Reproductive Biology and Endocrinology最新文献

Follitropin delta, a recombinant human follicle-stimulating hormone (r-hFSH), is administered using an individualized dosing algorithm based on serum anti-Müllerian hormone (AMH) levels and body weight and offers a different pharmacokinetic (PK) and pharmacodynamic (PD) profile compared to conventional gonadotropins. The retrospective analysis by Eggersmann et al. aimed to compare the cumulative live birth rate (CLBR) of r-hFSH delta versus r-hFSH alfa/beta using data from the German In-vitro Fertilization (IVF) registry (D.I.R.^®; Deutsches IVF-Register), encompassing 113,936 stimulation cycles from women aged 24-45 years between 2017 and 2022. The authors found no statistical differences in oocyte yield, pregnancy rate (PR), and live birth rate (LBR), and an increase in cumulative live birth rate (CLBR) in the group stimulated with r-hFSH delta. The study presents several methodological challenges, such as differences in dose exposure, insufficient adjustment for confounding variables, and the inclusion of diverse patient groups, which may affect the clarity of the comparative effectiveness of the treatments. Additionally, the exclusion of patients who did not undergo frozen embryo transfer may limit the interpretability and generalizability of the findings. While Eggersmann et al. added valuable and meaningful insights into the real-world effectiveness of r-hFSH delta, its conclusions warrant thoughtful consideration. Undertaking a comprehensive methodological assessment strengthens causal inferences drawn from observational data, especially when intended to inform clinical decision-making. This real-world study serves as an important piece of the broader evidence base, contributing to our understanding of assisted reproductive technology (ART) outcomes.

Background: There is a considerable proportion of false positive results when the result of preimplantation genetic testing for aneuploidy is chromosomal mosaicism. The aim of this study was to assess the concordance among clinical trophectoderm biopsy, second trophectoderm biopsy, and inner cell mass biopsy in mosaic human embryos with segmental deletion and evaluate a modified biopsy protocol.

Methods: This retrospective study included 100 pretested blastocysts, which were classified as segmental deletion mosaics with one to two chromosomes were affected, donated by 84 couples in a single, high-volume fertility center in Beijing China. Re-biopsy was taken from the inner cell mass and two symmetrical trophectoderm sites near the inner cell mass in each embryo. Samples from the inner cell mass and one of the two trophectoderm were prepared for modified protocol, which isolated portions into single cells, the cells with normal morphology were collected and cell debris were removed. Re-biopsy samples were analyzed by next-generation sequencing. Main outcome measures were concordance between clinical biopsy and blastocyst, and segmental mosaicism in modified protocol.

Results: Only six (6.5%) of 92 inner cell mass samples presented with concordant chromosomal aberrations, four (4.3%) presented with de novo segmental abnormalities, and 82 (89.1%) did not show any segmental abnormalities. For the trophectoderm samples, 62 (66.7%) of 93 s biopsies and 76 (80%) of 95 modified biopsies did not show any segmental deletion or duplication. The modified biopsy protocol was associated with fewer segmental abnormalities (20% versus 33.3%; odds ratio: 0.5, 95% confidence interval: 0.26 to 0.97) and fewer segmental deletion mosaics (10.5% versus 23.7%; odds ratio: 0.38, 95% confidence interval: 0.17 to 0.85) compared with the second biopsy.

Conclusions: A clinical mosaic embryo with simple segmental deletion was extremely low predictive of the embryo. Removal of cell debris from biopsy samples may reduce the incidence of segmental deletion mosaics.

Background: A link between idiopathic male infertility and viral infections exhibiting seminal carriage has emerged recently. In this respect, human papillomavirus (HPV) appears to be the most prevalent sexually transmitted agent worldwide. The viruses present in the genital environment comprise the genital virome. HPV infection reportedly disrupts homeostasis of the virome in women but this topic has not previously been studied in men.

Methods: This was a retrospective study of males attending the fertility clinic at Amiens University Medical Center (Amiens, France). Men with a multiple-type HPV infection in the sperm (n = 15) were considered to be cases, and men with no detectable HPV in the sperm were considered to be controls (n = 13). The molecular virome in cases and controls was described via metagenomic next-generation sequencing. The cases and controls were compared with regard to genomic, clinical and sperm-related characteristics.

Results: The seminal virome analysis revealed the predominance of Papillomaviridae in cases (63.4%). Other virus families found in both groups (albeit with lower proportions of reads in cases than in controls) were Herpesviridae (6.9% vs. 40.5%, respectively), Polyomaviridae (11.3% vs. 17.8%, respectively), and other viral sequences (18.4% vs. 40%, respectively). There was no difference in viral diversity between the two groups (p = 0.0692). Viral diversity was correlated with the semen sample volume, progressive sperm motility, total motility, and sperm vitality in cases but not in controls. Univariate and multivariate comparative analyses did not reveal significant differences in sperm parameters between cases and controls.

Conclusions: The male seminal virome mainly comprises viruses from the Papillomaviridae, Herpesviridae and Polyomaviridae families. The correlation between viral diversity and sperm parameters in HPV-positive patients suggests that HPV-specific interactions within the seminal virome are responsible for variations in sperm parameters. Hence, alterations in the seminal virome (due mostly to HPV infection) might impact sperm parameters and thus male fertility.

Background: The application of Artificial Intelligence (AI) to sperm selection during Intracytoplasmic Sperm Injection (ICSI) procedures represents one of the most innovative advances in assisted reproductive technology (ART). Traditional sperm selection relies heavily on the subjective assessment of embryologists, which can lead to variability in outcomes. This study aimed to evaluate the performance of an AI-based software, Sperm ID (SiD™) v.1.0, for sperm selection during ICSI and to compare its outcomes with those obtained by experienced embryologists. Additionally, the study assessed the potential impact of sperm and oocyte quality, particularly in autologous versus donor oocyte cycles.

Methods: A single-center, blind, observational study was conducted involving 102 infertile couples-60 undergoing treatment with autologous oocytes and 42 using oocytes from a donation program. Semen samples were analyzed in real time with SiD™ v.1.0, a software that quantifies progressive motility parameters and assigns each sperm a categorical score ('Best,' 'Good,' 'Medium,' or 'low'). Spermatozoa and oocytes were individually tracked from injection to embryo development. Oocyte quality was retrospectively analyzed using another AI tool, Magenta IVF R3.0. The performance of the Artificial Intelligence Sperm Selection (AISS) system was compared with that of senior embryologists (> 300 ICSI cycles/year). Statistical analysis included descriptive statistics and inferential tests to compare fertilization and embryo development rates across sperm categories and between autologous and donor cycles.

Results: Biological outcomes-such as fertilization and blastocyst development-were generally similar across all sperm quality categories. However, in cycles with autologous oocytes, the use of top-quality sperm ('Best' category) was associated with a significantly higher blastocyst formation rate. In contrast, no significant differences were observed in donor oocyte cycles, regardless of sperm quality. The AISS system demonstrated comparable performance to that of senior embryologists, with similar fertilization and embryo development rates.

Conclusions: The study highlights the promising role of AI-based tools in standardizing and enhancing sperm selection during ICSI. While AI-driven sperm selection showed limited impact in donor cycles, it may offer a distinct advantage in cases involving compromised oocyte quality. Furthermore, AISS may improve laboratory efficiency and support junior embryologists by reducing selection time and increasing procedural consistency.

Background: Pregnancy involves a fine-tuned hormonal interplay between the fetus, placenta, and mother, which shapes long-term developmental outcomes. Endometriosis has been hypothesized to originate in utero due to altered fetal exposure to sex steroids. This study investigates differences in umbilical cord estradiol and androgen levels in female fetuses born to women with and without endometriosis, exploring a potential role of altered in utero hormone exposure in the intergenerational transmission of endometriosis risk.

Methods: This is a case-control study nested within a cohort of women delivering singleton females at our institution between June 2022 and June 2023. Cases were women with endometriosis (diagnosed via imaging or surgery before pregnancy) and controls were women without endometriosis. Analyses were performed before and after propensity-score matching (PSM) at a 1:3 ratio to control for maternal age, gestational age, and delivery mode. Umbilical cord blood was collected at delivery, and hormonal levels of corticosteroids, progestins, androgens, and estradiol (E2) were measured using liquid chromatography-tandem mass spectrometry. Estradiol-to-androgens ratios were calculated, with 95% confidence intervals (CIs) determined using the bootstrapping method.

Results: The total cohort included 160 women, 17 (10.6%) of whom had endometriosis. After 1:3 matching, 51 controls without endometriosis were included. Women with endometriosis had higher E2 levels compared to controls, both before PSM (6.8 [4.3-9.1] mcg/L vs. 3.6 [1.4-8.6] mcg/L, p = 0.03) and after PSM (2.4 [1.1-6.6] mcg/L, p = 0.002). Estradiol-to-androgens ratios indicated a higher-estrogen and lower-androgens hormonal status in endometriosis, with higher E2-to-testosterone (p < 0.001), E2-to-androstenedione (p = 0.001), E2-to-dehydroepiandrosterone (DHEA) (p < 0.001), and E2-to-DHEA sulfate (DHEAS) ratios (p < 0.001) compared to controls. After PSM, the E2-to-testosterone, E2-to-androstenedione, E2-to-DHEA, and E2-to-DHEAS ratios were 4.38 (95% CI: 2.28-6.49), 3.28 (95% CI: 1.29-5.28), 2.52 (95% CI: 1.32-3.72), and 4.57 (95% CI: 1.86-7.27) times higher, respectively.

Conclusions: This is the first study showing that female newborns of women with endometriosis are exposed to higher in utero estradiol compared to controls. This high estrogen low androgens environment may influence fetal programming of reproductive traits and might drive the in utero susceptibility to endometriosis.

Background: Endometriosis is a gynecological disorder that affects 190 million reproductive age women worldwide. Laparoscopic surgery is considered the gold standard to diagnose the disease, creating a barrier to diagnosis and leading to long delays in disease recognition. MicroRNAs may be useful in the diagnosis of this disease, however the ability to detect early disease in adolescents may be improved by identifying microRNAs specific to this population.

Methods: This was a prospective clinical study evaluating adolescent patients with pelvic pain undergoing gynecologic surgery in an academic medical center. We enrolled 63 adolescent and young adult patients aged 13-26 years old undergoing gynecologic surgery between 2019 and 2024. Clinically relevant phenotypic and surgical information were recorded as well as evaluation of microRNAs abundance. We assessed microRNAs abundance by extracting total RNA from the serum samples and performed RNA-sequencing (RNAseq).

Results: The mean age of adolescent women in the study was 16.3 and 15.9 for the endometriosis (n = 31) and control groups (n = 20), respectively. The mean BMI was 24.5 kg/m2 and 29.0 kg/m2 in the endometriosis and control groups, respectively. RNA-seq data analysis showed differential abundance of 859 microRNAs. Among 859 microRNAs, 488 were increased and 391 were decreased. We next selected those that were most distinct, with little overlap between subjects and controls. Four microRNAs were highly significantly increased while eighteen microRNAs were highly significantly decreased. We defined a signature of microRNAs that best distinguished subjects with endometriosis from controls.

Conclusions: This is the first study to reveal the differential abundance of microRNAs specifically in adolescent patients with endometriosis. There are distinct differences from those identified in adult women with endometriosis. Our findings present a unique signature of microRNA found in the serum of adolescents with endometriosis. This finding may be useful as a noninvasive biomarker to diagnose early disease in adolescents. Non-invasive diagnosis may allow for early diagnosis and prevention of disease progression.

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.