Credits

• Section Writer: Dr. Om J Lakhani
• Section Editor: Dr. Om J Lakhani

Q. Enlist the causes of male infertility?

• Pretesticular
  • All causes of hypo hypo
  • Congenital Hypo hypo
  • Pituitary mass
  • Suprasellar mass
  • Lymphocytic hypophysitis
  • Malnutrition
  • Systemic illness
  • Drugs which act on GnRH
  • Hyperprolactinemia
• Testicular causes
  • Congenital
    • Kleinfelter syndrome
    • Yq microdeletion
    • Cryptorchidism
    • Testosterone biosynthesis defect
    • Androgen insensitivity syndromes
  • Acquired
    • Viral orchitis
    • Testicular trauma
    • Torsion
    • Varicocele
    • Testicular tumor
    • Torsion
    • Drugs
    • Environmental toxins
• Post testicular
  • Absent seminal vesicule or vas deferens
  • Obstruction of Sperm ejaculation pathway
  • Ejaculatory disorder- ED, Premature ejactation ,retrograde ejaculation
• Idiopathic
  • 40-50% cases

Q. How common is Yq microdeletion?

• More common than we thing
• 20% of infertile men have it

Q. Which region in chromosome Y is defective in Yq microdeletion?

• The defect lies in the long arm of chromosome Y
• The defect is in the Azospermic region (AZF)
• There are three regions of AZF- AZFa, b, and C
• Asia and b involvement- azoospermia
• AZFc- oligospermia

Q. What does the biopsy show?

• Germ cell arrest
• Sertoli only syndrome

Q. Which genes in these regions are defects?

• USP9Y
• DDX3Y

Q. Can this disease be transmitted?

• If the sperms of these males are used for ICSI- then yes, it is transmitted to offspring
• Hence Yq microdeletion testing is offered to these men before ICSI

Q. What test must be done if there is a bilateral absence of Vas Deferens?

• CFTR gene mutation for Cystic fibrosis

Genetic causes of Male infertility

Q. Name the key genetic causes of male infertility

• CFTR mutation
  • This produces a congenital absence of vas deferens
• Klienfelter syndrome - The most common cause
• Y chromosome microdeletions producing Y Chromosome infertility
• Genetic causes attribute to 15-30% of male infertility
• Chromosomal abnormalities produce more severe disorders like Azoospermia or severe oligospermia

Q. What is AZF?

• AZF is a region on the long arm of chromosome Y which is associated with infertility in men
• This produces a condition called Y Chromosome infertility
• There are three regions - AZFa, AZFb, AZFc
• Deletion in AZFa and AZFb produce Azoospermia
• Deletion in AZFc produce severe oligospermia - however, enough sperms are produced for sperm extraction using TESE and use for Intracytoplasmic sperm injection (ICSI)

Q. Summarize the genetic causes of male infertility

Q. What is Robertsonian translocation ?

• Answer from Wiki:
  • "Robertsonian translocation (ROB) is a chromosomal abnormality wherein a certain type of a chromosome becomes attached to another. It is the most common form of chromosomal translocation in humans, affecting 1 out of every 1,000 babies born."

Q. What does INSL3-LGR8 mutation produce ?

• It produces cryptorchidism

Q. What is Sertoli cell-only syndrome ?

• This is a histological syndrome.
• This is typically seen in young males between 20-40 years
• On Semen analysis they have Azoospermia or severe oligospermia
• On Histopathology- the seminiferous tubules are lined with Sertoli cells only and little or no spermatogenesis takes place
• the testis may be slightly atrophied
• Inhibin B levels may be low
• FSH is elevated with normal LH
• The male is otherwise normally virilized
• The likely etiology is likely to be Y Chromosome infertility due to AZF microdeletions
• Similar situation can also be acquired due to toxins which damage the sperm production

Q. What are the Androgen insensitivity syndrome

• There are three types of Androgen insensitivity syndrome
  • Complete Androgen insensitivity syndrome- 46, XY presenting as a female
  • Partial Androgen insensitivity syndrome- 46, XY DSD presenting with atypical genitalia
  • Mild androgen insensitivity syndrome- presenting as male phenotype with Gynecomastia and reduce androgenization

Q. Tell me something about congenital bilateral absence of vas deferens (CBAVD) ?

• This is caused by CFTR gene.
• The patient is a phenotype male with normal testicular sperm production but absent vas deferens leading to Azoospermia
• The same gene also produces cystic fibrosis
• The patient may or may not have clinical features of cystic fibrosis