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Purpose: The window of implantation (WOI) is a brief period during which the endometrium is receptive to embryo implantation. This study investigated the relationship between miR-135a-5p and endometrial receptivity., Methods: Peripheral blood was collected on the day of ovulation and the 5th day after ovulation for high-throughput sequencing from women who achieved clinical pregnancy through natural cycle frozen embryo transfer. RT-qPCR assessed miR-135a-5p expression in the endometrium tissue or cells during the mouse implantation window or decidualization. Scanning electron microscopy was utilized to observe pinopode morphology and quantity in mice overexpressing miR-135a-5p during the WOI. Human endometrial stromal cells (HESC) and artificial induction of mouse uterine decidualization were used to explore whether miR-135a-5p overexpression inhibits decidualization by regulating HOXA10 and BMPR2. Furthermore, the impact of miR-135a-5p on HESC proliferation and HTR8/SVneo invasion was explored., Results: A total of 54 women were enrolled in the study. bioinformatics analysis and animal models demonstrated that miR-135a-5p was significantly downregulated during the WOI, and its high expression can lead to abnormal pregnancy outcomes. Overexpression of miR-135a-5p resulted in the absence of pinopode in mouse endometrial tissue during the WOI. High miR-135a-5p levels were found to potentially inhibit endometrial tissue decidualization by downregulating HOXA10 and BMPR2 expression. Finally, CEBPD was identified as a potential regulator of miR-135a-5p, which would explain the decreased miR-135a-5p expression during the WOI., Conclusion: MiR-135a-5p expression is significantly downregulated during the WOI. High miR-135a-5p levels suppress pinopode development and endometrial tissue decidualization through HOXA10 and BMPR2, contributing to inadequate endometrial receptivity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although both subcutaneous injection and intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) have been reported to improve pregnancy outcomes in patients with recurrent implantation failure (RIF), how to administer it is still no consensus. The study aimed to investigate which administration route is optimal. We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to April 10, 2023, with language in both English and Chinese. The randomized controlled trials (RCTs) compared the effectiveness of G-CSF to treat patients with RIF were included in this network meta-analysis (NMA). The odds ratio (OR) and 95% confidence interval (CI) in pregnancy outcomes (implantation rate, IR; clinical pregnancy rate, CPR; live birth rate, LBR; miscarriage rate, MR; ectopic pregnancy rate, EPR) were summarized by NMA with a random-effects model. A total of 1360 RIF patients from 14 RCTs were included in this NMA, with no publication bias and small sample effects. No direct evidence compared the effectiveness of different administration routes of G-CSF on IR, LBR and MR. Both subcutaneous injection and intrauterine infusion of G-CSF increased the IR (OR = 2.81, 95% CI: 1.10-7.24; OR = 2.15, 95% CI: 1.50-3.07, respectively) and CPR (OR = 2.79, 95% CI: 1.86-4.17; OR = 1.74, 95% CI: 1.30-2.33, respectively) in patients with RIF. According to SUCRA, subcutaneous injection is more likely to be the optimal medication administration route. However, more high-quality studies were also needed to support these, especially IR and LBR., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaohong Wang reports a relationship with National Natural Science Foundation of China that includes: funding grants., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to investigate whether the extended culture of day 3 (D3) embryos with low blastomere number to blastocyst following frozen-thawed embryo transfer improved the clinical outcomes., Methods: This was a retrospective study of clinical data of women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in the Tangdu Hospital. The patients were divided into groups with 4-5, 6, 7-9 and > 9 cells based on the blastomere number of D3 embryos. The clinical outcomes were compared., Results: In fresh transfer cycles, the implantation and clinical pregnancy rates significantly decreased, while the abortion rate significantly increased in the groups with 4-5 and 6 cells compared with those with 7-9 and > 9 cells. In frozen-thawed transfer cycles, the clinical pregnancy and implantation rates for a single blastocyst transfer cycle showed no significant differences in the groups with 4-5 and 6 cells compared with those with 7-9 and > 9 cells. However, the abortion rate was significantly higher in the group with 4-5 cells than in that with 7-9 and > 9 cells. In the double blastocyst transfer cycle, the clinical pregnancy rate showed no significant differences among the groups with 4-5, 6, and 7-9 cells., Conclusion: The implantation and clinical pregnancy rates of D3 embryos with 6 cells significantly decreased; these embryos were not considered as high-quality embryos. Extended culture of D3 embryos with ≤ 6 blastomeres to blastocysts, particularly 6-cell embryos, resulted in a similar clinical pregnancy rate as that of blastocysts derived from D3 embryos with ≥ 7 blastomeres.

Purpose: To investigate the effectiveness and safety of 36 different therapies for recurrent implantation failure (RIF) patients. Methods: We searched PubMed, Embase, the Cochrane Library (CENTRAL), Web of Science, and China National Knowledge Internet (CNKI) from inception to August 24, 2022, with language in both English and Chinese. Randomized controlled trials (RCTs) and observational studies that provided data with one of pregnancy outcomes on RIF patients were included in the network meta-analysis (NMA). The odds ratios (OR) and 95% credible interval (CrI) on pregnancy outcomes were summarized by NMA with a random-effects model. We also analyzed data from only RCTs and compared whether the optimal treatment is the same for different failed embryo transfer attempts. Results: The total of 29,906 RIF patients from 154 clinical studies (74 RCTs and 80 non-RCTs) were included in the NMA. In terms of implantation rate (IR), growth hormone (GH) (OR: 3.32, 95% CrI: 1.95–5.67) is the best treatment in all included studies; IVIG+PBMC (5.84, 2.44–14.1) is the best for clinical pregnancy rate (CPR); hyaluronic acid (HA) (12.9, 2.37–112.0) for live birth rate (LBR); and aspirin combined with glucocorticoids (0.208, 0.0494–0.777) for miscarriage rate (MR). The two-dimensional graphs showed that GH could maximize IR and CPR simultaneously; HA and GH could simultaneously increase IR and LBR to a large extent; HA could maximize IR and minimize MR. Conclusion: IVIG+PBMC, GH, and embryo medium enriched with HA could significantly improve pregnancy outcomes in patients with RIF. It appears that combination therapy is a potential administration strategy. Trial registration: This study has been registered on PROSPERO (CRD42022353423). [ABSTRACT FROM AUTHOR]