Our objective was to investigate the impact of
methotrexate,
paclitaxel,
ifosfamide, and
cisplatin (M-TIP) on long-term fertility in poor-risk nonseminomatous
germ cell tumors (NSGCT). Thirty patients with poor-risk NSGCT (median age, 29 years; range, 17-62 years) were treated with
methotrexate 250 mg/m(2) with
folinic acid rescue (day 1) and
paclitaxel 175 mg/m(2) (day 1), followed by
ifosfamide 1.2 g/m(2) and
cisplatin 20 mg/m(2) (days 2-6). Treatment consisted of 4 cycles of M-TIP administered every 3 weeks. Twenty-one patients were continuously disease-free at a median follow-up of 5.3 years (range, 0.9-8.4 years). Sperm count and hormonal analyses were examined prechemotherapy (30 patients) and postchemotherapy (21 patients). Counts were classified as follows: lower than 1 x 10(6)/mL,
azoospermia; 1-20 x 10(6)/mL,
oligospermia (OS); higher than 20 x 10(6)/mL, normospermia (NS). Patients were followed for a median of 2.3 years (range, 0.9-3.8 years) postchemotherapy. The prechemotherapy median
luteinizing hormone (LH) serum levels were slightly above the upper normal limit, whereas the serum levels of
follicle-stimulating hormone (FSH) and
testosterone (T) were within the reference interval. Eleven (52.3%) patients had NS prechemotherapy. Among the patients with NS, 72.7% still had NS following
chemotherapy. Overall, 17 of 21 (80.9%; 33.3% OS and 47.6% NS) patients had recovery of spermatogenesis
after treatment. The median FSH serum levels were significantly elevated at least 1 year postchemotherapy when compared with the pretreatment levels. Eighteen months after the completion of
chemotherapy the median FSH levels had returned to the reference limits. Serum LH and T levels were unaffected by
chemotherapy. Prior to
chemotherapy 4 of 30 patients had fathered 5 children. Since completion of
chemotherapy, 5 patients have fathered 5 children. The majority of men with poor-risk
germ cell tumors who were treated with the M-
TIP regimen demonstrated recovery spermatogenesis
after treatment, and Leydig cell function was unaffected.