Abstract

Abstract Study question Does modified natural endometrial preparation in single euploid frozen-thawed embryo transfer (FET) cycles affect chance of pregnancy and risk of miscarriage compared to artificial? Summary answer The rate of clinical pregnancy and live birth increases while the rate of miscarriage decreases in modified natural FET cycles compared to artificial FET cycles. What is known already Corpus luteum produces growth factors, angiogenic factors and vasoactive substances as well as hormones. These substances play role for initial placentation. Early maternal endocrine milieu resulting exogenous estrogen and progesterone could damage placentation, which may in turn cause miscarriage. High estradiol levels might also be responsible for decreased pregnancy rates (Wu et al 2021). Study design, size, duration This retrospective, single center study evaluated 1890 frozen single euploid embryo transfer cycles in women between 20-43 years old from January 2017 to September 2021. The study is based on data obtained from Istanbul Memorial Hospital, ART and Reproductive Genetics Center. FET cycles were analyzed in two groups according to different endometrial preparation protocol. Group A (n = 1335): modified natural FET cycles (mNat/FET) and Group B (n = 555): artificial FET cycles (AC-FET). Participants/materials, setting, methods Only good prognosis patients with ages between 20-43 years old were included. Exclusion criterias were women age 44 and above, recurrent abortion history, BMI>35 kg/m 2, endometrial factor, uterin factor (adenomyosis, mullerian anomaly) history. NGS was used to study trophoectoderm biopsy material in all cases. Patients demographics, cycle characteristics and pregnancy outcomes were analyzed. Main results and the role of chance We analyzed the effect of endometrial preparation methods on pregnancy outcomes between the two groups after excluding confounding factors in single euploid embryo transfer cycles. There were no significant differences in patient demographics and cycle characteristics such as age, body-mass index, infertility duration, previous IVF attempts, AMH level, daily gonadotropin dosage used, number of oocytes obtained, mature oocytes and fertilized oocytes between the two groups. There was no significant difference between the morphologic grading of the transferred embryos in both groups. However, all pregnancy outcomes were statistically significantly different in two groups. In group A, biochemical pregnancy rate (76.9% vs. 73.9%, p:0.04), clinical pregnancy rate (71% vs. 65.7%, p < 0.01), live birth rate (65.4% vs. 50.5%, p < 0.01) were significantly higher than in group B. Also, biochemical pregnancy loss rate (7.7% vs. 11%, p:0.01), clinical pregnancy loss rate (6.7% vs. 21%, p < 0.01), second trimester pregnancy loss rate (0.8% vs. 1.5%, p:0.04) were significantly lower compared to group B. Limitations, reasons for caution The limitation of our study include the fact that this was a retrospective analysis. Prospective randomised studies are necessary to evaluate the differences between the two groups according to pregnancy outcomes. Wider implications of the findings This study shows that pregnancy outcomes are better in patients undergoing mNat/FET even after controlling for confounding factors when comparing mNat/FET and AC-FET in single euploid FET cycles. As a result, in appropriate patients, mNat/FET with higher pregnancy rate and live birth rate should be preferred as much as feasible. Trial registration number Not applicable

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