I’m searching for a good home for this piece, but in the meantime I think the information needs to get out! So, I’m dusting off this old blog.
The group I have seen most hesitant about taking the new COVID-19 vaccines is women of reproductive age who care about their fertility. I’d like to (1) acknowledge that, in general, large health organizations have not prioritized fertility, and (2) go through the available data on COVID-19 vaccines and fertility to argue that, for these vaccines, there is little cause for fertility concerns.
Who am I? I hold a PhD in Bioengineering from Rice University. In my day job, I develop medical devices to save newborn and maternal lives in low-resource settings like sub-Saharan Africa. I am a mom who has suffered infertility and miscarriage and who hopes for more children. I have practiced fertility awareness methods (FAMs) my whole marriage. I am also a survivor of another new virus, West Nile, which gave me symptoms lasting over 10 years similar to those experienced in long COVID – an experience I’m not eager to repeat.
In short, I’m someone who’s concerned about health and fertility and who also has the training to interpret the available data on COVID-19.
Fertility Concerns
First, I want to acknowledge that it is good to be cautious about fertility concerns.
When the first question a new OB/GYN asks you is, “What birth control are you on?,” you wonder if she shares your values.
When major healthcare funders address poverty primarily by promoting reduced family size, it’s hard to trust that they respect the life of your future children.
The dominant healthcare paradigm is that “fewer children is better.” When that same healthcare system tells you, “This product is safe for your fertility,” many women are skeptical.
This article, written by a female scientist and fellow skeptic, will help you look at the data to say that yes, in this case, the COVID-19 vaccines seem to be safe for fertility, pregnancy, and breastfeeding.
The Good News We Have on COVID-19 Vaccines
Let’s go through the available data in roughly chronological order.
Pfizer and Moderna’s mRNA vaccines were the first to be released. When the companies requested Emergency Use Authorization from the FDA, the public gained access to much of the data from their clinical trials. Here’s what that revealed.
Moderna’s application is here.
You’re looking at the section on the bottom of pg 44: “Pregnancies.”
First, let’s talk about trial design. For an assortment of reasons, pregnant women are typically excluded from clinical trials – this protects women, their babies, and manufacturers from awful tragedies like thalidomide, but also excludes pregnant women from the potential benefits of the research (For a fantastic article on this issue, read COVID-19 Trials Exclude Pregnant, Breastfeeding, Menstruating Women). Moderna intended to exclude pregnant women from the Phase 3 trial, but a few women got pregnant during the trial anyway, and Moderna reported the data to the FDA. In this trial, 6 women who got the vaccine became pregnant and 7 women in the placebo group got pregnant. At the time of data submission, the two problems reported were both in the placebo group (one miscarriage, one elective abortion). No cases of miscarriage, stillbirth, or other pregnancy-related problems were reported in the 6 pregnant women who received the vaccine.
The second paragraph in that section reports the results of the so-called DART studies (developmental and reproductive toxicity). In DART studies, the vaccine is given to rats, who have short pregnancies, to quickly get a sense of any potential problems for humans. Moderna saw no concerns in their DART studies for the mothers or babies. This test is not a perfect analog for humans, but it is another pointer towards the vaccine being safe for fertility.
These results are great news! It’s a small data set, but looks promising so far. Below is the same analysis for the other two vaccines approved for the US.
The section on pregnancy is at the bottom of pg 42. Like Moderna, they intended to exclude pregnant women but a few women got pregnant during the study. 12 pregnancies were in the vaccine group; 11 in the placebo group. The two issues noted at time of filing (1 miscarriage, 1 retained products of conception) were both in the placebo group. Pfizer completed their DART studies on rats after filing the Emergency Use Authorization (EUA) above (https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-commence-global-clinical-trial-evaluate). Like Moderna, no problems were noted.
Johnson and Johnson’s application is here. Pregnancy and DART data is on pg 52.
8 women became pregnant during the J&J trial, with 4 in the vaccine group and 4 in the placebo group. There were 2 adverse events in the vaccine group (1 miscarriage, 1 ectopic pregnancy) and 3 adverse events in the placebo group (1 incomplete abortion[1], 2 elective abortions). Because the rates were similar in vaccine and placebo groups, there is no evidence that the vaccine caused the adverse events. DART data on rats also showed no adverse effects on female reproduction, fetal/embryonal development, or postnatal development.
Studies are ongoing
Now that Phase 3 trials with non-pregnant women went well, we’re starting to see studies specifically targeting pregnancy. Pfizer has begun enrolling for a placebo-controlled clinical trial (the most rigorous kind!) for pregnant women. Data from this study likely won’t be out until next year, and it thus won’t help women who are currently pregnant make decisions about the vaccine.
v-safe is a CDC system collecting reports of side effects after people receive any of the vaccines (vsafe.cdc.gov). People who report pregnancy at the time of or after receiving the vaccine are invited to participate in the v-safe Pregnancy Registry Scientists are actively monitoring these reports for any warning signs, and those results will be shared with the public.
More Recent Data on COVID-19 Vaccines and Fertility
A recent publication followed pregnant and lactating women who had been given Pfizer or Moderna vaccines. They found:
- Similar vaccine-induced antibody levels in pregnant, lactating, and non-pregnant women, implying that the vaccines work well even during pregnancy
- That vaccines produced higher antibody titers in pregnant women than did natural infection with COVID-19, implying a greater protection against reinfection
- Vaccine-generated antibodies were in umbilical cord blood of babies delivered during the study and in breastmilk samples, implying that babies of vaccinated mothers receive some protection against COVID-19
Though their main purpose was looking at antibody levels, the researchers also tracked adverse events post-vaccination and noted no differences in reactions in pregnant vs. non-pregnant recipients.
We also have self-reported data from people who have received the vaccine in the v-safe system. That data was recently analyzed in a peer-reviewed study and contains women who received either the Moderna or the Pfizer vaccine. Remember that v-safe contains self-reported data and, without a control or placebo group, it is difficult to tell whether an event is due to the vaccine or would have happened anyway. Nevertheless, v-safe is a good way to monitor trends in side effects. The most important summary is in Table 4, where they compare rates of adverse events from before the pandemic (unvaccinated women) to rates in vaccinated pregnant women. The rates are very similar: 10-26% miscarriage rate in women before the pandemic; 12.6% in vaccinated pregnant women. Rates for stillbirth, preterm birth, small size for gestational age, congenital anomalies (birth defects), and neonatal death are all similar in non-vaccinated and in vaccinated women. This data strongly suggests that the vaccine is not responsible for any problems in pregnancy.
Both of these data sets are great news for pregnant and lactating women!
But I hear those of you trying to conceive saying, “What about me? Where’s my data?” Well, fertility data is hard to gather because so many variables affect a couple’s ability to conceive. A well-designed study to assess a vaccine’s effects specifically on conception rates would require a large number of participants and time (and thus funding).
However, we have two strong reasons for believing the COVID-19 vaccines will not affect fertility: (1) the above data that they have no adverse effects in pregnancy and (2) the biological mechanism of the vaccine.
No plausible biological mechanism for it to affect fertility
Let’s acknowledge that fertility is a really important topic to a lot of people (including you, since you’ve made it this far in this article!). That means that preying on your fear of infertility, miscarriage, or harm to your baby is a really profitable way for bad actors to get you to listen to them, or to buy their alternative health product. Bad news and conspiracy theories naturally travel faster than the careful science that seeks to discern the truth. Let’s carefully look at how the vaccines work and address some of the theories going around. I will focus on the mRNA technology used in Pfizer and Moderna’s vaccines because this is a new type of vaccine that has many people questioning its possible effects.
As a brief reminder of high school biology, the “central dogma” of biology states that DNA makes RNA makes proteins. DNA is housed in the nucleus of your cells and holds the “reference library” copy of all the information your body needs to make proteins. That information is copied into mRNA which is translated into a protein. It’s like going in to a reference library (nucleus), opening up a cookbook (DNA), and writing down a recipe on a piece of scratch paper (mRNA). You then take the scrap paper out of the library and go home to bake a cake (protein) in your kitchen. The mRNA, like scratch paper, is not very stable and gets destroyed rather quickly; the protein sticks around to build muscle or fight infection.
The Pfizer and Moderna mRNA vaccines use this natural process for building proteins by ignoring the DNA and nucleus altogether. In my baking analogy, the vaccine knocks on your kitchen door and hands your body a recipe it tore out of a magazine. Your body blindly follows the recipe (mRNA vaccine) to create a protein (in this case, the spike protein on the SARS-COV-2 virus), which it then recognizes as foreign and creates antibodies against it. The mRNA vaccine then degrades rather quickly: on the order of hours. This vaccine does not alter the reference library (nuclear DNA). All that’s left after the vaccine instructions degrade is your body’s cells that have learned how to make antibodies against COVID. Hooray! (For a different, entertaining explanation of the vaccine, check out this short video.)
This vaccine also does not have any plausible effect on your reproductive system; it’s simply telling cells to do what they already do naturally: turn mRNA into proteins. It has no specific focus on reproductive organs. Remember that we can ask all sorts of questions about a new treatment: “But will it cause my left big toe to itch? Did you study that?” And the answer, other than for foot anti-fungal cream, will be, “No, we didn’t specifically study the itchiness of big toes. There was no plausible biological mechanism for the treatment to affect big toes, and we didn’t see concerning reports of itchiness during the Phase 1-3 trials when we watch for all sorts of side effects.” Similarly for COVID-19 vaccines and fertility: I expect there will be studies down the road simply because fertility is so important, but there have not been many dedicated studies on fertility/conception rates because there is no plausible effect of the vaccine on fertility and no concerning signs were seen in the initial studies.
We do have one study beginning to look at any effects of COVID-19 and the vaccines on ovaries: a pre-print article analyzing the effect of COVID-19 infection and the Pfizer COVID vaccine on ovarian follicles was recently posted. Pre-print articles have not been yet reviewed by other scientists, but are posted to get information out quickly, especially for fast-moving issues like COVID. Take these findings with a large grain of salt until they are peer-reviewed. In this study, several small groups of women recovering from COVID-19 infection (9 women), vaccinated (9 women), and women who were uninfected and unvaccinated (14 women) were studied when they had eggs collected for IVF. The scientists found anti-COVID antibodies in the follicle fluid in both recovering and vaccinated women, but no differences among the three groups in terms of follicle quality (estradiol, progesterone, or number of eggs). We should continue to watch for the peer-reviewed version of this study to be published and for larger studies to follow, but this is really encouraging data for those who are trying to conceive and wish to get the vaccine.
“What about long-term effects? Aren’t drugs studied for years to observe long-term effects?” Great question! With medications, we tend to be more concerned about long-term effects because people take the medicines for such a long time. Blood pressure medication or anti-depressants are taken daily for years. That’s a long time for the medicine to affect your body. Vaccines, in contrast, are given in one or two doses and then your body never sees them again. Any systemic effects from vaccines should appear in the first few months after administration. That’s one of the things the Phase 3 trials looked for during 2020, and one of the reasons we had to wait for vaccines to be approved! With these vaccines, we see no indication of any long-term effects on fertility, or otherwise.
“I’m hearing reports about unusual periods after the vaccine.”
As I’m writing this article, social media is ramping up with reports from women about unusual bleeding after receiving the vaccine: early or late periods, heavier bleeding, or heavier cramping (https://tarahaelle.medium.com/lack-of-data-on-covid-19-vaccines-and-periods-inspired-two-feminist-scientists-to-learn-more-b4c29395fb5; https://www.health.com/condition/infectious-diseases/coronavirus/can-covid-vaccine-affect-my-period). We have not seen these side effects reported in any formal scientific studies. It’s too early to tell whether that’s a result of a systemic dismissal of women’s issues in medical research, a lack of true or strong association with the vaccine (for example, people who don’t normally pay attention to their periods pay more attention post-vaccine, known as “recall bias”), or some combination of both. Researchers at the University of Illinois are collecting reports from vaccinated women to study this effect (you can participate here). Comparisons to a placebo group, or at minimum women who haven’t received the vaccine, will be important to discern which effects are truly caused by the vaccine.
Most surveyed scientists believe that, if this is associated with the vaccine, the effects are temporary (1-2 cycles) and have no plausible effect on infertility or miscarriage. Possible reasons for changes in menstruation include stress associated with the vaccine and its unpleasant side effects (practitioners of FAMs are well aware of the effects of stress on menstrual cycles!) or that the lining of the uterus, a tissue involved in the immune response, is responding to the vaccine like the rest of the body is, and it manifests in increased bleeding. These mechanisms would also explain symptoms resolving within a cycle or two after vaccination, which agrees with many of the anecdotal reports on social media.
Continue to watch for reports on this issue, keeping in mind that correlation (“I got a vaccine and I had a wonky period”) does not always imply causation (“A vaccine caused my wonky period”). Good studies evaluating causation will also include women who did not receive the vaccine as a control group.
Weighing the Risks: COVID-19 infection vs. COVID-19 vaccination
Despite all of this really encouraging data, no one can tell you 100% that this vaccine will not negatively affect you. You and your doctor must weigh the risks of vaccination (which I have argued are low) against the risks of COVID-19 infection (which are known and high for pregnant women).
If you live in an isolated cabin in the woods and never encounter another person, your risk of contracting COVID-19 may be very low! Most of us, however, want to have some interaction with the outside world before we’ve gathered 20 years of data on the vaccine. That interaction carries risk of COVID-19 infection, and COVID-19 infection has known negative effects on pregnant women and on fertility:
- Pregnant women are more likely than non-pregnant women to require hospitalization for COVID-19. Pregnant women with underlying conditions are at especially high risk for complications from COVID-19.
- Pregnant women with COVID-19 have higher rates of pre-term birth than those not-infected and higher rates of their babies needing NICU care.
- Moms with COVID-19 had increased odds of maternal death compared to those without COVID-19.
- There are ongoing questions about COVID-19’s impact on the placenta and whether it is the cause of miscarriages and stillbirths due to COVID’s propensity to cause blood clots.
New studies are showing that COVID-19 infection in men reduces semen volume and sperm motility, morphology, and concentration. The authors believe these effects are temporary, but more research needs to be done.
The only study examining any effects of COVID-19 infection on female fertility (the pre-print mentioned above) showed no detrimental effects on ovarian follicles. Changes in female fertility, however, can take longer to study than changes in sperm.
Additionally, COVID-19 is such a contagious virus that your infection poses a risk to all the loved ones around you: your children, your husband, your parents, your friends.
Given the incomplete but good evidence for vaccine safety during pregnancy, the strong evidence of infection danger in pregnancy, and the known danger of spreading infection to our loved ones, can we really afford for all reproductive-aged women to abstain from the vaccine?
I think the answer is “no.” I’m grateful to be fully vaccinated with the Moderna shot.
I will try to answer questions posed in good faith in the comments, but I do have a day job and will not be actively moderating the comment section.
For new updates on these issues, one of my favorite lay-accessible sources is the Friendly Neighborhood Epidemiologist (Dr. Emily Smith). She’s an epidemiologist at Baylor University and has been posting a lot of great COVID updates for non-scientists. I highly recommend following her to stay up to date! https://www.facebook.com/friendlyneighborepidemiologist/ or emily-smith.net/covid-19-posts/
[1] A type of miscarriage.
Pathology Storybook 