Unraveling the H19/GAS1 axis in recurrent implantation failure: A potential biomarker for diagnosis and insight into immune microenvironment alteration.

Recurrent implantation failure (RIF) presents a significant clinical challenge due to the lack of established diagnostic and therapeutic guidelines. Emerging evidence underscores the crucial role of competitive endogenous RNA (ceRNA) regulatory networks in non-cancerous female reproductive disorders, yet the intricacies and operational characteristics of these networks in RIF are not fully understood. This study aims to demystify the ceRNA regulatory network and identify potential biomarkers for its diagnosis. We analyzed expression profiles of three RNA types (long noncoding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) sourced from the GEO database, leading to the identification of the H19-hsa-miR-301a-3p-GAS1 ceRNA network. This network demonstrates significant diagnostic relevance for RIF. Notably, the H19/GAS1 axis within this ceRNA network, identified through correlation analysis, emerged as a promising diagnostic marker, as evidenced by operating receiver operator characteristic (ROC) curve analysis. Further investigation into the binding potential of miR-301a-3p with H19 and GAS1 revealed a close association of these genes with endometrial disorders and embryo loss, as per the Comparative Toxicogenomics Database. Additionally, our immune infiltration analysis revealed a lower proportion of T cells gamma delta (γδ) in RIF, along with distinct differences in the expression of immune cell type-specific markers between fertile patients and those with RIF. We also observed a correlation between aberrant expression of H19/GAS1 and these immune markers, suggesting that the H19/GAS1 axis might play a role in modifying the immune microenvironment, contributing to the pathogenesis of RIF. In conclusion, the ceRNA-based H19/GAS1 axis holds promise as a novel diagnostic biomarker for RIF, potentially enhancing our understanding of its underlying mechanisms and improving the success rates of implantation.

Association Between Fresh Embryo Transfers and Frozen-Thawed Embryo Transfers Regarding Live Birth Rates Among Women Undergoing Long Gonadotropin-Releasing Hormone Antagonist Protocols.

Background: The availability and use of frozen-thawed embryos after controlled ovarian hyperstimulation for assisted reproduction have increased with improvements in vitrification techniques and the rise of gonadotropin-releasing hormone (GnRH) antagonist protocols. Although evidence has shown that frozen-thawed embryo transfers (FETs) result in higher live birth rates than fresh embryo transfers, it is uncertain whether this association exists in cycles employing the GnRH antagonist protocol. Objective: To test the hypothesis that FETs are more likely to result in a live birth than fresh embryo transfers in a GnRH antagonist protocol cycle and to investigate whether frozen blastocyst transfer increases live birth rates compared to fresh blastocyst transfer. Design: A retrospective historical cohort study was conducted using data collected from the Department of Reproductive Medicine of Liuzhou Maternity and Child Healthcare Hospital for 1,437 patients who underwent the GnRH antagonist protocol between 1 January 2015, and 31 December 2020. The primary outcome was the live birth rate, which was compared between fresh embryo transfer and FET, and the secondary outcomes were clinical pregnancy rate and miscarriage rate, which were compared between the two groups. Analyses were adjusted to account for the age of the patient, number of embryo transfers, day of embryo transfer, and type of infertility. Results: Fresh embryo transfers accounted for 1,026 (71.4%) of the 1,437 patients who underwent the GnRH antagonist protocol in our analysis, while FETs accounted for 411 (28.6%). Patients with fresh and frozen-thawed embryos had comparable median body mass index (body mass index; 22.3 [IQR, 24.6-20.0] vs. 22.0 [IQR, 24.5-19.9]). There was a significant difference in the median age of the fresh embryo transfer group (34.0 [IQR, 39.0-30.0]) and the Frozen-thawed embryo transfer group (32.0 [IQR, 37.0-29.0]). Blastocysts were transferred in 14.6% of the fresh embryo transfer cycles and 45.5% of the FET cycles, whereas they account for 10.4% and 13.0% of all patients, respectively. The mean number of embryos transferred was 2 (IQR, 2.0-1.0) for the fresh embryo transfer group and 1 (IQR, 2.0-1.0) for the FET group, with a significant difference in the mean number of embryos transferred. The live birth rate after fresh embryo transfer vs. FET was 28.7% vs. 34.5% (absolute difference, 5.9%; adjusted relative risk [aRR], 1.15 [95% CI, 0.88-1.51]). The clinical pregnancy rates were 39.9% vs. 46.0%, respectively (absolute difference, 6.1%; aRR, 1.10 [95% CI, 0.85-1.43]). The miscarriage rates were 22.5% vs. 23.8%, respectively (absolute difference, 1.3%; aRR, 1.13 [95% CI, 0.75-1.70]). Conclusion: In this retrospective study of women who underwent assisted reproduction using GnRH antagonists, FETs resulted in a higher live birth rates and clinical pregnancy rates than fresh embryo transfers, which parts of these differences were attributable to embryo stage. However, the interpretation of the findings is limited by the possibility of selection and confounding biases.

The intrauterine perfusion of granulocyte-colony stimulating factor (G-CSF) before frozen-thawed embryo transfer in patients with two or more implantation failures.

The objective of this study was to investigate the clinical benefits of intrauterine perfusion with G-CSF in patients undergoing a frozen-thawed embryo transfer (FET) after at least two previous implantation failures. This was a prospective, randomized, single-blind study. The intervention group received an intrauterine infusion of G-CSF whereas the placebo group was given an intrauterine infusion of physiological saline before embryo transfer. A third (control) group did not receive an intrauterine infusion prior to embryo transfer. The clinical pregnancy rates of both the intervention and placebo group were significantly higher than that in the control group (p < 0.05). But the miscarriage rates of the G-CSF were significantly lower than those of the other two groups (p < 0.05). The intrauterine infusion of G-CSF before frozen-thawed embryo transfer significantly reduced miscarriage rates and improve the live birth rates. While intrauterine perfusion with physiological saline did not reduce miscarriage rates.