Association between maternal androgen levels and early fetal sex differentiation: Anogenital distance and genital tubercle length in the first trimester

Abstract

Purpose

To evaluate the use of anogenital distance (AGD) and genital tubercle length (GTL) between 11 and 13 + 6 weeks of gestation for fetal sex determination and to assess the impact of maternal androgen levels on these measurements.

Methods

A cross-sectional study was conducted from February to June 2017 with patients undergoing first trimester Down syndrome screening. Inclusion criteria were: (1) female age 18–49, (2) gestational age between 11 and 13 + 6 weeks, (3) optimal visualization of AGD and GTL, and (4) nonsmoking status. Maternal androgen levels (total testosterone, free testosterone, androstenedione, and dehydroepiandrostenedione) were measured simultaneously with ultrasound.

Results

AGD was significantly higher in male fetuses compared to females. With a cutoff of 5.0 mm, fetal sex was identified in 82 % of female fetuses and 70 % of male fetuses after the 12th week. Linear regression analysis showed that only AGD was a significant predictor of fetal sex (β: 0.54, p < 0.001). In the 12–12 + 6 week group, a positive correlation between AGD and maternal androstenedione was found in female fetuses (r: 0.23, p = 0.038). In contrast, negative correlations were observed between AGD and both androstenedione (r: −0.475, p < 0.001) and total testosterone (r: −0.282, p = 0.026) in male fetuses.

Conclusion

AGD and GTL measurements show sexual dimorphism in the first trimester, with AGD correlating positively with maternal androstenedione in females and negatively in males. These findings suggest that AGD and GTL are reliable, non-invasive methods for early fetal sex determination.