How can the analysis of the genome change how patients with azoospermia are managed?

Azoospermia is the extreme form of male infertility due to the absence of sperm in the semen. In order to help couples become parents, it is necessary to do a testicular biopsy to retrieve live spermatozoa that can later be used for in vitro fertilization with intra cytoplasmic micro-injection or ICSI. However, this is an invasive surgical operation with a potential deleterous long-term effect due to a testosterone deficit. Even though the chances of finding live spermatozoa is high, close to 95% for obstructive azoospermia and 40% if the defect comes from the testicules and is non-obstructive. However, today no clinical and/or biological criteria exist that allow the evaluation of the chances to find spermatozoa in the latter situation.

A study published in Human Reproduction evaluated the relevancy of Whole Exome Sequencing (WES) analysis in patients for which a first testicular biopsy had been performed, revealing a homogenous blockage in sperm maturation during prophase I of meiosis. Scientists from the Reproductive, Environmental, Epigenetic and Developmental Biology Unit (BREED (UVSQ/UPSaclay, Poissy)) showed that after validation by immunohistochemistry, that this approach was more relevant than Target Sequencing (TS), with a genetic cause identified that explains the testicular phentoype in more than 50% of the patients and 100% inbred patients. In addition, these preliminary results showed that this analysis provides arguments to avoid performing a 2nd testicular biopsy in these patients, or even a 1st biopsy in inbred patients, and this despite interpretation problems and so-called incidental findings generated by this analysis.

Contacts :

• Béatrice Mandon-Pépin (BREED) : beatrice.mandon-pepin@inrae.fr

• François Vialard (BREED) : francois.vialard@inrae.fr