Infertility Associated to Endometriosis: Clarifying Some Important Controversies.

Abstract

Endometriosis is an estrogen-dependent gynecological disease characterized by the presence andgrowth of endometrial tissue (glands and/or stroma) outside the uterine cavity.1 The disease affects 10% of women of reproductive age2 and is strongly associated with infertility.3 It is estimated that more than 30% of infertile women have endometriosis2 and that 30 to 50% of thesewomen report difficulties in getting pregnant.4 Opinion remainsdivided as towhetherminor endometriosis (minimal andmild endometriosis—stages I and II, respectively) has an adverse effecton thelikelihoodofconception.5–9 In 1998, a study demonstrated that the fecundity of infertile women with minimal or mild endometriosis is not significantly lower thanthatofwomenwithunexplained infertility, suggesting that the initial stage of the disease is just a finding and not the cause of infertility.6 Otherwise, the findings of a randomized controlled trial showing improved natural conception rates following surgical treatment of visible endometriotic lesions suggest that the presence of visible minor lesions alone may have an adverse effect on natural conception.7 Additionally, a retrospective study of 192 fully investigated infertile couples (117 women with unexplained infertility and 75 with minimal/mild endometriosis without adhesive disease, both managedconservativelyafterdiagnostic laparoscopy)evaluated cumulativepregnancy rates inbothgroups followedup for up to 3 years following laparoscopy.8 This study demonstrated that women with endometriosis had a lower probability of pregnancycomparedwithwomenwith unexplained infertility (36% versus 55%, respectively), which confirmed the presence of lower cumulative pregnancy rates inwomen in the early stages of endometriosis compared with women with infertility of unknown cause,9 thus supporting the association between infertility and endometriosis in the early stages. Infertility presented by women with early endometriosis, inwhompelvic anatomical distortions are not present, raises questions about themechanisms involved in the impairment of fertility in patients with the disease. The research group under my supervision has extensively performed studies in this subject and published recent review articles approaching this topic.10–12 Although the mechanisms involved in endometriosis-related infertility are still not completely understood, in summary, there are studies suggesting the peritoneal, follicular, systemic, and endometrial microenvironments may be altered in these women, with consequent damages to folliculogenesis, oocyte quality, endometrial receptivity, and, even, sperm function.10–12 Another very controversial point is whether the indication of in-vitro fertilization (IVF) in infertile women with endometriosis is associated with a worse gestational prognosis after the procedure, and if the progression in disease staging further worsens the results of the IVF. A systematic review published in 200213 showed that patients with endometriosis who underwent ovarian stimulation for IVF had lower pregnancy rates when compared with infertile patients with tubal factor (relative risk (RR) 0.56, 95% confidence interval [95% CI] 0.44–0.70). However, when dividing endometriosis patients according to the staging of the disease (minimal/mild endometriosis—stages I/II and moderate/severe endometriosis—stages III/IV), it was observed that patients with endometriosis I/II presented pregnancy rates similar to those with tubal factor (RR 0.79, 95% CI 0.6–1.03), and patients with endometriosis III/IV had significantly lower rates than those without the disease (RR 0.46, 95% CI 0.28–0.74). Despite being a relevant review, itsmain limitation is that most of the included studies were published between 1980 and 1999, a period in which ovarian stimulation and technical conditionswerequitedifferent fromthecurrentones. However, more recent studies contradict the results of this meta-analysis published in 2002. Data from the latest published meta-analysis,14 which analyzed 36 cohort studies and randomized controlled trials, show that comparedwithwomenwithout endometriosis, womenwith endometriosis undergoing IVF and intracytoplasmic sperm injection (ICSI) had a Paula Andrea Navarro’s ORCID is https://orcid.org/0000-00032368-4188.