Journal of Assisted Reproduction and Genetics最新文献

Purpose: To determine the optimal hCG dose in a dual hCG/GnRH agonist trigger for comparable pregnancy outcomes to hCG, while maintaining low OHSS rates in good-prognosis patients.

Subjects: This retrospective cohort study included patients aged 18-41 years undergoing IVF or IVF/ICSI with fresh embryo transfer from 2013 to 2024. Patients received either hCG-only (5,000-10,000 IU hCG/250-500 mcg Ovidrel) or dual trigger (1,500-2,000 IU hCG + 2 mg GnRH agonist).

Results: A total of 2641 cycles were analyzed (1,939 hCG-only, 616 1,500 IU hCG dual trigger, and 86 2,000 IU hCG dual trigger). The 2,000 IU hCG dual trigger group yielded more mature oocytes (16.0 vs. 11.6, aRR 1.29), fertilized embryos (12.9 vs. 8.8, aRR 1.43), and blastocysts (8.0 vs. 4.9, aRR 1.55) than hCG-only. Implantation rates were higher with 2,000 IU hCG dual trigger than hCG-only (50.0% vs. 32.0%, RR 1.56), with a dose-dependent improvement within the dual trigger groups (50.0% at 2,000 IU vs. 36.4% at 1,500 IU, RR 1.37). Ongoing pregnancy rates were similar between 2,000 IU hCG dual trigger and hCG-only (46.8% vs. 39.5%, aRR 1.12), but lower with 1,500 IU hCG dual trigger (46.8% vs. 37.6%, aRR 1.37). OHSS rates were low across all groups.

Conclusion: 2,000 IU hCG appears to be the optimal dose in a dual hCG/GnRH agonist trigger, resulting in similar pregnancy outcomes to an hCG trigger and low rates of OHSS among good-responder patients. Ongoing pregnancy rates were significantly lower with hCG doses under 2,000 IU in the dual trigger protocol.

Purpose: The uterine microbiome of in vitro fertilization (IVF) patients was analyzed using next-generation sequencing (NGS) targeting 16S rRNA. Lactobacillus spp. were examined, with a special focus on Lactobacillus iners. The effects of antibiotic therapy on pregnancy outcomes were investigated.

Methods: A total of 257 IVF patients underwent endometrial microbiome testing. Patients were initially classified based on the percentage of Lactobacillus spp. into the Lactobacillus-dominant microbiome (LDM) group and the non-LDM group using a cutoff of 90%. Treatment was provided to non-LDM patients. Treated patients who improved on the second test were included in the Post-treatment group, and their pretreatment status was also examined.

Results: Lactobacillus was dominant in many IVF patients, but some patients showed Gardnerella or other bacteria associated with bacterial vaginosis. The treatment improvement rate for the non-LDM group was 81.4%, with an equivalent or better pregnancy success rate compared with the LDM group. The effect on pregnancy outcomes of Lactobacillus may differ by species, with L. crispatus and L. gasseri tending to act positively, whereas L. iners at ≥ 74.2% acts negatively.

Conclusions: This study shows that the recovery of an LDM in non-LDM IVF patients improves the composition of the endometrial microbiome, and pregnancy outcomes approach those of patients initially having an LDM. Furthermore, in LDM cases, L. iners species were also associated with lower pregnancy rates. These findings suggest that both the presence and type of Lactobacillus species are important for IVF success and that targeted microbiome treatment may improve reproductive outcomes.

Purpose: To evaluate the feasibility and potential therapeutic effect of intrauterine platelet-rich plasma (PRP) infusion in patients with recurrent implantation failure (RIF) undergoing frozen embryo transfer (FET); to characterize PRP cytokine/growth factor profiles by cycle phase and pregnancy outcomes.

Methods: In this single-blinded, pilot randomized controlled trial, 52 women with unexplained RIF, normal uterine cavity, and endometrial thickness > 7 mm were enrolled. Eleven did not complete the FET cycle, leaving 33 patients in the intention-to-treat analysis (PRP: n = 13; control: n = 20). Eight additional patients received PRP in a subsequent cycle. Participants were randomized to intrauterine PRP or saline infusion in the follicular phase (cycle day 9-12 or days 10-14 of estradiol) and luteal phase (2 days before FET). PRP was isolated from autologous peripheral blood, and 1 mL was infused. Standard treatments were continued. PRP cytokine profiling was performed via Luminex analysis.

Primary outcome: pregnancy rate (PR). Secondary: clinical PR, miscarriage rate (MR), live birth rate (LBR), and cytokine correlations.

Results: Baseline and embryo-related variables were similar between groups. In the intention-to-treat analysis, PR was 69% in the PRP group vs 50% in controls (p = 0.27); LBR was 46% vs 25% (p = 0.27); MR was 22% vs 50% (p = 0.35). PRP was well tolerated. Eight cytokines differed by cycle phase. Lower luteal levels of CCL1, CCL26, and IL-23 correlated with live birth; higher CCL1 and CCL26 correlated with miscarriage.

Conclusion: While not statistically significant, PRP showed trends toward improved outcomes in RIF and was safe. Cytokine profiles varied by cycle phase and may reflect markers of fertility or treatment response.

Trial registration: The study was prospectively registered in the ClinicalTrials.gov Protocol Registration System (NCT03379649, https://clinicaltrials.gov/search?locStr=Sunnyvale,%20CA&country=United%20States&state=California&city=Sunnyvale&cond=Recurrent%20Implantation%20Failure&intr=Platelet%20Rich%20Plasma ). The study was activated on 01/16/2019 and closed on 12/20/2023. The first patient was enrolled on 1/20/2019 and last patient was enrolled on 1/25/2023.

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.

Purpose: Transgender men (TGM) are individuals who identify as males but were assigned female sex at birth. Gender-affirming testosterone therapy (GATT) is used to induce virilization, and its effects on fertility are discussed. To provide TGM with complete fertility counseling, we synthesized data concerning the impact of GATT on ovarian reserve and oocyte quality.

Methods: We conducted a narrative review of published data on the ovarian and oocyte features induced by GATT in TGM.

Results: Data on ovarian morphology and histology showed a normal proportion of primordial, primary, pre-antral, and antral follicles, and a significantly higher number of atretic and cystic follicles. Additionally, ovaries exhibited diffuse ovarian stromal hyperplasia and a thicker ovarian cortex, tunica albuginea, and basal membrane. No impact on ovarian reserve was observed. Oocyte quality following ovarian stimulation did not appear to be impaired and led to the birth of healthy offspring.

Conclusion: These findings may reassure transgender patients and their care providers that satisfactory reproductive outcomes are possible, even if GATT has already been initiated. However, further investigation is needed to assess the reversibility and functional impact of these changes on ovarian folliculogenesis, ART success rates, pregnancy, and child health.

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.