The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles

Youngster, Michal; Avraham, Sarit; Yaakov, Odelia; Rabbi, Moran Landau; Gat, Itai; Yerushalmi, Gil M.; Baum, Micha; Maman, Ettie; Hourvitz, Ariel; Kedem, Alon

doi:10.1007/s10815-022-02517-w

Cited by 26 publications

(32 citation statements)

References 22 publications

(5 reference statements)

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“…The outcomes of the first fresh ART cycle in 121 patients with previous COVID-19 (within 12 months from diagnosis) were retrospectively compared with 121 patients that did not have COVID-19 previously ( Youngster et al , 2022a ). From this largest study to date, recent past SARS-CoV-2 infection was found to have no impact on oocyte yield, maturation rate, fertilization rate, number of vitrified embryos and clinical pregnancy rates.…”

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 China, the control of COVID-19 has been relaxed since December 2022, and the number of couples infected with SARS-CoV-2 during assisted reproductive technology (ART) treatment increased sharply during that period. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2) are expressed in the reproduction system in both males and females 1 ; therefore, reproductive function is theoretically vulnerable to SARS-CoV-2 infection, and many studies 2,3 have explored the possible effect of SARS-CoV-2 infection on the human reproductive system. A recent review 4 summarized published data and clarified the effect of SARS-CoV-2 and COVID-19 on human fertility and assisted reproduction.…”

Section: Introductionmentioning

confidence: 99%

Association of SARS-CoV-2 Infection During Controlled Ovarian Stimulation With Oocyte- and Embryo-Related Outcomes

Fen

et al. 2023

JAMA Netw Open

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ImportanceSARS-CoV-2 infection has had significant effects on the health of people worldwide. Whether SARS-CoV-2 infection during controlled ovarian stimulation (COS) is associated with laboratory outcomes in assisted reproductive technology remains unclear.ObjectiveTo investigate the association between SARS-CoV-2 infection during COS with oocyte- and embryo-related outcomes.Design, Setting, and ParticipantsA multicenter cohort study was conducted of couples undergoing assisted reproductive technology treatments in 7 reproductive centers in 4 provinces in China from October 1, 2022, to December 31, 2022. All couples received nucleic acid testing for SARS-CoV-2 during COS. The SARS-CoV-2–positive group included couples in which either partner was infected with SARS-CoV-2. The SARS-CoV-2–negative group comprised couples without infection.ExposureIn the SARS-CoV-2–positive group, either partner was infected with SARS-CoV-2 during COS, defined as a positive test result for the SARS-CoV-2 antigen.Main Outcomes and MeasuresPrimary outcomes were the available embryo and blastocyst and top-quality embryo and blastocyst rates. Secondary outcomes were the number of oocytes retrieved, the mature oocyte rate, normal fertilization (2 pronuclei observed on day 1 after insemination [2PN]), oocyte degeneration, 2PN cleavage, and blastocyst formation rates.ResultsA total of 585 heterosexual couples with infertility participated in the study (median [IQR] age for female partners, 33 [30-37] years), with 135 couples in the SARS-CoV-2–positive group and 450 in the SARS-CoV-2–negative group. The characteristics of the groups were similar. The SARS-CoV-2–positive group had a significantly lower top-quality embryo rate (odds ratio [OR], 0.83; 95% CI, 0.71-0.96), top-quality blastocyst rate (OR, 0.59; 95% CI, 0.45-0.77), available blastocyst rate (OR, 0.70; 95% CI, 0.59-0.82), and blastocyst formation rate (OR, 0.61; 95% CI, 0.52-0.71) than the SARS-CoV-2–negative group. Analysis of the associations of infection by sex showed that the female positive group had impaired oocyte and embryo quality regarding mature oocyte rate, 2PN cleavage rate, top-quality embryo rate, blastocyst formation rate, available blastocyst rate, and top-quality blastocyst rate compared with the SARS-CoV-2–negative group. Compared with the SARS-CoV-2–negative group, the male positive group and the group of couples with both positive partners had significantly decreased available blastocyst rate, top-quality blastocyst rate, and blastocyst formation rate compared with the SARS-CoV-2 negative group.Conclusions and RelevanceIn this cohort study, SARS-CoV-2 infection during COS was negatively associated with embryo and blastocyst quality. Reproductive physicians should be more attentive to patients with SARS-CoV-2 infection during COS and should give couples who have been infected adequate counseling.

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“…Nonetheless, it should be highlighted that it was not made clear in this study whether the control group underwent rigorous testing for SARS-CoV-2 infection [13]. Furthermore, in another study, the same group reported that patients with previous SARS-CoV-2 infection who underwent frozen embryo transfer cycles with oocytes retrieved prior to infection had lower pregnancy rates, notably those who had recovered fewer than 60 days before embryo transfer [33]. More importantly, the clinical outcomes of patients who underwent IVF during the acute period of SARS-CoV-2 infection are mostly described in case reports [17,18].…”

Section: Discussionmentioning

confidence: 78%

Effect of SARS-CoV-2 infection on IVF/ICSI-ET outcomes: A propensity score-matched cohort study

Ding

Luo

et al. 2023

Preprint

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Background: The SARS-CoV-2 virus is continually evolving, and the worldwide epidemic is still ongoing. There is conflicting evidence regarding how SAS-CoV-2 infection affects the outcomes of assisted reproductive technology (ART). The aim of the current study was to investigate whether the outcomes of in vitro fertilization (IVF) treatment were affected during the acute period of SARS-CoV-2 infection or immediately after recovery from COVID-19. Methods: In this retrospective cohort study, SARS-CoV-2-infected couples who underwent IVF treatment at Wuhan Union Hospital within the first three months following the lifting of the pandemic policy in mainland China were propensity-score matched (PSM) to uninfected couples who received IVF during the dynamic COVID-zero policy. Following matching, 358 and 698 patients were assigned to the SARS-CoV-2-infected and uninfected groups, respectively. The laboratory and clinical outcomes of the two groups were compared. Results: The average number of oocytes retrieved, mature oocyte rates, normal fertilization rates, abnormal fertilization rates, and cleavage rates did not differ significantly between the two groups. The blastocyst formation rates were considerably lower in the infected group than in the uninfected group. Stratification by time from SARS-CoV-2 infection to oocyte retrieval (≤ 30, 31-60, 61-90 and ≥90 days) revealed that both blastocyst formation and available blastocyst rates were significantly decreased when oocyte retrieval was performed 31-60 days after SARS-CoV-2 infection. However, after the first embryo transfer cycle, there were no significant differences in the rates of embryo implantation, biochemical pregnancy, clinical pregnancy or early abortion between the two matched cohorts. Conclusion: SARS-CoV-2 infection had no effect on clinical outcomes after the first embryo transfer cycle; however, the blastocyst formation rate was significantly lower in couples who underwent IVF treatment 31-60 days after SARS-CoV-2 infection, indicating that SARS-CoV-2 infection may still impair embryo developmental potential.

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The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles

Cited by 26 publications

References 22 publications

SARS-CoV-2, fertility and assisted reproduction

SARS-CoV-2, fertility and assisted reproduction

Association of SARS-CoV-2 Infection During Controlled Ovarian Stimulation With Oocyte- and Embryo-Related Outcomes

Effect of SARS-CoV-2 infection on IVF/ICSI-ET outcomes: A propensity score-matched cohort study

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