P-524 Ethnicity and aneuploidy rates in a global perspective: a comparative genomic study of 16,543 embryos from the United Kingdom, India and Japan
Authors: Beebeejaun Y , Bakalova D , Copeland T , Hsu H , Arora T , Sarris I 
Published: July 2024

Study question

Is embryonic aneuploidy, as determined by Next Generation Sequencing (NGS) based Pre-Implantation Genetic Testing for Aneuploidy (PGT-A) related to female ethnicity?

Summary answer

In this study, when determining aneuploidy through NGS-based PGT-A, female ethnicity did not have an impact on embryonic aneuploidy.

What is known already

Inequalities in pregnancy outcomes following in-vitro fertilization (IVF) have often been attributed to potential disparities in genetic susceptibility, with past studies showing higher pregnancy rates in older Caucasian patients compared to younger South-Asian patients. With aneuploidy as one of the best-characterized barriers to IVF success, critics argue that potential ethnic variations in aneuploidy rates may contribute to inequalities in IVF success, raising concerns about the appropriateness of standardized protocols. Proponents stress the importance of personalized medicine accounting for individual genetic backgrounds. Acknowledging genetic diversity and ensuring equitable access to successful fertility treatments remains a complex challenge.

Study design, size, duration

In this retrospective cohort review, data reflecting 4,354 women undergoing an IVF±ICSI cycle with concomitant NGS-based PGT-A from 65 centres in the United Kingdom, India and Japan was requested. Trophectoderm biopsy results from 16,513 embryos tested through a single genetic laboratory over a five-year period (2019-2023) were analysed. Patients were categorised by ethnicity (Caucasian, African, East Asian, or South Asian) and further stratified by age (&lt;35, 35-37, 38-39, 40-42, &gt;42).

Participants/materials, setting, methods

Women aged between 25–45 years undergoing an IVF±ICSI cycle with concomitant NGS-based PGT-A were included. Patients undergoing PGT for inherited genetic disorders (PGT-M) or gamete donation cycles were excluded, and only autologous oocyte cases were included. Trophectoderm biopsy was performed on day 5, 6 or 7 and NGS was performed from amplified deoxyribonucleic acid (DNA). Primary outcome of interest was aneuploidy rate (&gt;30% abnormality). Statistical analysis included ANOVA, Kruskal Wallis, and linear regression tests analysis.

Main results and the role of chance

In our analysis, the mean number of embryos tested overall was 3.46 (SD 2.07) and the mode was 4. The mean number was 3.84 for South Asian, 3.47 for Caucasian, 2.4 for African and 2.87 for East Asian. This was not statistically different between groups (P = 0.48). Subgroup analysis did not identify any statistically significant differences in the number of oocytes retrieved, MII oocytes retrieved and fertilization rates. When categorising by female age alone, there was a statistically significant difference in aneuploidy and female age overall (&lt;35: 32.1±29.7%; 35-37: 42.1±31.3%; 37-39: 50.4±29.3%;40-42: 64.7±33.5% and &gt; 42:73.9±38.7%, p-value: &lt;0.001). When subcategorised by ethnicity, linear regression analysis did not identify a significant association with aneuploidy rate and ethnicity. The was no statistically significant difference in mean aneuploidy rate by ethnicity: East Asian 67.2±32.2%, African 58.3±42.2%, European 55.6±35.6%, and South Asian 53±32.4% (p-value 0.57). With Caucasian as the reference population, coefficients for South Asian (3.20, p-value:0.61), East Asian (8.50 p-value: 0.31), and African (7.20, p-value: 0.60) were not statistically significant. No statistically significant differences in aneuploidy rates were observed across female age categories (&lt;35, 35-37, 38-39, 40-42, &gt;42) and ethnicities, with a p-value of 0.17.

Limitations, reasons for caution

The study type was retrospective in nature. Ethnic groups are not homogenous, and there can be significant genetic, cultural, and environmental diversity within a group. Failure to account for this heterogeneity may result in oversimplification and misinterpretation of findings. There was under representation of patients from African origin (2%).

Wider implications of the findings

These data do not support differences in embryonic aneuploidy among various ethnicities in patients undergoing IVF±ICSI /NGS-PGT-A. We limited our analysis to a single genetic laboratory to reduce reporting variation and technical confounders. It does not appear that specific recommendations for aneuploidy screening should be made based upon ethnic heritage.

Trial registration number

Not applicable