The greater incidence of small for gestational age newborns after gonadotropin-stimulated in vitro fertilization with a supra-physiological estradiol level on ovulation trigger day.

INTRODUCTION Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin stimulated in vitro fertilization compared to spontaneously conceived children: parental factors (age, health, duration of subfertility, and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved; and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn's being small for gestational age. MATERIAL AND METHODS We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, as they adjust for gestational age and sex. RESULTS The proportion of small for gestational age was 11.8% following conventional gonadotropin stimulated in vitro fertilization, and 2.9% after natural-cycle in vitro fertilization (P = 0.058). The odds of small for gestational age were significantly higher with supra-physiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35 to 15.55; P = 0.015). It remained significant after adjusting for maternal height, age, and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06 to 13.82; P = 0.041). CONCLUSIONS We found an associated risk of children being born small for gestational age after conventional gonadotropin stimulated in vitro fertilization compared to natural-cycle in vitro fertilization. This higher risk is significantly associated with supra-physiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small for gestational age and future health consequences. This article is protected by copyright. All rights reserved

Perinatal outcomes after in vitro fertilization – a comparison of the national live birth registry with a tertiary cohort and an IVF cohort.

Introduction: In vitro fertilization (IVF) treatment is performed increasingly in Switzerland. Conception by IVF negatively affects obstetric and perinatal outcomes. Possible risk factors are parental health and subfertility, gonadotropin stimulation, gamete manipulation or culture of the embryo. Our primary aim was to assess the impact of IVF on perinatal outcomes in comparison to i) children born in tertiary care (university hospital), ii) all children born in Switzerland in the same time; and secondary, to address the effect of gonadotropin stimulation. Methods: We performed IVF using 75IU-300IU gonadotropin per day to stimulate ovarian growth, or in the unstimulated natural cycle, where we collected the single oocyte. Fresh cleavage embryos were transferred on day 2 or 3. We recruited tertiary care births during first trimester check-up. We assessed differences in continuous perinatal outcomes, birthweight and gestational age, using linear regression; and the relative risk (RR) for preterm delivery (<37 GW), small for gestational age (<10th percentile) and low birthweight (<2500 g) using Poisson regression with robust error variance. We clustered for siblings and adjusted for maternal age, parity and foetal sex. Results: Of the 636'639 live births from 2010–2018, 311 were in the Bern IVF Cohort (167 unstimulated, 144 stimulated), 2332 in tertiary care and 633'996 from the Swiss Live Birth Registry (SLBR). IVF mothers were on average 3.6 years (95%CI 3.2, 4.1) older and more often primiparous (76 vs. 49%; p<0,001). Perinatal outcomes (RR or adjusted RR (aRR); 95% CI) after IVF did not differ compared to SLBR, beside the crude risk for being born small for gestational age (1.31; 1.01, 1.70; aRR 1.12; 0.87, 1.45). Children born following stimulated IVF had lower crude mean birthweight (−115 g; −212 g, −17 g) and higher risk for low birthweight (RR 2.17; 1.27, 3.69; aRR 1.72; 1.01, 2.93) and small for gestational age (RR 1.50; 1.05, 2.14; aRR 1.31; 0.92, 1.87) whereas the children born after natural IVF cycles had no increased risks compared to the LBR. Gestational age and birthweight were lower in tertiary care born children and their risk was increased for preterm birth (RR 1.19; 1.02, 1.40), low birthweight (RR 1.29; 1.09, 1.52), and small for gestational age (RR 1.11; 1.00, 1.24) compared to LBR. Cesarean delivery rate was 42% in IVF deliveries whereas it was 36% (p=0,03) in tertiary care and the Swiss average is 32%. Higher maternal age is mainly associated with higher section rate in IVF mothers (aRR for CS: 1.04; 0.89, 1.22). Discussion: IVF seems not to be a risk factor for adverse perinatal outcome in IVF births. Gonadotropin stimulation seems to affect birthweight and increased the risk for low birthweight and small for gestational age compared to the LBR. A strength of our study are the data quality and completeness. Selection bias for the tertiary care singletons with higher risk pregnancies explains worse outcome compared to SLBR

The greater incidence of small‐for‐gestational‐age newborns after gonadotropin‐stimulated in vitro fertilization with a supraphysiological estradiol level on ovulation trigger day

INTRODUCTION Reproductive scientists have postulated various risk factors for lower birthweight following conventional gonadotropin stimulated in vitro fertilization compared to spontaneously conceived children: parental factors (age, health, duration of subfertility, and smoking habits); ovarian stimulation; laboratory procedures; the number of oocytes retrieved; and the number of embryos transferred. Our aim was to investigate the impact of gonadotropin stimulation and serum estradiol level on the risk of a newborn's being small for gestational age. MATERIAL AND METHODS We conducted a cohort study (2010-2016) of singletons (n = 155) born either after conventional gonadotropin stimulated in vitro fertilization (using ≥150 IU/d human gonadotropin for stimulation) or after natural cycle in vitro fertilization without any stimulation. We analyzed perinatal outcomes using birthweight percentiles, as they adjust for gestational age and sex. RESULTS The proportion of small for gestational age was 11.8% following conventional gonadotropin stimulated in vitro fertilization, and 2.9% after natural-cycle in vitro fertilization (P = 0.058). The odds of small for gestational age were significantly higher with supra-physiological estradiol levels in maternal serum on ovulation trigger day (unadjusted odds ratio 4.58; 95% confidence interval 1.35 to 15.55; P = 0.015). It remained significant after adjusting for maternal height, age, and body mass index (adjusted odds ratio 3.83; 95% confidence interval 1.06 to 13.82; P = 0.041). CONCLUSIONS We found an associated risk of children being born small for gestational age after conventional gonadotropin stimulated in vitro fertilization compared to natural-cycle in vitro fertilization. This higher risk is significantly associated with supra-physiological estradiol levels. We propose a reduction in the dosage of gonadotropin to minimize the risk of small for gestational age and future health consequences. This article is protected by copyright. All rights reserved

Outcomes of monochorionic twin pregnancies complicated by Type-III selective fetal growth restriction.

OBJECTIVE: Type III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. Our objective was to describe the prospective risk of fetal death and the risk of adverse neonatal outcomes in a contemporary cohort. METHODS: We retrospectively reviewed all monochorionic diamniotic twin pregnancies complicated by type III sIUGR managed at nine fetal centers over a 12-year time period. Higher order multiples, major fetal anomalies or other monochorionicity related complications at initial presentation were excluded. Fetal and neonatal outcomes were collected and management strategies were reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture proven sepsis, necrotizing enterocolitis (NEC) requiring treatment, intraventricular hemorrhage (IVH) >grade I, retinopathy of prematurity (ROP) >stage II or periventricular leukomalacia (PVL). The prospective risk of fetal death and the risk of neonatal complications at each gestational age were evaluated. RESULTS: We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies which underwent selective reduction (n=18, 5.5%), there were 51 (8.3%) non-iatrogenic fetal deaths in 35 pregnancies (11.3%). Single deaths occurred in 19 (5.8%) pregnancies and double deaths in 16 (4.9%) pregnancies. The prospective risk of non-iatrogenic fetal death per fetus declined from 8.1% (95% CI 5.95-10.26) at 16 weeks, to less than 2% (95% CI 0.59-2.79) after 28.4 weeks and to less than 1% (95% CI -0.30-1.89) beyond 32.6 weeks. In otherwise uncomplicated type III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcomes was 29% (31/107 neonates). For twin pregnancies that continued to 34 weeks there was a very low risk of fetal demise (0.7%) and a low risk of adverse outcomes (11%). CONCLUSIONS: In this contemporary cohort from tertiary fetal centers, the risk of fetal death in type III sIUGR was lower than previously reported. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can safely continue beyond 33 weeks of gestation. This article is protected by copyright. All rights reserved.status: Published onlin

Outcome of monochorionic twin pregnancy complicated by Type-III selective intrauterine growth restriction.

Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade &gt; I, retinopathy of prematurity Stage &gt; II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n = 18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology

Prediction of fetal death in monochorionic twin pregnancies complicated by Type-III selective fetal growth restriction

Objective : Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. Methods : This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10th percentile and intertwin EFW discordance of ≥ 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis. Results : A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. Conclusions : Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort