Impact of intrauterine infusion of human chorionic gonadotropin and hyaluronic acid enriched medium on pregnancy outcomes in frozen-thawed cycles with recurrent implantation failure: An RCT.

Peivandi S, Jafarifard P, Zamaniyan M, Yazdani-Charati J
International journal of reproductive biomedicine · 2025 · doi:10.18502/ijrm.v23i9.20158 · PMID:41306463 · PMC12603573
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⚙ AI-generated summary by claude@2026-07, 2026-07-15 ⓘ

Combining intrauterine hCG infusion with hyaluronic acid-enriched transfer medium did not improve overall pregnancy rates but showed benefits for specific embryo transfer stages and numbers.

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⚙ AI-generated deep summary by claude@2026-07, 2026-07-15 · read from full text ⓘ

This single-blind randomized controlled trial studied whether intrauterine infusion of 500 IU hCG 20 minutes before transfer, combined with transfer of frozen-thawed embryos in a HA-enriched medium (EmbryoGlue) versus no HA, improves clinical pregnancy outcomes in women with recurrent implantation failure undergoing hormone-prepared FET cycles. Among 158 enrolled participants (152 analyzed after excluding arrested/underdeveloped embryos after thawing), the clinical pregnancy rate (fetal heartbeat at 6 weeks) was lower in the intervention group (26.66%) than the control group (38.96%), and chemical pregnancy, implantation rate, and ongoing pregnancy also showed no statistically significant differences. The main caveat explicitly noted is the trial’s single-blind design with limited ability to blind the interventions (double blinding was not possible). This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

BackgroundRecurrent implantation failure in assisted reproductive technology is a major challenge. Intrauterine human chorionic gonadotropin (hCG) infusion and hyaluronic acid enriched embryo transfer media have shown individual effects, but their combined effect in these cases undergoing frozen-thawed embryo transfer is unknown.ObjectiveThis study aims to investigate the effect of combined therapy on pregnancy outcomes.Materials and methodsThis is a single-blind, randomized controlled trial on 158 participants. The cases were randomly assigned to either the intervention group (pretransfer intrauterine hCG infusion and embryo loaded with hyaluronic acid-enriched embryo transfer medium at the time of transfer) or the control group (standard embryo transfer medium). The outcomes were chemical and clinical pregnancy rates, implantation, abortion, and ongoing pregnancy rates.ResultsA total of 158 participants were enrolled in this study in 2 equal groups. The intervention did not significantly improve the overall pregnancy rate compared to control (24% vs. 33.7%, p = 0.30). The results showed that, by controlling variables, the chance of clinical pregnancy in the intervention group was 12% lower than in the control group, although the difference was not statistically significant (p = 0.879). With each increase in the number of embryos, the chance of a pregnancy would be 2.26 times higher. Also, the chance of pregnancy in the morula stage was 68% lower than in the cleavage stage (p < 0.05).ConclusionThe combined approach of intrauterine hCG infusion and the hyaluronan-enriched embryo transfer medium did not significantly improve the overall pregnancy rate but had a significant effect on specific cases using the embryo at the cleavage stage for transfer and cases that received more than one embryo for transfer.
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S. Peivandi and P. Jafarifard contributed to the design and conceptualization of the study, selection of methodologies, and drafting of the manuscript. M. Zamaniyan was involved in data collection and editing the draft. J. Yazdani-charati was responsible for data analysis and interpretation of the findings. S. Peivandi played a key role in interpreting the results, editing the manuscript, and providing general feedback throughout all.

Coi Statement

The authors declare that there is no conflict of interest.

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