Association between a morphokinetic ploidy prediction model risk score and miscarriage and live birth: a multicentre cohort study

Abstract

Objective: To determine whether the aneuploidy risk score from a morphokinetic ploidy prediction model, Predicting Euploidy for Embryos in Reproductive Medicine (PREFER), is associated with miscarriage and live birth outcomes.

Design: Multicentre cohort study.

Setting: Nine in vitro fertilization clinics in the United Kingdom.

Patients: Data were obtained from the treatment of patients from 2016-2019. A total of 3587 fresh single embryo transfers were included; preimplantation genetic testing for aneuploidy) cycles were excluded.

Intervention: PREFER is a model developed using 8,147 biopsied blastocyst specimens to predict ploidy status using morphokinetic and clinical biodata. A second model using only morphokinetic (MK) predictors was developed, P PREFER-MK. The models will categorize embryos into the following three risk score categories for aneuploidy: "high risk," "medium risk," and "low risk."

Main outcome measures: The primary outcomes are miscarriage and live birth. Secondary outcomes include biochemical clinical pregnancy per single embryo transfer.

Results: When applying PREFER, the miscarriage rates were 12%, 14%, and 22% in the "low risk," "moderate risk," and "high risk" categories, respectively. Those embryos deemed "high risk" had a significantly higher egg provider age compared with "low risk," and there was little variation in risk categories in patients of the same age. The trend in miscarriage rate was not seen when using PREFER-MK; however, there was an association with live birth, increasing from 38%-49% and 50% in the "high risk," "moderate risk," and "low risk" groups, respectively. An adjusted logistic regression analysis demonstrated that PREFER-MK was not associated with miscarriage when comparing "high risk" to "moderate risk" embryos (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.63-1.63) or "high risk" to "low risk" embryos (OR, 1.07; 95% CI, 0.79-1.46). An embryo deemed "low risk" by PREFER-MK was significantly more likely to result in a live birth than those embryos graded "high risk" (OR, 1.95; 95% CI, 1.65-2.25).

Conclusion: The PREFER model's risk scores were significantly associated with live births and miscarriages. Importantly, this study also found that this model applied too much weight to clinical factors, such that it could no longer rank a patient's embryos effectively. Therefore, a model including only MKs would be preferred; this was similarly associated with live birth but not miscarriage.

Keywords: Morphokinetics; artificial intelligence; model; ploidy.