Impaired reproductive function and fertility preservation in a woman with a dyskeratosis congenita

Abstract

Purpose: To determine the impact of accelerated telomere shortening on the fertility parameters and treatment outcomes of a woman with dyskeratosis congenita (DKC). Methods: A case study of the clinical data, blood, discarded oocytes, and arrested embryos of a woman with DKC and donated cryopreserved embryos from unaffected patients. Mean telomere length in blood cells was analyzed by flow cytometry–fluorescence in situ hybridization (flow-FISH) and qPCR. The load of short telomeres in blood cells was measured by universal single telomere length analysis (Universal STELA). The mean telomere length in embryos was analyzed by single-cell amplification of telomere repeats (SCATR) PCR. Results: Comparison of clinical parameters revealed that the DKC patient had reduced anti-Mullerian hormone (0.3 vs 4.1 ± 5.7 ng/ML), reduced oocytes retrieved (7 vs 18.5 ± 9.5), reduced fertilization rate, and reduced euploidy rate relative to unaffected patients. Additionally, mean telomere length in DKC embryos were shorter than unaffected embryos. However, hormone treatment led to increased leukocyte telomere length, while the load of short telomeres was also shown to decrease during the course of treatment. Conclusions: We demonstrate for the first time the direct detrimental impacts of short telomeres on female fertility. We further demonstrate positive effects of hormone treatments for people with telomere disorders.