Objective Previous studies comparing the COVID-19 pandemic period to prepandemic periods reported either no change or a decrease in extremely preterm birth (PTB) rates during the pandemic. 1, 2 These studies evaluated a limited number of potential PTB confounders and a short pandemic period. We aimed to determine the change in PTB rate and neonatal outcomes during the pandemic in comparison to prepandemic periods by evaluating multiple obstetrical characteristics, during more than three pandemic months. Study design We compared maternal, obstetrical and neonatal outcomes of singleton pregnancies at the Sheba Medical Center, Israel, during three periods: from 20/03/2020 (date of implementation of governmental state of lockdown) to 27/06/2020 (group 1), a parallel period in 2019 (group 2), and to another group that included the parallel annual periods in 2011-2019 (group 3) (see Table). We also compared maternal and pregnancy characteristics during the pandemic and corresponding prepandemic period in 2019 between pregnancies complicated by PTB <34 0/7 versus ≥34 0/7 weeks (see Table). Multivariate regression analysis was performed in order to study independent factors associated with PTB. The institutional review board approved this study (7068-20-SMC, 03/30/2020). Results There were 2,594 deliveries during the pandemic period (group 1) and 2,742 and 28,686 deliveries in the prepandemic periods (groups 2 and 3, respectively). Maternal and obstetrical characteristics did not differ between groups 1 and 2. Predelivery hemoglobin levels were higher in the pandemic period. PTB <34 0/7 weeks rate was significantly lower in the pandemic period compared to group 2 (OR 0.45 95% CI 0.30-0.68, p<0.001), as was the rate of composite neonatal outcome (OR 0.76 95% CI 0.59-0.96, p=0.023). Age, body mass index, parity, diabetes rates and hematologic characteristics differed between groups 1 and 3 with significantly higher predelivery hemoglobin levels in group 1. PTB <34 0/7 weeks rate was lower in the pandemic period (OR 0.60 95% CI 0.41-0.85, p=0.004). On multivariate regression analysis, delivering during the pandemic period was independently associated with a decreased risk for delivery <34 0/7 weeks (adjusted OR 0.29, 95% CI 0.15-0.56, p=0.001). Conclusion We observed more than 50% reduction in the rate of PTB <34 0/7 weeks of gestation, possibly resulting in improved neonatal outcome.

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How chemotherapy affects dormant ovarian primordial follicles is unclear. The 'burnout' theory, studied only in mice, suggests cyclophosphamide enhances primordial follicle activation. Using 4-hydroperoxycyclophosphamide (4hc) and phosphoramide mustard (PM), this study assessed how the active cyclophosphamide metabolites 4-hydroxycyclophosphamide (4-OHC) and PM, affect human primordial follicles. Frozen-thawed human ovarian samples were sliced and cultured with basic culture medium (cultured controls) or with 4hc/PM (3 µmol/l/10 µmol/l) (treated samples) for 24-48 h. Follicular counts and classification, Ki67 and anti-Müllerian hormone (AMH) immunohistochemistry and an apoptosis assay were used for evaluation, and 17β-oestradiol and AMH were measured in spent media samples. Generally, there was primordial follicle decrease and elevated developing follicle rates in treated samples compared with cultured (P = 0.04 to P < 0.0005) and uncultured controls (P < 0.05 to P < 0.0001). No traces of apoptosis were found. There were almost twicethe levels of AMH and 17β-oestradiol in treated compared with untreated samples (AMH with 4hc 3 µmol/l; P = 0.04). All follicles stained positively for AMHincluded treated samples. Ki67 positive staining was noted in all samples. Cyclophosphamide metabolites seem to enhance human primordial follicle activation to developing follicles, in vitro. Study findings support the 'burnout' theory as the mechanism of chemotherapy-induced ovarian toxicity.