How to provide fertility treatment during COVID-19 pandemic.

PURPOSE OF REVIEW: The emergence of the novel coronavirus infection that arose in Wuhan, China in December 2019 has resulted in an epidemic that has quickly expanded to become one of the most significant public health threats in recent times. The objective of this review is to summarize how this pandemic has affected the activity of a Reproductive Medicine Center, which established a series of measures in parallel with governments decisions and scientific societies. RECENT FINDINGS: The control measures adopted for restarting the healthcare activity should be equitable and inclusive. Moreover, this pandemic has implied changes in treatments and strategies to be alert regarding the daily changing information. Finally, for ensuring a safe practice both for patients and staff, it is important to detect asymptomatic patients, so Reproductive Medicine centers must take special care with screening and testing procedures. SUMMARY: The pandemic has pushed up toward a new reality in terms of Assisted Reproductive treatments, where social distance and responsibility are protagonists. We face a new challenge of balancing between responding to the committed efforts of infertile couples to achieve pregnancy and safeguarding the health of the future parents and their children during this time of pandemic.

The impact of the COVID-19 pandemic on gestational carriers.

Reproductive medicine has been significantly impacted by the coronavirus (COVID-19) pandemic, and this includes the gestational carrier (GC) process. The objectives of this commentary are to evaluate the impact of COVID-19 on the GC process, as well to communicate Shady Grove Fertility's considerations of and response to COVID-19 on the GC process to the larger assisted reproductive technology (ART) community. We also gathered conclusions drawn from available data on the impact of COVID-19 infection on maternal and neonatal morbidity and mortality as well as on counseling patients on vaccination. We compiled proposals to mitigate risk and to maximize safe evaluation and treatment for GCs during the ongoing pandemic. Over 2 years after the onset of the pandemic, the multiple resurgences of cases in the USA have necessitated nimble strategies to provide ongoing and safe reproductive care and have posed unique challenges to the GC process. With the prospect of the virus continuing to spread globally well into the future, as healthcare professionals of the ART community, we will need to ensure effective collaboration and communication as we provide care during the ongoing pandemic.

The COVID-19 crisis and ART activity in France.

RESEARCH QUESTION: What was the impact of the COVID-19 pandemic on assisted reproductive technology (ART) activity in public and private hospitals in France in 2020? DESIGN: All women who underwent oocyte retrieval in 2020 (study group, n = 40,759) or in 2019 (comparison group, n = 52,403) were selected from French national health insurance databases. The weekly ART activity in 2020 was compared with the weekly ART activity in 2019. RESULTS: In 2020, annual ART activity dropped by nearly 30% compared with 2019. Whereas weekly ART activity was at its normal level at the beginning of 2020, it sharply decreased and was almost non-existent during the first French lockdown (March-May 2020) in both public and private hospitals. After the first lockdown, private hospitals returned to their normal activity level within 1 month. In contrast, the activity of public hospitals remained well below normal until the summer break, before peaking at 40% of normal activity compared with an expected level of 57%. During the second French lockdown, ART activity was only slightly affected, principally in public hospitals where ART activity was around 48% compared with an expected level of 57%. CONCLUSIONS: In countries where intensive care units are principally in public hospitals, greater disruption in public than in private hospitals may have led to an increase in health inequalities for ART activity, as for other healthcare.

COVID-19 vaccine hesitancy and associated factors among infertile couples undergoing assisted reproductive treatment.

Although periconception vaccination is important to maternal and neonatal health, little is known about the COVID-19 vaccine hesitancy among infertile couples seeking fertility treatment. Thus, we conducted this survey among infertile patients in a reproductive medicine center, between September 2021 and December 2021, to estimate the prevalence of COVID-19 vaccine hesitancy and its influencing factors. Information was collected through face-to-face interviews among volunteers. Among the 987 included interviewees, 17.33% reported hesitancy in primary vaccination, 25.63% reported hesitancy in booster vaccination, and 32.32% delayed the primary vaccination. Hesitancy in primary vaccination was associated with unexplained infertility (OR: 1.77, 95% CI: 1.05-2.98), ongoing IVF treatment (OR: 2.17, 95% CI: 1.22-3.89), concerns for vaccine safety (OR: 4.13, 95% CI: 2.66-6.42), effectiveness (OR: 1.62, 95% CI: 1.15-2.28), and influence on pregnancy (OR: 2.80, 95% CI: 1.68-4.67). These factors were also associated with hesitancy in booster vaccination. Delay of the primary vaccination was inversely associated with a college or above degree (OR: 0.49, 95% CI: 0.27-0.87), previous history of influenza vaccination (OR: 0.67, 95% CI: 0.46-0.98), and was positively associated with concerns for the influence on pregnancy (OR: 7.78, 95% CI: 5.01-12.07). It is necessary to carry out targeted education program by health professionals to publicize the benefits of periconception vaccination, and to reduce the resistance to COVID-19 vaccine among infertile couples.

A review of initial data on pregnancy during the COVID-19 outbreak: implications for assisted reproductive treatments.

The current outbreak of the novel 2019 coronavirus disease (COVID-19) started in China in December 2019 and has since spread to several other countries. On March 25, 2020, a total of 375,498 cases had been confirmed globally with 2,201 cases in Brazil, showing the urgency of reacting to this international public health emergency. While in most cases, mild symptoms are observed, in some cases the infection leads to serious pulmonary disease. As a result, the possible consequences of the COVID-19 outbreak for pregnant women and its potential effects on the management of assisted reproductive treatments, demand attention. In this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women, and discuss the current evidence of COVID-19 infections during pregnancy and its potential consequences for assisted reproductive treatments. Reported data suggest that symptoms in pregnant women are similar to those in other people, and that there is no evidence for higher maternal or fetal risks. However, considering the initial data and lack of comprehensive knowledge on the pathogenesis of SARS-CoV-2 during pregnancy, human reproduction societies have recommended postponing the embryo transfers and do not initiate new treatment cycles. New evidence must be considered carefully in order to adjust these recommendations accordingly at any time and to guide assisted reproductive treatments.

Review of the impact of COVID-19 on male reproduction, and its implications on assisted reproductive technology services.

The announcement in 2019 of a new coronavirus disease that quickly became a major pandemic, is an exceptional challenge to healthcare systems never seen before. Such a public health emergency can largely influence various aspects of people's health as well as reproductive outcome. IVF specialists should be vigilant, monitoring the situation whilst contributing by sharing novel evidence to counsel patients, both pregnant women and would-be mothers. Coronavirus infection might adversely affect pregnant women and their offspring. Consequently, this review paper aims to analyse its potential risks for reproductive health, as well as potential effects of the virus on gamete function and embryo development. In addition, reopening fertility clinics poses several concerns that need immediate addressing, such as the effect of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) on reproductive cells and also the potential risk of cross-contamination and viral transmission. Therefore, this manuscript summarizes what is currently known about the effect of the SARS-CoV-2 infection on medically assisted reproductive treatments and its effect on reproductive health and pregnancy.

Usage of mobile health interventions among overweight/obese PCOS patients undergoing assisted reproductive technology treatment during the COVID-19 pandemic.

Objective: In the context of the coronavirus disease 2019 (COVID-19) pandemic, telemedicine is a promising tool for providing clinical care for patients. Since the first-line treatment for infertile women with polycystic ovarian syndrome (PCOS) is lifestyle modification, a mobile-based service that provides lifestyle modification education would be helpful in the treatment of PCOS patients. In this observational study, the effect of a mobile Health (mHealth) application for lifestyle modification on PCOS patients undergoing assisted reproductive technology (ART) treatment was evaluated.Methods: A total of 79 overweight/obese patients (40 in the paper group and 39 in the WeChat application group) with PCOS from the First Affiliated Hospital of University of Science and Technology of China were enrolled in the study. The changes in the outcomes of BMI and ART treatment were analyzed between the two groups.Results: After three months of intervention, the BMIs in the control and mHealth groups were 24.5 ± 3.3 and 23.7 ± 3.1, respectively. The percentage of patients who lost weight was higher in the WeChat group than in the control group (87.2% vs. 67.5%). Furthermore, PCOS patients in the WeChat group were found to have a higher live birth rate than those in the control group (p = 0.005).Conclusion: Lifestyle modifications for PCOS patients undergoing ART treatment using the WeChat application improved weight loss and oocyte quality. Infertile patients with PCOS were more likely to make lifestyle modifications based on the usage of mobile applications during the COVID-19 pandemic.

Impact of COVID-19 pandemic on the pregnancy outcomes of women undergoing assisted reproductive techniques (ARTs): a systematic review and meta-analysis.

The global outbreak of the coronavirus disease 2019 (COVID-19) led to the suspension of most treatments with assisted reproductive technique (ART). However, with the recent successful control of the pandemic in China, there is an urgent public need to resume full reproductive care. To determine whether the COVID-19 pandemic had any adverse effects on female fertility and the pregnancy outcomes of women undergoing ART, a systematic review and meta-analysis was conducted using the electronic Chinese and English databases. Dichotomous outcomes were summarized as prevalence, and odds ratios (ORs) and continuous outcomes as standardized mean difference (SMD) with 95% confidence interval (CI). The risk of bias and subgroup analyses were assessed using Stata/SE 15.1 and R 4.1.2. The results showed that compared with women treated by ART in the pre-COVID-19 time frame, women undergoing ART after the COVID-19 pandemic exhibited no significant difference in the clinical pregnancy rate (OR 1.07, 95% CI 0.97 to 1.19; I2=0.0%), miscarriage rate (OR 0.95, 95% CI 0.79 to 1.14; I2=38.4%), embryo cryopreservation rate (OR 2.90, 95% CI 0.17 to 48.13; I2=85.4%), and oocyte cryopreservation rate (OR 0.30, 95% CI 0.03 to 3.65; I2=81.6%). This review provided additional evidence for gynecologists to guide the management of women undergoing ART treatment during the COVID-19 pandemic timeframe.

[The characteristics of reproductive demographic processes in economically developed countries in conditions of COVID-19 pandemic: international publications review].

The article presents current trends in reproductive demographic process economically developed countries. Today, the total fertility rate in all European countries is below the minimum required to ensure population reproduction in long term - 2.1 children per woman during her life. According statistic data, 4.167 million children were born in the EU in 2019 that corresponds to 9.3 births per 1000 of population. In the EU, 1.53 children went to one woman in 2019 (in 2018 - 1.54). The lowest total fertility rates in 2019 were registered in Malta (1.14), Spain (1.23) and Italy (1.27). In the United States, fall of rate of childless women with higher education disputes well-established observation of positive relationship between education and childlessness. The infertility affects approximately 8-12% of couples worldwide, at that in developed countries, up to 15% of all couples are infertile. In connection with the problem of birth rate reduction in developed countries, researchers highlight such problems as increasing of average age of mothers at delivery (30-35 years and older) and intervals between labors, development of subsidiary reproductive technologies, pregnancy outcomes, newborns health in short and long perspective. The global COVID-19 pandemic resulted in resources deficiency, complexities with medical services support related to reproductive health, risks for maternal and perinatal outcomes in pregnant women with COVID-19. However, actually still there is no complete picture of pandemic impact on global indices of reproductive demographic process.

The impact of COVID-19 mitigation measures on fertility patients and clinics around the world.

RESEARCH QUESTION: What is the impact of the response to COVID-19 on the management of fertility treatments and clinical practice around the world? DESIGN: Fertility clinic associates around the world were approached. They completed an online survey containing 33 questions focused on the country's response to the COVID-19 pandemic. Known fertility clinic associates that were contacted comprised scientific directors, medical directors and laboratory managers. RESULTS: There were 43 individual country responses from Asia (13), Africa (3), Europe (17), North America (3), Oceania (2) and South America (5). In nine countries, clinics followed their government body recommendations, in 22 countries there was a combination of recommendations, in 3 countries changes were made by clinic initiative, and 9 countries did not specify. In 34 countries IVF/intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (FET) treatments had an average delay of 56 days (IVF/ICSI) (minimum 0, maximum 160) and 57 days (FET) (minimum 0, maximum 166 days). During the shutdown, the number of freeze-all cycles increased in 22 countries. Only 23 countries reported patients having to undergo a SARS-CoV-2 test, and 20 countries did not report any COVID-19 testing in their clinic. Additional support counselling was offered in 28 countries, partner restrictions at clinics were reported in 41 countries and time between patients' appointments was increased in 39 countries. CONCLUSIONS: The implications of COVID-19 mitigation measures proved the need for government societies to introduce a set protocol that includes requirements such as increased patient counselling and additional guidelines for prioritizing couples who need care most urgently.

Healthcare workers' attitudes about vaccination of pregnant women and those wishing to become pregnant.

OBJECTIVES: We designed an electronic query that was distributed to healthcare workers in order to evaluate their attitudes towards COVID-19 vaccination of women that wish to conceive and those that are pregnant. METHODS: An electronic survey was designed and distributed through a network of 5.654 e-mails. The query was uploaded in Google Forms. RESULTS: Overall, 1,226 answers were retrieved. Ninety percent of respondents replied that they prescribe COVID-19 vaccination in women that wish to conceive, however, the rate falls to 80% for those that have schedules for imminent artificial reproductive techniques. Approximately 1 in 2 physicians (obstetricians and pediatricians) suggests that a delay in assisted reproduction following immunization is not recommended. At least 13% of women of reproductive age and 30% of women wishing to conceive with ART declined to do so according to respondents, report. Only 75% of respondents favored immunization during pregnancy and of those 48% responded that vaccination could be done in all trimesters of pregnancy. Approximately 40% of women decline; however, to receive vaccination. CONCLUSIONS: Despite the directions provided by international organizations; physician and patient hesitancy towards vaccination during pregnancy (and particularly the first trimester) remains an issue that deserves further attention.

The issue of infertility in times of COVID-19: what do we know about it?

ABSTRACT: Couple infertility constitutes a major source of concern and even distress for those involved, affecting roughly 50-80 million people in the world, according to World Health Organization data. There is no denying that medical and technological advancements in the field of as-sisted reproductive technology (ART) are among the greatest and most beneficial achievements of modern medicine. Countless couples have been able to achieve parenthood who in the past could not have, thanks to ART. Infertility itself used to be deemed insurmountable, especially when arising from uterine conditions (referred to as absolute uterine factor infertility, AUFI), neoplastic conditions or major complications affecting reproductive organs during previous pregnancies. The inability to have children is often considered by couples as a failure severely impacting their relationships, due to the unfulfilled biological potential in regard to parenting. However, in addition to its significance as a social problem, infertility is a medical issue which requires a strict and clearly defined path of diagnosis and treatment, particularly in times of COVID-19, when access to essential care has often been delayed with potentially harmful repercussions for patients seeking to achieve parenthood or to keep their fertility.

SARS-CoV-2 infection negatively affects ovarian function in ART patients.

Several organs, such as the heart, breasts, intestine, testes, and ovaries, have been reported to be target tissues of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To date, no studies have demonstrated SARS-CoV-2 infection in the female reproductive system. In the present study, we investigated the effects of SARS-CoV-2 infection on ovarian function by comparing follicular fluid (FF) from control and recovered coronavirus disease 2019 (COVID-19) patients and by evaluating the influence of these FF on human endothelial and non-luteinized granulosa cell cultures. Our results showed that most FFs (91.3%) from screened post COVID-19 patients were positive for IgG antibodies against SARS-CoV-2. Additionally, patients with higher levels of IgG against SARS-CoV-2 had lower numbers of retrieved oocytes. While VEGF and IL-1ß were significantly lower in post COVID-19 FF, IL-10 did not differ from that in control FF. Moreover, in COV434 cells stimulated with FF from post COVID-19 patients, steroidogenic acute regulatory protein (StAR), estrogen-receptor ß (Erß), and vascular endothelial growth factor (VEGF) expression were significantly decreased, whereas estrogen-receptor α (ERα) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) did not change. In endothelial cells stimulated with post COVID-19 FF, we observed a decrease in cell migration without changes in protein expression of certain angiogenic factors. Both cell types showed a significantly higher γH2AX expression when exposed to post COVID-19 FF. In conclusion, our results describe for the first time that the SARS-CoV-2 infection adversely affects the follicular microenvironment, thus dysregulating ovarian function.

State of assisted reproduction technology in the coronavirus disease 2019 era and consequences on human reproductive system.

The outbreak of the coronavirus disease 2019 (COVID-19) has created havoc on the socio-economic aspect of the world. With billions of lives being affected by this wrecking pandemic, global fertility services were also not left untouched by its impact. The possibility of sexual transmission of SARS-CoV-2 virus, its impact on male and female fertility, pregnancy, its potential teratogenic effect, and handling of gametes in the clinical laboratories were major concerns among reproductive medicine specialists, which led down all the reproductive health services, including IUI, IVF/ICSI in most of the countries. Even the people did not intend to conceive during the pandemic crisis and were hesitant to avail such services. Discrete evidence regarding the pathophysiology of COVID-19 infection and its impact on the human reproductive system is not very clear. In this review article, we intend to incorporate all the evidence related to the COVID-19 infection and its impact on human reproduction available to date. It is our responsibility to provide rightful information and to keep our patients familiar with the existing lack of clear evidence. In this COVID-19 era, it is important that the fertility management be prioritized in sub-fertile couples with diminished fertility reserve and high-risk conditions, like malignancies, that may affect their long-term fertility prospects.

The association between psychosocial interventions and fertility treatment outcome: A systematic review and meta-analysis.

OBJECTIVE: Does psychosocial intervention affect pregnancy outcomes in women and couples undergoing assisted reproductive technology (ART) treatment?. DESIGN: A systematic review and meta-analysis of Randomized Controlled Trials (RCTs) evaluating the efficacy of psychosocial intervention on pregnancy outcomes in women and couples undergoing ART treatment. The primary outcome was Pregnancy Rates. Secondary outcomes were Live Birth Rate (LBR) and Abortion Rate (AR). MATERIALS AND METHODS: Databases searched were Pubmed, PsycINFO, Embase, CINAHL and The Cochrane Library. 1439 records were screened, 15 were eligible and included in the meta-analyses (N = 2434). Data was extracted using the Covidence software. Effect sizes were reported as relative risks with 95% confidence-intervals and p-values. RESULTS: A positive association was found between psychosocial intervention and pregnancy rates (RR = 1.12 CI=(1.01;1.24), p = 0.033). Long-duration interventions and mind-body intervention types were found to be associated with increased pregnancy rates (RR 1.21, CI= (1.04;1.43), p = 0.017) and (RR = 1.25, CI= (1.00;1.55), p = 0.046) respectively. Q and I2tests suggested no to low heterogeneity. Funnel plots, Trim and Fill analyses and Fail-safe numbers were applied to adjust for possible publication bias. CONCLUSIONS: Our findings suggest a positive association between psychosocial interventions, particularly long-duration interventions, and pregnancy rate in infertile women and couples in ART treatment. The findings are in line with findings from other reviews and meta-analyses exploring the same topic. More good quality RCTs need to be performed to increase the quality of guidance for infertile women and couples. The effect of psychosocial interventions on LBR and AR remain to be examined.

The Impact of SARS-CoV-2 on Sperm Cryostorage, Theoretical or Real Risk?

Cryopreservation of human gametes and embryos as well as human reproductive tissues has been characterized as an essential process and aspect of assisted reproductive technology (ART). Notably, sperm cryopreservation is a fundamental aspect of cryopreservation in oncological patients or patients undergoing gonadotoxic treatment. Given that there is a risk of contamination or cross-contamination, either theoretical or real, during the procedures of cryopreservation and cryostorage, both the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) have provided updated guidelines for preventing or reducing the contamination risk of sexually transmitted viruses. Given the ongoing and worldwide COVID-19 pandemic, there is considerable interest in what measures should be taken to mitigate SARS-CoV-2 contamination during cryopreservation and cryostorage of semen samples. The SARS-CoV-2 virus is the virus that causes COVID-19, and whose transmission and infection is mainly aerosol-mediated. Several ART professional societies, including ESHRE and ASRM have proposed measures to mitigate the spread of the SARS-CoV-2 virus. Whether the proposed safety directives are enough to mitigate the possible SARS-CoV-2-contamination of sperm samples during cryopreservation or whether the policies should be re-evaluated will be discussed in this review. Additionally, insights regarding the possible impact of COVID-19 vaccination on the safety of sperm cryopreservation will be discussed.

Mild COVID-19 infection does not alter the ovarian reserve in women treated with ART.

RESEARCH QUESTION: Does mild COVID-19 infection affect the ovarian reserve of women undergoing an assisted reproductive technology (ART) protocol? DESIGN: A prospective observational study was conducted between June and December 2020 at the ART unit of Tenon Hospital, Paris. Women managed at the unit for fertility issues by in-vitro fecundation, intracytoplasmic sperm injection (IVF/ICSI), fertility preservation, frozen embryo transfer or artificial insemination, and with an anti-Müllerian hormone (AMH) test carried out within 12 months preceding ART treatment, were included. All the women underwent a COVID rapid detection test (RDT) and AMH concentrations between those who tested positive (RDT positive) and those who tested negative (RDT negative). RESULTS: The study population consisted of 118 women, 11.9% (14/118) of whom were COVID RDT positive. None of the tested women presented with a history of severe COVID-19 infection. The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (-1.33 ng/ml [-0.35 to -1.61) versus -0.59 ng/ml [-0.15 to -1.11], P = 0.22). CONCLUSION: A history of mild COVID-19 infection does not seem to alter the ovarian reserve as evaluated by AMH concentrations. Although these results are reassuring, further studies are necessary to assess the effect of COVID-19 on pregnancy outcomes in women undergoing ART.