key: cord-0951263-p12j4dkb
authors: Morris, Randy S.
title: SARS-CoV-2 spike protein seropositivity from vaccination or infection does not cause sterility
date: 2021-06-02
journal: F S Rep
DOI: 10.1016/j.xfre.2021.05.010
sha: a4fd188b7391e83c9f5ede2f41759d511c06460d
doc_id: 951263
cord_uid: p12j4dkb

Concern has arisen that the purported similarity between syncytin-1 and the SARS-CoV-2 spike protein may induce immune cross reactivity resulting in female sterility. We used frozen embryo transfer as a model to compare implantation rates between SARS-CoV-2 vaccine seropositive, infection seropositive and seronegative women. We found no difference in serum hCG documented implantation rates or sustained implantation rates between the three groups. The concern regarding Covid vaccines or illness causing female sterility are unfounded.

Vaccine hesitancy in reproductive aged women has been heightened as a result of misinformation spread on social media stating that Covid vaccines will cause sterility in women. (1) The proposed mechanism is the presumed similarity between the SARS-CoV-2 spike protein and syncytin-1, (2) a protein which is critical to the formation of the syncytiotrophoblast in a developing embryo. ( 3) The hypothetical ensuing immune cross reactivity would result in damage to the developing trophoblast, thereby preventing embryo implantation. If true, then this cross reactivity would cause sterility not just from vaccination but also from natural illness and would be life-long. Laboratory analysis has failed to demonstrate any such cross reactivity but there are no human clinical data available. (1) We utilized IVF frozen embryo transfer (FET) as a model to study the impact of Covid seropositivity on implantation. The detection of elevated maternal serum hCG after embryo transfer provides the earliest confirmation of syncytiotrophoblast formation and embryo implantation.

Prior to starting treatment, patients undergoing FET had serum analyzed to quantitatively determine the level of Anti-SARS-CoV-2 Spike IgG (Roche, Elecsys, Non-reactive < 0.79 U/mL, Specificity 100 % Baseline characteristics were analyzed using ANOVA. Chi square analysis was used to compare pregnancy rates and the Boneferonii correction applied to correct for multiple comparisons. Chi square testing and Boneferonii correction where performed using R version 4.0.2 (R Core Team, 2020). Chi square power calculation indicated a 99% chance to detect a 50% decrease in the ongoing pregnancy rate for all patients (n=143, sig level=0.05) and a 79% chance in euploid patients (n=67, sig level = 0.05) J o u r n a l P r e -p r o o f

Baseline characteristics for each of the 3 groups can be seen in Table 1 . There was no significant difference in mean age at the time of egg retrieval and cryopreservation (p=0.3277). The mean number of days of estradiol supplementation prior to starting progesterone (p=0.703) and the mean endometrial thickness before progesterone (p=0.08) were similar. However, the infection group had a higher mean BMI than either the vaccinated group or the non reactive group (p =0.005).

Embryo implantation was determined by a serum hCG level > 5 mIU/mL obtained 8 days after embryo transfer followed by a rising level two to three days later. The implantation rate (positive hCG per transfer) was not significantly different between seronegative (73.9%), vaccine seropositive (80.0%) or infection seropositive (73.7%) patients (P =0.99) ( Table 2 ).

Since trophoblast damage might also be manifest by reduced viability after implantation, we performed serial transvaginal ultrasounds on those women with hCG levels above 2000 mIU / mL. Visualization of a gestational sac, an indicator of continued trophoblast development, was similar between all three groups (non reactive 62.5%, vaccine reactive, 65.7%, infection reactive, 52.6%, p =0.63). (Table 2) The sustained implantation rate, defined as the presence of ultrasound visualized fetal heart tones at two time points at least one week apart is a close proxy for the delivery rate. (5) The sustained implantation rates for seronegative, vaccine seropositive and infection seropositive groups were similar (52.3%, 65.7%% and 47.4%, p=0.99 ) ( Table 2 ) and were consistent with pre-pandemic rates in our center (data not shown).

A total of 67 transfers were performed using euploid blastocysts. Implantation, clinical and sustained pregnancy rates were also no different between the three groups ( Table 2 ).

On December 1 st , 2020, the ex-Pfizer head of respiratory research filed an application with the European Medicine Agency calling for the immediate suspension of all SARS-CoV-2 vaccine studies. (2) One of the concerns laid out in the application was "infertility of indefinite duration in vaccinated women". It is important to note, however, that the theoretical danger was not from the vaccine per se, but from the subsequent production of antibodies against the virus spike protein and their cross reaction with syncytin-1. Why this would be different than the antibodies produced from natural infection was never explained.

Upon binding to its receptor, syncytin-1 promotes the fusion of cytotrophoblast into syncytiotrophoblast, an essential process in implantation. Interference with syncytiotrophoblast formation might manifest as failed implantation, early pregnancy loss or later problems related to abnormal placentation such as preeclampsia. However, the theory of infertility resulting from cross reactivity seemed unlikely for several reasons. IVF with frozen embryo transfer is an excellent model to study the impact of various factors on implantation since it bypasses many of the variables that normally impact a woman's ability to conceive such as ovulation, fertilization and preimplantation embryo development. The current study failed to find a difference in implantation or ongoing pregnancy in women with documented seropositivity to the spike protein compared to women without seropositivity.

We have documented, for the first time in women, that seropositivity to the SARS-CoV-2 spike protein, whether from vaccination or infection, does not prevent embryo implantation or early pregnancy development. Physicians and public health personnel can counsel women of reproductive age that neither previous illness with Covid-19 nor antibodies produced from vaccination to Covid-19 will cause sterility.

J o u r n a l P r e -p r o o f Tables   Table 1 Baseline 

The false rumors about vaccines that are scaring women. The New York Times

Head of Pfizer Research: Covid Vaccine is Female Sterilization

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Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

Why abandoning sustained implantation rate may be throwing the baby out with the bathwater

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19