Recurrent implantation failure remains a distressing challenge for both patients and clinicians, often leading to significant emotional and financial strain. Despite the transfer of high-quality embryos, many patients fail to conceive, suggesting that endometrial receptivity is the primary limiting factor. Endometrial scratching is a controversial yet intriguing intervention that seeks to maximize the window of implantation through mechanical provocation. Understanding its true clinical value is essential for evidence-based practice in reproductive medicine, especially as the industry shifts toward more personalized treatment pathways. This study provides necessary clarity by distinguishing between general IVF populations and those specifically afflicted by RIF. By establishing clearer parameters for the use of ES, this research assists in reducing trial-and-error in ART, potentially improving overall success rates and patient satisfaction while minimizing the reliance on more invasive or expensive diagnostic tests for receptivity.
The study aims to determine whether performing mechanical endometrial scratching in the pre-transfer mid-luteal phase significantly increases clinical pregnancy and live birth rates in patients undergoing fresh or frozen embryo transfer.
This prospective, randomized controlled trial involved 420 women (ages 22–41) undergoing IVF or ICSI at a tertiary fertility center. Participants were randomized into two groups: the ES group (n=212) and the control group (n=208). In the ES group, an endometrial biopsy was performed using a Pipelle catheter in the mid-luteal phase (days 21–24) of the spontaneous menstrual cycle preceding the stimulation or preparation cycle. The control group underwent a sham procedure. Exclusion criteria included severe endometriosis, hydrosalpinx, or untreated uterine anomalies. Both groups followed standardized ovarian stimulation protocols and underwent blastocyst-stage transfers. The primary outcome measure was the clinical pregnancy rate (CPR), defined by the presence of at least one gestational sac with fetal cardiac activity at 6–7 weeks’ gestation. Secondary outcomes included implantation rates (IR) and live birth rates (LBR). Statistical analysis was performed using SPPS version 26.0, employing Chi-square tests for categorical variables and independent t-tests for continuous data, with significance set at p < 0.05.
Final analysis included 398 patients (ES: n=201, Control: n=197). In the general study population, the clinical pregnancy rate (CPR) was 42.3% in the ES group compared to 36.5% in the control group (p=0.24), showing no significant difference. However, in a pre-specified sub-analysis of patients with two or more prior failed transfers (n=144), the ES group exhibited a significantly higher CPR (48.6% vs. 31.9%; OR 2.02, 95% CI 1.05–3.88, p=0.034). The live birth rate (LBR) in this RIF subgroup was also higher in the ES arm (38.9% vs. 25.0%; p=0.041). The implantation rate per embryo transferred was 31.2% in the ES group and 24.8% in the control group (p=0.057). No significant differences were observed in miscarriage rates (12.4% vs. 15.2%; p=0.61) or ectopic pregnancies between the two study arms. The data indicates that the therapeutic effect of endometrial scratching is most pronounced in patients with history-verified receptivity challenges rather than the broader IVF population.
Our findings indicate that endometrial scratching significantly enhances clinical pregnancy rates specifically within the RIF subgroup, potentially through the modulation of local cytokine profiles and improved decidual response. However, its routine application for all IVF patients—particularly those in their first or second cycles—did not yield statistically significant benefits. The study confirms that while ES is a viable low-cost intervention, its utility is highly dependent on patient history and the number of prior failed transfers. Clinicians should consider ES primarily as a secondary intervention for patients with unexplained implantation failure. Further molecular studies are required to elucidate the specific markers of receptivity triggered by mechanical injury, but the current data supports incorporating ES into personalized ART protocols for refractory cases. These results provide a framework for refining clinical guidelines regarding mechanical endometrial preparation.