Poor Response to Gonadotropin Stimulation and Perinatal Outcomes in Fresh In Vitro Fertilization Embryo Transfer Cycles-A Retrospective Cohort Study.

Objective: The objective was to examine the association between poor ovarian response to gonadotropin stimulation for in vitro fertilization (IVF) and adverse perinatal outcomes in singleton gestations in young patients. Methods: This was a retrospective cohort study including women aged 17-39 who underwent fresh embryo transfer and delivered a singleton neonate at a single center (pre-implantation genetic testing excluded) (2007-2022). Patients were classified as one of the following categories: poor responders-daily follicle-stimulating hormone (FSH) ≥ 150 IU yielding ≤ 3 retrieved oocytes; normal responders-4-15 oocytes; and high responders with ≥16 oocytes. The primary outcome was a composite of pre-eclampsia (mild or severe), small-for-gestational-age, gestational diabetes mellitus, and preterm birth (<37 weeks). We compared maternal and neonatal outcomes between the three groups. Multivariable logistic regression was used to control for confounders. Results: Overall, 507 women met the inclusion criteria. Of them, there were 44 (8.68%) poor responders, 342 (67.46%) normal responders, and 121 (23.87%) high responders. Poor responders, compared to normal and high responders, were characterized by a higher maternal age (34.64 ± 4.01 vs. 31.4 ± 5.04 vs. 30.01 ± 4.93, p < 0.001, respectively) and total FSH dosage (3028.41 ± 1792.05 IU vs. 2375.11 ± 1394.05 IU vs. 1869.31 ± 1089.63 IU, p < 0.001). The perinatal outcomes examined, including cesarean delivery (CD) rate and the composite outcome, were comparable between groups. Using multivariable logistic regression and adjusting for ovarian response group, maternal age, nulliparity, and estradiol level and endometrial thickness before ovulation triggering, poor response was not associated with CD rate or the composite outcome, with maternal age associated with CD (p = 0.005), and nulliparity with the composite outcome (p = 0.007). Similar results were obtained when comparing poor responders to each other group separately or to all other responders. Conclusions: Poor ovarian response is not associated with increased adverse maternal or neonatal outcomes.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

BACKGROUND: There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which the experts were asked to rate on a 5-point Likert scale (from "strongly disagree"=1 to "strongly agree"=5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of ≤3 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2-cm distance; (2) all pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; (3) when a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at approximately 32 weeks to rule out vasa previa; (4) outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; (5) asymptomatic patients with vasa previa should be delivered by scheduled cesarean delivery between 35 and 37 weeks of gestation; and (6) there was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSION: Through focus group discussion and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

Mammalian target of rapamycin inhibitors: A new-possible approach for in-utero medication therapy.

The mammalian/mechanistic target of rapamycin (mTOR) is a protein kinase that plays a crucial role in regulating cellular growth, metabolism, and survival. Although there is no absolute contraindication for the use of mTOR inhibitors during pregnancy, the specific fetal effects remain unknown. Available data from the past 2 decades have examined the use of mTOR inhibitors during pregnancy in patients with solid organ transplantation, showing no clear link to fetal complications or structural abnormalities. Recently, a handful of case reports and series have described transplacental therapy of mTOR inhibitors to control symptomatic and complicated pathologies in the fetus. The effect of these agents includes a significant reduction in lesion size in the fetus and a reduced need for mechanical ventilation in neonates. In this context, we delve into the potential of mTOR inhibitors as in-utero therapy for fetal abnormalities, with a primary focus on lymphatic malformation (LM) and cardiac rhabdomyoma (CR). While preliminary reports underscore the efficacy of mTOR inhibitors for the treatment of fetal CR and fetal brain lesions associated with tuberous sclerosis complex, chylothorax, and LMs, additional investigation and clinical trials are essential to comprehensively assess the safety and efficacy of these medications.

Prenatal diagnosis and postnatal outcome of closed spinal dysraphism.

OBJECTIVE: To evaluate the prenatal diagnosis of closed dysraphism (CD) and its correlation with postnatal findings and neonatal adverse outcomes. METHODS: A retrospective cohort study including pregnancies diagsnosed with fetal CD by prenatal ultrasound (US) and magnetic resonance imaging (MRI) at a single tertiary center between September 2011 and July 2021. RESULTS: CD was diagnosed prenatally and confirmed postnatally in 12 fetuses. The mean gestational age of prenatal imaging was 24.2 weeks, in 17% the head circumference was ≤fifth percentile and in 25% the cerebellar diameter was ≤fifth percentile. US findings included banana sign in 17%, and lemon sign in 33%. On MRI, posterior fossa anomalies were seen in 33% of cases, with hindbrain herniation below the foramen magnum in two cases. Mean clivus-supraocciput angle (CSA) was 74°. Additional anomalies outside the CNS were observed in 50%. Abnormal foot position was demonstrated prenatally in 17%. Neurogenic bladder was present in 90% of patients after birth. CONCLUSION: Arnold Chiari II malformation and impaired motor function can be present on prenatal imaging of fetuses with CD and may be associated with a specific type of CD. Prenatal distinction of CD can be challenging. Associated extra CNS anomalies are frequent and the rate of neurogenic urinary tract dysfunction is high.

Predicting adverse perinatal outcomes among gestational diabetes complicated pregnancies using neural network algorithm.

OBJECTIVE: The primary aim of this study is to utilize a neural network model to predict adverse neonatal outcomes in pregnancies complicated by gestational diabetes (GDM). DESIGN: Our model, based on XGBoost, was implemented using Python 3.6 with the Keras framework built on TensorFlow by Google. We sourced data from medical records of GDM-diagnosed individuals who delivered at our tertiary medical center between 2012 and 2016. The model included simple pregnancy parameters, maternal age, body mass index (BMI), parity, gravity, results of oral glucose tests, treatment modality, and glycemic control. The composite neonatal adverse outcomes defined as one of the following: large or small for gestational age, shoulder dystocia, fetal umbilical pH less than 7.2, neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), hyperbilirubinemia, or polycythemia. For the machine training phase, 70% of the cohort was randomly chosen. Each sample in this set consisted of baseline parameters and the composite outcome. The remaining samples were then employed to assess the accuracy of our model. RESULTS: The study encompassed a total of 452 participants. The composite adverse outcome occurred in 29% of cases. Our model exhibited prediction accuracies of 82% at the time of GDM diagnosis and 91% at delivery. The factors most contributing to the prediction model were maternal age, pre-pregnancy BMI, and the results of the single 3-h 100 g oral glucose tolerance test. CONCLUSION: Our advanced neural network algorithm has significant potential in predicting adverse neonatal outcomes in GDM-diagnosed individuals.

Antenatal Corticosteroids for Small for Gestational Age in Late Preterm Newborns.

BACKGROUND: The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear. OBJECTIVES: To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates. METHODS: We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34-36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012-December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea. RESULTS: Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41-4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23-3.78, P = 0.007). CONCLUSIONS: ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.

Fetoscopic laser photocoagulation versus expectant management for stage I twin-to-twin transfusion syndrome: A systematic review and meta-analysis.

To investigate the outcomes of asymptomatic stage I twin-to-twin transfusion syndrome (stage I TTTS) among patients treated with fetoscopic laser photocoagulation (FLP) versus expectant management. Databases such as PubMed, Web of Science and Scopus were systematically searched from inception up to March 1st, 2022. The primary outcome was at least one fetal survival at birth and secondary outcomes included gestational age at delivery, preterm premature rupture of membranes < 32 weeks, preterm birth < 32 weeks, and single and dual fetal survival. Five studies were included in the meta-analysis. There was no significant difference in terms of at least one survival (odds ratio (OR) = 1.40, 95%CI= (0.26, 7.43), P = 0.70), single survival (OR = 0.87, 95%CI= (0.51, 1.48), P = 0.60) and dual survival (OR = 1.63, 95%CI= (0.74, 3.62), P = 0.23) among FLP and expectant groups. Gestational age at delivery (mean difference = 1.19, 95%CI= (-0.25, 2.63), P = 0.10), the risk of PTB<32 weeks (OR = 0.88, 95%CI= (0.50, 1.54), P = 0.65), and pPROM<32 weeks (OR = 1.80, 95% CI= (0.41, 7.98), P = 0.44) were also comparable between the groups. Routine FLP of the placental anastomoses before 26 weeks of gestation is unlikely to be beneficial among asymptomatic stable stage I TTTS patients without cervical shortening as the procedure does not offer a survival advantage compared with expectant management.

Characterization of Suboptimal Responses to Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia.

INTRODUCTION: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH). METHODS: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity. RESULTS: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a <10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO <10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008-0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01-0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31-47.04; p = 0.024). CONCLUSION: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders.

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.

BACKGROUND: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. METHODS: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. RESULTS AND DISCUSSION: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.

Maternal and perinatal outcomes of failed prostaglandin induction of labour: A retrospective cohort study.

Background: Induction of labor is performed in up to 25% of pregnant women. When the cervix is unfavorable, cervical ripening may be safely and effectively performed using slow-release vaginal inserts of prostaglandin E2. However, the risk factors, management, and outcome of patients who fail to respond remain unclear. Objective: To evaluate the outcomes of women who fail to respond to cervical ripening with prostaglandins. Methods: A retrospective cohort analysis (2013-2019) was conducted. Women with a singleton gestation who underwent induction of labor due to post-date pregnancy using a slow-release prostaglandin E2 vaginal insert for cervical ripening were included. Data on clinical and outcome factors were derived from the medical files, and findings were compared between patients who achieved ripening within 24 h of treatment onset and those who did not. The primary outcome measure was the vaginal delivery rate following the ripening process. Secondary outcome measures were adverse composite maternal and neonatal outcomes. A model combining maternal characteristics and response rates to ripening was constructed. Results: The final cohort included 1285 women: 1202 responded to cervical ripening (93.54%) and 83 (6.46%) did not. Compared to non-responders, responders had higher rates of vaginal delivery (96.51% vs. 66.27%, P < 0.001); lower rates of adverse maternal composite outcome (12.81% vs. 24.10%, P = 0.031) and adverse neonatal composite respiratory outcome (1.33% vs. 6.02%, P = 0.009). Responders were younger than non-responders (mean 30.03 years vs 31.73 years, P = 0.005) and had a lower nulliparity rate (50.99% vs 76.92%, P < 0.001). On multivariate analysis, failure to achieve cervical ripening was an independent risk factor for intrapartum cesarean delivery due to prolonged labor (aOR 11.90, 95% CI 6.13-23.25). Conclusion: Women who achieve cervical ripening with prostaglandin E2 vaginal inserts are younger and more often multiparous than women who fail to respond. Good response to the cervical ripening process is associated with lower rates of intrapartum cesarean delivery and of adverse outcomes.