COVID-19 from gamete to post-partum: a mini-review of the current literature
EVMS Jones Institute for Reproductive Medicine: Eastern Virginia Medical School Jones Institute for Reproductive Medicine
It’s been nearly two years since the start of the pandemic, and over a year since the initial vaccines rolled out. There have been multiple claims and misinformation on how Covid-19 and the mRNA vaccines affect both male and female fertility (1). Those fears initially arose from false claims that antibodies against the SARS-CoV-2 spike protein could cross-react with placental protein syncitin-1 and ACE-2 receptors in both ovarian and testicular tissue(2).
Currently, there are three types of covid vaccine available in the US and at least six around the world. The majority of the available literature discusses BNT162b2 (Pfizer-BioNTech) vaccines and mRNA-1273 (Moderna) vaccines and their effect on fertility and pregnancy, with few to none on Ad26.COV.2.S (Janssen) and others (3).
Despite claims that the vaccine affects male fertility, there have been multiple studies proving otherwise. A prospective study of 45 healthy males assessed semen analysis pre and post Covid-19 mRNA vaccination. At a median of 75 days post-vaccination, sperm count, motility, and concentration significantly increased (4). Seven out of 8 men in the study were initially oligospermic, and after receiving the vaccine their sperm concentration increased to a normozoospermic range. Even though semen analysis is not a perfect indicator of fertility, this study reaffirms the absence of negative effects on male gametes.
In contrast, the SARS-CoV-2 illness has been associated with a short-term decrease in sperm production, erectile dysfunction, and orchitis in males (5,6). Parameters such as sperm concentration and total motility decreased and were even notable in participants without fever or symptoms. However, it is still unknown whether vaccinated men who later contracted Covid-19 suffered similar symptoms.
Neither SARS-CoV-2 nor the mRNA vaccine seem to have any significant effect on ovarian fertility. In September 2021, Morris et al evaluated embryo outcomes and fertilization rates in women who received the vaccine contracted SARS-CoV-2, or neither, and found no evidence of harm (7). Patients who had contracted covid before IVF treatment had no differences in their ovarian reserves, treatment outcomes, and pregnancy rates (8,9). In the most recent prospective trial by Palomino et al, they found no variation in AMH levels before and after SARS-CoV-2 infection in 46 women (1.73 ng/ml vs. 1.61 ng/ml, respectively). However, when they subdivided these groups according to their diagnosis, women with normal ovarian reserve had a decrease in their AMH level from 4.6 ng/ml to 3.1 ng/ml after infection (10).
Recently, Kharbanda et al published a study looking at miscarriage rates in the first and second trimesters in pregnant women who received the mRNA vaccine. Out of 105 446 pregnancies, 14.3 % of women had received an mRNA vaccine before 20 weeks’ gestation (11). Amongst those pregnancies, Covid-19 vaccine was received within 28 days prior to 8% of ongoing pregnancy periods and 8.6% of spontaneous abortions. This data highlights the odds of receiving a vaccine prior to a spontaneous abortion were not increased and is unlikely to be an instigating event in miscarriages (11). As we go further along in the pregnancy, women who received the mRNA Covid-19 vaccine had no increase in preterm birth, preeclampsia, c-section, or maternal morbidity in comparison to pre-pandemic pregnant women (12–14).
Conversely, pregnant and recently pregnant women infected with Covid-19 are more likely to be hospitalized even though they are less likely to exhibit symptoms such as fever and dyspnea (15). Women who did present with fever and shortness of breath were 2.5 times more likely to suffer severe maternal complications, and are 5 times more likely to require admission to an intensive care unit and require invasive ventilation (16). The risk of preterm birth is between 50-90% higher in covid infected mothers, and neonates born to Covid-19 positive mothers are more likely to be admitted to the neonatal intensive unit (15,16). Nevertheless, the most impactful statistic by far, is that pregnant women admitted to a hospital with Covid-19 had at least a 20-fold increase in their risk of death (15,16).
In the post-partum period, pregnant women who received the vaccine during pregnancy had equivalent IgG and IgM antibody titer reactions against SARS-CoV-2 compared to non-pregnant women (17). Women with immunity induced by SARS-CoV-2 infection during pregnancy had significantly lower titer levels compared to women who received the vaccine pregnant or otherwise. Antibodies were also detected in both umbilical cord blood and breast milk of lactating mothers, providing passive immunity to their newborns (17).
There are so many benefits to receiving the vaccine with no significant drawbacks, especially in reproductive-aged couples. A joint message by 3 major societies; ACOG, ASRM, and SMFM was released recommending that all eligible persons above 12 years of age, including pregnant and lactating individuals, receive a COVID-19 vaccine or vaccine series (18). It is imperative as patient advocates, we continue resonating this message until the majority of patients are vaccinated.
- Opinion | False Rumors About Covid-19 Vaccines Are Scaring Women - The New York Times [Internet]. Available from: https://www.nytimes.com/2021/01/26/opinion/covid-vaccine-rumors.html
- Head of Pfizer Research: Covid Vaccine is Female Sterilization – Health and Money News [Internet]. Available from: https://archive.is/q5ENl
- Riley LE, Beigi R, Jamieson DJ, Hughes BL, Swamy G, O’ L, et al. COVID-19 Vaccination Considerations for Obstetric-Gynecologic Care [Internet]. 2020;Available from: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/covid-19
- Gonzalez DC, Nassau DE, Khodamoradi K, Ibrahim E, Blachman-Braun R, Ory J, et al. Sperm Parameters Before and After COVID-19 mRNA Vaccination. JAMA 2021;326(3):273–4.
- Pazir Y, Eroglu T, Kose A, Bulut TB, Genc C, Kadihasanoglu M. Impaired semen parameters in patients with confirmed SARS-CoV-2 infection: A prospective cohort study. Andrologia 2021;53(9):e14157.
- Guo T-H, Sang M-Y, Bai S, Ma H, Wan Y-Y, Jiang X-H, et al. Semen parameters in men recovered from COVID-19. Asian J Androl 2021;23(5):479–83.
- Morris RS. SARS-CoV-2 spike protein seropositivity from vaccination or infection does not cause sterility. F&S reports 2021;2(3):253–5.
- Madjunkov M, Dviri M, Librach C. A comprehensive review of the impact of COVID-19 on human reproductive biology, assisted reproduction care and pregnancy: a Canadian perspective. J Ovarian Res 2020;13(1):140.
- Li F, Lu H, Zhang Q, Li X, Wang T, Liu Q, et al. Impact of COVID-19 on female fertility: a systematic review and meta-analysis protocol. BMJ Open 2021;11(2):e045524.
- Cruz Palomino M, González-Ravina C, Pacheco A, Requena A. O-079 Could ovarian reserve be affected after SARS-CoV-2 infection? Hum Reprod [Internet] 2021;36(Supplement_1). Available from: https://doi.org/10.1093/humrep/deab125.009
- Kharbanda EO, Haapala J, DeSilva M, Vazquez-Benitez G, Vesco KK, Naleway AL, et al. Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy. JAMA [Internet] 2021;Available from: https://doi.org/10.1001/jama.2021.15494
- Stafford IA, Parchem JG, Sibai BM. The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations. Am J Obstet Gynecol 2021;224(5):484–95.
- Blakeway H, Prasad S, Kalafat E, Heath PT, Ladhani SN, Le Doare K, et al. COVID-19 vaccination during pregnancy: coverage and safety. Am J Obstet Gynecol 2021;
- Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. N Engl J Med 2021;384(24):2273–82.
- Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ [Internet] 2020;370:m3320. Available from: http://www.bmj.com/content/370/bmj.m3320.abstract
- 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. JAMA Pediatr [Internet] 2021;175(8):817–26. Available from: https://doi.org/10.1001/jamapediatrics.2021.1050
- Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol 2021;225(3):303.e1-303.e17.
- Medical Experts Continue to Assert that COVID Vaccines Do Not Impact Fertility | ACOG [Internet]. Available from: https://www.acog.org/news/news-releases/2021/02/medical-experts-assert-covid-vaccines-do-not-impact-fertility