Genetic testing in male infertility
It is estimated that men are responsible for 40-50% infertility cases. Known genetic factors are responsible for 20% of male infertility 30-60% of azoospermia is idiopathic & require factor genetic testing.
2 important reasons for testing is-
(a)- To identify possible genetic defects with risk transmission to offspring through ART
(b)- To detects genetic disorders importing the ability to obtain spermatozoa through sperm retrieval techniques such as micro TESE etc.
Genetic tests- karyotyping CFTR mutation screening Y chromosome micro detection
- Karyotyping- recommended for all men having fetal notice sperm count <5 million &men with non-obstructive azoospermia.
- Chromosomal abnormalities are detected are aneuploidy (e.g.-trisomy) &structured ( e.g.- inversions /translocations)
- Genetic technique
(A) Karyotyping –Giemsa/trypsin staining on metaphase derived from peripheral blood lymphocytes
(B) Molecular genetic testing –FISH&CGH.
Klinefelter syndrome- 47XXY karyotyping most common chromosomal aneuploidy up to 12% of men in azoospermia .
Infertility due to defect in spermatogenesis leading to azoospermia /severe oligozoospermia.
80-90%-47xx4
10-20%- 46x4/47xx4,48xxxy or 48xxyy
Main genetic cause- meiotic nondisjunction
According to ASRM (American society for reproductive medicine)
Men with non-obstructive azoospermia & severe oligozoospermia must be offered high resolution karyotype before using sperm for ICSI.
- Y chromosome micro detections (AZF)- micro detections occurs most frequently on long arm of Y chromosome Y q. Y chromosome deleted regions are mapped to 3azoospermia factor (AZF)-AZFa ,AZFb& AZFc.
(1) AZFa detection-sertoli cell only syndrome.
(2) AZFb detetion- spermatogenic arrest
(3) AZFc- sectoli cell only syndrome to oligozoospermia
(Residual spermatogenesis – success rate 50-70%)
Technologies used –polymerase chain reaction technique.
(3)CFTR- gene defects & obstructive azoospermia –
CFTR related male infertility is subdivided into following phenotypes:--
- Congenital bilateral absence of vas deferens(CBAVD)
- CBAVD having unilateral renal anomalies
- Congenital unilateral absence of vas deferens (CBAVD)
- Ejaculatory duct obstruction
CFTR gene is on chromosome 7q 31.2 CFTR gene contains 27 axons &three are >2500 mutations repeated ranging from most lethal cystic fibrosis (CF) to mild phenotype CBAVD screening of female partner for CF carrier is essential for calculating accurate genetic risks & offering counseling & treatment option .PGS is recommended when female partner of CBAVD has CFTR mutation .
Algorithm for genetic investigations of male infertility.
Azoospermia
Testis testis>10 testis size< (8-10ml)
Low semen volume biopsy biopsy
Low PH hypermatogenesis germ cell at rest sertoli cell
Absent vas deference Y chromosome Y micro deletions C-kit/set
On palpation micro deletion meiotic arrest gene Bcl-W
CFTR gene testing ERX
Female partner carrier screening
Genetic counseling.
Testis size c 8-10 ml
Low (N)or high FSH
FSH /LH/T FSH receptor mutation
Kallmann syndrome Y micro detections
Meiotic arrest genes
Genetic counselling
Oligospermia-sperm count <5-10 million
Karyotyping
Y micro detecting
AR mutations
