Covid-19 Vaccination and Assisted Reproduction Outcomes: A Literature Review and Meta-Analysis

Objective: The COVID-19 pandemic remains a significant global health risk and poses an increased danger to pregnant mothers. There remains significant vaccination hesitancy amongst many in the population, in part due to unfounded claims regarding its effect on fertility (1). We conducted a literature review and meta-analysis comparing the available data on effects of COVID-19 vaccination on both ovarian stimulation and embryo transfer outcomes. Material(s) and Method(s): A literature search of PubMed was conducted using the search terms COVID-19, SarsCov2, vaccines, bnt162 vaccines, 2019-ncov vaccine mrna-1273, in vitro fertilization, egg retrieval, oocyte retrieval and embryo transfer. Reported ovarian stimulation outcomes included number of oocytes retrieved, number of mature oocytes, number of fertilized oocytes, and number of blastocysts formed, and were compared using Student's t-test. Embryo transfer outcomes included implantation rate, clinical pregnancy rate, and ongoing pregnancy rate, and were compared using chi square. Meta-analysis was performed by Standard Mean Difference method for oocyte outcomes and the Cochran-Mantel-Haenszel method for embryo transfer outcomes. Result(s): Our search retrieved 12 studies conducted between August 2021 and March 2022. Of them, only 6 compared outcomes between COVID-19 vaccinated and unvaccinated patients. Two included only ovarian stimulation outcomes, two included only embryo transfer outcomes, and two studies included outcomes for both. Of the ovarian stimulation outcomes reported, data adequate for meta-analyses were only included for the number of oocytes retrieved and number of mature oocytes. There were no statistically significant differences reported between vaccinated and unvaccinated patients amongst the pooled data from the four studies for the ovarian stimulation parameter - number of oocytes retrieved (mean 10.6 vs 10.6, 95% CI -0.144 - 0.157), or the number of MII oocytes (mean 7.43 vs 7.95, 95% CI -0.055 - 0.247). There were similarly no statistically significant differences amongst the pooled data from the four studies for any of the embryo transfer parameters - implantation rate (OR 0.97, 95% CI 0.76 - 1.24), clinical pregnancy rate (OR 0.88, 95% CI 0.70 - 1.11), or ongoing pregnancy rate (OR 1.22, 95% CI 0.78 - 1.91). Conclusion(s): The current literature demonstrates no differences in either ovarian stimulation or embryo transfer outcomes following COVID-19 vaccination. There remain several key parameters, however, that would benefit from additional investigation. Impact Statement: Patients can be reassured the current evidence reaffirms the safety profile of the mRNA COVID-19 vaccine and does not affect fertility. References: 1. Hsu AL, Johnson T, Phillips L, Nelson TB. Sources of Vaccine Hesitancy: Pregnancy, Infertility, Minority Concerns, and General Skepticism. Open forum infectious diseases 2022;9:ofab433-ofab. Copyright © 2022

FET OUTCOMES DURING THE COVID-19 PANDEMIC

OBJECTIVE: There has been significant uncertainty surrounding the COVID-19 pandemic and its effect on human reproduction which resulted in a temporary suspension of ART treatments in early stages of the pandemic. The ACE2 receptor used by the virus to infect pulmonary cells is also found in reproductive organs and has fueled speculation as to whether the disease can be sexually transmitted and whether it can cause infertility. Non-viral issues (e.g., pandemic related psychological stress, alternate methods of communication and interaction, and new clinic procedures) may also worsen outcomes. We sought to determine whether clinical outcomes following the frozen embryo transfer (FET) of a euploid embryo were different during the COVID-19 pandemic in 2020 when compared to prior to the pandemic in 2019. MATERIALS AND METHODS: Patients who tested negative for COVID-19 and underwent FET of a single euploid embryo at NYU Fertility Center in NYC over January 2020 through September 2020 were separated by treatment month and compared with patients from the corresponding month in 2019. Patient's age at cycle start and age at freeze were compared using Student's T-Test. Potential cycle outcomes included intrauterine pregnancy (IUG), biochemical pregnancy (Biochem), and no pregnancy, and outcomes were compared between the two years using contingency Chi Square. RESULTS: 1,044 patients were compared over the corresponding months. 558 transfers from 2019 and 486 patients from 2020, with no patients in April of 2020. There were no differences noted in patient's age at cycle start, or age at cryopreservation, between any of the months across the two years. Analysis of outcomes following FET further revealed no statistically significant differences between any of the months over the two years, X2 = 14.64, p > 0.05. Post hoc analyses comparing the combined months of March, April and May, or the combined 9-month periods, were also not statistically significant (X2 = 0.042, p > 0.05;X2 = 1.68, p > 0.05;respectively). CONCLUSIONS: In patients who tested negative for COVID-19, there were no differences in treatment outcomes following FET's when comparing patients treated during the COVID pandemic with those who were treated prior to the pandemic. IMPACT STATEMENT: Providers and patients can be reassured that with proper testing and sanitizing techniques FET outcomes remained unaffected by the pandemic. (Table Presented).

IVF/OOF OUTCOMES DURING THE COVID-19 PANDEMIC

OBJECTIVE: COVID-19 has affected nearly every facet of modern life, and has left many wondering what implications, if any, the virus has on reproductive health. Increased levels of psychological stress, concern for viral contamination in embryology labs, and reports of decreased male fertility following COVID infection, have also been thought to contribute negatively to ART outcomes.We sought to determine whether the pandemic resulted in any differences in IVF/OOF outcomes. MATERIALS AND METHODS: Patients who tested negative for COVID-19 and underwent GnRH-antagonist IVF and OOF cycles from January 2020 through December 2020 at NYU Fertility Center, a period marked by the COVID-19 pandemic, were separated by month of treatment and compared with patients from the corresponding month in the prior year. In patients with multiple cycles over this time period, only the first cycle was used. Patient age, AMH, #oocytes retrieved, #oocytes matured, #fertilized, #blastocysts, and #euploid embryos were compared using Student's T-test. RESULTS: 2,467 patients were compared. While the number of cycles were remarkably decreased over March and April of 2020 (59 and 25 respectively), the total number of cycles were very similar for the entire year (1,239 in 2019;1,228 in 2020). There were no consistently significant differences in age, AMH, #oocytes retrieved, #oocytes matured, #blastocysts formed, or #euploid embryos formed, between the two years. CONCLUSIONS: Despite initial concerns, and prior research suggesting otherwise, we did not detect any consistent quantitative or qualitative differences in retrieval outcomes amongst COVID negative patients receiving care during the pandemic. IMPACT STATEMENT: These results can reassure patients and their providers that IVF/OOF cycles can be continued safely during the pandemic without compromising outcomes.

ART outcomes during the COVID-19 pandemic

Background: To evaluate whether the ongoing coronavirus disease 2019 (COVID-19) pandemic has had an impact on assisted reproductive technology (ART) outcomes and assess the possible role of geographic differences in the pandemic's trajectory on these outcomes. Methods: Multi-center retrospective cohort study involving patients who underwent oocyte cryopreservation, in vitro fertilization (IVF), embryo cryopreservation, or frozen euploid embryo transfer in 2019 and 2020 at two academic fertility centers located in regionally distinct areas of the US with high coronavirus infection rates. Patients were screened for infectious symptoms, exposure to sick contacts, and fevers, and tested with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing within 5 days of oocyte retrieval. The primary outcomes were the number of oocytes retrieved, embryos fertilized, blastocyst or euploid embryos produced in oocyte retrieval and IVF cycles, and rates of embryo implantation, biochemical pregnancy or no pregnancy following frozen embryo transfer (FET). Results: We found no consistent significant differences in the number of oocytes retrieved, embryos fertilized, blastocysts or euploid embryos produced at either institution over the study period. Furthermore, we did not detect any differences in FET outcomes, including rates of embryo implantation, biochemical pregnancy, or no pregnancy, at either institution during the study time period. Conclusions: There were no significant differences in ART outcomes in patients who received fertility treatment during the pandemic at our centers. Patients and providers can be reassured that with proper testing, sanitizing, and distancing measures, treatments can continue safely during the pandemic without compromising outcomes. © 2022 S.O.G. CANADA Inc.. All rights reserved.

COVID-19 AND ART OUTCOMES

Objective: The ongoing COVID-19 pandemic has disrupted the normal methods of communication used by physicians and patients, as well as the standard protocols and procedures by which medical clinics operate. Pandemic related stresses may have also influenced patient’s fertility goals and/or their ovarian response. We questioned whether these changes resulted in any unanticipated effects in the treatments and outcomes of ART patients. Design: Retrospective cohort. Materials and Methods: Patients who underwent GnRH-antagonist IVF cycles from January 2020 through June 2020 at NYU Fertility Center, a period in New York City over which the COVID-19 pandemic escalated and life in the city drastically changed as a result of new social distancing measures, were separated by month of treatment and compared with patients from the corresponding month in the prior year (January 2019 through June 2019). Patient age, AMH, days gonadotropin, #oocytes retrieved, #oocytes matured, #fertilized, #blastocysts, and #euploid embryos were compared using Student’s T-test. Results: 1881 patients were compared over the parallel six-month periods. Clinic visits were markedly decreased over the months of March and April of 2020, when the pandemic was at its peak in NYC and treatments were suspended as per the ASRM pandemic guidelines. There were no differences in age, AMH, #oocytes retrieved, #mature oocytes, or #fertilized between the two years. In April of 2020 there were significantly more blastocysts per patient, as compared to April of 2019, however, in May and June of 2020 there were significantly fewer euploid embryos per patient, as compared to May and June of 2019 (see table). [Formula presented] Conclusions: In the months following the end of the COVID-19 treatment suspension, there were no apparent differences in patient characteristics or the quantitative responses to stimulation. However, there was a significant qualitative difference as expressed in the number of euploid embryos. It remains unclear if or how the pandemic is related to this difference.

PATIENT REACTIONS ON SOCIAL MEDIA TO THE ASRM COVID TREATMENTS SUSPENSIONS

Objective: On March 17, 2020, the American Society for Reproductive Medicine (ASRM) issued its initial recommendations regarding patient management and infertility treatment during the ongoing COVID-19 outbreak. Included were recommendations to suspend initiation of new treatment cycles, including those of patients of advanced age or diminished ovarian reserve. The purpose of this study was to survey patient opinions and reactions, as expressed on social media, to these recommendations and the three subsequent updates. Design: Cross sectional study. Materials and Methods: We surveyed “r/Infertility,” a group with 17,800 members on the social medial site Reddit, for reactions following each of the initial four ASRM recommendations. Comments were made in individual “COVID/Coronavirus Mega Threads” on the days surrounding the March 17th, March 30th, April 13th, and April 24thannouncements. We categorized posts based on their content, and quantified the number of posts per category. Categories included emotional reaction, resulting concerns, shared empathy, exchanges of advice and information. Results: 344 posts made by 148 users were categorized. The largest number of posts (n=90, 26.2%) expressed empathy to difficult news that was shared by another user. 82 posts (23.8%) discussed the future uncertainty, and 13 posts (3.8%) expressed an uncertainty in their clinics present policy. The most common emotional reaction was of disappointment (n=38, 11.1%), but others also expressed anger, anxiety, and frustration (5.2%, 6.4%, and 7.3% respectively). A total of 23 posts (6.7%) expressed frustration specifically at treatment being cancelled mid-cycle. A small number of comments questioned aspects of the guidelines, and expressed frustration with ASRM (7, 2.0%), but more users expressed concerns regarding the risk of becoming pregnant ((17, 4.9%), and none questioned the validity of the guidelines. A significant portion of users questioned whether patients with diminished ovarian reserve should be restricted as well, or whether they should be given priority when treatments resume (21, 6.1%). Several users questioned why the general population was not being cautioned about becoming pregnant (9, 2.6%), and also expressed annoyance regarding comments made in the general population of an upcoming COVID “baby boom” as a result of the self-quarantining taking place (13, 3.8%). 38 posts exchanged advice (11.1%) and 83 posts offered information (24.1%). Conclusions: We surveyed a popular social media site for patient responses to the recent ASRM COVID guidelines, and demonstrate that while users overwhelmingly endorsed the treatment suspension, they struggled with the disappointment, frustration and anxiety that came with the delay in their care, the backlog that will result when treatments resume, and the uncertainty surrounding present and future ASRM/clinic policies. In particular, patients with diminished ovarian reserve, and those whose treatment was canceled mid-cycle, were distraught by the lack of differentiation in the COVID guidelines.