Randomized controlled trial evaluating efficacy of autologous platelet -rich plasma therapy for patients with recurrent implantation failure in frozen-thawed embryo transfer after PGT-A

Abstract Study question To evaluate if the intrauterine perfusion with autologous PRP enhances frozen-thawed embryo transfer effectiveness in patients with recurrent implantation failure (RIF) after PGT-A. Summary answer The intrauterine perfusion (IP) with autologous PRP should be considered perspective, effective and safe therapeutic tool for patients with RIF What is known already Despite keen development of embryology, routine implementation of preimplantation genetic testing and assessment of endometrial receptivity, recurrent implantation failure (RIF) remains a challenging dilemma for fertility specialists. As it contains significant growth factors involved in delicate process of implantation, platelet –rich plasma (PRP) therapy should promote endometrial receptivity and improve assisted reproductive technology outcomes. Moreover, being autologous, PRP is not expected to trigger adverse immune event in the patient and is therefore perceived to be therapeutically safe. Pilot study conclusions have been inspiring however there is strong need for randomized controlled trials. Study design, size, duration Study type: Interventional. Study design: randomized controlled study Intervention Model: Parallel Assignment Masking: open-label Study size: 232 Duration: 40 months (July, 2019 - October, 2022) Multicenter trial: 3 ART clinics After obtaining institutional review board approval, 232 women aged 28 - 42 years were involved. Matching criteria: RIF, normal karyotype, absence of uterine factors of infertility, availability of euploid embryos after PGT-A Participants/materials, setting, methods 2 groups of patients: study group (N = 118): single intrauterine perfusion with 2.0 ml of PRP on day 10 -11 of menstrual cycle; Control group (N = 114): no therapy. Endometrium preparation was executed according to standardized protocol of hormone replacement therapy. PRP preparation was carried using patented tubes. In all cases SET was performed. Primary outcome measure was clinical pregnancy rate. Secondary outcome measures were pregnancy loss rate, endometrial thickness and adverse event. Main results and the role of chance The clinical pregnancy rate was higher in the study group (63.55% vs 38.59%) (χ2=14.462, OR = 2.775, 95% CI 1.630 - 4.722, p < 0,001). The endometrium thickness before intervention didn’t between groups (7.3 vs 7.4 mm), however, endometrium thickness measured just before embryo transfer was significantly higher in the study group (10.5 vs 8.4 mm, Student’s t-test value: 11.87; number of degrees of freedom f = 230; Critical value of Student’s t-test=1.972, at significance level α = 0.05). The pregnancy rate loss did not differ between groups (χ2=0.033, OR = 0.908, 95% CI 0.324 – 2.546, p > 0,05). No adverse event was noted. Limitations, reasons for caution The number of recruited participants was limited. Nevertheless, these data show statistically significant positive effect on ART outcomes. Further investigation and meta-analysis are required. Wider implications of the findings According to obtained results intrauterine perfusion with PRP should be recommended in FET cycles in patients with RIF. Given proven promotion effect on endometrial thickness the intrauterine perfusion (IP) with autologous PRP should be considered perspective and safe management method for patients with thin endometrium. Trial registration number 4765