Abstract

Abstract Study question Can standard morphological assessment of blastocyst quality accurately predict first trimester miscarriage? Summary answer Decreasing trophectoderm and inner cell mass grade equally predicted first trimester miscarriage independently. After adjusting for confounders, poor embryo quality was not associated with miscarriage. What is known already Embryo quality determined by morphological assessment is a well-established predictor of successful implantation and live birth with in vitro fertilization treatment. Chromosomal abnormalities account for over half of first trimester miscarriages, and links between ploidy status and embryo morphology have been demonstrated. However, the association between blastocyst morphology and first trimester miscarriage is still poorly understood with consensus opinion yet to be established. Study design, size, duration This single centre retrospective cohort study included 2020 fresh and frozen single embryo transfers between October 2010 and October 2020. Blastocyst degree of expansion, inner cell mass (ICM) grade, and trophectoderm (TE) grade were compared for 354 pregnancies ending in first trimester miscarriage and 1666 pregnancies that surpassed 12 weeks of gestation. The association between blastocyst morphology and miscarriage was examined by logistic regression analysis. Participants/materials, setting, methods All single blastocyst transfers over a 10-year period resulting in first trimester miscarriage or pregnancy beyond 12 weeks of gestation were included in our analysis. Cycles involving donor oocytes, preimplantation genetic testing, resulting in biochemical pregnancy, or ectopic pregnancy were excluded. Differences between groups were analysed with chi-square and logistic regression analysis. Odds ratios (aOR) for miscarriage versus ongoing pregnancy were adjusted for maternal age, cycle type, blastocyst expansion, ICM grade, and TE grade. Main results and the role of chance Out of 2020 single embryo transfer cycles, a total of 354 resulted in first trimester miscarriage (17.5%). Independently, miscarriage rates increased with decreasing ICM grade (A to C; 14.6%, 18.9%, and 26.5%, p = 0.003) and TE grade (A to C; 14.6%, 17.7%, and 26.6%, p = 0.004). Univariate logistic regression showed higher risks of miscarriage with ICM grade C compared to ICM grade A (OR 2.241, 95%CI 1.292-3.886, p = 0.004), TE grade C compared to TE grade A (OR 2.116, 95%CI 1.360 – 3.292, p = 0.001), and expansion grades of 1 and 2 compared to expansion of 5 and 6 (OR 2.514, 95%CI 1.477 – 4.278, p = 0.001). After multivariable logistic regression adjusting for maternal age at embryo transfer, cycle type, and all morphological parameters (degree of expansion, ICM, and TE), only expansion grade of 1 and 2 showed a statistically significant association with first trimester miscarriage. Limitations, reasons for caution The main limitation of this study is the retrospective design of the analysis, and subjective nature of embryo morphological assessment. There may also be residual confounding by unknown or unmeasured confounders such as paternal age or maternal BMI. Wider implications of the findings Embryo selection for transfer should continue to be guided by standard morphological assessment. Decreasing grade of ICM and TE are both positively associated with an increased miscarriage risk, while poorly expanded blastocysts are most predictive of first trimester miscarriage. Patients undergoing embryo transfer should be adequately counselled about these risks. Trial registration number Not applicable

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