loss of 6-7% if used continuously for more than 6 months. This bone loss can be controlled to some extent by the use of estrogen- progesterone add back therapy.

Gestrinone :

Gestrinone is a 19 nor steroid derivative with androgenic, progestogenic and antiestrogenic actions.

Because of its long half-life, this drug can be administered twice a week. Usually 1-25 - 2.5mg bi weekly is given.

The side effects are similar to danazol, though hypo-estrogenic effects are less severe.

SURGICAL TREATMENT :

The main advantage of surgery is that it can be performed at the same sitting as the diagnostic laparoscopy and the delays/side effects of medications are avoided. Surgical options available are multiple - again this has to be individualized depending on the presentation, stage of the disease as well as the age of the patient and duration of infertility. The aim of management whatever is the type of surgery, is to minimize tissue damage and avoid injury to adjacent organs.

Endometriotic implants may be treated by vaporization/coagulation or excision. This is done using electricity (40-60 weeks of cutting current) or laser (Co2/Nd-YAG/JTP). The Co2 laser is associated with least complications, and this can be further reduced by combining it with hydro dissection. This is especially useful when the endometriotic foci are close to the ureters, great vessels and bladder. Small ovarian endometriomas are usually fibrotic and difficult to enucleate. These may be vapourized after biopsy. Larger endometriomas must be removed completely (including the capsule) since there is increased risk of recurrence. Simple aspiration and frustration is generally avoided, as there is an associated risk of recurrence. Recent studies have shown that pre-operative GnRHa therapy 6-8 weeks reduces vascularity, thus reducing intra-operative haemorrhage and improves preservation of normal ovarian tissue. If the ovaries are adherent to the broad ligament, hydrodissection is used to remove the involved broad ligament to reduce the risk of leaving ovarian tissue behind.

Though, the effect of endometriosis on fertility is not yet defined - mechanical, inflammatory, hormonal and immunological factors have been postulated. Factors that may have an effect on the conception rates include extent and type of adhesions, presence of endometriomas and obliteration of posterior cul de sac.

Our policy is to fulgrate visible endometriotic spots at the time of diagnostic laparoscopy. Endometriotic cysts are removed and adhesions released. In case of minimal-mild endometrioses this initial management suffices. For severe endometrioses surgical therapy is followed by danazol/GnRHa treatment depending on convenience and affordability to the patient. Assisted conception follows soon after, in all those women aiming at conception. A waiting period will only increase the risk of recurrence of endometrioses and hence pregnancy should be planned soon after treatment of the endometrioses.