O-202 Novel use of hyaluronan enriched media for improving implantation in intrauterine insemination: a prospective randomised controlled trial (HEMI Trial)

Abstract

Abstract Study question Does the intrauterine instillation of hyaluronan-enriched media influence the implantation rate and reproductive outcomes in patients undergoing controlled ovarian stimulation and intrauterine insemination? Summary answer The intrauterine instillation of Hyaluronan-enriched media significantly improved the implantation rates and ongoing pregnancy rate in women undergoing controlled ovarian stimulation and intrauterine insemination treatment What is known already Hyaluronan is a macromolecule belonging to the glycosaminoglycans family, secreted by cumulus granulosa cells, and is naturally present in the female reproductive tract. Various mechanisms have been proposed to explain the implantation-enhancing properties of Hyaluronan including increased cell-cell and cell-matrix adhesion, by producing a viscous environment for the integration of embryo in intrauterine fluid and its autocrine and paracrine functions via CD44 receptors. This is probably the first trial studying the effect of hyaluronan-enriched media in intrauterine insemination treatment. The proposed novel intervention is based on the biological plausibility and proven safety of hyaluronan in IVF studies. Study design, size, duration This parallel group Randomised Controlled trial was conducted over 2 years of duration, from 2021 to 2023. A total of 100 couples diagnosed with unexplained infertility planned for controlled ovarian stimulation and intrauterine insemination (COS-IUI) treatment were randomized into the intervention and control arm of the trial. Before the commencement of the study, the trial was registered with the Clinical Trial Registry-India (CTRI), and institutional ethical approval was obtained. Participants/materials, setting, methods 100 couples diagnosed with unexplained infertility attending tertiary-level university hospital were allocated to the intervention and control group using block randomization in 1:1 allocation. In the intervention group, the participants underwent intrauterine instillation of 0.4 ml of hyaluronan enriched media, 4 days following intrauterine insemination treatment. The statistical package SPSS (version 21) was used for analysis and results were considered to be statistically significant if the P-value was <0.05. Main results and the role of chance The mean female age of the study population was 28.12±3.74 years with an average duration of infertility of 3.95 ±2.17 years. The study participants underwent an average of 1.7 IUI cycles in the control group and 1.6 cycles in the intervention group. A cumulative biochemical pregnancy rate of 36.5% and 16.6% was observed amid the the intervention group and control group respectively and the difference was statistically significant with a p-value of 0.039. Similarly, the cumulative ongoing pregnancy rate beyond 20 weeks of gestation was statistically significantly higher among the intervention arm of the trial as compared to the control group (31.7% vs 11.9%, p = 0.035). There was a trend of improved clinical pregnancy rate among the intervention participants, however, this difference did not reach statistical significance (34.1% vs 16.6%, p = 0.067). The miscarriage rate was comparable among both groups. The number needed to treat was estimated to be 5, which in effect meant that 5 women would have to receive intrauterine instillation of hyaluronan enriched media for 1 additional ongoing pregnancy. Limitations, reasons for caution The longer follow-up period would have allowed the reporting of live-birth rate which is undeniably the most meaningful parameter to appraise an intervention. Larger multicentric studies are required to establish the clinical benefit and generalisability of the proposed intervention. Wider implications of the findings The study proposes a potential novel, simple, minimally invasive, and patient-acceptable intervention to increase the success rates of intrauterine insemination. Being the first study on the topic, the study can provide a basis for future large multicentric studies on the topic. Trial registration number Clinical Trial Registry-India (CTRI) number- CTRI/2021/10/037064.