Reproductive Biology and Endocrinology最新文献

Background: The optimal duration of ovarian stimulation in GnRH antagonist protocols remains insufficiently explored, despite its potential impact on oocyte quality, embryo development, and endometrial receptivity. Identifying an optimal stimulation window may improve success rates in assisted reproductive technologies (ART) while minimizing unnecessary hormonal exposure. The aim of the study was to evaluate if the duration of ovarian stimulation in GnRH antagonist IVF/ICSI protocols influence cumulative ongoing pregnancy rates (COPR).

Methods: This retrospective single-centre study analyzed 1456 IVF/ICSI cycles conducted between 2019 and 2023 in women with normal ovarian reserve using an antagonist protocol. Stimulation duration was classified into three categories: ≤ 8 days, 9-13 days (reference), and ≥ 14 days corresponding to the ≤ 5th, 5th-95th, and ≥ 95th percentiles, respectively. Clinical, biological, and embryological outcomes were compared across groups using the Kruskal-Wallis test. Logistic regression was applied to identify independent predictors of cumulative ongoing pregnancy and pregnancy outcomes.

Results: A total of 1456 cycles were included in the study. At least one embryo was obtained in 95.2% of cycles, with 69.5% proceeding to fresh transfer. Cumulative ongoing pregnancy was assessed for 1339 cycles, among which 36.4% resulted in an ongoing pregnancy. Stimulation duration did not significantly influence COPR: ≤ 8 days (OR = 1.04, 95% CI 0.78-1.39), 9-13 days (reference), ≥ 14 days (OR = 0.84, 95% CI 0.64-1.11). Multivariate analysis identified younger age and higher AMH as independent predictors of COPR.

Conclusions: In women with normal ovarian reserve undergoing IVF/ICSI with a GnRH antagonist protocol, the duration of ovarian stimulation does not significantly impact cumulative pregnancy outcomes. These findings support a personalized approach to trigger timing based on ovarian response independent of stimulation length.

Background: Surrogacy is considered to be a method that allows infertile couples to have a child with the assistance of a third party, known as the surrogate mother. Two forms exist: traditional surrogacy, in which the surrogate provides the oocyte and is thus genetically related to the newborn, and gestational surrogacy, in which no genetic link is present. Over recent decades, the use of surrogacy has markedly increased, highlighting the need to evaluate its potential benefits and risks. This scoping review aims to summarize maternal, pregnancy, and neonatal outcomes reported in gestational surrogacy studies and to assess how these outcomes vary according to clinical protocols, including oocyte source and embryo transfer type.

Methods: The review considered surrogate mothers and newborns as the population, clinical outcomes as the concept, and surrogacy arrangements as the context. Peer-reviewed studies reporting maternal, pregnancy, or neonatal outcomes were included regardless of design, sample size, or geographical setting. Studies limited to ethical, legal, or psychosocial aspects were excluded. A systematic search was conducted in PubMed, Scopus, and Web of Science. Two reviewers independently screened articles, extracted data, and charted outcomes such as pregnancy and live birth rates, miscarriage rates, and maternal complications. Disagreements were resolved by consensus.

Results: From 2,077 articles identified, 19 studies met the inclusion criteria. Pregnancy rate ranged from 24.0% to 61.1%, while live birth rate from 15.8% to 55.5%. No major differences emerged between autologous and donor oocytes, nor between single and double embryo transfer. Miscarriage rates ranged from 3.0% to 17.6%, with minimal variation between fresh and frozen cycles for both autologous (10.5% and 9.8%) and donor oocytes (8.4% and 9.6%), and between fresh and frozen embryos transfers (10.9% and 12.3%). Gestational diabetes ranges from 0% to 27.8%, hypertensive disorder from 0% to 21.2%, and placenta previa from 0% to 4.9%. Preeclampsia showed substantial variability, ranging from 1.2% to 17.1%.

Conclusion: This scoping review suggests that heterogeneous clinical protocols in gestational surrogacy may adversely affect maternal and neonatal health. Further research- particularly prospective, multicenter studies- is needed to better understand and characterize these outcomes.

Background: Endometriosis is a chronic gynecological disease associated with pain, infertility, and delayed diagnosis. Non-invasive biomarkers are urgently needed to facilitate earlier detection and reduce the reliance on diagnostic laparoscopy. MicroRNAs (miRNAs) are stable in body fluids and hold promise as diagnostic tools.

Methods: In this pilot study, urine samples from 34 patients with histologically confirmed endometriosis and 18 control patients (laparoscopically confirmed absence of disease) were analyzed using next-generation miRNA sequencing. Differential expression analysis was performed with DESeq2. Feature selection applied variance filtering, univariate analysis, mutual information, and recursive feature elimination (RFE). The top 20 miRNAs were used to train four classification models: logistic regression, decision tree, random forest, and support vector machine (SVM). Model performance was evaluated by accuracy, precision, recall, F1-score, and area under the ROC curve (AUC).

Results: Among all detected miRNAs, hsa-miR-10400-5p was significantly downregulated in endometriosis compared to controls (log₂ fold change - 2.70; adjusted p = 0.015). RFE identified 20 miRNAs, including hsa-mir-183, hsa-mir-500a, hsa-miR-3184-5p, hsa-miR-151b, and hsa-mir-196a-1, as the most informative for classification. The random forest model achieved the best performance (AUC = 0.91; accuracy and F1-score = 0.81), outperforming logistic regression (AUC = 0.83) and SVM (AUC = 0.81). Several identified miRNAs have been previously implicated in endometriosis pathogenesis, and we additionally identified hsa-miR-10400-5p as a significantly downregulated and previously unreported biomarker candidate, representing a novel finding with potential diagnostic relevance.

Conclusions: Urinary miRNA profiling, combined with machine learning, shows promise as a completely non-invasive approach for the diagnosis of endometriosis. The identified miRNA signature, particularly the novel hsa-miR-10400-5p, warrants validation in larger, independent cohorts to confirm its clinical utility and potential to reduce diagnostic delays.

Background: Women are born with a limited number of eggs, which decline over time. Premature ovarian insufficiency (POI) occurs when this decline happens before age 40, causing infertility. Bone marrow (BM) stem cells may help restore ovarian function, as some women conceive after BM transplants. Studies suggest that mobilizing stem cells with Granulocyte Colony-Stimulating Factor (G-CSF) can improve ovarian response in women with diminished ovarian reserve, possibly without needing ovarian infusion. Our study aimed to evaluate if G-CSF injections alone could improve ovarian function in women with POI.

Methods: This was a pilot, non-randomized, open-label clinical trial including 11 women aged 25-40 years with clinical POI and menopausal symptoms, defined by elevated follicle-stimulating hormone (FSH) on two occasions, low anti-Müllerian hormone (AMH), and reduced antral follicle count (AFC). Participants received up to three rounds of subcutaneous G-CSF administered daily for four days per month over 60 days. Ovarian reserve markers (FSH, AMH, AFC), menstruation resumption, and menopausal symptoms were assessed at baseline and multiple follow-up points over 12 months.

Results: The mean age of participants was 34.1 ± 5.2 years (BMI 23.96 ± 4.0 kg/m²). GCS-F injections resulted in significant increases in white blood cells and mild elevation of liver enzymes which returned to baseline within one month. By four months, significant improvements in menopausal symptoms were reported. Exploratory analyses did not identify consistent correlations between clinical response and baseline characteristics. Mean FSH decreased from 54.3 ± 24.6 IU/L at baseline to 29.0 ± 8.1 IU/L at six months (p = 0.008). AMH and AFC rose modestly (0.21 ± 0.15 to 0.49 ± 1.13 pmol/L; 1.09 ± 1.0 to 2.18 ± 2.60) but did not reach statistical significance. Menstruation resumed in 7 of 11 women (63.6%, p = 0.031). One participant showed marked response including retrieval of three mature oocytes.

Conclusions: G-CSF injections were associated with menstrual resumption and symptom relief in most women with POI, suggesting biological activity. Although improvements in ovarian reserve markers were modest and disappointing in terms of the potential for assisted reproduction, these findings may support further evaluation of G-CSF in larger, controlled trials to clarify its clinical benefit and therapeutic potential.

Trial registration: NCT06117982. https://clinicaltrials.gov/study/NCT06117982?cond=The%20Impact%20of%20Granulocyte%20Colony%20Stimulating%20Factor%20on%20Premature%20Ovarian%20Insufficiency&rank=1 .