Fig. 3

The Esteves gonadotropin treatment protocol for infertile males with non-obstructive azoospermia and hypogonadism. The treatment involves the off-label use of human chorionic gonadotropin (hCG) alone or in combination with follicle-stimulating hormone (FSH). Given the off-label nature of the treatment, patients must provide signed informed consent before initiating therapy. Subcutaneous injections of choriogonadotropin alfa (recombinant human chorionic gonadotropin [rhCG], 250 μg/0.5 mL prefilled pen for injection) in doses of 80 μg (~ 2080 IU), are self-administered twice weekly. The dose is adjusted to keep the total testosterone (TT) level > 350 and up to 900 ng/dL. If the serum FSH level falls below 1.5 IU/L during rhCG stimulation, patients are also given recombinant FSH (follitropin alfa [rFSH], 300 IU/0.5 mL, using a prefilled multidose pen ready for injection). The rFSH is administered at a dose of 150–225 IU two (biw) to three (tiw) times a week, concurrent to the rhCG therapy, for at least 3 months. An aromatase inhibitor is prescribed off-label if the estradiol (E2) levels exceed 50 pg/mL or if the TT (ng/dL) to E2 (pg/mL) ratio (T/E2 ratio) falls below 10. The aromatase inhibitor is given orally (e.g., anastrozole, 1 mg daily) to keep the estradiol levels below 50 pg/mL and the T/E2 ratio above 10. Patients are monitored with hormone measurements (serum FSH, luteinizing hormone [LH], E2, TT, free testosterone, and 17-hydroxy-progesterone [17-OH-P]) and liver enzyme measurements for those taking aromatase inhibitors every 3–4 weeks. Semen analysis is carried out 3 months after starting the treatment and then every 4 weeks for patients who continue therapy for > 3 months. If viable sperm are found in any semen analysis during treatment, sperm cryopreservation is carried out. If not, patients undergo microdissection testicular sperm extraction (micro-TESE) after ≥ 3 months of treatment. ICSI, intracytoplasmic sperm injection; qd, once daily. Adapted with permission from Elsevier from Esteves SC, Achermann APP, Miyaoka R, Verza S Jr, Fregonesi A, Riccetto CLZ. Clinical factors impacting microdissection testicular sperm extraction success in hypogonadal men with nonobstructive azoospermia. Fertil Steril. 2024 Jun 22:S0015-0282(24)00544–2. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.fertnstert.2024.06.013.