Intentional endometrial injury significantly improves ongoing pregnancy rates of an oocyte donation program in patients without recurrent implantation failure (RIF): a randomized controlled trial.

Abstract Study question Is endometrial scratching a useful add-on to be applied in assisted reproduction patients without recurrent implantation failure (RIF)? Summary answer Endometrial scratching results in significantly higher clinical and ongoing pregnancy rates per intention to treat (ITT) among women undergoing oocyte donation without RIF. What is known already The effect of endometrial injury or endometrial scratch (ES) on reproductive outcomes has been widely studied by randomized controlled trials but from the information obtained regarding its benefit on improving endometrial receptivity remains controversial. Oocyte donation programs (OD) provides with the ideal setting for this research, as the recipient's endometrial priming guarantees the homogeneity of the endometrium avoiding a deleterious differential effect of the stimulation on endometrial receptivity and makes comparable the quality of the oocytes and transferred embryos, then limiting the confounding factors involved in studies with autologous oocytes and their frozen surplus embryos, better addressing the research question. Study design, size, duration A multicentric, open-label, randomized controlled trial has been conducted in a private setting from Oct 2013-Nov 2022. Eligible recipients were randomly assigned in a 1:1 ratio to either ES (by pipelle biopsy in the luteal phase of the menstrual cycle prior to the embryo transfer, n = 303) or no intervention (NES, n = 310), through a computer-generated randomization list, and embryo transfers (ET) performed in the cycle following the intervention. Participants/materials, setting, methods 18-44 years aged ovum recipients with preserved ovarian function, 19-29.9 kg/m2, first/ second OD fresh embryo transfer, endometrial thickness > 6 mms, and 1-2 optimal quality blastocysts transferred. Exclusion: any adverse condition, RIF with OD, ET not performed in the cycle following the intervention. Outcomes included ongoing implantation rate (ongoing sacs/ embryo transferred), biochemical, clinical and ongoing pregnancy rates analyzed per ITT basis and per protocol strictly completed (PP, treatment correctly received, embryo transfer achieved). Main results and the role of chance A total number of 458 recipients underwent OD-embryo transfer, 226 in scratching arm and 232 in the NES group. No differences existed in mean age and BMI of recipients and oocyte donors, oocytes retrieved and microinjected, fertilization rates, blastocysts transferred, endometrial thickness and estradiol /progesterone levels after their endometrial priming, nor other clinically relevant parameters. The biochemical pregnancy rate was 62.6%95%CI(56.6-68.3) and 55.6%95%CI(49.7-61.3) in the ES arm and in NES arm on the ITT analysis (OR 1.073 95%CI(0.990-1.163), p = 0.088); and 75.3%95%CI(69.0-80.7) vs. 70.7%95%CI(64.3-76.4), respectively PP (OR1.048 95%CI(0.965-1.137), p = 0.266. The clinical pregnancy rate was 57.1%95%CI(51.0-63.1) and 47.5% 95%CI(41.7-53.3) in the ES arm and in NES arm on the ITT analysis (OR = 1.102 95%CI(1.015-1.196); p = 0.021), and in the per protocol analysis, 68.6% 95%CI(62.0-74.6) vs 60.3%95%CI(53.7-66.6) respectively, OR = 1.086 95%CI(0.995-1.186), p = 0.066. The ongoing pregnancy rate was 45.1%95%CI(39.1-51.2) and 36.3% 95%CI(30.8-42.1) in the ES arm and in NES arm on the ITT analysis (OR = 1.092 95%CI(1.007-1.183); p = 0.033), and in the per protocol analysis, 53.8%95%CI(47.0-60.5) vs 46.1%95%CI(39.6-52.8) respectively, OR = 1.080 95%CI(0.985-1.184), p = 0.101. The ongoing implantation rate was in the PP analysis, 61.4%95%CI(55.1-67.8) in ES, and 56.5%95%CI(50.1-68.2) in NES respectively, p = 0.276, while in the ITT analysis, 51.3% 95%CI(45.4-57.2) vs 44.4% 95%CI(38.7-50.1), p = 0.098 in the ES arm and in NES arm. Limitations, reasons for caution The number of patients not fulfilling the complete procedure probably avoided to find significant differences on the PP analysis, and during the study, there may be some clinical and/or laboratory changes through the years, that should have been affecting outcomes on both groups. Wider implications of the findings This RCT shows that ES in the luteal phase of the cycle preceding the OD embryo transfer in recipients without RIF would pose a significant benefit thus its consideration for all IVF patients can be advised at this point. Trial registration number NCT01955356