COVID-19: What have we learned?
You have survived COVID-19, did you catch infertility?
HINT: The answer is “No!”
Restrictions are being relaxed and life is starting to move into whatever the new normal will be. Have we learned anything? This article will address some general findings on the effect the pandemic had on female reproduction, male reproduction, and what the early studies are telling us about pregnancy.
There is a major caveat to follow when considering information about COVID-19: it is important to remember that COVID-19 is a new variant of an old, known virus. That means that some of the behavior of COVID-19 can be implied by how other corona viruses have behaved. But because COVID-19 is a new variant, we do not have any long-term studies and, for the field of reproduction, no scientifically robust short-term studies to help us. Frustratingly, things will continue to change as more information is obtained but preliminary information suggests that many of the predictions are proving to be accurate.
Reuters released a piece on May 5th with the headlines” US birth rate falls to its lowest since 1979 as pandemic-led stress rises.” This statement satisfies what most people would assume is true: that COVID-19 caused a decline in US pregnancy rates. However, for those few who bothered to read the article, the author stated that the pregnancy rate has been on a steady decline for years. The article is very well written because the author goes on to explain why the pandemic may not be the direct cause of the pregnancy rate decline. The author notes that the CDC did not attribute the decline to the pandemic and the author gave alternative theories as to why the rate has been on a steady 6-year decline such as marrying later and delaying motherhood. In fact, the CDC data show a peak fertility rate occurring around 2007-2008 but then demonstrating a gradual decline for over 12 years.
COVID-19, or more correctly Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2), belongs to the CoV group of viruses that includes SARS and MERS. There are seven strains of CoV that are known to cause respiratory tract disease with the severity ranging from mild to severe. COVID-19 is less lethal than SARS or MERS but is more infectious. Infection primarily occurs directly from person-to-person respiratory droplets and less so by touching contaminated surfaces. Asymptomatic people can shed the virus, which has led to the need for masking with as much as 25 – 50 % of new infections coming from asymptomatic people.
Did COVID-19 identify a reason for some unexplained infertility?
Even if COVID-19 does not directly reduce a couple’s chance for conception, there are indirect consequences from the virus and the lock-down it caused. For example, many people gained weight during the lock-down due to decreased activity. Furthermore, stress has been shown to alter eating habits. Weight gain has a negative impact on female fertility and the catch phrase ‘20 in 20 or the ‘COVID 20’ seems to be an accurate picture for the lockdown. One area of research that has exploded is assessment of COVID-19 and stress. The lock down, the delayed treatment due to fertility centers suspending treatment, and the constant risk of pathology from COVID-19 (including death) all create a high-stress environment. While this burgeoning area of research is fascinating, it seems to fall into the “duh” category of usefulness.
Pardon the ‘obvious’
A group from Rome asked if COVID-19 could be used to evaluate a potential cause of unexplained infertility, specifically – frequency of intercourse. The authors identify factors which can causes a reduction in the frequency of intercourse. These include physical fatigue, lack of adequate time, geographical distance, and psychological stress. The evaluation of these factors is not a routine part of the infertility evaluation and some couples may embark on treatment, when addressing these issues could result in conception without treatment. The authors used the pandemic as an opportunity to study the impact of frequency of intercourse as a potential factor in unexplained infertility. The group studied 50 couples affected by the lock-down who had a diagnosis of unexplained infertility. Because of the lock-down, medical treatment for these couples was suspended. The study found that 7 /50 (14%) conceived during the lock-down. All the couples had extended periods of infertility. All seven couples were contacted, and they acknowledged an increase in sexual activity. The 14% spontaneous pregnancy rate is similar to the treatment expected pregnancy rate, so it is as if the increased sexual activity acted as a treatment. This study raises some interesting issues. The evaluation of unexplained infertility needs to include a frequency of intercourse assessment. If there is evidence of reduced coital frequency, then increasing coital activity may be one initial form of treatment. The study leaves open the questions of when is ‘enough enough’ and when is it time to move into treatment- that is a key question for the patient and their treating physician to determine.
Does COVID-19 or the vaccine reduce a woman’s chance for conception?
The short answer is no. However, in spite of a lack of evidence, there persists a fear that the vaccine reduces a woman’s fertility and thus many women are forgoing the vaccine. The myth that the vaccine may reduce a woman’s chance of conception seems to have originated with a statement by a German epidemiologist that COVID-19 vaccines MIGHT make the woman’s immune system react to a placental protein which will interfere with her fertility. However, the placental protein in question is not similar enough to the corona virus be affected by the vaccine. Furthermore, subsequent investigation has failed to substantiate this theory. During the clinical trials with the Pfizer vaccine, 23 women became pregnant (which defeats the “vaccine causes infertility” position.) While this is not a large number or expressed as a frequency in the clinical trial data, it is reassuring.
Pregnancy and COVID-19.
A number of studies have been published concerning the COVID-19 vaccine and pregnancy. The evidence supports the safety of having the vaccine while pregnant. A recent article by Shirmabukuro, et al evaluated over 35,000 pregnant women who received the vaccine while pregnant. Reassuringly, there was no increase in the risk of pregnancy loss, preterm delivery, adverse neonatal events and there was no neonatal death in the pregnant women who received the vaccine. Thus, the vaccine seems safe when given while a woman is pregnant.
What about those who contract COVID-19 while pregnant? Joseph, et al recent published a study concerning the effect of COVID-19 on pregnancy. To summarize what they found, for non-vaccinated pregnant women who contract COVID-19, there is an increase in ICU admissions, ventilation, and death. These recent results also suggest that there is an increased risk of C-section and preterm birth, but intrauterine transmission of the virus to the infant seems to be rare. Comparing the results of these studies, it seems imperative that if a woman is pregnant and has not been vaccinated, she needs to obtain a vaccine to prevent COVID-19 while she is pregnant. At the very least, she needs to observe social distancing and wearing a mask.
As of April 24th, 2021, The American College of Obstetricians and Gynecologist (ACOG) updated their advisory for vaccinating pregnant and lactating patients. The advisory also clearly addresses that the lack of effect of the vaccine on fertility. This is an excellent source for anyone interested in a comprehensive summary of the current status of vaccination for reproductive age women either trying to become pregnant or already pregnant. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/vaccinating-pregnant-and-lactating-patients-against-covid-19
What about COVID-19 and males?
We are beginning to see useable information about whether COVID-19 affects male reproduction, but all studies have a small population of patients and lack the effect of time. Patel DP, et al recently published an excellent review on the current effect of COVID-19 on males. The authors emphasize that the information is preliminary and may change over time. Some couples worry about sexual transmission of COVID-19 in the semen. Most reports have failed to identify the virus in the semen making sexual transmission unlikely. There is very little data on the effect of COVID-19 on semen analysis parameters. Preliminary reports suggest that active infection does negatively impact the parameters of the semen analysis such as concentration and motility. One study demonstrated a return to normal within 35 days from the onset of the symptoms of COVID-19. It is too soon to determine if the children of men who were conceived while the man was infected have any negative outcomes related to the male infection. This seems unlikely but definitive proof will require considerably more time in which to evaluate this question.
So … What did we learn?
Aside from the fact that COVID-19 is a royal pain in the tuchus, the current state of the art suggests two things: 1) attempts to conceive should not be put on hold and, 2) everyone should be vaccinated. COVID-19 has created an incredible amount of stress (deservedly so because of how deadly it can be), but the world is entering the new post – COVID-19 world.
Now would be a good time to heed the biblical phrase “be fruitful and multiply” (Genesis 1:28). There is an abundance of technology available to people today to help with this goal if nature seems to need a little guidance.
J S Rinehart MD, PhD
3 Pacchiarotti A, Frati G, Saccucci. A surprising link with unexplained infertility: a possible COVID-19 paradox? J Assit. Reprod. Genet. 2020 37: 2661
4 Shirmabukuro, et al. Preliminary findings of mRNA COVID-19 vaccine safety in pregnant patients 2021 NEJM May, 2021
5 Joseph NT, et al. The effect of COVID-19 on pregnancy and implications for reproductive medicine 2021 Fertil Steril 115:824
6 Patel D, et al .The impact of SARS- CoV-2 and COVID- 19 on male reproduction and men’s health 2021 Fertil Steril 115:813