Male infertilityMale infertilityWork up and Work up and

Management overviewManagement overview

Dr. Anmar Nassir, FRCS(C)Dr. Anmar Nassir, FRCS(C)

Canadian board in General UrologyCanadian board in General Urology

Fellowship in Andrology Fellowship in Andrology (U of Ottawa)(U of Ottawa)

Fellowship in EndoUrology and Laparoscopy Fellowship in EndoUrology and Laparoscopy (McMaster Univ)(McMaster Univ)

Assisstent Prof Assisstent Prof Umm Al-QuraUmm Al-Qura

Consultant Urology Consultant Urology KFSH & RC KFSH & RC

8-15% 8-15% of couplesof couples

Male = 50% Male = 50%

Pituitary-Pituitary-Gonadal AxisGonadal Axis

LH & FSHLH & FSH

LHLH Activate testicular T production from Leydig cellsActivate testicular T production from Leydig cells Feed back inhibition by testosteroneFeed back inhibition by testosterone

FSHFSH Stimulate Sertoli cells & spermatogonial membranesStimulate Sertoli cells & spermatogonial membranes The major stimulator of seminiferous tubule growth The major stimulator of seminiferous tubule growth

during developmentduring development Feed back inhibition by inhibin from Sertoli cellsFeed back inhibition by inhibin from Sertoli cells

Testosterone will initiate and maintain Testosterone will initiate and maintain spermatogenesisspermatogenesis

Sperm fertility maturation, achieved at the Sperm fertility maturation, achieved at the level of the distal corpus or proximal cauda level of the distal corpus or proximal cauda epididymis.epididymis.

PhysiologyPhysiology

Epididymis:Epididymis: MaturationMaturation TransportTransport StorageStorage

Vas:Vas: Transfer of spermTransfer of sperm

Seminal vesicles Seminal vesicles (The main bulk of the ejaculate):(The main bulk of the ejaculate): Secretory products: e.g. Secretory products: e.g.

fructose, prostaglandin, clotting factorsfructose, prostaglandin, clotting factors EjaculationEjaculation Coagulation of semenCoagulation of semen

Prostate:Prostate: LiquifactionLiquifaction Zn: antibacterial & sperm stabilizationZn: antibacterial & sperm stabilization

The scrotal temperature is is 2°C to 4°C The scrotal temperature is is 2°C to 4°C below rectal temperature due to counter-below rectal temperature due to counter-current mechanismcurrent mechanism

Anatomical PhysiologyAnatomical PhysiologyEpididymis:Epididymis:

MaturationMaturation TransportTransport StorageStorage

Vas:Vas: Transfer of spermTransfer of sperm

Seminal vesicles Seminal vesicles

(The main bulk of the ejaculate):(The main bulk of the ejaculate): Secretory products: e.g. Secretory products: e.g.

fructose, fructose,

prostaglandin, prostaglandin,

clotting factorsclotting factors EjaculationEjaculation Coagulation of semenCoagulation of semen

Prostate:Prostate: LiquifactionLiquifaction Zn: antibacterial & sperm Zn: antibacterial & sperm

stabilizationstabilizationSeminal vesicles 1.5 to 2.0 mL.

Prostate 0.5 mL, Cowper's glands 0.1 to 0.2 mL,

Evaluation ofEvaluation ofInfertile patientInfertile patient

Abnormalities in the woman are involved Abnormalities in the woman are involved in approximately 75% of infertile couples. in approximately 75% of infertile couples. 30% Ovulatory disorders 30% Ovulatory disorders 25% fallopian tube abnormalities 25% fallopian tube abnormalities 4% endometriosis 4% endometriosis 4% cervical mucus abnormalities 4% cervical mucus abnormalities 4% hyperprolactinemia 4% hyperprolactinemia

Conception rates drop more rapidly in the Conception rates drop more rapidly in the 35- to 39-year-old age group.35- to 39-year-old age group.

Many of the genes that affect male Many of the genes that affect male reproduction, including the androgen reproduction, including the androgen receptor gene, are located on the X receptor gene, are located on the X chromosome. chromosome.

Therefore, family history should focus on Therefore, family history should focus on the phenotype of the maternal uncles the phenotype of the maternal uncles

Impairing SpermatogenesisImpairing Spermatogenesis

Medications:Medications: nitrofurantoin , nitrofurantoin , cimetidine , cimetidine , sulfasalazine , sulfasalazine , Anabolic steroid Anabolic steroid

Substances:Substances: cocaine cocaine marijuanamarijuana NicotineNicotine pesticides pesticides

Infertility History

Physical Exam

Laboratory AssessmentLaboratory Assessment

Semen analysis X2Semen analysis X2 Quantitation of leukocytes in semen Quantitation of leukocytes in semen

Lab: Baseline, gluc. , U/ALab: Baseline, gluc. , U/A

Hormonal assay FSH, LH, Prol, TSH, Hormonal assay FSH, LH, Prol, TSH,

Antisperm antibodies: semen or bloodAntisperm antibodies: semen or blood

Advanced sperm fertility testsAdvanced sperm fertility tests

SemenSemen

The WHO (1999) defines the following reference The WHO (1999) defines the following reference values:values:

Volume: 2.0 ml or more

pH: 7.2 or more

Sperm concentration: 20 × 106  or more sperm/ml

Total sperm number: 40 × 106  or more spermatozoa per ejaculate

Motility: 50% or more with grade A + B motility

or 25% or more with grade A motility

Morphology: 30 %

15 % or more by strict criteria

Viability: 75% or more of sperm viable

White blood cells: Less than 1 million/ml

Hormonal EvaluationHormonal Evaluation

Diagnostic StudiesDiagnostic Studies

TRUSTRUS

US scrotumUS scrotum

Testicular biopsyTesticular biopsy

AsthenospermiaAsthenospermia Pretesticular Testicular PosttesticularPretesticular Testicular Posttesticular

Endocrine Varicocele AntispermantibodiesEndocrine Varicocele Antispermantibodies

Environment InfectionEnvironment Infection

Febrile illness Partial ductal obst.Febrile illness Partial ductal obst.

Intrinsic defectIntrinsic defect

VaricoceleVaricocele 15% of the population15% of the population 35% of male with 1ry infertility35% of male with 1ry infertility 75% of male with 2ry infertility75% of male with 2ry infertility 40% bilateral40% bilateral Varicocele repair:Varicocele repair:

75% improvement of semen75% improvement of semen 35% initiate pregnancy35% initiate pregnancy

Semen 3cc, 10m/cc, 34% motile, 29% normal morphology and 0.9(10x6) WBC.

On scrotal exam : bag of worms

VaricoceleVaricocele

Semen samples from infertile men with Semen samples from infertile men with varicoceles have demonstrated varicoceles have demonstrated decreased motility in 90% of patients decreased motility in 90% of patients and sperm concentrations less than 20 and sperm concentrations less than 20 million sperm/mL in 65%million sperm/mL in 65% of patients.of patients.

Improvement in seminal parameters is Improvement in seminal parameters is demonstrated in approximately 70% of demonstrated in approximately 70% of patients after surgical varicocele repair.patients after surgical varicocele repair.

Improvements in motility are most common, Improvements in motility are most common, occurring in 70% of patients, with improved occurring in 70% of patients, with improved sperm densities in 51% and improved sperm densities in 51% and improved morphology in 44% of patients. morphology in 44% of patients.

Conception rates have averaged 33% to 50%Conception rates have averaged 33% to 50% compared with 16% in the control group compared with 16% in the control group

TreatmentTreatmentSurgical:Surgical: InguinalInguinal RetroperitonialRetroperitonial Microscopic sub inguinalMicroscopic sub inguinal

LaparoscopicLaparoscopic

Percutaneous venous occlusionPercutaneous venous occlusion

PyospermiaPyospermia

Round cells: WBCs and immature germ cells.Round cells: WBCs and immature germ cells. Semen CultureSemen Culture

ED ObstructionED Obstruction

TRUS Dilated Ej Duct.TRUS Dilated Ej Duct. TUREDTURED

Semen: 0.9cc, 0.2m/cc,20% motile and negative post void sperm.

Causes of Obstructive AzospermiaCauses of Obstructive Azospermia

*

*CBAVD = congenital bilateral absence of the vas deference

.

Testicular BiopsyTesticular Biopsy

Diagnostic:Diagnostic: Obstruction Obstruction vs vs Sertoli Cell-only Sertoli Cell-only vs vs maturation arrestmaturation arrest

Therapeutic: Therapeutic: Harvesting sperms for ICSIHarvesting sperms for ICSI

Indications for ICSIIndications for ICSI

Immunological infertilityImmunological infertility

Severe oligoasthenospermia Severe oligoasthenospermia

Obstruction azospermiaObstruction azospermia

Nonobstruction azospermiaNonobstruction azospermia

Anejaculation ?Anejaculation ?

pregnancy rate 30 - 60%pregnancy rate 30 - 60% Live delivery / initial ICSI cycle 20-40% Live delivery / initial ICSI cycle 20-40%

Risk of Congenital Anomalies with Risk of Congenital Anomalies with ICSIICSI

1.8% congenital anomalies1.8% congenital anomalies

Miscarriage and congenital anomalies are Miscarriage and congenital anomalies are same for ICSI and IVFsame for ICSI and IVF

Genetic EvaluationGenetic EvaluationCF geneCF gene

Karyotyping abnormalityKaryotyping abnormality

Y-chromosome microdeletionY-chromosome microdeletion