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To investigate and analyze prevalence and risk factors of infertility at a representative rural site of Northern China. This is a cross-sectional study. We conducted a face-to-face questionnaire survey from July 2014 to October 2014 involving 5,131 women who were at childbearing age in Suizhong, a medium-sized, representative county located in Northern China. Finally, data from 4,232 valid questionnaires were analyzed. Infertility is defined as the failure to achieve a clinical pregnancy after 12 months or more of regularly unprotected sexual intercourse. Infertility prevalence in Suizhong County was 13.09% (95% CI, 12.09%-14.1%), of which the primary infertility incidence was 0.99% (95% CI, 0.72%-1.34%), and the secondary infertility incidence was 12.10% (95% CI, 11.13%-13.12%). For women, the infertility incidence of underweight women (Body Mass Index, BMI<18.5 kg/m2) was 1.5-fold higher than that of women with moderate BMI (18.5-24.9 kg/m2). The infertility incidence of women with little exercise was 4 times more than that of women with regular exercise, and 2 times more than that of women with heavy exercise. The group with moderate menstrual flow had the lowest prevalence of infertility, while both scant and excessive menstruation led to increased infertility incidence. Number of pregnancies (OR = 0.63; 95% CI, 0.51-0.79) was a protective factor for infertility, while the number of abortions (OR = 2.15; 95% CI, 1.58-2.93) was a risk factor for infertility. For men, those who stayed up late at night more than 3 times per week showed a significantly higher infertility incidence. Men who engaged in occupations with high-temperature working environment also suffered from an infertility incidence of about four times more than the others. We found significant association between women's infertility incidence with their BMI, state of exercise, amount of menstrual flow, number of pregnancies and number of abortions. As for men, both staying up late and engaging in high-temperature occupations are independent factors affecting their fertility.

Background Intrauterine adhesion (IUA) is a major cause of female secondary infertility. We previously demonstrated that menstrual blood-derived stromal cell (MenSC) transplantation helped severe IUA patients have pregnancy and endometrium regeneration. We also initiated platelet-rich plasma (PRP) acted as a beneficial supplement in MenSC culturing and a potential endometrial receptivity regulator. Here, we investigated the therapeutic effect of combined transplantation of MenSCs with PRP in rat IUA models and the mechanisms of MenSCs in endometrium regeneration. Methods Rat IUA models were established by intrauterine mechanical injured. Nine days later, all rats were randomly assigned to four groups received different treatment: placebo, MenSC transplantation, PRP transplantation, and MenSCs + PRP transplantation. The traces of MenSCs were tracked with GFP label. Endometrial morphology and pathology, tissue proliferation, inflammation, pregnancy outcomes, and mechanism of MenSCs in the regeneration of endometrium were investigated. Results Notably, at days 9 and 18 post-treatment, MenSC transplantation significantly improved endometrial proliferation, angiogenesis, and morphology recovery and decreased collagen fibrosis and inflammation in the uterus. MenSCs had lesion chemotaxis, colonized around the endometrial glands. Gene expression of human-derived secretory protein IGF-1 , SDF-1 , and TSP-1 was detected in the uterus received MenSCs at day 18. The three treatments can all improve fertility in IUA rats. Moreover, gene expressions of cell proliferation, developmental processes, and other biological processes were induced in MenSC transplantation group. Hippo signaling pathway was the most significantly changed pathway, and the downstream factors CTGF, Wnt5a, and Gdf5 were significantly regulated in treatment groups. PRP enhanced these parameters through a synergistic effect. Conclusions In summary, MenSCs could effectively improve uterine proliferation, markedly accelerate endometrial damage repairment and promote fertility restoration in IUA rats, suggesting a paracrine restorative effect and Hippo signaling pathway stimulation. Our results indicate MenSCs, a valuable source of cells for transplantation in the treatment intrauterine adhesion. Combined with PRP, this cell therapy was more effective.

Background Infertility has become a global health issue with the number of couples seeking in vitro fertilization (IVF) worldwide continuing to rise. Some couples remain childless after several IVF cycles. Women undergoing IVF face greater risks and financial burden. A prediction model to predict the live birth chance prior to the first IVF treatment is needed in clinical practice for patients counselling and shaping expectations. Methods Clinical data of 7188 women who underwent their first IVF treatment at the Reproductive Medical Center of Shengjing Hospital of China Medical University during 2014–2018 were retrospectively collected. Machine-learning based models were developed on 70% of the dataset using pre-treatment variables, and prediction performances were evaluated on the remaining 30% using receiver operating characteristic (ROC) analysis and calibration plot. Nested cross-validation was used to make an unbiased estimate of the generalization performance of the machine learning algorithms. Results The XGBoost model achieved an area under the ROC curve of 0.73 on the validation dataset and showed the best calibration compared with other machine learning algorithms. Nested cross-validation resulted in an average accuracy score of 0.70 ± 0.003 for the XGBoost model. Conclusions A prediction model based on XGBoost was developed using age, AMH, BMI, duration of infertility, previous live birth, previous miscarriage, previous abortion and type of infertility as predictors. This study might be a promising step to provide personalized estimates of the cumulative live birth chance of the first complete IVF cycle before treatment.

Diabetes mellitus (DM), a chronic metabolic disease with a high global prevalence, has increasingly been recognized for its adverse effects on the male reproductive system, particularly spermatogenesis. This review systematically summarizes the multifaceted impacts of diabetes on spermatogenesis, encompassing molecular mechanisms such as oxidative stress, endocrine disruption, dysregulated gene expression, metabolic imbalance, apoptosis, microcirculation impairment, and chronic inflammation, as revealed by recent studies. The intricate effects of these mechanisms on sperm quality, reproductive function, and offspring health are also thoroughly explored. A key innovation of this review lies in integrating recent advances, especially those highlighting the roles of epigenetic modifications, mitochondrial dysfunction, and insulin resistance (IR)-related pathways in spermatogenesis. Furthermore, the review evaluates the potential of personalized interventions, including glycemic control, antioxidant therapies, and lifestyle modifications, providing a scientific foundation for the development of more effective preventive and therapeutic strategies. This comprehensive analysis offers forward-looking guidance for future research and clinical interventions addressing diabetes-associated male infertility.

Background Infertility, an important source of stress, could affect sexual life. Extensive studies suggest that the incidence of sexual dysfunction is highly prevalent in infertile women. As the duration of infertility increases, the level of stress is also likely to increase even further, and this could aggravate psychological pain and cause sexual dysfunction. However, the effect of infertility duration on sexual health is unclear. Methods We conducted a case-control study in which 715 patients participated between September 1,2020 and December 25, 2020. We included patients diagnosed with infertility (aged between 20 to 45), who were divided into four groups according to their infertility durations: ≤ 2 years (Group I, n = 262), > 2 years but ≤ 5 years (Group II, n = 282), > 5 years but ≤ 8 years (Group III, n = 97), and > 8 years (Group IV, n = 74). A questionnaire survey on female sexual functions and psychological depression was administered to participants, and their female sexual functions and depression status were measured using the Female Sexual Function Index (FSFI) and Patient Health Questionnaire (PHQ-9), respectively. Results As the number of years of infertility increased, the PHQ-9 score as well as the incidence of psychological depression increased significantly ( p < 0.05), but the total score of FSFI and those of its six domains/sub-scales were not significantly different among the four groups. An analysis of the relevant factors affecting sexual functions, using the multivariable logistic regression model, revealed that when the infertility duration was greater than 8 years, there was a significant increase in the incidence of sexual dysfunction [adjusted odds ratios (AOR) = 5.158, 95% confidence interval (CI): 1.935–13.746, P = 0.001], arousal disorder (AOR = 2.955, 95% CI: 1.194–7.314, P = 0.019), coital pain (AOR = 3.811, 95% CI: 1.045–13.897, P = 0.043), and lubrication disorder (AOR = 5.077, 95% CI: 1.340–19.244, P = 0.017). Conclusions An increasing infertility duration is a risk factor for the occurrence of sexual dysfunction. Hence, as the infertility duration increases, the incidence of female sexual dysfunction and psychological distress could also increase, especially when the infertility duration is more than 8 years.

Background Premature ovarian insufficiency (POI) is one of the major causes of infertility. We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) effectively improved ovarian function in a murine model of POI. Recent studies indicated that mesenchymal stem cell-derived exosomes were important components in tissue repair. In this study, we investigated the therapeutic effects of MenSCs-derived exosomes (MenSCs-Exos) in a rat model of POI and its mechanism in restoring ovulation. Methods Ovaries of 4.5-day-old Sprague Dawley rats (SD rats) were cultured in vitro to evaluate the effects of MenSCs-Exos exposure on early follicle development. Furthermore, POI in rats was induced by intraperitoneal administration of 4-vinylcyclohexene diepoxide (VCD). Forty-eight POI rats were randomly assigned to four groups, each receiving a different treatment: PBS, MenSCs, MenSCs-Exos, and Exo-free culture supernatant of MenSCs. Estrous cyclicity, ovarian morphology, follicle dynamics, serum hormones, pregnancy outcomes, and molecular changes were investigated. Results Exposure to MenSCs-Exos promoted the proliferation of granulosa cells in primordial and primary follicles in vitro and increased the expression of early follicle markers Deleted In Azoospermia Like (DAZL) and Forkhead Box L2 (FOXL2) while inhibiting follicle apoptosis. In vivo, MenSCs-Exos transplantation effectively promoted follicle development in the rat model of POI and restored the estrous cyclicity and serum sex hormone levels, followed by improving the live birth outcome. In addition, transplantation of MenSCs-Exos regulated the composition of the ovarian extracellular matrix and accelerated the recruitment of dormant follicles in the ovarian cortex and increased proliferation of granulosa cells in these follicles. Conclusion MenSCs-Exos markedly promoted follicle development in vitro and in vivo and restored fertility in POI rats, suggesting a restorative effect on ovarian functions. The therapeutic effect of MenSCs-Exos transplantation was sustainable, consistent with that of MenSCs transplantation. Our results suggested that MenSCs-Exos transplantation may be a promising cell-free bioresource in the treatment of POI.

The microorganisms of the reproductive tract have been implicated to affect in vitro fertilization (IVF) outcomes. However, studies on the reproductive tract microbiota of infertile women are limited and the correlation between cervical microbiota and IVF outcome remains elusive. This study aimed to characterize the cervical microbiota of IVF patients undergoing embryo transfer (ET) and assess associations between the cervical microbiota and pregnancy outcomes while exploring the underlying contributing factors. We launched a nested case-control study of 100 patients with two fresh or frozen-thawed cleavage embryos transferred per IVF cycle. Cervical swabs were collected on the day of ET and divided into four groups according to clinical pregnancy outcomes. Variable regions 3 and 4 (V3-V4) of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. In fresh IVF-ET cycles, the clinical pregnancy group (FP, n = 25) demonstrated higher α diversity ( P = 0.0078) than the non-pregnancy group (FN, n = 26). Analysis of similarity (ANOSIM) revealed a significant difference in β diversity between the two groups (R = 0.242, P = 0.001). In frozen-thawed ET cycles, though not significant, similar higher α diversity was found in the clinical pregnancy group (TP, n = 27) compared to the non-pregnancy group (TN, n = 22) and ANOSIM analysis showed a significant difference between the two groups (R = 0.062, P = 0.045). For patients in fresh IVF-ET groups, Lactobacillus , Akkermansia , Desulfovibrio , Atopobium , and Gardnerella showed differentially abundance between pregnant and non-pregnant women and they accounted for the largest share of all taxa investigated. Among them, Lactobacillus was negatively correlated with the other genera and positively correlated with serum estradiol levels. Logistic regression analysis suggested that the composition of the cervical microbiota on the day of ET was associated with the clinical pregnancy in fresh IVF-ET cycles ( P = 0.030). Our results indicate that cervical microbiota composition has an impact on the outcome of assisted reproductive therapy.

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by polycystic ovaries, hyperandrogenism and anovulation. It is one of the main causes of infertility. RU486 is an antagonist of progesterone receptor, and most commonly used as a contraceptive. However, whether RU486 is correlated with PCOS remains unclear. Atrial natriuretic peptide (ANP) is a small peptide with natriuretic and diuretic functions, and its availability to be used in PCOS treatment is unknown. Here, we showed that the serum ANP level was lower in PCOS patients than that in healthy women, and it was also decreased in the serum and ovarian tissues of RU486-induced PCOS rats compared with the control rats. We also found that RU486 inhibited the proliferation and promoted the apoptosis of human KGN ovarian granulosa cells by downregulating progesterone receptor membrane component 1 (PGRMC1). Meantime, ANP promoted the proliferation and inhibited the apoptosis of KGN cells through upregulating ANP receptor A (NPRA). The promotive effects of ANP on ovarian functions were mediated through the formation of an NPRA/PGRMC1/EGFR complex, which further activated MAPK/ERK signaling and transcription factor AP1. Moreover, ANP treatment reversed the PCOS symptoms, and improved the fertility of RU486-induced PCOS rats. Collectively, these findings highlight that RU486 is associated with the pathogenesis of PCOS, and ANP treatment may be a promising therapeutic option for PCOS.

Background Maternal thyroid autoimmune condition on reproductive health is a topic worthy of attention. Current studies of different groups have produced conflicting results regarding the precise relationship between thyroid autoimmunity (TAI) and IVF/ICSI outcomes. Methods A retrospective cohort study included 3197 infertile euthyroid women undergoing their first fresh cycle of IVF/ICSI in our center between January 2015 to May 2024. Participants were split into two groups: the TAI group ( n  = 965) and the control group ( n  = 2232) based on the thyroid autoantibody status. Adjusted multivariate logistic regression models were employed to assess the association between TAI and embryo quality as well as pregnancy outcomes. The subgroup and stratified analyses were performed to evaluate the role of thyroid autoantibody types and titers. The subgroup analysis was conducted based on serum TSH levels and ovarian response. Results The TAI was negatively related to embryos with two-pronucleus (2PN), available cleavage embryos, and high-quality cleavage embryos, no matter which type of thyroid autoantibody is positive. Stratification analysis of thyroid autoantibody titers showed the association was greater as the thyroglobulin antibodies (TGAb) and thyroid peroxidase antibodies (TPOAb) titers increased, respectively. The subgroup analysis showed that TAI patients with high normal thyroid stimulating hormone (TSH) levels (≥ 2.5uIU/mL) and poor ovarian response (POR) were more likely to have fewer 2PN embryos, available cleavage embryos, and high-quality cleavage embryos. However, no association between TAI and pregnancy outcomes was found in all models. Conclusion This study provides comprehensive evidence for the adverse effects of TAI on embryo quality during IVF/ICSI. It is necessary to closely monitor the thyroid hormones and autoantibody levels during treatment, especially in TAI women with TSH ≥ 2.5 uIU/mL and POR.