1MALE INFERTILITY - IN GENERAL

• Infertility is the inability of a sexually active, non- contracepting couple to achieve spontaneous pregnancy in one year
• An estimated 15% of couples meet this criterion and are considered infertile, with approximately 35% due to female factors alone, 30% due to male factors alone, 20% due to a combination of female and malefactors, and 15% unexplained

Pre testicular causes of infertility

• Include congenital or acquired diseases of the hypothalamus, pituitary, or peripheral organs that alter the hypothalamic-pituitary axis
• Disorders of the hypothalamus leads to hypogonadotropic hypogonadism
• If gonadotropin-releasing hormone (GnRH) is not secreted, the pituitary does not release luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
• Kallmann syndrome 
• Prader-Willi syndrome 
• Laurence-Moon-Biedl syndrome 
• Central nervous system tumours
• Temporal lobe seizures
• Drugs - Antihypertensives, Antipsychotics, Dopamine antagonists, etc.
• Both pituitary insufficiency and pituitary excess cause infertility
• Pituitary failure may be congenital or acquired. Acquired causes include tumour, infarction, radiation, infection, or granulomatous disease
• Hyperprolactinemia & Prolactinoma 
• Isolated LH deficiency (fertile eunuch) - Patients have eunuchoidal body habitus, large testis, and a low ejaculatory volume
• Isolated FSH deficiency - Patients present with oligospermia but have LH levels within the reference range
• Thalassemia - Excess iron from multiple transfusions may be deposited in the pituitary gland and the testis, causing parenchymal damage and both pituitary and testicular insufficiency
• Cushing disease 
• Hormonally active peripheral tumors
• High cortisol 
• Cortical deficiency 
• Estrogen excess - seen in patients with Sertoli cell tumors, Leydig tumors, liver failure, or severe obesity. Estrogen causes negative feedback on the pituitary gland, inhibiting LH and FSH release.

Primary testicular causes of infertility

• May be chromosomal or non chromosomal in nature

Chromosomal

• Klinefelter syndrome
• XX male (sex reversal syndrome) 
• XYY male 
• Noonan syndrome (46, XY) 
• Mixed gonadal dysgenesis (45, X/46, XY) 
• Androgen receptor dysfunction
• Y chromosome microdeletion syndrome 
• Bilateral anorchia (vanishing testes syndrome)
• Down syndrome
• Myotonic dystrophy 

Nonchromosomal testicular failure

• Varicocele 
• Cryptorchidism 
• Trauma -Testicular trauma 
• Sertoli-cell-only syndrome(germinal cell aplasia) 
• Chemotherapy 
• Radiation therapy 
• Orchitis 
• Human-beta defensin abnormalities 
• Granulomatous disease 
• Sickle cell disease 
• Excessive use of alcohol, cigarettes, caffeine, or marijuana

 Post-testicular causes of infertility

• Post-testicular causes of infertility include problems with sperm transportation through the ductal system, either congenital or acquired

• Congenital blockage of the ductal system 
• Cystic fibrosis Acquired blockage of the ductal system 
• Young syndrome 
• Trauma, previous attempts at sperm aspiration, and inguinal surgery may also result in ductal blockage
• Scrotal surgery, including vasectomy, hydrocelectomy and spermatocelectomy 
• Antisperm antibodies 
• Defects in cilia Kartagener syndrome with situs inversus
• Ejaculatory duct obstruction 
• Ejaculation issues - Anejaculation/retrograde ejaculation

• Depends on the underlying condition 
• Diabetes may cause autonomic neuropathy, neurogenic impotence, and retrograde ejaculation
• Obesity alters hormonal metabolism, leading to increased peripheral conversion of testosterone to oestrogen and decreased luteinizing hormone (LH) pulse amplitude, and has been linked with reduced sperm concentration 
• Patients with sickle cell disease or thalassemia may have infertility due to haemosiderosis from multiple blood transfusions
• Almost all males with cystic fibrosis have a congenital bilateral absence of the vas deferens 
• Chronic kidney disease leads to hypogonadism and feminization
• Liver disease may result in decreased male secondary sexual characteristics, testicular atrophy, and gynecomastia due to increased oestrogen levels
• Haemochromatosis leads to hypogonadism and signs of androgen deficiency without gynaecomastia and is associated with decreased estradiol levels
• Postpubertal mumps may lead to testicular atrophy
• Sexually transmitted diseases and tuberculosis can cause obstruction of the vas deferens or epididymis
• Prostatitis, orchitis, seminal vesiculitis, and urethritis may lead to obstructive azoospermia
• Anesthesia, surgery, starvation, myocardial infarction, hepatic coma, head injury, stroke, respiratory failure, congestive heart failure, sepsis, and burns are associated with a suppression of gonadotropin release, possibly through an increase in dopamine and opiate levels
• Chronic medical illnesses may directly suppress sex hormone production and sperm production, leading to end-organ failure

• Medical history – General & Sexual history
• Physical examination – Thorough Examination of Body habitus, Penis, scrotum, Testes, Epididymis
• Semen Analysis 
• Hormone Assay - GNRH, Testosterone, Free Testosterone, FSH, LH, Prolactin, 17 OH progesterone, Thyroid Hormones 
• Scrotal Doppler ultrasound – To detect Varicocele, Spermatocele, Epididymal lesions
• Transrectal Ultrasound (TRUS) – Provides clear images of Seminal vesicles, Vas deferens, Prostate, ejaculatory ducts
• MRI
• CT
• Venography – to diagnose varicocele
• Anti sperm antibodies 
• Karyotype ( genetic testing)
• Testicular biopsy - In cryptorchidism, Testicular histology typically reveals a decreased number of Leydig cells and decreased spermatogenesis

The following causes of infertility, if identified, can often be treated by medical means: 

• Endocrinopathies 
• Antisperm antibodies 
• Retrograde ejaculation 
• Poor semen quality or number 
• Lifestyle issues 
• Infections 

Surgical interventions to be considered include: 

• Varicocelectomy 
• Vasovasostomy or vasoepididymostomy 
• Transurethral resection of the ejaculatory ducts 
• Sperm retrieval techniques 
• Electro ejaculation 
• Artificial insemination 
• Assisted reproduction techniques 
• In vitro fertilization 
• Gamete intra fallopian transfer (GIFT) and zygote intra fallopian transfer (ZIFT) 
• Intra cytoplasmic sperm injection