Endometriosis

Endometriosis is a prevalent disease that can be found in 25–50% of women with infertility and up to 80% of patients with pelvic pain (1). Hypothesized mechanisms for endometriosis-associated infertility include altered tubal function, altered peritoneal environment reducing ovum pick up and tubal transport, impaired fertilization, ovulatory disorders with altered luteal hormone production, impaired implantation, and poor oocyte/embryo quality (2). However, patients with severe endometriosis documented either surgically or by the presence of endometriomas and/or MRI evidence of extensive disease are often treated surgically in an attempt to restore anatomy.

Surgical excision of endometriomas and the endometrioma bed is required to reduce the incidence of recurrence. There is a body of evidence that reveals that patients with endometriomas have reduced follicle reserve in that ovary, whether or not the endometrioma is surgically excised and excision of the endometrioma does not restore follicle mass in that ovary. This seems to suggest that some of the damage on the follicle supply is caused from the invasion of the endometriosis into the ovary and already occurred by the time of diagnosis. Excision of the endometrioma may also be associated with further reductions in ovarian reserve since invariably, some normal ovarian tissue is excised despite careful precautions to remove just the cyst wall (3). Multiple surgeries will lead to significant reductions in ovarian reserve and response to gonadotropins with fewer oocytes retrieved (4). Therefore, in this group, preservation of their oocytes at a younger age will improve their chances of having a child in the future due to the likely more rapid decline in their egg supply compared to their non-affected counterparts. Ovarian stimulation and oocyte cryopreservation can be performed prior to ovarian cystectomy and patients who had undergone prior surgery for ovarian endometriosis had lower total oocyte yield (6.2 ± 5.8) compared to patients with unilateral cystectomy (5.0 ± 4.5) or bilateral cystectomy (4.5 ± 4.4)(5). Probability of having a child were age appropriate compared to patients without disease and were directly correlated to age of the patient and number of oocytes cryopreserved.

The difficult decision is to know which patients are at higher risk of future premature ovarian failure so that they can be appropriately counseled and directed to freeze their oocytes when they are ready to have children in the future but this conversation should at least be initiated with any young girl undergoing surgery for endometriomas or with severe (stage 3/4) disease. Ovarian stimulation in this group to obtain oocytes can also be a bit tricky as supraphysiologic levels of estradiol seen with ovarian stimulation may exacerbate symptoms and possibly cause more rapid progression of disease. In these situation, like and potentially estrogen sensitive disease, aromatase inhibitors may play a role.

There is no role for aspiration of endometriomas either before stimulation or at the time of oocyte retrieval, as these are very likely to recur in a short period of time, increase the risk of infection from the retrieval procedure, and will not result in an improved response to stimulation or increase pregnancy rates (6).

Ovarian tissue cryopreservation has been performed for patients with endometriosis but this approach is controversial at best. If the ovary is being removed due to extensive disease, transplanting tissue back into the patient in the future would result in physiologic estradiol levels and recurrence of the endometriosis. It would be better to not de-vascularize the ovary and remove as much visible disease during a surgery and then undergo possibly multiple cycles of ovarian stimulation to cryopreserve oocytes. Deep ovarian function suppression with GnRH agonists may provide similar pain relief as seen with surgical castration which cannot be reversed.

References:

1. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol. 2004;160(8):784-96.
2. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012;98(3):591-8
3. Muzii L, Bianchi A, Croce C, et alLaparoscopic excision of ovarian cysts: Is the stripping technique a tissue sparing procedure? Fertil Steril 2002;77:609-14
4. Aboulghar MA, Mansour RT, Serour GI, et al. The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study. Am J Obstet Gynecol 2003;188:371–5.
5. Cobo A, Giles J, Paolelli S, et al. Oocyte vitrification for fertility preservation in women with endometriosis: an observational study. Fertil Steril 2020;113:836-44
6. Garcia-Velasco JA, Somigliana E. Management of endometriomas in women requiring IVF: to touch or not to touch. Hum Reprod. 2009;24(3):496-501.