Journal of Assisted Reproduction and Genetics最新文献

Purpose: Assisted reproductive technologies (ART) have provided significant advancements in infertility treatment. Despite this, ART-conceived pregnancies are also associated with higher risks for adverse maternal and offspring outcomes. Recent evidence highlights the role of the reproductive tract microbiome (mainly the vaginal and endometrial microbiome) in implantation success and gestational physiology. The purpose of this review is to summarize the state of knowledge pertaining to the content, function, and disruption of the uterine and vaginal microbiome in ART contexts and to consider the adverse effects of changing the microbiome on maternal health, pregnancy outcomes, and development of progeny.

Methods: A narrative synthesis of the literature covering the period 2005-2025 was undertaken using the PubMed, Scopus, and CINAHL databases. Articles addressing microbiome changes associated with ART and reproductive outcomes were included.

Results: ART procedures such as vaginal antisepsis, oocyte retrieval, embryo transfers, hormone stimulation, and use of prophylactic antibiotics have caused observable disruptions to the reproductive tract microbiome. The loss of Lactobacillus dominance and the development of dysbiosis are linked with lower implantation rates, a higher incidence of gestational disorders, such as preeclampsia and gestational diabetes, a heavy risk of preterm delivery, and an increased risk of adverse neonatal outcomes, such as altered immune development and developmental delay. Furthermore, newer alternatives including probiotics, individual microbiome testing, and multi-omic platforms show promise, but are limited by variability in clinical approaches and a lack of empirical backing.

Conclusion: The uterine and vaginal microbiome profoundly impact ART outcomes by modulating implantation, immune tolerance, and fetal development. Integrating microbiome-informed diagnostics and therapies into fertility treatments offers a new frontier in precision reproductive medicine.

The mouse embryo assay (MEA) is the standard test used in assisted reproduction to evaluate the toxicity and effectiveness of culture media and consumables. However, the assay has been criticised for its limited sensitivity, inconsistencies between laboratories, and ethical concerns. Despite the 3Rs principles, over 111 million mice and rats were used in the USA in 2017, with an unknown proportion of these being used in the MEA. While the FDA has provided MEA guidelines, its aim is to phase out animal toxicity testing within 3-5 years. This article explores the possibility of replacing the MEA with the bovine embryo assay (BEA), providing justifications based on ethics, science, practicality, and economics. Through a review of MEA applications, market data, regulatory frameworks and industry disclosures, the article estimates the current impact of the MEA. Incorporating the BEA into regulations could eliminate the need to breed mice for the MEA and greatly reduce the use of animals. Standardising and validating the BEA would provide a reliable and ethically preferable alternative that aligns with the growing demand from regulators and society for non-animal testing methods.

Purpose: To assess the associations between vanishing twin (VT) and fetal reduction (FR) with obstetric and perinatal outcomes following in vitro fertilization (IVF)-frozen embryo transfer (FET).

Methods: This was a retrospective cohort study involving women who had undergone FR or experienced VT during the period from 2012 to 2022. Cohorts were stratified by timing into early (< 15 weeks) and late (≥ 15 weeks) VT/FR. Controls comprised primary singletons and non-reduced twins. The primary outcome measurements were maternal and birth complications.

Results: Among 33,238 ongoing pregnancies, there were 24,316 primary singletons, 7452 non-reduced twins, 1354 VTs, and 116 FRs. Multivariable analyses showed birth outcomes in the study groups were similar to or better than non-reduced twin deliveries. Compared to primary singletons, both early and late FRs were associated with increased risk of preterm birth (PTB); late FR also increased the risk of low birthweight (LBW). Early and late VTs similarly had higher risks of PTB and LBW versus primary singletons. Obstetric complications were generally comparable or lower in the study groups versus twin deliveries; however, late FR was linked to a higher risk of hypertensive disorders of pregnancy compared with primary singletons, and late VT was associated with increased abnormal placentation versus primary singletons and twins.

Conclusions: In this large IVF-FET cohort, most birth and maternal outcomes were comparable or better than in non-reduced twins, but certain complications remained more common in both VT and FR groups. Both exposures were linked to adverse perinatal outcomes versus primary singletons. Moreover, VT and FR appear to be more problematic when these occur later in pregnancy.

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: To investigate whether the levels of mTOR signaling and ribosome biogenesis proteins in cumulus cells (CCs) can serve as non-invasive biomarkers for predicting embryo quality and pregnancy outcomes in women undergoing IVF.

Methods: In this prospective study, discarded CCs were collected from 83 IVF patients. The protein levels of mTOR, phosphorylated mTOR (p-mTOR), ribosomal protein S6 (RPS6), and phosphorylated S6 (p-RPS6) were quantified by Western blot and normalized to β-actin. These molecular data were correlated with clinical parameters, including ovarian reserve, embryonic development, and pregnancy outcomes. Statistical analyses were performed to determine optimal predictive thresholds and to evaluate single and combined protein models.

Results: Reduced levels of p-mTOR, p-RPS6, and RPS6 in CCs were robustly associated with superior IVF outcomes. Specific cutoff values were identified (e.g., p-mTOR < 0.45, p-RPS6 < 0.80) for predicting enhanced blastocyst formation and higher clinical pregnancy rates. Combining these biomarkers into multi-protein models significantly improved predictive accuracy for both embryonic development and pregnancy success compared to any single protein alone.

Conclusion: The assessment of p-mTOR, p-RPS6, and RPS6 in cumulus cells provides a powerful, non-invasive strategy for prognostic assessment in IVF. A molecular profile characterized by lower levels of these proteins is indicative of high oocyte developmental competence and a greater likelihood of successful pregnancy, offering a valuable tool for clinical decision-making prior to embryo transfer.

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.

Purpose: Aneuploidy is the most common genetic abnormality in human embryos and is one of the leading causes of embryo transfer failure. We aimed to identify candidate genes linked to mitotic-origin aneuploidy.

Methods: A control group of 588 euploid embryos and a case group of 236 mosaic embryos were utilized. Sequence alignment was first conducted to identify single nucleotide polymorphism (SNP) loci. Quality control (QC) and principal component analysis (PCA) were then performed to filter the SNPs and samples. The association test was carried out to identify significant variants. Fine mapping and gene sorting were used to screen and sort the candidate genes.

Results: Following variant identification, 10,650,011 SNPs were detected in 824 enrolled embryos. After quality control (QC), principal component analysis (PCA), and imputation, 496,728 SNPs across 762 embryos (226 cases and 536 controls) were retained. Association analysis identified 70 SNPs reaching genome-wide significance (p < 5e^-8). Following annotation, 37 variants within 27 genes were considered functional. Gene Ontology (GO) analysis revealed enrichment in innate immune and protein homeostasis pathways. Fine mapping and gene prioritization highlighted EMP2 as a candidate gene of mitotic error. We found that EMP2 may play a critical role in cell-cycle control and endometrial receptivity.

Conclusion: In this study, we performed genome-wide association analysis on embryonic sequencing data and identified EMP2 on chromosome 16 as a potential gene implicated in mitotic-origin aneuploidy. Further verification experiments are required to confirm the functions of candidate genes during embryogenesis.

Objective: To evaluate follicular fluid (FF) SCUBE1 levels as a novel angiogenesis-associated biomarker and investigate its role in reflecting the follicular vascular microenvironment and predicting ovarian response in women undergoing assisted reproductive technology (ART).

Methods: This prospective pilot study included 63 women undergoing IVF/ICSI. Paired serum and FF samples were analyzed. Patients were stratified into Poor (< 4 oocytes), Normal (4-10), and High (> 10) responders. SCUBE1 levels were measured via ELISA. The study primarily investigated the relationship between intrafollicular SCUBE1 and the magnitude of ovarian response as an indicator of the follicular "angiogenic switch."

Results: Serum SCUBE1 levels decreased significantly during ovarian stimulation (p < 0.001). However, FF SCUBE1 levels were approximately twofold higher in High Responders compared to Poor Responders (174.04 ± 112.45 vs. 84.66 ± 73.15 ng/mL, p = 0.043). A significant upward trend was confirmed across responder categories (Jonckheere-Terpstra, p = 0.032). In ROC analysis, FF SCUBE1 demonstrated promising predictive value for high ovarian response (AUC = 0.718, 95% CI: 0.532-0.904, p = 0.048). Notably, a cut-off of 59.13 ng/mL yielded a clinically useful 100% Negative Predictive Value (NPV). SCUBE1 levels did not correlate with oocyte maturation, fertilization, or clinical pregnancy.

Conclusion: Follicular fluid SCUBE1 is a dynamic marker of the follicular vascular microenvironment rather than a direct indicator of oocyte genetic competence. Elevated levels in high responders reflect the intensified angiogenic support required for multiple follicle development. Low FF SCUBE1 may serve as a clinical "red flag" for compromised follicular vascularization in cases of unexpected poor response.