Urology treats urinary tract diseases in all genders and male reproductive issues, covering the kidneys, bladder, prostate, urethra, from infections to complex cancers.
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The diagnostic evaluation of male infertility begins with a semen analysis, but modern andrology goes far beyond the basic count and motility. Computer-Aided Sperm Analysis (CASA) uses high-speed cameras and algorithms to track individual sperm trajectories, providing precise measurements of kinematic parameters, such as curvilinear velocity and linearity. This technology eliminates subjective variability and provides a detailed assessment of sperm function.
Functional testing includes the assessment of sperm vitality using dye exclusion assays to distinguish between live immotile sperm and dead sperm. Leukocyte quantification is performed to rule out infection or inflammation. In cases of unexplained infertility, tests for sperm antibodies are conducted to detect immunological causes where the body’s immune system attacks the sperm.
Oxidative stress testing is becoming a standard part of the workup. Measuring the Oxidation Reduction Potential (ORP) of semen provides a global assessment of the balance between oxidants and antioxidants. High ORP values indicate oxidative stress, guiding the use of antioxidant therapies.
Sperm DNA integrity is a critical determinant of fertilization and embryo development. Standard semen parameters may be normal even in the presence of significant DNA damage. DNA Fragmentation Index (DFI) testing uses assays such as the Sperm Chromatin Structure Assay (SCSA), TUNEL, or HALO tests to quantify the percentage of sperm with fragmented DNA.
High DFI is associated with longer times to natural conception, lower IUI success rates, and an increased risk of miscarriage. Identifying high DFI allows clinicians to recommend interventions such as varicocelectomy, lifestyle modification, or the use of testicular sperm for ICSI, which often has lower DNA damage than ejaculated sperm.
A comprehensive hormonal evaluation assesses the integrity of the HPG axis. This includes measuring serum testosterone (total and bioavailable), FSH, LH, prolactin, and estradiol. Elevated FSH typically indicates primary testicular failure and damage to the germinal epithelium. Low testosterone with low gonadotropins suggests a central (hypothalamic or pituitary) cause.
Genetic testing is mandatory for men with severe oligospermia or azoospermia. Karyotyping detects chromosomal abnormalities, such as Klinefelter syndrome (47, XXY) and translocations. Y-chromosome microdeletion analysis screens for deletions in the AZF regions (AZFa, AZFb, AZFc), which control spermatogenesis. Testing for CFTR gene mutations is performed in men with congenital bilateral absence of the vas deferens. These genetic tests provide a diagnosis, predict the likelihood of retrieving sperm, and inform genetic counseling for the couple.
Scrotal ultrasound with color Doppler is the primary imaging modality for evaluating male infertility. It assesses testicular volume, echotexture, and perfusion. It is the gold standard for diagnosing varicocele and detecting subclinical reflux, even when palpable. Ultrasound can also identify epididymal cysts, hydroceles, and signs of obstruction, such as dilated rete testis.
Transrectal ultrasound (TRUS) is used to evaluate the prostate and seminal vesicles in cases of low semen volume or suspected ejaculatory duct obstruction. It can visualize cysts or calcifications blocking the ducts. In complex cases, such as descended testes or tumors, Multiparametric MRI provides high-resolution anatomical detail, aiding in surgical planning.
In men with azoospermia (no sperm in the ejaculate), distinguishing between obstructive and non-obstructive causes is crucial. If hormonal and genetic tests are inconclusive, a diagnostic testicular biopsy may be performed. This involves removing a small piece of testicular tissue to examine the seminiferous tubules.
Histological analysis can reveal patterns such as hypospermatogenesis (reduced sperm production), maturation arrest (developmental arrest), or Sertoli cell-only syndrome (absence of germ cells). In modern practice, this diagnostic step is often combined with therapeutic sperm retrieval to minimize trauma to the testis. The use of “mapping” biopsies can help locate focal areas of spermatogenesis in non-obstructive azoospermia, guiding future microdissection TESE procedures.
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According to the World Health Organization (WHO) criteria, a normal sperm count is at least 15 million sperm per milliliter of semen, or a total of 39 million sperm per ejaculate. However, fertility is a continuum, and men with lower counts can still conceive, while men with normal counts may have other functional issues affecting fertility.
Hormones drive sperm production. Checking FSH, LH, and testosterone helps determine if the problem lies in the testicles (primary failure) or the brain (secondary failure). High FSH usually indicates testicular damage, while low FSH suggests the brain isn’t sending the right signals. This distinction guides treatment, such as hormone replacement versus surgical retrieval.
DNA fragmentation testing assesses the quality of sperm DNA. High levels of fragmentation mean the DNA strands are broken, which can prevent fertilization or cause the embryo to stop developing. This test explains “unexplained” infertility or recurrent miscarriages in couples where the basic sperm numbers look normal.
Testicular biopsy is a minor surgical procedure usually performed under local anesthesia or light sedation. Patients may feel pressure or a pinch during the injection of anesthesia, but the procedure itself should not be painful. Afterward, there may be some soreness and swelling for a few days, which is managed with ice packs and over-the-counter pain relievers.
Color Doppler ultrasound is highly accurate and is the gold standard for diagnosing varicocele. It can detect blood flow direction and measure vein diameter. It can identify small “subclinical” varicoceles that cannot be felt during a physical exam but may still be contributing to infertility through thermal or oxidative stress mechanisms.
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