Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: A multicentre study

Study Type - Therapy (outcomes) Level of Evidence 2a What's known on the subject? and What does the study add? Clomiphene citrate, hCG and human menopausal gonadotropin (hMG) are widely used in treatment of oligospermia, because they increase FSH and testosterone which are essential for spermatogenesis. Finding a sperm in non-obstructive azoospermia for intracytoplasmic sperm injection is a challenge and much effort is required to reach the optimum method of sperm retrieval. The study shows that a new protocol of clomiphene citrate, hCG and hMG in the treatment of non-obstructive azoospermia achieves an increase in the levels of FSH, LH and total testosterone to the target levels that we set. Our target level of FSH was 1.5 times its initial level and for serum testosterone it was 600-800 ng/dL. Using our described medical treatment protocol in cases of non-obstructive azoospermia, sperm may be found in patients' ejaculate (∼11%) and if they remain azoospermic they will have a greater likelihood of sperms being obtained in testicular sperm extraction. Objective To evaluate the effect of optimizing serum level of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone on sperm retrieval for intracytoplasmic sperm injection. Patients and methods A total of 612 patients with non-obstructive azoospermia were evaluated with routine history, physical examination and hormonal assessment. Of these, 116 patients underwent microsurgical (micro)-testicular sperm extraction (TESE) without any medical treatment and formed the control group and the remaining 496 patients were administered clomiphene citrate in a titrated dose. Patients were classified into four groups according to their response to clomiphene citrate. Group 1: patients with an obvious increase in FSH and total testosterone (n= 372). Group 2: patients showing an increase in FSH with no or little increase in LH and total testosterone (n= 62). For these patients we continued with clomiphene citrate and added human chorionic gonadotrophin (hCG). Group 3: patients with no increase in the levels of the three hormones (n= 46). Group 4: included patients with continuously decreasing serum testosterone levels in response to the increasing dose of clomiphene citrate (n= 16). Accordingly, patients in groups 3 and 4 discontinued clomiphene citrate and started hCG and human menopausal gonadotropin (hMG). Semen analyses were performed periodically and, in patients who remained azoospermic, micro-TESE was performed. RESULTS Sperm were noted in 54 patients (10.9%) in semen analysis after treatment in all groups (with no significant difference) at a mean (sd) concentration of 2.3 (4.1) million/mL. For the 442 patients who remained azoospermic after treatment, successful sperm retrieval was significantly higher (57%) compared with the control group (33.6%). Conclusion For patients with non-obstructive azoospermia, clomiphene citrate, hCG and hMG administration, leading to an increased level of FSH and total testosterone, results in an increased rate of sperm in the ejaculate and increased likelihood of successful micro-TESE.