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MALE INFERTILITY

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CONTENTS Introduction

Spermatogenesis

Causes

Evaluation

Management

What’s new in male infertility

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INTRODUCTION INFERTILITY - one year of unprotected

intercourse without conception

SUBFERTILITY- couples who exhibit decreased reproductive efficiency

FECUNDABILITY - probability of achieving pregnancy within a single menstrual cycle

FECUNDITY - probability of achieving live birth within a cycle.

Speroff 15th ed.

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SPERMATOGENSIS

• During embryogensis, there are approximately 300 thousand spermatogonia in each gonad.

• Each undergoes mitotic division, and by puberty 600 million in each testis.

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Sperm production takes place in seminiferous tubules within testis.

Spermatogenesis takes about 70 daysAdult males produce 100-200 million sperm

each day.Leydig cells produce testosterone (which

along with FSH, stimulates spermatogenesis).Maturation of sperms takes place in

epididymis.Transport of sperms – vas deferens

Speroff 15th ed.

1.Plasma membrane2.Outer acrosomal membrane3.Acrosome4.Inner acrosomal membrane5.Nucleus6.Proximal centriole7.Rest of the distal centriole8.Thick outer longitudinal fibers

9.Mitochondrion10.Axoneme11.Anulus12.Ring fibersA.HeadB.NeckC.Mid pieceD.Principal pieceE.Tail

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SPERM STRUCTURE

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Physiology of Semen after Ejaculation1. Liquefaction2. Capacitation3. Acrosome reaction4. Cortical reaction

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Relative prevalence of the etiologies of infertility

Percentage

Male Factor 20-30

Both male & Female 10-40

Female Factor 40-55

Unexplained Infertility 10-20

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SEMEN ANALYSIS

• Abstinence for 2-3 days (Not less than 2 days & not more than 7 days)

• Abnormal sperm count - analysis at least after 4 weeks.

• Analysis: Volume, number, motility, morphology

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Short intervals of abstinence- decreases the sperm density and semen volume.

Longer abstinence intervals - increase in the proportion of dead, immotile and morphologically abnormal sperms.

Semen specimen should be collected in a clean container.

Semen can also be collected in a silastic condom, which does not contain any antispermicidal agents.

Semen sample should be examined within an hour after collection

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Parameters Normal Reference Values

Lower Reference Limits

Volume 1.5-5.0 mL 1.5 (1.4-1.7) mLP H >7.2

Viscosity <3Sperm Concentration

>20 million/mL 15 (12-16) million/mL

Total sperm number

>40 million/ejaculate 39 (33-46) million/ejaculate

Percent motility >50% 40 (38-42)%

Forward progression

>2 (scale 0-4) 32 (31-34)%

Normal morphology

>15,30,50% normal 4(3-4)%

Round cells <5 million/mLSperm agglutination

<2 (Scale 0-3)

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Semen analysis

Ejaculate volume and pH:• Low or absent – CBAVD, ejaculatory duct

obstruction, hypogonadism, retrograde ejaculation.

• High volume (>5ml)- Inflammation of accessory gland

Seminal vesicle secretions are alkaline and contains fructose.

EDO- semen is acidic (prostrate secretions), and has no sperm or fructose.

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Sperm concentration and total sperm count:

1. Azoospermia, Oligospermia

2. OBSTRUCTIVE: blockage in ductal system ( CBAVD, scrotal or inguinal surgery)

3. NON OBSTRUCTIVE: primary testicular failure, endocrinopathies that suppress spermatogenesis.

4. Endocrine and genetic evaluation indicated in men with severe oligospermia.

5. Total sperm count is the product of multiplying semen volume and sperm concentration.

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Abnormalities of sperm

Oligozoospermia - reduced sperm count

Asthenozoospermia – reduced sperm motility

Teratozoospermia- increased abnormal sperms

Oligoasthenoteratozoospermia – sperm variables are subnormal

Azoospermia- no sperm in semenAspermia – no ejaculateLeucocytospermia – increased WBCNecrozoospermia – all sperms are

nonvaiable and motile.

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Causes of Male InfertilityHypothalamic pitutary disorders

(1-2%)

Primary gonadal disorders (30-40%)

Disorders of sperm transport (10-20%)

Idiopathic (40-50%)

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Hypothalamic pitutary disorders Idiopathic isolated gonadotropin

deficiencyKallmann syndromeSingle gene mutations Hypothalamic and pitutary tumours Infiltrative disease Hyperprolactinemia Drugs Chronic systemic illness and

malnutrition Infections Obesity

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Primary gonadal disorders Klinefelter syndrome Y chromosome deletions Cryptorchidism Varicoceles Infections Drugs Radiation Environmental gonadotoxins Chronic illness

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Disorders of sperm transport Epididymal obstruction or dysfunction Infections causing obstruction to vas

deferns Vasectomy Kartagener syndrome Ejaculatory dysfunction Young syndrome

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CAUSES PRE TESTICULAR TESTICULAR POST

TESTICULAR ENDOCRINE: •

Hypogonadotropic hypogonadism

• Hypothyroidism •

Hyperprolactinaemia

• Diabetes

COITAL DISORDERS:• Erectile

dysfunction • Ejaculatory

failure

GENETIC:• Klinefelter

syndrome• Y chromosome

deletion• Immotile cilia

syndrome

CONGENITAL: • Cyptorchidism• Infective•

Antispermatogenic agents

heat, irradiation, drugs, chemotherapy

VASCULAR : Torsion VaricoceleIMMUNOLOGICAL

IDIOPATHIC

OBSTRUCTIVE: Epdidymal congenital infective Vasal Genetic: cystic fibrosis. Accquired: Vasectomy Ejaculatory duct obstructionAccessory gland infection Immunological Idiopathic post vasectomy

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Evaluation of male infertility To Identify and correct specific cause To identify the individuals whose fertility

cannot be corrected but could be over come by IUI and ART.

To identify- Genetic abnormality To identify any medical condition that

requires specific attentionTo identify the individuals whose

infertility can neither be corrected or overcome with ART, in whom adoption or donor sperm are considered.

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HISTORY Duration of infertility and previous infertility Coital frequency and sexual dysfunctionAny previous evaluation or treatment of

infertilityChildhood illness and developmental historyPrevious surgery and its outcome, systemic

medical illness History of exposure to STDExposure to environmental toxins Current medications and allergies Occupational exposure to tobacco, alcohol

and other drugs

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Physical examinations Examination of penis, Palpation of testes and measurement

of their size Presence and consistency of both vasa

and epididymides Presence of any varicoceleSecondary sexual characteristics, hair

distribution, and breast development Digital rectal examination

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Other investigations Absence of fructose: Congenital absence of seminal vesicle, Partial duct obstruction. Semen culture (If pus cells in microscopy)Urologic evaluationEndocrine evaluation - FSH, LH,

Testosterone. Transurethral or transcrotal USGRenal ultrasonography Testis biopsy- azoospermia Vasography

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Endocrine evaluation:

Indications: Abnormal semen analysis Serum FSH,LH and testosterone

Hypogonadotropic gonadism- FSH,LH,testosterone low

Abnormal spermatogenesis- FSH normal/increased, LH& testosterone normal

Testicular failure- high FSH and LH, low /normal testosterone

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Genetic evaluation1) Mutations within cystic fibrosis transmembrane conductance regualtor (CTFR gene)

2) Chromosomal anomalies resulting testicular dysfunction – klinefelter syndrome

3) Y chromosome deletions associated with abnormalities of spermatogeneis.

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Transrectal ultrasonography: less invasive

indicated in diagnosis severe oligospermia or azoospermia.

Renal ultrasonography: unilateral or bilateral vasal agenesis.

Trans scrotal ultrasonography: To confirm physical findings. Detect non palpable varicocele.

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Testis biopsy : diagnostic purpose in azoospermic men.

when the testicular biopsy shows normal spermatogenesis obstruction to the vas deferens is suspected.

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Drugs that impair male infertility

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TreatmentHypogonadotropic hypogonadism: Pulsatile GnRh, hCG, hMG, Testosterone,

Clomiphen citrate, Tamoxifen

Hypergonadotropic hypogonadism: 1. IVF/ICSE, Donor sperm, Adaptation2. Androgen, FSH, Clomiphen3. Hyperprolactinemia-Dopamine agonists4. Strict control of DM, Hypothyroid

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Pretesticular Erectile dysfunction- PDE5 Inhibitor (Sildenafil)For ejaculatory problems(Retrograde

ejaculation): Imipramine , Pseudoephedrine/Ephedrine , PhenylpropalamineRetrograde ejaculation, Neurogenic

impotence, Severe Hypospadias Intrauterine insemination (IUI)

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Post testicular Prior vasectomy (most common

cause)- microsurgical vasovasostomy (better if less than 5 years)

Epididymal or vasal obstructionMESAPESATESETESA/FNAICSI

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Surgical treatment for male infertility Vasovasotomy Vasoepididymostomy Transurethral resection of ejaculatory

ducts Varicocele repair OrchiopexyVibratory stimualtion and electro

ejacualtion

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surgical managementCryptorchidism- Orchidopexy at 2-3 year of ageVaricocele-High ligation of internal spermatic veinGonadal failure- Surgical retrieval of spermatozoa, followed by ICSI

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