Secondary sex ratio in assisted reproduction: an analysis of 1 376 454 treatment cycles performed in the UK.
Level 3 - non-randomized controlled study
Retrospective analysis of a national registry cohort
PubMed 31598568 · doi:10.1093/hropen/hoz020
What was done
A retrospective cohort analysis of 1,376,454 assisted reproductive technology (ART) cycles recorded in the UK Human Fertilisation and Embryology Authority (HFEA) registry between 1991 and 2016. The analysis examined 1,002,698 IVF and ICSI cycles (863,859 fresh, 124,654 frozen) resulting in 171,399 singleton live births to evaluate secondary sex ratios (SSR, males per 100 females). Findings were compared across fertilization methods, embryo transfer stages, and national population birth statistics from the Office for National Statistics. Multiple births were excluded.
What was found
The overall singleton live birth rate per cycle was 17.1% (n = 171,399). The overall SSR across all IVF/ICSI cycles was 104.0 males per 100 females (95% CI: 103.1–105.0), comparable to the national benchmark for England and Wales of 105.3 (95% CI: 105.2–105.4). Significant differences were observed by technique: - Fresh IVF favored male births with an SSR of 110.0 (95% CI: 108.6–111.5), compared to fresh ICSI which favored female births with an SSR of 97.8 (95% CI: 96.5–99.2; OR 1.16, 95% CI: 1.12–1.19, P < 0.0001). - Blastocyst-stage transfer yielded a higher male SSR of 104.8 (95% CI: 103.5–106.2) compared to cleavage-stage transfer at 101.2 (95% CI: 99.3–103.1; OR 1.03, 95% CI: 1.01–1.06, P = 0.011).
Why it matters
This study shows that while specific ART procedures bias offspring sex in opposite directions—IVF and blastocyst culture toward males, ICSI toward females—the combined clinical utilization of both techniques results in an overall population secondary sex ratio that mirrors natural conception.
Limits
Data quality depends on registry reporting accuracy, with 14,185 cycles (1.4%) excluded due to missing data. Multiple births were excluded to avoid duplication, limiting findings to singletons. Clinical practices, success rates, and the proportion of blastocyst-stage transfers changed substantially across the 25-year study period, introducing potential temporal confounding.
Cited by
- supports In the general human population, the secondary sex ratio is approximately 105 male births for every 100 female births.