Unexplained Female Infertility Associated with Genetic Disease Variants

This study investigated the genetic basis of unexplained female infertility by sequencing the exomes of 197 women with the condition. The researchers identified pathogenic or likely pathogenic variants in medically actionable genes (e.g., BRCA1, BRCA2, GLA) in 6.6% of participants, a significantly higher prevalence than in control populations (U.K. Biobank and eMERGE Network). Notably, 2% of women carried variants in *BRCA1/2*, suggesting elevated cancer risk. Additionally, 10.7% had highly penetrant variants linked to neurologic, cardiovascular, and metabolic disorders. The findings support a genetic link between infertility and future medical illness, though the study’s homogeneous sample (predominantly White women) limits generalizability.

This study investigated the genetic basis of unexplained female infertility by sequencing the exomes of 197 women with the condition. The researchers identified pathogenic or likely pathogenic variants in medically actionable genes (e.g., BRCA1, BRCA2, GLA) in 6.6% of participants, a significantly higher prevalence than in control populations (U.K. Biobank and eMERGE Network). Notably, 2% of women carried variants in *BRCA1/2*, suggesting elevated cancer risk. Additionally, 10.7% had highly penetrant variants linked to neurologic, cardiovascular, and metabolic disorders. The findings support a genetic link between infertility and future medical illness, though the study’s homogeneous sample (predominantly White women) limits generalizability.