Prediction of small-for-gestational-age neonates at 33-39 weeks' gestation in China: logistic regression modeling of the contributions of second- and third-trimester ultrasound data and maternal factors.

OBJECTIVES: A screening model for prediction of small-for-gestational-age (SGA) neonates (SGAp) was established by logistic regression using ultrasound data and maternal factors (MF). We aimed to evaluate the ability of SGAp as well as abdominal circumference (AC) and estimated fetal weight (EFW) measurements to predict SGA neonates at 33-39 weeks' gestation. METHODS: This retrospective study evaluated 5298 singleton pregnancies that had involved three ultrasound examinations at 21+0-27+6, 28+0-32+6, and 33+0-39+6 weeks. All ultrasound data were transformed to MoM values (multiple of the median). Multivariate logistic regression was used to analyze the correlation between SGA status and various variables (ultrasound data and MF) during pregnancy to build the SGAp model. EFW was calculated according to the Hadlock formula at 33-39 weeks of gestation. The predictive performance of SGAp, AC MoM value at 33+0-39+6 weeks (AC-M), EFW MoM value (EFW-M), EFW-M plus MF, AC value at 33+0-39+6 weeks (AC), AC growth velocity, EFW, and EFW plus MF was evaluated using ROC curves. The detection rate (DR) of SGA neonate with SGAp, AC-M, EFW-M, and EFW-M plus MF at false positive rate (FPR) of 5% and 10%, and the FPR at DR of 85%, 90%, and 95% were observed. RESULTS: The AUCs of SGAp, AC-M, EFW-M, EFW-M plus MF, AC, AC growth velocity, EFW, and EFW plus MF for SGA neonates screening were 0.933 (95%CI: 0.916-0.950), 0.906 (95%CI: 0.887-0.925), 0.920 (95%CI: 0.903-0.936), 0.925 (95%CI: 0.909-0.941), 0.818 (95%CI: 0.791-0.845), 0.786 (95%CI: 0.752-0.821), 0.810 (95%CI: 0.782-0.838), and 0.834 (95%CI: 0.807-0.860), respectively. The screening efficiency of SGAp, AC-M, EFW-M, and EFW-M plus MF are significantly higher than AC, AC growth velocity, EFW, and EFW plus MF. The DR of SGAp, AC-M, EFW-M, and EFW-M plus MF for SGA neonates were 80.4%, 69.6%, 73.8% and 74.3% at 10% FPR. The AUCs of SGAp, AC-M, EFW-M, and EFW-M plus MF 0.950 (95%CI: 0.932-0.967), 0.929 (95%CI: 0.909-0.948), 0.938 (95%CI: 0.921-0.956) and 0.941 (95%CI: 0.924-0.957), respectively for screening SGA neonates delivered within 2 weeks after the assessment. The DR for these births increased to 85.8%, 75.8%, 80.0%, and 82.5%, respectively. CONCLUSION: The rational use of ultrasound data can significantly improve the prediction of SGA statuses.

High androgen level during controlled ovarian stimulation cycle impairs endometrial receptivity in PCOS patients.

PCOS is one of the most common endocrine disorders among women of reproductive age. While the mechanism involved is not yet fully characterized. Our study aims to examine the pregnancy outcomes of embryo transfers in women with PCOS after pretreatment, and to explore the possible effect of high androgen levels on endometrial receptivity. Retrospective cohort study was conducted to analyze pregnancy outcomes among 2714 infertile women with tubal factor and 452 PCOS women. Endometrium samples were collected from 6 controls and 6 PCOS patients to detect the expression of endometrial receptivity marks. The implantation rate, clinical and ongoing pregnancy rates and live birth rate in women with PCOS followed fresh embryo transfers were obviously decreased even after the pretreatment. Similar pregnancy outcomes were found in frozen-thawed embryo transfer cycles between women with or without PCOS. Strikingly, serum total testosterone (TT) levels on trigger day were significantly higher in PCOS women. Women with high TT levels presented significantly lower clinical and ongoing pregnancy rates, and the expression of insulin-like growth factor binding protein 1 (IGFBP-1), and leukemia inhibitory factor (LIF) in the endometria decreased significantly as well. High doses of testosterone significantly down-regulated the expression of IGFBP-1 and LIF in Ishikawa cells. Although endocrine abnormalities had been improved before the controlled ovarian stimulation (COS) cycle started, higher serum TT levels were detected on the trigger day of the COS cycle in PCOS patients, which may contribute to the decreased fresh embryo implantation by impairing endometrial receptivity.

The importance of mitochondrial metabolic activity and mitochondrial DNA replication during oocyte maturation in vitro on oocyte quality and subsequent embryo developmental competence.

Mitochondrial metabolic capacity and DNA replication have both been shown to affect oocyte quality, but it is unclear which one is more critical. In this study, immature oocytes were treated with FCCP or ddC to independently inhibit the respective mitochondrial metabolic capacity or DNA replication of oocytes during in vitro maturation. To differentiate their roles, we evaluated various parameters related to oocyte maturation (germinal vesicle break down and nuclear maturation), quality (spindle formation, chromosome alignment, and mitochondrial distribution pattern), fertilization capability, and subsequent embryo developmental competence (blastocyst formation and cell number of blastocyst). Inhibition of mitochondrial metabolic capacity with FCCP resulted in a reduced percent of oocytes with nuclear maturation; normal spindle formation and chromosome alignment; evenly distributed mitochondria; and an ability to form blastocysts. Inhibition of mtDNA replication with ddC has no detectable effect on oocyte maturation and mitochondrial distribution, although high-dose ddC increased the percent of oocytes showing abnormal spindle formation and chromosome alignment. ddC did, however, reduce blastocyst formation significantly. Neither FCCP nor ddC exposure had an effect on the rate of fertilization. These findings suggest that the effects associated with lower mitochondrial DNA copy number do not coincide with the effects seen with reduced mitochondrial metabolic activity in oocytes. Inhibiting mitochondrial metabolic activity during oocyte maturation has a negative impact on oocyte maturation and subsequent embryo developmental competence. A reduction in mitochondrial DNA copy number, on the other hand, mainly affects embryonic development potential, but has little effect on oocyte maturation and in vitro fertilization.

Impaired mitochondrial function in murine oocytes is associated with controlled ovarian hyperstimulation and in vitro maturation.

The present study was designed to determine whether controlled ovarian hyperstimulation (COH) and in vitro maturation (IVM), two common clinical procedures in human IVF treatment, have an impact on mitochondrial DNA (mtDNA) copy number and mitochondrial function in oocytes. Matured mouse oocytes recovered following COH, IVM and natural cycles (NC), which simulated those treatments in human clinic IVF treatment. The copies of mtDNA, the activity of mitochondria as determined by inner mitochondrial membrane potential and oocyte adenosine trisphosphate (ATP) content, pattern of mitochondrial distribution, reactive oxygen species (ROS) levels and the integrity of the cytoskeleton were evaluated in oocytes. Significant differences were detected between COH and NC groups in all measures, except the pattern of mitochondrial distribution and ROS levels. There were also significant differences detected between IVM and NC treatment groups in the copies of mitochondrial DNA, the level of ROS and the integrity of the cytoskeleton in oocytes. In conclusion, the results of this investigation indicate that non-physiological COH and IVM treatments inhibit mtDNA replication, alter mitochondrial function and increase the percentage of abnormal cytoskeleton and ROS production. Damage related to the mitochondria may partly explain the low efficiency of IVF and high rate of embryonic loss associated with these clinical procedures.