I-2: Medical Treatment of Male Infertility

Male factor is the sole reason or a component for infertility in 20 and 30% of cases respectively. Medical treatment is preferred for patients with testicular failure due to endocrine or exocrine diseases. Although the infertility may be due to a pathology in the hypothalamic- pituitary axis, the majority of the cases occurs as results of testicular failure. In general medical treatment modalities may be listed as: 1. Hormonal treatment (Gonadotropins, Dopamine receptor agonists, Anti-ostrogens and Aromatase inhibitors) 2. Anti-oxidant therapy Gonadotropins: This is the mainstream treatment for hypogonadotropic hypogonadism presented with low FSH, LH and testosterone levels. Although the pulsatile GnRH treatment may be administered for these patients, it not preferred for difficulty of continuous infusion pumps. The treatment protocol is initiated by human chorionic gonadotropin (hCG) administration (1500-2000 IU 2-3 times/wk) to achieve normal range of testosterone in 48 hours. If patient continue to be azoospermic at 6. month, recombinant human FSH (100-150 IU 2-3 times/wk) may be added to hCG. Improvement for both testicular volume (4 to 12 cc)and total sperm concentration (5 million) had been achieved by using hCG alone. In patients who were refractory to hCG treatment but reached normal T levels, 84% of spermatogenesis was achieved after the administration of rhFSH. Testicular volume greater than 8 cc and post pubertal onset hypodonadism had been identified as positive prognostic factor for this treatment, while requirement of orchiopexy, small testis volume (<4 cc) count as poor prognostic factor. Although there is no evidence based study, the usage of rhFSH has been suggested in a study for select sub group of non HH oligo-asthenospermic patients with normal FSH values and maturation arrest histology. This treatment is still experimental and not approved by guidelines. Anti-estrogens (AE): Prior to introduction of ICSI, anti-estrogens such as tamoxifen and clomiphene were preferred for idiopathic male infertility in which these anti-estrogens improve testicular testosterone and spermatogenesis by blocking negative feedback of estrogen. In a meta-analysis, the pregnancy rate was reported as 15% in comparison with 12% of control group for oligoasthenospermic patients. In another placebo controlled study in which AEs were combined with vitamin E, the pregnancy rate was reported as 37 versus 13%. Clomiphene treatment was administered to NOA patients to achieve testosterone levels of 600-800 ng/dl and in 64% of patients who had a pathology of either maturation arrest or hypospermatogenesis, sperm was observed at the ejaculate (average 3.8 million sperm/ml). Aromatase inhibitors: These drugs improve androgen levels by blocking the conversion of them into estrogens. Although its usage has been suggested in trials without placebo, further scientific evidence is required. Aromatase inhibitors (anastrazole 1 mg 1x1, testalactone 100-200 mg 1x1, letrozole 2.5 mg 1x1) seems to restore T/E2 balance in patients with low testosterone and high estrodiole levels. Patients with T/E2 ratio lower than 10 and klinefelter may benefit from inhibitor treatment. Antioxidant therapy: Reactive oxygen species which present in higher levels of infertile males are suggested to effect the sperm function, DNA structure. Despite the numerous studies about the effects of anti-oxidant therapy on male infertility, most of them lack the necessary scientific design and mechanism of success had not been explained still. Current literature suggests carnitines, vitamin E and C for the improvement of semen parameters. A recent cochrane review had stated a 4-5 fold increase in pregnancy and live birth rates for men using anti-oxidants prior to ART. In another systemic review, an improvement in semen parameter or pregnancy rates had been reported in 82% of trials. Out of the 10 trials investigating pregnancy rates, 6 of them showed significant improvement. Despite all those trials, many more studies with better design and scientific approach should be performed before the rouıtine administration of anti-oxidants.