Diminished Ovarian Reserve in Girls and Adolescents with Trisomy X Syndrome


An extra X chromosome occurs in ~ 1 in 1000 females, resulting in a karyotype 47,XXX also known as trisomy X syndrome (TXS). Women with TXS appear to be at increased risk for premature ovarian insufficiency; however, very little research on this relationship has been conducted. The objective of this case-control study is to compare ovarian function, as measured by anti-mullerian hormone (AMH) levels, between girls with TXS and controls. Serum AMH concentrations were compared between 15 females with TXS (median age 13.4 years) and 26 controls (median age 15.1 years). Females with TXS had significantly lower serum AMH compared to controls (0.7 ng/mL (IQR 0.2–1.7) vs 2.7 (IQR 1.3–4.8), p < 0.001). Additionally, girls with TXS were much more likely to have an AMH below the 2.5th percentile for age with 67% of them meeting these criteria (OR 11, 95% CI 2.3–42). Lower AMH concentrations in females with TXS may represent an increased risk for primary ovarian insufficiency in these patients and potentially a narrow window of opportunity to pursue fertility preservation options. Additional research is needed to understand the natural history of low AMH concentrations and future risk of premature ovarian insufficiency in girls with TXS.

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The authors wish to thank the study participants in the eXtraordinarY Kids Clinic and their families. We also acknowledge Esoterix Laboratories, in particular Walt Chandler, PhD, Kelly Chun, PhD, and Steve Phagoo, PhD. Additionally, we acknowledge funding from the National Center for Advancing Translational Sciences (NIH/NCATS) Colorado CTSA (UL1TR002535), the National Institute of Child Health and Human Development (NIH/NICHD) (K23HD092588), the American Heart Association (13CRP14120015), the National Institute of Digestion, Diabetes, and Kidney Disease (NIH/NIDDK) (K23DK107871), the University of Colorado Departments of Obstetrics and Gynecology and Pediatrics.


This work was financially supported by the following: National Institute of Child Health and Human Development (NIH/NICHD) (K23HD092588), National Institute of Digestion, Diabetes, and Kidney Disease (NIH/NIDDK) (K23DK107871), National Center for Advancing Translational Sciences (NIH/NCATS) Colorado CTSA (UL1TR002535), American Heart Association (13CRP14120015), University of Colorado Department of Obstetrics and Gynecology Research Funds, and University of Colorado Department of Pediatrics. Availability of Data and Material

All data generated or analyzed during this study are included in this published article.

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Correspondence to Shanlee M. Davis.

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Conflict of Interest

NT and SD serve as medical advisors and SH on the board of directors for the advocacy group AXYS (Association for X&Y syndromes).

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The local institutional review board (COMIRB #08-0512 and #10-1288) approved these protocols and all parents provided written informed consent and girls provided assent as age appropriate. The study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.


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Davis, S.M., Soares, K., Howell, S. et al. Diminished Ovarian Reserve in Girls and Adolescents with Trisomy X Syndrome. Reprod. Sci. (2020). https://doi.org/10.1007/s43032-020-00216-4

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  • Trisomy X syndrome (TXS)
  • Primary ovarian insufficiency (POI)
  • Anti-mullerian hormone (AMH)
  • Sex chromosome aneuploidy
  • Fertility