MANAGEMENT OF MALE INFERTILTIY

By Dr Patrick I. Okonta

DELSU/DELSUTH

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.

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

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

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

SPERMATOGENESIS

SPERMATOGENESIS

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

AETIOLOGY

• Only in about 25% - 35% of cases can the cause for male infertility be found

• In 65% - 75% the cause is unknown- idiopathic

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

Aetiology2. Truama

• Testicular torsion• Transection of the vas deferens

– Complications of hernia repair– Vasectomy

3. 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

Aetiology5. Infections

• 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%)

Aetiology9. Varicoceole

• 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

Clinical EvaluationHistory 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

Clinical EvaluationPhysical 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

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

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

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

Medical Treatment for male infertility

1. Hypogonadotrophic hypogonadism

• One of the few specific and effective tx for male infetility

– HCG 3000 -6000IU/week x 6 months, then– FSH 75 -150IU 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

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

0.25-3mg weekly

– Cabergoline better than bromodryptine

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

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

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.

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)

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

Empirical Medical Treatment for Idiopathic Male Infertility

3. Anti-oestrogens (clomiphane, tamoxifen)

• MetanalysisAnti-oestrogen Placebo

Pregnanct rate 15.4% 12.5%

• Conclusion – No significant difference to recommend

antioestrogens for increasing fertility of males with idiopathic oligo-asthenospermia

• Vanderekhure et al 2007

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

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

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

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

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

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

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

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.

THANK YOU