eAppendix. Online Only Supplemental Material
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Jacobs E, Summers K, Sparks A, Mejia R. Fresh Embryo Transfer Cycle Characteristics and Outcomes Following In Vitro Fertilization via Intracytoplasmic Sperm Injection Among Patients With and Without COVID-19 Vaccination. JAMA Netw Open. 2022;5(4):e228625. doi:10.1001/jamanetworkopen.2022.8625
Women of reproductive age have been at the forefront of COVID-19 vaccine hesitancy, citing concerns about the vaccine’s effect on future fertility, current pregnancy, and breastfeeding (among others).1 As of February 2022, only 57% of pregnant patients were fully vaccinated against COVID-19 prior to becoming pregnant, a rate that lags that of the general population.2 To date, current literature surrounding COVID-19 vaccination and potential associations with infertility have been performed mainly in frozen embryo transfer cycles or in vitro fertilization cycles (IVF) using intracytoplasmic sperm injection (ICSI), both of which do not occur in in vivo conception.3,4 The aim of this study was to investigate the association of COVID-19 vaccination status with IVF-fresh embryo transfer cycle stimulation characteristics and clinical outcomes.
The University of Iowa institutional review board approved this retrospective cohort study. Patients undergoing IVF-fresh embryo transfer cycles at a single academic institution from December 14, 2020, to September 30, 2021, were included. All patients gave written informed consent to be included in our IVF institutional research database. Cycle characteristics and clinical outcomes were compared between COVID-19 vaccinated and unvaccinated patients. Vaccination status was determined by accessing immunization records in the electronic medical record for each patient. Bivariate analysis was performed using t tests, Mann-Whitney U tests, and χ2 tests. Generalized estimating equations were used to control for multiple cycles per patient and odds ratios were calculated adjusting for age and body mass index (BMI). In addition, subanalysis was performed for (1) exclusion of day 5 morula transfers and (2) standard insemination–only cycles. Additional methods are described in the eAppendix of the Supplement. Statistical analysis was performed using SPSS version 27 (IBM Corp), and a 2-sided P < .05 was considered statistically significant.
Study demographics and clinical characteristics are shown in Table 1; 142 patients were vaccinated against COVID-19 and 138 patients were unvaccinated. The majority of patients were young, nulliparous, and overweight. As seen in Table 1, the 2 groups were similar at baseline. In the vaccinated group, 127 patients (89.7%) were fully vaccinated and 15 patients (10.6%) were partially vaccinated. The mean (SD) time from last vaccination to oocyte retrieval was 93 (65) days. There was no difference in ovarian reserve (mean [SD] antral follicle count for vaccinated group: 23  vs unvaccinated group: 24 ; P = .42) or ovarian response (mean [SD] days of gonadotropin stimulation for vaccinated group: 9.8 [1.6] vs unvaccinated group: 9.6 [1.4]) (Table 1). The mean (SD) number of oocytes retrieved (vaccinated group: 14  vs unvaccinated group: 15 ) and mean (SD) number of useable embryos produced (vaccinated group: 4  vs unvaccinated group: 4 ) were also similar between groups (Table 2). Vaccinated patients had higher mean (SD) fertilization rates than unvaccinated patients (77.45% [41.45%] vs 68.66% [20.51%]; P = .03). In addition, after controlling for factors that can influence IVF success (age and BMI), there were no significant differences in ongoing clinical pregnancy rate (adjusted odds ratio [aOR], 0.79; 95% CI, 0.48-1.29) and miscarriage rate (aOR, 2.15; 95% CI, 0.62-7.47) in vaccinated vs unvaccinated patients. A subanalysis excluding day 5 morula transfers found no difference in ongoing clinical pregnancy rate (aOR, 0.82; 95% CI, 0.49-1.36) and miscarriage rate (aOR, 1.28; 95% CI, 0.32-5.07). Lastly, when comparing standard insemination-only cycles, there was also no difference in ongoing clinical pregnancy (aOR, 0.94; 95% CI, 0.47-1.87) or miscarriage rate (aOR, 4.09; 95% CI, 0.35-47.74).
To our knowledge, this is one of the first studies to evaluate the association of COVID-19 vaccination status with IVF-fresh embryo transfer cycles (including a high proportion of standard insemination cycles). We found no evidence to suggest that COVID-19 vaccination negatively affects cycle stimulation characteristics, embryological variables, or clinical outcomes in IVF. Current and emerging scientific evidence continues to support that COVID-19 vaccination is safe and effective and has no impact on fertility. The results of this study can be used to provide reassuring data to patients planning on pregnancy considering COVID-19 vaccination.
Accepted for Publication: March 7, 2022.
Published: April 22, 2022. doi:10.1001/jamanetworkopen.2022.8625
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Jacobs E et al. JAMA Network Open.
Corresponding Author: Emily Jacobs, MD, MS, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Iowa Hospital and Clinics, 200 Hawkins Dr, Iowa City, IA 52242 (email@example.com).
Author Contributions: Drs Jacobs and Mejia had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Jacobs, Sparks, Mejia.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Jacobs.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Jacobs, Summers.
Administrative, technical, or material support: Jacobs, Sparks.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: This study was presented as an oral presentation at the annual meeting of the Pacific Coast Reproductive Society; March 25, 2022; Indian Wells, California.