As of early January 2022, only 42% of pregnant individuals had received at least one dose of a coronavirus disease 2019 (COVID-19) vaccine,1 a rate that lags behind that of the general population in the United States. Lack of confidence about the safety of the vaccine in pregnancy as well as concern for potential risks to the fetus are the most common reasons for vaccine hesitancy in reproductive-aged women.2 The decision to exclude pregnant and lactating individuals from early COVID-19 vaccine clinical trials has confirmed what we knew all along—the absence of medical information can be just as harmful as misinformation.
To chip away at vaccine uncertainty, we must acknowledge and validate the desire most patients have to minimize risk and maximize benefit when it comes to their health choices. In a recently published study in Obstetrics & Gynecology, Edelman et al3 address concerns about COVID-19 vaccination and its potential effect on the menstrual cycle. Anecdotal reports of menstrual cycle disruptions after COVID-19 vaccination have provoked fear about the vaccine's effect on gynecologic health and future fertility. This study evaluated prospectively collected data on menstrual cycle characteristics before and after COVID-19 vaccination in 2,403 individuals compared with the menstrual cycle characteristics of 1,556 unvaccinated individuals. Vaccination against COVID-19 was associated with a clinically insignificant (increase in cycle duration of about 1 day) change in menstrual cycle length that was transient; menstrual cycle irregularities returned to baseline within approximately two menstrual cycles. Cycle disturbances were more pronounced when two vaccine doses were given within the same menstrual cycle. These findings are not entirely surprising; vaccines have been known to cause nonspecific side effects due to activation of the immune system. In addition, the menstrual cycle is considered a vital sign of gynecologic health and can be affected by various factors, including obesity, smoking, stress, environmental toxins, and the overall health of an individual. Recent studies have shown similar changes to the menstrual cycle in individuals with COVID-19 (primarily temporary amenorrhea, infrequent menses, or both).4 Although it would have been ideal to concurrently study other cycle characteristics (amount of bleeding, dysmenorrhea) in addition to cycle length and menses length, the results of this study can be used to reassure patients that any changes to their menstrual cycle from COVID-19 vaccination are temporary and clinically insignificant. Patients are less likely to perceive vaccination as a negative experience if they feel adequately counseled and appropriately informed about symptoms they may experience afterwards. Data from this study suggest no long-term effects on menstrual cyclicity and can reassure wary patients about vaccination.
A study published on January 25, 2022, in Obstetrics & Gynecology, performed by Aharon et al,5 examined in vitro fertilization (IVF) cycle characteristics and clinical outcomes in COVID-19–vaccinated and COVID-19–unvaccinated patients. Compared with natural conception, IVF has the advantage of allowing the study of numerous specific aspects of human reproduction. This study included patients in two overlapping cohorts: those who had controlled ovarian hyperstimulation for an IVF procedure and those who had frozen euploid embryo transfer. After controlling for factors known to affect IVF success, including age, body mass index (BMI), gravidity, parity, serum anti-müllerian hormone level, and stimulation protocol, there was no difference in any important clinical outcomes when comparing vaccinated with unvaccinated patients, including oocyte number, maturation, fertilization rates by intracytoplasmic sperm injection, euploid embryo rates, miscarriage rates, and clinical pregnancy rates. The detailed analysis of human reproduction in this study suggests strongly, and confirms previously published literature, that COVID-19 vaccination does not impair embryo implantation or cause sterility.6
There is now an abundance of data to support COVID-19 vaccine safety and efficacy. The studies by Edelman et al and Aharon et al add to the growing body of literature on this topic and can be used in counseling reproductive-aged individuals with vaccine concerns. When all else fails, one can combat the fear of the unknown with what is known: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy consistently and substantially increases the risk of severe maternal morbidity and mortality as well as neonatal complications.7 In accordance with the American College of Obstetricians and Gynecologists, the American Society for Reproductive Medicine, and the Society for Maternal-Fetal Medicine, obstetrician–gynecologists must stand united in continuing to strongly recommend COVID-19 vaccination in all individuals trying to conceive and in those who are currently pregnant or lactating. Lastly, in some circumstances, no amount of high-quality scientific data will overturn strongly upheld falsehoods of vaccine misinformation. In those cases, we must do what we have always done—provide compassionate and evidence-based care to all individuals.
1. Centers for Disease Control and Prevention. Covid-19 vaccination among pregnant people aged 18-49 years overall, by race/ethnicity, and date reported to CDC - Vaccine Safety Datalink,* United States. Accessed January 13, 2022. https://covid.cdc.gov/covid-data-tracker/#vaccinations-pregnant-women
2. Shook LL, Kishkovich TP, Edlow AG. Countering COVID-19 vaccine hesitancy in pregnancy: the “4 Cs”. Am J Perinatal 2021 Oct 19 [epub ahead of print]. doi: 10.1055/a-1673-5546
3. Edelman A, Boniface ER, Benhar E, Han L, Matteson KA, Favaro C, et al. Association between menstrual cycle length and coronavirus disease 2019 (COVID-19) vaccination: a U.S. cohort. Obstet Gynecol 2022 Jan 5 [Epub ahead of print]. doi: 10.1097/AOG.0000000000004695
4. Sharp GC, Fraser A, Sawyer G, Kountourides G, Easey KE, Ford G, et al. The COVID-19 pandemic and the menstrual cycle: research gaps and opportunities. Int J Epidemiol 2021 Dec 2 [Epub ahead of print]. doi: 10.1093/ije/dyab239
5. Aharon D, Lederman M, Ghofranian A, Hernandez-Nieto C, Canon C, Hanley W, et al. In vitro fertilization and early pregnancy outcomes after coronavirus disease 2019 (COVID-19) vaccination. Obstet Gynecol 2022 Jan 25 [epub ahead of print]. doi:10.1093/ije/dyab239
6. Morris RS. SARS-CoV-2 spike protein seropositivity from vaccination or infection does not cause sterility. F S Rep 2021;2:253–5. doi:10.1016/j.xfre.2021.05.010
7. Villar J, Ariff S, Gunier RB, Thiruvengadam R, Rauch S, Kholin A, et al. Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: The INTERCOVID Multinational Cohort Study [published erratum appears in JAMA Pediatr 2022;176:104]. JAMA Pediatr 2021;175:817–26. doi: 10.1001/jamapediatrics.2021.1050