Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks in human oocytes and early embryos. Unlike that in mouse oocytes, the permissive mark trimethylated histone H3 lysine 4 (H3K4me3) largely exhibits canonical patterns at promoters in human oocytes. After fertilization, prezygotic genome activation (pre-ZGA) embryos acquire permissive chromatin and widespread H3K4me3 in CpG-rich regulatory regions. By contrast, the repressive mark H3K27me3 undergoes global depletion. CpG-rich regulatory regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of H3K27me3 at developmental genes. Finally, by combining chromatin and transcriptome maps, we revealed transcription circuitry and asymmetric H3K27me3 patterning during early lineage specification. Collectively, our data unveil a priming phase connecting human parental-to-zygotic epigenetic transition.

Context:Recently, two patients with primary ovarian insufficiency (POI) delivered healthy babies after in vitro activation (IVA) treatment followed by auto-transplantation of frozen-thawed ovarian tissues.Objective:This study sought to report the first case of live birth after IVA treatment following fresh ovarian tissue grafting in patients with POI, together with monitoring of follicle development and serum hormonal changes.Design:This was a prospective observational cohort study.Setting:We performed IVA treatment in 14 patients with POI with mean age of 29 years, mean duration since last menses of 3.8 years, and average basal FSH level of 94.5 mIU/mL.Interventions:Prior to IVA treatment, all patients received routine hormonal treatments with no follicle development. We removed one ovary from patients with POI and treated them with Akt stimulators. We improved upon early procedures by grafting back fresh tissues using a simplified protocol.Main Outcome Measures:In six of the 14 patients (43%), a total of 15 follicle development waves were detected, and four patients had successful oocyte retrieval to yield six oocytes. For two patients showing no spontaneous follicle growth, human menopausal gonadotropin treatment induced follicle growth at 6–8 months after grafting. After vitro fertilization of oocyte retrieved, four early embryos were derived. Following embryo transfer, one patient became pregnant and delivered a healthy baby boy, with three other embryos under cryopreservation.Conclusion:IVA technology can effectively activate residual follicles in some patients with POI and allow them to conceive their own genetic offspring. IVA may also be useful for treating patients with ovarian dysfunction including aging women and cancer survivors.

In order to explore the relationship between serum progesterone (P) level on the day of human chorionic gonadotrophin (HCG) administration and cumulative live birth rate in patients with different ovarian response during in vitro fertilization (IVF), we carried out this retrospective cohort study including a total of 4,651 patients undergoing their first IVF cycles from January 2011 to December 2012. All patients with a final live birth outcome (4,332 patients) were divided into three groups according to ovarian response: poor ovarian responder (≤5 oocytes, 785 patients), intermediate ovarian responder (6–19 oocytes, 3065 patients) and high ovarian responder (≥20 oocytes, 482 patients). The thresholds for serum P elevation were 1.60 ng/ml, 2.24 ng/ml, and 2.50 ng/ml for poor, intermediate, and high ovarian responders, respectively. Cumulative live birth rate per oocyte retrieval cycle was calculated in each group. The relationship between serum P level and cumulative live birth rate was evaluated by both univariate and multivariate logistic regression analysis. Cumulative live birth rate per oocyte retrieval cycle was inversely associated with serum P level in patients with different ovarian response. For all responders, patients with elevated P level had significantly higher number of oocytes retrieved, but lower high quality embryo rate, and lower cumulative live birth rate compared with patients with normal serum P level. In addition, serum P level adversely affected cumulative live birth rate by both univariate and multivariate logistic regression analysis, independent of ovarian response. Serum P elevation on the day of HCG administration adversely affects cumulative live birth rate per oocyte retrieval cycle in patients with different ovarian response.

Irrespective of tubal infertility, for fresh IVF/ICSI cycles the rate of EP is positively associated with ovarian stimulation; for thawed IVF/ICSI cycles, blastocyst transfer or transfer with fewer embryos reduces the EP rate. In IUI cycles, EP is associated with sperm source.

In order to study the impact of procedures of IVF/ICSI technology on sex ratio in China, we conducted this multi-center retrospective study including 121,247 babies born to 93,895 women in China. There were 62,700 male babies and 58,477 female babies, making the sex ratio being 51.8% (Male: Female  = 107∶100). In univariate logistic regression analysis, sex ratio was imbalance toward females of 50.3% when ICSI was preformed compared to 47.7% when IVF was used (P<0.01). The sex ratio in IVF/ICSI babies was significantly higher toward males in transfers of blastocyst (54.9%) and thawed embryo (52.4%) when compared with transfers of cleavage stage embryo (51.4%) and fresh embryo (51.5%), respectively. Multiple delivery was not associated with sex ratio. However, in multivariable logistic regression analysis after controlling for related factors, only ICSI (adjusted OR = 0.90, 95%CI: 0.88–0.93; P<0.01) and blastocyst transfer (adjusted OR = 1.14, 95% CI: 1.09–1.20; P<0.01) were associated with sex ratio in IVF/ICSI babies. In conclusion, the live birth sex ratio in IVF/ICSI babies was influenced by the use of ICSI, which may decrease the percentage of male offspring, or the use of blastocyst transfer, which may increase the percentage of male offspring.

In order to explore the relationship between endometrial thickness on the day of embryo transfer and pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles, we retrospectively analyzed data from 2997 patients undergoing their first FET cycles from January 2010 to December 2012. All patients were divided into three groups (Group A, ≤8 mm; Group B, 9-13 mm; Group C, ≥14 mm) according to the endometrial thickness on embryo transfer day. Compared with patients in the other two groups, patients with thin endometrial thickness in Group A had significantly lower clinical pregnancy rate (33.4%, 41.3% and 45.4%, p < 0.01) and live birth rate (23.8%, 32.2% and 34.0%, p < 0.01). After adjusting for age, body mass index (BMI), baseline follicle stimulating hormone (FSH) FET protocol and number of embryos transferred, the associations between medium endometrial thickness (Group B) and clinical pregnancy rate [adjusted odds ratio (aOR): 1.39; 95% confidence interval (CI): 1.10-1.77, p < 0.01] and live birth rate (aOR: 1.50; 95% CI: 1.16-1.95, p < 0.01) were significant. We conclude that for patients undergoing FET, endometrial thickness on the embryo transfer day significantly affects IVF outcomes in cleavage embryo transfer cycles independent of other factors.

We provide evidence that three other HOX genes in addition to HOXA10 are involved in endometrial receptivity, and that part of their function is asserted through several known HOX target genes, suggesting the presence of a central HOX signal transduction pathway.

BackgroundPolycystic ovary syndrome (PCOS) is linked to obesity, impaired glucose tolerance and diabetes. Recently, studies have found that preptin enhances insulin secretion in rats and might play a role in the pathogenesis of diabetes and PCOS in humans. The aim of this study was to evaluate the relationship between PCOS, glucose tolerance status, and serum preptin level.MethodsThis study was conducted in a university-affiliated hospital from October 2010 to August 2011. Anthropometric parameters, sex hormone concentrations, blood pressure, lipid profiles, fasting glucose and insulin, 2-h blood glucose after glucose overloaded (2hOGTT), glycosylated haemoglobin (HbA1c), homeostasis model assessment-insulin resistance index (HOMA-IR), and serum preptin of the samples were analyzed.ResultsSixty-three PCOS patients, including 33 women with normal glucose tolerance (NGT) and 30 women with impaired glucose tolerance (IGT), and 63 patients without PCOS, including 35 women with NGT and 28 women with IGT were recruited in this study. For patients with and without PCOS, women with IGT had higher serum preptin levels compared with women with NGT. Preptin levels in PCOS patients were higher compared with patients without PCOS, but the difference was not significant. Fasting serum preptin levels correlated positively with TG, SBP, DBP, FBG, 2hOGTT, and HOMA-IR in simple regression analysis of the pooled data. While in multiple stepwise regression analysis, preptin levels were independently related with glucose tolerance, but not with PCOS.ConclusionsIrrespective of PCOS status, women with IGT had higher serum preptin levels compared with women with NGT. Preptin levels are related with glucose tolerance status, but not with PCOS status.