Rare male infertilities

Criteria before considering a discussion in MDM-FMG

In the event of co-prescription of a panel of infertility genes by NGS (CFTR, ADGRG2) and testing for microdeletions of the Y chromosome, the diagnostic strategy to be carried out in the laboratory will be as follows, unless explicitly stated otherwise:

• In the case of normal hormone levels (FSH, LH, testosterone, inhibin B) and testicular volume (probable obstructive azoospermia), the infertility panel (CFTR, ADGRG2) will be performed as a first-line test. Then, if the result is negative, testing for Y chromosome microdeletions will be performed as a second-line test.
• If hormone testing (FSH, LH, testosterone, inhibin B) shows primary hypogonadism and reduced testicular volume (probable non-obstructive azoospermia), testing for Y chromosome microdeletions will be performed as a first-line investigation. Then, if the result is negative, the infertility panel (CFTR, ADGRG2) will be performed as a second-line test with an exploration of the genes contained in the 46,XY DSD panel (NR5A1, AR, etc., see ‘Diagnosis of 46,XY DSD’ in Biobook for the complete list of genes).

In the event of a negative result, a request for whole genome analysis using very high-throughput sequencing may be discussed in an upstream multidisciplinary team meeting as part of the France Genomic Medicine 2025 plan.

Clinical criteria: confirmed male infertility factor

• Phenotypic criteria:
  • Testicular volume and azoospermia/sperm morphology abnormalities
  • Exclusion of a known syndrome
  • Testicular biopsy
• Age: reproductive age
• Other paraclinical tests: depending on the clinic (testicular ultrasound)
• Biological tests: hormonal assessment, seminal markers, etc.
• Testicular biopsy results
• Genetics depending on phenotype:
  • Karyotype
  • Y chromosome, CFTR, ADGRG2, AURKC, DPY19L2, SUN5
  • Family history: collected during a genetic consultation