Assisted reproductive technology induces different secondary sex ratio: parental and embryonic impacts

Assisted reproduction technology (ART) has advanced significantly, raising concerns regarding its impact on the secondary sex ratio (SSR), which is the sex ratio at birth in offspring. This study aimed to explore factors affecting SSR in singletons, singletons from twin gestation, and twins from twin gestation within the context of ART.

A retrospective analysis was conducted on data from 8335 births involving 6,223 couples undergoing ART. Binary logistic regression assessed relationships between parental and embryonic factors and SSR in singletons and singletons from twin gestation. Multinomial logistic regression models were utilized to identify factors influencing SSR in twins from twin gestation.

Secondary infertility (OR = 1.164, 95% CI: 1.009-1.342), advanced paternal age (OR = 1.261, 95% CI: 1.038-1.534), and blastocyst embryo transfer (OR = 1.339, 95% CI: 1.030-1.742) were associated with an increased SSR, while frozen embryo transfer (FET) showed a negative association with SSR (OR = 0.738, 95% CI: 0.597-0.912) in singletons. A longer duration of gonadotropin (Gn) usage reduced SSR in singletons (OR = 0.961, 95% CI: 0.932-0.990) and singletons from twin gestation (OR = 0.906, 95% CI: 0.838-0.980). In singletons from twin gestation, male-induced infertility (OR = 2.208, 95% CI: 1.120-4.348) and higher Gn dosage (OR = 1.250, 95% CI: 1.010-1.548) were significantly associated with an increased SSR. Women aged > 35 years and intracytoplasmic sperm injection (ICSI) were associated with lower SSR (OR = 0.539, 95% CI: 0.293-0.990 and OR = 0.331, 95% CI: 0.158-0.690, respectively). In twins from twin gestation, paternal age exceeded maternal age (OR = 0.682, 95% CI: 0.492-0.945) and higher Gn dosage (OR = 0.837, 95% CI: 0.715-0.980) were associated with a higher proportion of male twins. Cleavage stage transfer (OR = 1.754, 95% CI: 1.133-2.716) resulted in a higher percentage of boy-girl twins compared to blastocyst transfer.

This study demonstrates the complex interplay of various factors in determining the SSR in ART, highlighting the importance of considering infertility type, paternal age, fertilization method, embryo transfer stage, and Gn use duration when assessing SSR. Nevertheless, further research with a large sample size is necessary to confirm and expand upon the findings of this study.