Endometrial compaction and ongoing pregnancy in modified natural cycle frozen euploid embryo transfer: a prospective multicentre cohort study with standardized transvaginal ultrasound assessment

STUDY QUESTION: Does endometrial compaction, assessed by transvaginal ultrasound at two measurement time points, predict ongoing pregnancy in patients undergoing single euploid blastocyst transfer in a modified natural cycle frozen embryo transfer (mNC-FET)? SUMMARY ANSWER: Endometrial compaction of ≥5% between the day of ovulation triggering and the day of embryo transfer was not associated with ongoing pregnancy rate or any secondary reproductive outcome in this prospective multicentre cohort. WHAT IS KNOWN ALREADY: Endometrial compaction-a reduction in endometrial thickness (EMT) following progesterone-induced secretory transformation-has been proposed as a potential marker of endometrial receptivity in FET cycles. However, existing evidence is conflicting. Retrospective studies have reported positive associations between compaction and ongoing pregnancy in programmed cycles, while prospective data, including the only prior study restricted to euploid single FET, have not confirmed this relationship. Crucially, most studies have used transabdominal ultrasound for the transfer-day measurement, a recognized source of measurement error. No prospective study has examined compaction exclusively in mNC-FET using transvaginal ultrasound at both time points. STUDY DESIGN, SIZE, DURATION: Prospective multicentre observational cohort study conducted between March 2023 and March 2025 across six assisted reproduction units of Instituto Bernabeu group (Spain). A total of 207 patients who met all inclusion criteria and completed the full protocol were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-50 years undergoing mNC-FET with a single euploid blastocyst (confirmed by preimplantation genetic testing for aneuploidy via next-generation sequencing) were included. EMT was measured transvaginally at T1 (day of hCG trigger) and T2 (day of embryo transfer). Compaction was defined as a ≥5% reduction in EMT from T1 to T2. Additional thresholds of ≥10% and ≥15% were evaluated as sensitivity analyses. The primary outcome was ongoing pregnancy, defined as foetal cardiac activity at 10 weeks of gestation. Multivariable logistic regression was performed, adjusting for age, previous live births, previous miscarriages, BMI, and oocyte origin. MAIN RESULTS AND THE ROLE OF CHANCE: Of 207 patients, 58 (28.0%) met the compaction criterion (≥5%). The compaction group had a significantly greater T1 EMT (9.55 ± 1.54 mm vs 8.39 ± 1.14 mm, P < 0.001) and a lower T2 EMT (7.91 ± 1.19 mm vs 9.75 ± 1.55 mm, P < 0.001). Ongoing pregnancy rates were 50.0% in the compaction group versus 53.7% in the non-compaction group (P = 0.633). This difference was not significant on multivariable analysis (adjusted odds ratio 0.80, 95% CI 0.38-1.67, P = 0.546). The null association was consistent across all compaction thresholds (≥10%: P = 0.674; ≥15%: P = 0.928) and across all secondary outcomes, including clinical pregnancy rate (56.9% vs 59.1%, P = 0.777), biochemical pregnancy loss (10.8% vs 8.3%, P = 0.737), and early pregnancy loss rate (12.1% vs 9.1%, P = 0.734). The overall ongoing pregnancy rate was 52.7% (109/207). LIMITATIONS, REASONS FOR CAUTION: The distribution between groups was asymmetric (28% compaction vs 72% non-compaction), deviating from the balanced allocation anticipated at protocol design, which may reduce statistical power. Although both measurements were transvaginal, a subset of T1 measurements from international patients were performed at external centres and validated remotely by Instituto Bernabeu's physicians. Live birth data were only partially available at the time of analysis; however, ongoing pregnancy at 10 weeks is a validated and widely accepted surrogate for live birth in reproductive medicine trials. WIDER IMPLICATIONS OF THE FINDINGS: These findings do not support the hypothesis that endometrial compaction is associated with improved reproductive outcomes in mNC-FET with euploid embryos. The consistent null result across multiple thresholds and outcomes, obtained with a fully standardized transvaginal ultrasound methodology, strengthens the current evidence base. Routine assessment of endometrial compaction with the aim of identifying patients with a favourable prognosis does not appear to be clinically justified in this setting; indeed, acting upon compaction status could lead to unnecessary cycle cancellations in patients who would otherwise achieve ongoing pregnancy. FUNDING: This study was supported by a Doctoral Research Grant awarded by Miguel Hernandez Public University, Spain (Rectoral Resolution No. 04588/2021). The funding body had no role in the study design, data collection, analysis or interpretation of the data, preparation of the manuscript, or decision to submit the manuscript for publication. DISCLOSURES: The authors declare no competing interests related to the present study. No personal payments, financial incentives, or commercial benefits were received by any author in relation to this work. TRIAL REGISTRATION NUMBER: NCT05960370.