Endometriosis is a relatively common disorder affecting women of reproductive again. It is estimated that 25% to 50% of infertile women have endometriosis and that roughly 30%-to 50% of women with endometriosis are infertile.1 However, the exact causal relationship between infertility and endometriosis remains controversial. In some cases, the development of pelvic adhesions and distorted pelvic anatomy, clearly demonstrate a cause and effect relationship with expected decreased fecundity. Still, the causality with mild endometriosis is less obvious, and expected enhanced fertility with hormonal suppression of endometriosis is not supported by the literature.

Several mechanisms have been proposed as explanations for reduced fertility with endometriosis. With severe endometriosis and major pelvic adhesions, this could result in impaired oocyte release and/or inhibited ovum capture or transport. The increased peritoneal fluid that occurs in endometriosis has been shown, in some studies, to contain elevated prostaglandins, and inflammatory cytokines, thus leading to systemic inflammation. Increased IgG and IgM antibodies that may be present in women with endometriosis, could alter endometrial receptivity. Decreased expression of ∂Vβ3 integrin during time of implantation has been suggested in some women with endometriosis. It has also been suggested that women with endometriosis may have unruptured follicle syndrome.2

In current clinical practice, a surgical procedure such as laparoscopy is required to make a definitive diagnosis of endometriosis. In addition, if the diagnosis is not immediately obvious at the time of surgery, histology may be used to make the diagnosis. The question of whether and when to suggest diagnostic surgery in the case of infertility is controversial. In the clinical situation of infertility alone, without any pain and/or dysmenorrhea, the likelihood of making the diagnosis of endometriosis and the benefit of surgery must be considered. According to recent ASRM guidelines, laparoscopy of asymptomatic women with infertility is unwarranted. In addition, since 1996 the ASRM offers a classification for the staging system of endometriosis that is widely used. Unfortunately, the staging system does not correlate well with the chance of conception following treatment. However, a new classification system proposed in 2010, the Endometriosis Fertility Index, has been validated as a clinical tool that predicts pregnancy rates after endometriosis surgical staging.3 The EFI score takes into account the function of tube, fimbria, and ovaries on both sides, and accurately predicts pregnancy rates in patients with endometriosis, who attempt non-IVF conception.

Therapeutic options for the treatment of endometriosis-associated infertility, include medical and surgical approaches. For mild disease, stage I & II endometriosis, various medical approaches have been tried historically, with the goal of suppressing endometriosis. These have included combined estrogen-progestin therapy, progestin alone, danazol, and both GnRH agonists and antagonists. However, a meta-analysis that included 13 clinical trials and 800 infertile women, done by the Cochrane Review some years ago, concluded that no evidence exists that medical suppression was superior to placebo in women who wished to conceive.4 Newer agents such as aromatase inhibitors and SERMs have not been well studied in the medical management of endometriosis for fertility. On the contrary, in stage I/II endometriosis, laparoscopic ablation of endometrial implants has been associated with a small, but significant improvement in live birth rates. With advanced disease, stage III/IV endometriosis, surgical management may increase fertility, especially when large endometriomas (>4cm) are completely resected rather than just drained. However, the risks of surgery and its potential damage to ovarian reserve need to be balanced against complications associated with the persistence of endometriomas during IVF.5 Indeed, the continued debate in the literature rages on about the initial approach to ovarian endometriosis, whether surgery or IVF.6

When it comes to the utilization of superovulation and intrauterine insemination (IUI) in endometriosis, the results in the literature are confusing. In most studies, superovulation and IUI are started after initial surgery to ablate endometriosis in mild disease. In this specific setting, of stage I & II endometriosis, surgical treatment, followed by ovulation induction/IUI may be a viable option as an alternative to IVF. Particularly, in younger women mild endometriosis, expectant management after surgical therapy is considered an option. However, better data exists to suggest that in severe endometriosis, (stage III & IV), IVF likely maximizes cycle fecundity, especially in those with pelvic distortion. For women with stage III/IV endometriosis who fail to conceive following conservative surgery, IVF is an effective alternative.

Lastly, female age, duration of fertility, degree of pelvic pain, and stage of endometriosis should be considered when developing a management plan. Younger women (< 35) with mild disease, expectant management or ovulation induction/IUI can be considered as initial therapy. However, for women of advanced maternal age, more aggressive therapy, such as IVF should be considered.

References:

  1. Missmer SA, Hankinson SE, et al. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol 2004; 160: 784-96.
  2. Schenken RS, Asch RH, et al. Etiology of infertility in monkeys with endometriosis: luteinized unruptured follicles, luteal phase defects, pelvic adhesions, and spontaneous abortions. Fertil Steril 1984; 41:122-30.
  3. Adamson GD, Pasta DJ, et al. Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril 2010; 94:1609-15.
  4. Hughes E, Brown J, et al. Ovulation suppression for endometriosis. Cochrane Database Syst Rev 2007:CD000155.
  5. Donnez J, Garcia-Solares J, et al. Ovarian endometriosis and fertility preservation: a challenge. Minerva Ginecol 2018; 70:408-14.
  6. Lessey B, Gordts S, et al. Ovarian endometriosis and infertility: in vitro fertilization or surgery as the first approach? Fertil Steril 2018; 110: 1218-1226.