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Oocyte maturation is vital to attain full competence required for fertilization and embryogenesis. NLRP14 is preferentially expressed in mammalian oocytes and early embryos. Yet, the role and molecular mechanism of NLRP14 in oocyte maturation and early embryogenesis are poorly understood, and whether NLRP14 deficiency accounts for human infertility is unknown. Here, we found that maternal loss of Nlrp14 resulted in sterility with oocyte maturation defects and early embryonic arrest (EEA). Nlrp14 ablation compromised oocyte competence due to impaired cytoplasmic and nuclear maturation. Importantly, we revealed that NLRP14 maintained cytoplasmic UHRF1 abundance by protecting it from proteasome-dependent degradation and anchoring it from nuclear translocation in the oocyte. Furthermore, we identified compound heterozygous NLRP14 variants in women affected by infertility with EEA, which interrupted the NLRP14-UHRF1 interaction and decreased UHRF1 levels. Our data demonstrate NLRP14 as a cytoplasm-specific regulator of UHRF1 during oocyte maturation, providing insights into genetic diagnosis for female infertility., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: Was polycystic ovary syndrome (PCOS), which impairs fertility and adheres to the evolutionary paradox, subject to evolutionary selection during ancestral times and did rapidly diminish in prevalence?, Summary Answer: This study strengthened the hypothesis that positive selection of genetic variants occurred and may account for the high prevalence of PCOS observed today., What Is Known Already: PCOS is a complex endocrine disorder characterized by both reproductive and metabolic disturbances. As a heritable disease that impairs fertility, PCOS should diminish rapidly in prevalence; however, it is the most common cause of female subfertility globally. Few scientific genetic studies have attempted to provide evidence for the positive selection of gene variants underlying PCOS., Study Design, Size, Duration: We performed an evolutionary analysis of 2,504 individuals from 14 populations of the 1000 Genomes Project., Participants/materials, Setting, Methods: We tested the signature of positive selection for 37 single-nucleotide polymorphisms (SNPs) associated with PCOS in previous genome-wide association studies using six parameters of positive selection., Main Results and the Role of Chance: Analyzing the evolutionary indices together, there was obvious positive selection at the PCOS-related SNPs loci, especially within the original evolution window of humans, demonstrated by significant Tajima's D values. Compared to the genome background, six of the 37 SNPs in or close to five genes (DENN domain-containing protein 1A: DENND1A, chromosome 9 open reading frame 3: AOPEP, aminopeptidase O: THADA, diacylglycerol kinase iota: DGKI, and netrin receptor UNC5C: UNC5C) showed significant evidence of positive selection, among which DENND1A, AOPEP, and THADA represent the set of most established susceptibility genes for PCOS., Limitations, Reasons for Caution: First, only well-documented SNPs were selected from well-designed experiments. Second, it is difficult to determine which hypothesis of PCOS evolution is at play. After considering the most significant functions of these genes, we found that they had a wide variety of functions with no obvious association between them., Wider Implications of the Findings: Our findings provide additional evidence for the positive evolution of PCOS. Our analyses require confirmation in a larger study with more evolutionary indicators and larger data range. Further research to identify the roles of the DENND1A, AOPEP, THADA, DGKI, and UNC5C genes is also necessary., Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2021YFC2700400 and 2021YFC2700701), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (82192874, 31871509, and 82071606), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors have no conflicts of interest to disclose., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Question: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles?, Summary Answer: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day., What Is Known Already: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass., Study Design, Size, Duration: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021., Participants/materials, Setting, Methods: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy., Main Results and the Role of Chance: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups., Limitations, Reasons for Caution: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers., Wider Implications of the Findings: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation., Study Funding/competing Interest(s): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare., Trial Registration Number: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958., Trial Registration Date: May 2018., Date of First Patient’s Enrolment: November 2018., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Research Question: Do infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI-ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI-ET affect pregnancy and neonatal outcomes?, Design: This was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI-ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI-ET. The outcome measures were pregnancy outcomes and neonatal outcomes., Results: There were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05)., Conclusions: For infertile women undergoing IVF/ICSI-ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI-ET do not affect pregnancy or neonatal outcomes., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the effects of different ovarian stimulation protocols on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile women with adenomyosis., Methods: We carried out a retrospective cohort study among infertile women with adenomyosis receiving IVF/ICSI treatment, including 257 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles. In fresh ET cycles, ultra-long, long, short, and antagonist protocols were adopted. In FET cycles, patients received long-acting GnRH agonist (GnRHa) pretreatment or not. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes included implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR)., Results: In fresh ET cycles, compared with ultra-long and long protocols, IR (49.7%, 52.1% versus 28.2%, P=0.001) and CPR (64.3%, 57.4% versus 35.6%, P=0.004) significantly decreased in the short protocol. Similarly, compared with ultra-long and long protocols, a decreased inclination of IR (49.7%, 52.1% versus 33.3%) and CPR (57.4%, 64.3% versus 38.2%) existed in the antagonist protocol, although no statistical significance was detected because of strict P adjustment of Bonferroni method (P adj =0.008). Compared with long protocol, LBR in short protocol decreased obviously (48.2% versus 20.3%, P<0.001). In FET cycles, no matter which origin of embryos, there were no statistical differences in IR, CPR, and LBR. For women ≥35 years receiving fresh ET, CPR was higher in ultra-long and long protocols (52.1%, 50.0% versus 20.0%, 27.5%, P=0.031) compared to antagonist and short protocols. For women ≥35 years receiving FET, compared with ultra-long and antagonist protocols, cycles with embryos originating from long and short protocols had higher proportions of long-acting GnRHa pretreatment (30.4%,30.00 versus 63.9%, 51.4%, P=0.009). IR (61.1%, 48.6% versus 32.6%, 25.0%, P=0.020) and CPR (58.3%, 48.6% versus 30.4%, 25.0%, P=0.024) in long and short protocols were higher than rates of ultra-long and antagonist protocols, but no statistical differences were supported because of strict Bonferroni method (P adj =0.008)., Conclusion: In infertile women with adenomyosis, if a fresh embryo was planned for transfer, an ultra-long or long protocol might be beneficial. If antagonist and short protocols were used, whole embryos frozen followed by FET was recommended. In FET cycles, embryos derived from different protocols had no impact on pregnancy outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ge, Li, Guan, Cui and Chen.)

Objective: This study aimed to examine the relationship between the anxiety and depressive trajectory of women conceived through assisted reproductive technology (ART) and their children's emotional and behavioral problems., Methods: This prospective cohort study including 18,711 women, was conducted between July 2014 and December 2017. Self-rating scales for anxiety and depression were used before treatment, during the first trimester, and two to three years postpartum. A latent class growth analysis identified their maternal anxiety and depressive symptom trajectories. Multiple comparison and linear regression models were performed to assess the relationships between maternal trajectories and their offspring's emotional and behavioral problems., Results: Three longitudinal heterogeneous trajectories of maternal anxiety and depressive symptoms were identified: resilient, recurrent, and emergent. After adjusting for covariates, children with mothers in the recurrent and emergent trajectory groups had higher Child Behavior Checklist/2-3 scores. Additionally, the participants with a recurrent trajectory had lower education and employment levels and younger maternal age at delivery. They also had a history of ovarian surgery, primipara, secondary infertility, polycystic ovary syndrome, and more embryo transferred cycles, including intracytoplasmic sperm injections. Those with resilient trajectories had higher antral follicle counts and GnRH antagonist protocol. Finally, the participants with emergent trajectories had a lower monthly income, primipara, ectopic pregnancy, and fresh embryo transfers., Conclusions: Infertile women's psychological stress was not alleviated by the ART-sociodemographic, infertility-related and treatment-related characteristics determined three mental health trajectories. Children with mothers in recurrent and emergent trajectories showed higher odds of experiencing emotional and behavioral problems., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Premature ovarian insufficiency (POI) is one of the key aspects of ovarian infertility. Due to early cession of ovarian function, POI imposes great challenges on the physiological and psychological health of women and becomes a common cause of female infertility. In the worldwide, there has been a special outpouring of concern for about 4 million reproductive-aged women suffering from POI in China. Driven by advances in new technologies and efforts invested by Chinses researchers, understanding about POI has constantly been progressing over the past decade. Here, we comprehensively summarize and review the landmark development and achievements from POI studies in China spanning 2011-2020, which aims to provide key insights from bench to bedside., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To identify the influence of different infertility causes and assisted reproductive technology (ART) treatment on perinatal outcomes and clarify the relationship between the maternal pathophysiological changes and artificial interventions., Methods: A total of 1,629 fertile women and 27,112 infertile women with sole infertility causes were prospectively recruited from July 2014 to December 2017, and 9,894 singletons were finally enrolled into the study. Pregnancies with more than one cause of infertility and/or multiple births were excluded. According to the causes of infertility and the exposure of ART treatment, the participants were divided into four groups, namely, fertile naturally conceived (NC) group, infertile NC group, female factor ART group, and male factor ART group. Perinatal outcomes, including gestational age of delivery (GA), birth weight (BW), preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), and large for gestational age (LGA), were compared among groups. Logistic regression was performed for the adjustment of several covariates., Results: The birth outcomes of the infertile NC group and fertile NC group, female factor ART group, and infertile NC group were comparable. Compared to the fertile NC group, the female factor ART group had a shorter GA (39.0 ± 1.6 vs. 39.3 ± 1.5 weeks, BW: P < 0.05). An interaction test showed that ART treatment had an interaction on the effect of female infertility on GA (P = 0.023). The female factor ART group also had a higher risk of PTB (OR 1.56, 95% CI 1.18-2.07) and LGA (OR 1.27, 95% CI 1.10-1.47) compared to the fertile NC group. The risk of PTB was increased for tubal factor ART (OR 1.49, 95% CI 1.12-2.00), ovulatory dysfunction ART (OR 1.87, 95% CI 1.29-2.72), and unexplained infertility ART (OR 1.88, 95% CI 1.11-3.17). The risk of LGA was increased for tubal factor ART (OR 1.28, 95% CI 1.11-1.48) and ovulatory dysfunction ART (OR 1.27, 95% CI 1.03-1.57)., Conclusions: Our findings indicated that ART treatment could amplify the adverse effect of female infertility on neonates. Women with tubal factor infertility, ovulatory dysfunction, and unexplained infertility have a higher risk of PTB after ART treatment. Thus, clinicians should be vigilant in such patients and provide corresponding prevention strategies before and during pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Zhou, Feng, Hu, Hu, Cui and Chen.)

Objective: To evaluate the effect of dehydroepiandrosterone (DHEA) pre-treatment before in vitro fertilization and embryo transfer (IVF-ET) on the live birth rate in infertile women with poor ovarian response (POR) defined according to the Bologna criteria., Design: A randomized, double-blind, placebo-controlled trial., Setting: Nine reproductive medical centers in China., Population: A total of 821 participants with POR defined according to the Bologna criteria were enrolled in the study between April 2016 and December 2018., Methods: Eligible participants were randomly assigned to receive either DHEA (n = 410) or placebo (n = 411) treatments for 4-12 weeks prior to IVF-ET, in a 1:1 ratio., Main Outcome Measures: Live birth rate after the first embryo transfer., Results: Thirty-six (8.8%) of 410 women in the DHEA group and 37 (9.0%) of 411 women in the placebo group had a live birth, with no significant difference observed between groups (relative risk, 0.98, 95% CI, 0.63-1.51; p = 0.911). There were no significant differences in the number of retrieved oocytes, and the rates of clinical pregnancy, pregnancy loss, and cumulative live births between the two groups., Conclusions: DHEA administration prior to IVF-ET had no beneficial effect on the live birth rate relative to placebo in women with POR defined according to the Bologna criteria., Tweetable Abstract: No benefit was found in poor ovarian responders who received DHEA administration prior to IVF., (© 2021 John Wiley & Sons Ltd.)

Objective: Women with septate uteri are at risk for subfertility, recurrent miscarriage, and preterm birth. It is not clear if hysteroscopic septum resection is beneficial to subsequent in vitro fertilization-intracytoplasmic sperm injection o (IVF/ICSI) outcomes in women with primary infertility., Study Design: We analyzed all 278 women with uterine septum and primary infertility between January 2011 and January 2019. In this retrospective cohort study, the patients were divided into a surgery group and an expectant (non-surgery) group., Results: Among them, 87 had a complete and 191 a partial septate uterus. The IVF-ET characteristics of the two groups showed no significant differences in the patients' age, body mass index, or basal follicle-stimulating hormone, luteinizing hormone, and estradiol levels (P>0.05). The miscarriage rate in those who underwent hysteroscopic septum resection, however, was significantly reduced (5.1% vs. 12.9%, P = 0.035). In contrast, the live birth rate between the two groups revealed no significant difference (51.4% vs. 43.6%, P = 0.1771), nor did the obstetric and neonatal outcomes (P>0.05)., Conclusions: Hysteroscopic septum resection can be recommended prior to IVF/ICSI., Competing Interests: Declaration of Competing Interest All the authors state that they have no conflicts of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To examine different expression profiles of plasma exosomal microRNA (miRNA) in polycystic ovary syndrome (PCOS) patients and controls, and their potential roles in PCOS pathogenesis., Design: Experimental study., Setting: Center for reproductive medicine., Patient(s): Seventy-five PCOS patients and 75 age-matched controls., Intervention(s): Plasma exosomes miRNAs sequenced from 15 PCOS patients and 15 controls., Main Outcome Measure(s): Plasma exosomal miRNA expression and the correlation between PCOS phenotypes and miRNA expression., Result(s): The sequenced plasma exosomes miRNAs were further determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in a larger cohort, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Correlation analysis and receiver operating characteristic (ROC) curve analysis were used to determine the association between PCOS phenotypes and miRNA expression. The miRNA sequencing revealed 34 exosomal miRNAs were differentially expressed between PCOS patients and controls. Via qRT-PCR, five differentially expressed miRNAs (miR-126-3p, miR-146a-5p, miR-20b-5p, miR-106a-5p, and miR-18a-3p) were identified. The GO and KEGG analyses predicted their target functions included axon guidance, mitogen-activated protein kinase (MAPK) signaling, endocytosis, circadian rhythms, and cancer pathways. The expression of these miRNAs correlated with menstrual cycle, antral follicle count, hormone level, and combined yielded a ROC curve area of 0.781 in discriminating PCOS patients from the controls., Conclusion(s): Differential expression of plasma exosomal miRNAs may confer a risk of PCOS and may be helpful in distinguishing PCOS patients from controls. Certain miRNA expression may associated to the disease progression, which could help in an epigenetic understanding of the pathophysiology of PCOS., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Polycystic ovary syndrome (PCOS) is the most common reason of anovulatory infertility. Environmental factor is one of the main causes of PCOS, but its contribution to ovulatory dysfunction in PCOS remains unknown., Methods: A total of 2217 infertile women diagnosed as PCOS according to Rotterdam criteria were recruited, including 1979 women with oligo-anovulation (OA group) and 238 women with normal -anovulation (non OA group). Besides, 279 healthy control women of reproductive age were enrolled as controls., Results: Frequencies of snoring (PCOS-OA group, PCOS-non-OA group, control group: 29.30% vs 18.10% vs 11.50%, P < 0.01), smoking (37.70% vs 28.10% vs 12.20%, P < 0.01), plastic tableware usage (38.30% vs 28.10% vs 25.40%, P < 0.01) and indoor decoration (32.10% vs 24.80% vs 16.80%, P < 0.01) were highest in PCOS-OA group. After adjusted for multivariable, difference remained significant between PCOS-OA group and the other two groups. PCOS-OA women preferred a meat favorable diet compared to PCOS-non-OA group (54.60% vs 41.30%, P < 0.01). There was no difference between three groups in exercise, frequency of insomnia, and alcohol consumption., Conclusions: Smoking, snoring, hyper-caloric diet, plastic tableware usage and indoor decoration were found to be associated with an increased risk for ovulatory dysfunction in women suffering from PCOS.

Objective: With a high incidence of insulin resistance, central obesity and dyslipidemia, women with polycystic ovary syndrome are susceptible to metabolic syndrome (MetS). Our objective was to explore whether metabolic syndrome had an effect on overall female fertility and in vitro fertilization outcomes in infertile women with polycystic ovary syndrome., Study Design: This was a secondary analysis of a multicenter randomized trial in 1508 women with polycystic ovary syndrome, which was originally designed to compare the live birth rate after fresh-embryo transfer vs frozen embryo transfer (Frefro-PCOS). At baseline, metabolic parameters, including body mass index, waist and hip circumference, blood pressure, lipid profile, fasting, and 2 hour glucose and insulin levels after a 75 g oral glucose tolerance test were measured. All subjects were divided into a metabolic syndrome group (metabolic syndrome) and absence of metabolic syndrome group (nonmetabolic syndrome) according to diagnostic criteria. Descriptive statistics and logistic regression models tested the association between metabolic syndrome and overall fertility and in vitro fertilization cycle stimulation characteristics and clinical outcomes., Results: Metabolic syndrome was identified in 410 of 1508 infertile women with polycystic ovary syndrome (27.2%). Patients with metabolic syndrome had longer infertility duration (4.0 ± 2.2 vs 3.7 ± 2.2, P = .004) compared with those without metabolic syndrome. During ovarian stimulation, those with metabolic syndrome required significantly higher and longer doses of gonadotropin and had lower peak estradiol level, fewer retrieved oocytes, available embryos, a lower oocyte utilization rate, and ovarian hyperstimulation syndrome than those with nonmetabolic syndrome. The cumulative live birth rate did not show a significant between-group difference (57.8% vs 62.2%, P = .119). Multivariate logistic regression analysis adjusted for age, duration of infertility, body mass index, thyroid-stimulating hormone, metabolic syndrome group, homeostatic model assessment of insulin resistance, metformin utilization, number of available embryos, and embryos transferred showed that the number of embryos transferred and the number of available embryos were positively but metabolic syndrome negatively associated with the cumulative live birth rate (odds ratio, 2.18, 1.10, and 0.70, respectively, P < .05)., Conclusion: Women with polycystic ovary syndrome with metabolic syndrome have a negative impact from female fecundity, and this suggests an adverse effect on in vitro fertilization cycle stimulation characteristics and clinical outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Research Question: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China?, Design: Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy., Results: Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy., Conclusion: The prevalence of infertility in China is high, but the uptake of treatment is relatively low., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with poor ovarian respond (POR) always have very low clinical pregnancy rates. In previous data, dehydroepiandrosterone (DHEA) was suggested as a promising treatment and maybe has a good pregnancy outcome. But there is no sufficient evidence from randomized clinical trials evaluating the effect of DHEA preconceptional treatment on live birth in POR., Methods: This trial is a multicenter active-placebo double-blind clinical trial (1:1 treatment ratio of active versus placebo). The infertile POR patients undergoing IVF or ICSI will be enrolled and randomly assigned to two parallel groups. Participants in these two groups will be given 4-12 weeks' treatment of DHEA or placebo, respectively. The primary outcome is live birth rate., Discussion: The results of this study will provide evidence for the effect of preconceptional DHEA treatment on IVF outcome in POR., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-15006909 . Registered on November 9, 2015.

Background: Obese women have fewer oocytes retrieved, an increased cancelation rate, a higher miscarriage rate, and a lower live birth rate after assisted reproductive technology (ART) treatment compared with women with normal weight. Weight loss before ART treatment can significantly improve pregnancy rates and/or live births. An orlistat plus diet intervention could promote weight loss, but there is no evidence from randomized clinical trials evaluating the effect of orlistat preconceptional treatment on pregnancy outcome in overweight and obese women., Methods/design: We are conducting a multicenter, randomized placebo-controlled, double-blind clinical trial in overweight and obese women aged 20-40 years undergoing in-vitro fertilization and embryo transfer (IVF-ET) with or without intracytoplasmic sperm injection, to evaluate whether orlistat treatment for 1-3 months before IVF-ET can improve the live birth rate. The primary outcome is live birth., Discussion: The results of this study will provide evidence for the effect of preconceptional orlistat treatment on IVF outcome in overweight/obese women., Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-17011629 . Registered on 11 June 2017.

Objective: To evaluate the effect of frozen embryo transfer on maternal and neonatal complications of singleton and twin pregnancies compared with fresh embryo transfer in women with polycystic ovary syndrome (PCOS)., Design: A secondary analysis of a multicenter, randomized, controlled trial comparing live birth after frozen vs. fresh embryo transfer (FreFro-PCOS)., Setting: Reproductive medicine centers., Patient(s): A total of 1,508 patients with a diagnosis of PCOS who were undergoing IVF were enrolled., Intervention(s): On day of oocyte retrieval, eligible patients were randomized to the fresh or frozen embryo transfer groups. Up to two embryos were transferred in both groups. All pregnancies were followed up until delivery., Main Outcome Measure(s): Gestational diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and large for gestational age., Result(s): The risks of gestational diabetes mellitus, preterm birth, and small for gestational age were comparable between the frozen and fresh embryo transfer groups in both singleton and twin births. However, singleton infants born after frozen embryo transfer were more likely to be large for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval 1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%; relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after fresh embryo transfer., Conclusion(s): In women with PCOS, frozen embryo transfer resulted in an increased risk of large for gestational age in singleton pregnancy and a higher risk of pre-eclampsia in twin pregnancy., Clinical Trial Registration Number: NCT01841528., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Elective frozen-embryo transfer has been shown to result in a higher live-birth rate than fresh-embryo transfer among anovulatory women with the polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer increases live-birth rates among ovulatory women with infertility., Methods: In this multicenter, randomized trial, we randomly assigned 2157 women who were undergoing their first in vitro fertilization cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up to two cleavage-stage embryos were transferred in each participant. The primary outcome was a live birth after the first embryo transfer., Results: The live-birth rate did not differ significantly between the frozen-embryo group and the fresh-embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between-group differences in the rates of implantation, clinical pregnancy, overall pregnancy loss, and ongoing pregnancy. Frozen-embryo transfer resulted in a significantly lower risk of the ovarian hyperstimulation syndrome than fresh-embryo transfer (0.6% vs. 2.0%; relative risk, 0.32; 95% CI, 0.14 to 0.74; P=0.005). The risks of obstetrical and neonatal complications and other adverse outcomes did not differ significantly between the two groups., Conclusions: The live-birth rate did not differ significantly between fresh-embryo transfer and frozen-embryo transfer among ovulatory women with infertility, but frozen-embryo transfer resulted in a lower risk of the ovarian hyperstimulation syndrome. (Funded by the National Key Research and Development Program of China and the National Natural Science Foundation of China; Chinese Clinical Trial Registry number, ChiCTR-IOR-14005406 .).

Context: Women with polycystic ovary syndrome (PCOS) commonly have intrinsic insulin resistance and are recommended to undergo an oral glucose tolerance test (OGTT) for diabetes screening. However, the effect of preconception impaired glucose tolerance (IGT) on pregnancy is still unclear., Objective: To prospectively assess the effect of preconception IGT on pregnancy outcomes., Design, Setting, Patients, Interventions, and Main Outcome Measures: This was a secondary analysis of a multicenter randomized trial in 1508 women with PCOS comparing live birth and obstetric complications between fresh and frozen embryo transfer. At baseline, fasting and 2-hour glucose and insulin levels after 75-g OGTT were measured., Results: Women with preconception IGT had higher risks of gestational diabetes in both singleton pregnancy [9.5% vs 3.2%; odds ratio (OR) 3.13; 95% confidence interval (CI) 1.23to 7.69] and twin pregnancy (20.0% vs 3.2%; OR 7.69; 95% CI 2.78 to 20.00) than women with normoglycemia. Preconception IGT was associated with a higher risk of large for gestational age in singleton newborns compared with normoglycemia (34.7% vs 19.8%; OR 2.13; 95% CI 1.19 to 3.85) or isolated impaired fasting glucose (i-IFG) (34.7% vs 15.4%; OR 2.94; 95% CI 1.33 to 6.25). Women with preconception IGT had a higher singleton pregnancy loss rate than women with i-IFG (31.4% vs 17.5%; OR 2.17; 95% CI 1.11 to 4.17). After adjusting for age, body mass index, duration of infertility, total testosterone level, and treatment groups (frozen vs fresh embryo transfer), these associations remained., Conclusions: Preconception IGT, independent from BMI, was associated with adverse pregnancy outcome compared with i-IFG and normoglycemia., (Copyright © 2017 Endocrine Society)

Poor ovarian response is a significant problem encountered during in vitro fertilization and embryo transfer procedures. Many infertile women may suffer from poor ovarian response and its incidence tends to be increasing in young patients nowadays. It is a major cause of maternal infertility because it is associated with low pregnancy and live birth rates. However, the cause of poor ovarian response is not clear. In this study, we extracted microRNAs from human follicular fluid and performed miRNA sequencing to investigate a potential posttranscriptional mechanism underlying poor ovarian response. The results showed that many miRNAs were obviously different between the poor ovarian response and non-poor ovarian response groups. We then performed quantitative polymerase chain reaction, Western blot analysis and used an in vitro culture system to verify the sequencing results and to study the mechanism. Notably, we found that miRNA-15a-5p was significantly elevated in the young poor ovarian response group. Furthermore, we demonstrated that high levels of miR-15a-5p in the young poor ovarian response group repressed granulosa cell proliferation by regulating the PI3K-AKT-mTOR signaling pathway and promoted apoptosis through BCL2 and BAD. This could explain the reduced oocyte retrieval number seen in poor ovarian response patients., (© 2017 Society for Reproduction and Fertility.)

Empty follicle syndrome (EFS) is defined as the failure to aspirate oocytes from mature ovarian follicles during in vitro fertilization. Except for some cases caused by pharmacological or iatrogenic problems, the etiology of EFS remains enigmatic. In the present study, we describe a large family with a dominant inheritance pattern of female infertility characterized by recurrent EFS. Genome-wide linkage analyses and whole-exome sequencing revealed a paternally transmitted heterozygous missense mutation of c.400 G>A (p.Ala134Thr) in zona pellucida glycoprotein 3 (ZP3). The same mutation was identified in an unrelated EFS pedigree. Haplotype analysis revealed that the disease allele of these two families came from different origins. Furthermore, in a cohort of 21 cases of EFS, two were also found to have the ZP3 c.400 G>A mutation. Immunofluorescence and histological analysis indicated that the oocytes of the EFS female had degenerated and lacked the zona pellucida (ZP). ZP3 is a major component of the ZP filament. When mutant ZP3 was co-expressed with wild-type ZP3, the interaction between wild-type ZP3 and ZP2 was markedly decreased as a result of the binding of wild-type ZP3 and mutant ZP3, via dominant negative inhibition. As a result, the assembly of ZP was impeded and the communication between cumulus cells and the oocyte was prevented, resulting in oocyte degeneration. These results identified a genetic basis for EFS and oocyte degeneration and, moreover, might pave the way for genetic diagnosis of infertile females with this phenotype., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether the common variant rs2305957 spanning PLK4 (Polo-like kinase 4) confers risk to embryo development in Northern Chinese Han (CHN) women., Design: Genetic association study., Setting: University hospital., Patient(s): A total of 2,015 infertile women who underwent in vitro fertilization (IVF), 530 women with early recurrent miscarriage (ERM), and 600 fertile control women in the CHN population., Intervention(s): Genotyping of rs2305957 was performed by means of high-resolution melting analysis., Main Outcome Measure(s): Blastocyst formation, implantation, early miscarriage, and live birth rates in infertile women; genotype distribution at rs2305957 in ERM case and control subjects., Result(s): In the first cohort of this study, infertile women with AA genotype had a lower blastocyst formation rate than those with AG or GG genotype. No significant differences were observed in implantation rate, early miscarriage rate, or live birth rate among AA, AG, and GG subgroups. In the second cohort, common variant rs2305957 was related to ERM. Genotype frequency differences were also significant in both additive model and dominant model., Conclusion(s): Common variant rs2305957 is associated with blastocyst formation and ERM in CHN women. Further investigations of PLK4 gene during embryo development could be worthwhile., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA&#95;Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA&#95;Cre was associated with a significant decrease of 0.34 in AFC (β = -0.34, 95% CI = -0.60, -0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve., Competing Interests: The authors declare no conflict of interest.

Background: The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome., Methods: In this multicenter trial, we randomly assigned 1508 infertile women with the polycystic ovary syndrome who were undergoing their first IVF cycle to undergo either fresh-embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. After 3 days of embryo development, women underwent the transfer of up to two fresh or frozen embryos. The primary outcome was a live birth after the first embryo transfer., Results: Frozen-embryo transfer resulted in a higher frequency of live birth after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss (22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of 0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia (4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There were no significant between-group differences in rates of other pregnancy and neonatal complications. There were five neonatal deaths in the frozen-embryo group and none in the fresh-embryo group (P=0.06)., Conclusions: Among infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth, a lower risk of the ovarian hyperstimulation syndrome, and a higher risk of preeclampsia after the first transfer than was fresh-embryo transfer. (Funded by the National Basic Research Program of China and others; ClinicalTrials.gov number, NCT01841528.).

Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS.

Background: Polycystic ovary syndrome (PCOS) patients are at increased risk of pregnancy complications, which may impair pregnancy outcome. Transfer of fresh embryos after superovulation may lead to abnormal implantation and placentation and further increase risk for pregnancy loss and complications. Some preliminary data suggest that elective embryo cryopreservation followed by frozen-thawed embryo transfer into a hormonally primed endometrium could result in a higher clinical pregnancy rate than that achieved by fresh embryo transfer., Methods/design: This study is a multicenter, prospective, randomized controlled clinical trial (1:1 treatment ratio of fresh vs. elective frozen embryo transfers).. A total of 1,180 infertile PCOS patients undergoing the first cycle of in vitro fertilization (IVF) or intracytoplasmic sperm injection will be enrolled and randomized into two parallel groups. Participants in group A will undergo fresh embryo transfer on day 3 after oocyte retrieval, and participants in group B will undergo elective embryo cryopreservation after oocyte retrieval and frozen-thawed embryo transfer in programmed cycles. The primary outcome is the live birth rate. Our study is powered at 80 to detect an absolute difference of 10 at the significance level of 0.01 based on a two-sided test., Discussion: We hypothesize that elective embryo cryopreservation and frozen-thawed embryo transfer will reduce the incidence of pregnancy complications and increase the live birth rate in PCOS patients who need IVF to achieve pregnancy., Trial Registration: ClinicalTrials.gov Identifier: NCT01841528.

Purpose: This retrospective study analyzed fertilization protocols and pregnancy outcomes for oocytes with with narrow perivitelline space and heterogeneous zona pellucid (NPVS/HZP)., Methods: In 63 in-vitro fertilization cycles filled with NPVS/HZP oocytes (abnormal oocytes group) and 521 cycles with normal oocytes (normal oocytes group), major clinical and laboratory parameters were recorded and compared in different fertilization cycles (conventional IVF cycles, rescue ICSI cycles, and traditional ICSI cycles)., Results: NPVS/HZP oocytes meant lower MIIoocytes rates in both IVF and ICSI cycles compared with normal oocytes (p < 0.05). The 2PN rates for abnormal oocytes were significantly lower than those for normal oocytes in both conventional IVF cycles (58.8% VS 71.3%, P < 0.05) and rescue ICSI cycles (58.0% VS 78.0%, P = 0.0000). The high-quality embryo rates in normal oocytes groups were significantly higher than those in abnormal oocytes groups in different fertilization cycles (52.2% VS 35.0%, P < 0.01; 42.9% VS 23.9%, P < 0.001; 50.6% VS 31.0%, P = 0.0000, respectively). No clinical pregnancy was obtained from abnormal oocytes in 11 conventional IVF cycles. The clinical pregnancy rates in rescue ICSI and traditional ICSI cycles were comparatively lower in abnormal oocytes groups, but there was no significant difference as compared with normal oocytes groups (35.0% VS 48.1% and 26.7% VS 50.7%, P > 0.05, respectively)., Conclusions: Retrieval of oocytes characterized by NPVS/PZP from cycle to cycle was one of the reasons for obscure infertility. ICSI may be the right way to avoid fertilization failure and get pregnancy in women with NPVS/HZP oocytes.

Aims: To study the effect of adenomyosis on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile patients., Methods: We performed a retrospective, database-searched cohort study based on 10,268 patients undergoing controlled ovarian hyperstimulation and IVF/ICSI between 2009 and 2011 in our unit. Adenomyosis was diagnosed by transvaginal ultrasound. A high-quality matched cohort study with strict inclusion criteria was conducted. We compared the basic characteristics and main IVF/ICSI outcomes between the two groups., Results: We identified 83 patients with adenomyosis, of whom we included 77, and strictly matched them to 77 patients without adenomyosis. Higher day 3 estrogen levels and a longer duration of gonadotropin stimulation days were found in women with adenomyosis compared to control subjects. Patients with adenomyosis had a nonsignificant trend toward a lower clinical pregnancy rate and a higher miscarriage rate (p = 0.103 and 0.09, respectively). The delivery rate was significantly lower in the adenomyosis group in comparison to the matched controls (p = 0.022)., Conclusions: Within the limitations of a retrospective study (albeit with a remarkably large number of observations), our results suggest that transvaginal ultrasound-diagnosed adenomyosis could have a negative impact on the main IVF/ICSI outcomes. Improving the diagnostic validity and scoring of disease severity in patients with adenomyosis is suggested.

Objective: To investigate the effect of domestic urine-derived high-purity follicle- stimulating hormone (HP-FSH, Lishenbao) on the outcome of in vitro fertilization(IVF) embryo transfer (ET) in controlled ovarian stimulation (COS)., Methods: From 1 September 2010 to 31 March 2011, total of 3178 infertility patients from 14 Reproductive Center with IVF or intracytoplasmic sperm injection (ICSI) indications who accepted first IVF or ICSI cycle were studied retrospectively. Their causes of infertility include all infertility factors except ovulatory dysfunction infertility and uterine factor infertility. The only long luteal phase gonadotropin-releasing hormone agonist (GnRH-a) protocol was included. Patients were divided into 2 groups according to the type of follicle-stimulating hormone (FSH) agents used: 1932 cases in HP-FSH group and 1246 cases in recombinant FSH (rFSH)group. Patients in both groups were combined with human menopausal gonadotropin (hMG) at doses of 150 U when follicle with diameter reached to 14-16 mm. When 3 dominate follicle with diameter reached 18 mm, hCG at dose of 5000 to 10 000 U or recombinant hCG at dose of 250 µg was administered by intramuscular injection. After 34 to 36 hours, oocytes were obtained guided by ultrasound, then IVF-ET were underwent in their Reproductive Center. The primary endpoint was comparison of live birth rate between the two groups. The secondary endpoints were comparisons of clinical pregnancy rate, miscarriage rate, and implantation rate, as well as COS and IVF outcome between the two groups., Results: (1) There were significantly differences in baseline characteristics of the patients between two groups. The mean age was elder(32 ± 4 versus 30 ± 4, P < 0.01) , the infertility duration was longer (5 ± 4 versus 5 ± 3, P < 0.01) , and antral follicle count (AFC) was less (11 ± 5 versus 13 ± 7, P < 0.01) in patients of HP-FSH group compared with those in patients of rFSH group. (2) As compared with rFSH, the total doses of gonadotropin needed was (2348 ± 1011) U in HP-FSH group versus (2022 ± 659) U in rFSH group, the number of oocytes 13 ± 6 in HP-FSH group and 14 ± 7 in rFSH group, the rate of embryo frozen cycle of 66.30% (1281/1932) in HP-FSH group and 74.88% (933/1246) in rFSH group, which all reached statistical difference (P < 0.01). However, there were no significant different implantation rate [30.49% (1111/3644) versus 32.45% (737/2271)] between two groups. The other clinical parameters did not show significant difference, including clinical pregnancy rate per started cycle [41.61% (804/1932) versus 41.97% (523/1246) ] , clinical pregnancy rate per ET cycle[46.58% (804/1726) versus 48.47% (523/1079)], live birth rate per started cycle[34.21% (661/1932) versus 34.19% (426/1246)], live birth rate per ET cycle [38.30% (661/1726) versus 39.48% (426/1079)], miscarriage rate[13.6% (109/804) versus 16.4% (86/523)], and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate [5.80% (112/1932) versus 7.78% (97/1246)](P > 0.05).(3) Treatment cost: the cost of gonadotropins needed for the patients in HP-FSH group was lower than that in rFSH group (4005 ± 1650 versus 6482 ± 2095, P < 0.01)., Conclusion: In IVF/ICSI treatment cycles, domestic HP-FSH has similar live birth rate and lower financial burden when compared with rFSH.

A previous genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) identified several susceptibility loci, with P-values about 10⁻⁵. In the present study, an independent cohort was used for a replication study to evaluate the association of RAD54B and GREB1 with polycystic ovary syndrome (PCOS) in the Han Chinese population. Four single-nucleotide polymorphisms (SNP), rs2930961 (RAD54B), rs12470971, rs11686574 and rs6740248 (GREB1), were genotyped in 1124 PCOS patients and 1067 healthy controls from the Han Chinese population. Real-time quantitative PCR by TaqMan-MGB probe assay was applied for genotyping. The allele and genotype frequencies of these four SNP were not significantly different in the replication cohort. However, the minor allele frequency of rs2930961 was significantly different in hyperandrogenism of PCOS. After meta-analysis by combining the results of these two studies, there was a non-significant trend for the association of rs2930961 (RAD54B) with PCOS. RAD54B and GREB1 gene polymorphisms may not be associated with PCOS in the Han Chinese population. Nevertheless, RAD54B may contribute to hyperandrogenism in PCOS patients., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to explore the effects of cumulus cells on vitreous cryopreservation of human mature oocytes and clinical pregnancy outcomes. The study was divided into group A (cumulus cells were removed from the oocytes before freezing) containing 24 participants and 193 oocytes and group B (cumulus cells were retained with the oocytes before freezing) containing 26 participants and 240 oocytes. Based on no significant differences in age, duration of infertility, infertile causes, and number of retrieved oocytes between both groups when oocytes were retrieved from infertile women, we found that the survival rate of post thaw oocytes (88% vs 58%), cleavage rate (80% vs 56%), and high-quality embryo rate (75% vs 59%) were significantly higher in group B than in group A. Under the conditions that there were no significant differences between the 2 groups in the general status of the participants undergoing embryo transfer, the embryo implantation rate (37% vs 15%) and the clinical pregnancy rate (50% vs 17%) were significantly higher in group B than in group A, all with Ps < .05. We conclude that the retention of cumulus cells can improve the developmental competence of vitrified-thawed human mature oocytes and clinical pregnancy outcomes.

Objectives: To study pregnant outcomes of patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET), and analyze the differences of pregnant outcomes in patients with various phenotypes of PCOS., Methods: From Jan. 2005 to Feb. 2010, 631 PCOS patients (PCOS group) and 1423 patients with tubal infertility (control group) who underwent IVF-ET with matched age and body mass index were selected in Center for Reproductive Medicine of the Provincial Hospital Affiliated to Shandong University. Retrospective study was carried out, and pregnancy outcomes were compared between two groups., Results: The rates of abortion and preterm birth in PCOS group were significantly higher than those in control group [22.7% (143/631) vs. 18.69% (266/1423) and 11.2% (38/339) vs. 6.4% (51/794) respectively, all P < 0.05]. The rates of gestational diabetes mellitus were 1.5% (5/339) in PCOS and 0.6% (5/794) in control group, respectively; the rates of pregnancy induced hypertension syndrome were 4.7% (16/339) in PCOS and 3.0% (24/794) in control group; gestational days were (272 ± 13) days in PCOS and (273 ± 10) days in control group; the rates of neonatal deformity were 0.6% (2/339) in PCOS and 0.8% (6/794) in control group; weight of newborn infants in the two groups was (3.5 ± 0.5) kg; and there was no significant difference between two groups in the above index (all P > 0.05). Ovulatory PCOS patients had similar abortion rate [18.6% (19/102)] and preterm birth rate [8.2% (4/49)] when compared with those of control group (P > 0.05). Conversely, oligo-ovulatory PCOS patients showed higher abortion rate [23.4% (124/529)] and preterm birth rate [11.7% (34/290)] than those of control group (P < 0.05)., Conclusions: PCOS patients after IVF-ET have an increased abortion rate and preterm birth rate. However, ovulatory PCOS did not present various pregnancy complications. Non-polycystic ovary PCOS patients have worse pregnancy outcome. Ovarian dysfunction might be related to obstetric complications.

Objective: To study the clinical outcomes of assistant treatment proposals for infertile women with polycystic ovary syndrome (PCOS)., Methods: PCOS patients were divided into four groups according to the assistant treatment proposals between Jan 2003 and Dec 2007 in Reproductive Medicine Center of the Provincial Hospital Affiliated to Shandong University. The four proposals were letrozole (LE) or clomiphene (CC) citrate ovulation induction group, in vitro fertilization and embryo transplantation group, ultrasound-guided immature follicle puncture group, and in vitro maturation and fertilization of oocytes from unstimulated cycles group. The treatment results were analyzed., Results: (1) The ovulation rate was 66% (38/58) vs 47% (21/45). The mean endometrial thickness [(0.89 +/- 0.13) vs (0.78 +/- 0.08) cm] and cervical mucus score (11.9 +/- 1.8 vs 9.9 +/- 1.8) on the day of human chorionic gonadotropin (hCG) administration in LE group were both higher than that in CC group, while mature follicle (1.08 +/- 0.28 vs 1.73 +/- 0.59) and serum estradiol level [(983 +/- 138) vs (1676 +/- 372) pmol/L] in LE group were lower than that in CC group (P < 0.05). (2) One southend five hundred and eighty-four patients accepted in vitro fertilization-embryo transplantation therapy because of PCOS (PCOS group) and 1615 patients because of tube factors (control group). The patients' ages and infertility years were matched between the two groups. Total doses of Gn [(980 +/- 1192) vs (1194 +/- 1389) IU] of PCOS group were lower than those of control group. The mean days of using gonadotropin [(9.6 +/- 1.8) vs (9.5 +/- 1.8) d], serum estradiol (E(2)) levels on the hCG day [(15 752 +/- 6206) vs (9675 +/- 4818) pmol/L], mean obtained oocytes (21 +/- 6 vs 9 +/- 3), mean fertilized oocytes (15 +/- 6 vs 7 +/- 3) and mean cleavaged oocytes (12.9 +/- 5.7 vs 5.7 +/- 2.8) of PCOS group were higher than those of the control group (P < 0.05). Moderate and severe ovarian hyperstimulation syndrome (OHSS) rates (4.86% vs 1.67%) of PCOS group were higher than that of the control group. The pregnant rate (44.7% vs 45.0%)of PCOS group was similar to the control group (P > 0.05). (3) One hundred and nine PCOS patients were given ultrasound-guided immature follicle puncture therapy. After treatment, the testosterone level, luteinizing hormone (LH) level and LH/follicle stimulating hormone (FSH) ratio of the patients became normal. The basic follicle number decreased. (4) A total of 304 in vitro maturation cycles were performed. After embryo transfer, 76 pregnancies were reported., Conclusions: There are many choices for the infertile patients with PCOS, such as LE or CC citrate ovulation induction, in vitro fertilization and embryo transplantation, ultrasound-guided immature follicle puncture, and in vitro maturation and fertilization of oocytes from unstimulated cycles. We can provide individualized treatment according to the medical treatment conditions, doctors' professional capability and the patients' situation.

Objective: To study effect of drug treatment in polycystic ovary syndrome patients with hyperprolactinemia., Methods: We retrospectively studied 63 women with polycystic ovary syndrome and hyperprolactinemia from the Reproductive Medicine Center, Provincial Hospital between January 2005 and March 2007. According to the beginning time of bromocriptine, all women were divided into two groups. Group I was composed of 48 cases who received bromocriptine administration before induction of ovulation cycles, and the dose of bromocriptine was modulated depending on the level of serum prolactin. When serum prolactin was controlled at normal levels, we decreased the dosage of bromocriptine step by step (1.25 mg once), and then continued the treatment at maintenance dosage for no less than 3 weeks. After a baseline ultrasonographic examination on day 3, patients were treated with clomiphene citrate at a dosage of 100 mg (2 tablets/day) for 5 days of a normal cycle or progesterone-induced bleeding. On day 9, we monitored the growth conditions of follicles routinely with trans-vaginal ultrasound. If there was no dominant follicle, we added human menopausal hormone (hMG, 75 U/d) to the protocol. Human chorionic gonadotropin (hCG, 6000-10,000 IU) was given intramuscularly when the mean diameter of a follicle reached at least 18 mm. At the same time we instructed the patients to have sexual intercourses or carried out artificial inseminations before and after ovulation. Group II were 15 cases in which induction of ovulations were commenced almost simultaneously with beginning of bromocriptine. The same protocol was given to patients in group II. The procedures of ovulation induction and the outcomes of treatment were analyzed and compared., Results: Compared with group II , the days of using hMG in Group I was shorter by instructing the time of sexual intercourse. The difference was significant (P = 0.004). And there were similar results in the artificial insemination cycles (P = 0.009). The rate of pregnancy in group I (40%, 19/48) was higher than that in group II (27%, 4/15), but the difference was not obvious (P = 0.525 )., Conclusion: Bromocriptine administration before the stimulated ovulation therapy can decrease the total dosage and treatment course of ovulating drugs. Induction of ovulations simultaneously with start of bromocriptine therapy can shorten the treatment time of infertility.

Objective: Infertility is one of important issues in patients with premature ovarian failure (POF) during their reproductive life. This study would analyze the features of infertility women with POF., Patients: 138 Chinese infertility women with POF were accrued from the women who visited the Reproductive Medical Center in Shandong Provincal Hospital of Shandong University between May 2003 and November 2006., Method: This study analyzed the clinical, etiology features and karyotype of 138 patients, then evaluates the effect of the therapy., Results: It showed that most patients' physical situation were suitable for assisted reproductive therapy. The infertility women with POF had high rate of abnormal karyotype (11/65, 16.92%) and lower severe autoimmune disorders rate (2/138,1.45%). Some of them demonstrated family aggregation. FSH was dropped apparently after estrogen-progesterone therapy (p<0.05). The spontaneous pregnancy incidence of the women was 2.17% (3/138)., Conclusion: The infertility women with POF were suitable for assisted reproductive therapy and donor oocyte could be an alternate way. Their high chromosomal abnormality rate showed the importance of genetic screening. And estrogen-progesterone therapy was beneficial for improving their endocrine environment.

Objective: To investigate the effect of in vitro maturation (IVM) and fertilization of oocytes from unstimulated cycles in women with infertility due to polycystic ovary syndrome (PCOS)., Methods: Seventy women with PCOS, who came to our clinic during March to were involved in this trial. June 2003. Every cycle was given human chorionic gonadotropin 10,000 IU 36 h before oocyte retrieval. Immature oocytes were matured in vitro and fertilized, and the resulting embryos were replaced back to the uterus., Results: A total of 94 IVM cycles were performed and 1283 oocytes were obtained. The overall maturation, fertilization and cleavage rates were 65.3%, 66.0% and 48.0% respectively. Maturation, fertilization, cleavage and high quality embryo rates had no difference between metaphase I stage oocytes (69.7%, 71.7%, 52.2% and 26.1% respectively) and germinal vesical (GV) stage oocytes (67.7%, 66.4%, 47.6% and 24.1% respectively), but the rates in those oocytes which could not be classified (44.8%, 53.8%, 46.2% and 16.9% respectively) were much lower than the former two groups. After embryo transfer, 18 pregnancies were reported (24%)., Conclusion: IVM/IVF-ET in unstimulated cycles is a feasible treatment for women with PCOS.

Objective: To investigate the effect of ultrasound-guided immature follicle aspiration (IMFA) on polycystic ovarian syndrome (PCOS) in women with anovulatory infertility, such as the endocrinology of the patients and the basic follicles number in the ovaries, and to observe the ovarian response to human menopausal gonadotropin (hMG) stimulation and pregnancy after the therapy., Methods: Seventy-one PCOS patients were involved in this trial, and divided into 2 groups. Thirty-seven patients of group I were primed with slight amount of hMG, the other 34 patients did not use hMG. Ultrasound-guided IMFA was performed 36 hour after human chorionic gonadotropin (hCG) administration. In the next cycle, the basal endocrinology and the basic number of follicles were checked, then IMFA were performed continuously until the basic number of follicles were under 10 per ovary. Afterwards, hMG were used to stimulate ovulation and the pregnant results were followed up., Results: There were 37 cases (88 cycles) of PCOS patients in group I and 34 cases (87 cycles) in group II. After 2 to 3 treatment cycles, the testosterone level became normal in all of patients. The basic follicle number decreased to less than 10 per ovary in 33 cases (89%) in group I and 28 cases (82%) in group II. After hCG stimulation, all of them ovulated. Only 2 patients developed slight ovarian hyperstimulation syndrome (OHSS). Within 3 months after the procedure, 36 patients (51%) became pregnant by controlled ovarian hyperstimulation (COH) protocol after IMFA., Conclusions: Immature follicle aspiration treatment can improve the abnormal endocrinology, decrease the basic follicle number of the ovary, and achieve pregnancy in following COH cycles, meanwhile, avoid OHSS in PCOS patients.