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Male Reproductive Issues RICHARD E. FREEMAN MD MPH 2013 LOCK HAVEN UNIVERSITY SPERMATOGENESIS SPERMATOGENESIS INFERTILITY DEFINITION: Inability to conceive a child WHO – A couple may be considered infertile if, after two years of regular sexual intercourse, without contraception, the woman has not become pregnant (and there is no other reason, such as breastfeeding or postpartum amenorrhea) USA – a woman under 35 has not conceived after 12 months of contraceptive-free intercourse – a woman over 35 has not conceived after 6 months of contraceptive-free intercourse. Primary infertility is infertility in a couple who have never had a child. Secondary infertility is failure to conceive following a previous pregnancy. GENERAL ~ 10% couples are affected by infertility ~40% are from male factors! ~30% of the 40% male factors…cause is unknown History DETAILED SEXUAL HISTORY DETAILED PREGNANCY HISTORY Medical History Childhood illnesses – post pubertal mumps orchitis and testicular trauma or torsion Cancer chemotherapy/radiation – destroys germinal epithelium-dose dependent Diabetic neuropathy – may result in either retrograde ejaculation or impotence DES exposure – epididymal cysts or cryptochordism Precocious puberty – adrenal-genital syndrome • Congenital adrenal hyperplasia Delayed puberty – Klinefelter's syndrome or idiopathic hypogonadism History Hernia repair Cystic fibrosis (CBAVD) Mumps Thyroid disease Prolactinoma History - Drugs Influence Reproductive cycle and male hormone – anabolic steroids, cimetidine, and spironolactone Sperm Motility – sulfasalazine and nitrofurantoin Decrease count and hormone interference – Illicit drugs and alcohol (Liver failure) – Seizure meds… FSH SOCIAL HISTORY Occupational and environmental toxins, Excessive heat-iron foundry worker Radiation- x-ray tech Illicit drug use Physical Exam Look for HYPOGONADISM! – poorly developed secondary sexual characteristics – eunuchoidal skeletal proportions • Arm span longer than height • Crown to pubis:Pubis to floor ratio <1 – sparse male hair distribution – infantile genitalia – muscle mass & development Physical Exam Hypogonadism may be associated with: – anosmia- inability to smell – color blindness, – cerebellar ataxia, hair lip, and cleft palate. (Kallmann syndrome-isolated gonadotropin – FSH/LH – deficiency with anosmia) Thyroid Liver Neuro GU prostate exam LABS FSH, LH DHT TSH ACTH GH Post coital DFI Anti sperm antibodies SPA (semen penetration assay) Special Tests Vasography Testicular biopsy Ultrasound – color flow Sperm Count Fresh sample (to lab within 30 mins.) –most sperm in initial ejaculate Male should be abstinent for 48 to 72 hours sperm concentration > 20 million per ml total count > 60 million/SAMPLE ejaculate volume > 1.5 ml total motile count > 30 million viable sperm > 50% normal shapes (morphology) > 60% Sperm Terms Normozoospermia Normal ejaculate Asthenozoospermia Iatrogenic/abstinence Varioceles, cilia anomalies, Anti-spm Ab Normal ejaculate Sperm concentration >20 million/ml <50% spermatozoa with forward progression <30% spermatozoa with normal morphology Teratozoospermia Azoospermia Aspermia No spermatozoa in the ejaculate No ejaculate MALE INFERTILITY: CLASSIFICATION PRE-TESTICULAR TESTICULAR POST-TESTICULAR PRE-TESTICULAR CAUSES OF INFERTILITY:secondary testicular failure Hypothalamic disease HYPOGONADROTROPIC HYPOGONADISM – Isolated gonadotropin deficiency (Kallmann's syndrome) – Isolated LH deficiency • ("Fertile eunuch") – Isolated FSH deficiency – Congenital hypogonadrotropic syndromes PRE-TESTICULAR CAUSES OF INFERTILITY: secondary testicular failure Pituitary disease – Pituitary insufficiency • (tumors, infiltrative processes, operation, radiation) – Hemochromatosis – EXOGENOUS HORMONES – Estrogen excess – Androgen excess – Glucocorticoid excess – Hyperprolactinemia – Hyper and hypothyroidism ENDOCRINE CAUSES – EXOGENOUS HORMONES – Estrogen excess: – Inhibits GnRH » also direct effects on spermatogenesis – Low FSH/LH/Testosterone • ETIOLOGY – Hepatic disease – estrogen secreting tumor OBESITY – Androgen excess: – Direct feedback inhibition on the hypothalmus – Low intratesticular testosterone (necessary for spermatogenesis – Endogenous-congenital adrenal hyperplasia, tumors – Exogenous – anabolic steroids – Glucocorticoid excess – – Hyper and hypothyroidism Hyperprolactinemia ETIOLOGY: medications, stress, pituitary adenoma S/S: Dx: Screening-- low yield erectile dysfunction low testosterone decreased libido Prolactin level MRI –sella tursica TX: Surgical excession of pituitary tumor (adenoma) Cabergoline(Dostinex) dopamine 2 receptor agonist TESTICULAR CAUSES: GENETICS Primary Testicular failure Y Chromosomal abnormalities (Klinefelter's syndrome, XX disorder (sex reversal syndrome), XYY syndrome) Noonan's syndrome (male Turner's syndrome) Myotonic dystrophy Bilateral anorchia (vanishing testes syndrome) Sertoli-cell-only syndrome (germinal cell aplasia) TESTICULAR CAUSES: Primary Testicular failure VARICOCELE Gonadotoxins (drugs, radiation) Orchitis Trauma Systemic disease – (renal failure, hepatic disease, sickle cell disease) Defective androgen synthesis or action Cryptorchidism IDIOPATHIC-Majority VARICOCELE Most common Attributable cause of Primary and secondary infertility in males- 40% Left sided – -right angled insertion of L testicular vein into the L renal vein- less valves – Theories – Temperature elevation – Reflux of toxic renal and adrenal metabolites – Gonadotoxin metabolite clearance impairment Treatment: LIGATION – improves sperm count and semen quality INDICATIONS – – – – – – Palpable varicocele on exam known infertility Female partner has normal fertility Male- abnormal semen parameters +- discomfort ADOLESCENT MALE: Testicular hypotrophy (20% discrepancy in size) POST-TESTICULAR CAUSES OF INFERTILITY SPERM TRANSPORT Disorders of sperm transport – Congenital disorders• Congenital Bilateral absence of the Vas deferens (CBAVD) • - Cystic Fibrosis- CF transmembrane conductance regulator test – Acquired disorders – Functional disorders POST-TESTICULAR CAUSES OF INFERTILITY: SPERM MOTILITY Disorders of sperm motility or function – Congenital defects of the sperm tail • Primary Ciliary Dyskinesia (PCD) effects other organs with cilia – Maturation defects • Globozoospermia – – “round-headed sperm syndrome” – No acrosin-no penetration of zona pellucida • Fibrous Sheath Dysplasia– “stump tail syndrome” – short coiled immotile tails (genetic counseling suggested) – Immunologic disorders– Infection SPERM DNA FRAGMENTATION If greater than 30% have a DNA fragmentation index (DFI): – Reduced fertility potential – Reduction in term pregnancies – Doubling in miscarriages – “Normal” (morphology and motility) sperm may have DNA fragmentation! Causes of DFI Age…>46 Pollution Smoking Febrile illness Drugs Radiation Chemicals Testicular cancer Varicocele Prolonged heat: – Hot tubs – Truck drivers – Cyclists AZOOSPERMIA Obstructive – 40% TRUS=Transrectal ultrasound INFERTILITY Treatment Find the cause!!!! PESA/MESA – microsurgical epididymal sperm aspiration TESE – testicular sperm extraction IVF– invitro fertilization AIDS – –artificial insemination by donor TUREJD – -Transurethral resection of the ejaculatory ducts INFERTILITY MEDICATIONS Gonadotropin-Releasing hormone agonists Gonadotropins- LH FSH Anti-estrogens: • - Clomiphene, Tamoxifen Aromatase inhibitors: • – Testolactone /Anastrozole – aromatase converts testosterone to estradiol Antioxidants – -L-carnitine, Kallikrein, Thyroid Male Menopause Male Menopause - Andropause Occurs between 45-60 and is a gradual decline over the years 1/10 will experience hot flashes Also called… – – – – Hypogonadism Male climacteric Viropause ADAM (androgen decline in aging males) Andropause By age 80, testosterone levels are around pre-pubertal levels! Physical Symptoms Taking longer to recover from injuries and illness. Less endurance for physical activity. Feeling fat and gaining weight. Difficulty reading small print. Loss or thinning of hair. Sleep disturbances and fatigue. "Sore body syndrome" - stiffness. Excessive sweating. Cold hands and feet. Itching. Psychological Symptoms Irritability. Indecisiveness. Anxiety and fear. Depression. Loss of self-confidence and joy. Loss of purpose and direction in life. Feeling lonely, unattractive and unloved. Forgetfulness and difficulty concentrating. Sexual Symptoms Reduced interest in sex. Increased anxiety and fear about losing sexual potency. Increased fantasies about having sex with a new and younger partner. More relationship problems and fights over sex, love and intimacy. Loss of erection during sexual activity (impotence). Sexual Symptoms cont’d There is less of an urge to ejaculate. The force of ejaculation is not as strong as it once was. The amount of the ejaculate is less and one may have fewer sperm. The testicles shrink and the scrotal sack droops. The sack does not bunch up as much during arousal. Low T2 in men may cause… Angina Atherosclerosis High blood cholesterol High blood triglycerides High blood pressure. High body mass index (obesity). Osteoporosis Labs DHEA Sulfate Dihydrotesterone(DHT) Estradiol LH IGF-1 Testosterone, Total & Free Total Testosterone Free Testosterone %Free Thyroid Panel Free T3 Free T4 TSH PSA Treatment Viagra, Levitra, Cialis Testosterone replacement therapy TRT – Side Effects: • • • • • • • Increase cholesterol Increase blood pressure Growth of body hair Male-pattern baldness Acne Fluid retention aggression TRT – Cont’d Monthly injections Patch - scrotum Implants q 4 mos QUESTIONS ????? SOURCE: Wein: Campbell-Walsh Urology 10th ed Chapter 21 Male infertility 2011 Saunders Can be accessed on MD Consult