1. Male infertility

2. Defined as the inability to conceive after 1 year of unprotected sexual intercourse.
It affects approximately 15% of couples.
Roughly : 30% male factor
30% female factor
30% involve both sexes
10% unknown

3. Male reproductive physiology
The HPG axis.
The hypothalamus
receives neuronal input from many brain centers, and
anatomically linked to the pituitary gland by both
portal vascular system & neuronal pathway
It secrets GnRH or LHRH to stimulate the secretion of LH and FSH from the anterior pituitary
pulsatile in nature (½ life 2-7 min.) vary from once hourly to as seldom as once or twice in 24 h.

4. Anterior pituitary
The site of production and release of FSH & LH under the effect of GnRH
Both androgen and estrogen regulate LH secretion through negative feedback

5. FSH response to GnRH more difficult to measure, and its relatively independent on GnRH. the recently discovered gonadal proteins inhibin and activin may exert significant effect on FSH secretion.
Prolactin, can also have effect on HPG axis and fertility.

6. LH act on leydig cell stimulates the secretion of testosteron.
FSH major stimulator of seminiferous tubule growth during development and its essential for the initiation of spermatogenesis at puberity.
In adult its major physiologic role is to stimulates quantitatively normal levels of spermatogenesis.
Prolactin
Also have effect on HPG axis and fertility.
The normal role of prolactin in men is less clear, but it may increase the concentration of LH receptors on the leydig cell.

7. The testis
Normal male virility and fertility requires the collaboration of both the exocrine
and endocrine testis.
The interstitial compartment, (leydig cell)---- Steroidogenesis (endocrine).
The seminiferous tubules---- Spermatogenesis (exocrine).

8. Spermatogenesis
Is a complex process by which primitive, totipotent stem cells divide to either renew themselves or produce daughter cell that become spermatozoa.
Several cycles of spermatogenesis coexist within the germinal epithelium at any one time.
The duration of entire spermatogenesis is 74 days.
The transit time of sperm through the fine tubules of the epididymis which is essential for maturation is days.

9. Unlike the somatic cells which replicate by mitoses (identical daughter cells).
Germ cells are replicate by meioses in which the genetic material is halved to allow for reproduction.

10. Management
History --is the cornerstone of evaluation.
medical history
fevers,
systemic illness—diabetes, cancer, infection
genetic disease--cystic fibroses, klinefelter syndrom.
history of post puberital mumps.

11. surgical history
orchiopexy, cryptorchidism
herniorrhaphy
trauma, torsion
pelvic, bladder, or retroperitoneal surgery
transurethral resection for prostatism
fertility history
previous pregnancy (present or other partners)
duration of infertility
previous infertility treatments
female evaluation
sexual history---timing & frequency.

12. family history
cryptorchidism,
hypospadias
midline defect (kartagener syndrom)
medication history
nitrofurantoin, cimetidin, sulfasalszin, spirinolacton, alpha blockers
social history
ethanol, smoking, cocaine, anabolic steroids
occupational history
exposure to ionizing radiation
chronic heat exposure (saunas)
aniline dyes, pesticides, heavy metals (lead)

13. Physical examination
General examination:hair distribution, gynecomastia.
Genital examination
size & consistency of the testis induration, tenderness, or cyst of epididymis.
presence or absence of vas deferens.
varicocele (valsalva maneuver).
penile abnormalities, hypospadias, chordee.
DRE, to examine the prostate & seminal vesical

14. Laboratory GUE : infection, glucosuria, hematuria. Semen analysis
is the primary source of information on sperm production & reproductive tract patency.
sample collection, sexual abstinence duration, liquifaction.
should be examine 1 hr. transit at body temp.
WHO considered the minimum criteria for normal semen quality.
volume : 2—4 ml
concen,: 20—40 m/ml
motility: 40—60% progression score : 2 (on scale of 0 ,no movement to 4 excellent progression.
morphology : >30% (more than 4% kruger normal forms.)

15. CASA, used to remove the subjective variables in the manual semenalysis. but it can overestimate sperm counts by 30% in the presence of contaminating cells (immature sperm or leukocytes.) then motility
underestimated.
Seminal fructose and postejaculate urinalysis.
both are used to evaluate small ejaculate or unejaculate.
Fructose absent in semen-- Seminal vesicle agenesis or obstruction
Retrograde ejaculation-- Diabetes, medical therapy,
pelvic, bladder,or retroperitoneal surgery

16. Hormone assessment
Evaluation of pit. gonadal axis provide information on the state of sperm production.
hyperprolactinemia, gonadotropin deficiency, CAH.
FSH & testosterone assay recommended in sever oligospermia sperm densities of <10 million/ml.
this combination detect 99% of endocrine abnormalities
LH & prolactin levels may be obtained if testosterone & FSH are abnormal

17. Thyroid hormone, liver function, & other organ specific tests obtained if there is clinical evidence of active disease.
High FSH > double value +low testosterone in azospemic patient =testicular failure.
Low FSH + low testosterone =hypogonadotropic hypogonadism.
High FSH + high testosterone = androgen resistance.

18. Adjunctive tests
indicated if initial evaluation fail to lead to diagnosis & if they change the patient management.
Semen leukocyte analysis.
pyospermia >1 million leukocyte/ml. should differentiated from immature sperm by special stain like papanicolaou, peroxidase stain, or immunocytology.
pyospermia present in infection, immune sensitization, & low grade toxin like cigarette smoke & alcohol.

19. Antisperm antibody (ASA) test.
autoimmune infertility may occur when the blood testis barrier is broken & body is exposed to sperm antigens.
ASA indicated in:
1- sperm agglutination or clumping.
2- low motility + history of testis injury.
3- increase leukocyte.
4- unexplained infertility.

20. Hypoosmotic swelling (HOST) test
differentiate immotile from dead sperm (necrospermia).
using hypoosmotic environment 25mM citrate & 75mM fructose viable cells should swell when placed in the solution.
Sperm penetration assay (SPA)
bioassay of the sperm to penetrate the hamster egg help couple decide to use IUI if good SPA or use IVF and micromanipulation if poor SPA result.

21. Sperm –cervical mucus interaction
interaction between the sperm & cervical mucus if abnormal may suggest the treatment by IUI. (sperm placed beyond the cervix).
Chromosomal studies
2—15% of patients with azoospermia or sever oligospermia may have chromosomal abnormalities .
klinefelter syndrome (XXY) is the most frequently detected.
Cystic fibrosis mutation testing 80% of men with congenital absence of vas will harbor CF gene mutation.

22. Radiologic testing
A- scrotal ultrasound
hydrocele, abnormality of peritesticular region color doppler used to investigate varicocele.
B- venography
expensive, invasive & technician dependent. main indication simultaneous percutaneous treatment of varicocele & diagnosis of recurrence after treatment.
C- TRUS : imaging prostate, SV, &ejaculatory duct. Replace vasography in diagnosis of obstruction.

23. Testicular biopsy and vasography
indicated in
1- cases of azoospermia + normal hormone profile
2- sperm retrieval for ICSI in azoospermia.
multiple percutaneous fine needle aspiration (mapping) of the testis can detect sperm in 60% of men with unobstructed azoospermia.

24. Semen culture
semen is routinely contaminated with the passage through the urethra.thus used in selected situation like
1- history of genital tract infection
2- abnormal expressed prostatic secretion
3- >1000 bacteria /ml of semen
4- >1 million leukocyte /ml (pyospermia).

25. Causes of male infertility
Pretesticular causes
hypothalamic disease
gonadotropin deficiency (kallmann syndrome)
isolated LH deficiency isolated FSH deficiency
congenital hypogonadotropic syndrome

26. pituitary disease
pituitary insufficiency
(tumor, infiltrative process, operation, radiation, deposits)
Hyperprolactinemia
exogenous hormones (estrogen-androgen excess,
glucocorticoid excess)
Hyper-& hypothyrodism
growth hormone deficiency.

27. Testicular causes
chromosomal
(klinefelter syndrome [XXY], XXsex reversal,XYYsndrome)
noonan syndrome (male turner syndrome)
myotonic dystrophy
vanishing testis syndrome (bilateral anorchia)
sertoli-cell-only syndrome (germ cell aplasia)
Y chromosome microdeletions
gonadotoxins (radiation, drugs)
systemic disease (renal failure, liver failure, sickle cell anemia)
defective androgen activity
testis injury (orchitis, torsion, trauma)
cryptorchidism, varicocele, idiopathic

28. Posttesticular causes
reproductive tract obstruction
congenital blockage
CAVD
young syndrome
idiopathic epididymal obstruction
polycystic kidney disease
ejaculatory duct obstruction
acquired blockage
Vasectomy, groin surgery, infection, functional blockage sympathetic nerve injury
pharmacologic

29. disorder of sperm function or motility
immotile cilia syndrome
maturation defect
immunologic infertility
infection
disorder of coitus
impotence
hypospadias
timing & frequency

30. Treatment
Surgical treatment
Varicocele, vaso-vasostomy (optical magnification, microsuture & microneedles & smaller surgical instruments
ejaculatory duct obstruction (TURED).
Orchiopexy,
pituitary ablation
electroejaculation (spinal cord injuries).

31. Nonsurgical treatment
specific therapy need to reverse known pathohpysiologic effects
Pyospermia (20 leukocytes /HPF)
sperms posses little cytoplasm so they are highly susceptible to the effects of oxidative agents (infection: STD, penile discharge, prostatitis, epididymitis.)
chlmydia, mycoplasma are common
Doxycycline & trimethoprim-sulfa + antioxidant like vit. A, E,& C or glutathion.
Female partner should be treated

32. Coital therapy
timing & frequency is important. every other day around ovulation is the best to decrease the stress & the sperm reside for 48 h. in the cervical mucus. basal body temp. charting or home kit detect LH surge in urine
D. MEDICAL THERAPY
Hyperprolactinemia
2. Hypothyroidism
3. Congenital adrenal hyperplasia

33. 4. Testosterone excess/deficiency
Infertility associated with (Kallmann syndrome) lack GnRH that stimulates normal pituitary function can be very effectively treated with
hCG, 1000–2000 U three times weekly, and
recombinant FSH 75 IU twice weekly, to replace LH and FSH
One can expect to find sperm in the ejaculate beginning 9–12 months after therapy is started

34. Individuals with isolated LH deficiency respond well to hCG therapy alone.
Anabolic steroids are a common and underdiagnosed reason for testicular failure
in which excess exogenous testosterone and metabolites depress the pituitary-gonadal axis and spermatogenesis

35. Empiric Medical Therapy
This form of therapy seeks to overcome pathologic condition that are ill-defined idiopathic infertility or have identifiable but no proven treatment
a. Antiestrogen
blocks the action of the normally low levels of estrogen on the male hormone axis and results in increased secretion of GnRH, FSH, and LH
b. Antioxidant therapy
glutathione, 600 mg daily for 3–6 months, or vitamin E, 400–1200 U/ day or glutathione

36. ASSISTED REPRODUCTIVE TECHNOLOGIES
Intrauterine Insemination
In Vitro Fertilization
ICSI