Abstract

Abstract Study question Does endometriosis affect endometrial receptivity in frozen/thawed embryo transfer (FET) cycles? Summary answer Stage III/IV endometriosis-patients undergoing ART submitted to FET cycles have implantation, pregnancy and live-birth rates, as well as pregnancy outcomes, similar to control women. What is known already The increased infertility rate observed in women with endometriosis is supposed to be linked, among other factors, to molecular alterations already documented in the endometrial tissue of these affected women. These alterations might influence the interaction between the embryo and the endometrium, leading to a compromised implantation; however, data from the literature are controversial and do not always corroborate the hypothesis of a lower implantation rate in women with endometriosis. Study design, size, duration This is a retrospective matched case-control study including 101 women diagnosed with stage III/IV endometriosis. They were matched in a 1:1 ratio with patients undergoing frozen embryo transfers after ART treatments for other infertility-related indications at the Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico di Milano, between 2015 and 2022. Participants/materials, setting, methods Patients (n = 202) were submitted to ovarian stimulation according to standard protocols and only single embryo transfer cases and the 1st ART cycle with freeze-all protocol were included. To match, it was considered the women's age ( ± 1 year), and the number ( = ) and quality ( ± 1 top vs low) of blastocysts obtained in each cycle, considering the Istanbul consensus as the embryo standard assessment protocol. The main outcome evaluated in this study was implantation rate. Main results and the role of chance Baseline characteristics did not significantly vary between the two study groups, except for AMH levels, which was considerably lower in the endometriosis group compared to control (4.0 [2.7 - 5.4] vs 4.6 [3.7 - 6.5], respectively; p = 0.03). Considering the treatment outcomes, the number of oocytes inseminated/injected in each cycle was similar between endometriosis and control group (8 [7 - 10] vs 9 [7 - 11], respectively; p = 0.26). In line with the matching performed, the number of blastocysts generated did not differ between women with and without endometriosis (3 [2 - 4] vs 3 [2 - 4], respectively; p = 1.00), as well as the number of top-quality blastocysts (2 [1 - 3] vs 2 [1 - 3], respectively; p = 0.76). In regard to our main outcome evaluated, implantation rate in women with endometriosis and their controls were similar (36% vs 40%, respectively; p = 0.52). There was also no difference between the endometriosis group and controls considering cumulative pregnancy outcomes, such as pregnancy rate (58% vs 65%, respectively; p = 0.39), cumulative live birth rate (51% vs 59%, respectively; p = 0.26), pregnancy complications (6% vs 14%, respectively; p = 0.34), and pregnancy loss (16% vs 19%, respectively; p = 0.70). Limitations, reasons for caution As it is a retrospective study, our reports might be subjected to misclassification bias. Also, some of the women in the control group may have asymptomatic undiagnosed endometriosis; however, considering the incidence of this disease, it should not compromise our evaluation. Wider implications of the findings Our present findings give support to the idea that endometriosis does not influence the implantation rate in women with endometriosis undergoing ART submitted to FET. Considering fertility, this finding raises doubts about the clinical relevance of the molecular aberrations detected in the endometrium of women affected by endometriosis. Trial registration number not applicable

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