BNT162b2 COVID-19 Vaccine has no Adverse Effect on Women s In Vitro Fertilization Outcomes and Fertility

Research Article

Austin J Obstet Gynecol. 2022; 9(2): 1204.

BNT162b2 COVID-19 Vaccine has no Adverse Effect on Women’s In Vitro Fertilization Outcomes and Fertility

Safrai M1*, Rottenstreich A1, Herzberg S1, Imbar T1, Reubinoff B1,2 and Ben-Meir A1

1Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center and Faculty of Medicine, Israel

2The Sydney and Judy Swartz Embryonic Stem Cell Research Center of The GoldyneSavad Institution of Gene Therapy, Hadassah Hebrew University Medical Center, Israel

*Corresponding author: Myriam Safrai, Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Ein-Kerem, P.O. Box 12000, Jerusalem, Israel

Received: August 18, 2022; Accepted: September 12, 2022; Published: September 19, 2022

Abstract

Purpose: To investigate the effect of BNT162b2 COVID-19 vaccine on women’s fertility.

Methods: We prospectively collected data of women patients undergoing In Vitro Fertilization (IVF) treatment after completion of 2 doses of BNT162b2 vaccination between February and April 2021 (POST vaccine). For comparison, we reviewed records of the same patients before the vaccination (PRE vaccine) up to February 2019. Each woman served as self-control before and after vaccination. Study outcomes were compared between the PRE- and POSTvaccination groups. Clinical pregnancy values were assessed if data were available for both cycles.

Results: 47 women were eligible, with a mean interval of 362 ± 368 days between the two ovum pick-ups. The numbers of oocytes retrieved, matured oocytes, fertilization rates, and numbers and qualities of embryos at day 3 before-and-after vaccinations were similar for all parameters. The numbers and percentages of clinical pregnancies did not differ significantly between the two vaccination groups.

Conclusion: From our findings, the vaccine does not affect women’s in vitro outcomes and, therefore, fertility. This study repudiates misinformation from unreliable sources, reassuring patients to improve compliance and promote COVID-19 eradication.

Trial registration number: IRB(HMO-21-054), January 2020.

Keywords: BNT162b2; mRNA vaccine; COVID-19; Fertility; Women; SARS-CoV-2

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for causing Coronavirus Disease 19 (COVID-19), has affected over 160 million people worldwide since it was declared a pandemic in March 2020 by the World Health Organization (WHO) [1] and has caused over 3 million deaths [2] worldwide. The resulting urgent need for practical tools to combat COVID-19 has led to the accelerated development and recent approval of the BNT162b2 mRNA vaccine launched by BioNTech and Pfizer [3]. In a large trial, the two-dose regimen of BNT162b2 vaccine was assessed and found to confer a 95% protection rate against SARS-CoV-2 among individuals aged 16 and older [4,5]. Based on this information, a mass vaccination campaign using the BNT162b2 vaccine began in Israel [6], recommending vaccinate the entire population aged 16 and above [5]. The vaccine’s safety profile was previously assessed using self-reporting of local and systemic adverse events, the use of antipyretic or pain medication to treat minor side-effects of the vaccine, and unsolicited adverse severe events infrequently reported [3,7]. However, the effect of the vaccine on fertility has not been initially investigated.

Reproductive-aged women are considered a special population and often are not included in clinical. Indeed, pregnant women and women trying to conceive were excluded from the pivotal clinical trials evaluating the mRNA-based vaccines [3,8,9], resulting in many unanswered questions about the safety of the BNT162b2 vaccine on fertility. Since the vaccine’s launch, vaccination hesitancy has been a significant challenge in COVID eradication [10]. The social media panic has significantly increased the fear and hesitancy to receive the COVID-19 vaccine [11,12] in large parts of the population [10,13]. The impact of the vaccine on fertility has also been the subject of many rumors and misinformation.

The adult female population has another unique and challenging aspect to the morbidity of COVID-19: Pregnant women are at a higher risk of complications and increased risk of perinatal complications if they become infected with COVID-19 [9,14-19]. Therefore the American Society of Reproductive Medicine Task Force does not recommend withholding the vaccine from patients planning to conceive [20]. Despite recent studies showing no adverse effect of the vaccine on women’s fertility [21,22], long-term follow-ups from folliculogenesis through embryo formation and pregnancy rate are scarce. Due to the lack of information and clinical relevance, we aimed to investigate the possible impact of the BNT162b2 COVID-19 vaccine on women’s fertility.

Methods

This study was carried out in a large tertiary center. Our medical center is a university hospital with an In Vitro Fertilization (IVF) unit, which runs an average of 1000 fresh IVF cycles per year. Data were collected from all patients treated in the IVF unit, between February 2 and April 29, 2021, after vaccination of the general population began. Medical records of patients who had received two doses of the BNT162b2 vaccine were retrospectively reviewed (PRE-vaccine), using the hospital’s electronic database, up to January 15, 2017. They were compared to prospectively collected data of those patients (POST-vaccine).

To minimize bias, each woman served as self-control before and after vaccination. Women previously infected by COVID-19 were excluded. Additionally, to neutralize the effect of sperm on fertilization, only Intracytoplasmic Sperm Injection (ICSI) patients who were currently being treated with an ICSI cycle and had an earlier ICSI cycle available were included in the study.

Data obtained included: patient demographics (age and Body Mass Index (BMI)); indication for IVF treatment (i.e., female/male factor, unknown infertility, and need for Pre-implantation Genetic Diagnosis (PGD) or fertility preservation); Follicle Stimulating Hormone (FSH) value; data regarding the IVF cycle (length of Gonadotropin (GT) stimulation and total GT dose, estrogen level on the day before Ovum Pick Up (OPU), the number of oocytes retrieved, the number of mature oocytes, the number of fertilized oocytes, the number and quality of embryos at day 3); and the time since the first dose of the vaccine. The second vaccine dose was given as recommended, 21 days after the first dose [5,7]. The embryos’ quality at day 3 were determined by cell number, symmetry and fragmentation. According to the Society for Assisted Reproductive Technology (SART) grading guidelines, they were graded as good, fair or poor [23]. Clinical pregnancy based on the first hCG value was reported if the data were available for both cycles. Some patients didn’t proceed to embryo transfer, aiming for fertility preservation or PGD testing later on. The pregnancy rate was calculated for the total paired cycle with hCG value available for both cycles (n=15).

The primary outcomes were compared between the PRE and POST vaccination groups and consisted of: the IVF cycle outcomes, including the number of oocytes retrieved; the number of matured oocytes; the fertilization rate; and the number and quality of embryos at day 3.

Statistical Analysis

IVF treatment parameters are presented as median, interquartile range, mean, or percentage. Comparisons between PRE and POSTvaccine values were conducted with Mann Whitney test. A P-value of 0.05 or less was considered significant. The significance of pregnancy rate before and after vaccination was assessed by McNemar’s test. Statistical analyses were carried out using Excel 2013. A sample size of 32 women (in the entire cohort) was required to detect a significant difference of 30% in the number of oocytes retrieved (probability of Type 1 error of 0.05 and 80% power).

Ethical Approval

Approval was obtained from the Institutional Review Board (IRB) of the Hadassah-Hebrew University Medical Center. The requirement for written informed consent was waived by the IRB.

Results

During the study period, 297 women were treated in the IVF unit. More than half (n= 56%) had completed the two doses of the BNT162b2 vaccine. Thirteen percent (n=39) of the women had a prior history of SARS-CoV-2 infection, while 87% (n=258) were eligible for vaccination. In this subgroup of eligible women for vaccination, 64% had completed the two vaccine doses, 2% had received only one dose, and 34% chose not to be vaccinated for COVID-19 (Figure 1).