SARS-CoV-2 can infect human embryos

Montaño, Mauricio; Victor, Andrea; Griffin, Darren K.; Duong, Tommy; Bolduc, Nathalie; Farmer, Andrew; Garg, Vidur; Hadjantonakis, Anna‐Katerina; Coates, A.; Barnes, Frank L.; Zouves, Christo; Greene, Warner C.; Viotti, Manuel

doi:10.1038/s41598-022-18906-1

Cited by 8 publications

(8 citation statements)

References 57 publications

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“…Infection was most common in totally hatched blastocysts. Infected cells had signs of cell degeneration suggesting cytopathic effects of infection ( Montano et al , 2022 ). Studies evaluating the impact of COVID-19 on embryo developmental potential and ART outcomes are discussed in the next section.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2, fertility and assisted reproduction

Ata

Vermeulen

Mocanu

et al. 2022

Human Reproduction Update

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BACKGROUND In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain. OBJECTIVE AND RATIONALE This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals. SEARCH METHODS PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on ‘SARS-CoV-2’ and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible. OUTCOMES From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients’ performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients. WIDER IMPLICATIONS This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2, fertility and assisted reproduction

Ata

Vermeulen

Mocanu

et al. 2022

Human Reproduction Update

View full text Add to dashboard Cite

show abstract

“…In the ovary, ACE2 plays a vital role in the regulation of steroidogenesis, follicle development and oocyte maturation ( 10 , 11 ), and is also required for endometrial stromal decidualization ( 12 ). Additionally, in vitro experiments have proven a cytopathic effect of SARS-CoV-2 on human blastocyst, ranging from focal degradation to global collapse ( 13 ). These findings suggest that SARS-CoV-2 infection may negatively affect female fertility and the outcomes of assisted reproductive treatment.…”

Section: Introductionmentioning

confidence: 99%

Effect of prior female SARS-CoV-2 infection on IVF outcomes: a prospective cohort study

Huang,

Liu,

Xia

et al. 2023

Front. Endocrinol.

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IntroductionThe clinical impact of SARS-CoV-2 infection on human reproduction remains controversial. This prospective cohort study aimed to assess the effect of prior female SARS-CoV-2 infection on subsequent in vitro fertilization (IVF) outcomes.Materials and methodsA total of 451 women who underwent fresh IVF treatment between December 1, 2022 and April 30, 2023 were included from an academic fertility center. Participants were divided into the infected group if they had a prior COVID-19 history before cycle initiation (n = 252), while the control group were those uninfected (n = 199). The primary outcomes were the number of oocytes retrieved and clinical pregnancy rate after fresh embryo transfer. Multivariate linear and logistic regression analyses were conducted to control for potential confounders.ResultsThe number of oocytes retrieved (11.4 ± 8.3 vs. 11.6 ± 7.7; P = 0.457) and clinical pregnancy rate (70.3% vs. 73.7%; P = 0.590) were similar between infected and uninfected groups, with a fully adjusted β coefficient of 0 (95% confidence interval [CI]: -0.14–0.13) and odds ratio of 0.64 (95% CI: 0.20–2.07), respectively. Consistently, the two groups were comparable in cycle characteristics as well as other laboratory and pregnancy parameters. In both subgroup analyses and restricted cubic splines, different post-infection time intervals to IVF cycle initiation showed no significant associations with treatment outcomes.ConclusionPrior SARS-CoV-2 infection in females had no adverse influence on subsequent IVF treatment, regardless of the time interval following infection. Our findings provide reassurance for infected women planning for assisted reproduction. Additional prospective cohort studies with larger datasets and longer follow-up are required to confirm the conclusion.

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“…Another study utilizing donated human gametes evaluated the expression of SARS-CoV-2 receptor protein on embryos and found that the 5th-and 7th-day blastocysts showed the expression of ACE2 and BSG on the trophoblast and inner cell mass cell membrane, suggesting that SARS-CoV-2 could potentially infect embryos [22]. When human blastocysts are exposed to SARS-CoV-2, both trophoblast cells and inner cell mass cells are infected, displaying signs of cellular degeneration, indicating the pathogenic effect of infection [23]. The zonal pellucida seems to have a protective effect against SARS-CoV-2 infection [23].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 infection is detrimental to pregnancy outcomes after embryo transfer in IVF/ICSI: a prospective cohort study

Li,

Zhao,

et al. 2024

BMC Med

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Background To explore whether SARS-CoV-2 infection affects the pregnancy outcomes of assisted reproductive techniques (ART). Methods A prospective cohort study recruited patients for embryo transfer from December 01, 2022, to December 31, 2022. All patients were closely followed up for SARS-CoV-2 infection after embryo transfer. The SARS-CoV-2 “diagnosed group” was defined as RNA or antigen-positive. The SARS-CoV-2 “suspected infection group” was defined as having apparent SARS-CoV-2 symptoms without an RNA or antigen test, while the “uninfected group” was defined as having a negative SARS-CoV-2 RNA or antigen test and no SARS-CoV-2 symptoms. Results A total of 1330 patients participated in the study, 687 of whom were in the SARS-CoV-2 diagnosed group, 219 in the suspected infection group, and 424 in the uninfected group. There was no significant difference in basic characteristics among the three groups. The clinical pregnancy rate was 68% in the SARS-CoV-2 diagnosed group, 63% in the uninfected group, and 51% in the suspected infection group (P < 0.001). The ongoing pregnancy rate was 58% in the SARS-CoV-2 diagnosed group, 53% in the uninfected group, and 45% in the suspected infection group (P < 0.001). Upon analyzing the factors influencing clinical pregnancy, it was found that suspected infection (odds ratio [OR] 0.618, 95% CI 0.444–0.862, P = 0.005) and the short time (≤ 22 days) between embryo transfer and SARS-CoV-2 infection (OR 3.76, 95% CI 1.92–8.24, P < 0.001) were not conducive to clinical pregnancy. In addition, the concurrent presence of fever and dizziness/headache SARS-CoV-2 symptoms (OR 0.715, 95% CI 0.526–0.972, P = 0.032) decreased the clinical pregnancy rate. However, vaccination administered 2–3 times (OR 1.804, 95% CI 1.332–2.444, P < 0.001) was associated with an improvement in clinical pregnancy rate. Conclusions This prospective cohort study shows that SARS-CoV-2 infection in a short period of time after embryo transfer is not conducive to clinical pregnancy. Reproductive physicians should advise patients to avoid SARS-CoV-2 infection shortly after embryo transfer. Meanwhile, women should be encouraged to vaccinate at least 2–3 times before embryo transfer or pregnancy.

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SARS-CoV-2 can infect human embryos

Cited by 8 publications

References 57 publications

SARS-CoV-2, fertility and assisted reproduction

SARS-CoV-2, fertility and assisted reproduction

Effect of prior female SARS-CoV-2 infection on IVF outcomes: a prospective cohort study

SARS-CoV-2 infection is detrimental to pregnancy outcomes after embryo transfer in IVF/ICSI: a prospective cohort study

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