Reproductive Biology and Endocrinology最新文献

Background: Data regarding associations between polycystic ovary syndrome (PCOS) and female sexual function are limited.

Objective: To evaluate the association between a self-reported diagnosis of PCOS and female sexual dysfunction (FSD).

Methods: This cross-sectional study was performed in sexually active women, aged ≥ 20 years, who sought care at Mayo Clinic Women's Health specialty clinics between May 1, 2015, to December 31, 2019. Participants' sexual function was assessed with the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) questionnaires. Multivariable logistic regression was used to assess the association between a self-reported diagnosis of PCOS and FSD (defined by the combined diagnostic thresholds for the FSFI and FSDS-R), after adjusting for participant demographics and potential mediators known to impact female sexual function including age, BMI, hormone therapy use, anxiety, depression and relationship satisfaction.

Results: Responses from 4,405 sexually active women were analyzed including 1,481 pre/perimenopausal women and 2,924 postmenopausal women. History of PCOS was reported by 6.1% of pre/perimenopausal women and 3.9% of postmenopausal women. FSD was frequently reported in women with and without PCOS (52.7% among pre/perimenopausal; 64.6% among postmenopausal and 50.6% among pre/perimenopausal; 58.5% among postmenopausal, respectively). Independent of the reproductive stage, PCOS was not associated with FSD, but when adjusted for PCOS, FSD was associated with age less than 40 years, anxiety, depression, and relationship dissatisfaction.

Conclusion: In this large cross-sectional study, a self-reported history of PCOS was not independently associated with FSD after adjusting for key psychosocial and health-related factors.

Background: Morphological embryo assessment, time-lapse imaging or PGT-A can prioritize an embryo for transfer in IVF/ICSI cycles. Nevertheless, there remains potential to enhance the efficiency of ART cycles and reduce the time-to-pregnancy. Previously, a pregnancy predictive non-invasive cumulus cell (CC) test was developed and clinically validated for HP-hMG stimulated patients. In this study, CC gene expression profiles from r-hFSH and r-hFSH:r-hLH stimulated ICSI patients were evaluated for their potential to predict the most competent oocyte/embryo, resulting in live birth.

Methods: This observational cohort study comprises 113 patients allocated to the two study groups stimulated with either r-hFSH (n = 47) or r-hFSH:r-hLH (n = 66). RT-qPCR analysis was performed on 1135 CC samples for 11 predefined biomarkers (CAMK1D, EFNB2, SASH1, GOT1, SLC6A9, HAS2, PTGS2, HSPH1, VCAN, GSTA4, STC2) and 2 endogenous controls (UBC, B2M). Univariate (95%CI) and multivariable analyses (leave-one-out cross-validation and stepwise linear regression) were performed.

Results: The two study groups were first compared to verify if one prediction model could fit the two patient groups. While patient characteristics and stimulation were comparable, the biomarker expression for EFNB2 (e.g.: CC of all oocytes n = 1123, 95%CI: 0.27, 0.49) and GOT1 (CC of all oocytes n = 1123, 95%CI: -0.25, -0.11) significantly differed between the two groups. Stepwise linear regression models were therefore built for the two study groups. The biomarker expression in CC of oocytes developing into transferred blastocysts was compared based on transfer outcomes (live birth or not) and models contained only gene expression data. The strongest live birth predictive biomarkers were GOT1, HAS2, SASH1 and PTGS2 for r-hFSH patients (AUC 0.7284; 70% accuracy) and GOT1 with HAS2 (AUC 0.9529; 88% accuracy) for r-hFSH:r-hLH stimulated patients.

Conclusions: These findings merit further validation in an interventional prospective study. Predictive CC biomarkers are a promising non-invasive technology to shorten the time-to-pregnancy in ICSI patients stimulated with different types of recombinant gonadotropins.

Trial registration: Ethical approval was obtained from the Ethical Committee of Vrije Universiteit Brussel - UZ Brussel (IEC: 2020.335) and the study was registered at ClinicalTrials.gov (ID NCT04710264; registration date 14/1/2021).

Background: While the importance of male infertility management is well recognized and the role of individual lifestyle factors in reproductive health has been established, the combined effect of these factors-measured as a healthy lifestyle score (HLS)-on male infertility remains unexplored. Therefore, we assessed the association between HLS and infertility in Iranian men.

Methods: This population-based case-control study compared 300 infertile men with 300 fertile controls. A healthy lifestyle score was constructed using information about dietary intakes, dietary habits, physical activity, sleep quality, smoking, depression status, anxiety status, and psychological distress; data on these elements were collected using validated questionnaires. Male infertility was defined according to the sixth edition of the World Health Organization (WHO) criteria 2021 by an andrologist.

Results: Men in the highest HLS category had 44% lower infertility odds than those in the lowest category (OR = 0.56; 95%CI: 0.35-0.89). After full adjustments, this association remained significant, with 45% lower odds in the top vs. bottom quartile (OR = 0.55; 95%CI: 0.34-0.90). In addition, after adjusting for covariates, low psychological distress was the sole lifestyle factor that exhibited a significant inverse association with infertility (OR = 0.49, 95% CI: 0.34-0.71). Normal-weight men in the highest vs. lowest HLS category had 67% and 70% lower infertility odds in crude (OR = 0.33; 95%CI: 0.15-0.75) and fully-adjusted model (OR = 0.30; 95%CI: 0.12-0.74). No association was observed in men with overweight or obesity.

Conclusions: This study revealed that a combined healthy lifestyle score, rather than individual factors including dietary intakes, dietary habits, sleep quality, physical activity, smoking, depression status, anxiety status, and psychological distress, was associated with lower odds of infertility in Iranian men, especially among those with normal weight, suggesting that adherence to a healthy lifestyle pattern can be considered a management strategy for infertility.

Objective: The objective of this meta-analysis is to provide a comprehensive and up-to-date assessment of the prevalence of endometriosis and adenomyosis, addressing the limitations of existing research data and evaluating the quality of the data.

Methods: Adhering to the PRISMA 2020 guidelines, this study systematically searched the Web of Science, PubMed, Embase, and Google Scholar databases from their inception until January 2025 for studies related to adenomyosis and endometriosis. All studies that specifically reported the prevalence of adenomyosis and endometriosis, or provided data enabling calculation of their prevalence, were included. The research examined the occurrence of different subtypes of adenomyosis and endometriosis, as well as frequency in various populations. Furthermore, subgroup analyses were conducted to synthesize findings related to distinct diagnostic criteria, gynecological symptoms, and the prevalence of these two conditions across diverse populations. Meta-analyses were performed using meta software packages, and random-effects models with 95% confidence intervals (CI) were employed to determine the combined prevalence of adenomyosis.

Results: A total of 198,925,726 women from 127 studies (59 on adenomyosis and 68 on endometriosis) were included in this meta-analysis. The prevalence of focal and diffuse adenomyosis was found to be 17% (95%CI, 7%-30%) and 15% (95%CI, 9%-23%), respectively. The prevalence of peritoneal endometriosis, ovarian endometriosis, and deep endometriosis was recorded at 6% (95%CI, 1%-15%), 13% (95%CI, 5%-24%), and 10% (95%CI, 2%-24%), respectively. The prevalence of adenomyosis and endometriosis among women experiencing infertility was 31% (95%CI, 10%-58%) and 38% (95%CI, 25%-51%), respectively. Furthermore, among patients experiencing gynecologic symptoms, the pooled of adenomyosis and endometriosis was 41%-49%, and 18%-42%, respectively. The global prevalence of adenomyosis and endometriosis in the general population worldwide is 1% (95%CI, 0%-2%), and 5% (95%CI, 2%-9%), respectively.

Conclusions: In conclusion, endometriosis occurs more frequently than adenomyosis across various populations. Notably, it affects nearly 50% of individuals experiencing gynecological symptoms. This study provides valuables support for public health management and emphasizes the importance of prompt intervention and treatment for related conditions.

Background: Recent research in male infertility genetics has identified numerous candidate genes, some of which were also involved in DNA repair. Mismatch repair (MMR) genes, such as MSH4 and MSH5, have been linked to male infertility due to their role in meiosis, suggesting that other MMR genes may also contribute to impaired spermatogenesis. To investigate the role of MMR genes in male infertility, we first conducted a systematic review focusing on their involvement in impaired spermatogenesis, which was followed by a multicenter cohort study assessing the occurrence of rare deleterious variants in MMR genes among men with severely impaired fertility. The present study aimed to assess the contribution of MMR genes to male infertility and to evaluate their potential clinical utility in the diagnostic workup of men with severely impaired fertility.

Methods: A systematic review was conducted through a PubMed database search with a focus on the role of MMR genes in spermatogenesis. We additionally prepared a cohort study, including whole-exome sequencing data from 244 infertile men presenting azoospermia or severe oligozoospermia (< 5 million spermatozoa/ml). Rare, deleterious variants in MMR genes were classified using the ACGS Guidelines for Variant Classification 2020.

Results: Following a systematic review of the literature, we gathered robust evidence supporting the strong involvement of MSH4 and MSH5 variants in male infertility, moderate evidence for MLH3, and limited evidence for other MMR genes. From our cohort, we identified likely pathogenic or pathogenic variants in two individuals: one with two MSH4 variants and another with a PMS2 variant.

Conclusions: The present study identifies MSH4 and MSH5 as strong candidate genes for male infertility, supporting the integration of their testing into the clinical diagnosis of infertile men, particularly those exhibiting non-obstructive azoospermia. Although current evidence suggests that genetic variants in most MMR genes do not cause infertility, genetic defects in MMR genes can still impair spermatogenesis due to their critical role in sperm DNA repair and maintenance of genome integrity.

Background: Almost half of patients with functional hypothalamic amenorrhea (FHA) show polycystic ovarian morphology (PCOM) on the ultrasound, which leads to a diagnostic confusion. Although FHA and polycystic ovarian syndrome (PCOS) have been thought to co-exist and some FHA-patients seem to have had PCOS before developing FHA, respectively, once hypothalamic inhibition proceeds, the FHA phenotype predominates over the PCOS features, except from PCOM. This connection has never been shown longitudinally. Furthermore, it is still not clear if FHA-PCOM is actually related to preexisting PCOS or if these women constitute their very own heterogeneous subgroup. Thus, the aims of this study were to evaluate changes in hormonal parameters and PCOM after remission and to provide further insight into pathophysiological processes of PCOM in FHA.

Methods: Monocentric retrospective cohort study. Sixty women with FHA in remission were included. While anti-mullerian hormone (AMH) was the main outcome parameter, we also analyzed total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), sex hormone-binding globulin (SHBG) and dehydroepiandrosterone sulfate (DHEAS). PCOM was diagnosed using ultrasound.

Results: At baseline, FHA-PCOM patients revealed higher baseline prolactin (p = 0.029) and AMH levels (p < 0.001). At follow-up, compared to women without PCOM, these women had higher PCOM prevalence (48.1% versus 0%, p < 0.001), higher AMH levels (median 6.49 ng/mL, IQR 4.74-7.95 versus median 2.25 ng/mL, IQR 2.0-2.71; p < 0.001) and higher PCOS prevalence (22.2% versus 0%, p = 0.006). While overall median AMH levels increased significantly, FHA-PCOM patients revealed a significant median decrease in AMH levels (median AMH dynamics - 0.82 ng/mL, IQR - 2.30 - -0.16; p < 0.001).

Conclusions: Our data support the hypothesis that relative FSH deficiency in hypothalamic dysfunction can lead to lower AMH levels. In contrast, the decline in AMH levels and the resolution of PCOM in the FHA-PCOM group may indicate a reversible state of ovarian hyperactivation during FHA.

Trial registration: Not applicable.

Preeclampsia (PE) is a relatively common pregnancy complication that results in significant morbidity and mortality among mothers and children worldwide. It is critical to identify women who are at high risk of developing PE to provide timely treatment, in line with the general shift in medicine towards precision health, with an emphasis on disease prediction and prevention. However, independent and reliable predictors for PE are lacking, and clinical symptoms are typically resolved through delivery. Notably, there have been significant breakthroughs in the use of non-invasive approaches to predict PE, particularly the detection of cell-free RNAs (cfRNAs) in maternal peripheral blood, which are correlated with tissue-specific gene expression and provide a view of prenatal health throughout gestation. Unlike established protein markers such as sFlt-1/PlGF, which primarily reflect angiogenic imbalance and are most informative near the time of clinical presentation, cfRNAs provide a dynamic, tissue-resolved readout of gene expression programs throughout gestation from the placenta, fetus, and maternal organs. Their levels directly correlate with the current state of pregnancy, and cfRNA-based prediction models have demonstrated robust performance, with AUC values ranging from 0.70 to 0.99 and an average sensitivity exceeding 70%. We review recent research on circulating cfRNAs in PE as well as their innovative applications and associated challenges in diagnosing and predicting PE. This review is expected to prompt further research aimed at expanding the clinical applicability of cfRNAs as non-invasive and reliable biomarkers for PE.