Journal of Assisted Reproduction and Genetics最新文献

Purpose: To evaluate whether follicle size at hCG trigger influences reproductive outcomes in letrozole-modified natural frozen embryo transfer (let-mNC-FET) cycles among high-responder patients.

Methods: This observational cohort included 170 let-mNC-FET cycles. Patients were stratified by follicle-size percentiles at trigger: 0-25th (15-17 mm; n = 43), 25-75th (18-20 mm; n = 90), and > 75th (21-24 mm; n = 37). Oral dydrogesterone provided luteal support. Serum progesterone (P4) on embryo-transfer (ET) day was measured with an assay that does not detect dydrogesterone (reflecting endogenous luteal production). The primary outcome was the ongoing pregnancy rate (OPR). Group comparisons used ANOVA/Kruskal-Wallis and χ² tests; predictors of OPR were evaluated with logistic regression.

Results: Positive hCG and OPR did not differ across percentile groups (51.2%, 52.2%, 55.6%; p = 0.920 and 48.8%, 50.0%, 52.7%; p = 0.833, respectively). Endometrial thickness at trigger differed by group (medians 8.0, 9.0, 7.8 mm; p < 0.001), while ET-day P4 increased with larger follicles (medians 19.74, 21.00, 26.50 ng/mL; p = 0.001; post-hoc 0-25th vs > 75th p = 0.0009). In multivariable analysis, younger age (aOR 0.834; 95% CI 0.762-0.914; p = 0.0001), higher BMI (aOR 1.169; 1.015-1.346; p = 0.0303), fewer stimulation days (aOR 0.798; 0.647-0.983; p = 0.0343), larger leading follicle size (aOR 1.343; 1.059-1.703; p = 0.0151), and higher ET-day P4 (aOR 1.067; 1.027-1.108; p = 0.0007) independently predicted OPR; EMT and AMH were not associated (p ≥ 0.08 and p = 0.25).

Conclusions: Although OPR did not differ across follicle-size strata, larger follicle size at trigger and higher endogenous luteal P4 were independent predictors of OPR in highresponders. Confirmation in adequately powered prospective studies is warranted.

Purpose: This study aimed to develop a comprehensive scoring system for assessing the human oocyte meiotic spindle (MS) to predict embryological outcomes from both fresh and cryopreserved oocytes.

Methods: Human oocytes were evaluated using polarized light microscopy before and after cryopreservation. Each oocyte was scored using the MOL system, which assigns a three-digit code reflecting MS Morphology, Orientation, and Localization. Morphology categories included barrel-shaped, altered, enlarged, poor visualization, or absence of MS. Orientation was assessed in relation to the first polar body (PB1), and localization was measured by angular displacement from the PB1. Changes in MS characteristics due to cryopreservation were recorded, and their associations with fertilization and euploid blastocyst development were analyzed.

Results: Cryopreservation led to observable alterations in MS morphology, orientation, and localization, resulting in a redistribution of variants across the MOL classification. A strong correlation was found between specific MOL scores and the likelihood of successful fertilization and chromosomally normal embryo development. Each MOL category variant showed distinct predictive value for embryological outcomes in both fresh and cryopreserved oocytes.

Conclusions: The MOL scoring system provides a reliable, structured approach for predicting oocyte fertilization capacity and embryo developmental potential. Its applicability to both fresh and cryopreserved oocytes, along with its potential for automation, suggests significant clinical value in assisted reproductive technologies. Furthermore, the structured and quantifiable data generated by the MOL scoring system offer a valuable foundation for training machine learning models aimed at enhancing predictive accuracy and supporting decision-making in embryo selection.

Purpose: To investigate the optimal interval time between hCG and oocyte retrieval in polycystic ovary syndrome (PCOS) women undergoing progestin-primed ovarian stimulation (PPOS).

Methods: This retrospective cohort study included a total of 537 PCOS women undergoing PPOS cycles between January 2021 and July 2023 at a university-affiliated reproductive center. Patients were divided into three groups according to the quartiles of post-trigger intervals (Q1:36.0-36.60 h; Q2-3: 36.61-37.20 h; Q4: 37.21-38.0 h). The oocyte performances and pregnancy outcomes were compared among the three intervals.

Results: The number of mature oocytes in the Q4 group was increased compared to the other two groups (15.20 ± 7.87 vs. 12.43 ± 6.35 vs. 13.86 ± 7.46, P < 0.05), but the mature oocyte yield from follicles > 10 mm on the trigger day was comparable among the three groups (64.47 ± 27.18% vs. 63.18 ± 24.95% vs. 63.34 ± 25.54%, P > 0.05). The comparison of live birth outcomes was found no significant difference among the three groups (69.6% vs. 65.9% vs. 75.8%, P > 0.05).

Conclusion: The prolongation of the time intervals between hCG and oocyte retrieval from 36.0 to 38.0 h in PPOS cycles did not show an obvious improvement in terms of oocyte performances and pregnancy outcomes in the PCOS women. More well-designed prospective trials are necessary to verify the benefits and risks of prolonged intervals in PPOS cycles in the PCOS women.

Trial registration: No available.

Purpose: The ovarian renin-angiotensin system (OVRAS) plays a key role in ovarian physiology and pathology, regulating angiogenesis, steroidogenesis, follicular development, and ovulation. This study examines OVRAS expression in normal and dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS) mouse model to elucidate its role in PCOS pathogenesis.

Methods: Ovarian tissues from normal and DHT-treated mice were analyzed by double and triple immunofluorescence to localize angiotensin peptides (Ang II/III, Ang 1-7) and their receptors (AT1R, AT2R, MasR) within granulosa (GCs), theca (TCs), follicular contents, and interstitial cells (ICs) at preantral and antral stages.

Results: Normal ovaries exhibited stage-specific OVRAS expression, with Ang 1-7 progressively localizing toward the oocyte in antral follicles and Ang II-III showing strong expression in cells adjacent to the antrum. In DHT-treated ovaries, OVRAS was dysregulated, showing irregular Ang 1-7 staining in GCs, decreased AT1R, increased AT2R, and loss of Mas1R expression. DHT-PCOS follicles displayed impaired development, thickened theca layers, and OVRAS overexpression in ICs. The zona pellucida (ZP) was strongly stained in normal follicles but weakened in the distorted ZPs of DHT-treated mice.

Conclusions: OVRAS shows hormone-regulated expression during normal folliculogenesis and is disrupted in the DHT-induced PCOS mouse model, paralleling human pathology. Its upregulation in interstitial cells following androgen exposure is associated with theca cell hyperplasia and excess androgen production, suggesting a role in PCOS-related follicular dysfunction. These results position OVRAS as a potential molecular marker and therapeutic target in ovarian disorders. Further studies are needed to clarify its function in follicular maturation and oocyte quality. .

Purpose: Gaps in knowledge among women's healthcare providers have contributed to diagnostic delays and delayed care for women with fragile X-associated primary ovarian insufficiency (FXPOI). The objective of this study was to assess if an educational tool could improve women's healthcare providers' knowledge of FXPOI.

Methods: A one-page educational tool about the premutation and FXPOI was developed. To assess the impact, a pre- and post-intervention survey was given to 95 providers. The post-intervention survey was emailed approximately 1 month after the pre-intervention survey. Surveys consisted of 12 knowledge-based questions (12 points total). Additional information collected included demographics, routine POI workup, comfort level explaining carrier screening results, and feedback on the tool.

Results: Provider knowledge significantly improved from 7.34/12 (± 1.75) to 8.66/12 (± 2.30) (p < 0.0001). Significant predictors of pre-intervention knowledge included provider type, specialty, presence of a genetic counselor (GC) in clinic, and graduation year. Physicians outperformed nurse practitioners and nurse midwives (p < 0.0128). Reproductive endocrinologists and maternal-fetal medicine providers outperformed other specialties (p < 0.0001). Providers with a GC in the clinic performed better than those without (p = 0.0128). Providers who graduated between 2010 and 2019 outperformed more recent graduates (p = 0.0348). No significant predictors were identified for post-intervention scores.

Conclusions: The implementation of our novel educational tool led to measurable improvement in provider knowledge regarding FXPOI and the fragile X premutation. The absence of significant demographic predictor variables on the post-intervention survey suggests that the educational tool may help reduce provider gaps in knowledge and ultimately reduce time to diagnosis and improve reproductive care for women with FXPOI.

Purpose: This study systematically evaluates the impact of preimplantation genetic diagnosis (PGD) versus natural conception (NC) on per-attempt and cumulative live birth rates for chromosomal translocation carriers. It aims to differentiate PGD's role as an efficiency tool versus an efficacy modifier, examining translocation type and patient history as key prognostic factors.

Methods: A systematic search of seven databases up to July 2025 was conducted. A meta-analysis using a random-effects model was performed to separately pool the per-attempt live birth rate (LBR) and cumulative live birth rate (CLBR). Subgroup analyses and meta-regression were used to explore heterogeneity and prognostic factors.

Results: 49 studies involving 7,026 couples were included. The pooled LBR for PGD was significantly higher than for NC (32.0% vs. 18.5%; OR = 2.28, p < 0.0001). However, the CLBR for PGD (36.0%) was not significantly different from the good-prognosis NC group (36.6%). Robertsonian translocation carriers had significantly higher normal/balanced embryo rates than reciprocal carriers (38.3% vs. 22.5%, p = 0.000268).

Conclusion: PGD significantly improves the short-term efficiency of achieving a live birth for translocation carriers but may not alter long-term efficacy. Translocation type is a key predictor of PGD success, while carrier sex is not. Clinical guidance should be personalized based on patient goals for time-to-pregnancy.

Purpose: Intracellular pH (pH_i) in sperm cells plays a crucial role in various physiological processes, including motility, capacitation, and fertilization. While previous studies have shown a positive correlation between sperm pH_i and fertilization success in normozoospermic patients undergoing fertility treatments, its role in non-normozoospermic individuals is unclear.

Methods: This study investigates the relationship between sperm pH_i and fertilization outcomes in patients undergoing assisted reproduction techniques: in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Qualitative sperm pH_i evaluation was performed using time-lapse flow cytometry, and both basal pH_i and pH_i response capacity (delta pH_i) were assessed in sperm samples from patients diagnosed with teratozoospermia, asthenoteratozoospermia, or hypoteratozoospermia.

Results: Our results revealed significant differences in pH_i values among diagnostic groups and specific correlation patterns according to the ART used. In ICSI cycles, higher basal pHi values and reduced delta pH_i were significantly associated with higher fertilization rates in patients with teratozoospermia, while in IVF, the correlations were more variable.

Conclusions: These findings suggest that measuring sperm pH_i could potentially serve as a valuable tool for predicting fertilization success and guiding treatment decisions during assisted reproduction techniques (ART), contributing to a better understanding of the molecular mechanisms underlying male infertility.

Purpose: Widespread use of genome-wide testing during pregnancy and throughout life raises clinical, legal, and ethical questions. Results from such tests in the context of gamete donation have implications also for the donor and other recipients. Current guidelines do not fully address this matter. We aim to provide empirical data on clinician's perspectives towards pre-donation genetic counseling and recontacting sperm donors for additional genome-wide genetic testing.

Methods: In-depth interviews were conducted with 19 healthcare professionals across Israel from different disciplines (sperm bank directors, fertility and genetic specialists) and were analyzed using the grounded theory approach.

Results: Overall participants emphasized the importance of pre-donation comprehensive genetic counseling, which should cover future potential genetic tests findings, and their implications for both donor and offspring health, along with offering donors the choice to allow recontact later on. Approximately half of the participants believed recontacting donors should happen before performing broader genetic tests on the offspring, mainly due to possible implications for the donor's health. In contrast, about a third of participants advocated recontacting donors only if clinically significant findings are identified, driven by practical reasons concerning the benefit to the offspring and time-sensitive situations, like pregnancy.

Conclusion: This study highlights the need for clear guidelines regarding donor recontact in the context of expanding genetic testing. A strong consensus exists on the necessity of comprehensive pre-donation genetic counseling, divergent views on recontact emphasize the need to balance the implications for donor health with practical considerations for offspring and timely medical interventions.

Purpose: To evaluate the association between sperm DNA fragmentation index (DFI), which quantifies the proportion of sperm with damaged DNA (sperm DNA fragmentation), and sexual dysfunction (SD) using the Sexual Health Inventory for Men (SHIM), a validated 5-item tool assessing erectile dysfunction severity, and the Androgen Deficiency in Aging Male (ADAM) questionnaire, a 10-item screening instrument for symptoms of testosterone deficiency.

Methods: A retrospective cohort study was conducted at a university-affiliated male infertility clinic. A total of 703 infertile men (mean age 37.4 ± 5.6 years) who completed SHIM and ADAM questionnaires and underwent semen analysis and DFI testing between 2000 and 2020 were included. DFI was categorized as normal (< 30%) or abnormal (≥ 30%). Primary outcomes were intercourse frequency (IF), SHIM scores (erectile dysfunction severity), and ADAM scores (androgen deficiency symptoms). Multivariable regression models evaluated predictors of sexual function, with emphasis on DFI.

Results: Abnormal DFI was observed in 39% of men. Average IF was 7.2 ± 4.4 times/month, with no difference by DFI status. A positive ADAM score was reported in 41.1%, while moderate/severe ED (SHIM) was reported in 3%. Multivariable analysis showed that BMI above 30 (kg/m²) alone was associated with reduced IF. Abnormal SHIM scores were predictive of positive ADAM score. Worse SHIM scores were associated with smoking and a positive ADAM score. Men with abnormal DFI had significantly lower SHIM scores (p = 0.02): 65% had normal scores versus 73% in the normal DFI group. Mild and mild-moderate ED were reported in 25% and 9% of the abnormal DFI group versus 19% and 5% in the normal group, respectively.

Conclusion: Abnormal DFI was significantly associated with erectile dysfunction. These findings support incorporating sexual health assessments into male infertility evaluations.

Purpose: The study addresses whether maternal age, embryo morphology, and blastocyst developmental timing interact to influence pregnancy success rates in PGT-A selected single embryo transfer (PGT-A sSET), confirmed as euploid or exhibiting low-level (≤ 40%) mosaicism; and whether the chromosomal health of the embryo mitigates all aspects of age-related fertility decline.

Methods: We retrospectively analyzed 822 frozen PGT-A sSET cycles performed at Villa Mafalda private clinic (July 2020-December 2024): 771 autologous and 51 donor-oocyte transfers. Outcomes were ongoing pregnancy/live birth, implantation, and miscarriage rates, evaluated in relation to maternal age, considered both as categorical brackets (≤ 34, 35-38, 39-41, ≥ 42 years) and as a continuous variable.

Results: Women ≥ 42 yr showed lower ongoing-pregnancy and live-birth rates, poorer morphology, delayed blastocyst expansion than younger groups (all p < 0.05); no differences emerged among the younger brackets. In the multivariable logistic-regression model, embryo morphology emerged as the strongest determinant of success: Good-quality embryos showed 2.8-fold increase in ongoing pregnancy/live-birth odds (95% CI 1.61-4.92; p = 0.0003) and Excellent-quality embryos 4.6-fold increase (95% CI 2.63-8.05; p < 0.0001) versus Poor-quality category. Finally, each additional year of maternal age increased miscarriage risk by 11% (RR 1.11, 95% CI 1.03-1.19; p = 0.005).

Conclusions: Our results reinforce that, even among chromosomally normal blastocysts, morphological quality predominates over maternal age and blastocyst developmental timing in predicting pregnancy success. Maternal age exerts its effect largely by compromising embryo competence-beyond simply increasing aneuploidy rates-pointing to additional, age-related alterations in embryonic physiology.