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Diagnosis and management of male infertility
 

Diagnosis and management of male infertility

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    Diagnosis and management of male infertility Diagnosis and management of male infertility Presentation Transcript

    • DIAGNOSIS &DIAGNOSIS &MANAGEMENT OFMANAGEMENT OFMALE INFERTILITYMALE INFERTILITYDr. SHASHWAT K. JANIDr. SHASHWAT K. JANIAssistant ProfessorSheth V.S. Gen. HospitalAHMEDABAD.Mob : 99099 44160Mob : 99099 44160Email : drshashwatjani@gmail.comEmail : drshashwatjani@gmail.com
    • INTRODUCTIONINTRODUCTION• The number of couples affected by infertilityThe number of couples affected by infertilityis currently estimated to be 15%is currently estimated to be 15%• Of all couples attempting to have children.Of all couples attempting to have children.The difficulties are attributable to a significantThe difficulties are attributable to a significantmale factor alone in 30% of couples.male factor alone in 30% of couples.• Combination of male and female factors in anCombination of male and female factors in anadditional 20%.additional 20%.Therefore, in 50% of all infertile couples,Therefore, in 50% of all infertile couples,an abnormal male factor contributes toan abnormal male factor contributes toreproductive failure.reproductive failure.
    • INTRODUCTIONINTRODUCTION• The primary care practitioner often is the firstThe primary care practitioner often is the firsthealth care professional the patient seekshealth care professional the patient seeksAbsolute critical initial evaluation of theAbsolute critical initial evaluation of thesubfertile male.subfertile male.• Thorough history and physical examinationThorough history and physical examination• Laboratory tests, including at least a semenLaboratory tests, including at least a semenanalysisanalysis• Hormonal evaluation.Hormonal evaluation.Appropriate to refer the couple to anAppropriate to refer the couple to aninfertility specialist.infertility specialist.
    • Definition of "Infertility"Definition of "Infertility"• Infertility is a disease **. The duration of the failure toInfertility is a disease **. The duration of the failure toconceive should be twelve or more months before anconceive should be twelve or more months before aninvestigation is undertaken unless medical historyinvestigation is undertaken unless medical historyand physical findings dictate earlier evaluation andand physical findings dictate earlier evaluation andtreatment.treatment.• ** Any deviation from or interruption of the normal** Any deviation from or interruption of the normalstructure or function of any part, organ, or system, orstructure or function of any part, organ, or system, orcombination thereof, of the body that is manifested bycombination thereof, of the body that is manifested bya characteristic set of symptoms or signs, and whosea characteristic set of symptoms or signs, and whoseetiology, pathology, and prognosis may be known oretiology, pathology, and prognosis may be known orunknown:unknown: Dorlands Medical DictionaryDorlands Medical Dictionary 1988:481.1988:481.Approved by the Practice Committee of the American Society forApproved by the Practice Committee of the American Society forReproductive Medicine (Formerly The American FertilityReproductive Medicine (Formerly The American FertilitySociety), March 27, 1993.Society), March 27, 1993.Approved by the Board of Directors of the American Society forApproved by the Board of Directors of the American Society forReproductive Medicine (Formerly The American FertilityReproductive Medicine (Formerly The American FertilitySociety), July 17, 1993.Society), July 17, 1993.
    • PRE-TESTICULAR CAUSES OF INFERTILITYPRE-TESTICULAR CAUSES OF INFERTILITY• Hypothalamic diseaseHypothalamic disease   – Isolated gonadotropin deficiency (KallmannsIsolated gonadotropin deficiency (Kallmannssyndrome) syndrome) – Isolated LH deficiency ("Fertile eunuch") Isolated LH deficiency ("Fertile eunuch") – Isolated FSH deficiency CongenitalIsolated FSH deficiency Congenitalhypogonadrotropic syndromeshypogonadrotropic syndromes• Pituitary diseasePituitary disease   – Pituitary insufficiency (tumors, infiltrativePituitary insufficiency (tumors, infiltrativeprocesses, operation, radiation)processes, operation, radiation)–   Hyperprolactinemia Hyperprolactinemia – Hemochromatosis Hemochromatosis – Exogenous hormones (estrogen-androgen excess,Exogenous hormones (estrogen-androgen excess,glucocorticoid excess, hyper and hypothyroidism).glucocorticoid excess, hyper and hypothyroidism).
    • TESTICULAR CAUSES OF INFERTILITYTESTICULAR CAUSES OF INFERTILITY• Chromosomal abnormalities (KlinefeltersChromosomal abnormalities (Klinefelterssyndrome, XX disorder (sex reversal syndrome),syndrome, XX disorder (sex reversal syndrome),XYY syndrome)-XYY syndrome)-• Noonans syndrome (male Turners syndrome)-Noonans syndrome (male Turners syndrome)-• Myotonic dystrophy-Myotonic dystrophy-• Bilateral anorchia (vanishing testes syndrome)Bilateral anorchia (vanishing testes syndrome)• Sertoli-cell-only syndrome (germinal cell aplasia)Sertoli-cell-only syndrome (germinal cell aplasia)• Gonadotoxins (drugs, radiation)Gonadotoxins (drugs, radiation)• OrchitisOrchitis• TraumaTrauma• Systemic disease (renal failure, hepatic disease,Systemic disease (renal failure, hepatic disease,sickle cell disease)sickle cell disease)• Defective androgen synthesis or action-Defective androgen synthesis or action-CryptorchidismCryptorchidism• VaricoceleVaricocele
    • History of the Infertile MaleHistory of the Infertile Male• Male ReproductiveMale ReproductiveHistoryHistory• Duration ofDuration ofunprotectedunprotectedintercourseintercourse• Previous pregnanciesPrevious pregnancies• Previous infertilityPrevious infertilityevaluationsevaluations• FemaleFemaleReproductiveReproductiveHistoryHistory• AgeAge• Gravida/paraGravida/para• Physicians namePhysicians name• Ovulation withOvulation withtechnique to assesstechnique to assess• Current status ofCurrent status offemale infertilityfemale infertilityevaluationevaluation
    • Personal HistoryPersonal HistoryDevelopmentalDevelopmental• PubertyPuberty(normal/delayed/pre(normal/delayed/precocious)cocious)• History ofHistory ofundescended testesundescended testes• History ofHistory ofgynecomastiagynecomastiaSurgicalSurgical• Pelvic surgery (Y-VPelvic surgery (Y-Vplasty to bladderplasty to bladderneck, transurethralneck, transurethralsurgery)surgery)• Inguinal surgeryInguinal surgery(herniorrhaphy,(herniorrhaphy,orchidopexy)orchidopexy)
    • HistoryHistory• Sexual HistorySexual History• Potency/libidoPotency/libido• Coital techniqueCoital technique• Timing and frequencyTiming and frequencyof intercourseof intercourse• Use of lubricantsUse of lubricants• Family HistoryFamily History• Cystic fibrosisCystic fibrosis• Androgen receptorAndrogen receptordeficiencydeficiency• HypogonadismHypogonadism
    • GonadotoxinsGonadotoxins• Chemical exposureChemical exposure(work, therapeutic)(work, therapeutic)• Smoking (marijuana,Smoking (marijuana,cigarettes)cigarettes) --OccupationalOccupational• Thermal exposureThermal exposure(saunas, hot tubs,(saunas, hot tubs,briefs)briefs)• Radiation exposureRadiation exposure(work, diagnostic,(work, diagnostic,therapeutic)therapeutic)MedicationMedication• Maternal (DES)Maternal (DES)• Personal usePersonal use• SteroidsSteroids• EndocrineEndocrineHistoryHistory• Headaches, visualHeadaches, visualdisturbances,disturbances,anosmiaanosmia• Excessive growth ofExcessive growth ofhands, feet, jawhands, feet, jaw• Retardation of hairRetardation of hairgrowth (facial, body)growth (facial, body)• Breast changesBreast changes
    • The duration of the couples infertilityThe duration of the couples infertilityand whether or not other treatmentand whether or not other treatmenthas been attemptedhas been attemptedIn the past, the fertility evaluationsIn the past, the fertility evaluations• 1 year of unprotected intercourse.1 year of unprotected intercourse.Current philosophyCurrent philosophy• Evaluation of ones fertility may properly begin atEvaluation of ones fertility may properly begin atwhatever time patients express concern, andwhatever time patients express concern, andboth the male and female portions of a fertilityboth the male and female portions of a fertilityworkup can be undertaken simultaneously in anworkup can be undertaken simultaneously in anefficient, cost-effective, and timely fashionefficient, cost-effective, and timely fashion..
    • History of bladder, pelvic, orHistory of bladder, pelvic, orretroperitoneal surgeryretroperitoneal surgerySuggesting the possibility of..Suggesting the possibility of..• Ejaculatory dysfunction withEjaculatory dysfunction withassociatedassociated• Incomplete or retrograde ejaculation.Incomplete or retrograde ejaculation.
    • Sexual habitsSexual habits• TimingTiming: The optimal timing for intercourse is: The optimal timing for intercourse isevery 48 hours & time when ovulation is mostevery 48 hours & time when ovulation is mostlikely (usually at the females midcycle).likely (usually at the females midcycle).• Coital habitsCoital habits:Cautione- to use lubricants only:Cautione- to use lubricants onlyif necessary,only in limited amounts.if necessary,only in limited amounts.Spermatotoxic lubricants (such as K-Y Jelly,Spermatotoxic lubricants (such as K-Y Jelly,Lubifax, Surgilube, Keri LotionLubifax, Surgilube, Keri Lotion) and) and evenevensalivasaliva cancan impair sperm motility.impair sperm motility.• Other lubricantsOther lubricants, such as raw egg white,, such as raw egg white,vegetable oil, safflower oil, peanut oil, andvegetable oil, safflower oil, peanut oil, andpetroleum jelly,petroleum jelly, do not impairdo not impair in vivoin vivo spermspermmotility.motility.
    • Childhood illnesses and disordersChildhood illnesses and disorders• CryptorchidismCryptorchidism: both unilateral and bilateral,: both unilateral and bilateral,frequently is associated with oligospermia.frequently is associated with oligospermia.– 30% with unilateral cryptorchidism and30% with unilateral cryptorchidism and– 50% of men with bilateral cryptorchidism50% of men with bilateral cryptorchidism• have sperm densities below 20 million/mL,have sperm densities below 20 million/mL,• 80% with unilateral Cryptorchidism are fertile80% with unilateral Cryptorchidism are fertile..• fertility rate is only 50% for couples in whom the malefertility rate is only 50% for couples in whom the malehas a history of bilateral cryptorchidismhas a history of bilateral cryptorchidism..• testes remaining undescended until after puberty dotestes remaining undescended until after puberty donot function well and that fertility rates are notnot function well and that fertility rates are notimproved with postpubertal orchidopexy.improved with postpubertal orchidopexy.
    • Childhood illnesses and disordersChildhood illnesses and disordersTesticular trauma or a history of unilateralTesticular trauma or a history of unilateraltesticulartesticular torsion also may adversely affecttorsion also may adversely affectthe testes. Approximately 30% to 40% of menthe testes. Approximately 30% to 40% of menwith a history of unilateral testicular torsionwith a history of unilateral testicular torsionhave an abnormal semen analysis.have an abnormal semen analysis.???? A breakdown in the blood-testis barrierA breakdown in the blood-testis barrier maymaybe the causebe the causeThe testis susceptible to torsion may have hadThe testis susceptible to torsion may have hada preexisting spermatogenic defect (a higha preexisting spermatogenic defect (a highincidence of impaired spermatogenesis in theincidence of impaired spermatogenesis in thebiopsiedbiopsied contralateralcontralateral testis).testis).
    • Childhood illnesses and disordersChildhood illnesses and disorders• Delayed or incomplete pubertyDelayed or incomplete puberty may reveal anmay reveal anendocrinologic etiology (such as Klinefeltersendocrinologic etiology (such as Klinefelterssyndrome or idiopathic hypogonadism).syndrome or idiopathic hypogonadism).• gynecomastiagynecomastia may also suggest anmay also suggest anunderlying endocrine problem.underlying endocrine problem.• Bilateral mumps orchitisBilateral mumps orchitis experiencedexperiencedprepubertally seems to have no effect, butprepubertally seems to have no effect, butmumps orchitis experienced postpubertally ismumps orchitis experienced postpubertally isassociated with severe testicular damage inassociated with severe testicular damage in10% of patients.10% of patients.
    • • Diabetes mellitus or multiple sclerosisDiabetes mellitus or multiple sclerosiscan impair potency as well ascan impair potency as well asejaculation.ejaculation.• Treatment for cancer affects fertilityTreatment for cancer affects fertility..treated withtreated with radiation or chemotherapyradiation or chemotherapy forfortestis ,any other cancer is at risk oftestis ,any other cancer is at risk ofimpaired spermatogenesis.impaired spermatogenesis.Patients with testicular cancer arePatients with testicular cancer areparticularly affected.particularly affected.• Past history of a herniorrhaphyPast history of a herniorrhaphysuggests the possibility of an iatrogenicsuggests the possibility of an iatrogenicvasal injuryvasal injury..
    • Inflammatory processInflammatory process• Any inflammatory processAny inflammatory process that involvesthat involvesthe lower urinary tract may lead to adversethe lower urinary tract may lead to adversescarring of the ductal system,scarring of the ductal system,• e.g., ejaculatory duct stenosise.g., ejaculatory duct stenosis ororobstruction,obstruction, that may affect fertility.that may affect fertility.• AnyAny generalized febrile episodegeneralized febrile episode maymaytransiently impair spermatogenesis.transiently impair spermatogenesis.
    • • Immotile cilia syndromeImmotile cilia syndrome (nonmotile(nonmotilesperm secondary to an ultrastructuralsperm secondary to an ultrastructuraldefect in the sperm tail) may be thedefect in the sperm tail) may be thecause of infertility in the male withcause of infertility in the male withrecurrent respiratory infectionsrecurrent respiratory infections(Kartageners syndrome or Youngs(Kartageners syndrome or Youngssyndrome).syndrome).• A gene forA gene for cystic fibrosiscystic fibrosis is carriedis carriedwithout their knowledge by a number ofwithout their knowledge by a number ofmen who may also have congenitalmen who may also have congenitalabsence of the vasa and seminalabsence of the vasa and seminalvesicles and, consequently,vesicles and, consequently,A low ejaculate volume and azoospermia.A low ejaculate volume and azoospermia.
    • Exposure to elements increasingExposure to elements increasingthe overall scrotal temperaturethe overall scrotal temperature• CryptorchidismCryptorchidism• Scrotal varicocelesScrotal varicocelesimpaired spermatogenesis associatedimpaired spermatogenesis associatedwith these disorders.with these disorders.To optimize their sperm production, menTo optimize their sperm production, menare encouraged to avoid the use ofare encouraged to avoid the use ofsaunas and hot tubs.saunas and hot tubs.
    • Medications, Toxins, and DrugsMedications, Toxins, and DrugsAssociated with Male InfertilityAssociated with Male InfertilityMedicationsMedications ToxinsToxins• Androgenic steroidsAndrogenic steroids Agent OrangeAgent Orange• AntihypertensivesAntihypertensives Anesthetic gassesAnesthetic gasses• Cancer chemotherapyCancer chemotherapy BenzeneBenzene• HH22 blockersblockers DibromochloropropaneDibromochloropropane• KetoconazoleKetoconazole LeadLead• SpironolactoneSpironolactone ManganeseManganese• CychlosporineCychlosporine• NitrofurantoinNitrofurantoin Other DrugsOther Drugs• SulfasalazineSulfasalazine AlcoholAlcohol• ColchicineColchicine HeroinHeroin• AllopurinolAllopurinol MarijuanaMarijuana• TetracyclineTetracycline MethadoneMethadone• ErythromycinErythromycin TobaccoTobacco• GentamicinGentamicin
    • Physical ExaminationPhysical Examination• Body HabitusBody Habitus Decreased body hairDecreased body hairGynecomastiaGynecomastiaEunuchoid proportionsEunuchoid proportions• PhallusPhallus Peyronies diseasePeyronies diseaseCongenital curvatureCongenital curvatureHypospadiasHypospadias• ScrotumScrotum Testicular volumeTesticular volumeEpididymal indurationEpididymal indurationPresence/absence of vas deferensPresence/absence of vas deferensVaricoceleVaricocele• Digital Rectal ExaminationDigital Rectal ExaminationProstate sizeProstate sizeProstatic/seminal vesicularmass /Prostatic/seminal vesicularmass /induration/cystsinduration/cysts
    • Semen AnalysisSemen Analysis• 48 to 72 hours of abstinence.48 to 72 hours of abstinence.• Collection ideally, at the laboratoryCollection ideally, at the laboratory• By masturbationBy masturbation• Into a container furnished by theInto a container furnished by thelaboratory that has been tested tolaboratory that has been tested toensure that it will not alter the spermensure that it will not alter the spermsamples quality.samples quality.• Should be analyzed within 1 hour andShould be analyzed within 1 hour andkept at body temperature before.kept at body temperature before.
    • Semen AnalysisSemen Analysis• Characteristics analyzed are semenCharacteristics analyzed are semenvolume, sperm density, sperm motility,volume, sperm density, sperm motility,forward progression, and spermforward progression, and spermmorphology. In addition, the sample ismorphology. In addition, the sample isanalyzed for the presence of leukocytesanalyzed for the presence of leukocytesthat might indicate infection orthat might indicate infection orinflammationinflammation• An aliquot of the sample is air-dried onAn aliquot of the sample is air-dried ona slide and stained for determination ofa slide and stained for determination ofsperm shape or morphology. Normalsperm shape or morphology. Normalsemen samples contain at least 50%semen samples contain at least 50%morphologically normal sperm.morphologically normal sperm.
    • World Health Organization (WHO)World Health Organization (WHO)CriteriaCriteriaFor Normal Semen ValuesFor Normal Semen ValuesVolumeVolume 1.5 – 5.01.5 – 5.0mlmlpHpH 7.2-7.87.2-7.8Sperm concentrationSperm concentration > 20 million/ml> 20 million/mlViscosityViscosity < 3 scale ( 0< 3 scale ( 0– 4)– 4)Total sperm countTotal sperm count > 40 million/ejac> 40 million/ejacMotilityMotility > 50%> 50%Forward progressionForward progression >2 scale ( 0 –>2 scale ( 0 –4 )4 )MorphologyMorphology > 30% normal forms> 30% normal forms
    • Normal biochemical ValuesNormal biochemical Values• Acid PhosphataseAcid Phosphatase25,000-60,000 IU/ml25,000-60,000 IU/ml• ZincZinc 90-250 mg/100 ml90-250 mg/100 ml• FructoseFructose 150-600/100 ml150-600/100 ml
    • NomenclatureNomenclature• AspermiaAspermia- Failure of formation or emission- Failure of formation or emissionof semenof semen• Oligospermia/ Oligozoospermia-Oligospermia/ Oligozoospermia- TheThecount <20 million /mlcount <20 million /ml• Poly zoospermia-Poly zoospermia- Count >350 million /mlCount >350 million /ml• Azoospermia-Azoospermia- No spermatozoa in theNo spermatozoa in thesemensemen• Asthenospermia-Asthenospermia- reduction in vitality /reduction in vitality /Motility of spermatozoaMotility of spermatozoa• Necrospermia/Necrozooospermia-Necrospermia/Necrozooospermia-spermatozoa are dead or motionlessspermatozoa are dead or motionless• Teratospermia/ Teratozoospermia-Teratospermia/ Teratozoospermia-Presence of high number of malformedPresence of high number of malformedspermatozoaspermatozoa
    • Semen analysisSemen analysis• Color;Color; Whitish grey to yellow tends to be moreWhitish grey to yellow tends to be moreyellowish with longer abstinence, genital tractyellowish with longer abstinence, genital tractinfection-finally reddish in sever form.infection-finally reddish in sever form.• OdorOdor: Chestnut flowers/amniotic fluid like FromChestnut flowers/amniotic fluid like Fromoxidation of spermine –prostatic gland secretionoxidation of spermine –prostatic gland secretion• Coagulation and LiquefactionCoagulation and Liquefaction: within 5-40 mins: within 5-40 mins• Coagulative enzyme – in seminal vesicalCoagulative enzyme – in seminal vesical• Liquefying enzyme Seminine –prostate gland.Liquefying enzyme Seminine –prostate gland.Complete lack of coagulation –Complete lack of coagulation –Agenesis of seminal vesical orocclusion of ejaculatory ducts.Failure to liquefyFailure to liquefy - Poor prostate lytic activity.• Following liquefaction SF achieves viscous state.-Following liquefaction SF achieves viscous state.-Hyperviscocity impairs sperm motility.Hyperviscocity impairs sperm motility.
    • Semen analysisSemen analysis• VolumeVolumeHypospermia: Volume <1.5 mlHypospermia: Volume <1.5 mlHyperspermia:>5.5mlHyperspermia:>5.5mlPlasma : Vehicle/ DiluentPlasma : Vehicle/ Diluent/Buffering medium/Source of energy./Buffering medium/Source of energy.Semen volume mainly –Seminal vesicalSemen volume mainly –Seminal vesicalsecretions.secretions.↓↓↓↓S. Vol.- Androgen defi., proximal occlusionS. Vol.- Androgen defi., proximal occlusionof ejaculatory duct or incomplete ejaculation.of ejaculatory duct or incomplete ejaculation.• PHPH>8 –Acute disease of seminal vesical or>8 –Acute disease of seminal vesical ordelayed measurementdelayed measurement<7 occlusion of ejaculatory duct occlusion,<7 occlusion of ejaculatory duct occlusion,contamination with urinecontamination with urine
    • Microscopic ExaminationMicroscopic ExaminationMotilityMotilityGrade 4Grade 4 Rapid and Linearly progressiveRapid and Linearly progressiveGrade 3Grade 3 Slower sluggish linear or non linearSlower sluggish linear or non linearGrade 2Grade 2 Non progressive motilityNon progressive motilityGrade1Grade1 immotileimmotileFreshly ejaculated sperm cell velocity 75Freshly ejaculated sperm cell velocity 75µ/sµ/sStandardization of temperatureStandardization of temperatureMotility loss of 10-20% with in 3 hr consideredMotility loss of 10-20% with in 3 hr consideredWNL.WNL.
    • Automated Semen AnalysisAutomated Semen Analysis• Closed circuit- Video tape-digital data display-1973Closed circuit- Video tape-digital data display-1973• Doppler /turbidimetric method -1974-77Doppler /turbidimetric method -1974-77• Light scattering determination of motility 1978Light scattering determination of motility 1978• Multiple –Exposure photographic techniqueMultiple –Exposure photographic techniquePresent scenarioPresent scenario• Cellsoft system: cell size and luminosityCellsoft system: cell size and luminosity• The Hamilton Thorn system:infrared beamThe Hamilton Thorn system:infrared beamProvide Data forProvide Data for– ConcentrationConcentration– MotilityMotility– VelocityVelocity– LinearityLinearity– Lateral head displacement, circular motio ,MorphologyLateral head displacement, circular motio ,Morphology
    • Biochemical analysisBiochemical analysis• Epididymal fluid-Epididymal fluid-Glycerylphosphorycholine(GPC) &Glycerylphosphorycholine(GPC) &carnitinecarnitine• Inhibin by sertoly cellInhibin by sertoly cell ↓FSH control↓FSH control• Prostate gland fluid ; [Enzymes(AcidProstate gland fluid ; [Enzymes(AcidPhosphatase etc.), citric acid, Zinc,Phosphatase etc.), citric acid, Zinc,spermine]spermine]• Seminal Vesical ; Fructose,Seminal Vesical ; Fructose,ProstaglandinesProstaglandines• Sperm Creatine phosphokinaseSperm Creatine phosphokinase
    • Usual Findings of Hormonal StatusUsual Findings of Hormonal StatusCorrelated to Clinical DiagnosisCorrelated to Clinical DiagnosisClinical Status FSH (mIU/mL) LH (mIU/mL) Testosterone (ng/100 mL)Normal men Normal Normal NormalGerminal aplasia Elevated Normal Normal or decreasedTesticular failure Elevated Elevated Normal or decreasedHypogonadotropichypogonadismDecreased Decreased DecreasedHypergonadotropichypogonadismElevated Elevated Low-normal or decreased
    • AdditionalAdditional Laboratory TestsLaboratory Tests• Between 10% and 20% "unexplained"Between 10% and 20% "unexplained"infertility.infertility.• In the female, this percentage is rapidlyIn the female, this percentage is rapidlydecreasing as more sophisticateddecreasing as more sophisticatedtechniques have been developed totechniques have been developed toaccurately identify the efficacy ofaccurately identify the efficacy ofevaluation.evaluation.• In the male, additional tests to identifyIn the male, additional tests to identifyother abnormalities of semenother abnormalities of semenparameters. leukocyte and antispermparameters. leukocyte and antispermantibody identification, as well as testsantibody identification, as well as testsof sperm function.of sperm function.
    • Cervical Mucus/Sperm InteractionCervical Mucus/Sperm InteractionAssaysAssays• The postcoital test (PCT), first performed by Sims,The postcoital test (PCT), first performed by Sims,This test evaluates sperm concentration and motility inThis test evaluates sperm concentration and motility inan aspirate of cervical mucus at midcycle shortly afteran aspirate of cervical mucus at midcycle shortly afterthe couple has intercourse. a normal PCT- >20the couple has intercourse. a normal PCT- >20spermatozoa/hpf. An abnormal PCT secondary tospermatozoa/hpf. An abnormal PCT secondary toinappropriate timing of coitus,ASA, anovulation, aninappropriate timing of coitus,ASA, anovulation, anabnormal hormonal milieu, female or male genital tractabnormal hormonal milieu, female or male genital tractinfections, poor semen quality, and male sexualinfections, poor semen quality, and male sexualdysfunction.dysfunction.• presence of motile spermatozoa indicates thatpresence of motile spermatozoa indicates thatspermatozoa can survive in the cervical mucus, failurespermatozoa can survive in the cervical mucus, failureto find motile spermatozoa is more difficult to interpret.to find motile spermatozoa is more difficult to interpret.
    • Computer-Assisted Semen AnalysisComputer-Assisted Semen Analysis(CASA)(CASA)• introduced in the 1980s to provide an automated,introduced in the 1980s to provide an automated,objective, and standardized evaluation of spermobjective, and standardized evaluation of spermconcentration and movement.concentration and movement.• The variables measured are sperm density, percentThe variables measured are sperm density, percentmotility, straight-line velocity, curvilinear velocity,motility, straight-line velocity, curvilinear velocity,linearity, average path velocity, amplitude of laterallinearity, average path velocity, amplitude of lateralhead displacement, flagellar beat frequency, andhead displacement, flagellar beat frequency, andhyperactivation This technology is based onhyperactivation This technology is based ondigitalized sperm images that are visualized by adigitalized sperm images that are visualized by avideo camera and analyzed by a computer.video camera and analyzed by a computer.
    • • Viability stain assays.Viability stain assays.• Sperm Capacitation Assays,Sperm Capacitation Assays,• Mannose-Ligand Receptor Assays,Mannose-Ligand Receptor Assays,• Acrosome Reaction AssaysAcrosome Reaction Assays• Sperm Penetration Assay (SPA)Sperm Penetration Assay (SPA)• Reactive Oxygen Species (ROS) AssayReactive Oxygen Species (ROS) AssayOTHER TESTS ARE :OTHER TESTS ARE :
    • Diagnostic studiesDiagnostic studies• Transrectal ultrasound (TRUS) :1.1. Standard criteriaStandard criteria - low volume and acidic- low volume and acidicazoospermic semen specimens. These findingsazoospermic semen specimens. These findingssuggest absence of seminal vesicle fluid in thesuggest absence of seminal vesicle fluid in thesemen consistent with complete ejaculatory ductsemen consistent with complete ejaculatory ductobstruction. Also, dilated seminal vesicles areobstruction. Also, dilated seminal vesicles aresuggestive of ejaculatory duct obstruction due to asuggestive of ejaculatory duct obstruction due to amidline cyst, which may respond to a transurethralmidline cyst, which may respond to a transurethralresection of the ejaculatory ducts (TURED).resection of the ejaculatory ducts (TURED).2.2. Ultrasound guidance may be used during needleUltrasound guidance may be used during needleaspiration of the seminal vesicles, which may helpaspiration of the seminal vesicles, which may helpdetermine if there is ejaculatory duct obstruction.determine if there is ejaculatory duct obstruction.
    • VasographyVasography• Performed at the time of testicular biopsy ifPerformed at the time of testicular biopsy ifnormal spermatogenesis is demonstrated.normal spermatogenesis is demonstrated.• A transverse micro-incision in the vas near theA transverse micro-incision in the vas near thejunction of the straight and convoluted portionsjunction of the straight and convoluted portionswill allow immediate examination of thewill allow immediate examination of theeffluxing fluid for the presence of sperm as welleffluxing fluid for the presence of sperm as wellas localization of the level of obstruction.as localization of the level of obstruction.• Saline, Indigo caramine or hypaque orSaline, Indigo caramine or hypaque orrenograffin should be injected in antegraderenograffin should be injected in antegradedirection to check the level of obstruction .direction to check the level of obstruction .• A microsurgical technique should be used toA microsurgical technique should be used torepair the vasotomy site, i.e., closure with 10-0repair the vasotomy site, i.e., closure with 10-0and 9-0 monofilament microsutures.and 9-0 monofilament microsutures.
    • Testicular BiopsyTesticular Biopsy• Performed in patients with azoospermia,severe unexplainedPerformed in patients with azoospermia,severe unexplainedoligospermia,assymetrical testicular lesion,for mapping of theoligospermia,assymetrical testicular lesion,for mapping of thetestes for later sperm aspiration for ICSI,for screening of germtestes for later sperm aspiration for ICSI,for screening of germcell neoplasia or CIScell neoplasia or CIS• . Local anesthesia using a cord block and local infiltration often. Local anesthesia using a cord block and local infiltration oftenwith mild sedation utilized or general anesthesia. A "window"with mild sedation utilized or general anesthesia. A "window"techniqueis used.With a no-touch technique, the specimen istechniqueis used.With a no-touch technique, the specimen isexcised with sharp Iris scissors and promptly placed in Bouins,excised with sharp Iris scissors and promptly placed in Bouins,Zenkers, or buffered glutaraldehyde solution.Prior to placingZenkers, or buffered glutaraldehyde solution.Prior to placingthe specimen into the solution, a touch preparation slide can bethe specimen into the solution, a touch preparation slide can bemade for immediate review, i.e., testicular cytology.made for immediate review, i.e., testicular cytology.• Hemostasis is obtained with careful use of electrocautery, andHemostasis is obtained with careful use of electrocautery, andthe tunica albuginea is closed with fine, absorbable suture asthe tunica albuginea is closed with fine, absorbable suture asare the layers of the scrotum.are the layers of the scrotum.
    • Testicular BiopsyTesticular Biopsy• Testicular Needle Biopsy:Testicular Needle Biopsy: office procedure, withoffice procedure, withlittle pain and low morbidity, and yields adequatelittle pain and low morbidity, and yields adequateinformation. Techniques have been described usinginformation. Techniques have been described usingthe Vim-Silvermann26 or Tru-Cut biopsy needle27 tothe Vim-Silvermann26 or Tru-Cut biopsy needle27 toobtain a core of tissue or using fine-needle aspirationobtain a core of tissue or using fine-needle aspirationwith material smeared on the microscope slide..with material smeared on the microscope slide..• Testicular Fine-Needle Aspiration (FNA)Testicular Fine-Needle Aspiration (FNA)Cytology:Cytology: described as a minimally traumaticdescribed as a minimally traumaticprocedure having high correction with histologicprocedure having high correction with histologicstudies. Testicular FNAstudies. Testicular FNA hashas notnot gained widespreadgained widespreadacceptanceacceptance in the evaluation of the infertile male forin the evaluation of the infertile male fornumerous reasons. Although cellular detail isnumerous reasons. Although cellular detail isexcellent, information regarding peritubular fibrosis,excellent, information regarding peritubular fibrosis,the interstitial tissue, and cellular arrangement isthe interstitial tissue, and cellular arrangement islacking.lacking.• Testicular Cytology:Testicular Cytology: "touch imprint and cytospin"touch imprint and cytospintechniques.These methods provide a rapid means oftechniques.These methods provide a rapid means ofexamining the cellular contents of the seminiferousexamining the cellular contents of the seminiferoustubules.tubules.
    • VARICOCELEVARICOCELEDilatation of the pampiniform venous plexus.Dilatation of the pampiniform venous plexus.• 15%of general population15%of general population• Left > right, bilateral (30-50%)Left > right, bilateral (30-50%)• Pathophysiology : Renal and adrenal reflux,Pathophysiology : Renal and adrenal reflux,hypoxia,hormonal dysfunction,hyperthermia.hypoxia,hormonal dysfunction,hyperthermia.• Impaired fertility,scrotal pain,etc.Impaired fertility,scrotal pain,etc.• Surgical Rx : Scrotal, inguinal(modifiedSurgical Rx : Scrotal, inguinal(modifiedivanissevich),retroperitoneal(modified palomo)&ivanissevich),retroperitoneal(modified palomo)&laproscopic approch.laproscopic approch.• Nonsurgical Rx : Percutaneous venous occlusionNonsurgical Rx : Percutaneous venous occlusionwith use of detachable balloons,coils,andwith use of detachable balloons,coils,andsclerotherapysclerotherapy• 51-78% improvement in semen quality and 24-51-78% improvement in semen quality and 24-53% pregnancy rate after varicocele Rx.53% pregnancy rate after varicocele Rx.
    • Pituitary tumorsPituitary tumors• Mainly prolactin-secreting tumorsMainly prolactin-secreting tumors• S/S:-impaired libido,visual fieldS/S:-impaired libido,visual fieldchanges,elevated prolactin,lowchanges,elevated prolactin,lowtestosterone,normal LH.testosterone,normal LH.• Radiographic diagnosisRadiographic diagnosis• BromocryptineBromocryptine• Surgical Rx: Transsphenoidal surgicalSurgical Rx: Transsphenoidal surgicalablation or removalablation or removal
    • Procedures to Improve SpermProcedures to Improve SpermProductionProduction• VasovasostomyVasovasostomy::##IndicationIndication: for congenital absence of the: for congenital absence of theductal system,stricture followingductal system,stricture followinginfection,vasectomy,functional obstruction.infection,vasectomy,functional obstruction.##TechniqueTechnique:under GA,vertical scrotal:under GA,vertical scrotalincision,two layer anastomosis with 9-0 &incision,two layer anastomosis with 9-0 &10-0 nylon10-0 nylon
    • **Epididymovasotomy:Epididymovasotomy:• ForFor proximal obstructionproximal obstruction• If sperm are absent more proximal epididymalIf sperm are absent more proximal epididymalexploration is performedexploration is performed• Anastomosis with nylon 10-0 in two layersAnastomosis with nylon 10-0 in two layers• A new technique triangulation end-to-sideA new technique triangulation end-to-sidevasoepididymostomy with good results.vasoepididymostomy with good results.**Incision of ejaculatory ductsIncision of ejaculatory ducts ::• Patients with azoospermia or severePatients with azoospermia or severeoligospermia,low semen volumes,palpablyoligospermia,low semen volumes,palpablypresent vas deferenspresent vas deferens• Transurethral incision over ejaculatory ductTransurethral incision over ejaculatory duct
    • *Microscopic epididymal sperm*Microscopic epididymal spermaspiration(MESAaspiration(MESA):):• Popularized in 1988Popularized in 1988• A man in whom sperm transport from the testicle toA man in whom sperm transport from the testicle tothe the ejaculate in not possible b/o agenesis orthe the ejaculate in not possible b/o agenesis orobstructive problems.obstructive problems.• Through an operating microscope,sperms upto 10-Through an operating microscope,sperms upto 10-20million are directly aspirated from a single isolated20million are directly aspirated from a single isolatedepididymal tubuleepididymal tubule• Success of pregnancy-25%-40%Success of pregnancy-25%-40%**Percutaneous epididymal spermPercutaneous epididymal spermaspiration(PESAaspiration(PESA):):• Blind procedure increase the risk of damageBlind procedure increase the risk of damage• Appropriate when pt.has obstruction and desires onlyAppropriate when pt.has obstruction and desires onlyone childone child• Low success rate in copmare to MESALow success rate in copmare to MESA
    • TREATMENT :•A )A ) SPECIFICTHERAPY.•B ) EMPIRIC THERAPY.
    • SPECIFIC THERAPY :SPECIFIC THERAPY :• (A) Hypogonadotrophic hypogonadism :CC + Gonadotrophins.CC = 25 – 75 mg on alt. day.For 3 -9 months.First to initiate spermatogenesis:hCG = 2000-3000 iu twice a wkfor 6-8 wks till testosterone comes to normal.Then , HMG / uFSH / 75iu added thrice a wkand hCG once a wk.
    • • ( B ) Hyperprolactinemia:For Pituitary Macroadenoma:Surgically removed.For Microadenoma :Cabergolin 0.5mg – 2 mg. twice a wk.Maintain level : 10 – 15 microgm /ml.
    • ( C ) Genital tract infection:Chlamydia – Doxycycline.( D ) Disorders of ejaculation( E ) Immunological : no role of steroids.( F ) Isolated testosterone deficiency:hCG 2000 iu twice a wk.( G ) Congenital adrenal hyperplasia :dexamethasone 0.5mg HS.
    • EMPIRIC THERAPY :EMPIRIC THERAPY :• 1) CC :25 – 50 mg for 25 days for 3- 6 months.2) hCG :2500 – 5000 iu twice a wk.3 ) FSH + hCG:for idiopathic normogonadotrophicoligozoospermia4 ) Tamoxifen + Testosterone :20 mg/ day( for idiopathic oligozoospermia)
    • 5 ) Zinc : Very useful in low testosterone levelwith Zinc deficiency.120 -220 mg twice a day for 3 months.6 ) Ketotifen : histamine release inhibitor .1 mg BD for 3 – 6 months.7 ) Antiserotonin agents :Cyproheptadine HCL 4 mg TID for 3 mnths8) Captopril :ACE inhibitor . Kinase II inhibitor .50 mg / day for 3 months.
    • • 9 ) Anti – inflammatory drugs :Doxycycline : 100 mg bd for 14 days.Tetracycline & Metronidazole also effective.Helps in Oligoathenoteratozoospermia.10 ) Indomethacin :25 mg tds .increases sperm count & motility.11 ) Aanastrazole : Aromatase inhibitor1 mg / day.12 ) FSH + Nalotrexane :Improve spermatogenesis.
    • ROLE OF ANTIOXIDANTS:ROLE OF ANTIOXIDANTS:Systematic treatment of an infertileman with antioxidants has receivedgreat interest in recent years and itseems to have some clinicalbenefit , though the story remainssomewhat confused ….!!!
    • • 1 ) Vitamin E : ( Tocopherol )improves motility.300 – 600 mg/day for 6 -12 weeks.2 ) Vitamin C : ( Ascorbic acid )improves sperm quality & function.1000 mg / day.3 ) Vitamin B 12 :Useful for synthesis of DNA & RNA .For oligospermia & Asthenospermia.1000 – 1500 microgm / day for 6 months.
    • • 4 ) Folic Acid :Additive to other drugs to improve function.5 mg / day.5 ) Pentoxyphylline :improves microcirculation.improves count & motility.1.2 mg / day for 3 – 6 months.6 ) Arginine :improves motility.4 mg / day.
    • • 7 ) Selenium :Antioxidants as well as Anti inflammatory.Concentrated in Male reproductive tract.Highest concentration in prostate.225 microgm / day.8) Glutathione :Positive effect on sperm motility.600 mg IM daily .Not very popular.
    • • 9 ) L – Carnitine & L –Acetyl Carnitine :Imp role in sperm cell metabolism.Highest conc. in epididymal fluid.Useful in OAT and low grade varicocle.10 ) Co – enzyme Q10 :Component of mitochondrial respiratorychain.Available as 50 – 100 mg soft gel capsules thathas 100 % absorption.
    • • 11) Lycopene :Most potent lipophillic anti oxidants andCarotinoid anti oxidants.It protects sperm from damage by ROS .
    • THANK YOUTHANK YOU