ObjectivesTo evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19.MethodsSecondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI).ResultsMean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09–1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3–7.9; p=0.001) were independently associated with composite adverse fetal outcome.ConclusionsEarly gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Despite the increasing number of published studies, objective evidence is still needed to draw any conclusion on the course of SARS-COV-2 infection acquired during pregnancy. What are the clinical implications of this work? The study showed that in pregnancies complicated by SARS-COV-2, the risk of maternal mortality was 0.8%, but about 11% of women required admission to ICU. Pregnancies affected by SARS-COV-2 were also complicated by 23% rate preterm birth, and 4.1% rate of perinatal death. The risk of vertical transmission was negligible.

Objectives: To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods: Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratoryconfirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerasechain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results: Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/ 265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions: Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Objectives To evaluate maternal and perinatal outcomes in high compared to low-risk pregnancies complicated by SARS-COV-2 infection. Methods This was a multinational retrospective cohort study including women with laboratory-confirmed SARS-COV-2 from 76 centers from 25 different countries in Europe, United States, South America, Asia and Australia from 04 April 2020 till 28 October 2020. The primary outcome was a composite measure of maternal mortality and morbidity including admission to intensive care unit (ICU), use of mechanical ventilation, or death. Secondary outcome was a composite measure of adverse perinatal outcome, including miscarriage, fetal loss, neonatal (NND) and perinatal (PND) death, and admission to neonatal intensive care unit. All these outcomes were assessed in high-risk compared to low-risk pregnancies. Pregnancies were considered as high risk in case of either pre-existing chronic medical conditions pre-existing pregnancy or obstetric disorders occurring in pregnancy. Fisher-test and logistic regression analysis were used to analyze the data. Results 887 singleton pregnancies tested positive to SARS-COV-2 at RT-PCR nasal and pharyngeal swab were included in the study. The risk of composite adverse maternal outcome was higher in high compared to low risk-pregnancies with an OR of 1.52 (95% CU 1.03-2.24; p= 0.035). Likewise, women carrying a high risk-pregnancies were also at higher risk of hospital admission (OR: 1.48, 95% CI 1.07-2.04; p= 0.002), presence of severe respiratory symptoms (OR: 2.13, 95% CI .41-3.21; p= 0.001), admission to ICU (OR: 2.63, 95% CI 1.42-4.88) and invasive mechanical ventilation (OR: 2.65, 95% CI 1.19- 5.94; p= .002). When exploring perinatal outcomes, high-risk pregnancies were also at high risk of adverse perinatal outcome with an OR 0f 1.78 (95% CI .15-2.72; p= 0.009). However, such association was mainly due to the higher incidence of miscarriage in high risk compared to low risk pregnancies (5.3% vs 1.6%, p= 0.008), while there was no difference as regard as the other explored outcomes between the two study groups. At logistic regression analysis, maternal age (OR: 1.12, 95% CI 1.02-1.22, p= 0.023) and the presence of a high-risk pregnancies (OR: 4.21, 95% CI 3.90-5.11, p<0.001) were independently associated with adverse maternal outcome. Conclusions High-risk pregnancies complicated by SARS-COV-2 infection are at higher risk of adverse maternal outcome compared to low-risk gestations.

Following early embryonic germ cell migration, oocytes are surrounded by somatic cells and remain arrested at diplotene stage until luteinizing hormone (LH) surge. Strict regulation of both meiotic arrest and meiotic resumption during dormant stage are critical for future fertility. Inter-cellular signaling system between the somatic compartment and oocyte regulates these meiotic events and determines the follicle quality. As well as the collected number of eggs, their qualities are also important for in vitro fertilization (IVF) outcome. In spontaneous and IVF cycles, germinal vesicle (GV)–stage oocytes, premature GV breakdown, and persistence of first meiotic arrest limit the reproductive performance. Likewise, both women with premature ovarian aging and young cancer women are undergoing chemoradiotherapy under the risk of follicle loss because of unregulated meiotic events. Understanding of oocyte meiotic events is therefore critical for the prevention of functional ovarian reserve. High levels of cyclic guanosine monophophate (cGMP), cyclic adenosine monophophate (cAMP) and low phosphodiesterase (PDE) 3A enzyme activity inside the oocyte are responsible for maintaining of meiotic arrest before the LH surge. cGMP is produced in the somatic compartment, and natriuretic peptide precursor C (Nppc) and natriuretic peptide receptor 2 (Npr2) regulate its production. cGMP diffuses into the oocyte and reduces the PDE3A activity, which inhibits the conversion of cAMP to the 5′AMP, and cAMP levels are enhanced. In addition, oocyte itself has the ability to produce cAMP. Taken together, accumulation of cAMP inside the oocyte induces protein kinase activity, which leads to the inhibition of maturation-promoting factor and meiotic arrest also continues. By stimulating the expression of epidermal growth factor, LH inhibits the Nppc/Npr2 system, blocks cGMP synthesis, and initiates meiotic resumption. Oocytes lacking the functional of this pathway may lead to persistence of the GV oocyte, which reduces the number of good quality eggs. Selective regulation of somatic cell signals and oocyte meiotic events enhance progress in fertility preservation methods, which may give us the opportunity to prevent follicle loss in prematurely aging women and young women with cancer are undergoing chemoradiotherapy.