Anti-Müllerian hormone deficiency in females with Fanconi anemia.
BACKGROUND
In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI). POI is typically diagnosed only after perimenopausal symptoms are observed.


OBJECTIVE
The objective of the study was to assess whether serum anti-Müllerian hormone (AMH) levels can serve as a cycle-independent marker for the diagnosis of POI in patients with FA.


METHODS
This observational study used the National Cancer Institute's inherited bone marrow failure syndrome cohort at the National Institutes of Health Clinical Center.


METHODS
The study included 22 females with FA, 20 unaffected female relatives of patients with FA, and 21 unrelated healthy females under 41 years of age.


METHODS
Serum AMH, a marker of ovarian reserve, was measured in all participants.


RESULTS
Females with FA had very low AMH levels (median 0.05 ng/mL; range 0-2.32 ng/mL; P < .001) when compared with unaffected relatives (median 2.10 ng/mL; range 0.04-4.73 ng/mL) and unrelated healthy females (median 1.92 ng/mL; range 0.31-6.64 ng/mL). All patients with FA older than 25 years of age were diagnosed with POI and had undetectable AMH levels.


CONCLUSIONS
AMH deficiency appears to be a shared trait across this heterogeneous FA cohort. Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms.
Human Papillomavirus Immunology Laboratory (M.M.S., L.A.P.), Leidos Biomedical Research, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702; Clinical Genetics Branch (N.G., B.P.A.), Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892; and Program in Reproductive and Adult Endocrinology (P.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland 20814.
Martha M
MM
Sklavos
Neelam
N
Giri
Pamela
P
Stratton
Blanche P
BP
Alter
Ligia A
LA
Pinto
D000293:Adolescent; D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D003430:Cross-Sectional Studies; D005199:Fanconi Anemia / Q000097:blood*; D005260:Female; D006801:Humans; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000175:diagnosis*
D015415:Biomarkers; D054304:Anti-Mullerian Hormone