At present, safety of letrozole administration as an ovulation-inducing drug still remains controversial. Investigation of the safety of letrozole use for the induction of ovulation in the Chinese population is scant. The present study aimed to fill this gap. Data concerning mothers using letrozole and birth outcomes of their singleton offspring were collected as the letrozole group (n=194), equivalent data from mothers using non-letrozole drugs and their singleton offspring were included as the non-letrozole group (control, n=154). Birth outcomes, congenital anomalies and neonatal complications were compared and analyzed between the two groups. Univariate analysis, Spearman\'s rank correlation analysis and the logistic regression model were utilized. For birth outcomes, the percentage of caesarean section deliveries in the letrozole group was lower than the non-letrozole group (43.8 vs. 56.4%, P=0.019). For congenital anomalies, no significant difference was found between the two groups (all P>0.05). The statistical P-value for the correlation between the maternal use of letrozole and neonatal complications was marginal (P=0.051). Results from the logistic regression analysis confirmed that maternal use of letrozole was not a significant contributor for neonatal complications, independent of statistical adjustment [crude odds ratio (OR), 1.436; 95% confidence interval (CI), 0.803-2.569; P=0.223 vs. adjusted OR, 1.406; 95% CI, 0.748-2.643; P=0.290). The results of the present study suggested that maternal use of letrozole for ovulation induction does not associate with poorer birth outcomes or increased risk of congenital anomalies and neonatal complications.

BACKGROUND: Frozen-thawed embryo transfer (FET) is thought to be associated with obstetric and neonatal complications after in vitro fertilization/intracytoplasmic single sperm injection (IVF/ICSI) treatment. The study aimed to determine whether the endometrial preparation protocol is an influencing factor for these complications.
METHODS: We conducted a retrospective cohort study of 3,458 women who had singleton deliveries after IVF/ICSI-FET treatment at the Centre for Reproductive Medicine of Shanghai First Maternity and Infant Hospital between July 2016 and April 2021. The women were divided into three groups according to the endometrial preparation protocols: 2,029 women with programmed cycles, 959 with natural cycles, and 470 with minimal ovarian stimulation cycles. The primary outcomes were the incidence rates of obstetric and neonatal complications, namely, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), placenta previa, preterm rupture of membranes (PROM), preterm delivery, postpartum haemorrhage, large for gestational age (LGA), small for gestational age (SGA), and macrosomia.
RESULTS: After adjustments for confounding variables by multivariate logistic regression analysis, the results showed that programmed cycles had an increased risk of HDP (aOR = 1.743; 95% CI, 1.110-2.735; P = 0.016) and LGA (aOR = 1.269; 95% CI, 1.011-1.592; P = 0.040) compared with natural cycles. Moreover, programmed cycles also increased the risk of LGA (aOR = 1.459; 95% CI, 1.083-1.965; P = 0.013) but reduced the risk of SGA (aOR = 0.529; 95% CI, 0.348-0.805; P = 0.003) compared with minimal ovarian stimulation cycles. There were no significant differences between natural cycles and minimal ovarian stimulation cycles.
CONCLUSIONS: During IVF/ICSI-FET treatment, the risk of HDP and LGA was increased in women with programmed cycles. Therefore, for patients with thin endometrium, irregular menstruation or no spontaneous ovulation, minimal ovarian stimulation cycles may be a relatively safer option than programmed cycles.

Emerging evidence has shown that in-vitro fertilization (IVF) is associated with higher risks of certain placental abnormalities or complications, such as placental abruption, preeclampsia, and preterm birth. However, there is a lack of large population-based analysis focusing on placental abnormalities or complications following IVF treatment. This study aimed to estimate the absolute risk of placental abnormalities or complications during IVF-conceived pregnancy.
We conducted a retrospective cohort study of 16 535 852 singleton pregnancies with delivery outcomes in China between 2013 and 2018, based on the Hospital Quality Monitoring System databases. Main outcomes included placental abnormalities (placenta previa, placental abruption, placenta accrete, and abnormal morphology of placenta) and placenta-related complications (gestational hypertension, preeclampsia, eclampsia, preterm birth, fetal distress, and fetal growth restriction (FGR)). Poisson regression modeling with restricted cubic splines of exact maternal age was used to estimate the absolute risk in both the IVF and non-IVF groups.
The IVF group (n = 183 059) was more likely than the non-IVF group (n = 16 352 793) to present placenta previa (aRR: 1.87 [1.83-1.91]), placental abruption (aRR: 1.16 [1.11-1.21]), placenta accrete (aRR: 2.00 [1.96-2.04]), abnormal morphology of placenta (aRR: 2.12 [2.07 to 2.16]), gestational hypertension (aRR: 1.55 [1.51-1.59]), preeclampsia (aRR: 1.54 [1.51-1.57]), preterm birth (aRR: 1.48 [1.46-1.51]), fetal distress (aRR: 1.39 [1.37-1.42]), and FGR (aRR: 1.36 [1.30-1.42]), but no significant difference in eclampsia (aRR: 0.91 [0.80-1.04]) was found. The absolute risk of each outcome with increasing maternal age in both the IVF and non-IVF group presented two patterns: an upward curve showing in placenta previa, placenta accreta, abnormal morphology of placenta, and gestational hypertension; and a J-shape curve showing in placental abruption, preeclampsia, eclampsia, preterm birth, fetal distress, and FGR.
IVF is an independent risk factor for placental abnormalities and placental-related complications, and the risk is associated with maternal age. Further research is needed to evaluate the long-term placenta-related chronic diseases of IVF patients and their offspring.

Objective: Preterm birth is a leading contributor to childhood morbidity and mortality, and the incidence tends to increase and is higher in developing countries. The aim of this study was to analyze the potential impact of preterm birth in different etiology groups on neonatal complications and outcomes and to gain insight into preventive strategies. Methods: We performed a retrospective cohort study of preterm infants less than 32 weeks\' gestation in the Third Affiliated Hospital of Zhengzhou University from 2014 to 2019. Preterm births were categorized as spontaneous or iatrogenic, and these groups were compared for maternal and neonatal characteristics, neonatal complications, and outcomes. All infants surviving at discharge were followed up at 12 months of corrected age to compare the neurodevelopmental outcomes. Results: A total of 1,415 mothers and 1,689 neonates were included, and the preterm population consisted of 1,038 spontaneous preterm infants and 651 iatrogenic preterm infants. There was a significant difference in the incidence of small for gestational age between the two groups. Infants born following spontaneous labor presented with a higher risk of intraventricular hemorrhage, whereas iatrogenic preterm birth was associated with higher risk of necrotizing enterocolitis and coagulopathy and higher risk of pathoglycemia. There was no difference in mortality between the two groups. Follow-up data were available for 1,114 infants, and no differences in neurologic outcomes were observed between the two preterm birth subtypes. Conclusions: Preterm births with different etiologies were associated with some neonatal complications, but not with neurodevelopmental outcomes at 12 months of corrected age.

OBJECTIVE: Does repeated cryopreservation process affect embryo implantation potential and neonatal outcomes of human embryos?
METHODS: This retrospective cohort study was conducted in the Reproductive Medicine Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All assisted reproductive technology (ART) cycles were carried out between January 2014 and December 2018. Preferentially matched participants were divided into three groups according to the times of embryo cryopreservation: the fresh group (n = 249), the cryopreservation group (n = 244) and the re-cryopreservation group (n = 216). Embryo implantation rate, live birth rate, miscarriage rate and neonatal complication rate were compared among these three groups.
RESULTS: The embryo implantation rate, clinical pregnancy rate and live birth rate in the re-cryopreservation group were significantly lower, and the miscarriage rate also slightly increased. Logistic regression analysis indicated that embryos with repeated cryopreservation and lower trophectoderm scores were at higher risk of embryo implantation failure in single embryo transfer cycles (OR 1.79 and 1.56, respectively). No significant differences were observed in gender, gestational age, birthweight, neonatal abnormality and neonatal complications among the groups.
CONCLUSIONS: Our findings demonstrate the adverse effect of repeated cryopreservation on embryo implantation potential. The study offers embryologists and reproductive clinicians a warning of detrimental role of repeated cryopreservation. If unnecessary, it is strongly recommended to avoid repeated practice of vitrification and warming on embryos.