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Male Infertility (1 of 19)

Male Infertility (1 of 19)

Male (1 of 19)

1 Male patient presents w/ signs & symptoms of infertility

2 • Consider female factor infertility DIAGNOSIS No - See Infertility Do history, PE, & diagnostic tests confirm male factor management infertility? chart

Yes

3 EVALUATION What is the main cause of ?

Endocrine/ Post-testicular Genetic Idiopathic Systemic Disease Dysfunction Disorder1

A Non-pharmacological therapy • Counseling MANAGEMENT MANAGEMENT C Assisted Reproductive MANAGEMENT See next page See page 3 Techniques (ART) See page 4

E Specialist FOLLOWUP Yes referral Pregnant?

No

Further evaluation & © MIMSspecialist referral 1For genetic disorders causing , see Management of Endocrine/Systemic Not all products are available or approved for above use in all countries. Specifi c prescribing information may be found in the latest MIMS.

B1 © MIMS 2019 MALE INFERTILITY 2 1 Please refer to Urinary Tract - Complicated Disease Management Chart, & Urinary Tract Tract Management &Urinary refer toUrinary -UncomplicatedPlease Chart, Infection Disease -Complicated Infection Please refer to Hypogonadism in Males - Late-Onset Disease Management formore information. Chart Disease -Late-Onset refer inMales toHypogonadism Please Disease Management information. forfurther Chart Disease Management ofEndocrine/ B A Systemic Disease Systemic Pharmacological therapy Pharmacological therapy Non-pharmacological Hypogonadism • • • • • • -releasing (GnRH) hormone Gonadotropin-releasing agonists Dopamine Supplements Psychotherapy therapy &behavioral Counseling © MIMS Primary Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing 1 Do not treat w/ treat not Do Determine specifiDetermine ofhypogonadism c cause Patient’s infertility caused by by Patient’s caused infertility endocrine/systemic disease endocrine/systemic Male Infertility(2of19) EVALUATION Hypogonadism Secondary Secondary 3 B2 1 B Pharmacological therapy Pharmacological • • Further evaluation & Further evaluation specialist referral specialist Glucocorticoids Antibiotics E Immunological Immunological FOLLOWUP C Pregnant? disorders Follow-up ART E No 2 / Specialist Specialist referral © MIMS Yes 2019 MALE INFERTILITY  refer Management Management toPenilePlease formore & information. Chart Cancer Chart Cancer Disease Disease Please refer to Disease Management &Premature Chart Disease Management information. refer forfurther Dysfunction Chart toErectile Please Disease Management ofPost-Testicular • • • • • Seminal VesiclesSeminal Ejaculatory duct Intratesticular D Obstruction Anatomical Anatomical Surgery Dysfunction

©C B MIMSA ART therapy Pharmacological Non-pharmacological Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not • • • • • therapy Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Empirical treatmentsEmpirical Supplements therapyBehavioral modifiLifestyle cations Counselling E FOLLOWUP Determine specifiDetermine dysfunction c post-testicular Pregnant? evaluation & evaluation Follow-up Malignancy specialist specialist Further referral E No Patient’s infertility caused by by Patient’s caused infertility post-testicular dysfunction post-testicular Male Infertility(3of19) 1 EVALUATION therapy D B 3 B3 • • Surgery Pharmacological transport transport sperm Developmental Developmental • hCG disorder Specialist Specialist referral Yes Further evaluation & specialist referral &specialist Further evaluation Yes C B A • • • • • • • ART therapy Pharmacological Non-pharmacological Retrograde obstruction Mechanical dysfunction Erectile ejaculationDelayed ejaculationAnesthetic Anorgasmia Sexual • • • • • • • • • • therapy Tramadol inhibitors Phosphodiesterase-5 anesthetics Local Dapoxetine Antihistamines Antidepressants Supplements Psychotherapy modifiLifestyle cations Counselling FOLLOWUP Pregnant? E No © 2 MIMS 2019 MALE INFERTILITY Management ofEndocrine/ © MIMS Disease Systemic Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing B A Pharmacological therapy Pharmacological therapy Non-pharmacological • • • • • • Male Infertility(4of19) Empirical treatmentEmpirical Gonadotropins Supplements Psychotherapy modifiLifestyle cations Counseling Further evaluation & Further evaluation Idiopathic infertility Idiopathic specialist referral specialist E FOLLOWUP C Pregnant? Follow-up ART E No B4 Yes Specialist referral Specialist © MIMS 2019 MALE INFERTILITY • • • • Analysis Sperm • • • Examination Physical • History Reproductive • History Medical Evaluation Clinical • • • Infertility ofMale Causes • • • • • • • • or severe oligozoospermia) oligozoospermia) orsevere azoospermia 3 analysis sperm Repeat isabnormal (earliermths if1st analysis initial test after to due ifabnormalityis Initially, taken analysis 1mth twosperm apartisrecommended ofinfertility the severity toevaluate Used formaleinfertility test Primary necessary as performed may exam be rectal A digital characteristics sexual &secondary gynecomastia, Note forthe presence ofvaricoceles, forenlargement inspect Vas deferens ormasses, -palpate forpresence &epididymis ofnodules - Testis -measurement & - ofthe urethral -palpate, meatus &include inspection - Should include anexamination ofthe following: gonadotoxin exposure including STDs, history sexual of allergies, history surgery, history, previous & presenthistory, , past disease systemic duration ofinfertility, , &timing, coitalIncludes previous medical frequency childhood/developmental &alcohol history) smoking, drugs, recreational , anabolic of (include use history history, reproductive Obtain the &social patient’s family ofsystems, complete review - Cryptorchidism - Varicocele ofmaleinfertility) cause common (most known - &transport production Disorders ofsperm torsion) (eg Klinefelter’s myotonic dystrophy, disease testicular cryptorchidism, syndrome, testicular Primary , defi inficiencies, ltrative disorders) nutritional hyperprolactinemia, Kallmansyndrome, (eg craniopharyngioma, disease pituitary Hypothalamic incouples toinfertility accounts factor thecause sole acontributory as infertility for20%,&30-40%as Male the inability intercourse toconceive sexual unprotected Infertility: regular for1year despite - hepatic cirrhosis, bronchiectasis, sinusitis, dextrocardia) sinusitis, bronchiectasis, hepatic cirrhosis, chronic (egChronic liver renal illness , infection, myocardial rheumatoid DM, failure, , Iatrogenic (post-, causes post-surgery) Immune disorders system Infections isunclear, ofinfertility Cause evaluation partner &normal analysis w/normal even - Idiopathic -accounts infertility for30-40%ofcases Y-chromosome microdeletions - abnormalities chromosomal Karyotypic - Cystic fibrosis - disorders Genetic microcalcifi andtesticular cell Germ malignancy cation -

ducts prostate, ejaculatory vesicles, seminal deferens, inthe abnormalities vas by caused azoospermia Obstructive © MIMS orautonomic dysfunction cord disease tospinal secondary dysfunction premature ejaculatory dysfunction: Sexual ejaculation, dysfunction, erectile 1 Male Infertility(5of19) MALE INFERTILITY 2 DIAGNOSIS B5 © MIMS 2019 MALE INFERTILITY • • • Tests Semen/Sperm Specialized Values Reference ofAccepted Limits Lower Analysis: Sperm (Cont’d) Analysis Sperm • • • • • • Evaluation Endocrine • • • Screening Genetic • • • • • Adapted from: Cooper TG, Noonan E, von Eckardstein S, et al. WHO referencevalues forhuman 2010. vonEckardstein WHO semencharacteristics. S,etal. Noonan TG, E, Cooper Adapted from: - antiglobulin reaction mixed (IBT), Eg test immunobead tests (ASA) Antisperm - Quantifi insemen cation ofleukocytes - High & low testosterone levels may be indicative of a prolactin-secreting pituitary tumor pituitary indicative may of aprolactin-secreting levels be testosterone High prolactin &low hypergonadotropic indicates FSH, hypogonadism levels &testosterone Low LH FSH mayPatients levels have abnormalities w/elevated hypergonadotrophic failure, testicular hypogonadism) (complete hypogonadism may levels indicate primary testosterone tolow FSH, &normal High serum LH diseases suspicionforendocrine orw/highclinical function, sexual concentration, forpatients ifw/<10millions/mLsperm Indicated esp w/abnormal impaired (<300ng/mL) low was prolactin level -iftotaltestosterone LH, testosterone, free Serum - FSH LH, levels &testosterone Measure Indications forY-chromosome oligozoospermia &severe include azoospermia testing of<10million/mL oroligospermia formen isrecommended w/azoospermia analysis gene) [CFTR] regulating Y-chromosome fi cystic abnormalities, microdeletions, (eg karyotype transmembranebrosis conductance (<5millionsperm/mL) oligospermia &severe azoospermia forpatientsRecommended w/non-obstructive interaction mucus sperm-cervical measurement, creatine kinase sperm assays, penetration sperm Other testing: - fragmentation tests DNA Sperm the examining sperm’s by the ofnonmotilesperm viability todetermine Used cell membranes - tests viability Sperm testing) aneuploidy Fluorescent DNA InSitu (forsperm Hybridization considered May for samples be w/presence ofinfl cellsammatory - Semen culture mucus penetration may inspermatozoal result incervical Presence failure antibodies ofsurface - agglutination analysis orsperm onsperm forpatients asthenospermia indicated w/isolated May be -

esp in patients w/ history of trauma, torsion,biopsy, carcinoma &testicular oftrauma, orchitis, inpatientsesp w/history barrier, ofabreach aresult inthe antigen blood-testis as orpost- sperm appears exposure, ASA &motility function count semen may indicate (>106wbc/mL) topoor presence leading of genital infection leukocyte Increased infertility routinelyShould not be off toconfi more studies are needed as ered, benefi its rm ofmale t inthe evaluation © MIMSembryo’s development that damage & integrity DNA may affsperm Helps identify a couple’s ect or an performance reproductive Viscosity agglutinationSperm Vitality morphology Normal progression Forward concentrationSperm pH Ejaculate volume Percentage motility Total number sperm Parameter 2 Male Infertility(6of19) DIAGNOSIS (CONT’D) B6 <2 cm thread after liquefaction <2 cmthread after Absent >58% livespermatozoa >4% normal >32% >40% >39 x10 >15 x10 7.2-7.5 >1.5 mL 6 6 Reference values Reference spermatozoa/ejaculate spermatozoa/mL © MIMS 2019 MALE INFERTILITY Penile ultrasound • • • • (Testicular Origin) Hypogonadism Primary • Disease Endocrine/Systemic • • forEvaluation Indications • • ofEvaluation Goals • • Vasography • • (TRUS) Transrectal ultrasound • • • ultrasound Scrotal • Ultrasonography • • • • Testicular Biopsy • • Urinalysis Post-ejaculatory • Modalities Imaging Other damage, alkylating agents, Ketoconazole, glucocorticoids Ketoconazole, damage, agents, alkylating chronic renal radiation, torsion, autoimmune failure, testicular hepatic cirrhosis, hypophysitis, lymphocytic infi tumors, Acquired disorders: orchitis), tuberculosis, sarcoidosis, infections, (eg fungal ltrative diseases syndrome Klinefelter Prader-WilliCongenital syndrome, disorders: oculocerebellar Lowe cerebellar familial syndrome, ataxia, include: hypogonadism primary with Disorders associated forhypogonadism origin FSH failure suggest atesticular &LH w/increased level testosterone Low orandrogen defi impaired spermatogenesis, dysfunction, ciency impairment/ either production by sperm caused hypogonadism, orsecondary primary men80-90% infertile has interventions intercoursemth notconceived vaginal ofage 6 yr has ofregular w/ocontraceptive after If female >35 partner intercourse >12mth sexual unprotected after ofregular spontaneous Inability toachieve confi therm malepartner’s potential fertility iffemale isat ofinfertility, partner risk ofbilateral cryptorchidism, if>35 esp history ofage,known yr or to Evaluation into intercourse 1year donebefore may the &w/unprotected be isw/ ifmalepartner the off inthespring future life-threatening conditions underlying infertility, techniques, reproductive that & genetic causes may aff ect To ofmaleinfertility, assisted correctable by managed causes that be able causes can toidentify be irreversible - Indications: duct orejaculatory deferens, vas epididymis, vesicles, seminal fl the inthe presence vasal ofsperm toidentify examination used Radiographic w/inthe uid &obstruction pathologies iehypospadia, penile Helps detect size testicular & normal ejaculate low volume, palpable vasa, inpatients w/azoospermia, ductobstruction ejaculatory todiagnose Used anatomic defects & other in the , sac, small scrotal upper examination of patients located better w/ testes Provides obstruction microlithiasis, testicular deferens aplasia, vas spermatoceles, tumors, physical examination ievaricoceles, pathologies during notcommonly scrotal seen Helps detect mass testicular inmaleinfertility, test w/suspected Mandatory those esp pathologies orpenile ofscrotal forthe detection Used extraction forspermatozoa upon ispositive azoospermia 50% ofmen w/non-obstructive sample isrecommended Obtaining >1biopsy techniques) reproductive (forassisted consideredMay w/the be intention forcryopreservation ofobtainingsperm to exclude w/spermatogenic failure those & ofhaving acquired ductobstruction seminal suspected azoospermia patients w/obstructive Helps identify diferentiavasa (CBAVD) ejaculation, outretrograde except congenital torule w/hypogonadism, forthose Done bilateral absence ofthe An ejaculate volumeof<1mLsignifi urinalysis forpost-ejaculatory thees need MRI & CT Scan may be considered in patients w/ hypogonadism suspected to be caused by atumor by caused tobe considered may inpatients be Scan suspected w/hypogonadism &CT MRI -

biopsy plus biopsy plus indications -azoospermia Absolute low semen volume, grades 0-2 motilitygrades semen volume, sperm low antibodies, sperm-bound biopsy, ontesticular butnormal Relative increased indications -severe

© MIMS 1palpable vas at least 2 Male Infertility(7of19) DIAGNOSIS (CONT’D) 3 complete &numerous spermatogenesis mature on EVALUATION B7

© MIMS 2019 (Synder PJ. Causes of primary hypogonadism in hypogonadism ofprimary (Synder PJ.Causes males. UpToDate.males. http://www.uptodate.com/ contents/causes-of-primary-hypogonadism-in- males?source=see_link. Jan 2016. Accessed 12Apr males?source=see_link. 2016) MALE INFERTILITY • • Dysfunction Sexual • • • • • Cryptorchidism • • • Varicocele • • • • • • Obstruction Anatomical • Post-Testicular Dysfunction • • Autoimmunity Semen Tract refertoUrinary Please Management Infection formoreinformation Chart Disease -Complicated • • • Infections Management formoreinformation Chart Disease refertoHypogonadism inPlease Males -Late-Onset • Hypogonadism Hypogonadotropic Idiopathic • DefiAndrogen ciency • • Origin) (Hypothalamic-Pituitary Hypogonadism Secondary May be caused by problems in ejaculation from spinal cord trauma/disease or autonomic disease problems by orautonomic inejaculation spinalcord disease from caused May trauma/disease be premature (, obstruction ejaculation, &mechanical diaphragm) , ejaculation, retrograde aesthenic ejaculation, anorgasmia, dysfunction, erectile Includes cancer fortesticular risk are at increased ofcryptorchidism Men w/history forinfertility FSH highrisk indicates level inhibinB&increased serum Low ofthe testes on the location duration depends ofsuprascrotal Severity Aff count sperm toimpaired resulting semen ielow parameters &quality malebabies, 2-5%ofnewborn ects or gene defects commonMost congenital regulation ofendocrine malegenital disruption by abnormality that caused may be through -visible the scrotum; III palpable Grade at rest - palpable w/oValsalva -notvisible; II Grade maneuver - palpable onlyw/Valsalva I-notvisible; Grade maneuver - detection ultrasound inDoppler palpation; positive upon notevident -notvisible; Subclinical - Classifi cation: Accompanied &hypogonadism ,malesubfertility failure, ipsilateral growth/development by testicular Valsalva of>0.3mmduring increase diameter maneuver enlargementAbnormal ordilatation ofthe veins inthe spermatic pampiniform plexusofthe scrotum w/a azoospermia inmenof infertility w/obstructive formation orpost-infectious fi either by cystic caused Ejaculatory ductobstruction, accounts for1-3% brosis, - repair orhernia deferens ofthe vasectomy isthe common vas after most ofacquiredObstruction cause obstruction accountsEpididymal azoospermia obstruction men for30-67%ofinfertile w/obstructive Accounts azoospermia for15%ofmen w/obstructive - in the seminiferous anobstruction tubules orw/inthe by testis rete caused mayIntratesticular be obstruction results evaluation endocrine &normal testes normal-sized men w/ oligozoospermic orseverely considered forazoospermic shouldbe Investigations forobstruction azoospermia obstructive may ducts cause seminal duct, ejaculatory deferens, vas epididymis, inthe ducts, testicular Obstruction Aff 15-20%ofmen w/ infertility ects mucus penetration motility&impaired sperm-cervical indecreased result antibodies Presence ofsperm Present men in 4-6%ofinfertile & orchitis may sterility cause ofmumps &history obstruction, &vas STDs) w/c may epididymal cause (iegonorrhea, genital infections Past genitalmay partial tractobstruction cause quality, sperm inthe ejaculate may decrease infl inleukocytes causing anincrease Chronic infections ammation through wherestructures semen passes &urethra &other ducts prostate, epididymal inthe testis, urogenital infection includes Male tractinfection axis hypothalamic-pituitary-gonadal inthe defects anatomical orfunctional w/oexisting even Presence testosterone/FSH/LH levels oflow Testicular feminisation causes &Reifenstein resistance syndrome ofthe at skull,hyperprolactinemia the base located fractures sella syndrome, emptyPrader Willi, , receptor orleptin leptin gonadotropin subunitmutation, craniopharyngioma, include Kallmann’s hypogonadism w/secondary Disorders associated DAX-1 syndrome, &GPR54mutations, ofdisease origin FSH issuggestive ofahypothalamic-pituitary &LH w/decreased level testosterone Low

© MIMSobstruction deferensCongenital bilateral (CBAVD) ofvas aplasia isthe common most deferens congenital ofvas cause 3 EVALUATION (CONT’D) EVALUATION Male Infertility(8of19) B8 © MIMS 2019 MALE INFERTILITY • • • Defects Genetic • • • Y-Chromosome Microdeletions • • • Abnormalities Chromosomal • • • • • • Cystic Gene Fibrosis Disorders Genetic • • Testicular Microlithiasis • • Malignancy • • • orAnejaculation ejaculation Delayed • • • Premature Ejaculation - Complete: female genitalia external syndrome) w/absent pubichair(Morris - work-up onlyupon formaleinfertility diagnosed Mild:asymptomatic; - severity presentation onits Clinical of patients depends w/androgen syndrome insensitivity patients presentKallman syndrome hypogonadism w/hypogonadotropic disorders &other x-linked mildandrogen syndrome, insensitivity Kallmansyndrome, genetic x-linked Includes disorders, Noonan’s myotonic dystrophy, syndrome, defi 5-a reductase ciency, etc include disorders infertility Prader-Willi disorders w/known Inherited Bardet-Biedl syndrome, syndrome, - deletions transmissiontomaleoff AZF isguaranteed spring - oligozoospermia orsevere azoospermia causes the common most type, AZFc deletions, -  especifi the effc deletion onthe ofthe determines longarm Ychromosome onspermatogenesis ect defi testicular as Increases increases ciency - Aff men oligozoospermic orseverely 16%azoospermic impaired spermatogenesis, men 5-7%ofinfertile w/severe ects paracenteric &marker chromosomes inversions, translocations, reciprocal translocations, common includeMost abnormalities Robertsonian chromosome autosomal hypogonadism common ofprimary cause Klinefelter’s accounts syndrome &therefore men abnormalities for2/3ofinfertile w/chromosomal the most Aff volumes sperm &1%men w/normal oligozoospermia, men, 5%men w/severe 10-15%azoospermic ects gene mutations forCFTR is positive &malepartner gene carrier defect considered ifthe be female isaCFTR shouldalso partner sequencing Gene bilateral gene diferentia absence abnormalities ofthe vasa butw/oCFTR forpatientsAdditional studies ofthe agenesis imaging issuggested renal &congenital w/unilateral system vasal oragenesis hypoplasia vesicle forseminal Patients w/this evaluated condition be shouldalso gene inthe adefect CFTR by Caused Patient semen volume&nonpalpable w/low usuallypresents vasa commonMost ofcongenital cause bilateral diferentia absence ofthe vasa (CBAVD) & atrophy, etc Klinefelter’s cysts, epididymal hypogonadism, syndrome, germ inmencell w/testicular seen torsion Commonly tumor, testicular dysgenesis, testicular cryptorchidism, <3mmindiameter measuring Intratesticular w/oshadowing hyperechogenic lesions cancer thefortesticular risk increases &dysgenic testis hypospadias, Cryptorchidism, may treatment occur after dysfunction &sexual Hypogonadism - cell dysfunction Leydig failure& Testicular duetospermatogenic w/cmay be todiagnosis, quality prior sperm low tumor may as manifest ejaculation w/ delayed hypothyroidismare & hyperprolactinemia all associated levels, testosterone low Hypogonadism, diffiDisturbance orinterpersonal distress marked causes alifelong oranacquired be culty &can problem activity Persistent excitement orrecurrent sexual delay sexual during anormal after in,orabsence phase of, diffi culty) consequences bother, negative personal (egCauses distress, avoidance frustration, & interpersonal intimacy of sexual Either present the from fi latency change bothersome inejaculatory anew experience orfollowing rst sexual inpatients 3minutesabout orless w/premature ejaculation or a significlinically penetration minutein 1 of vaginal to time, often in latency reduction cant & bothersome involuntarily stimulated controlled,Short, ejaculation that easily orw/ before always ornearly occurs always

perineal hypospadias, &cryptorchidism hypospadias, perineal w/micropenis, ormalephenotype genitalia, w/ambiguous female (Reifenstein phenotype Partial syndrome): © 2.5-8fold by for oligozoospermia Y-chromosome 1/2ofthe deletion removes genes inthe AZFcsignifi gr/gr region, thecantly risk increasing MIMS 3 EVALUATION (CONT’D) EVALUATION Male Infertility(9of19) B9 © MIMS 2019 MALE INFERTILITY • • Psychotherapy &Behavioral erapy • • Counselling Genetic • • • • • • Couple Counselling Counselling • • • • Supplements • OffDiscontinue &Exposures Medications ending • • • TemperatureControl ofBody • Caff Intake eine • • • WeightBody • • • Alcohol andSmoking ModifiLifestyle cations • - ofpsychotherapy inmen &couplesGoals suff are: dysfunction sexual from ering w/delayed those ejaculation esp &anorgasmia May help dysfunction men w/sexual there is50%chance parents ofthe Ifboth are off carriers, defect aclinical developing spring - their w/treatments couples child future ontheBrief might toproceeding risks incurprior Y-deletions maleoff by are inherited springs - techniques reproductive to treatments prior & diseases for couples w/ hereditary Recommended & those w/ genetic abnormalities - Timing intercourse ofsexual may help couples conceive ofintercourse) frequency , reduced the coupleInform that the onboth stress male&female may partner contribute problems tofertility (decreased  that ecouple addressed ofoptimism& despair shouldbe may experience cycles - treatments fertility are &after advised to,during, prior Counselling couples the about &cons pros Advise ofavailable treatments consultations during seen shouldbe partners Both &emotional effShould the address psychological oncouples ofinfertility &individually ects the toprove Further effi studiesare needed ofdiffcacy erent supplements formaleinfertility males rates insubfertile &livebirths May improve pregnancy thathave cited antioxidant intake may help ininfertility studies forw/cseveral tothe spermatogenesis, contributory may during stress Oxidative be Selenium, VitaminPentoxifylline, Vitamin Zinc) E, C, Q10,Kallikrein, Coenzyme &mineral Cinnoxicam, supplements vitamin (EgEg , antioxidants, anti- many &steroids antihypertensives, anti-arrhythmics, antipsychotics, Eg antidepressants, - Many common &occupational may hazards medications aff function malesexual ect Avoid temperature scrotal going tohotbaths increase w/ccan &saunas are more advisable Wearing underwear &loose boxer shorts temperature scrotal semenTight quality w/elevated &reduced are associated underwear  ere are inconsistent concerning evidences the eff ofconsumption ect ofcaff onfertility einated beverages & impaired thermoregulation scrotal Weight axis encouraged forpatients shouldbe esp loss w/alterations inthe hypothalamic-pituitary-testicular resistance toinsulin secondary levels, may toandrogen lead SHBG toestrogen conversion, decreased Men w/BMIof>30kg/mare infertile at ofbeing greater risk Excessive alcohol intake &smokingmay aff quality sperm ect encouraged ofsmokingshouldbe Cessation Alcohol consumption to3-4units/day limited shouldbe ejaculation dysfunction improving relationshipejaculation dysfunction concerns self-confi &sexual dence Psychotherapy off ers men, women &couples benefi address including the skills, developmentt, ofsexual -

broadening their sexual scripts, increasing sexual self-confi sexual increasing broadening their scripts, sexual dence anxiety & diminishingperformance Help skills that sexual men develop enable will them to delay ejaculation while an orgasm or achieve of infertility Vaginal thedays chances may 2-3 ofconception, increase onthe intercourse cause sexual depending every consequence for the ofthe orcouple man,partner symptom © that issues &interpersonal the may orbe have maintained Focus precipitated, psychological onresolving MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing A NON-PHARMACOLOGICAL THERAPY Male Infertility(10of19) B10 © MIMS 2019 MALE INFERTILITY • • Glucocorticoids Management formoreinformation Charts Disease refertoHyperprolactinemia Please • • • • Agonists Dopamine • • • Dapoxetine • • Antihistamines • • • Antidepressants • • • Antibiotics • • • • • • • Used for patients w/ sperm autoimmunity forpatientsUsed w/sperm Eg Prednisone &restoration shrinkage ofgonadal ofadenomas cause function May also inhibit prolactin secretion of action: ergotMechanism alkaloid that binds to & stimulates dopamine on receptors lactotroph cells to adenomas pituitary by caused tohyperprolactinemia forpatients secondary Used hypogonadism w/hypogonadotropic Cabergoline Eg Bromocriptine, satisfaction &increased distress, control, ejaculatory decreased & increased that have intercourse trials hrs before eff shown iftakenClinical 1-2 itwas the from fiective onIELTrst dose Studies that have shown Dapoxetine significantly timetoejaculation improved anon-demand oraltreatment as forpremature designed ejaculationPotent especially that SSRI been has ejaculation inmen w/retrograde ordelayed ejaculation used May be Eg Brompheniramine, Ephedrine Eff delaysectively ejaculation, w/eff ofdailytreatment start after days to2wks afew seen ects Treatment optionforpatients w/premature ejaculation Fluoxetine,Eg Imipramine,Paroxetine, Clomipramine,Desipramine, Sertraline control infl purposes ammation, forfertility parameters &improve sperm eradication aimstoreduceInfection the causative organisms contained inthe semen &prostatic secretions, intheir semen w/identifi forleukocytes formen positive used May be infection ed Norfl Erythromycin, Eg Doxycycline, oxacin, Trimethoprim instead used shouldbe &GnRH hMG) (hCG, Gonadotropins - treatmentwho are seeking forinfertility Testosterone replacement androgen as isnotrecommended replacement therapy formen w/hypogonadism orearlier stage cellcell at &Germ primary arrest onlysyndrome,  Sertoli microdeletions, Ychromosome treatment ere by are stillnoproven medical caused forinfertility dysfunction &sexual hypogonadism, Pharmacologic management w/hypogonadotropic applicable may ofmale infertility forpatients be diagnosed toinitiationprior &benefi risks ofthe possible Patients informed shouldbe treatments acquired that various from be ts can old female is>35yr partner ifthe especially established, been has diagnosis Treatment as soon as started shouldbe ofmaleinfertility oftreatment &fertility,Goals include function restoration ofsexual &toobtainmaintain virility techniques Treatment involves psychotherapy, management, medical treatment, surgical & different reproductive assisted © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing B PRINCIPLES OF MANAGEMENT PHARMACOLOGICAL THERAPY Male Infertility(11of19) B11 © MIMS 2019 MALE INFERTILITY • • • • Tamoxifene Raloxifene, citrate, Clomiphene • • Androgens TreatmentsEmpirical • • Tramadol • • • • • • (PO) Inhibitors Phosphodiesterase-5 • • • Anesthetics Local • • • • (GnRH) Hormone Gonadotropin-Releasing • • • Human (rhFSH) FSH Recombinant Human (hFSH), (hMG), FSH Gonadotropin Human Menopausal • • • (hCG) Human Gonadotropin Chorionic Gonadotropins couples Clomiphene given citrate therapy Studies signifi have shown concentration insperm conception ratescant in increases &motilityincreased ofFSH, &testosterone the LH secretion increasing thereby axis, ofestrogens inthe the hypothalamic-pituitary feedback negative ofaction:blocks Mechanism inmalepatientsinfertility the toprove Further effi studiesare needed ofClomiphene citrate &Tamoxifenecacy inthe management of forthe management used Have ofunexplained/idiopathic been infertility maturationsperm w/ the assumption that used Have may these been “rebound” cause spermatogenesis stimulation & epididymal Testosterone,Eg low-dose Mesterolone Delays ejaculation stimulation by ofthe inthe &serotonin m- receptors production CNS premature ejaculation ofTramadolOn-demand oraldoses comparable was toDapoxetine indelaying ejaculation inpatients w/ muscle &enhances smooth inthe cavernosa rigidity relaxation corpora penile Increases - 5,which isfoundinthe tissue penile type phosphodiesterase Works inhibits peripherally; stimulationSexual isstillrequired in patientsContraindicated takingnitrates ofpatientssubgroups (eg whohave men&those w/DM hadaprostatectomy) Have proven effi &inspecifi ofmen dysfunction populations w/erectile non-selected inboth &safety cacy c off (PDE5)inhibitorsshouldbe Oral phosphodiesterase-5 a1st-line as ered therapy dysfunction forerectile Eg Sildenafil, Tadalafi l, Udenafi l, Vardenafi l theofthis use treatment limits anesthetics sensation topical option duetoresidual vaginal Reduced ofthe glanspenis sensitivity agents help that studies have indelaying desensitizing the shown topical ejaculation reducing by Several Prilocaine Eg Lidocaine, FSH; &FSH stimulates inturn forspermatogenesis LH production production testosterone thereby inthe toreplace system, Used GnRH initiating & stimulation glandtoproduce LH ofthe pituitary disease hypothalamic dueto for men hypogonadism w/hypogonadotropic analternative optiontohCG as isused Pulsatile GnRH luliberlin gonadoliberin, (LH-RH), hormone hormone-releasing (FSH-RH), follicle-stimulating hormone luteinizing as hormone-releasing known Also Eg Gonadorelin Eff inmen hypogonadism w/hypogonadotropic production stimulatesectively sperm incombination stimulationUsed forspermatogenesis w/hCG containshMG acombination human from urine postmenopausal ofFSH derived &LH atreatment considered Also infertility as optionforunexplained - tostimulateUsed when w/ inmen given spermatogenesis hypogonadism w/hypogonadotropic treatment after may testis later reascend w/hCG inlife Descended toinduce descent testicular cryptorchidism totreat prepubertal Used © MIMS B Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing PHARMACOLOGICAL THERAPY (CONT’D) Male Infertility(12of19) B12 © MIMS 2019 MALE INFERTILITY • Procedures Other • • Vibrostimulation &Electroejaculation • • • • Testicular (TESE) Extraction Sperm • • Post-Orgasmic Urine • • TechniquesAspiration • Techniques Retrieval Sperm • • In (IVF) Vitro Fertilization • • • (IUI) Insemination Intrauterine • • • (ICSI) Injection Sperm Intracytoplasmic • • • failed w/ other assisted reproductive techniques reproductive w/other assisted failed Artifi whohave considered may infertility couples cial insemination by w/male-factor be w/donorsperm sperm ifvibrostimulation toretrieve fails isused Electroejaculation indelayed ejaculation ejaculation &retrograde used be May also - spinalcordlumbosacral segment Vibrostimulation isthe 1st-line therapy formen w/anejaculation duetospinalcord butw/intact  in patients w/intratesticular obstruction retrieval that eonlyprocedure sperm allows consideredMay formen be w/CBAVD & toeff used Procedure the orepididymis from testis sperm retrieve ectively spermatozoathe cryopreserved obtained Technique biopsy, testicular during ofICSI part w/ as ofchoice azoospermia forpatients w/non-obstructive considered treatmentMay ifw/spinalcord be &after failure injury inART use ejaculation inmen w/retrograde forpossible onthe sperm day ofovulation toretrieve Used consideredMay formen be w/CBAVD Testicular (TESA) Aspiration Sperm Eg (MESA),Percutaneous Epididymal Microsurgical Aspiration (PESA), Sperm Epididymal Aspiration Sperm reproduction the partner’s tofertilize assisted during &isused ova azoospermia men from w/obstructive isobtained Sperm abnormality w/autosomal Amniocentesis orpre-implantation diagnosed considered may ifpreviously genetic be diagnosis consideredMay forcouples be unable toconceive ejaculation duetoretrograde ormoderate oligospermia antibodies mucus-antisperm considered incouples be May w/cervical also consideredMay forcouples be unable toconceive ejaculation duetoretrograde ormildmaleinfertility toovulation into prior cavity the uterine sperm placementInvolves upper direct ofwashed motility, autoantibodies sperm positive morphology, wprogressive sperm <5%sperm <5%normal <2millionmotilesperm/ejaculate, Indications: azoospermia &non-obstructive , asthenospermia, Treatment autoimmunity, tosperm oligospermia, severe secondary optionformaleinfertility very ofanoocyte into the ofasinglesperm cytoplasm injection Involves direct consideredShould treatments forcouples be radical w/persistent despite infertility tubules the from seminiferous extracted forsperm butpositive insemen analysis forpatients w/azoospermia used May be &azoospermia oligospermia Techniques w/moderate-severe incouples w/the diagnosed malepartner toinitiate pregnancy used © MIMS C ASSISTED REPRODUCTIVE TECHNIQUES Male Infertility(13of19) B13 © MIMS 2019 MALE INFERTILITY • Semen • • • Failed Fertilization • • • Surgery After • • • • • • • • Orchidopexy/ • • (TURED) Ducts oftheEjaculatory Transurethral Resection • Sclerotherapy • • • Varicocelectomy • • • • obstruction forepididymal recommended Procedures • • A process thatA process semen stores at subzero temperatures (-196 IVF considered may failed ICSI after be interaction including inthe other sperm- defects reassessed, shouldbe binding&penetration ofsperm Examination fails of oocyte fertilization Refer after the couple toaspecialist removal genital after tractobstruction or other spermatogenic defects autoimmunity, sperm persistent obstruction, forpossible Patient examined post-operative should be atrophy, occurs 3mth oruntil surgery pregnancy after every isrequired Semen analysis forpatients whounderwent ismandatory Annual ultrasound inpatients isrecommended w/KlinefelterAnnual syndrome follow-up partner ofinfertility, include duration factors &etiology Prognostic fi semen analysis offemale &assessment ndings, obstruction proximal vasa inpatients isrequired w/post-vasectomy reversal vasectomy Microsurgical vasectomy inmen orICSI w/previous than MESAw/IVF results better Produces vasectomy toreverse ofthe vas Involves reanastomoses Treatment w/inthe fi spermatogenesis inbetter ofliferesults rst 2yr men Studies that have azoospermic shown successfully this induce can procedure inpreviously spermatogenesis &children adults inboth testis totreat undescended Surgical used procedure the orunroof cyst incise to used may be intraoperative ultrasound transrectal For duetointraprostatic obstructions midlinecysts, forlargeUsed post-infl emptying into &ducts anintraprostatic obstruction midlinecyst ammatory sclerotherapy &retrograde Antegrade considered may forpatients be w/varicocele w/ confi post-procedure rate of35-44%1yr pregnancy rmed Studies signifi have shown varicocelectomy, much 60-80%after as cant as improvements by analysis insperm improve &semen quality, spermatogenesis cell &enhance function Leydig damage damage, & androgen function testicular prevent DNA further defi sperm ableMay to reverse be ciency, infertility of>2 infertility forpatientsConsidered w/varicocele w/oligozoospermia, duration, orunexplained yr obstruction forepididymal ispreferred intussusception Microsurgical tubulovasectomy - reconstruction Microsurgical &cryopreservation aspiration sperm explorationScrotal epididymal w/microsurgical Tubulovastomy Vasectomy reversal offers restoration ofpatency that studies have management shown as surgical considered azoospermia, Should inmen be w/obstructive of spermatogenesis inmen hypogonadism of spermatogenesis w/hypogonadotropic thatprocedures may aff fertility, induction & after ect quality due to a chronic sperm illness, men w/ decreasing offShould be patients undergoing cancer topatientsered retrieval, treatment undergoing orsperm or biopsy © MIMS Male Infertility(14of19) E D FOLLOW-UP SURGERY B14 o C) tointerrupt cellC) metabolism © MIMS 2019 MALE INFERTILITY Mesterolone 100 mg PO 24hrly 100mgPO Mesterolone enantate Testosterone undecanoate Testosterone Drug Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non- women, women, &non-breastfeeding non-pregnant for are recommendations dosage All x 90days 8-12hrly 25 mgPO or 3-6 wk 250 mgIMevery dose: Maintenance 2-3 wk 250 mgIMevery © at 6wks) interval (1stinj 10-14 wks 1000 mgIMevery or 24 hrly 40-120 mgPO MIMS dose: Maintenance 24 hrly x2-3wk 120-160 mgPO dose: Initial Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not ANDROGENS &RELATED SYNTHETICDRUGS Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Guidelines Male Infertility(15of19) • • • • Instructions Special • Reactions Adverse • • • • Instructions Special • Reactions Adverse • • • Instructions Special • Reactions Adverse intra-abdominal hemorrhage monitorforliver tumors, prostate isadvised; exam Regular Use w/caution inpatients w/liver tumors liveror existing tumors previous in patientsContraindicated w/prostatic carcinoma, occurs Reduce ordiscontinue iffrequent orpersistent dose Frequent orpersistent erection increasing physical ability increasing forenhancing muscular development orfor used Not be polycythemia therapyin patients whoare todetect inlong-term the examine prostate theRegularly &check Hb&hematocrit apnea sleep &preexisting toedema predisposed those skeletal metastases, HTN, epilepsy, or DM migraine, disease), ischemic heart Use w/caution inpatients impairment w/cardiac (including patients w/androgens treated therapy, starting Before exclude prostatic inolder carcinoma ,precocious gynecomastia) , formation, asthenia, bone closure, increased epiphyseal disorder, system circulatory hypercalcemia, premature eff liver tumor, (benign/malignant ects polycythemia, libido, water retention, Other abnormal spermatogenesis); effGenitourinary PSA;increased/decreased (increased ects jaundice, liver enlargement, intra-abdominal hemorrhage); male pattern GIeff baldness); abnormal LFTs, (nausea, ects effDermatological pruritus, urticaria, rash, (acne,alopecia, ects effCNS (depression, anxiety,ects paresthesia); , Monitor skeletal maturation, &Hbregularly hematocrit skeletal metastases hypernephroma, prostatic hypertrophy, orbronchial carcinoma, mammary renal orhepatic impairment, HTN, epilepsy, benign migraine, Use w/ caution inpatients w/latent failure, cardiac orovert hypercalcemia w/malignant tumors carcinoma, prostatic & inpatientsContraindicated w/suspected wt) increased HTN, polycythemia, retention inthe tissues, Other eff irritation); hematoma, erythema, fl (, ects uid PSA);Inj (pruritus, sitereactions increased prostatic growth, formation, gynecomastia, sperm , disturbed desire, eff disturbances); Genitourinary mood (changes insexual ects LFTs/cholesterol eff CNS levels); (depression, nervousness, ects effDermatological acne);GIeff (pruritus, ects (changes in ects B15 Remarks © MIMS 2019 MALE INFERTILITY Udenafi l Tadalafi l Sildenafi l Dysfunction onErectile Used Drugs Apomorphine 2 mg sublingually 20min 2mgsublingually Apomorphine Agonist Dopamine Drug DRUGS FORERECTILEDYSFUNCTION &EJACULATORY DISORDERS Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed 200 mg/dose 1dose/day, dose: Max reactions adverse &tolerance to response onpatient 200 mgbased to dose May increase activity sexual to 30min-12hrprior PO 100mg &elderly: Adults 20 mg/dose 1dose/day, dose: Max response ontheir own based Patient may adjust timing intercoursesexual to 30min-36hrprior PO 20mg &elderly: Adults 100 mg/dose 1dose/day, dose: Max response onpatient 25 mgbased to 100 mgordecrease to dose May increase intercourse tosexual 1 hrprior 25mgPO impairment: orrenal hepatic (>65 yr), forelderly dose Initial intercourse tosexual prior 1hr 50mgPO dose: Initial doses Minimum of8hrbetween 2 mg/dose impairment: renal Severe response onpatientdepending to3mg dose May increase activity tosexual prior & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Dosage Guidelines Male Infertility(16of19) • • • • • • • • Instructions Special • Reactions Adverse • • • • Instructions Special • Reactions Adverse immediately if erection lasts >4hr immediately lasts iferection assistance medical toseek Patient informed should be ulcerproblems oractivepeptic uncontrolled 6months, bleeding w/inthe DM, last CABG BP, patients w/cerebral hemorrhage/infarction, stroke, MI, impaired autonomic orw/severely controlobstruction of w/ caution inpatients ventricular outfl w/left ow Use failure). heart severe (eg unstable angina, disease CV Udenafi inpatientsl: Contraindicated whohave underlying hepatic impairmentsevere recent stroke orMI,patients w/impaired renal function, hypotension, severe disorders, CV patients w/severe in Contraindicated mild-moderate hepatic failure. Tadalafi safeinpatients appears w/ l: 10mgdose recent stroke orMI,degenerative disorders retinal hypotension, hepatic impairment, severe severe disorders, Sildenafi CV inpatientsl: Contraindicated w/severe patients deformities w/penile sickle topriapism cell eg anemia, in patients predisposed factors, risk Use w/caution inpatients CV w/preexisting inhibitors phosphodiesterase of may doses require theDiabetics max Coadministration w/nitrates iscontraindicated eff tobe stimulationSexual fordrugs isrequired ective congestion, priapism nasal (eg transient color altered dizziness, vision), flHeadache, disturbances visual stomach upset, ushing, recent stroke orMI hypotension, renal orhepatic impairment, severe severe disorders, CV in patientsContraindicated w/severe patients deformities w/penile sickle topriapism cell eg anemia, in patients predisposed inpatientshypotension), w/renal orhepatic impairment, includingantihypertensives nitrates (may cause uncontrolled patients w/ treated hypertension, being factors, risk Use w/caution inpatients CV w/preexisting tablet under the tongue Patient smallamt shoulddrink ofwater dissolving before eff ective stimulation tobe Sexual forApomorphine isrequired somnolence rhinitis, N/V, yawning, dizziness, headache, B16 Remarks © MIMS 2019 MALE INFERTILITY Dapoxetine Urologicals Other Vardenafi l (cont’d) Dysfunction onErectile Used Drugs Drug DRUGS FORERECTILEDYSFUNCTION &EJACULATORY DISORDERS(CONT’D) Max dose: 60mg/day dose: Max activity sexual to 1-3hrprior PO needed, as 30mg, Adult 18-64yr: 20 mg/dose 1dose/day, dose: Max on patient response to5mgbased or decrease to20mg dose May increase activity tosexual 25-60 minprior 10mgPO &elderly: Adults Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Dosage Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Dosage Guidelines Male Infertility(17of19) • • • • • Instructions Special • Reactions Adverse • • • • • • Instructions Special • Reactions Adverse  ofsuicidal thinking risk &suicidality ere isanincreased Maintaining adequate hydration isadvised men w/outpremature ejaculation atreatmentShould notbe ofejaculation-delaying eff in ects inhibitors CYP3A4 w/serotonerigc effmedicinal/herbal products potent ects, orother TCAs SNRIs, serotonin inhibitors, reuptake thioridazine, concomitantly used Should notbe w/MAOIs, ofsyncope history hepatic impairment; moderate &severe disease; or valvular permanent pacemaker, signifi disease cant ischemic heart w/a nottreated conduction abnormalities, conditions, in patientsContraindicated w/pathologic cardiac orthostatic hypotension syncope, , insomnia, diarrhea, nausea, dizziness, Headache, >4hr immediately lasts iferection assistance medical toseek Patient informed shouldbe °enerativeangina disorders retinal recent hypotension, stroke severe orMI,unstable dialysis, renal hepatic failure, requiring patients failure w/severe Ritonavir, in Contraindicated Indinavir &Erythromycin. Itraconazole, Ketoconazole, 3A4inhibitors; CYP450 inpatient’s adjustment isnecessary Dose takingpotent patients deformities w/penile sickle topriapism cell eg anemia, in patients predisposed factors, risk Use w/caution inpatients CV w/preexisting inhibitors ofphosphodiesterase may doses require theDiabetics max Coadministration w/nitrates iscontraindicated eff tobe stimulationSexual fordrugs isrequired ective congestion, priapism nasal (eg transient color altered dizziness, vision), flHeadache, disturbances visual stomach upset, ushing, B17 Remarks © MIMS 2019 MALE INFERTILITY 1 extract Bulgaricum L. Tribulus terrestris Bromocriptine Selenium extract) ali, EIJ extract (Tongkat Jack longifolia Eurycoma Combination w/ other supplements is available. Please see theCombination forspecifi w/other latest MIMS supplements see isavailable. Please information. c prescribing Drug Drug 1 Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly TROPHIC &RELATED SYNTHETICDRUGS All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All 250-500 mg PO 8hrly x90days 250-500 mgPO stimulation: Spermatogenesis 8hrly x30-40days PO 250-500 mg dysfunction: Erectile 8 hrly Hormone defi 250mgPO ciency: g PO 24hrly 200 µgPO © MIMS 2-3 days8-12 hrly after to2.5mgPO dose May increase 20mg/day PO dose: Max bedtime at 1.25-2.5mgPO dose: Initial hypogonadism: Male day PO 200-300mg/ Spermatogenesis: defi ciency: Hypogonadism/Hormone Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing SUPPLEMENTS &ADJUVANT THERAPY 200-400 mg/day PO Dosage Dosage Dosage Guidelines Male Infertility(18of19) B18 • Instructions Special • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse Should be taken w/ food or after meals orafter taken w/food Should be Should be taken w/food Should be irritability,GI discomfort, headache acromegaly ulcer, phenomenon, peptic angina, , disorder, psychiatric of dementia, Raynaud’s malignancy, hepatic/renal impairment, history Use w/ caution inpatients w/breast disorder psychiatric ofserious ofhistory symptoms disease, valve conditions heart including CAD, CV inpatientsContraindicated w/severe libido, , compulsive spending) Other eff (impulse control inc ects disorders, eff pleural (dyspnea; pulmonary); usion; pleural, agitation, tinnitus);psychomotor Pulmoeff ects hallucination, dyskinesia, confusion, dizziness, drowsiness, headache, paresthesia, eff CNS hypertension); (seizures, ects eff valvulopathy, arrhythmia, usion; pericarditis, firetroperitoneal eff CV brosis); (pericardial ects GI eff (pain,hemorrhage, ulcer,ects mouth, dry moreConsume water whileontherapy taken w/food Should be warmth body Increased Remarks Remarks © MIMS 2019 MALE INFERTILITY Clomiphene citrate 50 mg PO 50mgPO Clomiphene citrate human FSH) (Recombinant Follitropin α (Recombinant FSH) Follitropin β gonadotropin (hCG) Human chorionic gonadotropin, hMG) menopausal (human Drug TROPHIC HORMONES&RELATED SYNTHETICDRUGS(CONT’D) Products listed above may not be mentioned in the disease management chart but have been been have but chart management disease the in mentioned be not may above listed Products placed here based on indications listed in regional manufacturers’ product information. product manufacturers’ regional in listed indications on based here placed & non-elderly adults w/ normal renal & hepatic function unless otherwise stated. otherwise unless function &hepatic renal w/ normal adults & non-elderly All dosage recommendations are for non-pregnant & non-breastfeeding women, women, &non-breastfeeding non-pregnant for are recommendations dosage All © MIMS 24 hrly x 40-90 days hCG concomitantly w/ Administered mth 4 150 IU SC3x/wkx hypogonadism: Hypogonadotropic hCG concomitantly w/ Administered x3-4mthIU/dose of150 doses divided 450 IU/wkSCin3 3000 IU/wkIM/SC spermatogenesis: ofdeficases cient selected in Sterility 2-3 x/wk 500-1000 IUIM/SC hypogonadism: Hypogonadotropic 3x/wk IM/SC 75-150 IULH 75-150 IUFSH + Not all products are available or approved for above use in all countries. all in use above for approved or available are products all Not Specifi c prescribing information may be found in the latest MIMS. latest the in found be may information Specific prescribing Please see the end of this section for the reference list. reference the for section this of end the see Please Dosage Dosage Guidelines Male Infertility(19of19) • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse • • Instructions Special • Reactions Adverse • Instructions Special • • Reactions Adverse depression, thrombophlebitisdepression, mental preexisting tumors, hormone-dependent Use w/caution inpatients w/liver dysfunction, neoplasia in patientsContraindicated w/liver diseases, N/V, fatigue) Other effinsomnia); weight gain, , (breast ects effPsychological tension, (depression, nervous ects lightheadedness), dizziness, convulsions, disturbances, effCNS ects visual (headache, ofvision, blurring malformation, thromboembolic events malformation, thromboembolic congenital , system reproductive defiadrenocortical ciency, hyperprolactinemia, hypothyroidism, Use w/caution inpatients w/porphyria, tumor,hypothalamic gonadal failure primary in patientsContraindicated w/breast/testis/pituitary/ headache) gain, wt site reactions, GI eff Other eff pain,N/V); abdominal (lower ects (inj ects Use w/ caution in patients w/ elevated FSHUse w/caution inpatients levels w/elevated tumor,hypothalamic gonadal failure primary in patientsContraindicated w/breast/testis/pituitary/ site induration); Other eff (gynecomastia) ects effDermatologic inj cyst, epididymal (acne,rashes, ects migraine epilepsy, hypertension, renalfailure, dysfunction, Use w/ caution inpatients w/latent cardiac orovert androgen-dependent tumours orsuspected inpatientsContraindicated w/known Other eff (flects uid &saltretention, gynecomastia) effDermatologic inj sitereactions); (acne,rashes, ects normalization treatment hCG Administered after & testosterone Ab formation use: Long-term hydrothorax) Other eff , reactions, (hypersensitivity oliguria, ects eff CV reactions); thromboembolism); (hypotension, ects GI eff (N/V,ects eff Dermatologic ascites); (inj site ects B19 Remarks © MIMS 2019

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