In the name of GodIn the name of God

Dr Dr SoltanzadehSoltanzadeh MD,UrologistMD,Urologist

M l F t I f tilit A d T t tM l F t I f tilit A d T t tMale Factor Infertility And TreatmentMale Factor Infertility And Treatment

Male factor:Male factor:11 Pure 20%Pure 20%1.1. Pure 20%Pure 20%2.2. Both 30Both 30--40% 50%40% 50%

E al ationE al ationEvaluation:Evaluation:

HistoryHistoryPh/ExPh/ExPh/ExPh/ExLab dataLab data

G l f l ti i id tifi dG l f l ti i id tifi dGoals of evaluation is identified :Goals of evaluation is identified :

1.1. Reversible conditionReversible condition22 Irreversible causeIrreversible cause ARTART2.2. Irreversible cause Irreversible cause ARTART3.3. Irreversible cause Irreversible cause Donor insemination adoptionDonor insemination adoption

Si ifi t d l i th lSi ifi t d l i th l4.4. Significant underlying pathologySignificant underlying pathology5.5. Genetic abnormalityGenetic abnormality effect offspringeffect offspring

HistoHistoHistoryHistory

Infertility historyInfertility historySexual historySexual historySexual historySexual historyFamily historyFamily historyP t hi tP t hi tPast historyPast history

PMHPMHPMHPMH

Childhood Childhood DM DM ND ND INF INF Renal D Renal D Cancer Cancer Surgical Surgical Medication Medication GonadotoxinGonadotoxin

Ph sical E aminationPh sical E aminationPhysical Examination:Physical Examination:

HypospadiasHypospadias & & ChordeeChordeeTestis volumeTestis volumeTestis volumeTestis volumeVas & Vas & epididymisepididymisDREDREDREDRESitusSitus inversusinversusVirilizationVirilizationGeneral ExaminationGeneral ExaminationGeneral Examination General Examination

Basic Lab TestsBasic Lab TestsBasic Lab TestsBasic Lab Tests

semen Analysissemen Analysis

NumberNumberCollection: abstinenceCollection: abstinence

containercontainerMethodology : Physical characteristicsMethodology : Physical characteristicsgy ygy y

1.1. LiquefactionLiquefaction2.2. VolumeVolume3.3. CountCount4.4. MotilityMotilityyy5.5. WBCWBC6.6. MorphologyMorphology

CASACASA1.1. VelocityVelocityyy2.2. Flagellar beat frequencyFlagellar beat frequency3.3. Lateral head Lateral head

PHPHFructose Fructose

Ho monal assaHo monal assaHormonal assayHormonal assay

TestosteroneTestosteroneFSHFSHFSHFSHLHLHP l tiP l tiProlactineProlactine

Additional TestingAdditional TestingAdditional TestingAdditional Testing

Le koc te stainingLe koc te stainingLeukocyte stainingLeukocyte staining

11//3 3 RC RC WBCWBCIndication : RC :Indication : RC : 1010--1515% / HPF% / HPFIndication : RC : Indication : RC : 1010 1515% / HPF% / HPF

11**101066 /mL/mLi l t ii l t i papanicolaou stainpapanicolaou stain

peroxidaseperoxidase

Antispe mAntispe m AntibodAntibodAntispermAntisperm AntibodyAntibody

Semen c lt eSemen c lt eSemen culture:Semen culture:

Indication: pyospermia + clinical symptomIndication: pyospermia + clinical symptomMycoplasma genitaliumMycoplasma genitaliumMycoplasma genitaliumMycoplasma genitaliumChlamydia trachomatis (PCR)Chlamydia trachomatis (PCR)

DNA Integrity Testing:DNA Integrity Testing:DNA Integrity Testing:DNA Integrity Testing:Indications:Indications:

11 Unexplained infertilityUnexplained infertility1.1. Unexplained infertilityUnexplained infertility2.2. Repeated IVF failureRepeated IVF failure

Recurrent miscarriageRecurrent miscarriage3.3. Recurrent miscarriageRecurrent miscarriageRisk factors:Risk factors:

1.1. SmokingSmoking2.2. ToxinsToxins3.3. CancerCancer4.4. feverfever

Ult a st ct al e al ationUlt a st ct al e al ationUltra structural evaluation:Ultra structural evaluation:

Indication: < Indication: < 55--1010%%MitochondriaMitochondriaMitochondriaMitochondriaOuter dense fiberOuter dense fiberMi t b lMi t b lMicrotubulesMicrotubules

Radiologic e al ationRadiologic e al ationRadiologic evaluation:Radiologic evaluation:

VasographyVasographyVesiculographyVesiculographyVesiculographyVesiculographyTRUSTRUSV hV hVenographyVenographyScrotal USScrotal USAbdominal USAbdominal US

Ac osome eactionAc osome eactionAcrosome reaction:Acrosome reaction:

Differentiation of acrosome intact from Differentiation of acrosome intact from reactedreactedUnexplained infertilityUnexplained infertilityICSIICSIICSIICSI

Sperm Penetration Assay:Sperm Penetration Assay:R f ZPR f ZPRemove of ZPRemove of ZPScoring :Scoring :% of ova% of ova 1010 3030%%1.1. % of ova % of ova 1010--3030%%

2.2. Num of sperm/ovaNum of sperm/ovaEvaluation of :Evaluation of :Evaluation of :Evaluation of :

1.1. CapacitationCapacitation22 Acrosome reactionAcrosome reaction2.2. Acrosome reactionAcrosome reaction3.3. Fusion oolemaFusion oolema44 Incorporation into ooplasmIncorporation into ooplasm4.4. Incorporation into ooplasmIncorporation into ooplasm

Unexplained infertilityUnexplained infertilityGood sperm but low numberGood sperm but low numberGood sperm but low numberGood sperm but low numberAbnormal Abnormal ICSIICSI

Hemizona AssayHemizona AssayS i t tiS i t ti1.1. Sperm zona interactionSperm zona interaction

2.2. ICSIICSI3.3. Not indicatedNot indicated

Reactive Oxygen TestingReactive Oxygen TestingROS/TACROS/TACSperm Viability AssaySperm Viability AssaySperm Viability AssaySperm Viability Assay

1.1. Eosin YEosin Y22 Trypan blueTrypan blue2.2. Trypan blueTrypan blue3.3. HOSTHOST

Genetic TestingGenetic TestingGenetic Testing:Genetic Testing:

Prevalence increase with SC Prevalence increase with SC Karyotypic abnormalityKaryotypic abnormalityKaryotypic abnormalityKaryotypic abnormalityY chromosome MDY chromosome MDG t ti (AZF)G t ti (AZF)Gene mutation (AZF)Gene mutation (AZF)

Indication: sever oligospermiaIndication: sever oligospermianon obs. azoospermianon obs. azoospermia

Testicular biopsy:Testicular biopsy:p yp yIndicationIndicationNormal: obs.AzoospermiaNormal: obs.AzoospermiaHypospermatogenesis: all germinal elementHypospermatogenesis: all germinal elementoligo>azoooligo>azooM t ti t t t tidM t ti t t t tidMaturation arrest : spermatocyte or spermatidMaturation arrest : spermatocyte or spermatid

azoo>oligoazoo>oligoGerm cell aplastia : normal to small size testisGerm cell aplastia : normal to small size testisGerm cell aplastia : normal to small size testisGerm cell aplastia : normal to small size testis

regionalregionalEnd stage testis : Tubular & Pretubular SclerosisEnd stage testis : Tubular & Pretubular Sclerosisgg

germ cell germ cell ––sertoly sertoly ±±l dl dleydig leydig ±±

Diso de of spe matogenesisDiso de of spe matogenesisDisorder of spermatogenesisDisorder of spermatogenesis

Pit ita diseasePit ita diseasePituitary disease :Pituitary disease :

Time of onsetTime of onsetTestis size & consistencyTestis size & consistencyTestis size & consistency Testis size & consistency EthiologyEthiology

Isolated Hypogonadotrpic Hypogonadism :Isolated Hypogonadotrpic Hypogonadism :Isolated Hypogonadotrpic Hypogonadism :Isolated Hypogonadotrpic Hypogonadism :

Congenital or IdiopathicCongenital or IdiopathicXL > AD AR & Mutation (XL > AD AR & Mutation (3030%)%)XL > AD,AR & Mutation (XL > AD,AR & Mutation (3030%)%)SymptomsSymptomsHCG FSHHCG FSH G RHG RH T t tT t tHCG, FSH, HCG, FSH, GnRHGnRH, Testosterone , Testosterone ,,clomipheneclomiphene

Isolated FSH DeficiencIsolated FSH DeficiencIsolated FSH DeficiencyIsolated FSH Deficiency

Normal size testisNormal size testisOligo or AzooOligo or AzooOligo or AzooOligo or AzoohMGhMG

And ogen E cessAnd ogen E cessAndrogen Excess:Androgen Excess:

CAH CAH 21 21 Hydroxilase >Hydroxilase >Adrenal & Testicular TumorAdrenal & Testicular TumorAdrenal & Testicular TumorAdrenal & Testicular TumorExogenousExogenousMRI CT USMRI CT USMRI , CT , USMRI , CT , US

Est ogen e cessEst ogen e cessEstrogen excess :Estrogen excess :

Testicular Testicular SertoliSertoli Cell TumorCell TumorLeydigLeydig Cell TumorCell TumorLeydigLeydig Cell TumorCell TumorObesity ,hepatic Obesity ,hepatic disdisG tiG ti ED T ti At hED T ti At hGynecomastiaGynecomastia , ED , Testis Atrophy, ED , Testis Atrophy

P olactin E cessP olactin E cessProlactin Excess:Prolactin Excess:

TumorTumorStress Medication IdiopathicStress Medication IdiopathicStress , Medication , IdiopathicStress , Medication , IdiopathicED & InfertilityED & InfertilityL t di dL t di dLater diagnosedLater diagnosedRuled out Hypothyroidism Ruled out Hypothyroidism

Th oid Abno malitTh oid Abno malitThyroid Abnormality:Thyroid Abnormality:

Hyper & HypoHyper & Hypo

A d I iti it S dA d I iti it S dAndrogen Insensitivity SyndromeAndrogen Insensitivity Syndrome

XLXLPhenotype male to femalePhenotype male to femalePhenotype male to femalePhenotype male to femaleAzoo or OligoAzoo or Oligo

Genetic S nd omesGenetic S nd omesGenetic SyndromesGenetic Syndromes

Chromosomal disordersChromosomal disordersklineFelterklineFelter’’s Syndromes SyndromeXXY PXXY P 11//6006001.1. XXY , P XXY , P 11//600600

2.2. Pure or mosaicismPure or mosaicism3.3. AzoospermiaAzoospermiapp4.4. Tubular sclerosisTubular sclerosis5.5. GenicomastiaGenicomastia

B b d kB b d k6.6. Barbody karyotypeBarbody karyotype7.7. 50 50 fold higher risk of breast cancerfold higher risk of breast cancer88 MosaicismMosaicism ICSIICSI8.8. Mosaicism Mosaicism ICSIICSI

XX MaleXX MaleXX Male:XX Male:

Similar to klinfelter syndromeSimilar to klinfelter syndromePortion of Y ch or SRY genePortion of Y ch or SRY genePortion of Y ch or SRY genePortion of Y ch or SRY geneazooazoo

XYY S nd omeXYY S nd omeXYY Syndrome:XYY Syndrome:

Tall , AggressiveTall , AggressiveOligo or AzooOligo or AzooOligo or AzooOligo or AzooARTART

Y ch omosome mic o deletionY ch omosome mic o deletionY chromosome micro deletion:Y chromosome micro deletion:

Not inheritedNot inheritedAZFcAZFc >> AZFbAZFb AZFaAZFaAZFcAZFc > > AZFbAZFb , , AZFaAZFaART & genetic counseling ART & genetic counseling

Bilate al Ano chiaBilate al Ano chiaBilateral Anorchia:Bilateral Anorchia:

Infection , Vascular or torsionInfection , Vascular or torsionTestosteroneTestosteroneTestosterone Testosterone

UDTUDTUDT:UDT:

11//3 3 bilateralbilateralDependent to testis levelDependent to testis levelDependent to testis levelDependent to testis levelUnilateral corrected Unilateral corrected fertility fertility 8080--9090%%Bil t l t dBil t l t d f tilitf tilit 3030 5050%%Bilateral corrected Bilateral corrected fertility fertility 3030--5050% % Retractile Testis Retractile Testis M h iM h iMechanismMechanism

Va icoceleVa icoceleVaricocele:Varicocele:

Prevalence: L Prevalence: L 9090% ; bilateral % ; bilateral 1010%%Secondary > PrimarySecondary > Primaryy yy yHigher T & reflux of metabolites &Impaired Higher T & reflux of metabolites &Impaired venous drainagevenous drainageMotility > SC > MorphologyMotility > SC > MorphologyDiagnosisDiagnosisggGradingGradingSurgical approachSurgical approachSurgical approachSurgical approachSuccessful predictorsSuccessful predictors

O chitisO chitisOrchitis:Orchitis:

MumpsMumps3030% at puberty% at puberty3030% at puberty% at puberty1010--3030% bilateral% bilateralI fI f 22b &b & G RHG RHInfInf αα22b & b & GnRHGnRHTESATESASyphilis, Gonorrhea , Leprosy , Syphilis, Gonorrhea , Leprosy , MononucleosisMononucleosis

Chemothe apChemothe apChemotherapy:Chemotherapy:

Spermatogonia & SpermatocytesSpermatogonia & SpermatocytesDose & AgeDose & AgeDose & AgeDose & AgeAlkylating >Alkylating >H d kiH d ki ’’ (MOPP & COPP)(MOPP & COPP) NOVPNOVPHodgkinHodgkin’’s (MOPP & COPP)s (MOPP & COPP) NOVPNOVPRecovery : Recovery : 44yySperm banking & contraceptiveSperm banking & contraceptive

RadiationRadiationRadiation:Radiation:

Dose & AgeDose & AgeRecoveryRecovery 22yyRecovery Recovery 22yy¼¼ permanentpermanentC t tiC t ti 66 2424Contraceptive Contraceptive 66--24 24 mm

Drug & MedicationDrug & MedicationMarijuana: Marijuana: pyospermiapyospermia. . Tes.genicomastiaTes.genicomastia , SC , SC CocainCocain : : morphology,motilitymorphology,motility & SC& SCSpironolactoneSpironolactone : ( : ( aldostronealdostrone antagonist)antagonist)

antiandrogenantiandrogen effect effect SC SC Ca channel blocker : functional defectCa channel blocker : functional defectCa channel blocker : functional defect Ca channel blocker : functional defect DES : UDT & Cyst of DES : UDT & Cyst of epididymepididymNitrofurantoinNitrofurantoinNitrofurantoinNitrofurantoin,,Gentamycin,Erythromycin,TetracyclineGentamycin,Erythromycin,Tetracycline: : gonadotoxicgonadotoxic & function& functionCimetidinCimetidin : germ cell: germ cellCimetidinCimetidin : germ cell: germ cellSulfazalazineSulfazalazine: SC & motility: SC & motilityAlcohol :Alcohol : peritubularperitubular fibrosis & germ cellfibrosis & germ cellAlcohol : Alcohol : peritubularperitubular fibrosis & germ cellfibrosis & germ cell

free free testesSmoking : female > maleSmoking : female > male

Idiopathic infe tilitIdiopathic infe tilitIdiopathic infertility:Idiopathic infertility:

3030% of patients% of patients2626% pregnancy rate% pregnancy ratep g yp g yGnRHGnRHGonadotropinsGonadotropinsGo adot op sGo adot op sClomiphenClomiphen & & TamoxifenTamoxifen & & TestolactoneTestolactone & & AnastrozoleAnastrozoleAndrogensAndrogensThyroxineThyroxine ,, argininarginin ,, corticostroidscorticostroids,, VitVit A,E,CA,E,CThyroxineThyroxine , , argininarginin , , corticostroidscorticostroids, , VitVit A,E,CA,E,CL L CarnitineCarnitine & & KallekreinKallekrein

Spe m deli e diso de sSpe m deli e diso de sSperm delivery disorders:Sperm delivery disorders:

DuctalDuctal obstructionobstructionCBAVD ICSI + Genetic counselingCBAVD ICSI + Genetic counselingCBAVD , ICSI + Genetic counselingCBAVD , ICSI + Genetic counselingEjEj. . DuctalDuctal Obstruction : TUREDObstruction : TUREDVV d fd f && idid lidid l bbVas Vas deferendeferen & & epididymalepididymal obs.obs.

Vasectom e e salVasectom e e salVasectomy reversal :Vasectomy reversal :

66% of men who have undergone % of men who have undergone vasectomyvasectomyyySecondary ep.obs (Secondary ep.obs (6262%% 1515yo)yo)Sperm & fluid copious and clearSperm & fluid copious and clearSperm & fluid copious and clearSperm & fluid copious and clear

Vasoepid mostomVasoepid mostomVasoepidymostomy:Vasoepidymostomy:

VasectomyVasectomyInfectionInfectionInfectionInfectionCFCF

End to End End to End AnastomosisAnastomosis

End to Side End to Side AnastomosisAnastomosis

Ejaculatory problems:Ejaculatory problems:Distinguish from Distinguish from anorgasmiaanorgasmiaPharmacologic therapy:Pharmacologic therapy:Pharmacologic therapy: Pharmacologic therapy:

1.1. Normal B.NNormal B.N2.2. EmissionEmission

PsuedoephedrinePsuedoephedrine 60 60 mg QIDmg QIDpp g Qg QImipraminImipramin 25 25 mg BDmg BDCyclicCyclicRecovery of spermRecovery of sperm

11 Fluid intakeFluid intake1.1. Fluid intakeFluid intake2.2. Sodium bicarbonateSodium bicarbonate3.3. Media into bladderMedia into bladder

SCISCI1.1. Vibration Vibration 7070% UMN% UMN2.2. TT11--TT6 6 BCR or Hip RBCR or Hip R3.3. TT77--TT12 12 both reflexboth reflex

Electro ejaculation:Electro ejaculation:Electro ejaculation:Electro ejaculation:1.1. SCISCI2.2. RPLNDRPLND3.3. MSMS

A iA i d fl id fl i b Tb T444.4. Autonomic Autonomic dysreflexiadysreflexia above Tabove T44

Spe m f nction diso deSpe m f nction diso deSperm function disorderSperm function disorder

Immunologic infertility Immunologic infertility SppressSppress AbAb :: corticostroidcorticostroid:: high dose cyclichigh dose cyclicSppressSppress AbAb : : corticostroidcorticostroid: : high dose cyclichigh dose cyclic

low dose low dose longtermlongterm3030 4040%%3030--4040%%

Processing technique : Processing technique : chymotripsinchymotripsinICSIICSI

Ult a st ct al Abno malitUlt a st ct al Abno malitUltra structural Abnormality:Ultra structural Abnormality:

Electron microscopyElectron microscopyOuter dense fiberOuter dense fiberMicrotubulMicrotubulMicrotubulMicrotubulMitochondriaMitochondriaConnecting pieceConnecting pieceAc osomeAc osomeAcrosomeAcrosome

Immotile cilia syndrome ARImmotile cilia syndrome ARDysplasia fibrous sheath (stump tail Dysplasia fibrous sheath (stump tail synsyn) I,II) I,IIRound head sperm: Round head sperm: acrosomeacrosome & & cytoskeletalcytoskeletal Pr (Pr (--) I,II) I,IIConnecting piece : pin headConnecting piece : pin headConnecting piece : pin headConnecting piece : pin headICSIICSI