Male infertility Work up and Management overview Dr. Anmar Nassir, FRCS(C) Canadian board in General Urology Fellowship in Andrology (U of Ottawa) Fellowship in EndoUrology and Laparoscopy (McMaster Univ) Assisstent Prof Umm Al-Qura Consultant Urology KFSH & RC

8-15% of couples Male = 50%

Pituitary-Gonadal Axis

LH & FSH LH Activate testicular T production from Leydig cells Feed back inhibition by testosterone FSH Stimulate Sertoli cells & spermatogonial membranes The major stimulator of seminiferous tubule growth during development Feed back inhibition by inhibin from Sertoli cells

Testosterone will initiate and maintain spermatogenesis Sperm fertility maturation, achieved at the level of the distal corpus or proximal cauda epididymis.

Physiology Epididymis: Vas: Seminal vesicles Prostate: Maturation Transport Storage Vas: Transfer of sperm Seminal vesicles (The main bulk of the ejaculate): Secretory products: e.g. fructose, prostaglandin, clotting factors Ejaculation Coagulation of semen Prostate: Liquifaction Zn: antibacterial & sperm stabilization

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

Anatomical Physiology Epididymis: Maturation Transport Storage Vas: Transfer of sperm Seminal vesicles (The main bulk of the ejaculate): Secretory products: e.g. fructose, prostaglandin, clotting factors Ejaculation Coagulation of semen Prostate: Liquifaction Zn: antibacterial & sperm stabilization Seminal vesicles  1.5 to 2.0 mL. Prostate  0.5 mL, Cowper's glands  0.1 to 0.2 mL,

Evaluation of Infertile patient

Abnormalities in the woman are involved in approximately 75% of infertile couples. 30% Ovulatory disorders 25% fallopian tube abnormalities 4% endometriosis 4% cervical mucus abnormalities 4% hyperprolactinemia Conception rates drop more rapidly in the 35- to 39-year-old age group.

Many of the genes that affect male reproduction, including the androgen receptor gene, are located on the X chromosome. Therefore, family history should focus on the phenotype of the maternal uncles

Impairing Spermatogenesis Medications: nitrofurantoin , cimetidine , sulfasalazine , Anabolic steroid Substances: cocaine marijuana Nicotine pesticides

Infertility History

Physical Exam

Laboratory Assessment Semen analysis X2 Quantitation of leukocytes in semen Lab: Baseline, gluc. , U/A Hormonal assay FSH, LH, Prol, TSH, Antisperm antibodies: semen or blood Advanced sperm fertility tests

Semen The WHO (1999) defines the following reference 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 Evaluation

Diagnostic Studies TRUS US scrotum Testicular biopsy

Asthenospermia Pretesticular Testicular Posttesticular Endocrine Varicocele Antispermantibodies Environment Infection Febrile illness Partial ductal obst. Intrinsic defect

Varicocele 15% of the population 35% of male with 1ry infertility Semen 3cc, 10m/cc, 34% motile, 29% normal morphology and 0.9(10x6) WBC. On scrotal exam : bag of worms Varicocele 15% of the population 35% of male with 1ry infertility 75% of male with 2ry infertility 40% bilateral Varicocele repair: 75% improvement of semen 35% initiate pregnancy

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

Improvement in seminal parameters is demonstrated in approximately 70% of patients after surgical varicocele repair. Improvements in motility are most common, occurring in 70% of patients, with improved sperm densities in 51% and improved morphology in 44% of patients. Conception rates have averaged 33% to 50% compared with 16% in the control group

Treatment Surgical: Inguinal Retroperitonial Microscopic sub inguinal Laparoscopic Percutaneous venous occlusion

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

ED Obstruction TRUS Dilated Ej Duct. TURED Semen: 0.9cc, 0.2m/cc,20% motile and negative post void sperm. ED Obstruction TRUS Dilated Ej Duct. TURED

Causes of Obstructive Azospermia *CBAVD = congenital bilateral absence of the vas deference . Causes of Obstructive Azospermia *

Testicular Biopsy Diagnostic: Therapeutic: Harvesting sperms for ICSI Obstruction vs Sertoli Cell-only maturation arrest Therapeutic: Harvesting sperms for ICSI

Indications for ICSI Immunological infertility Severe oligoasthenospermia Obstruction azospermia Nonobstruction azospermia Anejaculation ? pregnancy rate 30 - 60% Live delivery / initial ICSI cycle 20-40%

Risk of Congenital Anomalies with ICSI Miscarriage and congenital anomalies are same for ICSI and IVF

Genetic Evaluation CF gene Karyotyping abnormality Y-chromosome microdeletion