Effects of SARS-COV-2 infection during the frozen-thawed embryo transfer cycle on embryo implantation and pregnancy outcomes.

STUDY QUESTION: Does severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the frozen-thawed embryo transfer (FET) cycle affect embryo implantation and pregnancy rates? SUMMARY ANSWER: There is no evidence that SARS-CoV-2 infection of women during the FET cycle negatively affects embryo implantation and pregnancy rates. WHAT IS KNOWN ALREADY: Coronavirus disease 2019 (COVID-19), as a multi-systemic disease, poses a threat to reproductive health. However, the effects of SARS-CoV-2 infection on embryo implantation and pregnancy following fertility treatments, particularly FET, remain largely unknown. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, included women who underwent FET cycles between 1 November 2022 and 31 December 2022 at an academic fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who tested positive for SARS-CoV-2 during their FET cycles were included in the COVID-19 group, while those who tested negative during the same study period were included in the non-COVID-19 group. The primary outcome was ongoing pregnancy rate. Secondary outcomes included rates of implantation, biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy. Multivariate logistic regression models were applied to adjust for potential confounders including age, body mass index, gravidity, vaccination status, and endometrial preparation regimen. Subgroup analyses were conducted by time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) and by level of fever (no fever, fever <39°C, or fever ≥39°C). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 243 and 305 women were included in the COVID-19 and non-COVID-19 group, respectively. The rates of biochemical pregnancy (58.8% vs 62.0%, P = 0.46), clinical pregnancy (53.1% vs 54.4%, P = 0.76), implantation (46.4% vs 46.2%, P = 0.95), early pregnancy loss (24.5% vs 26.5%, P = 0.68), and ongoing pregnancy (44.4% vs 45.6%, P = 0.79) were all comparable between groups with or without infection. Results of logistic regression models, both before and after adjustment, revealed no associations between SARS-CoV-2 infection and rates of biochemical pregnancy, clinical pregnancy, early pregnancy loss, or ongoing pregnancy. Moreover, neither the time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) nor the level of fever (no fever, fever <39°C, or fever ≥39°C) was found to be related to pregnancy rates. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study is subject to possible selection bias. Additionally, although the sample size was relatively large for the COVID-19 group, the sample sizes for certain subgroups were relatively small and lacked adequate power, so these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection during the FET cycle in females does not affect embryo implantation and pregnancy rates including biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy, indicating that cycle cancellation due to SARS-CoV-2 infection may not be necessary. Further studies are warranted to verify these findings. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2019YFA0802604), National Natural Science Foundation of China (82130046, 82101747), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SSMU-ZLCX20180401), Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai Sailing Program (21YF1425000), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161413). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The effect of peak serum estradiol level during ovarian stimulation on cumulative live birth and obstetric outcomes in freeze-all cycles.

Objective: To determine whether the peak serum estradiol (E2) level during ovarian stimulation affects the cumulative live birth rate (CLBR) and obstetric outcomes in freeze-all cycles. Methods: This retrospective cohort study involved patients who underwent their first cycle of in vitro fertilization followed by a freeze-all strategy and frozen embryo transfer cycles between January 2014 and June 2019 at a tertiary care center. Patients were categorized into four groups according to quartiles of peak serum E2 levels during ovarian stimulation (Q1-Q4). The primary outcome was CLBR. Secondary outcomes included obstetric and neonatal outcomes of singleton and twin pregnancies. Poisson or logistic regression was applied to control for potential confounders for outcome measures, as appropriate. Generalized estimating equations were used to account for multiple cycles from the same patient for the outcome of CLBR. Results: A total of 11237 patients were included in the analysis. Cumulatively, live births occurred in 8410 women (74.8%). The live birth rate (LBR) and CLBR improved as quartiles of peak E2 levels increased (49.7%, 52.1%, 54.9%, and 56.4% for LBR; 65.1%, 74.3%, 78.4%, and 81.6% for CLBR, from the lowest to the highest quartile of estradiol levels, respectively, P<0.001). Such association remained significant for CLBR after accounting for potential confounders in multivariable regression models, whereas the relationship between LBR and peak E2 levels did not reach statistical significance. In addition, no significant differences were noticed in adverse obstetric and neonatal outcomes (gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, placental disorders, preterm birth, low birthweight, and small for gestational age) amongst E2 quartiles for either singleton or twin live births, both before and after adjustment. Conclusion: In freeze-all cycles, higher peak serum E2 levels during ovarian stimulation were associated with increased CLBR, without increasing the risks of adverse obstetric and neonatal outcomes.