Male Factor Infertility

Summary

Male infertility is a multifactorial condition that may result from spermatogenic failure, obstructive pathology, endocrine dysfunction, sperm abnormalities, sexual disorders, or lifestyle and environmental factors. A structured approach involving thorough history, examination, and semen analysis is essential. Management ranges from lifestyle modification to medical or surgical therapy, with assisted reproductive techniques playing a central role in many cases.

Overview

Male factor infertility contributes to nearly 40% of infertility cases in couples, either as an isolated cause or in combination with female factors. It is defined as the inability to achieve conception due to abnormalities in sperm production, function, or transport, or due to disorders of sexual or ejaculatory function. A comprehensive evaluation is essential to identify reversible causes, guide management, and optimize reproductive outcomes.

Causes

1. Spermatogenic Failure

Spermatogenic failure refers to impaired sperm production and is the most common cause of male infertility.

• Congenital: absence of testes, cryptorchidism, genetic abnormalities.

• Acquired: testicular trauma or torsion, mumps orchitis, testicular tumors, systemic diseases (e.g., cirrhosis), varicocele, or exposure to cytotoxic agents (chemotherapy, radiotherapy).

• Idiopathic: no identifiable cause despite evaluation.

• Genetic syndromes:

• Klinefelter’s syndrome (47,XXY) – associated with hypergonadotropic hypogonadism.

• Kallmann syndrome – hypogonadotropic hypogonadism due to GnRH deficiency.

• Androgen insensitivity syndrome – XY karyotype with end-organ resistance to androgens.

2. Obstructive Azoospermia

Defined as complete absence of sperm in the ejaculate despite normal spermatogenesis, caused by bilateral obstruction of the seminal ducts.

• Causes: congenital bilateral absence of the vas deferens (often associated with cystic fibrosis), infections (e.g., gonorrhea, chlamydia), iatrogenic injury (e.g., post-surgery, vasectomy), or ejaculatory duct obstruction.
  
  

3. Varicocele

An abnormal enlargement of the pampiniform venous plexus in the scrotum, present in approximately 25% of men with abnormal semen parameters. Although the exact mechanism remains unclear, it is thought to impair spermatogenesis by increasing scrotal temperature and inducing oxidative stress.

4. Endocrine and Hypogonadal Disorders

• Primary (hypergonadotropic) hypogonadism: testicular failure with elevated FSH/LH.

• Secondary (hypogonadotropic) hypogonadism: impaired hypothalamic or pituitary function, reducing GnRH, FSH, and LH secretion.

• Androgen insensitivity: end-organ resistance to androgen action despite normal hormone levels.

5. Sperm Functional Abnormalities

• Oligospermia: reduced sperm concentration.

• Asthenospermia: reduced sperm motility.

• Teratospermia: abnormal sperm morphology.
  Causes include childhood mumps, testicular trauma, sexually transmitted infections, varicocele, toxins, and systemic disease.

6. Sexual Dysfunction

Erectile dysfunction, ejaculatory disorders (e.g., retrograde ejaculation, anejaculation, premature ejaculation), or psychogenic factors may impair fertility despite normal spermatogenesis.

7. Lifestyle and Environmental Factors

Obesity, smoking  (can increase the risk of erectile dysfunction and a low sperm count in men), excessive alcohol intake (can decrease sperm count and motility), recreational drug use, high scrotal temperatures, and exposure to environmental toxins contribute to impaired fertility.Smoking.

Initial Evaluation

A thorough assessment of both partners is essential, ideally with both present during the initial consultation.

History

• Reproductive: duration of infertility, previous pregnancies, attempts at assisted reproduction.

• Sexual: frequency and timing of intercourse, erectile/ejaculatory problems, use of lubricants (some spermicidal).

• Medical: history of mumps orchitis, testicular trauma, systemic disease, STIs, chemotherapy/radiotherapy.

• Surgical: orchidopexy, hernia repair, scrotal/urogenital procedures.

• Medications: sulfasalazine, anabolic steroids, chemotherapy, cytotoxics.

• Family history: genetic disorders (e.g., cystic fibrosis, Klinefelter syndrome).

• Social/occupational: smoking, alcohol, recreational drugs, heat exposure, toxins.

• Female partner: menstrual regularity, PCOS symptoms (acne, hirsutism), features of endometriosis (dysmenorrhea, dyspareunia).

Physical Examination

• General: BMI, signs of hypogonadism (gynecomastia, decreased body hair, muscle wasting).

• Genital: testicular volume and consistency, varicocele, epididymal thickening, vas deferens presence, urethral meatus location, penile abnormalities, undescended testes.

• Signs of anabolic steroid use should also be noted.

Investigations

Primary Care

• Semen Analysis: first-line test, The interval of abstinence should be 2-7 days, at least two specimens should be examined at least several weeks apart, interpreted according to WHO reference values:

• Volume ≥ 1.5-5 ml

• pH ≥ 7.2

• Sperm concentration ≥ 15 million/ml

• Total sperm count ≥ 39 million/ejaculate

• Motility ≥ 40% total or ≥ 32% progressive

• Vitality ≥ 58% live sperm

• Morphology ≥ 4% normal forms

• Repeat semen analysis: required after 3 months if abnormal (earlier if azoospermia or severe deficiency).

• Chlamydia testing.

Secondary Care

Indicated after two abnormal semen analyses or earlier if significant pathology is suspected. May include:

• Hormonal evaluation: FSH, LH, testosterone, prolactin, TSH.

• Genetic testing: karyotype, CFTR mutation analysis.

• Imaging: scrotal or transrectal ultrasound.

• Testicular biopsy: to distinguish obstructive from non-obstructive azoospermia.

• Sperm culture and antisperm antibody testing when appropriate.
  

Management

Lifestyle and Supportive Measures

• Weight management, smoking/alcohol/drug cessation.

• Stress reduction and counseling for psychosexual dysfunction.

• Avoidance of heat exposure and gonadotoxic agents.
  
  

Medical Management

• Hypogonadotropic hypogonadism: treated with gonadotropins (hCG, FSH) or pulsatile GnRH.

• Other idiopathic semen abnormalities: pharmacological treatment (e.g., anti-estrogens, empiric gonadotropins) is not recommended by NICE due to lack of proven benefit.

Surgical Management

• Obstructive azoospermia: surgical reconstruction or sperm retrieval for assisted reproduction.

• Varicocele: surgical correction is not recommended as part of routine infertility treatment since it does not improve pregnancy rates.

Assisted Reproductive Techniques

• Intrauterine insemination (IUI).

• In vitro fertilization (IVF).

• Intracytoplasmic sperm injection (ICSI): particularly useful in severe oligospermia, asthenospermia, teratospermia, or after sperm retrieval in azoospermia.