11/16- Evaluation of Male Infertility Flashcards
Describe basic male anatomy and sperm transport
- Seminiferous tubules within the testis
- Sperm made in testicle, stored in epididymus
- Travel through vas deferens, through prostate into urethra
What is seen here?
Spermatogenesis occurring in seminiferous tubule
Describe the process of spermatogenesis
- Spermatogonia (46chrom)
- (mitosis)
- Primary spermatocytes
- (meiosis)
- Secondary spermatocytes (2)
- (divides)
- Spermatids (4)
- Develop flagella to become mature sperm cells with 23 chromosomes
What is the vas deferens?
- Function
- Tubular structure, 30 cm
- Connects tail of the epididymis to the ejaculatory ducts
- Muscular; contraction with ejaculation propels sperm forward into posterior urethra
What are the seminal vesicles?
- Function
- Paired structures behind prostate and under bladder, 6cm in length
- Joins up with vas deferens to form the ejaculatory ducts
- Produces 70% of ejaculatory volume- alkaline fluid rich in fructose; pH 7.4-7.8
What are the ejaculatory ducts?
- Function
- Paired structures; form confluence of seminal vesicles and vas deferens
- Travel through prostate and exit at verumontanum
- Prevent reflux of fluid back into vas and seminal vesicle
Describe the male hypothalamic pituitary gonadal axis
- GnRH causes release of FSH and LH
- FSH stimulates Sertoli cells
- Produce inhibin to shut down anterior pituitary
- LH stimulates Leydig cells
- Produce testosterone to shut down anterior pituitary and hypothalamus
- Exogenous testosterone shuts down FSH and LH production (how testosterone is a male contraceptive)
What is the definition of male infertility?
Inability to conceive via unprotected natural intercourse over 12 months
- (12 months is the time it takes 90-95% of normal, fertile couples to conceive)
What is the most common cause of male infertility?
Varicocele: enlargement of venous drainage of pampiniform plexus (draining the testis)
Is male or female infertility more common?
- Female (50%)
- Male (30%)
- Combined (20%)
What are the etiologies of male infertility?
- Varicocele (35%)
- Idiopathic (25%)
- Infection of GU tract (10%)
- Genetic (10%)
- Endocrine
- Immunologic
- Obstruction
- Developmental
- Lifestyle: smoking, diet, heat…
What are the grades of a varicocele?
- Palpable with valsalva
- Palpable without valsalva
- Visible at rest
How does a varicocele contribute to infertility?
What else could it cause?
Varicocele causes increased temperature of the testicle (pooling of blood)
Can lead to:
- Testicular atrophy
- Decreased sperm counts
Which side is a varicocele more common on? Why?
Left - Vein crosses L renal vein??
What provides arterial supply for the testis? Sources of the arteries?
- Aorta -> Gonadal -> Testicular
- Internal iliac -> Inferior vesical -> Deferential
- External iliac -> Inferior epigastric -> Cremasteric
What provides venous drainage of the testis? Destination?
Internal spermatic -> IVC / Left renal vein
Deferential -> Superior vesical v. -> Hypogastric v.
External spermatic (cremasteric) -> Pudendal v. -> Saphenous v.
What is the epididymis?
- Where is it
- Connections
- Function
- Posterolateral to testis
- Connected to testicle by efferent ducts
- 3 parts:
- head (caput)
- body (corpus)
- tail (cauda)
- Central role in sperm maturation (mobility and fertilizing capacity)
What is seen here?
Epididymitis- inflammation of epididymis
Describe prostatitis
- Acute or chronic
- Symptoms
- Cause
- Treatment
- Acute or chronic
- Symptoms: asymptomatic to severe irritative / systemic symptoms
- Cause: Bacterial or Non-bacterial
- Treatment:
- antibiotics
- anti-inflammatories
- warm baths
- pelvic floor relaxation
What are some genetic causes of abnormal sperm development?
- Klinefelters (XXY)
- Y chromosome microdeletions
- Prune belly Sx
- Kartageners syndrome
What are some endocrine causes of pre-testicular failure?
Hypothalamic:
- Congenital
- Kallman’s syndrome
Primary pituitary problem
- Pituitary adenoma
Describe Kallman’s syndrome
- Inheritance pattern
- Gene mutation involved
- Other symptoms
- X linked
- Deletion of KAL-1 gene
- Anosmia, no GnRH production
Describe pituitary adenoma
- Other symptom
- Lab values
- Visual field changes, headache
- Elevated prolactin -> prolactinoma
Where could obstruction occur to cause infertility?
- Examples
- Seminiferous tubules (adrenal rests)
- Epididymis (previous surgery, infection
- Vas deferens (vasectomy, congenital absence of vas deferens)
- Ejaculatory duct (prostatic cyst, stones, stenosis)
What is seen here?
Vasogram ?
What is CBAVD?
- Associations
Congenital bilateral absence of the vas deferens
- Congenital absence of all or part of vas deferens and epididymis
Associated with cystic fibrosis
- Almost all patients with CF have CBAVD
- Most patients with CBAVD are at least carriers of CFTR mutations
What is a spermatocele?
- Cystic fluid collection connected to epididymis
- Contains dead sperm
What is seen here?
Transrectal US (TRUS)
- Left: ejaculatory duct stones
- Right: seminal vesicle dilation
What congenital structural problems may involve abnormal sperm development?
- Cryptorchidism (undescended testicles)
- Neonatal testicular torsion
What are some gonadotoxins?
Chemicals:
- Pesticide
- Solvents
Recreational drugs:
- Excessive alcohol
- Anabolic steroids (exogenous testosterone shuts down HPA axis)
- Cocaine
- Marijuana
- Tobacco
What are some meds which can affect male fertility?
- Testosterone
- Nitrofurantoin
- Sulfasalazine
- Cimetidine
- Cyclosporine
- Colchicine
What should the history focus on in male fertility?
- Duration of infertility
- Previous pregnancies
- Health of partner
- Medical illnesses, previous surgeries
- Medications (legal and illicit)
- Family history
In cryptorchidism, what factors contribute to male infertility?
Decrease in sperm production and semen quality (regardless of the timing or orchidopexy)
In hypospadias, what factors contribute to male infertility?
May not place the semen at the cervical os
- (Incomplete closure of meatus at development)
In past surgeries, what factors contribute to male infertility?
The vasal deferential or testicular blood supply may be injured or ligated at the time of inguinal surgery, hernia repair, hydrocelectomy, or varicocelectomy
How does testicular torsion/trauma contribute to male infertility?
You can form antisperm antibodies
What should be evaluated during physical exam?
- General appearance
- Axillary, pubic hair
- Testis volume, consistency
- Epididymidal induration
- Varicocele
- Penile exam
- Digital rectal exam
What should be assume about a solid testis mass?
Cancer until proven otherwise!
Describe considerations with testicular cancer
- Affects on fertility
- What type of tumors
Increased risk with history of infertility and/or undescended testicle
- 90-95% germ cells tumors (seminona and non-seminomatous)
- Others Leydig and Sertoli cell
What is seen here?
Testicular cancer (seminoma)
What is a hydrocele?
Collection of fluid between parietal and visceral layers of tunica vaginalis
- Result of trauma, inflammation, irritation, patent processus vaginalis…
- Can light it up and ensure testis is posterior to the collection
What is seen here?
Hydrocele
T/F: Once you form antisperm antibodies, your chances at fertility are shot
False; not great, but can try other things (meds, intrauterine insemination…)
Testicular torsion is a true surgical emergency. Why?
- Irreversible ischemic injury to the testicular parenchyma after 4 hours (from when pain starts)
- Likelihood of testicular salvage ↓ as duration of torsion↑
Describe the pain of testicular torsion
- Sudden onset of severe pain
- Typically 1 testicle
Which of these shows testicular torsion?
Torsion is on right picture
- No flow inside the testicle
How often should semen analysis be done on someone complaining of male infertility?
- What is seen
- What to do if no sperm?
- What to do if ejaculate vol under 1 mL
Perform at least twice (parameters are highly variable)
- If no sperm, “pellet” inspected after sample centrifugation
- If ejaculate vol under 1 mL (as in retrograde ejaculation with diabetic pts), postejaculatory urine should be examined
What are the normals for the following parameters of semen analysis?
- Volume
- Concentration
- Motility
- Morphology
- Round cells
- Semen pH
- Volume: 1.5 - 5mL
- Concentration: > 15 million sperm/mL
- Motility: > 40%
- Morphology: > 4% normal forms
- Round cells: < 1 million/mL
- Semen pH: 7.2 - 7.8
These numbers are based on the 5th %ile
What can semen analysis tell you? Not tell you?
Semen analysis can only tell you if they are absolutely infertile (no sperm at all) but cannot tell if you if they are fertile (some people with low sperm count can get pregnant and high cannot)
What is the definition of: oligospermia?
Sperm concentration < 15 million/mL
What is the definition of: asthenozoospermia?
< 40% motile spermatozoa
What is the definition of: teratozoospermia?
< 4% spermatozoa with normal morphology
What is the definition of: azoospermia?
Lack of sperm in ejaculate
- Absolutely infertile
What is the definition of: aspermia?
Lack of ejaculate or sperm in the ejaculate
What is the definition of: cryptospermia?
Sperm found only in centrifuged pellet
- No sperm in ejaculate when just looking in microscope
- Only seen when concentrated in pellet (they’re “hiding”)
What is the definition of: necrospermia?
All sperm dead
What can round cell be in ejaculate?
- Immature sperm
- WBCs
Case 1)
- 28 year old male with a history of subfertility, no other medical history, no prior pregnancies
Semen analysis:
- Oligospermia
- Volume 3cc
- Concentration: 12 million sperm / ml
- Motility: 30%
- Morphology: 50% normal forms by WHO criteria
What should be done/next steps?
- Physical exam
- In this case, found large left varicocele on left
- Repeat semen analysis
- In this case, showed higher concentration of sperm, worse morphology, and almost normal motility
- Fix varicocele
What are the sexual response areas of the brain?
What neurochemicals are involved?
Hypothalamus:
- Medial preoptic nucleus
- Paraventricular nucleus
Neurochemicals
- Norepinephrine, serotonin: inhibit libido, erectile response, ability to climax
- SSRIs increase serotonin/NE and cause sexual dysfunction!
- Anorgasmia is most common symptom
- Dopamine: promotes the above
Describe the neuroanatomy of:
- Erectile response pathway
- Detumescence pathway
- Ejaculation
Erectile response pathway: S2-S4 PS -> corpora cavernosa
Detumescence pathway: T10-L3 S (spinal cord) -> superior hypogastric plexus -> corpora cavernosa
Ejaculation: T10-L3 S
- Nerves at risk from retroperitoneal/aortic surgery
Describe the functions of the following components of penile anatomy:
- Corpora cavernosa
- Tunica albuginea
- Smooth muscle
- Ischiocavernosus
- Bulbocavernosus
- Corpus spongiosum
- Glans
- Corpora cavernosa: support corpus spongiosum and glans
- Tunica albuginea: promotes rigidity of corpora cavernosa, participates in veno-occlusion
- Smooth muscle: regulates blood flow
- Ischiocavernosus: pumps blood to hasten erection, provides additional rigidity during erection
- Bulbocavernosus: compresses bulb to expel semen
- Corpus spongiosum: pressurizes / constricts urethral lumen to permit forceful expulsion of semen; becomes the glans
- Glans: cushions penile impact on the female, sensory input for pleasure, facilitates intromission (cone shape)
Describe the arterial supply of the penis
Describe the venous drainage of the penis
Sinusoidal venules -> subtunical venous plexus -> emissary veins -> deep dorsal vein -> DVC/internal pudendal
___ (PS/S) tone predominates in the flaccid state
Sympathetic tone predominates in the flaccid state
Describe the physioanatomy of an erection
- Blood flow increases 20-40x through cavernosal arteries
- Cavernosal smooth muscle relaxes
- Increased intracavernosal pressure -> blood trapping via compression of venules perforating tunica albuginea
Note:
- Parallel cAMP-based system present
- Inhibit BOTH via non-specific PDE5i (papaverine)
Describe the physioanatomy of ejaculation
- Separate event from erection!
- Thus, can occur in the ABSENCE of erection!
- Consists of seminal emission -> expulsion
Sensory input: glans (S2-S4)
- Periurethral muscle contraction
Sympathetic input (T10-L3)
- Vas deferens contraction
- SV, prostate contraction
- Bladder neck contraction -> bulbocavernosus/spongiosus contraction -> projectile ejaculation
What is the definition of erectile dysfunction (ED)?
The consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity
Describe the epidemiology of ED
- Prevalence
- More common in what group?
- __% physical, __% psychological
- 1/5 men
- >30 million American men
- More common in older men
- 90% physical, 10% psychological
What are broad causes of ED (4)? Examples?
Organic
- Vascular (arterial insufficiency or venous leak)
- Endocrine
- Neurologic
- Trauma
Iatrogenic
- Prior surgery (prostate, retroperitoneal)
- Meds
Anatomic
- Peyronie’s disease
- Phimosis
Psychogenic
- Marital conflicts
- Guilt
- Performance anxiety
What are current treatment options for ED?
- Medical (hormonal): Androgens
- Sildenafil (Viagra)
- Now also: Vardenafil (Levitra), Tadalafil (Cialis), Avanafil (Stendra)
- ICI therapy: Caverject, Trimix
- Intraurethral Rx: MUSE
- Vacuum Constriction Device
- Oral therapy: PDE5 Inhibitors
- Penile Prosthesis
How to PDE5 inhibitors work?
- Prevent breakdown of cGMP to GMP/GTP
- Allows prolonged action of cGMP (smooth muscle relaxation)
- (cGMP is formed by guanylate cyclase in response to NO released by endothelial cells and NANC neurons)
Describe the parts of a 3-piece penile implant?
- Reservoir
- Cylinder
- Pump
