2223 MD210 Topic 2.pptx

Q and A Male Factor Infertility Topic Two Plan Erectile Dysfunction Could mpf inhibition act as a potential target for developing contraceptives? • The specificity of Meiosis to gamete production means that factors involved in the control of this process offer a good target for contraception •...

Q and A Male Factor Infertility Topic Two Plan Erectile Dysfunction Could mpf inhibition act as a potential target for developing contraceptives? • The specificity of Meiosis to gamete production means that factors involved in the control of this process offer a good target for contraception • Therefore the inhibition of MPF activation could offer a target to prevent oocyte maturation and ovulation • Question – What enzyme/second messenger/signal molecule along the activation pathway would be target? What is the function of anti-mullerian hormone? In Males – • Produced by seroli cells following testicular differentiation in the fetus • Regression of Müllerian ducts (uterus and fallopian tubes) In Females – • Produced by ovarian granulosa cells • Involved in follicular recruitment, selection and growth • Serum AMH levels used clinically to assess ovarian function • Serum highest at puberty (many large follicles) - negligible by menopause • Serum AMH levels are predictive of ovarian reserve that will respond to hormonal treatment in IVF Q and A Male Factor Infertility Topic Two Plan Erectile Dysfunction Male Factor Infertility A 35-year-old man, whose partner is a 32-year-old woman, presents with difficulty to conceive for 1 year. What is the male diagnostic workup? Male Factor Infertility Male Factor Infertility History Physical exam Semen Analysis Focused Male Fertility History • Infertility history: duration, primary or secondary, • Primary infertility - a pregnancy has never been achieved by a person • Secondary infertility – at least one prior pregnancy has been achieved • Sexual function and activity • General health: Diabetes A schematic diagram illustrating a hypothetical model of the impact of diabetes mellitus (DM)-caused metabolic disorder and insulin abnormality on male sexual and reproductive dysfunction. ZUBIN HE et al. In Vivo 2021;35:2503-2511 Focused Male Fertility History • Illness/infection, genitourinary, testicular, or Scrotal or Pelvic Trauma • Any surgery of reproductive tract including testicular • Cancer • Hydrocelectomy • A hydrocele is a collection of fluid in the scrotum. • Spermatocelectomy, • A spermatocele - abnormal cyst that develops in epididymis • Vasectomy • Varicocelectomy • Focused male fertility history • Medication use: • steroid therapy, • antibiotic use, • chemotherapy, • narcotics • • • • Environmental exposures: pesticides, exposure of testicles to heat Drug and alcohol use Review of any genetic abnormalities and infertility History noted in family Male Factor Infertility Male Factor Infertility History Physical exam Semen Analysis Focused Male Fertility Physical Examination • Virilization state, Body habitus, Gynecomastia • Scrotal examination: • Presence of varicocele, Vas deferens, Testicle and Epididymis Development • Abdominal examination • Inguinal scars (possible cryptorchidism repair or inguinal hernia repair) other abdominal scars, radiation tattoo markers • Special circumstances e.g. sense of smell (Kallmann syndrome) • Genetic Disorder – Hypo-gonadotrophic, Hypo-gonadism, Hyposmia Male Factor Infertility Male Factor Infertility History Physical exam Semen Analysis Terminology • Aspermia: No semen ejaculated • Hematospermia: Blood present in semen • Leucocytospermia: White blood cells present in semen • Azospermia: No spermatozoa found in semen • Normospermia: Normal semen parameters • Oligospermia: Low sperm concentration • Asthenospermia: Poor motility and/or forward progression • Teratospermia: Reduced % of morphologically normal sperm • Necrospermia: No live sperm in semen BACKGROUND What is semen, exactly? Mixture of seminal plasma and cells • Seminal plasma contains: • Prostatic fluid (~30% of the volume) • Epididymal fluid (~5% of the volume) • Seminal vesicle fluid (the remainder of the ejaculate) • The cells are: • Spermatozoa • Leukocytes of various types, Bacteria, Epithelial cells Reference Ranges • Volume • pH 2.0-6.0 ml (1.5) 7.2-8.0 • Count >100 million/ml (15) • Motility > 40% (30) • Viability > 75% (56%) • WBC < 1million/ml • Morphology >30% (4) • RBC none SEMEN ANALYSIS Semen biochemistry • Seminal Vesicle • Fructose Marker for seminal vesicle function - Energy source • Prostaglandins • Alkaline Sperm motility, Egg activation?, Immunity? Neutralize acidic prostate secretion, Female tract • Ascorbic acid Anti oxidant, Protection against ROS • Semenogelin Coagulation of sperm after ejaculation Protection of sperm, Inhibits motility Rapidly cleaved by prostatic protease prostate-specific antigen SEMEN ANALYSIS Semen biochemistry • Epididymis • Neutral  -Glucosidase Marker for epididymal function. NAG in patients with oligospermia May reflect partial obstruction of the epididymis Associated with infections or inflammatory disease • CD52 Seminal glycoprotein incorporated into sperm membrane Major maturation-associated sperm membrane antigen • Glycogen • Free L-Carnitine Functional Maturation and Motility • Glycerophosphocholine Positively associated with Sperm Number Inhibit Capacitation Until Fertilisation Low SEMEN ANALYSIS • Prostate Secretions • Calcium • Zinc Semen biochemistry Motility, Capability for fertilisation Inhibits the enzyme responsible for oxidation of citrate increasing citrate concentration Studies have reported that zinc is markedly decreased (~60–80%) in prostate cancer • Citrate Calcium ion buffer major regulator of ionized calcium concentration in seminal plasma Levels reduced in Prostate Cancer • Prostatic specific acid phosphatase (PSAP) • Albumin • Prostatic specific antigen (PSA) Cleavage of Semenogelin marker for prostatic function increased in prostate cancer Protein Produced by prostate epithelial cells Biomarker for Prostate Cancer (>4ng/ml) SEMEN ANALYSIS • pH is important because sperm die at pH < 6.9 • The normal pH range is 7.2–8.4 • Inflammatory disorders of the accessory glands can take the pH outside of this range Spermatozoa Motility Motility assessment – differential motility • Differential motility classified based on distance swum over time: –Rapid progressive: > 25 µm/s –Slow progressive: 5 – 25 µm/s –Non-progressive: < 5 µm/s –Immotile: no flagellar movement Sperm Motility • Semen analysis • Cornerstone of assessment • Can have a single functional defect not detected by basic methods • Specialized semen tests to evaluate specific aspects of sperm function • SCD • Sperm Chromatin Dispersion • Tunel • Terminal deoxynucleotidyl transferase dUTP nick end labeling • Sperm Chromatin Structure Assay • Single Cell Electrophoresis Assay Hemizone Assay Antisperm Antibodies Male Factor Infertility Topic Two Plan Erectile Dysfunction Erectile Dysfunction • ED is highly age-dependent • 5%-10% < 40yrs, 40 22% at age 40, 49% by age 70 • Major risk factors are • DM, CVD, Hypertension, Decreased HDL levels • Increased by • Medications for - DM, hypertension, CVD and depression • Post radiation or surgery for prostate cancer, • Lower spinal cord injury • Neurological diseases (e.g. Parkinson’s disease, multiple sclerosis) • Life style factors – Smoking, alcohol consumption and sedentary behavior Delivery of Sperm to the female tract - Erection • Parasympathetic Reflex • Arterioles Dilate • Smooth Muscle relaxation via Nitric Oxide • Penis Engorged with Blood • Expansion Compresses the Veins • Slows Blood Leaving Penis • Reflex is Initiated by a Sensory Stimuli Physiological Basis of Erectile Dysfunction Treatment with Viagra Delivery of Sperm to the female tract-Ejaculation Spinal Reflex is Initiated Sympathetic Discharge to the Genital Organs Reproductive Ducts/Accessory Glands Contract Peristaltically Discharging their Contents into the Urethra Bulbocarvenous muscle at the Base of the Penis Rapid series of Contractions Propelling Semen From the Urethra Physiological Basis of Erectile Dysfunction Treatment with Viagra • Penile Erection • ACH  NO cGMP • cGMP Causes Smooth Muscle Relaxation • Relaxation of Arterioles   Blood Flow to Penis • Normally cGMP is Degraded by Phosphodiesterase 5 • Terminates its Action • Action of Viagra • Inhibits the PDE5 therefore cGMP breakdown • Prolonged Arteriolar Dilatation • Prolonged Erection