STUDY QUESTION: Does the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have an association with ovarian reserve as expressed by circulating anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER: Ovarian reserve as assessed by serum AMH levels is not altered at 3 months following mRNA SARS-CoV-2 vaccination. WHAT IS KNOWN ALREADY: A possible impact of SARS-CoV-2 infection or vaccination through an interaction between the oocyte and the somatic cells could not be ruled out, however, data are limited. STUDY DESIGN, SIZE, DURATION: This is a prospective study conducted at a university affiliated tertiary medical center between February and March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study population included reproductive aged women (18-42 years) that were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart). Women with ovarian failure, under fertility treatments, during pregnancy, previous Covid-19 infection or vaccinated were excluded from the study. Blood samples were collected for AMH levels before the first mRNA vaccine administration. Additional blood samples after 3 months were collected for AMH and anti-Covid-19 antibody levels. Primary outcome was defined as the absolute and percentage change in AMH levels. MAIN RESULTS AND THE ROLE OF CHANCE: The study group consisted of 129 women who received two mRNA vaccinations. Mean AMH levels were 5.3 (±SD 4.29) µg/l and 5.3 (±SD 4.50) µg/l at baseline and after 3 months, respectively (P = 0.11). To account for possible age-specific changes of AMH, sub-analyses were performed for three age groups: <30, 30-35 and >35 years. AMH levels were significantly lower for women older than 35 years at all times (P = 0.001 for pre and post vaccination AMH levels versus younger women). However, no significant differences for the changes in AMH levels before and after vaccinations (Delta AMH) were observed for the three age groups (P = 0.46). Additionally, after controlling for age, no association was found between the degree of immunity response and AMH levels. LIMITATIONS, REASONS FOR CAUTION: Although it was prospectively designed, for ethical reasons we could not assign a priori a randomized unvaccinated control group. This study examined plasma AMH levels at 3 months after the first vaccination. It could be argued that possible deleterious ovarian and AMH changes caused by the SARS-CoV-2 mRNA vaccinations might take effect only at a later time. Only longer-term studies will be able to examine this issue. WIDER IMPLICATIONS OF THE FINDINGS: The results of the study provide reassurance for women hesitant to complete vaccination against Covid 19 due to concerns regarding its effect on future fertility. This information could be of significant value to physicians and patients alike. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by Sheba Medical Center institutional sources. All authors have nothing to disclose. TRIAL REGISTRATION NUMBER: The study protocol was approved by the 'Sheba Medical Center' Ethical Committee Review Board (ID 8121-21-SMC) on 8 February 2021 and was registered at the National Institutes of Health (NCT04748172).
STUDY QUESTION: Does the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have an association with ovarian reserve as expressed by circulating anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER: Ovarian reserve as assessed by serum AMH levels is not altered at 3 months following mRNA SARS-CoV-2 vaccination. WHAT IS KNOWN ALREADY: A possible impact of SARS-CoV-2 infection or vaccination through an interaction between the oocyte and the somatic cells could not be ruled out, however, data are limited. STUDY DESIGN, SIZE, DURATION: This is a prospective study conducted at a university affiliated tertiary medical center between February and March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study population included reproductive aged women (18-42 years) that were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart). Women with ovarian failure, under fertility treatments, during pregnancy, previous Covid-19 infection or vaccinated were excluded from the study. Blood samples were collected for AMH levels before the first mRNA vaccine administration. Additional blood samples after 3 months were collected for AMH and anti-Covid-19 antibody levels. Primary outcome was defined as the absolute and percentage change in AMH levels. MAIN RESULTS AND THE ROLE OF CHANCE: The study group consisted of 129 women who received two mRNA vaccinations. Mean AMH levels were 5.3 (±SD 4.29) µg/l and 5.3 (±SD 4.50) µg/l at baseline and after 3 months, respectively (P = 0.11). To account for possible age-specific changes of AMH, sub-analyses were performed for three age groups: <30, 30-35 and >35 years. AMH levels were significantly lower for women older than 35 years at all times (P = 0.001 for pre and post vaccination AMH levels versus younger women). However, no significant differences for the changes in AMH levels before and after vaccinations (Delta AMH) were observed for the three age groups (P = 0.46). Additionally, after controlling for age, no association was found between the degree of immunity response and AMH levels. LIMITATIONS, REASONS FOR CAUTION: Although it was prospectively designed, for ethical reasons we could not assign a priori a randomized unvaccinated control group. This study examined plasma AMH levels at 3 months after the first vaccination. It could be argued that possible deleterious ovarian and AMH changes caused by the SARS-CoV-2 mRNA vaccinations might take effect only at a later time. Only longer-term studies will be able to examine this issue. WIDER IMPLICATIONS OF THE FINDINGS: The results of the study provide reassurance for women hesitant to complete vaccination against Covid 19 due to concerns regarding its effect on future fertility. This information could be of significant value to physicians and patients alike. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by Sheba Medical Center institutional sources. All authors have nothing to disclose. TRIAL REGISTRATION NUMBER: The study protocol was approved by the 'Sheba Medical Center' Ethical Committee Review Board (ID 8121-21-SMC) on 8 February 2021 and was registered at the National Institutes of Health (NCT04748172).
Authors: Pedro Brandão; Antonio Pellicer; Marcos Meseguer; José Remohí; Nicolás Garrido; Juan Antonio García-Velasco Journal: Reprod Biomed Online Date: 2022-05-29 Impact factor: 4.567