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Primary ovarian insufficiency in classic galactosemia: current understanding and future research opportunities

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Abstract

Classic galactosemia is an inborn error of the metabolism with devastating consequences. Newborn screening has been successful in markedly reducing the acute neonatal symptoms from this disorder. The dramatic response to dietary treatment is one of the major success stories of newborn screening. However, as children with galactosemia achieve adulthood, they face long-term complications. A majority of women with classic galactosemia develop primary ovarian insufficiency and resulting morbidity. The underlying pathophysiology of this complication is not clear. This review focuses on the reproductive issues seen in girls and women with classic galactosemia. Literature on the effects of classic galactosemia on the female reproductive system was reviewed by an extensive Pubmed search (publications from January 1975 to January 2017) using the keywords: galactosemia, ovarian function/dysfunction, primary ovarian insufficiency/failure, FSH, oxidative stress, fertility preservation. In addition, articles cited in the search articles and literature known to the authors was also included in the review. Our understanding of the role of galactose metabolism in the ovary is limited and the pathogenic mechanisms involved in causing primary ovarian insufficiency are unclear. The relative rarity of galactosemia makes it difficult to accumulate data to determine factors defining timing of ovarian dysfunction or treatment/fertility preservation options for this group of women. In this review, we present reproductive challenges faced by women with classic galactosemia, highlight the gaps in our understanding of mechanisms leading to primary ovarian insufficiency in this population, discuss new advances in fertility preservation options, and recommend collaboration between reproductive medicine and metabolic specialists to improve fertility in these women.

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Acknowledgements

The authors thank the health care providers and researchers for valuable contributions regarding the care of patients with classic galactosemia presented in this paper. This work is dedicated to women with galactosemia and their families.

Author’s role

Conception and design (MT), search strategy (MT, GF, EEP), data extraction and analysis (MT, GF, EEP), interpretation (MT, GF, EEP), drafting the manuscript (MT), critical revision of manuscript (MT, GF, EEP), final approval of manuscript to be published (MT, GF, EEP).

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Authors and Affiliations

  1. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Mili Thakur & Elizabeth E. Puscheck

  2. Division of Genetic, Genomic and Metabolic Disorders, Department of Pediatrics and Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Mili Thakur & Gerald Feldman

  3. The Fertility Center, 3230 Eagle Park Dr. NE, Suite 100, Grand Rapids, MI, 49525, USA

    Mili Thakur

  4. Department of Pathology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Gerald Feldman

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  1. Mili Thakur
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  2. Gerald Feldman
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  3. Elizabeth E. Puscheck
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Correspondence to Mili Thakur.

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Thakur, M., Feldman, G. & Puscheck, E.E. Primary ovarian insufficiency in classic galactosemia: current understanding and future research opportunities. J Assist Reprod Genet 35, 3–16 (2018). https://doi.org/10.1007/s10815-017-1039-7

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  • DOI: https://doi.org/10.1007/s10815-017-1039-7

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