We found that fetal sex determination by measuring the angle of the caudal or cranial notch in the mid-sagittal plane as a part of a routine ultrasound was successful in 78% of fetuses at the time of the first trimester screen. Of the successful studies, a high accuracy (94.4%) for fetal sex was achieved. The overall accuracy was improved with increasing CRL and did not vary significantly by the fetal sex. The sensitivity of identifying males (96.6) was higher than females (90.7), but with overlapping of the 95% confidence intervals.
A study conducted by Efrat et al. (2006) reported 93% success in identifying fetal sex with 99–100% males correctly identified, and 91.5–100% of females correctly identified with increasing CRL [3]. Efrat et al recommended waiting until the CRL was at least 62.5 mm prior to proceeding with invasive testing. Our findings support this suggestion. Similar to our findings, Efrat et al. found in the 2006 study that the overall sensitivity was higher in identifying males (99.6%) than females (97.4%). Additionally, after 12 weeks’ gestation, the accuracy of correctly identifying a male fetus approaches 100%, indicating ultrasonography can be helpful in determining risk assessment of sex-linked genetic conditions, specifically X-linked recessive conditions affecting males. This could provide for earlier detection for counseling and/or treatment.
Other methods of sonographically determining fetal gender in the first trimester have been proposed. These include measuring the ano-genital distance (AGD) and 3D ultrasound. In 2016, Arfi et al. reported sensitivities for determination for male sex at 87% and female sex at 89% by measuring the AGD in 310 fetuses at 11–14 weeks’ gestation [5]. Najdi et al. reported in 2018 their experience with using the AGD to determine fetal sex in 316 cases. Their accuracy increased from 70.4% at 11 weeks’ gestation to 96.0% at 13 weeks’ gestation [6]. However, the threshold AGD for sex determination in this study was gestational age dependent, increasing the complexity of this technique. Youssef et al in 2011 ascertained the feasibility of fetal gender determination utilizing 3D ultrasound to measure the genital tubercle angle in 85 cases, with a 100% accuracy [7]. However, Bogers et al in 2018 only achieved 56% accuracy for fetal sex determination with 3D ultrasound in the first trimester and concluded when even using advanced 3D techniques accurate results were not possible [8]. Advantages of utilizing the genital tubercle angle measurement first described by Efrat in 1999, includes the familiarity of sonographers with obtaining the mid-sagittal plane, which is the same as for the nuchal translucency measurement, and the relatively small amount of time required to perform this measurement compared to the more difficult ano-genital measurement and 3D volume acquisition and offline volume manipulation and calculation.
Strengths of this study included the relatively large population size (n = 567) which contributes to the statistical significance of the results. Our study was conducted with contemporary ultrasound equipment compared to the earlier investigations which may explain the greater accuracy [2, 3]. Limitations include a higher proportion of male fetuses (62.3%) than expected. We suspect this was due to the greater technical difficulty with female fetuses in identifying the genital tubercle and those exams being more commonly classified as unsuccessful. We used sex determination at the 20-week anatomy scan rather than sex determination at birth as the gold standard. Future investigations may compare first trimester sex determination to cell-free DNA. However, our approach has been shown to be extremely accurate [1]. In addition, the study included ultrasounds performed by skilled sonographers in a specialized unit which may limit the generalizability of the results. Some may argue that in the age of cell-free DNA testing determination of fetal sex by ultrasound in the first trimester is no longer necessary. However, there are clinical scenarios where determination of fetal sex by ultrasound in the first trimester may be critical. For example, in the instance where a patient is a carrier for an X-linked condition and presents for prenatal care at the time of a first trimester ultrasound screen, this determination can help in her decision regarding early diagnostic fetal testing. It is true that a cell-free fetal DNA test for fetal sex can be done but it takes at least one week to get a result. This delay may make a difference between being able to perform chorionic villus sampling and having to wait until an amniocentesis can be performed. This delay along with the fact that molecular analysis looking for a X-linked mutation can take weeks, may also be especially problematic in areas where availability for pregnancy termination is limited.