Endometriosis is a common gynecologic problem, and one that is of special significance in infertility. In recent years, there seems to be an increased incidence in the finding of endometriosis associated with infertility. One explanation for this apparent increase is the general use of the laparoscope in infertility diagnosis, and thus the finding of many cases of early endometriosis unassociated with the usual signs and symptoms of the disease. Another cause may be the late onset of marriage, and the discovery of infertility at a later age. Endometriosis is associated more commonly with nulliparous women in their late 20s or 30s rather than with younger age groups.
The primary treatment of endometriosis, unassociated with infertility, is medical, with surgery used only when disease progresses despite the use of medical therapy. On the other hand, when endometriosis is associated with infertility, surgery should often be the primary approach.
Surgical Treatment of Endometriosis
When laparoscopy reveals the existence of adhesions between the tubes, ovary, and peritoneum, when the ovaries are fixed to the posterior leaf of the broad ligament, or when there are enlarged endometriotic cysts of the ovaries, as in stage 3 and stage 4 disease, surgery is the primary treatment. Medical treatment will not dissolve the adhesions or eliminate large cysts of the ovaries. The primary goal of surgery is to preserve as much ovarian function as possible and to improve tubo-ovum pickup. The adhesions to the ovaries are divided with microsurgical techniques (). The adhesions between the ovary and broad ligament are carefully dissected. It is usually difficult to clamp this area. The cut edges of the broad ligament can be sutured if there is no tension. If the involvement of the ovary is minimal, a small wedge of ovarian tissue can be removed at the site of the previous adherence, and the ovary repaired with fine nonreactive sutures. Adhesions associated with fallopian tubes can be handled easily. Endometrial implants over the peritoneum should be surgically excised if there is not too much deep scarring, and the peritoneum should be sutured, rather than cauterized, because cautery leaves a raw area with a potential for future adhesions.
Large chocolate cysts should be shelled out of the ovary. Deep sutures are then placed in the ovarian tissue for hemostasis and the cortex is closed with a fine nonreactive continuous suture. An anterior suspension is often needed, particularly if the uterus has been freed from its previous third-degree position with adherence to the rectosigmoid. Suspension of the ovary to the uterus prevents it from adhering again to the broad ligament. It is not always necessary to excise all implants, particularly those in surgically dangerous areas, i.e., uterosacral ligaments or bowel. The goal of surgery is improvement of tubo-ovum pickup; other areas can be treated medically.
The use of the laser during a laparotomy provides a significant improvement (). Adhesions can be lysed quickly and atraumatically, and peritoneal implants can be vaporized. The greatest advantage comes in the treatment of significant endometriotic cysts of the ovaries. With surgery alone, often a great deal of normal tissue had to be sacrificed in attempting a thorough removal of the cyst. With the laser, the cyst can be unroofed with an incision through the ovarian cortex over the cyst. The inner lining of the cyst can be dissected away, and then the base of the cyst can be vaporized with a low-intensity laser beam, thus destroying any remaining endometriotic tissue. The walls of the cyst are approximated with sutures and the capsule closed. Thus, little if any normal tissue is removed.
In surgery for endometriosis, whenever possible, microsurgical techniques should be utilized. Steps to reduce postoperative adhesions should also be taken, such as the use of dextran 70.
Laparoscopic laser and pelviscopic surgery are being used more and more in the surgical therapy for endometriosis. For many, laparotomies are being utilized less and less, but the laparoscopic approach is probably best for only the milder degrees of the disease.
Results of Surgical Treatment
There is a decline in pregnancy rates as the condition becomes more severe. However, a 28% to 40% pregnancy rate for severe endometriosis does seem to indicate that the procedure is worthwhile. Overall success rates for mild endometriosis are at about 61%. It is difficult to know whether or not surgery is really helpful in mild endometriosis because pregnancy rates without any treatment can approximate these numbers.
Medical Treatment of Endometriosis
The medical treatment of endometriosis is based on the observations that certain physiologic states, i.e., anovulation, pregnancy, and the menopause, are associated with a regression of endometriosis. Consequently, various phar-macologic avenues were developed to imitate these states in the treatment of endometriosis. In the 1950s, oral contraceptives were utilized to produce either an anovulatory state or a pseudopregnancy. The results of this form of therapy were quite successful. In the past 10 or 12 years, danazol has been the agent of choice. It has been generally believed that danazol works by inhibiting the hypothalamic-pituitary-ovarian axis, thus creating a pseudomenopausal condition. However, there are some recent studies that question this mechanism of action. Some studies indicate that danazol has a diverse number of phar-macologic actions including a direct effect upon steroidogenesis. Another study described an unfavorable shift in lipoprotein levels as well. In any event, a pseudomenopausal condition is produced. The latest approach is to use analogues of gonadotropin-releasing hormone to likewise produce a pseu-domenopausal state caused by low levels of estrogen.
Indications for Medical Treatment
In general, the less severe degrees of endometriosis are treated medically. In the 1970s, after danazol first became available and when laparoscopy began to be widely utilized in infertility, a number of reports were published describing significant improvement in the appearance of endometriotic lesions along with pregnancy rates varying from 48% to 83% following danazol therapy. It was difficult to accurately assess these studies because no controls were available, and it is difficult to know how many of these had only minimal or mild endometriosis without the enlargement or fixation of the ovary. A number of these individuals might have conceived without treatment.
Studies in subsequent years utilizing controls have demonstrated that patients with minimal and even mild endometriosis who are not treated for endometriosis achieve pregnancy rates that are compatible with those achieved by patients receiving danazol. It appears from these reports that minimal and even mild endometriosis are only incidental findings in these patients, and treatment with medical methods does not directly help their infertility. Treatment should be withheld until there is further evidence of a beneficial effect.
On the other hand, mild endometriosis should be treated if there is any ovarian involvement. Moderate endometriosis should always be treated, not because there is evidence of a clinical effect on infertility, but to prevent further progression of the disease. Medical treatment is also used preoperatively in severe endometriosis to reduce the size of the lesions and to facilitate surgery. Medical treatment is also used postoperatively in those cases where it is suspected that all the endometriosis has not been removed.
Treatment with Danazol
The starting dosage of danazol is 800 mg/day administered in four separate doses. Treatment should begin within the first few days of the onset of a menstrual cycle. The usual length of a treatment course is 6 months, although when it is given preoperatively or postoperatively, the course can be limited to 3 months. If the patient is observed at 2-month intervals and is doing well, the dosage can be reduced to one capsule three times daily and then to one capsule twice daily. These occur in about 5% to 10% of patients, but most patients tolerate the medication well.
Analogues of Gonadotropin-Releasing Hormone
The use of gonadotropin-releasing hormone (GnRH) analogues for endometriosis is still new and relatively experimental, but numerous studies have been reported. Since analogues of GnRH have a relatively long life, daily administration results in sustained levels of GnRH, and the pulsatile secretion of natural GnRH is overcome. As a result, pituitary gonadotropin hormone excretion declines, and ovarian secretion of estrogen is diminished. This pseudomenopausal state will result in atrophy of endometriotic tissue.
Depo-type preparations with a potential for once-a-month injection are being readied for the market. There are claims of fewer side effects with GnRH analogues than with danazol. These two facts suggest that some form of GnRH analogue may play a vital role in the medical treatment of endometriosis in the very near future.
Selections from the book: “Infertility: A Clinician’s Guide to Diagnosis and Treatment”. Edited by Melvin L. Taymor, M.D., 1990.