Fertility rates and birth outcomes after ChAdOx1 nCoV-19 (AZD1222) vaccination

Fears of adverse effects of COVID-19 vaccination on fertility have affected vaccine uptake in some communities. Despite the absence of supporting evidence for such a risk, low biological plausibility, and preliminary data supporting the safety of mRNA vaccines in pregnancy, this claim has become widespread, and it has been challenged by WHO.

Vaccine hesitancy during pregnancy, or among women of childbearing age, could have substantial public health consequences because infection with SARS-CoV-2 during pregnancy is a risk factor for severe maternal illness and complications.We have analysed pregnancies that have occurred in four ongoing phase 1, phase 2, and phase 3 clinical trials of ChAdOx1 nCoV-19 (AZD1222)

121 (1%) of 9755 participants reported a pregnancy during the trials. The fertility outcome analysis set included 93 pregnant women, 50 of whom received ChAdOx1 nCoV-19, and 43 of whom received the control vaccine). The pregnancy outcome analysis set included 107 women (72 of whom received ChAdOx1 nCoV-19, and 35 of whom received the control vaccine; appendix p 1). Miscarriage was defined as pregnancy loss before 23 weeks of gestation. Baseline characteristics were similar between the vaccine and control groups, with the biggest differences being age and current alcohol use (appendix p 2).

We found no evidence of an association between reduced fertility and vaccination with ChAdOx1 nCoV-19 (p=0·53–0·80; table 1; for fertility rates by site, see appendix p 3). Analysis of pregnancy outcomes (table 2) excluded women in the control vaccine groups who had received either ChAdOx1 nCoV-19 or an mRNA vaccine as part of a national vaccine roll-out programme (n=14, including 11 women vaccinated after unmasking and during pregnancy (table 1), plus three additional women who received an mRNA vaccine before pregnancy; appendix p 2). 56 (52%) of 107 pregnancies in the pregnancy outcome analysis set were ongoing at the time of data lock on July 1, 2021.

Notably, the rate of miscarriage was no higher in the ChAdOx1 nCoV-19 group than in the control group, with a risk ratio (RR) of 0·67 (p=0·51). Adjusting the analysis for the effect of possible confounders kept the RR below but closer to unity at 0·84 (appendix p 4). 15 livebirths had taken place by the time of the analysis, and the three preterm births in the ChAdOx1 nCoV-19 group were in the late preterm stage (34–37 weeks of gestation). No stillbirths or neonatal deaths were reported in either group.

No terminations of pregnancy were reported in Brazil. However, termination of pregnancy is illegal in Brazil, and uncertainty remains about whether the reports of early pregnancy losses were all miscarriages. Therefore, a combined analysis of either miscarriage or termination was done for all sites (table 2), with separate subgroup analyses for termination alone and for miscarriage alone, excluding the Brazilian data. This subgroup included 24 participants who received a control vaccine and 43 participants who received ChAdOx1 nCoV-19.

Fertility was unaffected by vaccination with ChAdOx1 nCoV-19. Furthermore, compared with women who received the control vaccine, there was no increased risk of miscarriage and no instances of stillbirth in women vaccinated before pregnancy in global clinical trials of ChAdOx1 nCoV-19.

With increasing availability of misinformation, which continues to affect vaccine uptake, these data, along with published data on mRNA vaccines,

can provide evidence to support women in making decisions regarding vaccination.