Male Infertility

Male Infertility: Definitions
By:Jeanne O’Brien MD
Assistant Professor of Urology and Male Infertility
University of Rochester Medical Center, Department of Urology

Definitions
* Primary infertility: inability to achieve pregnancy > 1yr
* Secondary infertility: previously fertile, now unable >1 yr
* Azoospermia: no sperm in semen
* Oligospermia: reduced sperm concentration <20 million/ml
* Asthenospermia: reduced percent motility <50%
* Teratospermia: reduced percent normal forms <30%
* IVF: in vitro fertilization
* ICSI: intra-cytoplasmic sperm injection

Etiology of Male Infertility
* Varicocele
* Idiopathic
* Infection
* Genetic
* Endocrine
* Immunologic
* Obstruction
* Cryptorchidism

Male Infertility: Evaluation
* Basic Evaluation:
o History (Questionnaire)
o Physical examination
o Standard semen analysis
o Hormonal evaluation
* Optional Additional Evaluation:
o Genetic counseling and evaluation
o Specialized sperm function tests
o Imaging studies
o Testis biopsy

Male Infertility: History
* Duration of infertility
o Previous treatments
o Female-factor (anovulation, tubal obstruction)
* Sexual history
o timing and mechanics of intercourse
o lubricants (peanut oil, olive oil, egg whites ok)

History
* Childhood & Development
o cryptorchidism
o pubertal development
* Medical History
o systemic illness
* Surgical History
o abdominal, pelvic or scrotal surgery
* Infections
o STDs, prostatitis, orchitis (post-pubertal mumps)
* Environmental gonadotoxins
o smoking
o ETOH
o radiation, chemicals, pesticides, chemotherapy
o Heat exposure (short order cook, tanning booths, hot tub/bath)
* Medications (steroids, herbal supplements, hair growth products)

History: Medications
* Hormonal (pre-testicular)
o e.g. androgens, anti-androgens, estrogens
* Gonadotoxic (testicular)
o e.g. chemotherapy/alkylating agents
* Sperm-toxic (post-testicular)
o e.g. Ca-channel blockers

Anatomy of the male reproductive tract

Physical Examination
* General
o Body habitus (muscle mass), hair distribution
o Evidence of normal virilization
* CNS
o visual fields (r/o pituitary adenoma)
o sense of smell (Kallmann’s Syndrome - HypoHypo)
* Abdomen/Pelvis
o Surgical scars
* Genital/Prostate
* Penis:
o length (normal development)
o position of urethral meatus (deposition of semen)
* Prostate :
o size
o firmness
o tenderness
o presence of cysts (ejaculatory duct)
* Testis:
o -position (cryptorchid?)
o -volume (normal ~15-25ml)
o -firmness (normal = firm)

Testis:
o -Seminiferous tubules
+ Germ cells
+ Sertoli cells
o -Interstitium
+ Leydig cells
+ macrophages, endothelial cells
Spermatogenesis
o ~74 days in humans (epididymal transit ~15 days)
o Clinical correlate: Need to wait 3 months after any intervention (medical or surgical) to see a change in semen quality
* Epididymis:
o -fullness
o -cystic changes
* Vas deferens:
o -congenital absence of vas (CAVD)
+ Cystic fibrosis mutations
+ Woolfian duct anomalies

Genital tubercule Penis
Overview of sexual differentiation in the male
(modified from Male Reproductive Biology, eds Lipshultz, Howards)
Varicocele: Diagnosis
* Definition: dilated testicular veins due to reflux of blood
* Established by physical examination (in a warm room)
* Other modalities used to diagnose a sub-clinical varicocele:ultrasound, venography, doppler stethoscope
* However, the subclinical varicocele does not require repair!
* WHO Fertil Steril 1985
* Howards Fertil Steril 1992

Varicocele
* Etiology: probably multi-factorial
Varicocele: Prevalence
Varicocele-Induced Pathology
* Testis atrophy
* Testis histology (non-specific)
* Leydig cell dysfunction
o Lower serum Testosterone (T) levels
o Blunted T rise in response to LH stimulation
* Testicular Pain
o Mechanism unknown

Semen Analysis
* Semen Parameters Normal range (WHO)
* Volume (1.5 - 5 mL)
* Sperm density (>20 million/mL)
* Sperm motility (>50%)
* Sperm morphology (>30% normal forms)
* Leukocyte density (<1 million/mL)
* Need at least 2 S/As (because parameters are highly variable)
* S/A is not a measure of fertility but fertility potential

In Vitro Maturation of Germ Cells
* Spermatogenesis: orderly differentiation of immature germ cells to mature spermatozoa
* 1. Mitotic phase
* 2. Meiotic phase
* 3. Spermiogenesis
Two separate events observed in vitro
1. Spermatid differentiation (round to elongated)
2. Meiotic progression (spermatocyte to spermatid)
In Vitro Maturation of Germ Cells:
* Sperm head defects
* Sperm mid-piece defects
* Sperm tail defects
Semen Analysis: Critical Review
* Evaluated 765 infertile men and 696 fertile controls to
* determine semen parameter thresholds that best
* discriminate between fertile and infertile men.
* Infertile couples
* Fertile controls
* Methods:
2 semen samples were collected from each patient.
Technicians from the 9 centers were trained at a central site.
Stained sperm smears were sent to a central site for
strict morphology assessment (by a single technician).
* Statistical Analysis:
Classification-and-regression-tree (CART) analysis was
used to define thresholds for classifying infertility
Receiver-operating-characteristic (ROC) curves were used
to test the discriminatory power of each variable

* Results:
* Conclusions:
Spermatogenesis
Abnormal Morphology
Sperm DNA Integrity
Why examine sperm DNA integrity?
Fertilization Pregnancy
Human Sperm DNA: Characteristics
Sperm DNA Packaging
Evolution During Epididymal Transit
Human Sperm DNA Damage: Etiology
Potential causes of DNA fragmentation
Antisperm Antibodies (ASAs)
Etiology & Incidence
Antisperm Antibodies: Testing
Hypo-Osmotic Swelling Test (HOST)
Hormonal Evaluation
Azoospermia: Normal semen volume
Genetic Evaluation
Non-Obstructive Azoospermia (NOA):
Etiology
Management Options
Micro-Testicular Dissection
Obstructive Azoospermia (OA):
Clinical features
Etiology
Management Options
Conclusion

* Male infertility is multifactorial
* Hormones, physiology, environment, anatomy and DNA all play a role
* It is the delicate balance of all of these factors that must be weighed in order to optimize male fertility
* Every evaluation is different and every treatment strategy is geared toward the individual patient and circumstance and must always take into account the female partner

Male Infertility.ppt