Is there a reason to be anxious about claim that COVID-19 vaccine could turn out to be inducing infertility in females?

Question

There is a petition written on December 1, 2020 to European Medicines Agency (EMA) by Dr. med. Wolfgang Wodarg and Dr. Michael Yeadon. You can see it here. Both of them are well known for spreading misinformation about COVID-19. Yeadon used to work in Pfizer till 2011, and he is "Allergy & Respiratory Therapeutic Area expert". Some sources falsely claim that he was "head of research" in Pfizer, which was debunked by snopes.com, he was in fact a "vice president and chief scientist for allergy and respiratory".

Among other things, they want EMA to "stay the Phase III trial of BNT162" and "stay the clinical trials of all vaccine candidates [...]". "Stay" here means "to stop", I guess. They provide some reasons for why this should be done. In said petition, in section "C" ("STATEMENT OF GROUNDS") in point "XI" there is a claim about fertility:

Several vaccine candidates are expected to induce the formation of humoral antibodies against spike proteins of SARS-CoV-2. Syncytin-1 (see Gallaher, B., “Response to nCoV2019 Against Backdrop of Endogenous Retroviruses” - http://virological.org/t/response-to-ncov2019-against-backdrop-of-endogenous-retroviruses/396), which is derived from human endogenous retroviruses (HERV) and is responsible for the development of a placenta in mammals and humans and is therefore an essential prerequisite for a successful pregnancy, is also found in homologous form in the spike proteins of SARS viruses. There is no indication whether antibodies against spike proteins of SARS viruses would also act like anti-Syncytin-1 antibodies. However, if this were to be the case this would then also prevent the formation of a placenta which would result in vaccinated women essentially becoming infertile. To my knowledge, Pfizer/BioNTech has yet to release any samples of written materials provided to patients, so it is unclear what, if any, information regarding (potential) fertility-specific risks caused by antibodies is included.

According to section 10.4.2 of the Pfizer/BioNTech trial protocol, a woman of childbearing potential (WOCBP) is eligible to participate if she is not pregnant or breastfeeding, and is using an acceptable contraceptive method as described in the trial protocol during the intervention period (for a minimum of 28 days after the last dose of study intervention).

This means that it could take a relatively long time before a noticeable number of cases of postvaccination infertility could be observed.

I understand that this two gentlemans are not very credible. But is it true, that there is a significant chance that antibody response against spike proteins of SARS-CoV-2 could result also in antibody response against syncytin-1, which is important in formation of placenta and then basically would cause intertility of unknown duration? I know that we are never 100% sure with things that complicated, but is it a valid concern scientifically, or something very unlikely and he just abuses the fact that he found some connection between spike protein of SARS-CoV-2 and human placenta?

In other words: does the authors of this petition ommited some important difference between antibody reaction to SARS-CoV-2 spike protein and reaction to syncytin-1 that is forming human placenta? Something that could be use to ease people's minds, that was taken into consideration by teams developing SARS-CoV-2 mRNA vaccines?

Another way to put this in question would be: what are the chances that antibodies against spike proteins of SARS viruses would also act like anti-Syncytin-1 antibodies?

Answer 1

This is probably as good as it gets for now, but experts quoted by AP have dismissed the idea as highly improbable, basically on the argument that the common sequence is too short to be of concern and that other viral fusion proteins e.g. used in the flu vaccine haven't been observed to cause such an effect (on fertility):

Experts say there is no evidence that the Pfizer vaccine would result in sterilization of women.

Rebecca Dutch, chair of University of Kentucky’s department of molecular and cellular biochemistry, said in an email that while syncytin-1 and the spike protein broadly share some features, they are quite different in the details that antibodies recognize.

Aside from the fact that COVID-19’s spike protein and syncytin-1 are viral fusion proteins that cause membrane fusion, they are not related at all, Dutch said.

[...]

Jacob Yount, an associate professor of the department of microbial infection and immunity at Ohio State University, College of Medicine, has studied the syncytin proteins as well as SARS-CoV-2. Yount said the COVID vaccines do not contain syncytin-1 protein or mRNA encoding syncytin-1, and thus there is no reason to think that an immune response against syncytin-1 would be developed.

“We don’t see infertility with the flu vaccine and that is also targeting a viral fusion protein in a similar way that the spike is a viral fusion protein of the coronavirus,” he said.

[...]

Pfizer spokeswoman Jerica Pitts confirmed to The Associated Press that their vaccine candidate has not been found to cause infertility.

“It has been incorrectly suggested that COVID-19 vaccines will cause infertility because of a shared amino acid sequence in the spike protein of SARS-CoV-2 and a placental protein,” she said in an email. “The sequence, however, is too short to plausibly give rise to autoimmunity.”

N.B. some of this info (i.e. what Yount said) can be gleaned from Wikipedia:

Class I fusion proteins resemble influenzavirus hemagluttinin in their structure.

From a more detailed paper (see table 1 in there) the coronaviruses fusion proteins also belong to this class I.

Also from Wikipedia:

Syncytin-1 shares many structural elements with class I retroviral glycoproteins (such as, Murine Leukemia Virus gp, Ebolavirus gp, and HIV gp120, gp41).

So it seems that viruses (or vaccines against them) from the filoviridae family would be even more likely (out of all in class I) to produce an effect like this on fertility. Alas these are more obscure in the sense that there haven't been many vaccines against filoviridae, nor were such vaccines in widespread use (compared to influenza), e.g. the ones for Ebola have seen some use, but in more limited areas. The Wikipedia page doesn't mention any effects on fertility or pregnancy from these.

... but (for what's worth it) there is actually a March 2020 CDC paper on "Pregnancy Outcomes among Women Receiving rVSV?-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola"

Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73–2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

Alas because of were the study was conducted it

had several limitations, however, beyond the small sample size and inability to adjust for confounding factors. In cases of pregnancy loss, information on the timing of the loss was often lacking, limiting our ability to differentiate between early and late pregnancy loss.

Regarding influenza vaccination and fertility, I also found a recent study Jun 2020 on a fairly large US sample (thousands), with the conclusion:

Compared with couples in which neither participant was vaccinated, FRs [fecundability ratios] were 1.13 for female-only vaccination (95% CI: 0.99-1.29), 0.94 for male-only vaccination (95% CI: 0.78-1.12), and 1.07 when both partners were vaccinated (95% CI: 0.94-1.21). When restricted to recent vaccination before peak influenza season, results were similar.

Conclusions: Our data indicate no adverse effect of influenza vaccination on fecundability