Fumarase Deficiency and Its Effect on Infertility: A Case Series

Jessica  Wesley Schwartz; Alexandra  Peyser; Miriam  Tarrash; Randi  Heather Goldman

doi:10.18502/jri.v24i3.13277

Jessica Wesley Schwartz Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, New York, USA
Alexandra Peyser Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Northwell Health Fertility, North Shore University Hospital, New York, USA
Miriam Tarrash Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Northwell Health Fertility, North Shore University Hospital, New York, USA
Randi Heather Goldman Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, New York, USA

DOI: https://doi.org/10.18502/jri.v24i3.13277

Keywords: Fibroids, Fumarate hydratase, Genetic counseling, Hereditary leiomyomatosis and renal cell cancer (HLRCC), Infertility, Leiomyoma.

Abstract

Background: Fumarase deficiency is an autosomal recessive condition characterized by severe neurologic abnormalities due to homozygous mutations in the fumarate hydratase (FH) gene. Heterozygous carriers of FH mutations have increased risk of developing uterine fibroids that can be associated with hereditary leiomyomatosis and renal cell cancer (HLRCC). The association between FH mutations and infertility remains uncertain. The objective of our study was to characterize the infertility diagnoses, treatments, and outcomes in women presenting to a fertility center who were found to be carriers of fumarase deficiency based on the presence of heterozygous FH mutations.

Case Presentation: A retrospective case series was conducted including 10 women presenting to an academic fertility center who were found to be FH carriers based on genetic carrier screening. Of the 9 women who were engaged in further workup, 2 had imaging results consistent with uterine fibroids. One woman underwent hysteroscopic myomectomy prior to two courses of ovulation induction with timed intercourse (OI/TIC) followed by one successful cycle of IVF. Of the remaining patients, only 1 woman successfully delivered after a cycle of ovulation induction with intrauterine insemination (OI/IUI). Other patients pursuing OI/IUI, OI/TIC, or monitored natural cycles had unsuccessful experiences.

Conclusion: Patients with infertility who are offered genetic testing should be screened for FH mutations, as the carriers are at risk of developing HLRCC-associ-ated uterine fibroids, which can influence fertility and pregnancy. Additional research is needed to investigate the impacts of FH mutations on infertility.