Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Association of sleep duration and sleep quality with gestational diabetes mellitus in pregnant women after treatment with assisted reproductive technology: A birth cohort study.

Maternal sleep is closely related to subsequent gestational diabetes mellitus (GDM) in natural pregnancies. However, whether this connection exists in pregnant women conceiving with the help of assisted reproductive technology (ART) has not been confirmed. Hence, in this study, we evaluated whether early pregnancy sleep duration or sleep quality is associated with gestational diabetes mellitus in ART-pregnant women, as well as the influence of maternal age on this association. This prospective birth cohort study included 856 pregnant women who successfully conceived with the help of ART treatment. The sleep parameters of ART-pregnant women were assessed using the Pittsburgh Sleep Quality Index (PSQI) in early pregnancy. We explored the association between sleep and the risk of gestational diabetes mellitus using an unconditional binary logistic regression model. Different models were constructed to examine the robustness of the estimation by incorporating different confounding factors. Multivariable logistic regression revealed that sleep duration of more than 10 h among ART-pregnant women was significantly associated with the risk of GDM, and the association between sleep duration and gestational diabetes mellitus varied by maternal age. We found an increased risk of subsequent gestational diabetes mellitus with increasing sleep duration only in pregnant women aged <35 years. Additionally, no statistically significant association between sleep quality and gestational diabetes mellitus was found in this study. In conclusion, excessive sleep duration (≥10 h) is associated with a high risk of gestational diabetes mellitus in pregnant women who conceived with the help of assisted reproductive technology, and maternal age may modify this effect.

Effect of male HBV infection on the outcomes of IVF/ICSI cycles: a retrospective cohort study based on propensity score matching.

ABSTRACT: This study aimed to investigate the effects of male hepatitis B virus (HBV) infection on male fertility, embryonic development, and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. We performed a retrospective cohort study that included 3965 infertile couples who received fresh embryo transfer cycles for the first time at the Fujian Maternity and Child Health Hospital (Fuzhou, China) from January 2018 to January 2021. Infertile couples were categorized based on their HBV infection status into the HBV group (HBV-positive men and HBV-negative women) and the control group (HBV-negative couples). A 1:1 propensity score matching was performed with relatively balanced covariates. Baseline characteristics, semen parameters, laboratory outcomes, clinical outcomes, and obstetric and neonatal outcomes were compared between groups. After propensity score matching, 821 couples were included in each group. Both groups had similar semen parameters and obstetric and neonatal outcomes. The HBV group showed a significantly lower live birth rate than the control group (P < 0.05). The HBV group had a significantly higher abortion rate than the control group (P < 0.05). The rates of high-quality embryos and blastocyst formation were significantly lower in the HBV group than those in the control group (both P < 0.05). In conclusion, in couples who undergo IVF/ICSI, male HBV infection reduces the live birth rate and increases the risk of miscarriage. However, the incidence of low birth weight in women with IVF/ICSI does not increase with male HBV infection.

Mfn2 regulates mitochondria-associated ER membranes to affect PCOS oocyte development.

This study aimed to investigate the role of mitochondrial-related protein Mfn2 in polycystic ovary syndrome (PCOS) and its impact on oocyte development. The pathological features of PCOS model mice were confirmed by hematoxylin-eosin staining and immunohistochemistry. The expression of Mfn2 and mitochondrial-related proteins in PCOS oocytes and granulosa cells was detected by qRT-PCR and Western blot. Mitochondrial quantity was measured by Mito-Tracker staining, and the structure of mitochondria-associated ER membranes (MAMs) was observed by transmission electron microscopy. The results showed that Mfn2 was significantly downregulated in PCOS oocytes and granulosa cells, and its expression was inhibited in oocytes at different developmental stages. Moreover, the structure of MAMs was also disrupted. Downregulation of Mfn2 expression led to a reduction in mitochondrial quantity in oocytes and granulosa cells, as well as disruption of MAM structure, while overexpression of Mfn2 had the opposite effect. In conclusion, this study indicates that Mfn2 affects the development of PCOS oocytes by regulating MAMs and may be involved in maintaining the stability of MAM structure and function, thereby affecting mitochondrial quantity and function. These findings provide new insights into the pathogenesis and treatment of PCOS.

Development and validation of a nomogram model for predicting clinical pregnancy in endometriosis patients undergoing fresh embryo transfer.

PURPOSE: To construct and validate a nomogram model for predicting clinical pregnancy in individuals with endometriosis undergoing fersh embryo transfer (ET). METHODS: A retrospective analysis was conducted on 1630 individuals with endometriosis who underwent in vitro fertilization (IVF) with fresh embryo transfer at the Reproductive Medicine Center of Fujian Maternity and Child Health Hospital from January 2018 to January 2022. The research population was sorted into two groups through random sampling, namely, the model group (n = 1141) and the validation group (n = 489), with a ratio of 7:3. Univariate analysis was utilized to determine the influencing factors for clinical pregnancy in the model group. The LASSO algorithm was utilized to select the optimal matching factors, which were then included in a multifactorial forward stepwise logistic regression to determine independent influencing factors and develop a nomogram. The discrimination, accuracy, and clinical efficacy of the prediction model were analyzed utilizing the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve. RESULTS: Through multivariate-logistic-regression analysis, these factors were identified as independent influencing factors for the clinical pregnancy in endometriosis patients undergoing fresh embryo transfer: female age (OR = 0.933, 95% CI = 0.902-0.965, P < 0.001), ASRM stage (OR = 0.384, 95% CI = 0.276-0.532, P < 0.001), postoperative to IVF duration (OR = 0.496, 95% CI = 0.356-0.688, P < 0.001), antral follicle count (AFC) (OR = 1.076, 95% CI = 1.013-1.161, P = 0.045), anti-Müllerian hormone (AMH) (OR = 1.202, 95% CI = 1.073-1.35, P = 0.002), Gonadotrophin-releasing hormone (GnRH) agonist protocol (OR = 1.536, 95% CI = 1.109-2.131, P = 0.01), number of oocytes retrieved (OR = 1.154, 95% CI = 1.067-1.249, P < 0.001), number of high-quality cleavage embryos (OR = 1.261, 95% CI = 1.164-1.369, P < 0.001), and number of embryos transferred (OR = 1.957, 95% CI = 1.435-2.679, P < 0.001). A prediction model for estimating the clinical pregnancy probability in individuals with endometriosis was constructed per these identified independent factors. The ROC showed an area under the curve (AUC) of 0.807 (95% CI = 0.782-0.832) in the model group and 0.800 (95% CI = 0.761-0.84) in the validation group. The Hosmer-Lemeshow test demonstrated no statistically significant difference between predicted and actual clinical pregnancy probabilities (P > 0.05). The clinical decision curve demonstrated that both the model and the validation groups achieved maximum net benefit at threshold probability values of 0.08-0.96 and 0.16-0.96, indicating good clinical efficacy within this range of threshold probabilities. CONCLUSION: Female age, ASRM stage, postoperative to IVF duration, stimulation protocol, AFC, AMH, number of oocytes retrieved, number of high-quality cleavage embryos and number of transferred embryos are independent influencing factors for the clinical pregnancy rate in individuals with endometriosis receiving fresh embryo transfer. The nomogram model based on these factors demonstrates good clinical predictive value and efficacy, providing a basis for clinical prognosis, intervention, and individualized medical treatment planning.

Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility.

Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.

Impact of thyroid autoimmunity on pregnancy outcomes in euthyroid women following fresh/frozen-thawed embryo transfer.

OBJECTIVE: To investigate whether thyroid autoimmunity (TAI) is associated with assisted reproductive technology (ART) outcomes in euthyroid women undergoing fresh embryo transfer (ET) and frozen-thawed embryo transfer (FET). DESIGN: A retrospective cohort study. Pregnancy and neonatal outcome after fresh ET or FET were compared between the positive and negative thyroid autoimmune antibody groups. PATIENTS: A total of 5439 euthyroid women who started their ART cycle at our centre between 2015 and 2019 were included. RESULTS: The thyroid antibody positive group had a greater mean age than the thyroid antibody negative group (32(29,35) vs. 31(28,34), p < .001). Women with positive thyroid antibody presented with a higher prevalence of diminished ovarian reserve (DOR) (9.1% vs. 7.1%, p = .026) and lower number of oocyte retrieved (9(5,15) vs. 10(6,15), p = .020), but difference was not significant after adjusting for age. The pregnancy rate, live birth rate, pregnancy loss rate, preterm delivery rate and low birthweight rate between the thyroid antibody positive and thyroid antibody negative groups were comparable both in fresh ET cycles and FET cycles. Subanalysis of the treatment outcomes when using a stricter threshold of TSH of 2.5 mIU/L showed no difference to that achieved when using an upper limit of 4.78 mIU/L. CONCLUSIONS: The present study reveals that patients with anti-thyroid peroxidase antibodies (TPOAbs) and/or antithyroglobulin antibodies (TgAbs) showed no significant differences in pregnancy outcomes following fresh ET and FET when compared with patients with negative thyroid antibodies.

GOLPH3 modulates expression and alternative splicing of transcription factors associated with endometrial decidualization in human endometrial stromal cells.

Endometrial decidualization is a decidual tissue formed by the proliferation and re-differentiation of endometrial stroma stimulated by decidualization inducing factors. It is very important for the proper maintenance of pregnancy. Previous studies speculated that Golgi phosphoprotein 3 (GOLPH3) may have a regulatory role in the process of endometrial decidualization, while the specific molecular mechanisms of GOLPH3 is unclear. In this part, GOLPH3 was silenced in human endometrial stromal cells (hESCs), and the transcriptome data (RNA-seq) by GOLPH3 knockdown (siGOLPH3) was obtained by high-throughput sequencing technology so as to analyze the potential targets of GOLPH3 at expression and alternative splicing levels in hESCs. Through bioinformatics analysis, we found that siGOLPH3 can significantly affect the overall transcriptional level of hESCs. A total of 6,025 differentially expressed genes (DEGs) and 4,131 differentially alternative splicing events (DASEs) were identified. Through functional cluster analysis of these DEGs and genes where differential alternative splicing events are located, it is found that they are enriched in the PI3K/Akt signaling pathway, RNA splicing and processing, transcription factors and other pathways related to endometrial decidualization and important biological processes, indicating the important biological function of GOLPH3. At the same time, we focused on the analysis of the transcription factors regulated by GOLPH3, including gene expression regulation and the regulation of variable splicing. We found that GOLPH3can regulate the expression of transcription factors such as LD1, FOSL2, GATA2, CSDC2 and CREB3L1. At the same time, it affects the variable splicing mode of FOXM1 and TCF3. The function of these transcription factors is directly related to decidualization of endometrium. Therefore, we infer that GOLPH3 may participate in endometrial de membrane by regulating expression and alternative splicing levels of transcription factors. We further identified the role of GOLPH3 in the transcriptional mechanism. At the same time, it also expands the function mode of GOLPH3 protein molecule, and provides a theoretical basis for downstream targeted drug research and development and clinical application.

Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH-agonist or GnRH-antagonist protocols: A retrospective study by propensity score matching.

OBJECTIVES: Although in vitro fertilization with embryo transfer is the most effective treatment for infertile patients with endometriosis, ovarian stimulation protocols are controversial. STUDY DESIGN: We recruited 639 patients with endometriosis from January 2016 to June 2020; 111 and 528 patients were treated with the gonadotropin-releasing hormone (GnRH) antagonist and ultra-long GnRH agonist protocols, respectively. Potential baseline differences between the regimens were adjusted by propensity score matching. Clinical and laboratory data, including the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR), were compared. RESULTS: Ovulation induction required significantly longer use of gonadotropins in the GnRH agonist group. However, the GnRH agonist group had a lower starting dose of gonadotropin (all p < 0.05). Furthermore, significantly lower clinical pregnancy, implantation, and live birth rates were observed in the GnRH antagonist group receiving fresh assisted reproductive technology cycles (all p < 0.05); however, pregnancy outcomes using the subsequent freeze-thaw cycles for the same oocyte retrieval were not significantly different. CCPR and CLBR for the oocyte retrieval cycles of the antagonist and ultra-long agonist protocols were similar. The ultra-long agonist protocol resulted in more favorable implantation of fresh embryos and improved clinical outcomes of the fresh cycle. CONCLUSIONS: This novel strategy could be appropriate for endometriosis patients who are temporarily unsuitable for fresh embryo transfer. The GnRH antagonist protocol can be combined with the whole embryo freezing strategy to achieve CCPR and CLBR similar to the ultra-long agonist regimen, thus simultaneously avoiding the long pre-treatment duration of GnRH agonists during the ultra-long agonist protocol.

Analysis of relative factors and prediction model for optimal ovarian response with gonadotropin-releasing hormone antagonist protocol.

Objective: To explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with the gonadotropin-releasing hormone antagonist protocol and to establish a nomogram prediction model of ovarian response. Methods: A retrospective cohort analysis of the clinical data of 1,944 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from April 1, 2018, to June 30, 2020. According to the number of oocytes obtained, there were 659 cases in the low ovarian response group (no more than five oocytes were retrieved), 920 cases in the normal ovarian response group (the number of retrieved oocytes was >5 but ≤18), and 365 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian responsiveness were screened by logistic regression, which were the model entry variables, and a nomogram prediction model was established based on the regression coefficients. Results: There were statistically significant differences in age, anti-Mullerian hormone, antral follicle count, the diagnosis of endometriosis, decreased ovarian reserve, polycystic ovary syndrome, basal follicle-stimulating hormone and basal luteinizing hormone among the three groups (P < 0.001). Multifactorial stepwise regression analysis showed that female age (0.95 [0.92-0.97], P = 0.000), decreased ovarian reserve (0.27 [0.19-0.38]), P = 0.000), endometriosis (0.81 [0.56-0.86], P = 0.000), antral follicle count (1.09 [1.06-1.12], P = 0.000), basal follicle-stimulating hormone (0.90 [0.85-0.96], P = 0.001), Anti-Mullerian hormone (1.19 [1.13-1.26], P= 0.000) and luteinizing hormone on trigger day (0.73 [0.66-0.80], P= 0.000), were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The predictive model of ovarian responsiveness was constructed based on the above factors, and the model was verified with 589 patients' data from July 1, 2020, to December 31, 2020, at this center. The predicted ovarian response (number of eggs obtained) of a total of 450 patients was consistent with the actual results, with a coincidence degree of 76.4%, and the consistency index of the model is 0.77. Conclusion: The nomogram model was successfully developed to effectively, intuitively, and visually predict the ovary reactivity in the gonadotropin-releasing hormone antagonist protocol and provide guidance for clinical practice.

The Impact of Malignancy on Assisted Reproductive Outcomes for Cancer Survivors: A Retrospective Case-Control Study.

Background: Related studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes. Methods: This retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes. Results: This study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P<0.001) between the two groups. The total gonadotropin dose, number of oocytes retrieved, fertilization rate, cleavage rate, high-quality embryo rate, blastocyst rate and first-time embryo-transfer (ET) implantation rate were nonsignificantly lower in the cancer group than in the control group (P>0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes. Conclusions: Overall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes.

Emerging Bioactive Agent Delivery-Based Regenerative Therapies for Lower Genitourinary Tissues.

Injury to lower genitourinary (GU) tissues, which may result in either infertility and/or organ dysfunctions, threatens the overall health of humans. Bioactive agent-based regenerative therapy is a promising therapeutic method. However, strategies for spatiotemporal delivery of bioactive agents with optimal stability, activity, and tunable delivery for effective sustained disease management are still in need and present challenges. In this review, we present the advancements of the pivotal components in delivery systems, including biomedical innovations, system fabrication methods, and loading strategies, which may improve the performance of delivery systems for better regenerative effects. We also review the most recent developments in the application of these technologies, and the potential for delivery-based regenerative therapies to treat lower GU injuries. Recent progress suggests that the use of advanced strategies have not only made it possible to develop better and more diverse functionalities, but also more precise, and smarter bioactive agent delivery systems for regenerative therapy. Their application in lower GU injury treatment has achieved certain effects in both patients with lower genitourinary injuries and/or in model animals. The continuous evolution of biomaterials and therapeutic agents, advances in three-dimensional printing, as well as emerging techniques all show a promising future for the treatment of lower GU-related disorders and dysfunctions.

Age-specific random day serum antimüllerian hormone reference values for women of reproductive age in the general population: a large Chinese nationwide population-based survey.

BACKGROUND: Antimüllerian hormone, the most reliable biomarker of ovarian reserve, is widely used in various clinical situations. Antimüllerian hormone levels consistently decrease with age. However, there is no standard, age-specific reference values for antimüllerian hormone in women of reproductive age, which limits its application. OBJECTIVE: This study aimed to establish age-specific antimüllerian hormone percentile reference values for women of reproductive age. STUDY DESIGN: A nationwide, population-based cross-sectional survey was conducted between May 2019 and April 2021 in 15 provinces and municipalities in mainland China. A total of 10,053 eligible women aged 20 to 49 years were selected using a multistage stratified sampling procedure. Women who were pregnant, had undergone ovarian surgery, took hormone drugs in the past 3 months, or had an antimüllerian hormone outlier value were excluded from establishing antimüllerian hormone percentile reference values. Serum antimüllerian hormone concentrations were measured using ultrasensitive, 2-site enzyme-linked immunosorbent assays (Ansh Lab, Webster, TX) in the Reproductive Endocrinology Laboratory of Peking University Third Hospital. Generalized additive models for location scale and shape with the Box-Cox t original distribution were used to estimate the fitted antimüllerian hormone percentile reference values. RESULTS: A total of 9112 eligible women aged 21 to 49 years were included in the fitting model. The fitted 50th (2.5th-97.5th) percentiles of antimüllerian hormone values for women aged 21, 25, 30, 35, 40, 45, and 49 years were 4.83 (0.79-18.41), 4.47 (0.72-16.58), 3.67 (0.50-13.82), 2.59 (0.24-10.35), 1.35 (0.05-6.68), 0.33 (<0.01 to 3.40), and 0.04 (<0.01 to 1.77) ng/mL, respectively. The population-based decline rate of antimüllerian hormone accelerated with increasing age, especially age >35 years. The magnitude of the decline of the 25th antimüllerian hormone percentile curve was greater than that of the 75th percentile curve. CONCLUSION: This study established age-specific antimüllerian hormone percentile reference values for women of reproductive age based on a large representative sample of the general population and described antimüllerian hormone changes. These findings may facilitate antimüllerian hormone application in clinical practices.

Changes in the prevalence of polycystic ovary syndrome in China over the past decade.

Background: Polycystic ovary syndrome (PCOS) has become a major international public health concern. However, because of controversy about the diagnostic criteria and patient selection, estimates of its absolute prevalence and change with time vary greatly. Methods: We conducted two consecutive nationwide epidemiological surveys of the prevalence of PCOS in representative samples of reproductive-aged women in China in 2010 and 2020. Face-to-face interviews were performed by trained interviewers in each survey. All participants completed a questionnaire and underwent a physical examination, blood sampling, and transvaginal pelvic ultrasound. We assessed hyperandrogenism (H), chronic anovulation (O), and polycystic ovaries (P) to classify the presence of PCOS using the Rotterdam criteria. The prevalence of PCOS among reproductive-aged women was estimated after consideration of differential probabilities of selection and population distribution. We conducted a logistic regression analysis by using the probability of PCOS as a function of the survey year to acquire the trend information across the years. Findings: 28,739 respondents completed the survey, including 15,924 in the previously published 2010 survey and 12,815 in the new 2020 survey. In 2020, 826 participants could be diagnosed as having PCOS, with a weighted prevalence of 7.8% (95%CI: 7.0%, 9.0%) among women aged 20-49 years, leading to an estimate of 24.0 million women of reproductive age affected by this condition in China as a whole. The estimated prevalence in 2020 was higher than that of a decade ago despite identical research methods suggesting a two-thirds increase over the study period. Women with PCOS in 2020 also appeared to have a more severe phenotype overall than those of a decade ago, possibly reflecting a significantly higher prevalence of obesity, hyperandrogenism, and infertility. Interpretation: The prevalence of PCOS in Chinese women has increased significantly over the past 10 years. PCOS is a significant public health problem in women of reproductive age in China and national policy and guidelines should be re-examined in the light of the current data. Funding: National Key R&D Program of China and the National Natural Science Foundation of China.

Neonatal exposure of bisphenol A led to increased lipolysis of visceral adipose tissue in adult rats with DNA hypomethylation of Atgl being one of the possible underlying mechanisms.

Accumulating evidence suggests the role of developmental exposure of bisphenol A (BPA) in metabolic disorders. However, the underlying mechanism remains unclear. Using a rat model, we investigated the neonatal exposure of BPA on lipid metabolism in adult and the underlying mechanisms. From postnatal day1(PND1) to PND10, male rats were exposed to BPA via daily subcutaneous injection with 10 µg/100 µL BPA (1.24-0.5 mg/kg body weight/day, a dose below the US-EPA LOAEL). After fasting for 8 h, adult rats aged 80 days showed elevated levels of serum free fatty acid (FFA), glycerol and glucose, and increased levels of FFA and glycerol in visceral adipose tissue. The expression levels of key enzymes of lipolysis, adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl), were increased in visceral adipose tissue from BPA-exposed rats after fasting. On the other hand, transcription levels of lipogenic genes remained unchanged. Differentiation of visceral adipocyte in rats takes place neonatally. In our study, neonatal BPA exposure induced DNA hypomethylation of Atgl in visceral adipose tissue. In 3T3-L1 cell, administration of 10-7 mol/L BPA throughout the differentiation stage led to DNA hypomethylation and increased expression of Atgl. Our results suggest that neonatal exposure of BPA led to increased lipolysis of visceral adipose tissue in young adults, which will predispose individuals to multiple metabolic disorders. The DNA hypomethylation of Atgl might be one of the mechanisms underneath the long-lasting effect of neonatal BPA exposure.

A Randomized Cohort Study: Is It Worth the Time to Receive Antiandrogenic Pretreatment Before Ovulation Induction for Women With Polycystic Ovary Syndrome?

Objective: To assess the effect of antiandrogenic pretreatment using combined oral contraceptives (COCs) before ovulation induction in infertile patients with polycystic ovary syndrome (PCOS) with hyperandrogenism. Design: Prospective, randomized open-labeled cohort study. Setting: Multicenter. Patients: PCOS patients with hyperandrogenism and requiring infertility treatments. Interventions: Randomization to direct ovulation induction of letrozole (letrozole group) or ethinylestradiol/cyproterone acetate (EE/CPA) for 3 months and subsequent letrozole-induced ovulation (EE/CPA+ letrozole group). The maximum number of ovulation induction cycle was three to four. Main Outcome Measures: Ovulation rate, conception rate, ongoing pregnancy rate, and live birth rate were the main outcomes of the study. Results: There were no significant differences in the cumulative ovulation, conception, ongoing pregnancy, and live birth rates between the letrozole and EE/CPA+ letrozole groups (cumulative ovulation: 206/254 [81.10%] vs. 169/205 [82.44%], risk ratio [RR]= 1.09 [0.68,1.76], P=0.713; conception: 44/90 [48.89%] vs. 42/76 [55.26%], RR= 1.29 [0.70,2.38], P=0.413; ongoing pregnancy: 33/90 [36.67%] vs. 33/76 [43.42%], RR=1.33 [0.71,2.47], P=0.376; and live birth: 32/90 [35.56%] vs. 31/76 [40.79%], RR=1.25 [0.67, 2.34], P=0.489). Conclusions: The results of this study showed that COC pretreatment was not superior to direct letrozole-induced ovulation therapy in improving ovulation and pregnancy results in women with PCOS. There is no benefit to perform antiandrogenic therapy before ovulation induction in patients with PCOS in clinical practice. Clinical Trial Registration: www.clinicaltrials.gov, identifier ChiCTR1900022839.

Tripronuclear Zygotes in IVF Laboratory Quality Control: Experimental Evaluation and Potential Applications.

This study set out to evaluate quality control within a new in vitro fertilization (IVF) laboratory environment and of new incubators based on the culture results of tripronuclear zygotes. The representative environmental indicators within new and old IVF laboratories were monitored, and tripronuclear zygotes were cultured in the two laboratories; the results were analyzed and compared. Subsequently, tripronuclear (3PN) zygotes were cultured in both new and old incubators and the culture results were compared. No differences were found in embryo development between 3PN zygotes in the old and new laboratories. However, in the quality control test, the degeneration rate and developmental arrest rate in the new incubator early phase group were significantly increased when compared with the old incubators. Moreover, the grade I embryo rate also decreased significantly. Nevertheless, all the above comparisons in the new incubator later phase group showed no statistical significance as compared to those observed in old incubators. Tripronuclear zygotes are sensitive to the environment in IVF laboratories and can be considered useful during quality control trials of new IVF laboratories and new equipment including incubators.

The effect of age and abstinence time on semen quality: a retrospective study.

This study analyzed the effects of male age and abstinence time on semen quality and explored the best abstinence time for Chinese males among different age groups. Semen parameters, including sperm kinetics, morphology, and DNA fragmentation index (DFI), were reviewed from 2952 men. Samples were divided into six age groups (≤25 years, 26-30 years, 31-35 years, 36-40 years, 41-45 years, and >45 years) and were divided into six groups according to different abstinence time (2 days, 3 days, 4 days, 5 days, 6 days, and 7 days). The differences in semen quality between the groups were compared, and the effect of age and abstinence time on semen quality was analyzed. Significant differences were observed in semen volume, progressive motility (PR), and DFI among the age groups (all P < 0.05), and no significant differences were observed in sperm morphological parameters (all P > 0.05). There were significant differences in semen volume, PR, and DFI among different abstinence time groups (all P < 0.05) and no significant differences in sperm morphological parameters (all P > 0.05). Pearson analysis showed that male age and abstinence time were both significantly correlated with sperm kinetics and DFI (both P < 0.05), while no significant correlation was found with sperm morphological parameters (all P > 0.05). The box plots and histograms of men's age, abstinence time, and semen quality show that most semen quality parameters differ significantly between the 2 days and 7 days abstinence groups and other groups at different ages. Except for the sperm morphology parameters, sperm kinetic parameters and sperm DFI are linearly related to male age and abstinence time.

Cryopreservation of human spermatozoa by freezing testicular seminiferous tubule with novel cryopiece.

This study was carried out to evaluate the effectiveness of cryopreservation of human spermatozoa by freezing testicular seminiferous tubule with a new cryocarrier named 'novel cryopiece'. Testicular tissue (TT) was collected from patients who underwent diagnostic testicular biopsy. Overall, 35 TT samples were obtained. Each TT sample was equally divided into four groups named (e.g. G1, G2, G3 and Gc). G1 was frozen as testicular seminiferous tubule using novel cryopiece, G2 was frozen as testicular cell suspensions using novel cryopiece, G3 was frozen as testicular cell suspensions using 0.25 ml straw, and Gc was not frozen. The samples in G1 and G2 experimental groups were cryopreserved in five separate aliquots and stored in the same cryovial. The freeze-thaw sperm DNA fragmentation index (DFI) of G2 was lower than that of G3 (20.27 ± 5.40 vs 23.55 ± 6.02; p = 0.004). After thawing, spermatozoa could be found in all 35 testicular seminiferous tubule specimens in G1; however, it could not be found in 2 of 35 (5.7%) and 1 of 35 (2.9%) testicular cell suspensions samples in G2 and G3 respectively. This study indicates that novel cryopiece presented for the cryopreservation of testicular seminiferous tubules and testicular cell suspension is simple and effective.