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Genetic diagnosis of subfertility: the impact of meiosis and maternal effects
  1. Alexander Gheldof1,2,
  2. Deborah J G Mackay3,
  3. Ying Cheong4,
  4. Willem Verpoest2,5
  1. 1 Center for Medical Genetics, Universitair Ziekenhuis Brussel, Brussels, Belgium
  2. 2 Reproduction and Genetics Department, Vrije Universiteit Brussel, Brussels, Belgium
  3. 3 Faculty of Medicine, University of Southampton, Southampton University Hospital, Southampton, UK
  4. 4 Complete Fertility, Human Development of Health, Faculty of Medicine, University of Southampton, Southampton, UK
  5. 5 Center for Reproductive Medicine, Universitair Ziekenhuis Brussel, Brussels, Belgium
  1. Correspondence to Dr Alexander Gheldof, Center of Medical Genetics, Universitair Ziekenhuis Brussel, Brussels 1090, Belgium; alexander.gheldof{at}


During reproductive age, approximately one in seven couples are confronted with fertility problems. While the aetiology is diverse, including infections, metabolic diseases, hormonal imbalances and iatrogenic effects, it is becoming increasingly clear that genetic factors have a significant contribution. Due to the complex nature of infertility that often hints at a multifactorial cause, the search for potentially causal gene mutations in idiopathic infertile couples has remained difficult. Idiopathic infertility patients with a suspicion of an underlying genetic cause can be expected to have mutations in genes that do not readily affect general health but are only essential in certain processes connected to fertility. In this review, we specifically focus on genes involved in meiosis and maternal-effect processes, which are of critical importance for reproduction and initial embryonic development. We give an overview of genes that have already been linked to infertility in human, as well as good candidates which have been described in other organisms. Finally, we propose a phenotypic range in which we expect an optimal diagnostic yield of a meiotic/maternal-effect gene panel.

  • clinical genetics
  • diagnostics
  • genetic screening/counselling
  • obstetrics and gynaecology

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Contributors AG wrote the main text; DJGM and YC wrote the sections concerning maternal effect genes and critically read the manuscript; WV conceptualised the study and critically reviewed the manuscript.

  • Funding This project was funded by a Willy Gepts Scholarship.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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