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

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

Design: Multicentre cohort study.

Subjects: Data were obtained from the treatment of patients from 2016 to 2019 at nine IVF clinics in the UK. A total of 3587 fresh single embryo transfers were included; PGT-A (pre-implantation genetic testing for aneuploidy) cycles were excluded.

Exposure: PREFER is a model developed using 8147 biopsied blastocysts to predict ploidy status using morphokinetic and clinical biodata. A second model using only morphokinetic predictors was developed, PREFER-MK. The models will categorize embryos in to three risk scores for aneuploidy, ‘high’, ‘medium’ 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 birth and miscarriage. Importantly, this study also found this model applied too much weight to clinical factors, such that they could no longer effectively rank a patient’s embryos. Therefore, a model including only morphokinetics would be preferred, this was similarly associated with live birth, but not miscarriage.