Study Question Does prior SARS-CoV-2 infection in women undergoing fertility treatments affect the outcomes of fresh ART cycles? Summary Answer SARS-CoV-2 infection does not affect fresh ART treatment outcomes, except for a possible long term negative effect on oocyte yield (>180 days post infection). What Is Known Already A single previous study suggested no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes. Study Design, Size, Duration Retrospective cohort study, including all SARS-CoV-2 infected women who underwent fresh ART cycles within a year from infection (the first cycle post infection), between October 2020 and June 2021, matched to non-diagnosed controls. Participants/Materials, Setting, Methods Patients from two large IVF units in Israel who were infected with SARS-CoV-2 and later underwent fresh ART cycles were matched by age to non-diagnosed, non-vaccinated controls. Demographics, cycle characteristics and cycle outcomes, including oocyte yield, maturation rate, fertilization rate, number of frozen embryos per cycle, and clinical pregnancy rates, were compared between groups. Main Results And The Role Of Chance One hundred and twenty-one infected patients and 121 controls who underwent fresh ART cycles were included. Oocyte yield (12.50 versus 11.29; p = 0.169) and mature oocyte rate (78% versus 82%; p = 0.144) in all fresh cycles were similar between groups, as were fertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (43% versus 40%; p = 0.737) in fresh cycles with an embryo transfer. In a logistic regression model, SARS-CoV-2 infection more than 180 days prior to retrieval had a negative effect on oocyte yield (p = 0.018, Slope=-4.08, 95% CI -7.41 – -0.75), although the sample size was small. Limitations, Reasons For Caution A retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group. Wider Implications Of The Findings The study findings suggest that SARS-CoV-2 infection does not affect treatment outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos, and clinical pregnancy rates, in fresh ART cycles, except for a possible long term negative effect on oocyte yield when retrieval occurs > 180 days post SARS-CoV-2 infection. Further studies are warranted to support these findings. Study funding/competing interest(s) None. Trial registration number 0010-21-HMC, 0094-21-ASF

Purpose To study the effect of SARS-CoV-2 infection on pregnancy rates in frozen embryo transfer (FET) cycles. Methods A retrospective cohort study including women under the age of 42 with documented SARS-CoV-2 infection up to 1 year prior to treatment, undergoing FET cycles in the first half of 2021, with transfer of embryos generated prior to the infection. Controls were SARS-CoV-2 non-diagnosed, non-vaccinated women matched by age, number, and day of embryo transfer. Demographic and cycle characteristics and outcomes were compared. Results Forty-one recovered women and 41 controls were included. Pregnancy rates were 29% and 49% respectively ( p = 0.070). Stratification by time from SARS-CoV-2 infection to transfer into ≤ 60 and > 60 days revealed a difference in pregnancy rates, with women in the COVID group having lower pregnancy rates if infected in proximity to the transfer (21% vs. 55%; p = 0.006). In a logistic regression model, infection was a significant variable ( p = 0.05, OR 0.325, 95% CI 0.106–0.998). Logistic regression applied on the subgroup of women infected in proximity to the transfer further strengthened the univariate results, with COVID-19 remaining a significant parameter ( p = 0.005, OR 0.072, 95% CI 0.012–0.450). Conclusions In FET cycles of patients with past SARS-CoV-2 infection, in which oocytes were retrieved prior to infection, decreased pregnancy rates were observed, specifically in patients who recovered less than 60 days prior to embryo transfer. Pending further studies, in cases of FET cycles with limited number of embryos, postponing embryo transfer for at least 60 days following recovery from COVID-19 might be considered when feasible. Supplementary Information The online version contains supplementary material available at 10.1007/s10815-022-02517-w.

Objectives Compare the levels of neutralizing Anti-Spike Protein IgG (Anti-S-IgG) during twin pregnancies in women who were immunized by the BNT-62b2-Pfizer/BioNTech vaccine for COVID-19 before conception vs. during pregnancy. Methods In this prospective study, three blood samples were collected from 83 pregnant and 200 age-matched non-pregnant women and subjected to Anti-S-IgG immunodiagnostics. Patient’s medical records were collected from the hospital’s electronic database, including vaccination and PCR test results. Results Of the 83 women with twin pregnancies, 74 were dichorionic diamniotic (DCDA) and 9 were monochorionic diamniotic (MCDA), 49 were vaccinated before conception, 21 were vaccinated during pregnancy, and 13 were non-vaccinated. Nine non-vaccinated women experienced an uneventful pregnancy, one contracted COVID-19 before conception, three became positive during pregnancy, and all three were severely ill and required hospitalization in the 3rd trimester. By contrast, in two (9.5%) of the 21 women who were vaccinated during pregnancy and 7 (14.3%) of the 46 women vaccinated before conception COVID-19 infection during pregnancy caused only mild symptoms. The levels of neutralizing Anti-S-IgG in the 3rd trimester in the women vaccinated before conception were 1,475 Au/mL [IQR 392-3,020] vs. 112 [54–357] (ten-fold lower) in women vaccinated during pregnancy (p < 0.001)). No difference was found between DCDA and MCDA. Third-trimester Anti-S-IgG levels in twin pregnancies were higher compared to non-pregnant women and to gravid women with singletons (according to reported levels). In women vaccinated at 13–16 weeks gestation, neutralizing Anti-S-IgG at 20–22 weeks went up to 372 Au/mL[120–1598], but rapidly dropped to 112[54–357) at 28–30 weeks, (p < 0.001), a faster decline than in women vaccinated before conception, or women with singleton pregnancies, or non-pregnant women (p < 0.001). Infection before conception was associated with having low Anti-S-IgG levels during pregnancy, whereas COVID-19 during pregnancy led to a very high response in the 3rd trimester, as previously reported for singleton pregnancies. Conclusion Lower neutralizing Anti-S-IgG levels were observed in women who were vaccinated during pregnancy compared to those who were vaccinated before conception, and they also declined faster. Vaccinated women who came down with COVID-19 had milder symptoms than unvaccinated women. Thus, a full course of vaccination before conception is recommended. ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: October 4, 2021 ClinicalTrials.gov ID: NCT04595214

Study question Does prior SARS-CoV-2 infection in women undergoing fertility treatments affect outcomes of fresh ART cycles?  Summary answer SARS-CoV-2 infection does not affect fresh ART treatment outcomes. A possible long term negative effect on oocyte yield should be further explored. What is known already There is evidence that the renin–angiotensin–aldosterone system (RAS) is involved in female reproductive processes such as folliculogenesis, steroidogenesis, oocyte maturation and ovulation. The existence of the ACE2 axis and ACE2 markers were confirmed in all stages of follicular maturation in the human ovary, including the granulosa cells and follicular fluid. A single previous study found no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes.  Study design, size, duration Retrospective cohort study, including all SARS-CoV-2 infected women that underwent fresh ART cycles within a year from infection (the first cycle post infection), between October 2020 and June 2021, matched to uninfected controls.  Participants/materials, setting, methods Retrospective cohort study, including all SARS-CoV-2 infected women that underwent fresh ART cycles within a year from infection (the first cycle post infection), between October 2020 and June 2021, matched to uninfected controls.  Main results and the role of chance 121 infected patients and 121 controls that underwent fresh ART cycles were included. Oocyte yield (12.50 vs. 11.29; p = 0.169) and mature oocyte rate (77.71 vs. 81.76; p = 0.144) in all fresh cycles were similar between groups, as werefertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (42.9% vs. 40.4%; p = 0.737) in fresh cycles with an embryo transfer. Stratification by time from COVID-19 infection by time from infection &lt;90 day, 90-180 days and &gt; 180 days revealed similar results with no difference in pregnancy rates. In a logistic regression model, COVID-19 infection did not affect pregnancy rates except for the small subgroup of patients who recovered more than 180 days prior to retrieval with a negative effect on oocyte yield (p = 0.018, Slope=-4.08, 95%CI 95% CI -0.7.41 – -0.75). Limitations, reasons for caution A retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group.  Wider implications of the findings The study findings suggest that COVID-19 infection does not affect treatment outcomes in fresh ART cycles, except for a possible long term negative effect on oocyte yield when retrieval occurs &gt; 180 days post COVID-19 infection. Further studies are warranted in order to support these findings.  Trial registration number HMC-0010-21

Study question What is the effect of COVID-19 infection on pregnancy rates in frozen embryo transfer (FET) cycles? Summary answer Past COVID-19 infection decreased pregnancy rates in FET cycles, especially in patients with recent infection. What is known already ACE2 and TMPRSS2 are expressed in the endometrium, potentially enabling SARS-COV-2 viral invasion of the cells. Unlike with bacterial infections, the effect of viral infections in general on implantation and pregnancy rates is unclear. Some evidence suggests that early embryonic and trophoblastic infection, may result in impaired implantation or placentation. A recently published study including both recovered and vaccinated patients did not find an effect of COVID-19 immunity on FET cycle outcomes. The study did not stratify by time from infection thus the immediate consequences of infection on pregnancy rates could not be properly evaluated. Study design, size, duration A retrospective cohort study, including 41 COVID-19 recovered women, aged 20-42 years that underwent FET cycles, and 41 controls between January 1, and June 31, 2021, at a large IVF unit. Participants/materials, setting, methods Embryos transferred were the product of fresh cycles performed prior to infection. Maximal time from infection to transfer was defined as one year. The study group was matched by age, number of embryos transferred and day of transfer, to unvaccinated patients, with no history of past infection that underwent FET cycles during the same period. Demographics and cycle characteristics were recorded. Clinical and ongoing pregnancy rates were compared, with further stratification by time from infection. Main results and the role of chance Clinical pregnancy rates were 29.3% and 48.8% for the recovered and control patients respectively (p = 0.070). Ongoing pregnancy rates were 26.6% vs. 43.4% (p = 0.093). Mean age at ovum pickup (30.72 vs. 30.69; p = 0.929) and at transfer (31.56 vs. 31.58; p = 0.966) was similar between groups, as were the demographic characteristics and previous retrievals and transfers. The predominant transfer protocol used was different between groups with higher rates of natural cycle (NC) protocol in the COVID group (61% vs. 33.3%; p = 0.013. All other cycle characteristics including endometrial width, number of embryos transferred, day of embryo transfer and embryo grade were similar. Stratification by time from COVID-19 infection to transfer into ≤60 and &gt;60 days revealed a significant difference in pregnancy rates, with recovered women having lower pregnancy rates if infected in proximity to the transfer (20.7% vs. 55.2%; p = 0.006). In a logistic regression model, infection was a significant variable (p = 0.05, OR 0.325, 95% CI 0.106-0.998). Logistic regression applied on the subgroup of women infected in proximity to the transfer, further strengthened the univariate results, with COVID-19 infection remaining a significant parameter (p = 0.005, OR 0.072, 95% CI 0.012-0.450). Limitations, reasons for caution A retrospective study, with a limited sample size, but nevertheless our results showed significant differences.  Wider implications of the findings Further studies with larger groups are warranted to support these findings. Pending further information, in cases of FET cycles with limited numbers of embryos (advanced age, embryo donation, fertility preservation, embryos following sperm extraction), postponing embryo transfer for at least 60 days following recovery might be considered, if feasible. Trial registration number HMC-0010-21