Abstract

Abstract Study question Does endometrial thickness (EMT) predict the occurrence of live birth following oocyte donation? Summary answer Our study found that EMT is predictive of live birth in oocyte donation. What is known already EMT is a widely used surrogate marker of endometrial receptivity and is believed to be associated with in vitro fertilization pregnancy outcomes. However, the evidence thus far is mixed, with many studies (and even meta-analyses) suggesting that EMT may have little/no predictive value. One potential reason for the heterogeneity in results may be that most studies assessed mostly fresh autologous embryo transfers, without accounting for embryo quality nor the effect exogenous ovarian stimulation may have on endometrial receptivity and subsequent pregnancy/perinatal outcomes. Moreover, most subcategorized EMT to facilitate interpretation, which may have inadvertently introduced bias to the analyses. Study design, size, duration This retrospective, multicentre, cohort study analyzed all single blastocyst embryo transfers following oocyte donation from 2010-2019 subdivided into regular intervals of EMT (<7.0 mm, 7.0-8.9 mm, 9.0-10.9 mm, ≥11.0 mm). EMT was also evaluated as a continuous variable, comparing the best-fitting fractional polynomial against the linear function, to minimize bias due to residual confounding that may occur following the categorization of continuous variables. Confounder adjustment was performed using multivariable generalized estimating equations regression analysis. Participants/materials, setting, methods The oocyte donation model was chosen to minimize the influence of potential confounding factors such as poor embryo quality and the effect of ovarian stimulation on endometrial receptivity. The main objective of the study was to compare live birth rates (LBR). Our secondary outcomes included other surrogate pregnancy (hCG-positive pregnancy, clinical pregnancy, and miscarriage rates) and perinatal (gestational age at birth, preterm birth under 37 weeks, birthweight z-score, small and large for gestational age) outcomes. Main results and the role of chance In total, 33915 embryo transfers were analyzed. Confounder variables included were female donor and recipient age, recipient BMI, female factor infertility, male factor infertility, number of mature oocytes donated, oocyte status (fresh versus vitrified), sperm source (partner or donor), embryo status (fresh versus vitrified), embryo quality, endometrial preparation (natural or artificial cycle) and year of transfer. When compared to the reference EMT of 9.0-11.0 mm, EMT <7.0 mm was associated with lower hCG positive pregnancy rates (51.3% vs 57.6%; aOR 0.82 CI 0.75-0.89), lower clinical pregnancy (41.9% vs 49.1%; aOR 0.79 CI 0.73-0.86), higher miscarriage rates per hCG positive pregnancy (37.5% vs 31.4%; aOR 1.31 CI 1.16-1.47) and lower LBRs per transfer (32.1% vs 39.5%; aOR 0.76 CI 0.69-0.83). Regarding perinatal outcomes, we found significantly higher preterm delivery rates following an EMT <7.0 mm (14.1% vs 9.9%; aOR 1.54 CI 1.21-1.96) and higher large for gestational age rates associated with EMT ≥11.0 mm (16.4% vs 12.2%; aOR 1.40 CI 1.07-1.83). The fractional polynomial analysis revealed that the subcategorization of EMT caused clinically-relevant residual confounding. Specifically, LBRs assumed an approximate bell-shaped relationship with EMT, with LBR rates decreasing for both thinner EMTs (<7 mm subgroup) and thicker EMTs (≥11.0 mm subgroup). Limitations, reasons for caution The retrospective nature of the study and the inherent risk of bias related to unmeasured confounding may have impacted the results. Another potential limitation is the lack of perinatal outcome data due to loss of follow-up, which should be considered when interpreting these results. Wider implications of the findings Our results support the use of EMT as a predictor of live birth and as a marker of endometrial receptivity and competence. Moreover, it stresses the potential danger of subcategorizing all EMT <7.0 mm and >11.0 mm as equivalent, as the study found that these subgroups have varying LBR. Trial registration number not applicable

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