STUDY QUESTION Do inactivated coronavirus disease-2019 (COVID-19) vaccines affect IVF outcomes among the vaccine recipients? SUMMARY ANSWER The receipt of inactivated COVID-19 vaccines before ovarian stimulation has little effect on the outcomes of IVF, including ovarian stimulation outcomes, embryo development and pregnancy rates. WHAT IS KNOWN ALREADY Limited studies have reported that COVID-19 vaccines do not affect ovarian function, embryo development or pregnancy outcomes. STUDY DESIGN, SIZE, DURATION This was a retrospective cohort study performed at the Third Affiliated Hospital of Guangzhou Medical University on 240 women vaccinated with either CoronaVac or Sinopharm COVID-19 before ovarian stimulation in the exposed group and 1343 unvaccinated women before ovarian stimulation in the unexposed group. All participants received fresh embryo transfers between 1 March 2021 and 15 September 2021. The included women were followed up until 12 weeks of gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS Vaccination information of all subjects was followed up by a nurse, and the IVF data were obtained from the IVF data system. The following aspects were compared between the vaccinated and the unvaccinated groups: parameters of ovarian stimulation, embryo development and pregnancy rates. Regression analyses were performed to control for confounders of embryo development and pregnancy rates. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups. The primary outcome was the ongoing pregnancy rate. MAIN RESULTS AND THE ROLE OF CHANCE Liner regression analysis revealed that the number of oocytes retrieved (regression coefficient (B) = −0.299, P = 0.264), embryos suitable for transfer (B = −0.203, P = 0.127) and blastocysts (B = −0.250, P = 0.105) were not associated with the status of vaccination before ovarian stimulation, after adjusting for the confounders. The ongoing pregnancy rate in the women of the vaccinated group was not significantly lower than that in the unvaccinated group (36.3% vs 40.7%, P = 0.199) (adjust odd ratio = 0.91, 95% CI = 0.68–1.22, P = 0.52). After PSM, the rates of ongoing pregnancy (36.0% vs 39.9%, P = 0.272), implantation (35.4% vs 38.3%, P = 0.325), biochemical pregnancy (47.3% vs 51.6%, P = 0.232), clinical pregnancy (44.4% vs 47.4%, P = 0.398) and early miscarriage (15.0% vs 12.1%, P = 0.399) were not significantly different between the vaccinated and the unvaccinated groups. LIMITATIONS, REASONS FOR CAUTION This is a retrospective study of women with infertility. The results from the present study warrant confirmation by prospective studies with a larger cohort. WIDER IMPLICATIONS OF THE FINDINGS This is the first study with a large sample size on the effect of inactivated COVID-19 vaccines on ongoing pregnancy rates of women undergoing IVF. The present results showed that vaccination has no detrimental effect on IVF outcomes. Therefore, women are recommended to receive COVID-19 vaccines before undergoing their IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (No. 2018YFC1003803 to J.L.), the Guangzhou Science and Technology Plan Project (No. 202102010076 to H.L.) and the Medical Key Discipline of Guangzhou (2021-2023), as well as the Sino-German Center for Research Promotion Rapid Response Funding Call for Bilateral Collaborative Proposals between China and Germany in COVID-19 Related Research (No. C-0032 to Xingfei Pan). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

STUDY QUESTION Does inoculation with inactivated vaccines against coronavirus 19 (Covid-19) before frozen-thawed embryo transfer (FET) affect live birth and neonatal outcomes? SUMMARY ANSWER Inactivated Covid-19 vaccines did not undermine live birth and neonatal outcomes of women planning for FET. WHAT IS KNOWN ALREADY Accumulating reports are now available indicating the safe use of mRNA vaccines against Covid-19 in pregnant and lactating women, and a few reports indicate that they are not associated with adverse effects on ovarian stimulation or early pregnancy outcomes following IVF. Evidence about the safety of inactivated Covid-19 vaccines is very limited. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort analysis from Reproductive Medical Center of a tertiary teaching hospital. Clinical records and vaccination record of 2574 couples with embryos transferred between March 1st 2021 and Sept 30th 2021, were screened for eligibility of this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Clinical and vaccination data of infertile couples planning for FET were screened for eligibility of the study. The reproductive and neonatal outcomes of FET women inoculated with inactivated Covid-19 vaccines or not were compared. The primary outcomes were live birth rate per embryo transfer cycle and newborns’ birth height and weight. Secondary outcomes included rates of ongoing pregnancy, clinical pregnancy, biochemical pregnancy, spontaneous miscarriage. Multivariate logistical regression and propensity score matching (PSM) analyses were performed to minimize the influence of confounding factors. Subgroup analyses including single dose versus double dose of the vaccines, and the time intervals between the first vaccination and embryo transfer were also performed. MAIN RESULTS AND ROLE OF CHANCE Vaccinated women have comparable live birth rates (43.6% versus 45.0% before PSM, P = 0.590; and 42.9% versus 43.9% after PSM, P = 0.688), ongoing pregnancy rates (48.2% versus 48.1% before PSM, P = 0.980; and 52.2% versus 52.7% after PSM, P = 0.875), clinical pregnancy rate (55.0% versus 54.8% before PSM, P = 0.928; and 54.7% versus 54.2% after PSM, P = 0.868) when compared with unvaccinated counterparts. The newborns’ birth length (50.0 ± 1.6 versus 49.0 ± 2.9 cm before PSM, P = 0.116; and 49.9 ± 1.7 versus 49.3 ± 2.6 cm after PSM, P = 0.141) and birth weight (3111.2 ± 349.9 versus 3030.3 ± 588.5 g before PSM, P = 0.544; and 3053.8 ± 372.5 versus 3039.2 ± 496.8 g after PSM, P = 0.347) were all similar between the two groups. Neither single dose nor double dose of vaccines, as well as different intervals between vaccination and embryo transfer showed any significant impacts on reproductive and neonatal outcomes. LIMITATIONS, REASONS FOR CAUTION The main findings might be limited by retrospective design. Besides, inoculations of triple dose of Covid-19 vaccines were not available by the time of data collection, thus the results cannot reflect the safe use of triple dose of inactivated Covid-19 vaccines. Finally, history of Covid-19 infection was based on patients’ self-report rather than objective laboratory tests. WIDE IMPLICATIONS OF THE FINDINGS Eligible individuals of inactivated vaccines against Covid-19 should not postpone vaccination plan because of their embryo transfer schedule, or vice versa. STUDY FUNDING/COMPETING INTEREST(S) This study was support by The Medical Key Discipline of Guangzhou (2021-2023). All authors had nothing to disclose. TRAIL REGISTRATION NUMBER Not applicable.

Introduction: Infertility is a significant health problem, and the prevalence of infertility among women is increasing in developing countries. This study aims to explore whether social support plays a mediating role in the links between exogenous variables, sleep quality, anxiety, and depressive symptoms in Chinese women undergoing in vitro fertilization. Methods: This is a cross-sectional study comprising a sample of Chinese women undergoing in vitro fertilization treatment at a tertiary reproductive medicine center located in South China. Results: The final testing model showed good fit, with normed χ2 = 39.317, p = 0.055, comparative fit index = 0.948, Tucker–Lewis index = 0.902, incremental fit index = 0.951, normed fit index = 0.906, root mean square error of approximation = 0.046). The final path model supported the proposed model: partner relationship, a woman’s age, financial strain, duration of infertility, and cycles of in vitro fertilization were exogenous variables for depressive symptoms, while social support was a significant mediator between sleep quality, anxiety, and depressive symptoms. Conclusion: The empirical support from this study could facilitate the development of appropriate interventions to reduce depressive symptoms, and to promote the mental health of Chinese women undergoing in vitro fertilization treatment.

BackgroundVaccine hesitancy was found in couples seeking artificial reproductive technology (ART) services. As the main vaccine used in China, investigations into the influence of inactivated coronavirus disease 2019 (COVID-19) vaccines on human fertility is needed.MethodsThis retrospective cohort study included data on COVID-19 vaccination, clinical characteristics, and reproductive outcome of 1,000 intrauterine insemination (IUI) cycles in 653 couples from March 2021 to March 2022 in a single university hospital-based center for reproductive medicine. The IUI cycles were divided into two categories based on sperm source, including 725 cycles in 492 women undergoing artificial insemination with their husband's sperm (AIH) and 275 cycles in 161 women undergoing artificial insemination with donor sperm (AID). Women were then divided into two groups. The vaccine exposed group included women vaccinated prior to insemination and the unexposed group included women who were not vaccinated or vaccinated after insemination. Reproductive outcomes including ongoing pregnancy rate, clinical pregnancy rate, and miscarriage rate were assessed.ResultsInactivated COVID-19 vaccinated women prior to intrauterine insemination in AIH cycles have comparable ongoing pregnancy rate (11.1 vs. 10.3%, P = 0.73), clinical pregnancy rate (12.5 vs. 11.3%, P = 0.60) as compared with unvaccinated counterparts. Similarly, there were no significant differences in ongoing pregnancy rate (20.9 vs. 28.1%, P = 0.17), clinical pregnancy rate (21.7 vs. 28.8%, P = 0.19) between vaccine exposed and unexposed groups in AID cycles. Multivariable logistic regression analyses showed that inactivated COVID-19 vaccination status cannot independently influence the reproductive outcomes of AIH and AID cycles. Subgroup analysis of vaccine exposed cycles showed that doses of vaccination and Interval between the last dose of vaccination and insemination have no influence on the reproductive outcomes of AIH cycles.ConclusionsNo negative effects were found on female fertility in IUI cycles following exposure to the inactivated COVID-19 vaccine. These findings indirectly reflect the safety of inactivated COVID-19 vaccine toward reproductive health and help to mitigate vaccine hesitancy among people planning to conceive.

Background Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood. Methods To clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS. Results miR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells. Conclusions miR-194 is increased in PCOS granulosa cell and may function as a novel biomarker and therapeutic target for KGN cells via HB-EGF regulation.