During the rollout of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), much controversy surrounded the alleged severe or chronic side effects of these agents. One particular concern was the effect of coronavirus disease 2019 (COVID-19) vaccines on fertility, especially in females.
A new Fertility and Sterility study assesses the impact of COVID-19 vaccination in women undergoing assisted reproduction.
Study: COVID-19 Vaccination and Infertility Treatment Outcomes. Image Credit: Rido / Shutterstock.com
Clinical trials for the messenger ribonucleic acid (mRNA) vaccines developed by both Pfizer and Moderna did not include pregnant women due to the risk of unknown effects on the fetus and pregnancy outcomes. After these vaccines received emergency use approval (EUA), most government health agencies recommended that the vaccine be given to all pregnant women, as the complications of COVID-19 were thought to be both more common and severe in these patients than in the non-pregnant population.
However, continuing doubts about the vaccine’s effect on fertility and pregnancy outcomes led to persistently lower-than-expected vaccine uptake. For example, some have suspected that the SARS-CoV-2 vaccine spike protein is antigenically similar to syncytin-1, which is a fusion protein in the human placenta.
Recently, some scientists confirmed that this concern is an extremely unlikely issue because of the low similarity in sequence between these two proteins. Early studies on vaccinated pregnant women showed no safety concerns, with similar results obtained from a study of vaccinated men.
The rate of spontaneous conception among healthy women trying to conceive was also comparable among vaccinated and unvaccinated individuals, though these results were limited by the potential for selection bias, lack of any attempt to identify infertility, and the possibility that very early pregnancy loss could have been overlooked.
In order to provide more reliable safety data, the current study focused on the effect of vaccination with the COVID-19 vaccine.
About the study participants
The Israeli study, conducted at Shamir Medical Center and Herzliya Medical Center, included all vaccinated women between 20 and 42 years of age, treated with in vitro fertilization (IVF). All study participants had received two doses of the PfizerBioNTech BNT162b2 vaccine two or more weeks before starting the treatment cycle.
The scientists looked at the average number of oocytes retrieved per cycle, pregnancy rate, oocyte maturation rate, fertilization rate, number of embryos frozen per cycle, and chemical pregnancy rate.
Of the 200 participants and a similar number of controls who were unvaccinated and also had no history of prior COVID-19, the results showed similar outcomes. The mean number of oocytes retrieved per cycle was about 11 as compared to 10 in cases and controls, respectively. Almost 85% of oocytes matured during intracytoplasmic sperm injection (ICSI) cycles in vaccinated study participants as compared to 80% in the controls.
A much larger number of patients in the vaccinated group had all their embryos frozen, which amounted to approximately 2.5 times as many as the 47 in the control group. This was due to the desire to preserve fertility, for genetic testing, to have surrogate pregnancies, or for ovarian hyperstimulation.
Other risk factors such as smoking, body mass index (BMI), partner’s or patient’s age, cause of infertility, and previous IVF attempts were comparable between the groups. The number of oocytes retrieved per cycle was about 15 in the vaccinated group as compared to about 14 in the control group among freeze-all cycle participants.
No differences were observed in maturation or fertilization rate, and the number of frozen embryos per cycle was 3.3 as compared to 3.6 in the vaccinated women and controls, respectively. At later stages, the number of cleavage embryos was also highly comparable, though day five blastocyst formation was higher in the study group at 2 as compared to 0.6 in the control group.
Fresh embryo transfer
The number of transfer cycles between vaccinated and unvaccinated women was almost the same. The mean number of embryos transferred per cycle was similar, with both cleavage embryos and blastocysts reaching similar numbers.
The clinical pregnancy rate was about 33% in both groups, while the chemical pregnancy rate was similar at 5% and 10% in the vaccinated and control groups, respectively. The number of oocytes retrieved per cycle was eight per cycle, with over 80% maturation and 60% fertilization rates in both groups.
Age remained the major influence on oocyte retrieval rates. With each new year, 0.6 fewer oocytes were retrieved. The duration between vaccination and pregnancy rates showed no correlation, nor did the vaccination show any association with oocyte yields.
The current study showed no difference in the ovarian response to stimulation protocols in terms of oocyte retrieval rates, maturation, fertilization, or pregnancy rates following vaccination with the mRNA vaccine prior to IVF. This refutes the allegation of adverse effects on conception or fertility treatment outcomes.
The study findings corroborate earlier research that showed a pronounced lack of association between oocyte yield or embryo quality following treatment in vaccinated women as compared to the results in the same women with the same treatment before vaccination.
Only one study has explored the effect of COVID-19 on the ovaries, showing no observable impact on their function following recovery from the illness. The fears that SARS-CoV-2 may cause gonadal hormone synthesis to be disrupted, with accompanying reductions in follicle growth and ovulation, through its action on the renin-angiotensin axis in the ovaries or because of systemic hyper-inflammation appear misplaced.
Even in the group of women over the age of 39 years, treatment outcomes were similar in the study and control groups, even though these women are thought to have lower ovarian reserve and thus a decreased fertility potential. Clearly, this is not affected by the COVID-19 vaccines. Early data also suggests that COVID-19 vaccines do not affect sperm parameters.
“In conclusion, this study found no effect of COVID-19 mRNA vaccine on oocyte yield during hormonal stimulation or on pregnancy rates during IVF treatments.”
The study findings demonstrate that COVID-19 vaccination is safe for fertility up to eight weeks of pregnancy. When coupled with the higher risk for complications associated with COVID-19 in pregnancy, the study findings support recommendations for women to receive the COVID-19 vaccine before beginning fertility treatment.