Transcript Male Reproductive Issues

Male
Reproductive
Issues
RICHARD E. FREEMAN MD MPH
2013
LOCK HAVEN UNIVERSITY
SPERMATOGENESIS
SPERMATOGENESIS
INFERTILITY
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DEFINITION: Inability to conceive a child
WHO
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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
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a woman under 35 has not conceived after 12 months of contraceptive-free intercourse
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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
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History
DETAILED SEXUAL HISTORY
 DETAILED PREGNANCY HISTORY
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Medical History
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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
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History - Drugs
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Influence Reproductive cycle and male
hormone
– anabolic steroids, cimetidine, and
spironolactone
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Sperm Motility
– sulfasalazine and nitrofurantoin
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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
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Physical Exam
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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
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LABS
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FSH, LH
DHT
TSH
ACTH
GH
Post coital
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DFI
 Anti sperm
antibodies
 SPA (semen
penetration assay)
Special Tests
Vasography
 Testicular biopsy
 Ultrasound – color flow
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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
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MALE INFERTILITY:
CLASSIFICATION
PRE-TESTICULAR
 TESTICULAR
 POST-TESTICULAR
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PRE-TESTICULAR CAUSES OF
INFERTILITY:secondary testicular failure
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Hypothalamic disease
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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
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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
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– Hyper and hypothyroidism
Hyperprolactinemia
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ETIOLOGY:
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medications, stress, pituitary adenoma
S/S:
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Dx: Screening-- low yield
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erectile dysfunction
low testosterone
decreased libido
Prolactin level MRI –sella tursica
TX:
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Surgical excession of pituitary tumor
(adenoma)
Cabergoline(Dostinex)
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dopamine 2 receptor agonist
TESTICULAR CAUSES: GENETICS
Primary Testicular failure
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Y Chromosomal abnormalities (Klinefelter's syndrome,
XX disorder (sex reversal syndrome), XYY syndrome)
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Noonan's syndrome (male Turner's syndrome)
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Myotonic dystrophy
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Bilateral anorchia (vanishing testes syndrome)
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Sertoli-cell-only syndrome (germinal cell aplasia)
TESTICULAR CAUSES:
Primary Testicular failure
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VARICOCELE
Gonadotoxins (drugs, radiation)
Orchitis
Trauma
Systemic disease
– (renal failure, hepatic disease, sickle cell
disease)
Defective androgen synthesis or action
 Cryptorchidism
 IDIOPATHIC-Majority
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VARICOCELE
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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
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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
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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
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POST-TESTICULAR CAUSES OF INFERTILITY:
SPERM MOTILITY
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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
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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
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Age…>46
Pollution
Smoking
Febrile illness
Drugs
Radiation
Chemicals
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Testicular cancer
 Varicocele
 Prolonged heat:
– Hot tubs
– Truck drivers
– Cyclists
AZOOSPERMIA
Obstructive – 40%
TRUS=Transrectal ultrasound
INFERTILITY Treatment
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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:
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• - Clomiphene, Tamoxifen
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Aromatase inhibitors:
• – Testolactone /Anastrozole
– aromatase converts testosterone to estradiol
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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…
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Hypogonadism
Male climacteric
Viropause
ADAM (androgen decline in aging males)
Andropause
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By age 80, testosterone levels are
around pre-pubertal levels!
Physical Symptoms
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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
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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).
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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.
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Low T2 in men may cause…
Angina
 Atherosclerosis
 High blood cholesterol
 High blood triglycerides
 High blood pressure.
 High body mass index (obesity).
 Osteoporosis
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Labs
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DHEA Sulfate
Dihydrotesterone(DHT)
Estradiol
LH
IGF-1
Testosterone, Total &
Free
Total Testosterone
Free Testosterone
%Free
Thyroid Panel
Free T3
Free T4
TSH
 PSA
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Treatment
Viagra, Levitra, Cialis
 Testosterone replacement therapy TRT
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– Side Effects:
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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
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QUESTIONS ?????
SOURCE:
 Wein: Campbell-Walsh Urology 10th ed
 Chapter 21 Male infertility
 2011 Saunders
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Can be accessed on MD Consult