COMMENTARY

The Management of Endometriosis-related Infertility

Peter Kovacs, MD, PhD

Disclosures

December 11, 2015

Treatment of Infertility Associated With Deep Endometriosis: Definition of Therapeutic Balances

Somigliana E, Garcia-Velasco JA
Fertil Steril. 2015;104:764-770

Endometriosis and Infertility

Endometriosis is a benign gynecologic disease characterized by the extrauterine finding of endometrial stroma and glands. It can by diagnosed in 10%-15% of the general population. Endometriosis may appear in multiple forms. In some women, small peritoneal lesions are seen ("gunpowder lesions"), whereas in others, large nodules are found, primarily in the pelvis. Still other women present with ovarian cysts (endometrioma, chocolate cysts), but adhesions and deeper lesions or lesions distant from the pelvis may also be found. Endometriosis is staged according to extent, laterality, and ovarian or other organ involvement.[1]

The symptoms of endometriosis are typically cyclic and depend on the location and extent of the disease. A characteristic symptom is pain recurring with menstruation. Further symptoms depend more on the location of the endometriotic lesions. Dyspareunia, dyschezia, dysuria, rectal bleeding, hematuria, and ureteral or bowel obstruction may all be associated with endometriosis.[2]

Clinical signs, ultrasound findings, and laboratory results can suggest the condition, but the diagnosis of endometriosis is typically made by the pathologist using biopsy specimens.[3]Many women are asymptomatic, and the condition is discovered incidentally during surgery for other conditions. Other cases are discovered during a workup for infertility; as many as one third of women with endometriosis are infertile.

Asymptomatic endometriosis does not need to be treated. For patients with recurrent or constant symptoms, medical or surgical treatments can be offered. Medical treatments can keep the symptoms under control[2]; these are aimed either at suspending ovarian cyclic function or inducing a pseudopregnant state that usually results in regression of endometriosis. Surgery typically involves the excision of the lesions or the affected area.

The management of endometriosis in infertile women is somewhat controversial. There is even more controversy surrounding the issue of surgical treatment of deep, infiltrating endometriosis in infertile women. This opinion paper addresses this latter issue.

Management Considerations

High-quality scientific evidence to support the treatment of deep endometriosis in the setting of infertility is scant. Part of the problem is that in 50%-70% of affected women, superficial endometriosis can be found in addition to deep endometriosis. Superficial endometriosis, compared with deeply buried, infiltrating lesions, is more likely to release inflammatory cytokines that can affect reproduction. Furthermore, a sizeable proportion of cases are complicated by the presence of adenomyosis, which interferes with successful implantation. Therefore, it is difficult to draw solid conclusions about the management of women with deep endometriosis only.

Natural fecundity and success rates of assisted reproduction seem to be negatively affected by endometriosis.[4]However, endometriosis (either deep or superficial) is not associated with an all-or-nothing effect on fertility. Some women do conceive successfully despite being diagnosed with endometriosis. The chance may be lower, but it is not zero.

Multiple studies have shown that expectant management could have a role for early- or advanced-stage endometriosis.[5,6] Moreover, it has been shown that the removal of deep as well as peritoneal endometriosis will not improve the chance of achieving a successful pregnancy over removal of peritoneal endometriosis alone.[7]

In vitro fertilization (IVF) can be offered as an option to treat infertility in women with deep endometriosis. Conflicting results have been published about the added benefit of pre-IVF surgical excision of deep endometriosis. Controversy may arise from the fact that many patients with deep endometriosis have superficial lesions as well, and the surgical intervention will remove both.

Care must be taken during IVF, because the distorted anatomy may increase the surgical risks at the time of the retrieval.

The opinion statement concludes that the current evidence is confounded by the lack of pure studies on deep endometriosis that are free of the negative impact of superficial endometriosis and adenomyosis. Women who are asymptomatic or whose symptoms can be managed by medical therapy should probably go straight to IVF without any surgery beforehand. Women whose symptoms are refractory to medical therapy or those who need immediate surgery for ureteral or bowel stenosis should undergo operative treatment before IVF, however. Surgery can also be considered for asymptomatic patients with multiple failed assisted reproduction cycles.

Viewpoint

How to manage endometriosis in infertile women is a complex question, and age, ovarian reserve, previous operative history, medical risks with surgery, surgeon skills, and overall expected success rate need to be considered. Good evidence shows a benefit with surgical treatment of stage I-II (mostly superficial) endometriosis.[4] Deep lesions, however, are not in direct contact with the peritoneum and, therefore, with the gametes and the intratubal or intrauterine environment. In these cases, any secretions from the lesions are unlikely to affect the reproductive process.

Deep endometriosis often coexists with superficial endometriosis and adenomyosis, all of which can have a negative impact on fertility—an important consideration in making treatment recommendations. During IVF, some of the negative effect of endometriosis on fertility is eliminated, because fertilization and embryo development take place in an endometriosis-free laboratory environment. Still, some reports suggest that pregnancy rates could be improved by the surgical management of deep endometriosis.

It also has to be taken into consideration that these surgeries are not easy and could involve bowel and bladder resection, with potential long-term consequences. The situation is more straightforward when another indication for the surgery exists (eg, bowel or ureter stenosis, severe pain, repeated IVF failures). Without such indications, the less invasive route may be the better alternative. In cases of assisted reproduction failure, a more invasive approach can be considered.

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