The effect of SARS-CoV-2 infection or vaccination on controlled ovarian stimulation and in vitro fertilization: A multicenter retrospective cohort study

Abstract Study question Are the ovarian response to controlled ovarian stimulation (COS) and embryo development after in vitro fertilization (IVF) affected by SARS-CoV-2 infection and immunization? Summary answer Both SARS-CoV-2 infection and SARS-CoV-2 mRNA or inactivated vaccinations do not affect ovarian responsiveness to COS or embryo development following IVF. What is known already SARS-CoV-2 infects the target cell by binding to angiotensin-converting enzyme 2 (ACE2) via its surface spike protein. ACE2 receptors are present in the vagina, uterus, fallopian tubes, and ovaries of the female reproductive system. They regulate ovarian steroidogenesis, follicular development, oocyte maturation, and follicle atresia. The virus downregulates ACE2 levels, resulting in decreased conversion of Angiotensin II (ANGII) to Ang (1-7) and increased accumulation of (ANGII). This may impair reproductive fertility. However, initial studies conclude that both SARS-CoV-2 infection and vaccination would not affect reproductive outcomes, but it is necessary to develop new studies that confirm their applicability. Study design, size, duration A retrospective multicentric cohort study of 428 patients who underwent COS for oocyte donation between January 1st, 2018 and July 31th, 2022 were screened for eligibility and followed up to September 18th, 2022. Oocyte donation cycles were utilized because this model is an excellent choice for controlling known female characteristics Participants/materials, setting, methods Eligibility criteria were donors between 18 to 32 years. Patients were categorized into the vaccinated group if they had received SARS-CoV-2 vaccines (BNT162b2 mRNA Pfizer-Biontech, mRNA-1273 Moderna or inactivated SARS-CoV-2 vaccine Sinovac). The control group was chosen from medical records before March 2020 ensure they were neither infected or vaccinated. Demographic, cycle characteristics, and laboratory outcomes were compared. Normally, distributed data were compared across groups by univariate ANOVA. All P-values were considered significant at < 0.05. Main results and the role of chance In total, 428 patients were included in the study, with 12 recovering from SARS–CoV-2 infection (Group 1), 92 reporting vaccination (Group 2), and 324 patients who underwent COS before March 2020 assigned to the non-exposed group (Group 3). The mean time from recovery to oocyte aspiration was 122 days (range 39-315 days) and 213 days from the first vaccine dose to oocyte aspiration (range 17–249 days). The study's participants had an average age of 24.8 years. Age was found to be normally distributed and did not differ significantly between the three groups (P-value 0,953). Similarly, ovarian reserve markers, as measured by AFC and AMH, did not differ between groups (P-values of 0,787 and 0,423 respectively). No significant differences were observed regarding stimulation duration and total gonadotropin dose. The number of retrieved oocytes, MII oocytes, fertilized oocytes, and good-quality day 5 embryos were also similar between the three groups. Comparing oocyte retrieval rate, mature oocyte rate, normal fertilization rate, and blastocyst formation rate consistently revealed no statistically significant differences. Limitations, reasons for caution The main limitation is its retrospective design. Other limitations include the small sample size of recovered patients, the absence of sperm analyses, and data of live birth rates and neonatal outcomes. Wider implications of the findings SARS-CoV-2 infection and vaccination seem unrelated to detrimental effects on ovarian response or embryo development. These findings contribute to the growing body evidence that supports vaccination in women trying to conceive. Further prospective studies with larger cohort sizes and longer follow-ups are warranted to validate our conclusion. Trial registration number NCT05562479