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 ejaculateMale should be abstinent for 48 to 72 hours

sperm concentration > 20 million per mltotal count > 60 million/SAMPLEejaculate volume > 1.5 mltotal motile count > 30 millionviable sperm > 50%normal shapes (morphology) > 60%

Sperm TermsNormozoospermiaNormal ejaculate

AsthenozoospermiaIatrogenic/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 ejaculateNo ejaculate

MALE INFERTILITY:CLASSIFICATION PRE-TESTICULAR TESTICULAR POST-TESTICULAR

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

PRE-TESTICULAR CAUSES OF INFERTILITY: secondary testicular failure

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)

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 INFERTILITYSPERM TRANSPORT

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

TRUS=Transrectal ultrasound

Obstructive – 40%

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.shtml

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 SulfateDihydrotesterone(DHT)EstradiolLHIGF-1Testosterone, 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