INFERTILITY: It is the condition in which pregnancy does not occur despite one year of regular sexual intercourse without any contraceptive method. It is observed in 15–20% of married couples and in 50% of cases the male is responsible.

Over the past 15–20 years, developments in assisted reproductive techniques (ART) have made significant contributions to infertility treatment. However, many couples primarily prefer to have children naturally and therefore seek various medical treatments. Some couples also use different medical treatments to increase the success rates of ART.

The main approach in infertility treatment is to correct the underlying treatable cause. In male infertility treatment, there are two main approaches: treatments directed at the underlying disease (specific treatments) and treatments using various drugs that improve sperm parameters, especially in idiopathic cases (non-specific treatments).

Although indications for specific treatment protocols are more clearly defined and their results are more evident, there is still no consensus on non-specific treatments and the results vary.

Especially in cases of idiopathic oligoasthenoteratozoospermia (OAT), many different agents such as estrogen agonists, gonadotropins, aromatase inhibitors, vitamin preparations, and antioxidants are used for empirical treatment.

The group that benefits most from treatment in male infertility is patients with hypogonadotropic hypogonadism. In idiopathic cases, although there is no clear consensus on empirical treatment indications, it is widely used.

Due to significant differences in patient selection, definition of treatment outcomes, evaluation of patients and their partners, dosage regimens, treatment durations, adequacy of control groups, and follow-up periods, it is difficult to evaluate the effectiveness of empirical medical treatments. Empirical treatments are classified into two groups: hormonal and non-hormonal. Hormonal treatments aim to increase sperm production by affecting the hypothalamic-pituitary-testicular axis, while non-hormonal treatments act by blocking prostaglandin synthesis, increasing testicular microcirculation, or neutralizing free oxygen radicals toxic to sperm.

HORMONAL TREATMENTS

ANTI-ESTROGENS
TAMOXIFEN
CLOMIPHENE CITRATE

These are the most commonly used agents in empirical treatment. Some studies show significant improvements in sperm parameters with these agents, while others report the opposite. These agents act on the hypothalamus, removing the inhibitory effect of estrogen and stimulating the release of gonadotropins (FSH, LH), thereby increasing intratesticular testosterone production, which stimulates sperm production.

Although there is no standard dose, the recommended doses are 10–15 mg twice daily for Tamoxifen and 25–50 mg once daily for Clomiphene Citrate.

AROMATASE INHIBITORS
-anastrozole, testolactone

Aromatase is a cytochrome P450 enzyme that converts testosterone into estradiol (E2).

When this enzyme is blocked by aromatase inhibitors, serum testosterone levels increase and gonadotropins rise due to decreased E2 levels.

These drugs are used in patients with low testosterone/estradiol ratios. Studies show no change in semen parameters in non-obstructive azoospermia cases, while increases in sperm concentration and motility are observed in OAT cases.

GONADOTROPIN ANALOGS

Gonadotropin analogs (hCG, FSH) are mainly used in hypogonadotropic hypogonadism.

However, they are also frequently used in empirical treatments. Many studies exist, although most are not comparative. Some studies report increased pregnancy rates when used before ICSI (IVF). Additionally, in patients undergoing TESE (testicular sperm extraction) where no sperm was found, administering gonadotropins for 3–5 months before a second TESE has resulted in sperm retrieval rates of 15–20%. Testicular histopathology is important in this context.

NON-HORMONAL TREATMENTS

High levels of reactive oxygen species (ROS) in seminal plasma have been found in infertile men, and their role in sperm dysfunction and DNA damage has led to the use of antioxidant therapy. However, the exact mechanism of action is still unclear. Many studies have shown improvements in sperm quality and pregnancy rates with antioxidant therapy.

For this purpose, L-carnitine, L-arginine, Vitamin E, Vitamin C, folic acid, zinc, selenium, nonsteroidal anti-inflammatory drugs, N-acetylcysteine, mast cell stabilizers, pentoxifylline, coenzyme Q10, and lycopene are used.

In conclusion, the condition where medical treatment is clearly recommended in male infertility is hypogonadotropic hypogonadism. Patience is essential, and treatment may need to continue for up to one year.

Currently, there is no universally accepted treatment protocol for idiopathic OAT. Moreover, large comparative studies are insufficient. Nevertheless, these treatments are widely used by urologists. Treatment duration should generally be limited to 3–6 months to cover a full spermatogenic cycle and to avoid potential side effects.

Finally, all infertile men should consult a urology specialist, undergo physical examination and laboratory tests, and receive appropriate treatment planning.

 

Specialist Dr. ALİM TOPÇU / Urology Specialist / İRENBE