Definition.
According to the WHO 1995 definition, infertility is defined as a person who has normal sexual function, has not used contraception for more than one year and is unable to impregnate the woman. Approximately 15% of couples fail to conceive after 1 year of marriage and will seek treatment. Less than 5% of patients will reluctantly accept that they cannot have children.
Prognostic factors.
The main prognostic factors affecting infertility are.
-Duration of infertility
-Whether the infertility is primary or secondary
-the results of semen analysis
-The age and fertility of the female partner.
The urological male specialist should first examine all infertile male patients for genitourinary malformations in order to treat them appropriately.
Diagnosis
Some common abnormalities must be noted in the diagnosis of male infertility (Table 1). It is important to note that even if it is clear that the male partner has an abnormality, the female partner should also be examined at the same time. This is because according to WHO statistics, about 1/4 of the patients who visit the clinic for infertility have problems with both partners.
Table 1 Main causes of male infertility
-Congenital factors (cryptorchidism and testicular dysplasia, congenital defects of the vas deferens)
-Acquired genitourinary malformations (obstruction, testicular torsion, testicular tumors)
-Infections of the genitourinary tract
-Increased temperature of the scrotum (e.g. consequences of varicocele)
-Endocrine disorders
-genetic abnormalities
-Immune factors
-systemic diseases
-Exogenous factors (drugs, toxins, radiation and heat)
-Idiopathic factors (40-50% of patients)
Semen analysis
The results of semen analysis are a prerequisite for appropriate treatment. The results of semen analysis made in the laboratory should be combined with national quality control standards (Table 2).
Parameters Reference values
Semen volume (mL) 1.5 (1.4C1.7)
Total sperm count (106/per ejaculation) 39 (33C46)
Sperm density (106/mL) 15 (12C16)
Sperm motility (PR+NP, %) 40 (38C42)
Forward motion sperm ratio (PR, %) 32 (31C34)
Sperm viability (%) 58 (55C63)
Normal sperm morphology ratio (%) 4 (3.0C4.0)
pH ≥7.2
Number of peroxidase-positive leukocytes (106/ mL) < 1.0
Mixed antiglobulin reaction (MAR) < 50% of spermatozoa with agglutination
Immunobead test (IBT) <50% sperm agglutination
Seminal plasma zinc (μmol/per ejaculate) ≥ 2.4
Seminal plasma fructose (mU/per ejaculation) ≥ 13
Seminal plasma neutral glucosidase (mU/per ejaculation) ≥ 20
Note: PR = forward motion; NP = non-forward motion
Frequency of semen analysis
If the semen analysis result is normal according to the WHO standard, one examination is sufficient. If the semen analysis result is abnormal, then this test needs to be repeated.
The following need to be identified
- Oligospermia: sperm count <15 million/ml
- Weak spermatozoa: motile sperm count <40%
- Teratozoospermia: <4% normal sperm count
In most cases, all three pathological conditions occur together and are referred to as oligo-weak teratogenic sperm syndrome. In cases of extreme OAT syndrome (<1 million/ml), such as azoospermia, there is an increasing incidence of male reproductive tract obstruction and genetic abnormalities.
Hormone level screening
Patients with infertility are more likely to have endocrine abnormalities than the average normal person, but these are relatively rare. When there are abnormal semen indicators, the only hormone tests we need to perform are limited to follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) levels. It is essential to identify whether azoospermia or extreme OAT syndrome is caused by obstructive or non-obstructive factors. A reasonable predictive value reflecting obstruction is a normal FSH with normal bilateral testicular volume, which would otherwise indicate a non-obstructive factor; however, approximately 29% of men with normal FSH levels still have impaired spermatogenesis, i.e., a non-obstructive factor is present.
Hypergonadotropic hypogonadism (elevated FSH/LH)
Spermatogenic dysfunction associated with elevated gonadotropin levels is a common condition that is not usually caused by disruption of the endocrine system; possible causes include.
-Congenital factors -Kernicterus syndrome, azoospermia, cryptorchidism (testicular hypoplasia), Y chromosome microdeletion
Acquired factors – post-testicular inflammation, testicular torsion, testicular tumors, systemic diseases, cytotoxic treatment
Hypogonadotropic hypogonadism (reduced FSH/ LH)
Hypogonadotropic hypogonadism due to hypothalamic or pituitary dysfunction is generally rare and can be caused by
-Congenital factors – idiopathic hypogonadotropic hypogonadism, Kallmann’s syndrome (often with loss of olfaction)
-Acquired pituitary diseases (tumors, granulomatous diseases, hyperprolactinemia)
-Exogenous factors – drugs (metabolic steroids, obesity, radiation)
In patients with unexplained hypogonadotropic hypogonadism, further investigations should include MRI/CT of the pituitary gland.
Microbiological examination
Indications for microbiological evaluation are a combination of: urine abnormalities, urinary tract infections, male accessory gonadal infections and sexually transmitted diseases. Although the clinical significance of leukocytes in semen specimens is still uncertain. However, in combination with low ejaculate volume, the possible cause is incomplete obstruction of the ejaculatory ducts due to chronic inflammation of the prostate or seminal vesicles. Reproductive tract infections can cause the production of oxygen radicals with sperm toxicity. Gonococci and Chlamydia trachomatis can also cause obstruction of the genital tract. Although antibiotic treatment of male accessory gonadal
infections can improve sperm quality, they do not necessarily improve pregnancy rates.
Genetic evaluation
A significant number of male fertility abnormalities, previously often dismissed as idiopathic male infertility, in fact have a genetic origin. Many of these patients can be detected by taking an extensive family history and performing karyotyping, which allows for not only diagnosis but also appropriate genetic counseling, especially since the latter has become important with the advent of ICSI (intracytoplasmic sperm injection), since fertility abnormalities and possibly associated genetic defects can be passed on to offspring.
Chromosomal abnormalities are very common in patients with extreme OAT syndrome and azoospermia. The most common sex chromosome abnormality is Klinefelter syndrome, which presents as 47XXY,and accounts for approximately 10% of azoospermia patients. Klinefelter’s syndrome is characterized by hypergonadotropic hypogonadism. In about 60% of patients, testosterone levels decrease with age and therefore require androgen supplementation. Both testes are small and the pathology presents as sclerosis of the spermatogenic tubules. Karyotyping is recommended for those patients with extreme OAT syndrome who are to undergo intracytoplasmic sperm injection.
In patients with very poor semen quality, chromosomal translocations and deletions are often found, and this chromosomal abnormality can be passed on to the next generation and can also lead to habitual abortions and congenital malformations in the offspring. In patients with azoospermia and extreme OAT syndrome, deletions of the AZF (azoospermia factor) region of the Y chromosome can occur and testing is recommended. Y chromosome deletions occur at a high rate of about 5% in these patients. If a Y chromosome deletion is found it indicates that this defect will be able to be passed on to the son and cause him to develop infertility.
When sperm is surgically obtained for intracytoplasmic single sperm injection (ICSI), for patients diagnosed with congenital vas deferens, the couple needs to be checked for mutations in the CFTR (cystic fibrosis transmembrane regulator) gene, which in addition to causing CF (cystic fibrosis), is also associated with CBAVD (congenital bilateral vas deferens). 85% of CBAVD Patients can be detected with 1-2 mutations in the CFTR gene. If a partner carries a CFTR mutation, there is a 25% chance that the offspring will have cystic fibrosis or congenital vas deferens, and genetic counseling is therefore required for such patients.
Ultrasonography
Ultrasound has become the primary screening tool for detecting lesions in the scrotum. Ultrasound Doppler examination of the scrotum can detect varicocele in 30% of infertile patients, testicular tumors in 0.5% of infertile patients, and testicular microcalcifications (potential precancerous lesions) in 2-5% of infertile patients, especially those with a combined history of cryptorchidism. Transrectal ultrasonography can exclude those infertility patients with low ejaculate volume (<1.5 ml) due to midline prostate cysts or ejaculatory duct obstruction due to ejaculatory duct stenosis.
Testicular biopsy
Diagnostic testicular biopsy is indicated in patients with azoospermia or extreme oligo-abnormal spermatozoa syndrome with normal testicular volume and serum FSH levels. The purpose of the biopsy is to distinguish between testicular insufficiency and male genital tract obstruction. Testicular biopsy in patients with non-obstructive azoospermia is intended to be performed as a therapeutic tool, only when sperm are obtained by ICSI. Testicular tissue obtained by testicular biopsy containing sufficient sperm should be frozen and preserved for ICSI.
The pathology is classified as follows.
-Germinal tubular sclerosis -Germinal tubular agenesis.
-Sertoli cell syndrome – only supporting cells are present in the seminiferous tubules without any spermatogenic cells.
-Sperm maturation disorder – incomplete spermatogenesis, impaired differentiation of spermatocytes.
-Reduced spermatogenesis – spermatogenesis is present but the spermatogenic epithelium is thinned and spermatogonia and spermatozoa are uniformly reduced at all levels.
In patients who are at high risk for testicular germ cell tumors (e.g., infertility, cryptorchidism, history of testicular cancer, testicular atrophy) and testicular microcalcifications, testicular biopsy can be performed to detect testicular carcinoma in situ.
Treatment
Consultation
There are times when some lifestyle habits may also lead to decreased semen quality, such as: smoking, alcohol abuse, metabolic steroid application, excessive exercise (endurance training, excessive strength training), wearing insulated underwear that leads to high temperatures in the scrotum, sauna or hot tub use, or engaging in occupations with high heat exposure. All of these factors can lead to a decrease in semen quality. In addition a considerable number of medications can also affect spermatogenesis.
Medication (hormone) therapy
There are no studies proving that hormonal treatments such as HMG/HCG (purified from the urine of menopausal women and pregnant women, respectively), androgens, anti-estrogens (clomiphene and tamoxifen), prolactin inhibitors (bromocriptine) and steroid therapy can improve the pregnancy rate in patients with idiopathic OAT syndrome. However, medications that can be used for some primary endocrine pathological abnormalities include.
-Low testosterone levels -Testosterone replacement therapy is recommended; if replacement therapy exceeds normal physiological values, it can have side effects on spermatogenesis.
-Low gonadotropin hypogonadism – using certain doses of HCG and HMG intramuscularly, twice a week.
-High PRL (prolactin)emia -treated with dopamine receptor agonists
For patients with auto-anti-sperm antibodies, high dose steroid treatment is not recommended because although it will produce some efficacy but also serious side effects.
Surgical treatment
Varicocele
The treatment of varicocele is a controversial issue in clinical male medicine. The controversy centers on the need for treatment of varicocele. There is evidence that treatment of varicocele in infertile patients results in a significant improvement in semen parameters. Current data support the hypothesis that varicocele leads to progressive impairment of testicular function and reduced fertility in some patients beginning in adolescence. Although treatment of varicocele in adolescent boys may be effective, there is a significant risk of overtreatment. An evidence-based Meta-analysis of randomized studies of infertile patients treated for varicocele showed that spermatic vein ligation did not significantly improve pregnancy rates. We conclude from our observations that aggressive treatment of patients with normal semen analysis and subclinical forms of varicocele seems to be of no benefit. However, repair surgery may be effective in patients with abnormal semen analysis, infertility that cannot be explained by other causes (unexplained infertility), and clinically detectable varicocele. Whether this subgroup will benefit by treatment needs to be confirmed by further randomized studies.
Microsurgery/Vasectomy Epididymal Anastomosis
This treatment should be performed by urologists experienced in microsurgery and, given the limited improvement in conception rates (approximately 20-30%), is recommended in combination with microsurgical epididymal sperm retrieval (MESA) and freezing for ICSI. indications for vasectopic epididymal anastomosis are congenital or acquired obstructive azoospermia at the level of the epididymis and normal testicular spermatogenesis (testicular biopsy). testicular biopsy).
Vasectomy
Although microsurgical vasectomy is equally effective in improving conception rates, open surgery can also be performed. The likelihood of initial postoperative conception is inversely proportional to the duration of obstruction, with the likelihood of conception dropping to less than 50% after 8 years. Other important prognostic factors include the presence of antisperm antibodies, semen quality, and age of the partner. Approximately 15% of patients who have undergone vasectomy have sperm quality that deteriorates to the point of azoospermia or profound oligospermia within one year. Poor semen quality and the development of autoantibodies to sperm usually prevent spontaneous conception rates, so assisted reproduction techniques can be performed in such cases.
Microsurgical epididymal sperm acquisition (MESA)
MESA in combination with ICSI may be considered in cases of obstructive azoospermia when vasectomy or vasecto-epidididymal anastomosis to reconstruct the duct has failed or is unsuitable for such procedures. Another option is percutaneous epididymal head puncture for fine needle aspiration of sperm (PESA). If sperm or sufficient numbers of motile sperm cannot be obtained by MESA or PESA, testicular biopsy may be used to obtain sperm (TESE) followed by ICSI.
Testicular Sperm Extraction (TESE)
About 50-60% of patients with non-obstructive azoospermia can be treated with ICSI by obtaining sperm from their testes. Most experts recommend the use of multiple testicular biopsies to obtain additional testicular tissue. There is no significant correlation between FSH levels, inhibin B and testicular volume and the success of testicular sperm acquisition. Testicular tissue from patients with microdeletions in chromosomal AZFa and AZFb regions had no accessible sperm. Testicular sperm acquisition is an alternative method and has good reproducibility. Microsurgical testicular sperm retrieval may increase the rate of sperm retrieval.
Transurethral ejaculatory duct or midline prostate cystectomy
Distal obstruction of the genital tract is usually caused by infection of the prostatic urethra and accessory gonads or by a midline prostate cyst.
This is usually caused by infection of the prostatic urethra and accessory gonads or by a midline prostate cyst. Removal of the obstruction by transurethral ejaculatory ducts or midline prostate cysts may improve semen quality and occasionally allow for spontaneous conception. However, the long-term results of this treatment have been disappointing.
Sexual dysfunction
The treatment of sexual dysfunction can be referred to the European Association of Urology (EAU) guidelines for the management of male sexual dysfunction.
Ejaculatory dysfunction
Etiology of retrograde ejaculation and non-ejaculation.
-Neurogenic: multiple sclerosis, diabetes mellitus (autonomic neuropathy) and spinal cord injury
-Medical: prostate and bladder neck surgery, sympathectomy and retroperitoneal surgery (retroperitoneal lymph node dissection for testicular tumors)
-Drug-related: antidepressants
We are usually unable to specify the etiology of retrograde ejaculation. The diagnosis of retrograde ejaculation currently relies on detailed questioning of the patient’s past medication history and laboratory microscopic analysis of post-ejaculatory urine. When a person has a small amount of semen after ejaculation, there should be a high degree of suspicion that he or she has partial retrograde ejaculation. The basic goal of treating retrograde ejaculation is to remove the cause or collect sperm in the urine after intercourse.
Non-ejaculation can be treated with penile vibratory stimulation or electrical stimulation of ejaculation. Ejaculation can be induced in about 90% of patients with spinal cord injury. However, the quality of the sperm is often poor, as evidenced by the low number of motile sperm. This explains the poor efficacy of assisted reproductive techniques such as intrauterine insemination (IUI) in patients with spinal cord injury. Such patients usually require in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).