Comparative efficacy of regenerative medicine approaches in patients with recurrent implantation failure undergoing euploid embryo transfer

Background: Recurrent implantation failure occupies a central place among the unresolved challenges of contemporary reproductive medicine, occurring in 15–20% of women undergoing in vitro fertilization treatment. Despite the implementation of preimplantation genetic testing for aneuploidy, which allows for the embryonic factor to be excluded, the pregnancy rate following euploid embryo transfer in patients with recurrent implantation failure remains substantially lower than in fertile women. Effective methods for correcting endometrial dysfunction in this patient population are still absent from clinical guidelines. Aim: The aim of this study was to compare, in patients with recurrent implantation failure, the efficacy of two regenerative medicine approaches (intrauterine perfusion of platelet rich plasma and subcutaneous administration of granulocyte colony stimulating factor) in frozen–thawed euploid embryo transfer cycles. Methods: This randomized controlled trial was conducted involving patients with recurrent implantation failure and confirmed euploid embryos. Four groups of 47 patients each were formed: Group 1 received intrauterine perfusion of 1 ml of autologous platelet rich plasma on days 10–11 of the menstrual cycle; Group 2 received subcutaneous injections of 300 μg of recombinant human granulocyte colony stimulating factor (filgrastim) daily for 3 consecutive days, starting on the day of embryo transfer; Group 3 underwent standard endometrial preparation without any regenerative intervention; and the control group consisted of gestational surrogates (fertile women) who received an identical hormonal preparation protocol. The primary outcome was the clinical pregnancy rate, defined as visualization of a gestational sac on transvaginal ultrasound at 6–7 weeks. Secondary outcomes included the live birth rate, the miscarriage rate up to 12 weeks of gestation, and endometrial thickness. Results: The clinical pregnancy rates in Groups 1, 2, 3, and the control group differed significantly: 63.8% (30/47), 48.9% (23/47), 27.7% (13/47), and 68.1% (32/47), respectively. Group 1 demonstrated a significant superiority over Groups 2 and 3 (p 0.010), while the difference versus the control group did not reach significance (p 0.050). The live birth rates were 55.3% (26/47) in Group 1, 40.4% (19/47) in Group 2, 21.3% (10/47) in Group 3, and 61.7% (29/47) in the control group, with significant differences identified between Group 1 and Groups 2 and 3 (p 0.010). Factor analysis demonstrated that patient age, endometrial thickness, and the absence of chronic endometritis are independent predictors of clinical pregnancy and live birth. Conclusion: Intrauterine perfusion of platelet rich plasma is a highly effective method for increasing the clinical pregnancy and live birth rates in patients with recurrent implantation failure, yielding outcomes comparable to those achieved in fertile women.