Personalizing gonadotropin treatment in male infertility: how APHRODITE may help

Sandro Esteves brings the logic of personalisation to the male factor, presenting the APHRODITE criteria — endocrine phenotyping of men as a symmetrical counterpart to POSEIDON in women.

The physiological basis: spermatogenesis relies on intratesticular testosterone, synthesised by Leydig cells under LH, and on Sertoli-cell support from FSH. Without an adequate hormonal milieu inside the testis, full spermatogenesis is impossible.

The acronym APHRODITE (Addressing male Patients with Hypogonadism and/or infertility Owing to altered, iDiopathic TestIcular function) describes men with idiopathic or functional testicular dysfunction — those once lumped together as a vague "male factor."

The system defines five endocrine phenotypes by the combination of FSH and testosterone: Group 1 — hypogonadotropic hypogonadism; Groups 2–4 — idiopathic testicular dysfunction; Group 5 — unexplained infertility with normal values.

Group 1 is the only one where gonadotropins are mandatory (hCG ± FSH) and where surgical sperm retrieval is not performed before hormonal treatment: spermatogenesis is restored first.

Group 3 (low testosterone with normal FSH) is the key phenotype for the hCG + FSH combination. Group 4 (raised FSH, non-obstructive azoospermia) is especially important: 80% of such patients turn out to have biochemical hypogonadism that previously went unnoticed.

The central evidence is Esteves's own study of more than 600 patients with non-obstructive azoospermia: pre-operative gonadotropin therapy proved the strongest predictor of micro-TESE success, and the APHRODITE-3 group gave the best response.

The practical conclusion, captured in the thesis: "don't diagnose male infertility from the semen analysis alone." The semen analysis records the result but not the cause; hormonal stratification reveals reversible conditions.