Infertility is defined as the failure to conceive after 12 months of unprotected and sufficiently frequent intercourse. In the past it was generally believed that this situation was mainly due to female causes, but it has now been demonstrated that the male factor is present in at least 50% of cases (male factor alone or combination of male and female factors).  Certainly an important role is played by the fact that, for social reasons, couples try to conceive at an ever later age. Besides this, there are a series of risk factors for male fertility that must be carefully researched and possibly treated. In particular, these are factors which, throughout life, can negatively affect the reproductive capacity, both  transiently or permanently. For example, conditions such as cryptorchidism (the “undescended testicle”), infections of the genitourinary tract and prostate disease, varicocele, postmumps orchitis, torsion of the spermatic cord, trauma and previous invasive surgery of the inguinal scrotal region, endocrine disorders, medication ( eg, exposure to chemotherapy for neoplastic diseases), chromosomal genetic (the most common is Klinefelter Syndrome) and gene diseases ( the most common are microdeletions of the Y chromosome ), alcohol and drug/ substance abuse diseases, professional diseases (eg, exposure to ionizing radiation or chemical pollutants with proven toxicity to spermatogenesis). In addition there are systemic or organ diseases which severely debilitate the body and all the disorders that have implications on erectile and ejaculatory function, situations which, in one way or another all negatively affect the male reproductive capacity.
The task of the clinical andrologist (Endocrinologist Andrologist) is to determine the possible male “contribution” in infertility of the couple and to establish a precise diagnosis that assesses degree and, when possible, identifies the causes.
The first visit has to include a thorough medical history which, for example, inquires into whether the patient has had problems of cryptorchidism as a child, if he had normal pubertal development,  if he had undergone major trauma in the inguinal- scrotal region, if he had infections of the uro -genital tract or contracted mumps complicated by orchitis; investigation must also include work and physical activity, lifestyle, alcohol or drug abuse, other significant systemic or organ diseases and whether there are other cases of infertility in the family or premature menopause. The visit should essentially be of an inquiring nature to exclude the risk factors described above.
It is also advisable, in the assessment of male infertility, to gather some information  about the female partner (age of the partner, regularity or not of menstrual cycles, previous pregnancies and/or spontaneous or provoked miscarriages) as well as frequency and sexual modalities (eg, if sexual activity occurs with regular frequency, if there are erection problems, if ejaculation occurs regularly in the vagina, if activity is mainly concentrated in the fertile period of the woman). It should be emphasized that information about the partners is based purely on male evaluation and can in no way be considered as an alternative to assessment of the female partner, which is the competence of a gynecologist.
A careful examination of the genital region is equally important and should include evaluation of the testes in search of a possible varicocele, the epididymis and the first section of the deferens duct, the penis, prostate and seminal vesicles.
This will be followed by a series of instrumental and laboratory investigations, which can be considered as first level:
– Analysis of the seminal fluid  (semen analysis), which is the cornerstone of diagnostic procedure in evaluating male fertility
– Microbiological tests (spermioculture, screening for chlamydial trachomatis and mycoplasma urealiticum)
– Hormonal profile (especially gonadotropins, testosterone, prolactin, TSH, and whatever else is necessary)
– Scrotal ecocolor Doppler of spermatic funicles to assess the presence of varicocele or other testicular disorders.
Based on the results of these initial investigations, it will be decided whether or not to proceed with a further instrumental and laboratory evaluation, which can be defined as second or third level. This can include, for example, further tests of seminal fluid (eg search for agglutinating antisperm antibodies), investigation of the hormonal situation through stimulation tests, prostate-vesicular ultrasonograph, a series of genetic analyses (eg, karyotype, detection of chromosome Y microdeletions and mutation of the CFTR gene or others if indicated).  More invasive diagnostic tests such as cyto-aspiration or testicular biopsy might also be necessary.
Regarding the therapeutic perspectives related to male infertility, treatment aims to achieve the best possible conditions regarding spermatogenesis and quality of the semen. If, for example, genital infections have emerged from the tests, it is necessary to treat them with an appropriate antibiotic and anti-inflammatory therapy.  Having excluded or treated these, an important therapeutic approach is hormonal therapy, in particular with gonadotropins (especially FSH). Hormonal therapy can be used either in a rational way (i.e. in case of documented hormonal deficiency), or in an empirical way, when, even with no evidence of gonadotropins secretion deficiency, a stimulatory effect on spermatogenesis is exerted. The latter situation is by far the most frequent in clinical situations and is indicated in case of impaired spermatogenesis (i.e. a process called oligospermia) . Numerous studies document the efficacy of this treatment; however, predictive criteria of response to this therapy still remain unclear.
Another therapeutic aid, which has proved to be effective in controlled clinical trials for the treatment of male infertility, is antioxidants. The production of free radicals with oxidizing activity is an inevitable price that biological systems have to pay, mainly due to energy metabolism. Their excess can be harmful to the integrity and functioning of biological molecules, so that, within certain limits, the systems themselves are equipped with antioxidants, molecules that are able to block free radicals; this activity of neutralizing free radicals is called “scavenging ability”. It has been shown that sperm from patients with dyspermia presents a reduced ability to scavenge free radicals with a consequent excess of oxidant free radicals. Based on these assumptions clinical trials were conducted where antioxidants were effectively used as a therapeutic aid. In particular the use of Coenzyme Q10 (ubidecarenone) should be stressed, as oral administration of this molecule increases its levels in seminal fluid, correlated with an improvement in semen parameters and pregnancy rate. Another molecule of proven effectiveness is carnitine, whose oral administration improved semen parameters, the scavenging capacity of seminal fluid against free radicals and an increase in the number of pregnancies.
From the andrological point of view, techniques of medically assisted procreation should be considered above all when, in spite of improved semen quality, the couple does not manage to conceive within a reasonable period of time; when attempts to improve the quality of the seed and therefore the degree of male fertility have failed; when there is no real prospect of therapeutic improvement of male fertility; when the age of the couple (especially the female partner) is advanced. It must be explained to the patient that, as the physiological time of a spermatogenic cycle is approximately three months, this will be the length of time necessary to identify possible therapeutic effects on the quality of his semen. Medically assisted procreation must, however, be carried out in close coordination with the gynecologist who assists the partner. It should also be stressed that the choice of therapeutic strategy of the infertile male depends on the andrologist, and is based on clinical, laboratory and instrumental data obtained after appropriate diagnostic procedure.

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Giancarlo Balercia

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