Investigating Male Infertility

Male infertility is a significant issue for many couples who wish to have a child. Proper investigation of male infertility is critical for effective management of the problem. The following are the basic methods for investigating male infertility, with detailed information for each procedure.

1. Medical history and clinical examination

The investigation begins with a detailed medical history and clinical examination. The medical history includes questions about:

Sexual life: Information about the frequency of sexual intercourse, use of condoms, presence of erectile or ejaculatory dysfunction.
Previous illnesses: History of infections, such as mumps after puberty, sexually transmitted infections, or chronic diseases.
Injuries: Injuries to the genital area or inguinal region.
Medications and toxic substances: Use of medications that may affect fertility, exposure to toxic substances or radiation.
Surgical interventions: Previous surgical procedures in the genital area or inguinal region.

The clinical examination includes inspection and palpation of the testicles, penis, and when indicated, the prostate. Signs of varicocele, hydrocele, cryptorchidism, or other abnormalities are sought. Palpation of the prostate through digital rectal examination can detect inflammation or other medical conditions.

2. Semen analysis

Semen analysis is the main test for assessing male fertility. It involves the analysis of a semen sample collected through masturbation. The sample should be produced after two to seven days of abstinence, unless the laboratory advises otherwise. The following parameters are analysed:

Semen volume: lower fifth-percentile reference value, 1.4 mL.

A reduced semen volume can have several causes, including incomplete collection, retrograde ejaculation, an obstruction or a problem with the seminal vesicles.

Sperm concentration: lower fifth-percentile reference value, 16 million sperm per mL.
Motility: the percentage of sperm that are moving. The lower fifth-percentile reference values in WHO 2021 data are 42% for total motility and 30% for progressive motility. These values are not strict cut-offs between fertility and infertility and must be interpreted with the full semen assessment.
Morphology: The percentage of sperm with normal shape.

Lower fifth-percentile reference value: 4% normal forms.

Vitality: The percentage of living sperm.

Normal values: at least 58% of sperm should be alive.

If a repeat sample is needed, its timing should be guided by the clinical question; repeating the test after about 11 weeks reflects a new cycle of sperm production.

3. Hormonal tests

Hormonal tests evaluate the function of the testicles and the hypothalamic-pituitary-testicular axis. They include:

FSH (Follicle Stimulating Hormone): Elevated levels may indicate primary testicular failure.
LH (Luteinizing Hormone): Elevated levels combined with low testosterone may indicate primary testicular failure.
Testosterone: Both total and free testosterone are evaluated. Low testosterone can affect fertility.
Prolactin: Elevated levels can affect testosterone production, erectile function, and fertility.

Oestrogens: measured to detect raised oestrogen levels, which may be linked to obesity or to excessive conversion (aromatisation) of testosterone.

4. Genetic testing

Genetic testing detects chromosomal abnormalities or gene mutations that affect fertility:

Cytogenetic Analysis (Karyotype): Checks for abnormalities in the number and structure of chromosomes. Examples include Klinefelter syndrome (47,XXY) and other chromosomal abnormalities.
Y Chromosome Microdeletions: Tests for microdeletions in the AZF region of the Y chromosome which is critical for spermatogenesis.
CFTR Gene Analysis: Checks for mutations in the CFTR gene related to cystic fibrosis and absence of the vas deferens, causing obstructive azoospermia.

5. Imaging studies

Imaging studies help detect anatomical abnormalities and other medical conditions:

Scrotal Ultrasound: Examines the testicles and spermatic veins for abnormalities such as varicocele, hydrocele, or tumours. Varicocele can cause increased testicular temperature, negatively affecting sperm production.
Transrectal Ultrasound of Prostate and Seminal Vesicles: Checks for obstructions or abnormalities in the sperm ducts and seminal vesicles that may affect sperm flow.
Magnetic Resonance Imaging (MRI): Used for imaging the genital area with greater detail when there are suspicions of anatomical abnormalities or tumours.

6. Testicular biopsy

Testicular biopsy is used to detect spermatogenesis, especially in cases of azoospermia (absence of sperm in the semen). The procedure involves taking a small amount of tissue from the testis and examining it microscopically. It can reveal whether there are sperm in the testicles, indicating the presence or absence of spermatogenesis.

7. Anti-sperm antibodies

Some men produce antibodies against their own sperm, which can affect fertility. These antibodies can make sperm clump together (agglutination) and can affect their movement and function. The test detects the presence of these antibodies in the semen or blood and can be used to evaluate the immunological cause of infertility.

8. Sperm DNA Fragmentation Index (DFI)

The DNA fragmentation index (DFI) evaluates damage to sperm DNA. Elevated levels of DNA fragmentation can affect fertilisation ability and embryo quality. The DFI test is particularly useful in cases of recurrent miscarriages or failed in vitro fertilisation attempts. DFI can be assessed by methods such as SCSA (Sperm Chromatin Structure Assay) or TUNEL assay.

The investigation of male infertility requires a thorough, step-by-step approach. The combined use of the above methods can help diagnose the cause of infertility and lead to personalised treatments, increasing the chances of success in assisted reproduction. Each step of the investigation offers valuable information for identifying contributing factors and planning appropriate care, ensuring the best possible management for each couple.