“International sharing of data and expertise is essential to increase the statistical robustness and medical relevance of our genomics studies in male infertility.”

Clinical Assessment of Infertility Genes

Advances in genetic testing result in the discovery of numerous novel genetic variants that may play a role in male infertility each year. To assist in this feedback of knowledge, the IMIGC continuously screens the clinical validity of gene to certain types of male infertility. Following the pioneering work published in Human Reproduction [May 2019] we submitted an update in 2021 published in Human Reproduction Update) and in the table below we present the assessment for each infertility gene made by our panel of experts.

 It is the aim of this consortium to regularly review and publish our assessments in peer-review journals and display the results here for all to see.

Frequently asked questions:

Where can find the full list of assessed genes?

An interactive table show be found below in this page, but should it not be visible for whatever reason you can find the manuscript and associated data here or the entire table can be downloaded from here.

How was this scoring performed?

Scoring is performed by at least two independent reviewers according to the Smith et al. system and we classified genes into no evidence (<3 points), limited (3-8 points), moderate (9-12 points), strong (13-15 points) or definitive (>15 points), with of a maximum of 17 points.

Why do some genes have the classification “Unable to classify”?

For some genes the inheritance pattern remains unclear or suggests polygenic inheritance, the technical quality of the identification method was too poor or the exact variant information could not be retrieved.

When is the next release scheduled?

The next release is scheduled for 2025.

Spotted a mistake, what can I do?

Please contact us via this website or email a member of this consortium.

Improved Phenotypic Classification of Male Infertility

An increasing number of genes are being described in the context of non-syndromic male infertility. Linking the underlying genetic causes of non-syndromic male infertility with clinical data from patients is important to establish new genotype-phenotype correlations. This process can be facilitated by using universal nomenclature, but no standardized vocabulary is available in the field of non-syndromic male infertility. The International Male Infertility Genomics Consortium aimed at filling this gap, providing a standardized vocabulary containing nomenclature based on the Human Phenotype Ontology (HPO).

The “HPO tree” was substantially revised compared with the previous version and is based on the clinical work-up of infertile men, including physical examination and hormonal assessment. Some causes of male infertility can already be suspected based on the patient’s clinical history, whereas in other instances, a testicular biopsy is needed for diagnosis.

We assembled 49 HPO terms that are linked in a logical hierarchy and showed examples of morphological features of spermatozoa and testicular histology of infertile men with identified genetic diagnoses to describe the phenotypes. This work will help to record patients’ phenotypes systematically and facilitate communication between geneticists and andrologists.

Where can find the HPO decision tree?

The HPO tree can ve found below in this page, but should it not be visible for whatever reason you can find the manuscript and associated data here or the full-scale image can be downloaded from here.

Where can find the HPO terms and associated semen and testicular phenotypes descriptions?

This HPO tree can ve found below in this page, but should it not be visible for whatever reason you can find the manuscript and associated data here or the full-scale image can be downloaded from here.

List of CLINICAL ASSESSED INFERTILITY GENES – HOUSTON et AL 2021