Male Infertility
About 15% of couples are unable to conceive after a year of unprotected sexual intercourse. The male factor is solely responsible for 20% of infertile couples and also contributes about 30-40% in cases, in which the female factor is involved. If there is a male infertility factor, an abnormal sperm analysis is almost always found, although other factors may play a role in infertility even when sperm analysis is normal.
Male infertility can be due to various conditions. Some of these conditions are recognizable and reversible, such as sperm duct obstruction and hypogonadotropic hypogonadism. Other conditions are recognizable but irreversible, such as bilateral testicular atrophy after viral orchitis. When it is not possible to identify the etiology of pathological sperm analysis, as is the case with many patients, the condition is called idiopathic. When the cause of infertility is not clear, with a normal sperm analysis and also with a partner with normal fertility, infertility is defined as unexplained. The recognition and treatment of reversible conditions can improve male fertility and increases the chances of natural conception. Even azoospermic patients may have active sperm production or induced sperm production after treatment. Also, recognizing conditions for which there is no cure can save the couple from the agony of trying ineffective treatments. Detecting certain genetic causes of male infertility allows couples to be informed about the chances of inherited genetic abnormalities that may affect the health of their offspring. Thus, a proper assessment of male infertility can allow the couple to better understand the basis of their infertility and help them seek the right genetic guidance. If specific treatments are not available, assisted reproduction technologies may be used, such as testicular or epididymal sperm retrieval and intracytoplasmic sperm injection (ICSI). Finally, male infertility can occasionally be a manifestation of the presence of a life-threatening condition such as testicular cancer or pituitary tumors.
In summary, the objectives of the male infertility assessment are to identify:
- Potentially reversible situations
- Irreversible conditions capable of assisted reproduction technologies using the sperm of the patient
- Irreversible conditions that are not capable of assisted reproduction techniques and for which the use of donor sperm or adoption are possible options
- Life-threatening or health-threatening conditions that may be the underlying cause of infertility and require immediate medical attention
- Genetic abnormalities that can affect the health of the offspring if assisted reproduction technologies are used
Evaluating infertility
A couple trying to conceive should be examined for possible infertility if they do not succeed in conception within a year by having regular unprotected sexual intercourse. The examination should be done earlier in cases where 1) there are known risk factors for male infertility, such as a history of bilateral cryptorchidism 2) there are female risk factors for infertility, including the age of the partner (over 35 years) 3) couple wants to know the fertility potential of the partner.
A complete evaluation for male infertility should include a complete medical and reproductive history, a clinical examination by a specialist urologist or other specialists in male reproduction, and at least two sperm analyses. If possible, the two analyses should be conducted at least one month apart. Based on the results of the total evaluation of male infertility, the doctor may recommend other tests to clarify the etiology of the patient's infertility. These tests may include additional specialized sperm tests, endocrinological evaluation, urine analysis after ejaculation, ultrasound, and genetic testing. In general, specialized laboratory tests should be performed only in those cases in which the identification of the cause of male infertility may direct the treatment.
Medical history
The medical history of the patient is used to identify risk factors that could affect male infertility.
Clinical examination
A general clinical examination is an integral part of male infertility evaluation. The clinical examination is performed by a specialist Urologist.
Semen analysis
Semen analysis (Sperm Analysis, Comprehensive) is the cornerstone of laboratory evaluation of male infertility and helps determine the severity of the condition. Detailed laboratory protocols for sperm analysis have been published by the World Health Organization (WHO). Semen analysis provides information about sperm volume as well as its concentration, motility, and morphology. Although methods for the assessment of sperm concentration and motility have changed little over the past two decades, estimation of sperm morphology has evolved significantly. The WHO (1999) criteria for assessing sperm morphology are similar to those of Kruger (Tygerberg). When these criteria are applied to assess sperm morphology, relatively few spermatozoa are characterized as having a normal morphology, even in semen from fertile males.
Evaluation of sperm morphology with these criteria has been used to identify couples who have a low chance of fertilization by standard IVF and are more likely to be fertilized by ICSI. Actual reference values have not been documented for the various sperm parameters. The reference values we use come from the clinical literature. Results outside these reference ranges suggest the presence of male infertility and indicate the need for additional clinical and/or laboratory tests. It should be noted that the reference values for the various sperm parameters are not the same as the minimum values required for fertilization and that men with sperm analysis results outside the reference range may be fertile. In contrast, patients with results within the range of reference values may be infertile.
Evaluation of the endocrine system
Hormonal abnormalities of the hypothalamic-pituitary-testicular axis are known, although they are not common causes of male infertility. Examination of the endocrine system should be performed if there are:
- Abnormal sperm analysis, especially if the sperm concentration is less than 10 million / ml
- Abnormal sexual function
- Other clinical findings that indicate a specific endocrine disease
The minimum initial hormonal evaluation should include measurements of follicle-stimulating hormone (FSH) and testosterone (total and/or free) as well as the determination of luteinizing hormone (LH) and prolactin (PRL) levels. Although the levels of these hormones vary because they are secreted in a particular way, one measurement is usually enough to determine the patient's clinical endocrinological condition. The relationship between testosterone, LH, FSH, and prolactin helps to determine the clinical condition. A normal serum FSH level does not guarantee normal spermatogenesis. However, an FSH result even in the upper range of the normal reference range may be indicative of a spermatogenesis abnormality.
Post Ejaculation Urine analysis
Low sperm volume or absence of ejaculation may indicate retrograde ejaculation, lack of arousal, vas deferens obstruction, hypogonadism, or various congenital abnormalities. Ιn patients with a sperm volume of less than 1.0 ml, and in whom no hypogonadism or congenital sperm defect has been diagnosed, a post-ejaculation urinalysis should be performed in order to diagnose possible retrograde ejaculation. Of course, it is also important to exclude as a cause of the low sperm volume, incomplete collection, and very short abstinence period (less than 1 day). For more information see the Post Ejaculation Urine Analysis.
Sperm morphology (Kruger strict criteria)
The clinical implications of the pathological effects of sperm morphology remain highly controversial. With the exception of some rare morphological abnormalities, such as spermatozoa without acrosome, which are highly predictive of egg fertilization failure, in most cases, fertilization and pregnancy can be achieved even with very low morphology scores. The evidence so far shows that, in general, sperm morphology alone should not be used to make critical prognosis and/or treatment decisions for patients. Sperm morphology examination is part of the comprehensive semen analysis.
Sperm DNA fragmentation
DNA integrity testing refers to various tests that are used to assess the degree of fragmentation of sperm DNA. Several studies show that the pregnancy rate is lower in patients with reduced sperm DNA integrity, a result that seems to be statistically significant. However, many couples with reduced sperm DNA integrity can have children normally. Other studies suggested that DNA integrity can be examined as a prognostic factor in semen samples used for artificial insemination, IVF, and ICSI. Other data suggest the examination of DNA fragmentation, in order to identify patients at risk for recurrent miscarriage. For more information see the Sperm DNA Fragmentation test.
Reactive Oxygen Species (ROS)
Reactive oxygen species are produced by both the semen white blood cells and the spermatozoa themselves. Reactive oxygen species play an important role in regulating sperm maturation and acrosome reaction. However, increased levels of oxygen radicals can affect sperm function due to the peroxidation of membrane lipids. Elevated levels of oxygen free radicals have been implicated in male infertility.
Quantification of semen leukocytes
Increased white blood cell count in semen has been linked to problems with spermatozoa function and motility. On optical microscopy, both leukocytes and immature sperm cells appear the same and the correct term for both is "round cells". Many laboratories incorrectly refer to "round cells" as leukocytes. Various tests are available to differentiate leukocytes from immature sperm cells. Patients with true pyospermia (>106/ml) should be screened for urogenital infections.
Test for anti-sperm antibodies
Pregnancy rates may be reduced due to the presence of semen anti-sperm antibodies. Risk factors for developing anti-sperm antibodies include blockage of the vas deferens, previous genital infection, testicular injury, and previous genital surgery. The presence of anti-sperm antibodies should be investigated when there is asthenospermia with normal sperm concentration or sperm agglutination. Some specialists recommend this test in couples with unexplained infertility. Anti-sperm antibodies located on the surface of the spermatozoa (direct test) are more important than anti-sperm antibodies found in seminal plasma (indirect test). Testing for anti-sperm antibodies is not required if the sperm is used for ICSI. For more information see test Anti-Sperm Antibodies, Semen.
Examination of spermatozoa viability (vitality)
Sperm viability can be assessed with specific dyes or using the Hypoosmotic Swelling Test (HOS). These tests determine if the immobile spermatozoa are alive by identifying which spermatozoa have an intact cell membrane. Immobile but live sperm, as determined by the hypoosmotic swelling test, can be used successfully for ICSI. For more information see the Hypoosmotic Swelling Test.
Genetic testing
Genetic abnormalities can cause infertility by affecting sperm production or transport. The three most common genetic abnormalities associated with male infertility are 1) cystic fibrosis gene mutations associated with congenital vas deferens absence 2) chromosomal abnormalities related to abnormal testicular function and 3) Y chromosome microdeletions associated with spermatogenesis disorders. Azoospermia and severe oligospermia may be related to genetic abnormalities. An infertile man is more likely to have a gene mutation or a chromosomal abnormality in comparison with the general population.
Cystic fibrosis gene mutations (CFTR)
The most common cause of congenital bilateral absence of the vas deferens (CBAVD) is a mutation in the CFTR gene. Almost all men with clinical cystic fibrosis have CBAVD and about 70% of men with CBAVD and no clinical evidence of cystic fibrosis have a recognizable mutation in the CFTR gene. Most patients with vas deferens agenesis also have hypoplasia or agenesis of the seminal vesicles. For more information see the Cystic Fibrosis Mutation Analysis.
Karyotype
The karyotype analyzes all chromosomes for the detection of a potential addition or loss of whole chromosomes, as well as for the presence of structural abnormalities, such as chromosomal translocations, duplications, deletions, and inversions. Chromosomal abnormalities account for about 6% of all male infertility cases. The hereditary transfer of the chromosomal abnormality from the father to the fetus can lead to pregnancy loss, congenital disorders, male infertility, and other genetic abnormalities. For more information see the Karyotype test.
Y chromosome microdeletions
Approximately 13% of men with non-obstructive azoospermia or severe oligospermia have an underlying Y chromosome deletion. For more information see the Y Chromosome Microdeletions test.
