Journal of Assisted Reproduction and Genetics最新文献

Purpose: To investigate the incidence of mosaic embryos and identify factors influencing their occurrence.

Methods: In this retrospective cohort study, 5168 blastocysts from patients who underwent preimplantation genetic testing were analyzed. Mosaic embryos were further analyzed based on mosaic classification, number of affected chromosomes, degree of mosaicism, and chromosomal distribution patterns. To assess the factors influencing mosaicism, a generalized estimating equation (GEE) model was utilized.

Results: Mosaic embryos accounted for 23.53% of all blastocysts, with aneuploid-aneuploid mosaics (59.29%) being more prevalent than euploid-aneuploid mosaics (40.71%). Whole-chromosome and segmental mosaicism occurred at comparable frequencies, with single-chromosome mosaicism being the most common. High-level mosaicism was slightly more frequent than low-level mosaicism. The GEE model analysis revealed that the blastocyst biopsy day, embryo quality, and ovarian stimulation protocol were independent factors significantly associated with the occurrence of mosaic embryos. Specifically, the GnRH antagonist protocol, good embryo quality, and D5 blastocyst biopsy day were associated with a lower risk of mosaicism. Clinical pregnancy, miscarriage, and live birth rates did not differ significantly between mosaic and euploid embryos (p > 0.05). However, embryos with lower mosaicism levels exhibited a trend toward higher clinical pregnancy and live birth rates.

Conclusion: Mosaic embryo occurrence is influenced by the biopsy timing, embryo quality, and ovarian stimulation protocols. Mosaic embryos, particularly those with lower mosaicism levels, retain clinical value and may be considered for transfer when euploid embryos are unavailable. These findings support the need for individualized embryo-transfer strategies based on mosaicism proportions and patient-specific factors.

Purpose: Infertility affects 1 in 6 couples, yet male fertility assessments often rely on semen analysis alone, which has limited predictive value for treatment success. This study evaluates an epigenetic tool for assessing sperm quality, aiming to provide a more comprehensive view of male fertility and improve personalized treatment strategies.

Methods: De-identified pregnancy outcomes from 537 couples treated at 10 US fertility clinics were analyzed. Partner ages, total motile sperm count, treatment type, and sperm epigenetic quality were considered to assess associations with fertility treatment outcomes.

Results: Men with abnormal sperm epigenetic profiles had significantly lower pregnancy success rates with intrauterine insemination (IUI) compared to those with normal profiles, despite similar sperm motility and concentration. In contrast, pregnancy rates did not differ between abnormal and normal profiles among couples undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), suggesting that ICSI may overcome sperm epigenetic quality issues.

Conclusion: This real-world analysis was limited by the availability of detailed clinical and phenotypic data, which may introduce potential confounders. Nevertheless, the findings highlight the clinical value of epigenetic sperm assessment as part of male fertility evaluation and support its potential to guide more effective, personalized fertility treatment pathways.

Purpose: To assess whether the endometrial receptivity analysis (ERA) captures receptivity changes attributed to endometrial aging and whether it may be useful for older patients undergoing fertility treatment.

Methods: Retrospective cohort study of patients who underwent ERA testing at an academic center (01/2019-05/2024). The ERA inferred transcriptomic levels of canonical receptivity markers from biopsies obtained at standard timing. Demographic and treatment-related variables were analyzed by age group. The proportion of non-receptive ERA results (pre- and post-receptive combined) was compared using Fisher's exact test. Univariable and multivariable logistic regression assessed associations between predictors and non-receptive ERA.

Results: Of 210 patients, 205 were included. Age distribution was < 35 (n = 35, 17%), 35-37 (n = 58, 28.3%), 38-40 (n = 53, 25.8%), and ≥ 41 (n = 59, 28.8%). Overall, 166 (81.0%) ERAs were receptive, 33 (16.1%) pre-receptive, and 6 (2.9%) post-receptive. BMI, infertility diagnosis, and prior implantation or miscarriage history did not differ by age. Non-receptive ERA proportions were 20% (< 35), 17.2% (35-37), 17.0% (38-40), and 22.0% (≥ 41) (p = 0.52). In multivariable analysis adjusting for BMI and number of prior failed euploid transfers, age was not associated with non-receptive ERA (aOR 0.98, 95% CI 0.34-2.30, p = 0.97).

Conclusion: Uterine age was not associated with increased odds of non-receptive ERA, suggesting that the test does not capture age-related changes in endometrial receptivity. Although endometrial aging is implicated in reduced embryo transfer success, the ERA should not be ordered solely on the basis of uterine age. The ERA may not reliably detect age-related endometrial differences in the window of implantation at a clinical level.

Purpose: To compare dual triggering versus hCG-only triggering in poor responders undergoing controlled ovarian stimulation with a GnRH antagonist protocol in ART cycles.

Methods: A systematic review and meta-analysis was performed. The primary outcome was the number of mature oocytes (MII). The number of oocytes retrieved, clinical pregnancy, and miscarriage rates were analyzed as secondary outcomes. Subgroup analyses were conducted according to the Bologna and POSEIDON classifications.

Results: Ten studies were included. Dual triggering significantly increased the number of retrieved and mature oocytes in patients classified according to the Bologna criteria, but not in those classified by the POSEIDON criteria. Age-related differences across studies appeared to influence the efficacy of dual triggering. A borderline improvement in clinical pregnancy rates was observed among Bologna-defined patients. Miscarriage rates did not differ significantly between the groups.

Conclusions: Dual triggering appears to improve oocyte yield and maturity in Bologna-defined patients, but this effect is unlikely to apply uniformly across all phenotypes. Persistent heterogeneity in poor responder definitions limits the understanding of the benefits of dual triggering in this population. Well-designed prospective studies with rigorous phenotypic stratification are warranted to identify which patients are most likely to benefit from dual triggering.

Purpose: To evaluate the effectiveness and safety of personalized embryo transfer (pET) guided by TERTs compared with standard embryo transfer (sET) in assisted reproductive technology.

Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies (CS) at low or moderate risk of bias was conducted. PubMed/MEDLINE, EMBASE, CENTRAL, LILACS, and CINAHL were searched to November 2025 without restrictions. Conference abstracts and reference lists were also screened. Reviewers independently screened, extracted data, and assessed risk of bias. RCTs and CS were pooled separately using random-effects models. Odds ratios (ORs) were synthesized using the generic inverse-variance method. Prespecified subgroups included prior failures and euploid transfers.

Results: We included 44 studies (4 RCTs; 40 CS). Thirty-five studies evaluated ERA, six rsERT, and four other platforms. In women with limited or no prior failures, two low-risk RCTs showed pET with ERA probably results in little or no difference in LBR versus sET (RR 0.98, 95% CI 0.88-1.10; 1069 women; moderate certainty). In women with recurrent implantation failure (RIF) transferring untested embryos, nine low/moderate-risk CS showed a probable increase in LBR with TERT-guided pET (OR 1.58, 95% CI 1.34-1.86; 4754 women; moderate certainty), with similar direction of effect across ERA, rsERT, and ERT. Among RIF women undergoing euploid transfers, five studies provided very uncertain evidence of benefit (OR 1.36, 95% CI 0.83-2.22; 852 women; very low certainty). Findings were heterogeneous and imprecise, yielding very low certainty of evidence.

Conclusion: Current evidence does not support routine use of TERTs in non-RIF. In RIF, TERT-guided pET is probably associated with higher LBR when untested embryos are transferred, but benefits remain uncertain in euploid transfers, reflecting either a small biological effect, methodological bias, or inconsistent protocol implementation. Future research should prioritize adequately powered RCTs in RIF, especially with euploid embryos, and direct comparisons of TERT platforms and assessment of test reproducibility.

Purpose: Sickle-cell disease (SCD) is a severe autosomal recessive disorder. At-risk couples may prevent transmission either through prenatal diagnosis with possible termination of pregnancy or preimplantation genetic testing for monogenic disease (PGT-M). Data on PGT-M outcomes in this population remain scarce.

Methods: We conducted a monocentric retrospective study (2006-2021). To assess ovarian response to stimulation, each PGT-M cycle for SCD was matched with two control cycles.

Results: Sixty couples underwent at least one ovarian stimulation for PGT procedure for SCD. Eight couples (13.3%) had one affected partner (S/S or S/C) and one carrier (A/S), while 52 couples (86.7%) were both carriers (A/S). Thirty-five couples (58.3%) already had an affected child, and 17 couples (28.3%) requested PGT-M with HLA typing. Median female age at first attempt was 33 years. Overall, 19 couples (31.7%) achieved at least one live birth following fresh or frozen embryo transfer. Among the 17 couples requesting HLA typing, three HLA-matched births (15.7%) and one unmatched healthy birth were achieved. None of the five women affected by SCD achieved a live birth. Ovarian response did not differ significantly between women with sickle cell trait and the controls.

Conclusion: PGT-M is as a viable option for obtaining healthy offspring. These results bolster the argument that PGT-M serves as an alternative to prenatal diagnosis for eligible couples. Our study aims to assist geneticists, gynecologists, and hematologists in providing the necessary guidance before embarking couples on this long and often challenging journey.

Purpose: To compare live birth rates (LBRs) between mosaic and euploid embryos.

Methods: Retrospective cohort study analyzing frozen mosaic (56) and euploid (819) embryos tested with next generation sequencing, transferred between October 2018 and December 2023. The primary outcome was LBR per embryo transferred. Secondary outcomes included LBR per embryo transfer cycle, implantation rate (IR), miscarriage rate (MR), double embryo transfer (DET) rate, twin rate, high-level (HL) versus low-level (LL) mosaicism, segmental or whole chromosomal mosaicism, freeze day and grade, and neonatal outcomes. Chi-squared and student t-test were applied, with significance set at p < 0.01.

Results: Per embryo, mosaic and euploid embryos had similar LBR (50.0% versus 51.8%, p = 0.80) and IR (55% versus 56%, p = 0.88). Per cycle, biochemical pregnancy (22.0% versus 17.8%, p = 0.41), clinical pregnancy rate (53.1% versus 56.2%, p = 0.77), and MR (7.7% versus 7.6%, p = 1.00) were not significantly different. LBR in LL versus HL mosaics was 59.4% versus 37.5% (p = 0.18) and 48% versus 50% for segmental versus whole chromosomal defects (p = 1.00). Mosaic embryos were transferred in significantly older patients (37.5 vs 36.1 years, p = 0.01), but age did not affect LBR after adjustment at the time of embryo transfer (p = 0.65). DET was more frequent with mosaic than euploid embryos (41% versus 4.8%, p < 0.001), yielding a higher twin LBR (21% versus 2.7%, p < 0.001).

Conclusion: Mosaic embryos had nearly identical LBR and MR to euploid embryos, supporting transfer before repeating IVF retrieval. Given the elevated twin risk with mosaic DET, single embryo transfer should be prioritized for all tested embryos.