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Research Question: What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles?, Design: This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used., Results: In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17-2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03-3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles., Conclusions: A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls?, Design: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort., Results: The control group exhibited higher relative abundance of Lactobacillus crispatus in comparison with the polypoid lesions group (P = 0.0427). Beta diversity of vaginal microbiota differed significantly between the groups (P < 0.05). Comparing the polyps group with the not-polyps group, Leptotrichia spp. and Cutibacterium spp. were more abundant in the polyps group, and Fannyhessea spp., Acinetobacter spp. and Achromobacter spp. were more abundant in the not-polyps group. The control group exhibited higher abundance of Bifidobacterium spp., Achromobacter spp. and Escherichia/Shigella spp. (false discovery rate < 0.05). Furthermore, the polyps group and not-polyps group displayed more complex co-occurrence networks compared with the control group., Conclusions: The results of this study provide compelling evidence supporting associations between vaginal microbiota and endometrial polypoid lesions, highlighting the potential relationship between a well-balanced vaginal microbial ecosystem and a healthy intrauterine environment., (Copyright © 2023. Published by Elsevier Ltd.)

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.)

Research Question: Adenomyosis is a common uterine disorder of uncertain causes. Can transcriptomic analyses of the endometrium and myometrium reveal potential mechanisms underlying adenomyosis pathogenesis?, Design: Transcriptomic profiles of eutopic endometrium and myometrium from women with and without diffuse adenomyosis and with symptomatic FIGO type 2-5 fibroids in the proliferative phase of the menstrual cycle were assessed using RNA sequencing and bioinformatic analysis. Differentially expressed genes (DEG) and potential pathways were validated by quantitative reverse transcription polymerase chain reaction, immunoblotting and Masson staining, using additional clinical samples., Results: Top biological processes in the endometrium of women with versus without adenomyosis, enriched from DEG, comprised inflammation, extracellular matrix (ECM) organization, collagen degradation and hyaluronan synthesis, which are key in cell migration and cell movement. Top biological processes enriched from DEG in the myometrium of women with versus without adenomyosis revealed ECM organization dysfunction, abnormal sensory pain perception and gamma aminobutyric acid (GABA) synaptic transmission. Dysregulation of prolactin signalling was also enriched in eutopic endometrium and in the myometrium of women with adenomyosis., Conclusions: Overall, our results support the invasive endometrium theory in the pathogenesis of adenomyosis, in which inflammation induces ECM remodelling resulting in a track for subsequent endometrial collective cell migration and onset of adenomyosis. Moreover, abnormal myometrial GABA synaptic transmission may contribute to dysmenorrhoea in women with adenomyosis and is a possible target for novel therapeutic development. Prolactin signalling abnormalities may serve as another opportunity for therapeutic intervention., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research Question: Is there a difference in live birth rate between a freeze-only strategy and fresh embryo transfer, and what is the effect of varying progesterone concentrations on the day of human chorionic gonadotrophin (HCG) administration?, Design: A secondary analysis of data from three randomized trials comparing the live birth rate after elective frozen versus fresh embryo transfer, which respectively enrolled 1508 women with polycystic ovary syndrome, 2157 ovulatory women who underwent cleavage-stage embryo transfer and 1650 ovulatory women who underwent single blastocyst transfer. Women were randomly assigned to the frozen or fresh embryo transfer group in the original trials. The primary outcome was live birth rate after the initial embryo transfer., Results: The live birth rate after a freeze-only strategy was consistently higher than fresh embryo transfer at any progesterone concentration on the day of HCG administration. Nonetheless, the between-group difference in live birth rate after frozen versus fresh embryo transfer was greater in women with progesterone concentrations ≥1.14 ng/ml (52.7% versus 37.3%, odds ratio (OR) 1.88, 95% confidence interval (CI) 1.55-2.27, P = 7.89  ×  10 -11 ) than in women with progesterone concentrations <1.14 ng/ml (53.3% versus 48.1%, OR 1.23, 95% CI 1.08-1.41, P = 0.002). In women with progesterone concentration ≥1.14 ng/ml, frozen embryo transfer also resulted in higher rates of conception and clinical pregnancy than fresh embryo transfer., Conclusion: In women with normal or high ovarian response, a freeze-only strategy resulted in a higher live birth rate than fresh embryo transfer, irrespective of progesterone concentration. Moreover, women with progesterone concentration ≥1.14 ng/ml may benefit more from a freeze-only strategy., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. 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.)

Research Question: Does an association exist between serum anti-Müllerian hormone (AMH) level, the marker of biological ovarian age, and embryonic aneuploidy risk in recurrent spontaneous miscarriage (RSM) patients of reproductive age?, Design: This retrospective study included a total of 422 IVF cycles of 394 unexplained RSM patients undergoing preimplantation genetic testing for aneuploidy (PGT-A), enrolled from January 2014 to December 2016. Subjects were divided into three groups according to the 25th (1.50 ng/ml) and 75th (5.60 ng/ml) percentiles of AMH level (Group 1: low AMH <1.50 ng/ml [N = 107], Group 2: normal AMH 1.50- < 5.60 ng/ml [N = 210] and Group 3: high AMH ≥ 5.60 ng/ml [N = 105])., Results: There was a significant difference in embryonic aneuploid rate between AMH groups (66.7% versus 42.9% versus 50.0%, Groups 1 to 3, respectively, P = 0.006). It was significantly higher in the low AMH group (Group 1) compared with that in the normal AMH group (Group 2, P 1vs2 = 0.002) and high AMH group (Group 3, P 1vs3 = 0.015). After age stratification, embryonic aneuploidy rate was still significantly different among AMH groups with a similar trend in women ≥35 years old (68.2% versus 54.4% versus 51.0%, P = 0.038, P 1vs2 = 0.025, P 1vs3 = 0.035), but not in young subjects., Conclusions: These findings indicate that low AMH level was associated with increased risk of embryo aneuploidy only in women of advanced age. Maternal diminished ovarian reserve along with oocyte ageing may contribute to impaired chromosomal competence of the embryo., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Leukaemia inhibitory factor (LIF) affects many reproductive activities, including follicular development, embryo implantation and growth. The aim of this study was to evaluate LIF concentrations in serum and follicular fluid of women with PCOS and controls who underwent IVF with embryo transfer (IVF-ET). Serum and follicular fluid LIF concentrations were lower in women with PCOS compared with controls. Oestradiol concentrations in follicular fluid were higher in PCOS subjects compared with controls. LIF concentrations in serum (r = 0.6263, P < 0.05) and follicular fluid (r = 0.7093, P < 0.05) were negatively correlated with oestradiol concentration in the PCOS group. LIF concentrations in follicular fluid showed no difference between women who conceived and women who did not in both PCOS and control groups. However, LIF concentrations in embryo culture medium were higher in women who conceived following IVF compared with women who did not, in combined PCOS and control groups. The findings indicate that low LIF concentrations in serum and follicular fluid may contribute to disordered folliculogenesis in PCOS. LIF concentrations in embryo culture medium may predict the outcome of IVF treatment., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disease. Previous studies indicate that genes GGT1 and HNF1A may contribute to the abnormal glucose metabolism and altered lipid profile that are important clinical features of PCOS. In the current study, the correlation between polymorphisms in the GGT1 and HNF1A genes and PCOS was explored. A total of 310 family trios were studied and the transmission disequilibrium test (TDT) was used to assess the linkage between PCOS and three single-nucleotide polymorphisms (SNP) (rs4820599 of GGT1, rs7305618 and rs2393791 of HNF1A). No deviations from HWE were detected. None of the three SNP markers showed significant transmission disequilibrium in PCOS family trios (rs4820599: GGT1 gene, χ 2 = 1.067; rs7305618: HNF1A gene, χ 2 = 0.013; rs2393791: HNF1A gene, χ 2 = 0.031). In conclusion, no significant evidence supported a relationship between genes GGT1 and HNF1A and PCOS in the current family trios., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Autoimmune pathogenesis is responsible for a subset of primary ovarian insufficiency (POI) cases. The significance of autoantibodies for POI, however, remains unclear. A total of 250 women with idiopathic POI and 256 age-matched healthy women were enrolled. The presence in serum of adrenal cortex autoantibody (AAA), detected by indirect immunofluorescence and non-organ-specific antibodies, including antinuclear antibody, anti-cardiolipin antibody, and anti-double stranded DNA antibody, detected by enzyme-linked immunosorbent assay, was compared. Ovarian biopsy was carried out for histology assessment. Adrenal function was followed-up in 15 women with POI who were positive for AAA. Higher frequency of positive AAA was observed in women with POI (19.2%) compared with controls (5.9%, P < 0.01). No difference in anti-cardiolipin antibody, antinuclear antibody and anti-double stranded DNA antibody was found between the two groups. Ovarian biopsies in 13 women with POI (six AAA positive and seven negative) showed atrophic ovaries devoid of follicles. One out of fifteen women positive for AAA had symptoms of adrenal insufficiency 3 years after POI diagnosis. Significantly higher positive frequency of AAA in POI patients suggests the role of autoimmune disturbance in pathogenesis. Therefore, AAA may serve as a biomarker for ovarian autoimmunity., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Insights into common genetic susceptibility between primary ovarian insufficiency (POI) and natural or early menopause have delivered an innovative way of assessing the genetic mechanisms involved in POI. PRIM1 plays a crucial role in DNA replication by synthesizing RNA primers for Okazaki fragments. It is closely associated with age at natural menopause, early menopause and POI in European women. In this study, we aimed to investigate whether mutations in PRIM1 contribute to POI in Chinese women. All exons and exon-intron boundaries of PRIM1 gene were sequenced in 192 Han Chinese women with non-syndromic POI. No plausible mutations were identified. The results suggest that the perturbations in PRIM1 gene are not a common explanation for POI in Chinese women., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This retrospective cohort study observed the live birth rates as well as cumulative live birth rates in women with poor ovarian response (POR) undergoing IVF-embryo transfer treatment, stratified for age and cycle number. Four hundred and one patients with POR diagnosed according to the Bologna criteria were enrolled and 700 IVF-ET cycles were analysed. The overall live-birth rate per cycle was 18.3%. From cycle 1 up to cycle 3, the live-birth rates decreased significantly from 22.2% to 11.1%. The live-birth rate fell to 2.4% in cycles 4 and over. When age advanced, the live birth rates decreased obviously (P < 0.01): 30.0% for women < 35 years old, 17.0% for those 35-40 years old, and 9.0% for women older than 40 years. Similarly, the cumulative live birth rates dropped from 48.0% (< 35 years) to 16.9% (≥ 40 years) accordingly. Younger patients (< 35 years old) with POR achieved better pregnancy results compared with patients of advanced age. Extremely low live-birth rates could be anticipated after three unsuccessful cycles; therefore it may not be appropriate to suggest more IVF cycles in POR women., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Exonuclease 1 (EXO1) is required for both DNA repair and meiosis. Inactivation of EXO1 gene in mice leads to infertility. This study aimed to investigate whether variants in the EXO1 gene contribute to human premature ovarian failure (POF). The coding region of EXO1 was sequenced in 186 Han Chinese patients with non-syndromic POF. No plausible mutation was detected. The results suggest that mutations in the coding region of EXO1 may not be responsible for POF in Han Chinese women., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

HELQ, a member of DNA repair gene family, is an enzyme required for DNA strands cross-links repair and closely related to age at natural menopause. It also possesses a critical role in the germ cell maintenance, and loss of HELQ gene leads to subfertility. The aim of the present study was to investigate whether mutations in HELQ contribute to premature ovarian failure (POF) in Chinese women. A cohort of 192 patients with POF was enrolled. All exons and exon-intron boundaries of genomic DNA were amplified and sequenced. Six known single-nucleotide polymorphisms were identified in both POF and control groups, including rs1494961, rs13141136, rs7665103, rs11099600, rs2047210 and rs12645412. No mutation was identified. Our study indicates for the first time that mutations in the coding sequence of the HELQ gene may not be responsible for premature ovarian failure in Chinese Han population., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In this retrospective study, the relationship between demographic characteristics, past medical history, general lifestyle habits and susceptibility of premature ovarian failure (POF) in Han Chinese population was investigated. Five hundred and fifty-three patients with POF and 400 women with normal ovarian function were recruited. A questionnaire was designed to gather information from responders. Logistic regression was carried out to calculate odds ratios (OR), 95% confidence intervals (95% CI) and P-values. History of pelvic surgery, mumps, having relatives with menstrual abnormalities and exposure to chemical agents were significantly associated with increased risk of POF (OR 5.53 [2.15 to 14.23]; 3.26 [2.38 to 4.47]; 28.12 [8.84 to 89.46]; 4.47 [2.09 to 9.58]). Vegetarian diet, tea and mineral water consumption reduced the risk of POF (OR 0.27 [0.19 to 0.37]; 0.04 [0.03 to 0.07]; 0.63 [0.47 to 0.85], respectively). Heredity, pelvic surgery, mumps and exposure to chemical agents were identified as risk factors for POF, whereas vegetarian diet, tea consumption and mineral water drinking were protective. Therefore, genetic consultation could help those women whose relatives manifested an early or premature menopause to avoid the consequences of possible premature ovarian function cessation. Avoidance of exposure to endocrine disrupters and flavonoids intake should be considered., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

KIAA0319L, PXK and JAZF1 gene polymorphisms were investigated to determine whether they conferred susceptibility to unexplained recurrent pregnancy loss (URPL) in a group of Chinese Han patients. Genotyping and sequencing of the single nucleotide polymorphisms (SNP) rs2275247(A/G) in KIAA0319L, rs2176082(C/T) and rs6445975(G/T) in PXK and the rs1635852(C/T) in JAZF1 were carried out in 84 couples with URPL and 102 healthy couples with at least one live birth. Frequencies of the SNP rs2176082(C/T) in PXK gene were significantly different between women with URPL and control women: P < 0.05; OR 95% CI 0.530 (0.287 to 0.979); OR 95% CI 0.482 (0.254 to 0.911) but were not significantly different after Bonferroni correction. The frequencies of the SNP rs2176082(C/T) in PXK gene showed no difference between the husband of a woman with URPL and a control husband: OR 95% CI 1.494 (0.821 to 2.721); OR 95% CI 1.567 (0.841 to 2.921). No statistically significant differences were observed in the distribution of any genotype or allele frequency or any genetic model of the other three SNPs between couples with URPL and control couples. Therefore, the rs2176082(C/T) polymorphism of PXK might play a possible role in the development of URPL in Chinese Han women., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A previous genome-wide association study of polycystic ovary syndrome (PCOS) identified several susceptibility loci. TOX3 is the nearest gene to signal rs4784165. In the present study, all exons and exon-intron boundaries of TOX3 were amplified and sequenced in 200 Chinese women with PCOS. A 3-bp nucleotide deletion of CAG repeat and two known single nucleotide polymorphisms were identified. No plausible pathogenic mutations were detected. The results suggest that mutations in TOX3 are not common in Chinese Han women with PCOS., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

HOXA genes in groups 7-13 have been proven to play a role in determining positional identity along the genitalia axis. The aim of the present study was to explore the relationship between HOXA7 and HOXA9 mutations and Müllerian duct abnormalities (MDA). One hundred and ninety-two Chinese patients with MDA abnormalities and 192 healthy controls were recruited. All coding regions of HOXA7 and HOXA9 were amplified and sequenced directly. Rs2301721 and rs2301720 in HOXA7, rs35355140 and rs7810502 in HOXA9 were identified in patients with MDA and controls. One rare single nucleotide polymorphism rs189587233 in 3' UTR of HOXA9 gene was detected in one patient with didelphic uterus and absent in the 192 controls. This polymorphism, however, is known to exist in the normal Chinese population. Our results indicated that variants in the HOXA7 and HOXA9 genes were not common in Chinese women with Müllerian duct abnormalities., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a complex disease involving genetic and environmental components. Tumour necrosis factor a (TNFa) is a proinflammatory cytokine in the pathogenesis of PCOS. The genetic association between polymorphisms of TNFa gene and PCOS was investigated. A family based study was conducted with 216 family trios (648 participants) having a proband with PCOS. Transmission disequilibrium test (TDT) was used to analyse the association between two single nucleotide polymorphisms (SNP) (rs1799964, rs1799724) of TNFa gene and PCOS. Minor allele frequencies of the SNP were 0.178 (rs1799964) and 0.118 (rs1799724). The two SNP were in Hardy-Weinberg equilibrium; TDT was only conducted when one parent was heterozygous. Of 216 trios, 112 trios of rs1799964 and 76 trios of rs1799724 were tested. A significant difference in transmission was found for rs1799964 (transmitted: non-transmitted = 73 : 39; χ(2) = 10.321; P = 0.0013). rs1799724 showed no evidence of an association with PCOS; risk alleles were over transmitted (transmitted: non-transmitted = 43 : 33; χ(2) = 1.316). Transmission disequilibrium of the two SNP indicated that rs1799964 may participate in the pathogenesis of PCOS in Chinese women. These data provide a basis for further studies of TNFa in the cause of PCOS., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The gene PGRMC1 is highly expressed in the granulose and luteal cells of rodent and primate ovaries. Its role in anti-apoptosis and regulating cell-cycle progression suggests a role in regulating follicle growth. The hypothesis is supported by the study in mice and studies in Sweden. In this study, the coding exons of PGRMC1 were sequenced among 196 Chinese women with premature ovarian failure (POF) and 200 controls, and one novel missense mutation was identified (C.556C>T, p. Pro186Ser) in the POF group and one novel SNP (C.533C>T, p. Trh177Ile) was identified in both groups. The mutation is not considered causative because protein prediction did not indicate a deleterious effect. It is concluded that coding mutations of PGRMC1 do not seem to be a common cause of the disease in Han Chinese women. Future studies in larger cohorts from other ethnic groups are necessary to establish the role of PGRMC1 in POF., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The insulin receptor (INSR), which is an indispensable component of the insulin-signalling pathway, could be a plausible candidate gene for polycystic ovary syndrome (PCOS). This study was designed to determine whether an association exists between three SNP variants (rs3786681, rs17253937 and rs2252673) of the INSR gene and PCOS in Han Chinese. A total of 224 family trios (672 participants in total) were enrolled in this family-based transmission disequilibrium test. Genotypes were obtained by sequencing. A weak association was detected in rs2252673 (P = 0.027), which indicated that INSR may confer an increased susceptibility to PCOS in Chinese. Additionally, the association between INSR gene variants and clinical and metabolic characteristics of women with PCOS was investigated. Carriers of the CG and GG genotypes in women with PCOS were slightly associated with higher cholesterol concentration (t = 2.072, P = 0.048) and lower high-density lipoprotein cholesterol concentration (t = 2.274, P = 0.026). The minor allele conferred increased odds of PCOS independently of body mass index. The present data may provide a basis for further studies of the role of the INSR in the aetiology of PCOS., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

As a member of the homeobox (HOX) gene family, HOXA11 is expressed in the primordia of lower uterus and cervix during fetal life and is essential for endometrial development and embryo implantation in the adults. The aim of the present study was to investigate whether mutations in HOXA11 contribute to Müllerian duct anomalies (MDA) in Chinese. A cohort of 192 patients with MDA and 192 healthy controls was enrolled. Genomic DNA was extracted. All exons and exon-intron boundaries were amplified and sequenced. One novel synonymous variant (c.774G>A) and one known single-nucleotide polymorphism were identified, both of which were not found in the matched controls. The results suggest that mutations in the coding region of HOXA11 are not common in Chinese women with MDA. As a member of the homeobox gene family, HOXA11 is expressed in the primordia of lower uterus and cervix during fetal life and is essential for endometrial development and embryo implantation in the adults. The aim of the present study was to investigate whether mutations in HOXA11 contribute to Müllerian duct anomalies (MDA) in Chinese. A cohort of 192 patients with MDA and 192 healthy controls was enrolled. Genomic DNA was extracted. All exons and exon-intron boundaries were amplified and sequenced. One novel synonymous variant (c.774G>A) and one known single-nucleotide polymorphism were identified, both of which were not found in the matched controls. The results suggest that mutations in the coding region of HOXA11 are not common in Chinese women with MDA., (Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The WNT9B gene is a common organizing signal regulating different segments of the mammalian urogenital system and plays a primary role in the development of the female reproductive tract. The aim of the present work was to examine the presence of WNT mutations in a population of women with Müllerian duct abnormalities (MDA) in order to elucidate whether mutations in WNT9B are causative for MDA in Chinese women. Initially, 191 Chinese MDA patients and 192 healthy individuals (controls) were recruited. All coding regions were amplified by PCR and sequenced to search for variants. To verify the initial results, the numbers of patients and ethnic-matched controls were expanded to 542 and 563, respectively. One known single-nucleotide polymorphism and four novel variants were identified in the first stage: two were synonymous; the other two were rare nonsynonymous novel variants (c.566G>A (p.Arg189Gln) and c.773G>A (p.Arg258His)). None of the four novel variants was found in controls. In the second stage, both novel nonsynonymous variants were detected in MDA cases and controls. The results indicate that mutations in the coding sequence of WNT9B are not responsible for MDA in the Chinese population., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether an association exists between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). A significant difference was found in rs2287798 between PCOS cases and controls (P=0.0007). Possible associations between AQP8 genotypes and three different phenotypes of this syndrome were investigated. The results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role. Aquaporin 8 (AQP8) has been identified as a novel gene participating in female reproductive physiology. The present study was designed to determine whether there is an association between AQP8 and polycystic ovary syndrome (PCOS). This study recruited 192 women with PCOS and 191 controls. High-resolution melting and sequencing were employed to investigate the genotypes of six single-nucleotide polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798 and rs2287796). We observed a significant difference in allele frequency of rs2287798 between PCOS cases and controls (P=0.0007). The possible association between AQP8 genotypes and three different phenotypes of this syndrome in this locus were investigated. Our results support the earlier evidence for a possible role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to elucidate its functional role., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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.)

This study assessed the true accuracy of follicular output rate (FORT) as a prognostic indicator of response to FSH and reproductive competence after IVF/intracytoplasmic sperm injection. A total of 1643 cycles, including 140 polycystic ovary syndrome (PCOS) patients who underwent ovarian stimulation, were studied. FORT was calculated as the ratio of preovulatory follicle count on the day of stimulation×100/small antral follicle count (3-10mm in diameter) at baseline. Low, medium and high FORT groups were defined according to tertile values. Among 1503 non-PCOS cycles, numbers of retrieved oocytes and of all embryos that could be transferred, as well as rates of good-quality embryos, embryo implantations and clinical pregnancies, progressively increased with FORT. In PCOS patients, FORT were significantly lower in patients who achieved clinical pregnancy compared with those who did not (0.56±0.21 versus 0.66±0.29, P=0.031). Fertilization and good-quality embryo rates were significantly higher with medium FORT than low and high FORT (P=0.001 and P=0.047, respectively). Medium FORT in PCOS patients and high FORT in non-PCOS patients may predict better outcomes for IVF/ICSI., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

P27 and SKP2, a major regulator of P27, play a crucial role in ovarian function in mice. Both P27-deficient and SKP2-deficient female mice develop premature ovarian failure (POF). The coding regions of SKP2 and P27 were examined in 200 Chinese women with POF and 200 control volunteers. This study is the first to investigate SKP2 in POF. No plausible pathogenic mutations were detected. The results suggest that mutations in SKP2 and P27 are not common in Chinese Han women with POF., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to determine if mutations in WNT5A contribute to the aetiology of Müllerian duct abnormalities (MDA) in 189 Chinese women. Three novel single-nucleotide polymorphisms (SNP; IVS2 - 115G >A, IVS4 + 66T >A, IVS4 + 102G >T) in introns 2 and 4 as well as one known SNP (rs62620048) in exon 6 were detected, but no causal mutations were observed. The results suggested that mutations in WNT5A may be not responsible for MDA in Chinese women. Genetic factors are considered to be one of the major causes of Müllerian duct abnormalities (MDA). Previous studies have shown that the WNT5A gene is crucial for the patterning and cytodifferentiation of the female reproductive tract. The study included 189 well-characterized patients with MDA who were screened for variants of WNT5A for the first time. Three novel single-nucleotide polymorphisms (IVS2 - 115G >A, IVS4 + 66T >A, IVS4 + 102G >T) in introns 2 and 4 as well as one known single-nucleotide polymorphism (rs62620048) in exon 6 were detected, but no causal mutations were observed., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The coding region of the disrupted meiotic cDNA gene (DMC1) was examined in 192 Chinese women with premature ovarian failure. Two known single-nucleotide polymorphisms, c.8632C>T in intron 4 and c.32377G>C in intron 10, were identified. The results suggest that mutations in the coding sequence of DMC1 are not associated with premature ovarian failure in Chinese women. The coding region of the disrupted meiotic cDNA gene (DMC1) was examined in 192 Chinese women with premature ovarian failure. Premature ovarian failure is defined as secondary amenorrhoea, infertility, oestrogen deficiency, and elevated gonadotrophin concentration in women younger than 40 years. DMC1 is a meiosis-specific gene, encoding a protein essential for meiotic homologous recombination. It participates in the formation of synaptonemal complexes and repair of double-strand breaks at recombination hotspots. Two known single-nucleotide polymorphisms, c.8632C>T in intron 4 and c.32377G>C in intron 10, were identified. No additional single-nucleotide polymorphisms or mutations were found. The results suggested mutations in the coding sequence of DMC1 are not associated with premature ovarian failure in Chinese women., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

As an abundant source that involves fewer ethical considerations, human abnormally fertilized zygotes are superior to oocytes as therapeutic cloning recipients of nuclear transfer. However, more effective manipulation conditions should be developed for somatic cell nuclear transfer (SCNT) studies using human abnormally fertilized zygotes as recipients. The present study found that the use of cytochalasin B was not necessary for, and even harmful to, the enucleation of human zygotes. This study also decreased the DNA methylation levels in reconstructed embryos using a DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), in an attempt to correct the abnormalities in DNA methylation that might play an important role in the failure of embryo development. After 5-aza-dC treatment and nuclear transfer (NT-Aza group), 32.7% of reconstructed embryos developed to the 8-cell stage, which is a much higher percentage than that of the nuclear transfer only (NT) group (11.1%). The DNA methylation level in the NT-Aza group was significantly lower than that of the NT group, as determined by 5-methylcytosine immunodetection. Based on the present results, this study recommends performing the enucleation procedure without cytochalasin B treatment and using 5-aza-dC in the culture of reconstructed embryos in human SCNT studies., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The paired box gene 2 (PAX2) has been proven to be a crucial gene during organogenesis of the urogenital system in mice models. This study was aimed to explore the relationship between PAX2 mutations and human Müllerian duct abnormalities (MDA). A total of 192 Chinese MDA patients (15 cases of uterine aplasia and 177 of incomplete Müllerian fusion) and 192 ethnic-matched controls were recruited from 2009 to 2011. Coding regions of PAX2 of MDA cases were amplified and sequenced. One rare novel synonymous variant (c.320G>A) was discovered in one patient with uterus didelphys, whereas this variant was not found in the control group. Mutations in PAX2 may be not a common cause of MDA., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This is a retrospective, observational study to determine how often repeated consecutive miscarriages occur consistently in the same gestational period, including 1589 miscarriages among 543 women with recurrent miscarriage. In women who had two miscarriages only, 49.17% of both miscarriages occurred in the same gestational period, which was significantly higher than the expected probability of 34.54% (P<0.01). The proportions of all miscarriages occurring in the same gestational period in women with three, four and five or more miscarriages were 28.72%, 19.44% and 18.60%, compared with the expected probabilities of 14.36% (P<0.01), 6.57% (P<0.05) and <3.15% (P<0.05). The proportions of miscarriages occurring consistently in the same gestational period are higher than the theoretical probabilities calculated for the whole population., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The WNT4 gene plays a crucial role in sexual differentiation and female genital tract development. This study screened WNT4 for mutation in 189 Chinese women with Müllerian duct abnormalities (10 Mayer-Rokitansky-Küster-Hauser syndrome, five Müllerian aplasia and 174 incomplete Müllerian fusion) and detected no perturbation that would indicate a major role for WNT4. Only one novel synonymous mutation (c.1091G>A) in exon 5 and one known single-nucleotide polymorphism (rs16826648) in exon 2 were found. The results suggest that WNT4 might not contribute to the aetiology of Müllerian duct abnormalities in Chinese women., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)