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MALE INFERTILITY
Dr. Mahmoud Faisal Rashad.
MD
Main Items
• 1- Introduction.
• 2- Classifications.
• 3- Causes.
• 4- Work up.
• 5- Treatment options.
Introduction
Definition:
Inability of a couple to conceive after one year
of regular unprotected intercourse.
It affects about 15% of
couples
40% are due to male
cause.
40% are due to female
cause.
 20%are due to
combined cause
(Male reproductive physiology)
• The physiology of hypothalamic-pituitary-
gonadal axis plays the critical role.
Components of the HPG axis
Hypothalamus:
• Is the pulse generator for the cyclic secretion of
the pituitary and gonadal hormones.
• The most important hormone produced is GnRH
(LHRH), which stimulates the production of both
LH, and FSH from the anterior pituitary.
• LHRH produced in a pulsatile manner which
governs the concomitant cyclic release of
gonadotropins.
Anterior Pituitary:
• Is the site of action of LHRH, which
stimulates release of LH, and FSH.
• LH stimulate steroidogenesis in Leydig cells.
(production of testosterone)
• FSH binds to Sertoli cells and spermatogonial
membrane and stimulates semineferous tubules
growth during development.
• it is essential for
initiation of spermatogenesis at puberty
maintenance normal levels of sperm production in
adults.
• Prolactin is another hormone of anterior pituitary
which important for lactating women.
 Its function is not known in males.
 Abnormal high level may abolish gonadotropin
pulsatile pattern.
Hypothalamo pituitary gonadal
axis
The testis
Is composed of
endocrine part (Lyedig cells)
exocrine part (seminiferous tubules)
both under direct control of HPG axis.
Endocrine testis:
Responsible for testosterone production by
Lyedig cells.
Only 2% of testosterone is free (unbound), and
active, while the rest is bound to either albumin
or sex hormone binding glublin (SHBG).
Testosterone is either metabolized by 5α-
reductase into DHT, the potent androgen, or by
aromatase into estradiol.
Exocrine testis:
On FSH stimulation, Sertoli cells make a host
of secretory products important for germ cell
growth, including androgen-binding protein.
Through these actions seminiferous tubule
growth is stimulated during development,
and sperm production is initiated during
puberty as well as a normal level of
spermatogenesis is maintained in adults.
Spermatogenesis
• Occurs in semineferous tubules
• Spermatogenesis requies:
• -FSH
• -Intra luminal Testosterone
• -Intact blood testicular barrier
• -Appropriate temperature (36 ‘C)
• Spermatozoa have very poor motility and are
incapable of naturally fertilizing an egg.
• They become functional only after traversing the
epididymis(10-15 days) where further maturation
occurs ( Sperm maturation).
• Capacitation”. Fertilization in the ampullary part
of the fallopian tube requires further maturation
stages
• A change in the type of flagellar movement and
release of lytic enzymes from the acrosome.
Classifications of male infertility
• 1- Primary or secondary.
• 2-Location of the abnormality.
• -Pre testicular.
• - Testicular
• - Post testicular
Classifications of male infertility
• 3-Sperm parameter
• Normospermia
• Azoospermia
• Oligospermia
• Ashenospermia.
• Teratospermia.
• Aspermia.
• 4-Obstructive or non obstructive
CAUSES OF MALE INFERTILITY
Pretesticular
Testicular
posttesticular
Pretesticular causes
• Hypothalamic disease:
Gonadotropin deficiency “kallmann syndrome”:
 familial, x linked or autosomal,
 due to disturbance of neuronal migration from the
olfactory placode which contain neurons responsible
for both olfaction and LH release.
 The patient complains of hypogonadism and
anosmia.
Pituitary disease:
Pituitary insufficiency: tumors, infarcts, radiation
Hyperprolactinemia:
 pituitary adenoma.
secondary to stress, medications, and systemic
disease.
High prolactin induces a negative feedback on
gonadotropin secretion.
Exogenous and endogenous hormones: androgens,
estrogens, thyroid hormones, or corticosteroid.
Testicular Causes
A. Chromosomal causes
 Klinefelter syndrome (47XXY):
 the most common genetic cause for azospermia.
 classic triad of small firm testis, gynecomastia and
azospermia.
 They have delayed sexual maturation, increased height,
obesity and diabetes.
 Increased malignancy risk by 20 folds.
 Sertoli cell only syndrome:
 azospermic men with testicular biopsy show absence of
germinal epithelium.
 The patients have normal virilization, with small testis with
normal consistency.
 There is no gynecomastia
B. Gonadotoxins:
 Radiation
 Drugs: ca+2
channel blockers, allopurinol, cimitidine,
spironolactone, alpha blockers, TCA
 Liver cirrhosis: increased s. estrogen causes
testicular atrophy, gynecomastia, and impotence.
C. Defective androgen activity
 5 α reductase deficiency: causes normal internal
genitalia, but ambiguous external genitalia as
hypospadias, and cryptorchidism.
 Androgen receptor deficiency: no receptor for DHT
to bind, so no action, in turn both the internal and
external genitalia are affected.
D. Testis injury:
 Orchitis e.g post puberty mumps
 Torsion and ischemic injury
 Trauma cause either fibrosis or immune
infertility
E. Cryptorchidism:
20% of unilateral, and 50% of bilateral crypt have
abnormal semen count
F. Varicocele: usually left sided, it is associated with
testicular atrophy which is reversible on varicocele
correction.
-Unilateral varicocele can affect both testes.
Post-testicular causes
A. Reproductive tract obstruction
 Congenital obstruction
• Cystic fibrosis (CBAVD, obstructive azospermia,
bronchiactasis, sinusitis, pancreatic dis.)
• Young syndrome(obstructive azospermia,
bronchiactasis, sinusitis, abnormal vas)
• CBAVD
• Blockage of ejaculatory duct
Post-testicular causes
 Acquired blockage
• Vasectomy
• Groin and hernia surgery
• Bacterial infection
 Functional blockage (nerve injury/drugs)
B. Disorders of sperm function or motility
 Immotile cilia syndrome: immotile spermatoza
 Maturation defects
 Immunologic infertility
 Infection: T.B epdidmoorchitis
C. Disorders of coitus
 Impotence
 Ejaculatory disorders.
 Hypospadias
 Timing and frequency
Diagnosis Of Male Infertility
It is important to evaluate both partners in parallel.
If the couple are presented before one year, try to reassure
them and advice them on healthy productive sex.
 History:
 Duration of infertility
 Earlier pregnancies with present of previous partner
 Sexual history, timing and use of lubricants
 General medical and surgical history (fever, hernial repair)
 Childhood diseases as mumps
 Cryptorchidism
 Exposure to medications, and chemicals (anabolic steroids)
 Family history of infertility
Physical examination:
 Degree of virilization
 Gynecomastia
 Testicular size and consistancy
 Status of epididymis
 Vas deferens
 Varicocele
 Penis and prostate
Lab investigations
• Semen analysis: is the primary source of
information on sperm production and reproductive tract
patency.
– Sample collection:
– Abstinence of 48-72 hours, but les than 7 days.
– Sample should be examined within one hour.
– Two samples should be taken as a baseline, one month
apart.
– -Ensure complete sample collection.
– - Store the sample at body temperature.
Hormonal assessment:
 To evaluate the HPG axis
 LH, FSH, testosterone, and prolactine are assessed
 Estradiol is reserved for underanderogenized males or
with gynecomastia
– Indications:
Low sperm count<10million/ml
Impairment of sexual function (impotence, low libido)
Other endocrinopathy (thyroid dis.)
Lab investigations
• Post coital urine analysis:
• Indication: semen volume less than 1.5 ml in
absence of CBAVD or hypogonadism.
Radiological tests
• Scrotal US, Doppler
• Vasography
• TRUS: ED obst.
Testis biopsy
• Provides direct information about spermatogenesis.
• Azospermic patients which difficult to distinguish
between failure of sperm production and obstruction.
• Now used for recovery of sperms for ICSI.
Methods of testicular biopsy
• Open.
• Percutanous ( Aspiration technique )
• Unilateral (preferred in the larger testicle)
or bilateral .
What should be done with the
biopsy?
• 1- Send to pathologist for diagnosis ( use
Bouin’s or Zinker’s solution ) avoid
formalin.
• 2- Send to embryologist for sperm
harvesting.
• 3- Cryopreserve testicular tissue for IVF.
Adjunctive tests
Semen leukocyte analysis:
pyospermia is defined as >1million leukocytes /ml.
Semen fructose: if suspected seminal vesicle obstruction( low
volume acidic semen)
Antisperm antibody test: when:
 Sperm agglutination or clumping
 Low sperm motility+history of testis surgery/trauma
 Increased leukocyte count
 Unexplained infertility
Treatment Options
• 1- General recommendations
• 2- Surgical treatment
• 3- Medical treatment
• 4- ARTs
Treatment Of Male Infertility
General recommendations:
1-Avoid smoking, alcohol or drugs.
2-Intercourse every other day around ovulation.
3-Avoid hyperthermia (hot bath, sauna or jacuzzi)
Surgical treatment:
-Vasovasostomy: should be done by
microsurgical technique.
Transurethral resection of ejaculatory duct
obstruction.
Orchidopexy
Pituitary ablatoin
Correction of Varicocele.
Correction of Varicocele.
• Varicocele repair improve semen quality in
70% of men.
• In NOA , Varicocele repair may lead to
presence of sperms in the ejaculate
sufficient for IVF.
Nonsurgical Treatment
Hormonal replacement.
Nonsurgical Treatment
Specific therapy:
 Pyospermia: by broad spectrum antibiotics
 Immunologic infertility:
 it is difficult to treat, options include steroids, sperm wash,
IUI,IVF, and ICSI.
 Medical therapy:
 Hyperprolactinemia: by bromocriptine
 Hypo-hyperthyroidism
 Anabolic steroids excess: stop them.
Empiric medical therapy
Clomiphene citrate: synthetic antiestrogen that
results in increased secretion of GnRH, LH,& FSH.
Tamoxifin.
Antioxidant therapy:
Assisted Reproductive Techniques
• Steps:
• 1-Ovarian stimulation
• 2-Oocyte retrieval.
• 3- Sperm retrieval.
• 4-Semen processing.
• 5-Fertilization.( incubation or ICI).
• 6-Embryo transfer ( intrauterine or
intrafallopian).
Sperm Retrieval Methods
• 1-Normal ejaculation.
• 2- Retrieval from bladder : in RGE
• 3-Penile vibratory stimulation: SC. injury above
T10.
• 4-Electroejaculation: not depend on ejaculation
reflex, done under anaesthesia.
• 5-Aspiration: SV, vas, epididymis( PESA or MESA)
• 6- Testicular sperm retrieval : ( TESA or TESE).
Assisted Reproductive Techniques
Used when both surgical and medical therapy
fail to treat infertility, specially of unknown
cause.
Intrauterine insemination:
placement of washed pellet
of ejaculated sperm within
the female uterus beyond the
cervical barrier. The major
indication is cervical hostility
and mechanical causes as
hypospadias.
Assisted Reproductive Techniques
In vitro fertilization:
oval and sperm retrieval, then the eggs are
fertilized in petri dishes and embryo
reimplanted in the uterus. 500,000 to 5,000,000
sperms are required.
Intracytoplasmic sperm injection: one sperm is
enough for this procedure.
Draw back of IVF,ICSI is that they bypass the
natural selection barriers so offspring are more
liable for chromosomal abn, and genetic causes
of infertility are passed to them.
Cryopreservation
• Indications:
• 1- Before potential sterilizing chemo or radiotherapy for
malignant diseases
• 2-Before surgeries which might interfere with fertility e.g :
Orcheictomy for tumours or Bladder neck surgery in young
male.
• 3- Progressive decrease in semen quality
• 4- Induced ejaculation ( PVS or EE).
• 5- After gonadotropin ttt induced spermatogenesis in
hypogonadotrophic hypogonadism.
• 6-Testicular sperm retrieval .
Cryopreservation
Inguinal LN Dissection
Complications
Seroma.
Wound infection.
Skin flap necrosis.
Lower limb oedema.
• Postoperative stocking,and prophylactic
antibiotic may prevent complications.

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Male infertility 2 2018)

  • 1. MALE INFERTILITY Dr. Mahmoud Faisal Rashad. MD
  • 2. Main Items • 1- Introduction. • 2- Classifications. • 3- Causes. • 4- Work up. • 5- Treatment options.
  • 3. Introduction Definition: Inability of a couple to conceive after one year of regular unprotected intercourse. It affects about 15% of couples 40% are due to male cause. 40% are due to female cause.  20%are due to combined cause
  • 4. (Male reproductive physiology) • The physiology of hypothalamic-pituitary- gonadal axis plays the critical role.
  • 5. Components of the HPG axis Hypothalamus: • Is the pulse generator for the cyclic secretion of the pituitary and gonadal hormones. • The most important hormone produced is GnRH (LHRH), which stimulates the production of both LH, and FSH from the anterior pituitary. • LHRH produced in a pulsatile manner which governs the concomitant cyclic release of gonadotropins.
  • 6. Anterior Pituitary: • Is the site of action of LHRH, which stimulates release of LH, and FSH. • LH stimulate steroidogenesis in Leydig cells. (production of testosterone)
  • 7. • FSH binds to Sertoli cells and spermatogonial membrane and stimulates semineferous tubules growth during development. • it is essential for initiation of spermatogenesis at puberty maintenance normal levels of sperm production in adults. • Prolactin is another hormone of anterior pituitary which important for lactating women.  Its function is not known in males.  Abnormal high level may abolish gonadotropin pulsatile pattern.
  • 9. The testis Is composed of endocrine part (Lyedig cells) exocrine part (seminiferous tubules) both under direct control of HPG axis.
  • 10. Endocrine testis: Responsible for testosterone production by Lyedig cells. Only 2% of testosterone is free (unbound), and active, while the rest is bound to either albumin or sex hormone binding glublin (SHBG). Testosterone is either metabolized by 5α- reductase into DHT, the potent androgen, or by aromatase into estradiol.
  • 11. Exocrine testis: On FSH stimulation, Sertoli cells make a host of secretory products important for germ cell growth, including androgen-binding protein. Through these actions seminiferous tubule growth is stimulated during development, and sperm production is initiated during puberty as well as a normal level of spermatogenesis is maintained in adults.
  • 12. Spermatogenesis • Occurs in semineferous tubules • Spermatogenesis requies: • -FSH • -Intra luminal Testosterone • -Intact blood testicular barrier • -Appropriate temperature (36 ‘C)
  • 13.
  • 14.
  • 15. • Spermatozoa have very poor motility and are incapable of naturally fertilizing an egg. • They become functional only after traversing the epididymis(10-15 days) where further maturation occurs ( Sperm maturation). • Capacitation”. Fertilization in the ampullary part of the fallopian tube requires further maturation stages • A change in the type of flagellar movement and release of lytic enzymes from the acrosome.
  • 16. Classifications of male infertility • 1- Primary or secondary. • 2-Location of the abnormality. • -Pre testicular. • - Testicular • - Post testicular
  • 17. Classifications of male infertility • 3-Sperm parameter • Normospermia • Azoospermia • Oligospermia • Ashenospermia. • Teratospermia. • Aspermia. • 4-Obstructive or non obstructive
  • 18. CAUSES OF MALE INFERTILITY Pretesticular Testicular posttesticular
  • 19. Pretesticular causes • Hypothalamic disease: Gonadotropin deficiency “kallmann syndrome”:  familial, x linked or autosomal,  due to disturbance of neuronal migration from the olfactory placode which contain neurons responsible for both olfaction and LH release.  The patient complains of hypogonadism and anosmia.
  • 20. Pituitary disease: Pituitary insufficiency: tumors, infarcts, radiation Hyperprolactinemia:  pituitary adenoma. secondary to stress, medications, and systemic disease. High prolactin induces a negative feedback on gonadotropin secretion. Exogenous and endogenous hormones: androgens, estrogens, thyroid hormones, or corticosteroid.
  • 21. Testicular Causes A. Chromosomal causes  Klinefelter syndrome (47XXY):  the most common genetic cause for azospermia.  classic triad of small firm testis, gynecomastia and azospermia.  They have delayed sexual maturation, increased height, obesity and diabetes.  Increased malignancy risk by 20 folds.  Sertoli cell only syndrome:  azospermic men with testicular biopsy show absence of germinal epithelium.  The patients have normal virilization, with small testis with normal consistency.  There is no gynecomastia
  • 22. B. Gonadotoxins:  Radiation  Drugs: ca+2 channel blockers, allopurinol, cimitidine, spironolactone, alpha blockers, TCA  Liver cirrhosis: increased s. estrogen causes testicular atrophy, gynecomastia, and impotence. C. Defective androgen activity  5 α reductase deficiency: causes normal internal genitalia, but ambiguous external genitalia as hypospadias, and cryptorchidism.  Androgen receptor deficiency: no receptor for DHT to bind, so no action, in turn both the internal and external genitalia are affected.
  • 23. D. Testis injury:  Orchitis e.g post puberty mumps  Torsion and ischemic injury  Trauma cause either fibrosis or immune infertility E. Cryptorchidism: 20% of unilateral, and 50% of bilateral crypt have abnormal semen count F. Varicocele: usually left sided, it is associated with testicular atrophy which is reversible on varicocele correction. -Unilateral varicocele can affect both testes.
  • 24. Post-testicular causes A. Reproductive tract obstruction  Congenital obstruction • Cystic fibrosis (CBAVD, obstructive azospermia, bronchiactasis, sinusitis, pancreatic dis.) • Young syndrome(obstructive azospermia, bronchiactasis, sinusitis, abnormal vas) • CBAVD • Blockage of ejaculatory duct
  • 25. Post-testicular causes  Acquired blockage • Vasectomy • Groin and hernia surgery • Bacterial infection  Functional blockage (nerve injury/drugs)
  • 26. B. Disorders of sperm function or motility  Immotile cilia syndrome: immotile spermatoza  Maturation defects  Immunologic infertility  Infection: T.B epdidmoorchitis C. Disorders of coitus  Impotence  Ejaculatory disorders.  Hypospadias  Timing and frequency
  • 27. Diagnosis Of Male Infertility It is important to evaluate both partners in parallel. If the couple are presented before one year, try to reassure them and advice them on healthy productive sex.  History:  Duration of infertility  Earlier pregnancies with present of previous partner  Sexual history, timing and use of lubricants  General medical and surgical history (fever, hernial repair)  Childhood diseases as mumps  Cryptorchidism  Exposure to medications, and chemicals (anabolic steroids)  Family history of infertility
  • 28. Physical examination:  Degree of virilization  Gynecomastia  Testicular size and consistancy  Status of epididymis  Vas deferens  Varicocele  Penis and prostate
  • 29. Lab investigations • Semen analysis: is the primary source of information on sperm production and reproductive tract patency. – Sample collection: – Abstinence of 48-72 hours, but les than 7 days. – Sample should be examined within one hour. – Two samples should be taken as a baseline, one month apart. – -Ensure complete sample collection. – - Store the sample at body temperature.
  • 30.
  • 31. Hormonal assessment:  To evaluate the HPG axis  LH, FSH, testosterone, and prolactine are assessed  Estradiol is reserved for underanderogenized males or with gynecomastia – Indications: Low sperm count<10million/ml Impairment of sexual function (impotence, low libido) Other endocrinopathy (thyroid dis.)
  • 32. Lab investigations • Post coital urine analysis: • Indication: semen volume less than 1.5 ml in absence of CBAVD or hypogonadism.
  • 33. Radiological tests • Scrotal US, Doppler • Vasography • TRUS: ED obst.
  • 34. Testis biopsy • Provides direct information about spermatogenesis. • Azospermic patients which difficult to distinguish between failure of sperm production and obstruction. • Now used for recovery of sperms for ICSI.
  • 35. Methods of testicular biopsy • Open. • Percutanous ( Aspiration technique ) • Unilateral (preferred in the larger testicle) or bilateral .
  • 36. What should be done with the biopsy? • 1- Send to pathologist for diagnosis ( use Bouin’s or Zinker’s solution ) avoid formalin. • 2- Send to embryologist for sperm harvesting. • 3- Cryopreserve testicular tissue for IVF.
  • 37. Adjunctive tests Semen leukocyte analysis: pyospermia is defined as >1million leukocytes /ml. Semen fructose: if suspected seminal vesicle obstruction( low volume acidic semen) Antisperm antibody test: when:  Sperm agglutination or clumping  Low sperm motility+history of testis surgery/trauma  Increased leukocyte count  Unexplained infertility
  • 38. Treatment Options • 1- General recommendations • 2- Surgical treatment • 3- Medical treatment • 4- ARTs
  • 39. Treatment Of Male Infertility General recommendations: 1-Avoid smoking, alcohol or drugs. 2-Intercourse every other day around ovulation. 3-Avoid hyperthermia (hot bath, sauna or jacuzzi)
  • 40. Surgical treatment: -Vasovasostomy: should be done by microsurgical technique. Transurethral resection of ejaculatory duct obstruction. Orchidopexy Pituitary ablatoin
  • 42. Correction of Varicocele. • Varicocele repair improve semen quality in 70% of men. • In NOA , Varicocele repair may lead to presence of sperms in the ejaculate sufficient for IVF.
  • 44. Nonsurgical Treatment Specific therapy:  Pyospermia: by broad spectrum antibiotics  Immunologic infertility:  it is difficult to treat, options include steroids, sperm wash, IUI,IVF, and ICSI.  Medical therapy:  Hyperprolactinemia: by bromocriptine  Hypo-hyperthyroidism  Anabolic steroids excess: stop them.
  • 45. Empiric medical therapy Clomiphene citrate: synthetic antiestrogen that results in increased secretion of GnRH, LH,& FSH. Tamoxifin. Antioxidant therapy:
  • 46. Assisted Reproductive Techniques • Steps: • 1-Ovarian stimulation • 2-Oocyte retrieval. • 3- Sperm retrieval. • 4-Semen processing. • 5-Fertilization.( incubation or ICI). • 6-Embryo transfer ( intrauterine or intrafallopian).
  • 47. Sperm Retrieval Methods • 1-Normal ejaculation. • 2- Retrieval from bladder : in RGE • 3-Penile vibratory stimulation: SC. injury above T10. • 4-Electroejaculation: not depend on ejaculation reflex, done under anaesthesia. • 5-Aspiration: SV, vas, epididymis( PESA or MESA) • 6- Testicular sperm retrieval : ( TESA or TESE).
  • 48. Assisted Reproductive Techniques Used when both surgical and medical therapy fail to treat infertility, specially of unknown cause. Intrauterine insemination: placement of washed pellet of ejaculated sperm within the female uterus beyond the cervical barrier. The major indication is cervical hostility and mechanical causes as hypospadias.
  • 49. Assisted Reproductive Techniques In vitro fertilization: oval and sperm retrieval, then the eggs are fertilized in petri dishes and embryo reimplanted in the uterus. 500,000 to 5,000,000 sperms are required. Intracytoplasmic sperm injection: one sperm is enough for this procedure. Draw back of IVF,ICSI is that they bypass the natural selection barriers so offspring are more liable for chromosomal abn, and genetic causes of infertility are passed to them.
  • 50. Cryopreservation • Indications: • 1- Before potential sterilizing chemo or radiotherapy for malignant diseases • 2-Before surgeries which might interfere with fertility e.g : Orcheictomy for tumours or Bladder neck surgery in young male. • 3- Progressive decrease in semen quality • 4- Induced ejaculation ( PVS or EE). • 5- After gonadotropin ttt induced spermatogenesis in hypogonadotrophic hypogonadism. • 6-Testicular sperm retrieval .
  • 52. Inguinal LN Dissection Complications Seroma. Wound infection. Skin flap necrosis. Lower limb oedema. • Postoperative stocking,and prophylactic antibiotic may prevent complications.