CARE_Testis biology related to infertility.pdf

IVF

1. Testis Biology related to
infertility

2. Gonadal differentiation and testis development

3. Testes

4. Seminiferous Tubule
•Organized into seminiferous tubules
made of simple columnar epithelium
of Sertoli cells
•Spermatogenesisoccurs from the
basal surface of the seminiferous
tubule to the lumen
•Leydig cellsfound between adjacent
seminiferous tubules synthesize
testosterone
•Fluid within the seminiferous tubules
flows toward the epididymis carrying
the sperm

6. Hormonal Control of Testicular Function
•Testosterone secretion
controlled by gonadotropic
releasing hormone (GnRH) –
hypothalamus
•Testosterone supports
spermatogenesis
•Leutenizing hormone (LH) -
stimulates the synthesis of
testosterone
•Testosterone -increase in bone
and muscle density; facial,
axillary and genital hair growth,
lengthening of vocal cords

7. Etiology of Male Infertility Due to Testicular Dysfunction
ETIOLOGY
Environmental FactorsLifestyle Factors
Acquired
Other causes
Genetic Developmental

8. Anorchia
Adisorder of sex development, in which a male has single (unilateral anorchia) or no testes (bilateral)
Congenital
▪Vascular & genetic disturbances
▪Intrauterine infections
▪Trauma / teratogenic
Acquired
▪Accidental/Medical/Legal Castration
▪Trauma
▪Torsion
Bilateralcongenitalanorchia
▪Duringgonadaldifferentiationiftestesdoesnotproducetestosterone→malepseudohermaphroditismincluding
femaleexternalgenitalia
▪Ifleftuntreated–nopubertaldevelopment
Unilateralcongenitalanorchia
▪Unilateral retention of female genitalia may be seen but no disorders of sexual differentiation and puberty

9. ▪Whenbothtestesarelost,testosteronemustbepermanentlysubstitutedfromthetimeof
theexpectedbeginningofpubertyandinanadultimmediatelyaftertesticularlossto
maintainthevariousandrogen-dependentfunctions
▪Infertility(bilateralanorchia):useofdonorsperm
Medical Management

10. Cryptorchidism
•Failure of both or single testis to
descend into scrotum
•Uni/ bilateral
•Functional/ non-functional testes
•Incidence -1% to 4%
•Spontaneously get corrected by 3
months of age
•Abdomen/ groin/ misplaced in
scrotum
•Higher risk of developing
testicular cancer and infertility
10
❖Unilateralorbilateral
❖Lowspermcount
❖Increasedcasesofinfertility

11. Medical Management

12. Varicocele
Vascularabnormality–abnormaldilationandenlargementofscrotalveinsleadingtoswellingand
pain
Causes
•Increase in testicular temperature
•Abnormal flow of adrenal or renal metabolites down the left spermatic vein
•Testicular hypoxia
•Testicular metabolic defects etc
Treatment options
❖Infertility treatment –surgery, if required (low sperm count/motility or chronic pain)
❖ART if needed

13. Klinefelter Syndrome (47,XXY -male)
•1 in 500/1000 males with variants (48, XXXY or 49, XXXXY)
•Only 10% diagnosed before 14yrs
•14% of non-obstructive azoospermia –KS
•Not inherited
•Various extents of spermatogenic failure, micro/cryptorchidism,
hypospadias, micropenis, delayed speech and language development
•Low testosterone production –delayed puberty, gynecomastia,
reduced facial/body hair, mostly infertile
•Variants –severe signs -intellectual disabilities, distinctive facial
features, skeletal abnormalities, poor coordination, and severe
speech problems
•Treatment options: Fertility preservation for adolescents,
testosterone therapy, donor sperm

14. Y chromosome infertility
SRY gene mutations : 10-15% of 46, XY gonadal dysgenesis patients show absence
of puberty
-Presence of female reproductive components ; Undermasculinizationof 46, XY
males
•Absence of puberty, a normal vulva, vagina, and uterus, and streak gonads
•Risk of developing germ cell tumoursdue to presence of streak gonads
•5–15% of men with nonobstructive azoospermia and severe oligozoospermia
have a Y chromosome microdeletion
AZF microdeletions -long arm of the Y chromosome in multiple genes -AZFa,
AZFb, AZFc
•8.2% of infertile males and 0.4% of fertile males were found to have deletions of
one or more AZF regions
•Inherited microdeletion & will pass on to subsequent male offsprings

15. Spermatogenesis genes –Yq11
•AZFa–SCO syndrome
•AZFb–Maturation arrest
•AZFc–Mild/severe oligozoospermia, azoospermia
(most common)
•AZFabc-Anormal karyotype such as presence of
two X chromosomes and the absence of Y
chromosome material in a phenotypic male (46, XX
male) or the presence of a Y isochromosome (iso(Y)
•ICSI, TESE, micro-TESE, donor sperm, PGD –
treatment options

16. Other causes of testicular dysfunction
•Other testicular disorders –46XX male syndrome, Kartagener’s
syndrome, genital tract abnormalities
•Infections –genitourinary, viral, TB
•Cancer and/or its treatment
•Lifestyle –obesity, alcohol, smoking, drug abuse
•Exposure to hazardous chemicals
•Idiopathic

18. ART options
•Adequate Counselling
•ICSI/IMSI
•TESE, microTESE
•Pre-implantation genetic
testing
3
rd
party reproduction
•Donor sperm
Detection of DNA fragmentation
•TUNEL, SCD