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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

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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


FSH, LH

DHT

TSH

ACTH

GH

Post coital

DFI

Anti sperm antibodies

SPA (semen penetration assay)

LABS


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

  • Teratozoospermia

  • Azoospermia

  • Aspermia

  • Normal ejaculate

  • Sperm concentration >20 million/ml

  • <50% spermatozoa with forward progression

  • <30% spermatozoa with normal morphology

  • 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:

      • erectile dysfunction

      • low testosterone

      • decreased libido

  • Dx: Screening-- low yield

    • Prolactin level MRI –sella tursica

  • TX:

    • Surgical excession of pituitary tumor (adenoma)

    • Cabergoline(Dostinex)

      • dopamine 2 receptor agonist


  • TESTICULAR CAUSES: GENETICSPrimary 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!


    Age…>46

    Pollution

    Smoking

    Febrile illness

    Drugs

    Radiation

    Chemicals

    Testicular cancer

    Varicocele

    Prolonged heat:

    Hot tubs

    Truck drivers

    Cyclists

    Causes of DFI


    AZOOSPERMIA

    Obstructive – 40%

    TRUS=Transrectalultrasound


    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

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    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


    DHEA SulfateDihydrotesterone(DHT)EstradiolLHIGF-1Testosterone, Total & Free          Total Testosterone          Free Testosterone%Free

    Thyroid Panel           Free T3          Free T4          TSH

    PSA

    Labs


    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


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