Fetal death as an outcome of acute respiratory distress in pregnancy, during the COVID-19 pandemic: a population-based cohort study in Bahia, Brazil.

BACKGROUND: Fetal loss is one of the most serious adverse outcomes of pregnancy. Since the onset of the COVID-19 pandemic, Brazil has recorded an unprecedented number of hospitalizations of pregnant women due to acute respiratory distress (ARD), thereby, we aimed to assess the risk of fetal deaths associated to ARD during pregnancy in Bahia state, Brazil, in the context of the COVID-19 pandemic. METHODS: This is an observational population-based retrospective cohort study, developed with women at or after 20 weeks of pregnancy, residents in Bahia, Brazil. Women who had acute respiratory distress (ARD) in pregnancy during the COVID-19 pandemic (Jan 2020 to Jun 2021) were considered 'exposed'. Women who did not have ARD in pregnancy, and whose pregnancy occurred before the onset of the COVID-19 pandemic (Jan 2019 to Dec 2019) were considered 'non-exposed'. The main outcome was fetal death. We linked administrative data (under mandatory registration) on live births, fetal deaths, and acute respiratory syndrome, using a probabilistic linkage method, and analyzed them with multivariable logistic regression models. RESULTS: 200,979 pregnant women participated in this study, 765 exposed and 200,214 unexposed. We found four times higher chance of fetal death in women with ARD during pregnancy, of all etiologies (adjusted odds ratio [aOR] 4.06 confidence interval [CI] 95% 2.66; 6.21), and due to SARS-CoV-2 (aOR 4.45 CI 95% 2.41; 8.20). The risk of fetal death increased more when ARD in pregnancy was accompanied by vaginal delivery (aOR 7.06 CI 95% 4.21; 11.83), or admission to Intensive Care Unit (aOR 8.79 CI 95% 4.96; 15.58), or use of invasive mechanical ventilation (aOR 21.22 CI 95% 9.93; 45.36). CONCLUSION: Our findings can contribute to expanding the understanding of health professionals and managers about the harmful effects of SARS-CoV-2 on maternal-fetal health and alerts the need to prioritize pregnant women in preventive actions against SARS-CoV-2 and other respiratory viruses. It also suggests that pregnant women, infected with SARS-CoV-2, need to be monitored to prevent complications of ARD, including a careful assessment of the risks and benefits of early delivery to prevent fetal death.

National data linkage assessment of live births and deaths in Mexico: Estimating under-five mortality rate ratios for vulnerable newborns and trends from 2008 to 2019.

BACKGROUND: Linked datasets that enable longitudinal assessments are scarce in low and middle-income countries. OBJECTIVES: We aimed to assess the linkage of administrative databases of live births and under-five child deaths to explore mortality and trends for preterm, small (SGA) and large for gestational age (LGA) in Mexico. METHODS: We linked individual-level datasets collected by National statistics from 2008 to 2019. Linkage was performed based on agreement on birthday, sex, residential address. We used the Centre for Data and Knowledge Integration for Health software to identify the best candidate pairs based on similarity. Accuracy was assessed by calculating the area under the receiver operating characteristic curve. We evaluated completeness by comparing the number of linked records with reported deaths. We described the percentage of linked records by baseline characteristics to identify potential bias. Using the linked dataset, we calculated mortality rate ratios (RR) in neonatal, infants, and children under-five according to gestational age, birthweight, and size. RESULTS: For the period 2008-2019, a total of 24,955,172 live births and 321,165 under-five deaths were available for linkage. We excluded 1,539,046 records (6.2%) with missing or implausible values. We succesfully linked 231,765 deaths (72.2%: range 57.1% in 2009 and 84.3% in 2011). The rate of neonatal mortality was higher for preterm compared with term (RR 3.83, 95% confidence interval, [CI] 3.78, 3.88) and for SGA compared with appropriate for gestational age (AGA) (RR 1.22 95% CI, 1.19, 1.24). Births at <28 weeks had the highest mortality (RR 35.92, 95% CI, 34.97, 36.88). LGA had no additional risk vs AGA among children under five (RR 0.92, 95% CI, 0.90, 0.93). CONCLUSIONS: We demonstrated the utility of linked data to understand neonatal vulnerability and child mortality. We created a linked dataset that would be a valuable resource for future population-based research.

Laparoscopic management of second trimester ruptured cornual heterotopic pregnancy with subsequent live birth delivery: A case report and literature review.

OBJECTIVE: Heterotopic pregnancy (HP) is the coexistence of extra- and intrauterine gestation implantation sites. A rare case of a second-trimester ruptured cornual HP (CHP) treated with laparoscopic cornual resection with the primary repair is presented. Risk factors, clinical presentations, treatments, and outcomes of CHPs are also reviewed. CASE REPORT: A 35-year-old pregnant woman with CHP presented with lower abdominal pain with hemoperitoneum and her hemoglobin level dropped. Laparoscopic management of a ruptured HP was performed, leaving the surplus intrauterine fetus intact. She delivered a 2360 g male infant via cesarean section at 34 weeks' gestation due to preterm premature rupture of membranes. We found a well-healed wound over the left uterine cornua during the cesarean section. CONCLUSION: Ruptured CHP is a rare but life-threatening complication of an obstetric emergency. Although the pregnant uterus becomes congested and fragile, using reliable laparoscopic energy devices and barbed sutures, successful treatment is feasible.

Effect of female coronavirus disease 2019 vaccination on assisted reproductive outcomes: a systematic review and meta-analysis.

IMPORTANCE: The effect of coronavirus disease 2019 (COVID-19) vaccination on fertility warrants clarification in women undergoing assisted reproductive treatment. OBJECTIVE: To study the association between female COVID-19 vaccination and outcomes of assisted reproductive treatment. DATA SOURCES: PubMed, Embase, the Web of Science, Cochrane Library, and medRxiv and bioRxiv were searched for eligible studies from December 1, 2019, to November 30, 2022, with no language restrictions. STUDY SELECTION AND SYNTHESIS: Observational studies comparing assisted reproductive outcomes between women with and without COVID-19 vaccination were included. The pooled estimates were calculated using the random-effects models as mean differences (MDs), standardized MDs, or odds ratios with 95% confidence intervals (CIs). Heterogeneity was evaluated using the I2 statistic. MAIN OUTCOMES: The number of oocytes retrieved and clinical pregnancy rate. RESULTS: Twenty-one cohort studies involving a total of 19,687 treatment cycles were included. In a comparison of the vaccinated vs. unvaccinated groups, the pooled MD for oocyte number was -0.06 (95% CI, -0.51 to 0.39; I2 = 0), and the pooled odds ratio for clinical pregnancy was 0.95 (95% CI, 0.85-1.05; I2 = 0). Similarly, there were no statistically significant adverse effects identified in other outcomes determined a priori, including 4 cycle characteristics, 6 laboratory parameters, and 3 pregnancy indicators. Most results were consistently unchanged in subgroup and sensitivity analyses, with no evidence of publication bias according to Egger's test. CONCLUSION AND RELEVANCE: Our work did not find significant differences in assisted reproductive outcomes between vaccinated and unvaccinated women. However, more data are warranted to confirm the safety of COVID-19 vaccination for assisted reproductive treatment and in female fertility in general.

The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis.

STUDY QUESTION: What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines? SUMMARY ANSWER: There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage. WHAT IS KNOWN ALREADY: In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity, and mortality. Still, many were concerned about the safety of vaccines for pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy. STUDY DESIGN, SIZE, DURATION: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception until June 2022 using a combination of keywords and MeSH terms. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational and interventional studies that enrolled pregnant women and evaluated any of the available COVID-19 vaccines compared to placebo or no vaccination. We primarily reported on miscarriage in addition to ongoing pregnancy and/or live birth. MAIN RESULTS AND THE ROLE OF CHANCE: We included data from 21 studies (5 randomized trials and 16 observational studies) reporting on 149 685 women. The pooled rate of miscarriage among women who received a COVID-19 vaccine was 9% (n = 14 749/123 185, 95% CI 0.05-0.14). Compared to those who received a placebo or no vaccination, women who received a COVID-19 vaccine did not have a higher risk of miscarriage (risk ratio (RR) 1.07, 95% CI 0.89-1.28, I2 35.8%) and had comparable rates for ongoing pregnancy or live birth (RR 1.00, 95% CI 0.97-1.03, I2 10.72%). LIMITATIONS, REASONS FOR CAUTION: Our analysis was limited to observational evidence with varied reporting, high heterogeneity and risk of bias across included studies, which may limit the generalizability and confidence in our findings. WIDER IMPLICATIONS OF THE FINDINGS: COVID-19 vaccines are not associated with an increase in the risk of miscarriage or reduced rates of ongoing pregnancy or live birth among women of reproductive age. The current evidence remains limited and larger population studies are needed to further evaluate the effectiveness and safety of COVID-19 vaccination in pregnancy. STUDY FUNDING/COMPETING INTEREST(S): No direct funding was provided to support this work. M.P.R. was funded by the Medical Research Council Centre for Reproductive Health Grant No: MR/N022556/1. B.H.A.W. hold a personal development award from the National Institute of Health Research in the UK. All authors declare no conflict of interest. REGISTRATION NUMBER: CRD42021289098.

Impact of the first wave of the COVID-19 pandemic on birth rates in Europe: a time series analysis in 24 countries.

STUDY QUESTION: Did the first wave of the COVID-19 pandemic have an impact on monthly birth rates in Europe? SUMMARY ANSWER: Using datasets on live births per month in Europe, collected from the Human Fertility Database, we found a -14.1% decline in live births in January 2021 (i.e. 9-10 months after the epidemic peaks and first lockdowns), compared to the average number of live births in January 2018 and 2019. WHAT IS KNOWN ALREADY: Previous pandemics in the 20th and 21st centuries have been associated with a decline in birth rates 9 months after their peak, and a rebound in births over time. Lockdowns were necessary to control the first wave of the COVID-19 pandemic and may have had an impact on subsequent birth rates. STUDY DESIGN, SIZE, DURATION: Monthly time series data on live births from January 2018 to March 2021 were extracted to provide a time-series analysis of birthrates during and after the first wave of the COVID-19 pandemic in 24 European countries. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted a random-effect generalized least squares regression to assess the seasonality of births from January 2018 to March 2021, and to identify potential differences in monthly live births after the first wave of the COVID-19 pandemic, considering the seasonality of births. To quantify these potential differences, we estimated the variation rate between the monthly live births observed during 2020 and 2021 and the mean of the 2018-2019 monthly live births in Europe. Factors potentially associated with a variation in monthly birth rates were assessed using univariable and multivariable generalized linear regressions. MAIN RESULTS AND THE ROLE OF CHANCE: When considering the seasonality of births, January 2021 was the only month with a significant difference in live births. A drop of -14.1% was observed compared to the average number of live births in January 2018 and 2019. At the national level, this drop was observed 9-10 months after the epidemic peaks in 13 countries. The duration of lockdowns was the variable that had the stronger association with this decrease, whereas higher incomes per capita could be a factor limiting this decline. A rebound in births compared to the previous years occurred in March 2021 in 13 countries. LIMITATIONS, REASONS FOR CAUTION: Our data are based on national data, limiting the power in the multivariable models used and the identification of other potential factors contributing to a decrease or an increase in birth rates. In addition, we collected only live births up to April 2021, which precludes the identification of a difference in births seasonality in 2021. WIDER IMPLICATIONS OF THE FINDINGS: As with previous pandemics, the COVID-19 outbreak was associated with a decline in births 9 months after its first wave. This trend may be associated with the duration of the lockdowns. Although there was a rebound in births in the following months, it does not seem to compensate for this decline. STUDY FUNDING/COMPETING INTEREST(S): The authors receive no external funding and have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Inactivated Covid-19 vaccine did not undermine live birth and neonatal outcomes of women with frozen-thawed embryo transfer.

STUDY QUESTION: Does inoculation with inactivated vaccines against coronavirus disease 2019 (Covid-19) before frozen-thawed embryo transfer (FET) affect live birth and neonatal outcomes? SUMMARY ANSWER: Inactivated Covid-19 vaccines did not undermine live birth and neonatal outcomes of women planning for FET. WHAT IS KNOWN ALREADY: Accumulating reports are now available indicating the safe use of mRNA vaccines against Covid-19 in pregnant and lactating women, and a few reports indicate that they are not associated with adverse effects on ovarian stimulation or early pregnancy outcomes following IVF. Evidence about the safety of inactivated Covid-19 vaccines is very limited. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort analysis from Reproductive Medical Center of a tertiary teaching hospital. Clinical records and vaccination record of 2574 couples with embryos transferred between 1 March 2021 and 30 September 2021 were screened for eligibility of this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical and vaccination data of infertile couples planning for FET were screened for eligibility of the study. The reproductive and neonatal outcomes of FET women inoculated with inactivated Covid-19 vaccines or not were compared. The primary outcomes were live birth rate per embryo transfer cycle and newborns' birth height and weight. Secondary outcomes included rates of ongoing pregnancy, clinical pregnancy, biochemical pregnancy and spontaneous miscarriage. Multivariate logistical regression and propensity score matching (PSM) analyses were performed to minimize the influence of confounding factors. Subgroup analyses, including single dose versus double dose of the vaccines and the time intervals between the first vaccination and embryo transfer, were also performed. MAIN RESULTS AND THE ROLE OF CHANCE: Vaccinated women have comparable live birth rates (43.6% versus 45.0% before PSM, P = 0.590; and 42.9% versus 43.9% after PSM, P = 0.688), ongoing pregnancy rates (48.2% versus 48.1% before PSM, P = 0.980; and 52.2% versus 52.7% after PSM, P = 0.875) and clinical pregnancy rate (55.0% versus 54.8% before PSM, P = 0.928; and 54.7% versus 54.2% after PSM, P = 0.868) when compared with unvaccinated counterparts. The newborns' birth length (50.0 ± 1.6 versus 49.0 ± 2.9 cm before PSM, P = 0.116; and 49.9 ± 1.7 versus 49.3 ± 2.6 cm after PSM, P = 0.141) and birth weight (3111.2 ± 349.9 versus 3030.3 ± 588.5 g before PSM, P = 0.544; and 3053.8 ± 372.5 versus 3039.2 ± 496.8 g after PSM, P = 0.347) were all similar between the two groups. Neither single dose nor double dose of vaccines, as well as different intervals between vaccination and embryo transfer showed any significant impacts on reproductive and neonatal outcomes. LIMITATIONS, REASONS FOR CAUTION: The main findings might be limited by retrospective design. Besides, inoculations of triple dose of Covid-19 vaccines were not available by the time of data collection, thus the results cannot reflect the safe use of triple dose of inactivated Covid-19 vaccines. Finally, history of Covid-19 infection was based on patients' self-report rather than objective laboratory tests. WIDER IMPLICATIONS OF THE FINDINGS: Eligible individuals of inactivated vaccines against Covid-19 should not postpone vaccination plan because of their embryo transfer schedule, or vice versa. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Medical Key Discipline of Guangzhou (2021-2023). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Preterm birth rates were slightly lower in Denmark during the first year of the COVID-19 pandemic compared with the previous 4 years.

AIM: Our aim was to investigate the rates of preterm births, live births and stillbirths in Denmark during the first year of the COVID-19 pandemic. METHODS: This was a national, cross-sectional registry-based study that used the Danish Newborn Quality database, which covers all births in Denmark. The proportions of preterm births were compared between the COVID-19 pandemic period of 1 March 2020 to 28 February 2021 and the preceding 4-year pre-pandemic period. RESULTS: We studied 60 323 and 244 481 newborn infants from the pandemic and pre-pandemic periods, respectively. The proportion of preterm live births and stillbirths declined slightly, from 6.29% during the pre-pandemic period to 6.02% during the pandemic period. This corresponded to a relative risk (RR) of 0.96, with a 95% confidence interval (CI) of 0.93-0.99 during the pandemic. The RRs for extremely preterm, very preterm and moderately preterm infants were 0.88 (95% CI 0.76-1.02), 0.91 (95% CI 0.82-1.02) and 0.97 (95% CI 0.93-1.01), respectively. CONCLUSION: This comparative study showed a small reduction in just over 4%, from 6.29 to 6.02% in the proportion of all preterm births during the pandemic period, compared with the previous four pandemic-free years. There were no differences between subcategories of preterm births.

The Effects of City Lockdown Policy on Frozen Embryo Transfer Outcome during COVID-19 Epidemic in Hubei Province, China.

Objective: To evaluate whether there is a difference in clinical pregnancy rate and live birth rate between the corresponding period in 2019 and COVID-19 city lockdown period in 2020 in frozen embryo transfer (FET). Methods: In one single in vitro fertilization (IVF) center (Shiyan, Hubei province, China), a retrospective cohort analysis was conducted, with a sample size of 59 patients in the lockdown period (2020.1.23-2020.2.23, 2020 group) and 34 patients in the corresponding 2019 period (2019.1.23-2019.2.23, 2019 group). Implantation, biochemical and clinical pregnancy, miscarriage, and live birth rates were all measured. Results: Age, basal serum follicle-stimulating hormone (FSH), basal serum luteinizing hormone (LH), basal serum E2, and serum total T were all comparable between the two groups. On the day of progesterone administration, endometrial thickness was similar (8.5 ± 1.3 vs. 8.2 ± 1.4, P = 0.356). The number of transferred blastocysts was not significantly different. The two groups had similar clinical pregnancy rate (61.8% vs. 61.0%, P > 0.05) and live birth rate (47.1% vs. 49.2%, P > 0.05), which did not significantly differ. Nonetheless, there was a significant difference in the cancelled cycle rate between the two groups (0% vs. 28.0%, P = 0.043). Conclusions: Lockdown period FET versus corresponding period FET outcome did not show any significant difference in terms of pregnancy rate and live birth rate between two groups of patients. Although there was no significant difference, in the 2020 group, the live birth rate was higher compared with that in the 2019 group. There was a significant difference in the rate of cancelled cycles due to the seal off control. In summary, artificial endometrial preparation is an appropriate protocol for special periods.

IVF under COVID-19: treatment outcomes of fresh ART cycles.

STUDY QUESTION: Does prior severe acute respiratory syndrome coronavirus-2 (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 postinfection). 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 postinfection), 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 to -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.

Excess mortality caused by the COVID-19 pandemic negatively impacts birth numbers in European countries.

STUDY QUESTION: How did the coronavirus disease 2019 (COVID-19) pandemic affect live birth numbers in Europe? SUMMARY ANSWER: In 14 European countries with validated datasets on live birth numbers during the ongoing COVID-19 pandemic, excess mortality was inversely correlated with live birth numbers. WHAT IS KNOWN ALREADY: Since March 2020, in order to minimize spread of severe acute respiratory syndrome coronavirus 2 and reducing strain on the health care systems, many national authorities have imposed containments and restricted both indoor and outdoor recreational activities. Historical events, such as electricity blackouts, have repeatedly been shown to exert incremental effects on birth numbers. STUDY DESIGN, SIZE, DURATION: We evaluated the effect of the COVID-19 pandemic and the containments on reproduction and birth numbers in 14 European countries with complete and validated datasets, until March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The national demographic offices of 20 European countries were requested to provide the monthly birth numbers from 2015 to March 2021. Among them, 14 countries provided those data. Taking into account seasonal variations, the live birth numbers were compared with excess mortality at two different time intervals during the pandemic. MAIN RESULTS AND THE ROLE OF CHANCE: At 9 months after the initiation of containments in many European countries, 11 of 14 European countries (78.5%) experienced a decline in live birth numbers, ranging between -0.5% and -11.4%. The decline in live birth numbers was most pronounced in eight European countries with the highest degree of excess mortality. From January to March 2021, live birth numbers continued to decline in 5 of 8 European countries with high excess mortality, whereas live births started to recover in 8 of 14 countries (57.1%). LIMITATIONS, REASONS FOR CAUTION: The live birth numbers of some key European countries were not available. WIDER IMPLICATIONS OF THE FINDINGS: The demographic changes linked to the COVID-19 pandemic may add to the overall socio-economic consequences, most particularly in those countries with pre-existing reduced reproduction rates. STUDY FUNDING/COMPETING INTEREST(S): This study did not receive specific funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Association of BNT162b2 COVID-19 Vaccination During Pregnancy With Neonatal and Early Infant Outcomes.

Importance: Pregnant women were excluded from the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech) preauthorization trial. Therefore, observational data on vaccine safety for prenatally exposed newborns are critical to inform recommendations on maternal immunization. Objective: To examine whether BNT162b2 mRNA vaccination during pregnancy is associated with adverse neonatal and early infant outcomes among the newborns. Design, Setting, and Participants: Population-based cohort study comprising all singleton live births in March through September 2021, within a large state-mandated health care organization in Israel, followed up until October 31, 2021. Exposure: Maternal BNT162b2 mRNA vaccination during pregnancy. Main Outcomes and Measures: Risk ratios (RR) of preterm birth, small birth weight for gestational age (SGA), congenital malformations, all-cause hospitalizations, and infant death. Stabilized inverse probability weighting was used to adjust for maternal age, timing of conception, parity, socioeconomic status, population subgroup, and maternal influenza immunization status. Results: The cohort included 24 288 eligible newborns (49% female, 96% born at ≥37 weeks' gestation), of whom 16 697 were exposed (n = 2134 and n = 9364 in the first and second trimesters, respectively) to maternal vaccination in utero. Median (IQR) follow-up after birth was 126 days (76-179) among exposed and 152 days (88-209) among unexposed newborns. No substantial differences were observed in preterm birth rates between exposed and unexposed newborns (RR = 0.95; 95% CI, 0.83-1.10) or SGA (RR = 0.97; 95% CI, 0.87-1.08). No significant differences were observed in the incidence of all-cause neonatal hospitalizations (RR = 0.99; 95% CI, 0.88-1.12), postneonatal hospitalizations after birth (RR = 0.95; 95% CI, 0.84-1.07), congenital anomalies (RR = 0.69; 95% CI, 0.44-1.04), or infant mortality over the study period (RR = 0.84; 95% CI, 0.43-1.72). Conclusions and Relevance: This large population-based study found no evident differences between newborns of women who received BNT162b2 mRNA vaccination during pregnancy, vs those of women who were not vaccinated, and contributes to current evidence in establishing the safety of prenatal vaccine exposure to the newborns. Interpretation of study findings is limited by the observational design.

Impact of Lockdown Measures during COVID-19 Pandemic on Pregnancy and Preterm Birth.

OBJECTIVE: The objective of this study is to assess the effect of the lockdown measures during the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes of women who were not affected by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: We used data from the perinatal health program and neonatal databases to conduct a cohort analysis of pregnancy outcomes during the COVID-19 lockdown in the Calgary region, Canada. Rates of preterm birth were compared between the lockdown period (March 16 to June 15, 2020) and the corresponding pre-COVID period of 2015 to 2019. We also compared maternal and neonatal characteristics of preterm infants admitted to neonatal intensive care units (NICUs) in Calgary between the two periods. FINDINGS: A total of 4,357 and 24,160 live births occurred in the lockdown and corresponding pre-COVID period, respectively. There were 366 (84.0 per 1,000 live births) and 2,240 (92.7 per 1,000 live births) preterm births in the lockdown and corresponding pre-COVID period, respectively (p = 0.07). Rates of very preterm and very-low-birth-weight births were lower in the lockdown period compared with the corresponding pre-COVID period (11.0 vs. 15.6 and 9.0 vs. 14.4 per 1,000 live births, p = 0.02 and p = 0.005, respectively). There was no difference in spontaneous stillbirth between the two periods (3.7 vs. 4.1 per 1,000 live birth, p = 0.71). During the lockdown period, the likelihood of multiple births was lower (risk ratio [RR] 0.73, 95% confidence interval [CI]: 0.60-0.88), while gestational hypertension and clinical chorioamnionitis increased (RR 1.24, 95%CI: 1.10-1.40; RR 1.33, 95%CI 1.10-1.61, respectively). CONCLUSION: Observed rates of very preterm and very-low-birth-weight births decreased during the COVID-19 lockdown. Pregnant women who delivered during the lockdown period were diagnosed with gestational hypertension and chorioamnionitis more frequently than mothers in the corresponding pre-COVID period. KEY POINTS: · Lockdown measures to reduce COVID-19 transmission were associated with a lower rate of preterm birth.. · Mental and physical wellbeing of pregnant women were significantly affected by the lockdown measures.. · A comprehensive public health plan to relieve psychosocial stress during pregnancy is required..

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.

Surgical or radiological treatment for varicoceles in subfertile men.

BACKGROUND: Varicoceles are associated with male subfertility; however, the mechanisms by which varicoceles affect fertility have yet to be satisfactorily explained. Several treatment options exist, including surgical or radiological treatment, however the safest and most efficient treatment remains unclear.  OBJECTIVES: To evaluate the effectiveness and safety of surgical and radiological treatment of varicoceles on live birth rate, adverse events, pregnancy rate, varicocele recurrence, and quality of life amongst couples where the adult male has a varicocele, and the female partner of childbearing age has no fertility problems. SEARCH METHODS: We searched the following databases on 4 April 2020: the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. We also searched the trial registries and reference lists of articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) if they were relevant to the clinical question posed and compared different forms of surgical ligation, different forms of radiological treatments, surgical treatment compared to radiological treatment, or one of these aforementioned treatment forms compared to non-surgical methods, delayed treatment, or no treatment. We extracted data if the studies reported on live birth, adverse events, pregnancy, varicocele recurrence, and quality of life. DATA COLLECTION AND ANALYSIS: Screening of abstracts and full-text publications, alongside data extraction and 'Risk of bias' assessment, were done dually using the Covidence software. When we had sufficient data, we calculated random-effects (Mantel-Haenszel) meta-analyses; otherwise, we reported results narratively. We used the I2 statistic to analyse statistical heterogeneity. We planned to use funnel plots to assess publication bias in meta-analyses with at least 10 included studies. We dually rated the risk of bias of studies using the Cochrane 'Risk of bias' tool, and the certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified 1897 citations after de-duplicating the search results. We excluded 1773 during title and abstract screening. From the 113 new full texts assessed in addition to the 10 studies (11 references) included in the previous version of this review, we included 38 new studies, resulting in a total of 48 studies (59 references) in the review providing data for 5384 participants. Two studies (three references) are ongoing studies and two studies are awaiting classification. Treatment versus non-surgical, non-radiological, delayed, or no treatment Two studies comparing surgical or radiological treatment versus no treatment reported on live birth with differing directions of effect. As a result, we are uncertain whether surgical or radiological treatment improves live birth rates when compared to no treatment (risk ratio (RR) 2.27, 95% confidence interval (CI) 0.19 to 26.93; 2 RCTs, N = 204; I2 = 74%, very low-certainty evidence). Treatment may improve pregnancy rates compared to delayed or no treatment (RR 1.55, 95% CI 1.06 to 2.26; 13 RCTs, N = 1193; I2 = 65%, low-certainty evidence). This suggests that couples with no or delayed treatment have a 21% chance of pregnancy, whilst the pregnancy rate after surgical or radiological treatment is between 22% and 48%. We identified no evidence on adverse events, varicocele recurrence, or quality of life for this comparison. Surgical versus radiological treatment We are uncertain about the effect of surgical versus radiological treatment on live birth and on the following adverse events: hydrocele formation, pain, epididymitis, haematoma, and suture granuloma. We are uncertain about the effect of surgical versus radiological treatment on pregnancy rate (RR 1.13, 95% CI 0.75 to 1.70; 5 RCTs, N = 456, low-certainty evidence) and varicocele recurrence (RR 1.31, 95% CI 0.82 to 2.08; 3 RCTs, N = 380, low-certainty evidence). We identified no evidence on quality of life for this comparison. Surgery versus other surgical treatment We identified 19 studies comparing microscopic subinguinal surgical treatment to any other surgical treatment. Microscopic subinguinal surgical treatment probably improves pregnancy rates slightly compared to other surgical treatments (RR 1.18, 95% CI 1.02 to 1.36; 12 RCTs, N = 1473, moderate-certainty evidence). This suggests that couples with microscopic subinguinal surgical treatment have a 10% to 14% chance of pregnancy after treatment, whilst the pregnancy rate in couples after other surgical treatments is 10%. This procedure also probably reduces the risk of varicocele recurrence (RR 0.48, 95% CI 0.29, 0.79; 14 RCTs, N = 1565, moderate-certainty evidence). This suggests that 0.4% to 1.1% of men undergoing microscopic subinguinal surgical treatment experience recurrent varicocele, whilst 1.4% of men undergoing other surgical treatments do. Results for the following adverse events were inconclusive: hydrocele formation, haematoma, abdominal distension, testicular atrophy, wound infection, scrotal pain, and oedema. We identified no evidence on live birth or quality of life for this comparison. Nine studies compared open inguinal surgical treatment to retroperitoneal surgical treatment. Due to small sample sizes and methodological limitations, we identified neither treatment type as superior or inferior to the other regarding adverse events, pregnancy rates, or varicocele recurrence. We identified no evidence on live birth or quality of life for this comparison. Radiological versus other radiological treatment One study compared two types of radiological treatment (sclerotherapy versus embolisation) and reported 13% varicocele recurrence in both groups. Due to the broad confidence interval, no valid conclusion could be drawn (RR 1.00, 95% CI 0.16 to 6.20; 1 RCT, N = 30, very low-certainty evidence). We identified no evidence on live birth, adverse events, pregnancy, or quality of life for this comparison. AUTHORS' CONCLUSIONS: Based on the limited evidence, it remains uncertain whether any treatment (surgical or radiological) compared to no treatment in subfertile men may be of benefit on live birth rates; however, treatment may improve the chances for pregnancy. The evidence was also insufficient to determine whether surgical treatment was superior to radiological treatment. However, microscopic subinguinal surgical treatment probably improves pregnancy rates and reduces the risk of varicocele recurrence compared to other surgical treatments. High-quality, head-to-head comparative RCTs focusing on live birth rate and also assessing adverse events and quality of life are warranted.

Immediate versus postponed frozen embryo transfer after IVF/ICSI: a systematic review and meta-analysis.

BACKGROUND: In Europe, the number of frozen embryo transfer (FET) cycles is steadily increasing, now accounting for more than 190 000 cycles per year. It is standard clinical practice to postpone FET for at least one menstrual cycle following a failed fresh transfer or after a freeze-all cycle. The purpose of this practice is to minimise the possible residual negative effect of ovarian stimulation on the resumption of a normal ovulatory cycle and receptivity of the endometrium. Although elective deferral of FET may unnecessarily delay time to pregnancy, immediate FET may be inefficient in a clinical setting, following an increased risk of irregular ovulatory cycles and the presence of functional cysts, increasing the risk of cycle cancellation. OBJECTIVE AND RATIONALE: This review explores the impact of timing of FET in the first cycle (immediate FET) versus the second or subsequent cycle (postponed FET) following a failed fresh transfer or a freeze-all cycle on live birth rate (LBR). Secondary endpoints were implantation, pregnancy and clinical pregnancy rates (CPR) as well as miscarriage rate (MR). SEARCH METHODS: We searched PubMed (MEDLINE) and EMBASE databases for MeSH and Emtree terms, as well as text words related to timing of FET, up to March 2020, in English language. There were no limitations regarding year of publication or duration of follow-up. Inclusion criteria were subfertile women aged 18-46 years with any indication for treatment with IVF/ICSI. Studies on oocyte donation were excluded. All original studies were included, except for case reports, study protocols and abstracts only. Covidence, a Cochrane-tool, was used for sorting and screening of literature. Risk of bias was assessed using the Robins-I tool and the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework. OUTCOMES: Out of 4124 search results, 15 studies were included in the review. Studies reporting adjusted odds ratios (aOR) for LBR, CPR and MR were included in meta-analyses. All studies (n = 15) were retrospective cohort studies involving a total of 6,304 immediate FET cycles and 13,851 postponed FET cycles including 8,019 matched controls. Twelve studies of very low to moderate quality reported no difference in LBR with immediate versus postponed FET. Two studies of moderate quality reported a statistically significant increase in LBR with immediate FET and one small study of very low quality reported better LBR with postponed FET. Trends in rates of secondary outcomes followed trends in LBR regarding timing of FET. The meta-analyses showed a significant advantage of immediate FET (n =2,076) compared to postponed FET (n =3,833), with a pooled aOR of 1.20 (95% CI 1.01-1.44) for LBR and a pooled aOR of 1.22 (95% CI 1.07-1.39) for CPR. WIDER IMPLICATIONS: The results of this review indicate a slightly higher LBR and CPR in immediate versus postponed FET. Thus, the standard clinical practice of postponing FET for at least one menstrual cycle following a failed fresh transfer or a freeze-all cycle may not be best clinical practice. However, as only retrospective cohort studies were assessed, the presence of selection bias is apparent, and the quality of evidence thus seems low. Randomised controlled trials including data on cancellation rates and reasons for cancellation are highly needed to provide high-grade evidence regarding clinical practice and patient counselling.

Two cases of severe COVID-19 in gestational week 27 and 28 respectively, after which both pregnancies proceeded to term.

COVID-19 in pregnancy increases the risk of caesarean section. We present two cases of late gestation pregnant women with severe COVID-19. Both were successfully treated with mechanical ventilation without termination of pregnancy and, following recovery from COVID-19, had vaginal deliveries at term. These two cases demonstrate the possibility of treating pregnant women with severe COVID-19 with mechanical ventilation in the late second and early third trimesters without them having a pre-term delivery. With a multidisciplinary approach, such management could avoid the maternal risks of surgery during a severe infection and, at the same time, enable term birth with a lower risk of neonatal complications.