Understanding Male Infertility: A Comprehensive Overview

Dr. Madhu Juneja says, infertility is a medical condition defined as the inability of a couple to achieve a pregnancy after one year of regular, unprotected intercourse. While it’s often mistakenly perceived as a “female issue”, the male partner is the sole or contributing factor in a significant percentage of cases, ranging from 30% as a sole factor to another 20% as a contributing factor alongside female issues.

Causes of Male Infertility

Male infertility is caused by several factors that can be grouped broadly into difficulties faced during sperm production, sperm delivery, and sperm function.

Azoospermia and Oligozoospermia

These are some of the most common. Azoospermia is the condition where there is no

sperm whatsoever in the ejaculate, and oligozoospermia is a reduced sperm count. These may be caused by:

• Genetic or Chromosomal Abnormalities: Disorders such as Klinefelter syndrome (an additional X-chromosome or Y-chromosome microdeletions can significantly disrupt sperm production.
• Hormonal Dysregulation: The intricate hormonal mechanism between the pituitary gland, hypothalamus, and testes is responsible for the process of spermatogenesis. Lack of a

hormone, either testosterone or FSH, can lead to minimal or no sperm production.

• Testicular damage can be brought about by numerous causes, such as infection (e.g., mumps after puberty), trauma, undescended testes (cryptorchidism), or e x p o s u r e to chemotherapy or irradiation.

Varicocele

A varicocele is a common and often curable cause

of male infertility, found in about 15% of men. A varicocele is a dilation of the veins which occur in the scrotum, similar to varicose veins which occur in the legs. While the mechanism is unclear, it is thought that varicoceles cause increased temperature in the testicles and interference with the flow of blood, thereby decreasing sperm quality and number.

Anatomical Obstruction or Ejaculatory Issues

In some cases, sperm generation can be at normal levels; however, delivery is inhibited by an obstruction. This has been termed obstructive azoospermia. Etiologic causes are:

• Congenital Absence of the Vas Deferens (CAVD) is a congenital defect that is normally associated with cystic fibrosis, a situation wherein the tubes where the sperm pass through are absent.
• Infections: Reproductive tract scar tissue due to prior infections may cause a block to sperm movement through.
• Previous Procedures: Vasectomy or hernia repair procedures unknowingly can lead to the obstructions.
• Retrograde Ejaculation:

Semen flows backward into the bladder instead of exiting the penis. This can be caused by diabetes, spinal injuries, certain medications, or prostate/bladder surgery.

Lifestyle & Environmental Contributors

• Obesity
• Smoking
• Alcohol consumption
• Illicit drug use of anabolic steroids • Heat exposure
• Diet and nutrition

Assessment and Analysis

The assessment of male infertility begins with a thorough detailed medical history and physical examination. The primary diagnostic equipment includes:

• Semen Analysis: This is the foundation of the evaluation of male infertility. Semen is obtained and analysed to evaluate sperm volume, count, motility (movement), and morphology (form). Multiple samples may be required over time since sperm counts may vary.
• Hormone Testing: A blood test measures the levels of hormones like testosterone,

follicle-stimulating hormone (FSH), and luteinising hormone (LH) to check for possible

endocrine abnormalities like thyroid.

• Scrotal ultrasound is a non-invasive diagnostic method, which enables visualisation of testes and adjacent structures and therefore the detection of varicoceles or other anatomical defects.
• Genetic Testing: Where the person has a severely low or zero sperm count, genetic testing may be recommended to look for possible chromosomal or genetic defects that might be the cause of the condition likey chromosome microdeletion XXY syndrome.

Therapeutic Alternatives

Male infertility treatment is highly individualised and depends on the etiology.

• Lifestyle Changes: Healthy lifestyle changes can enhance the sperm parameters in some men. This involves quitting smoking, decreased alcohol consumption, normal weight, and avoiding excessive heat on the testes.
• In instances of hormonal dysregulation, pharmacological treatment can be employed to induce hormone secretion and to facilitate spermatogenesis. In infections, treatment can be done with antibiotics.
• Surgical Procedures:

– Varicocelectomy, or surgical correction of a varicocele, typically improves sperm quality and allows for natural conception.

– Sperm Retrieval: Sperm can be retrieved by surgery alone in obstructive azoospermia or in severe defects of sperm production in men.

The sperm retrieved can be used in assisted reproductive technologies.

• Assisted Reproductive Technologies (ART):

In case of failure or inappropriateness of routine treatments, ART offers a strong solution.

– Intrauterine Insemination (IUl) refers to the direct injection of concentrated healthy semen into the uterus during the fertile time of t h e partner.

– In Vitro Fertilisation (IVF) and Intracytoplasmic Sperm Injection (ICSI): ICSI is a procedure in which a single healthy sperm is injected into an oocyte with a very high fertilization success rate. It is particularly useful in the case of severe male factor infertility.

Glimpsing the Horizon:

• Future Directions and Unanswered Questions:

Despite significant advancements, there are still areas in male infertility where our understanding and treatment options are evolving.

• Sperm DNA Fragmentation: There’s increasing recognition of the role of high sperm DNA fragmentation in recurrent pregnancy loss and poorer ART outcomes. While tests exist, clear clinical guidelines for treatment strategies to reduce fragmentation and improve live birth rates are still evolving.
• Regenerative Medicine and Emerging Therapies

– Stem Cell Therapy: While highly experimental, research into spermatogonial stem cell transplantation (SSCT) aims to restore fertility in men with non-obstructive azoospermia, particularly in pre-pubertal boys

– In Vitro Spermatogenesis: Attempts to generate mature sperm from immature germ cells in a laboratory setting are underway.

– Genetic Editing: While controversial for human germline editing, understanding and potentially correcting genetic defects could, in the very distant future, lead to novel therapeutic interventions.