1. MANAGEMENT OF MALE INFERTILTIYBy
Dr Patrick I. Okonta
DELSU/DELSUTH

2. PRE TEST
1. Male factor infertility is the sole contributor in 20% of all cases of infertility 2. The cause of male infertility can be diagnosed in about 65% of cases 3. Only one abnormal result of semen analysis is sufficient to make a diagnosis of male infertility 4. Sperm cells can still be obtained in semen samples with a diagnosis of complete azoospermia 5. Clomiphane citrate has been found to be effective in the treatment of male infertility.

3. LEARNING OBJECTIVES
To understand the various causes and pathophysiology of male infertility
To evaluate the evidence base for medical treatment of male infertility
To discuss the role of surgery in the management of male infertility
To appreciate the role of assisted conception in the management of male infertility

4. OUTLINE Introduction Physiology of spermatogenesis
Aetiology and pathophysiology of male infertiltiy
Medical management of male infertility
Surgical management of male infertility
Assisted conception in management of male infertility
Take home points/ Conclusion

5. INTRODUCTION
About 15% of couples are unable to achieve conception after one year of unprotected regular sexual intercourse
Male factor is the sole contributor in 20% of cases of infertility.
It is also a part contributor in another 30-40% of infertility.
About 7% of all males are confronted with fertility problems
It is important to rule out male factor early in the investigation of infertility in a couple

6. SPERMATOGENESIS

7. SPERMATOGENESIS

8. SPERMATOGENESIS It takes approx 72 days for sperm to fully develop
About 50 days is in the semineferous tubules
About 20 days in the epididymis undergoing further maturation
Events that occurred within the previous 2 months can affect semen quality.
Leydig cells produce about 5-10mg of testosterone daily
Leydig cells have receptors for prolactin

9. AETIOLOGY
Only in about 25% - 35% of cases can the cause for male infertility be found
In 65% - 75% the cause is unknown- idiopathic

10. AETIOLOGY 1. Endocrine Hypogonadotrophic hypogonadism (<1%)
Congenital :
kallmann syndrome, Prader-Willi syndrome
Acquired :
Pituitary tumours, Craniopharyngioma, Prolonged anabolic steroid abuse
Hyperprolactineamia (<1%) Associated with sexual dysfunction (ED, ↓ libido)
Drugs
Antidopamine agents –tricyclic antidepressants, Opiates, Cocaine
Pituitary adenoma
Hypothyroidism
Idiopathic

11. Aetiology 2. Truama Immunological - Antisperm antibodies 4. Genetic
Testicular torsion
Transection of the vas deferens
Complications of hernia repair
Vasectomy
Immunological - Antisperm antibodies
ASA found in 3- 10% of semen samples of infertile men
Pathophysiology
Immobilsation of sperm
Stimulation of complement mediated cell lysis
Phagocytosis by macrophages
Interference with sperm capacitation or acrsome reaction
Defective sperm-oocyte interaction
4. Genetic
Kliinefelta’s syndrome (XYY)
Y chromosome microdeletion

12. Aetiology 5. Infections 6. Congenital urogenital abnormalities
Childhood Mumps orchitis, Urethritis, Prostatitis, Orchitis, Epididymitis
Pathophysiology
Poor sperm motility
Low sperm concentration
Decrease ejaculate volume
Increase oxidative stress
DNA damage
Poor capacity to fuse with oocyte
6. Congenital urogenital abnormalities
Congenital absence of vas deferens
Cryptochidism
Anorchia (absence of the testes)
7. Erectile dysfunction (< 1%)
8. Ejaculatory dysfunction (0.3 – 2%)

13. Aetiology Varicoceole 10. Exogenous factors 11. Systemic disease
Associated with decreased testicular volume
Affects sertoli cells → decreased spermatogenesis
Affects leydig cells → decreased testosterone production
Pathophysiology
↑ temperature
↑ oxidative stress
↑ elaboration of proteins related to germ cell apoptosis
10. Exogenous factors
Drugs e.g cytotoxic drugs
Irradiation
Heat
Chemicals
11. Systemic disease
Liver cirrhosis
Renal failure

14. Clinical Evaluation History
To identify risk factors or behavioural pattern
STI
Previous surgery
Sexual history/ coital pattern
Alcohol and drug use
Exposure to toxicants
Occupational history
Systemic disease
Previous fertility

15. Clinical Evaluation Physical Examination
Secondary sex characteristics: hair distribution and escutcheon, voice.
Gynaecomastia
Genitalia
Penis ; ext meatus to rule out hypospadias
Testicular volume
Vas deferens
Palpate for varicoceole

16. Semen Analysis 2 or 3 samples to obtain baseline
Preferable atleast 2 months apart
Best collected in a room near the lab
Duration of abstinence 2-7 days
Sample obtained by masturbation
Must not miss any portion of the semen during collection
Kept at ambient temp of 20oC – 37oC

17. Lower reference values (5th centile) of semen of fertile men (WHO, 2010)

19. Further investigations
Pellet sample after centrifugation for patients with azoospermia
Hormonal assay
LH, FSH, Testosterone, Prolactin,
Semen, Urine m/c/s
Scrotal and testicula USS with colour doppler
Genetic/chromosomal studies

20. Medical Treatment for male infertility
Hypogonadotrophic hypogonadism
One of the few specific and effective tx for male infetility
HCG IU/week x 6 months, then
FSH IU 3 times/week
Sperm is produced within 6-9 months of therapy
IVF/ICSI may be considered if no pregnancy after 12 months or sperm density remains low <5 x 106

21. Medical Treatment for male infertility
2. Hyperprolactineamia
Dopamine agonist
Bromocryptine
0.625mg – 1.25 mg dly, then increase to upto 2.5mg -10mg
Cabergoline
Initial dose 0.25mg – 0.5mg weekly, then mg weekly
Cabergoline better than bromodryptine

22. Medical Treatment for male infertility
3. Genital infection
Treat according to antibiotics sensitivity pattern
Empirical tx
Single dose of fluoroquinolone followed by a 2 week tx with doxycycline
3rd generation quinolones (levofloxacin, sparfloxacin)
Tx results in increase quality but no evidence of increase probability of conception

23. Medical Treatment for male infertility
4. Ejaculatory dysfunction
Treatnment depends on the cause
Spinal cord injury (86% of cases)
Tx = Electrical stimulation
Non spinal cord causes
α – agonist
Eg pseudoephedrine 60mg PO daily, Imipramine 25mg PO bd, ephedrine 50mg PO qid
Chlorpheniramine , phenylpropanalamine

24. Medical Treatment for male infertility
5. Erectile dysfunction
Definition
Consistent inability to attain or maintain a penile erection of sufficient quality to permit satisfactory sexual intercourse (NIH 1993)
Treatment
Treat or remove indentified course
Psychological counselling
Phosphodiesterase type 5 inhibitors eg Sildenafil (Viagra), Tadalafil (Cialis) .
This is better than hormone tx for ED
Penile injection with Alprostadil (caverject impulse), papaverine
Penile pumps
Penile implants.

25. Empirical Medical Treatment for Idiopathic Male Infertility
1. Gonadotrophin injection
Tx should be atleast for 9 months
Systematic review of evidence
Compared with placebo tx showed a significantly higher pregnancy rate per couple within 3 months of completing tx
13.4% Vs 4.4%
(Attia et al 2007)

26. Empirical Medical Treatment for Idiopathic Male Infertility
2. Dopamine agonist (Bromocryptine)
Meta analysis of evidence
Compared with placebo :
Bromocryptine Placebo
Pregnacy rate 5% 7%
Conclusion
Bromocryptine offers no benefit for ideopathic male infertility
Vanderekhure et al 2001

27. Empirical Medical Treatment for Idiopathic Male Infertility
3. Anti-oestrogens (clomiphane, tamoxifen)
Metanalysis
Anti-oestrogen Placebo
Pregnanct rate 15.4% %
Conclusion
No significant difference to recommend antioestrogens for increasing fertility of males with idiopathic oligo-asthenospermia
Vanderekhure et al 2007

28. Empirical Medical Treatment for Idiopathic Male Infertility
4. Aromatase inhibitors
Eg Testolactone, Anastrozole)
These prevent breakdown of testosterone to oestrogen → reduction in negative feedback of E2
Conclusion
No effect on semen parameters

29. Empirical Medical Treatment for Idiopathic Male Infertility
5. Androgens
Based on the belief that testosterone could have either
A direct effect on spermatogenesis, or
An indirect effect via rebound increase in gonadotrophins after initial suppression after cessation of tx
Systematic review of evidence base
No direct benefit on sperm parameters and pregnancy rate

30. Empirical Medical Treatment for Idiopathic Male Infertility
6. Anti-oxidants
Vit C,E, Zinc, Selenium
Based on the fact that high levels of reactive oxygen species decrease fertility through
Sperm DNA damage; Decrease sperm motility; Defective sperm membrane integrity; Defective oocyte-sperm fusion
Systematic review of evidence
Anti-oxidants could improve sperm motility, but less impact on sperm conc. & morphology
Conclusion: Oral anti-oxidants might improve pregnancy rate in couples with male infertility
-Ross et al 2011

31. Surgical management of Male Infertility
Varicocoelectomy
Benefits to fertility somewhat controversial
Cochrane review of 2009 concluded that varicocoele repair for otherwise unexplained infertility could not be recommended
However other reports suggests an improvement in semen parameters
Agarwal et al 2007, Borman et al 2008
Conclusion
There seems to be a benefit of surgical tx of varicocoele on the rate of spontaneous pregnancy

32. Assisted conception in male infertility
1. Intra uterine insemination
Indication
Mild to moderate oligospermia
Note
Sperm has to be prepared
Atleast 3 cycles, therafter abandon the procedure
Often done with ovulation induction
Success actually better with unexplained infertility and sperms with good motility

33. Assisted conception in male infertility
2. Intrcytoplasmic sperm injection ICSI
Has revolutionalised outcome for male infertility
Only a single sperm is needed for fertilisation
Indication
Severe oligospermia
Mild to moderate oligospermia after failed IUI
Azospermia

34. Take home points/Conclusion
Male infertility contributes equally to infertility in couples.
Male factor infertility should be excluded early in the investigation of the infertile couple.
Medical treatment is only effective in a minority of cases.
Empirical medical therapy has a limited role in the treatment of idiopathic male infertility.
Varicocoelectomy can improve semen parameters in patients with severe varicocoele
Assisted reproduction has a significant role in helping couples with male factor infertility achieve a pregnancy

35. POST TEST
1. Male factor infertility is the sole contributor in 20% of all cases of infertility
2. The cause of male infertility can be diagnosed in about 65% of cases
3. Only one abnormal result of semen analysis is sufficient to make a diagnosis of male infertility
4. Sperm cells can still be obtained in semen samples with a diagnosis of complete azoospermia
5. Clomiphane citrate has been found to be effective in the treatment of male infertility.

36. THANK YOU