Results from a case-control study comparing mean aneuploidy rates and pregnancy outcomes in women with and without endometriosis undergoing In Vitro Fertilization (IVF) cycles

Study question: Do women with and without endometriosis undergoing IVF with Pre-implantation genetic test for aneuploidies (PGT-A) before blastocysts transfer differ for aneuploidy rates and reproductive outcomes? Summary answer: Endometriosis patients do not differ from their age and MII obtained oocytes-matched healthy peers for mean aneuploidy rates and for pregnancy outcomes in IVF cycles. What is known already: It has been estimated that 30-50% of women with endometriosis can’t conceive naturally and affected IVF patients have worse outcomes than women without endometriosis, such as lower number of oocytes retreived, reduced fertilization, implantation and pregnancy rates. Several pathways have been exploited to explain the endometriosis-related subfertility, both at ovarian than at the endometrial side. The evidence that peritoneal higher levels of reactive oxygen species and inflammatory cytokines can cause oocyte microtubule and chromosome instability has suggested that even the rate of embryo aneuploidy could be increased in these patients, contributing to the poorer IVF outcomes of endometriosis patients. Study design, size, duration: This study retrospectively evaluated data of women producing at least one blastocyst subjected to PGT-A after Intracytoplasmic Sperm Injection from November 2008 to March 2017. To limit the potential bias of the analysis, a case-control study design was adopted. Age at pick-up, number of previous IVF failures and number of MII oocytes were chosen as matching criteria, since they are reported among the strongest success predictors in IVF. Every case was matched with two controls. Participants/materials, setting, methods: Data available from the entire PGT-A population were reviewed and the study population was divided into two groups, according to the presence or the absence of endometriosis. Demographic (age, previous miscarriage, previous failed IVF) and IVF-related information (number of MII, injected and fertilized oocytes, of blastocysts, of euploid blastocysts, of single embryo transfers, of positive beta-Human chorionic gonadotropin, biochemical pregnancy, clinical pregnancy loss, miscarriage and live birth rates) were collected and compared between groups. Main results and the role of chance: In this study, 249 women affected by endometriosis were matched with 498 women without the disease, according to maternal age at pick-up (38.1 ± 2.9 years), previous IVF failure (0.6 ± 0.8 cycles) and number of MII oocyte retrieved (7.1 ± 3.8 per pick-up). In our population, the percentage of fertilized oocytes per number of MII oocyte was significantly lower in women with endometriosis than in control groups (77 vs 74%). Percentage of blastocysts obtained per fertilized oocytes (51.0 vs 53.3%), mean blastocyst rate per fertilized oocyte per cycle (56.5 ± 25.2% vs 58.3 ± 26.8%), percentage of euploid blastocysts per biopsied embryo (49.4 vs 50.1%) and mean euploidy rate per blastocyst per cycle (46.8 ± 38.7% vs 43.7 ± 37.3%) did not differ between control patients and women with endometriosis. Moreover, no significantly differences in terms of percentage of positive pregnancy tests per Single Euploid Embryo Transfer (eSET) (52.4 vs 57.7%), percentage of Biochemical Pregnancy Loss per positive pregnancy test (11 vs 10.6%), percentage of miscarriages per clinical pregnancy (12.3 vs 12.9%) and percentage of ongoing implanted blastocysts or babies born per SET (41.0 vs 44.9%) were detected between group. According to Post-hoc power calculation, we had 80% power to detect a 10% difference in the mean euploidy rate per cycle between groups. Limitations, reasons for caution: This is a first retrospective analysis performed in 3 IVF Italian centers undergoing PGT-a cycles and eSET. Prospective studies could allow better stratification of endometriosis type and stage. Moreover, only patients which obtained at least one blastocysts have been included in the final analysis. Wider implications of the findings: Our preliminary data demonstrate that the rate of aneuploidy and the pregnancy outcomes are not statistically significantly different between women with endometriosis as compared with agematched controls in the IVF population. Aneuploidy therefore could not be related to the poorer IVF outcomes of endometriosis patients. Trial registration number: not applicable.