Transcript MALE INFERTILITY

MALE INFERTILITY
AMIT K SHARMA
UROLOGIST
HSB
At the end of this talk
• 1.Understand the performance characteristics
of Semen Analysis
• 2.Describe the role of semen analysis in
prognosticating pregnancy, and consequently
its utility in defining fertility
• 3.Understand the role of semen analysis as a
marker for significant underlying disease
• 4.Provide evidence-based recommendations
to your patients
Semen Analysis - Introduction
• Primary infertility affects approximately 15%
of couples with male factor infertility
accounting for 50% of cases
• Semen analysis has traditionally been the
initial test of choice in the evaluation of the
infertile male.
What is Semen?
Sperm + Seminal Plasma
Source
Volume
1.Testis/vas
2.Epididymis
3.SV
4.Ampullae
5.Prostate
6.Bulbourethral
glands
7.Glands of Littre
<0.1 ml
1.5-2.0 ml
0.5 ml
0.1 ml
0.1 ml
• Because the human spermatozoa show marked
heterogeneity, at least two semen samples
should be evaluated
• collected at least 7 days between specimens
• 3 months after any febrile illness.
• Samples are collected after a period of
abstinence of greater than 48 h
• Specimens should be analyzed within 1 h of
collection
– as semen liquefies at room temperature within 60 min
• If the results of semen analysis are normal
according to WHO criteria, one test should be
sufficient
• If the results are abnormal in at least two
tests, further andrological investigation is
indicated
• Natural conception may occur for men even
when SA values are less than WHO reference
ranges and, conversely, men with normal SA
parameters may have difficulty initiating a
pregnancy.
Biological Variation
• A 33 yo male with a 1 year history of infertility
presents to your clinic today and provides a
SA. History and physical are unremarkable.
Partner is normal
• On questioning, he abstained for 1 day before
providing a semen analysis
• Volume 2.5 cc
• Concentration 15 million/ml
• Motility 60%
• Morphology 8%
Questions
• 1.Does the season matter?
• 2.Would have abstaining for longer time have
made a difference? If so, how much of a
difference?
• 3.Does it matter how many times he
ejaculated last week
• 4.If he repeated the SA the exact same way
several times, how much variation would
there be? Would some of the parameters vary
more than the others?
• 5.He’s 33 now. Would his results have been
different last year
• 1. Does the season of collection matter?
A: MAYBE (sperm maybe best in spring)
• 2. Would have abstaining for longer time have
made a difference?
A: DEFINITELY (by about 25% per day up to day 4)
• 3. Does it matter how many times he had
intercourse last week?
A: MAYBE (less than 1-2/7 days may maximize)
• 4. How much difference between could you
expect with between 2 samples.
• A: A LOT (about 30-50% CV in all parameters
between 2 samples)
• 5. Would his SA likely have been any different
when he was younger?
• A: NO (except for the volume)
Definations
• Infertility is a disease defined by the failure to
achieve pregnancy after 12 months or more of
regular unprotected intercourse
• Fertility is defined by the actual production of live
children
• Sterility is the absence of the capacity to
reproduce
Conception rates
• Per cycle is 25%
• Per year 85%
• Therefore, 10-15% of couples meet the
definition of infertility
INFERTILITY ≠ ABSENCE OF
FERTILITY
INFERTILITY ≠STERILITY
INFERTILE OFTEN BECOME
FERTILE
Prognostic Performance of SA for
Pregnancy
Starting at TIME 1 YEAR
(i.e. Infertile)
• Approximately 29%of couples with
concentrations of <20 x106/ml will conceive
within 2 years of being declared ‘infertile’
(Collins Fertil Steril 1995)
• Approximately 27% of couples with total
motile counts <5 x106/ml will conceive within
2 years of being declared ‘infertile’ (Snick
Human Reprod 1997)
• If the SA is within the reference range, the
probability of conception is 50-70% within 2-3
years
Drawbacks
• There are still a significant proportion of patients
with normal semen analyses but with unexplained
infertility.
• A normal spermiogram does not necessarily
correlate with fertility potential, because it does not
assess sperm function.
• Standard semen analysis has been unable to detect
some functional deficiency in about 40% of men
presenting for sub-fertility
• Semen analysis is not a diagnostic test for
infertility or fertility
• Semen analysis parameters are crude
prognosticators of fertility. Concentration and
morphology are the strongest parameters.
• Don’t rely on the ‘reference range’ on the SA
report
• Even using everything which is currently
measurable, only a small portion of the
probability of future success can be
prognosticated.
Male Infertility Causes
• Idiopathic male infertility
31 %
• Maldescended testes
7.8 %
• Urogenital infection
8.0 %
• Disturbances of semen deposition and sexual
factors
5.9 %
• General and systemic disease 3.1 %
• Varicocele
15.6 %
• Hypogonadism
8.9 %
• Immunological factors
4.5 %
• Obstructions
1.7 %
• Other abnormalities
5.5%
Classification
• I.Non obstructive infertility 60%: inadequate
sperm production by the testes
• II. Obstructive infertility 38%: normal sperm
production but there is a blockage in the genital
tract
• III. Coital infertility 2%: normal sperm production
and patent genital tract; however infertility is
secondary to sexual dysfunction which impairs
intromission or ejaculation.
Causes Of Non Obstructive Infertility
• Hormonal
-Hypogonadotrophic Hypogonadism
-Thyroid gland disorders
-Hyperprolactinaemia
• Genetic
- Y Chromosomal microdeletions,translocations
and aneuploidy
- KS
• Varicocele
• Undescended testis
• Gonadotoxins
• Systemic illness
• Orchitis,torsion,trauma and tumours
• Autoimmune infertility
Severe Male Factor Infertility
• number < 1 m/ejaculate
• motility < 20%
• progression < 2/4
• abnormal forms > 85%
• Structural and chromosomal abnormalities found in
5 % infertile man and 14% azospermic man
• In addition to the SRY gene which is involved in
determining the fate of the embryonic bipotential
gonad, the Y chromosome also contains the ‘‘malespecific Y’’ (MSY) which contains chromosomal
material not represented elsewhere in the genome
and contains numerous genes involved in
spermatogenesis
• An AZFc microdeletion quantitatively impairs
spermatogenesis however men with such deletion
may be oligozospermic and even father children
naturally
• Unlike AZFc microdeletion; AZFa and AZFb
microdeletions are associated with azoospermia and
complete spermatogenic failure and sperm will not
be found in the testes of men with these deletions
via surgical sperm retrieval (TESE)
• Klinefelter syndrome (KS) is the most common
example of a numerical abnormality
• KS is associated with primary testicular failure,
patients present with hypogonadal features,
azoospermia, gynecomastia,small sized testes
and some may have learning difficulties.
• Micro-TESE yields sperm in up to 50% of cases
with a 30—50% pregnancy rate via ICSI
• The younger the age of male the better the
TESE outcome, so it has been suggested that
TESE should be performed on KS patients
before the age of 35 years
How do Y deletions cause male
infertility
Code for proteins essential for
spermatogensis
Causes of Obstructive Infertility
• Intratesticular obstruction
• Epididymal Obstruction
• CBAVD
• EDO
• Vasectomy-post hernia surgery, orchidopexy
Coital Infertility
• ED
• PE
• Penile deformities
• Anejaculation
• Retrograde Ejaculation
History
• Time the couple has been engaging in unprotected
intercourse and how long they have been
deliberately trying to conceive
• The frequency and timing of vaginal intercourse with
respect to the female partner’s menstrual cycle
should be assessed
• Technically, the infertility diagnosis only applies to
couples engaging in unprotected vaginal intercourse
at least twice a week on average for a year, although
evaluation may occur earlier when the female
partner is older than 35 years
• Primary or secondary infertility
• Medical Conditions
• Lifestyle factors
• Medications
• Infection and inflammation
• Surgery
• Family History
• Female factors
female partner age(age greater than 35 years suggests greater
likelihood of fertility impairment), menstrual cycle regularity,
increased serum anti-mu¨llerian hormone or day 3 serum FSH
and pregnancy history
• Physical Examination
-Secondary sexual characteristics
-Penis
-Testis
-Epidydimis
-Cord
Investigations
• SFA
• Hormonal Profile
• Ultrasound Scrotum & Testis
• TRUS
• Male Reproductive Genetic profile
• Post orgasmic urine analysis
• DNA fragmentation
• Sperm Antibodies
• Check for karyotype abnormalities and yMicrodeletions in any infertile man with a
sperm concentration of < 5 x 105/ml, especially
with azoospermia.
• Check an FSH, testoserone and PRL in every
infertile male, regardless of the semen
analysis.
Tests of Spermatozoa DNA damage
• Factors that can contribute to increased sperm DNA
fragmentation include smoking, testicular
hyperthermia, increase in seminal reactive oxygen
species due to the presence of seminal leukocytes in
response to infection and presence of varicocele
• In men who are at increased risk for elevated sperm
DNA fragmentation or aneuploidy due to lifestyle
factors, advanced age or varicocele and in men who
have undergone previous failed IVF cycles these
factors should be evaluated to determine the best
future treatment options.
• FSH levels and testicular longitudinal axis provide an
accurate means to distinguish between NOA and OA
without biopsy
• A patient with FSH ≥7.6 mIU/ml and testicular
longitudinal axis ≤4.6 cm has an 89% chance of
having spermatogenic dysfunction as a cause of
azoospermia rather than OA
• Conversely, a man with FSH <7.6 mIU/ml and testis
longitudinal axis >4.6 has a 96% likelihood of having
OA
• Diagnostic biopsy before surgical sperm retrieval
purely to discriminate OA from NOA is no longer
recommended
Analysis
Finding
Conclusion
Ejaculate volume
Low (< 1.5 mL)
Post ejaculation urine (retrograde ejaculation)
TRUS (absence of vas deferens)
Hormonal evaluation (hypogonadism), ,meds
High (>5 mL)
Likely contaminant
Does not coagulate
TRUS (ejaculatory duct obstruction)
Does not liquefy
Hormonal analysis
Oligospermia
(< 15 million per mL)
TRUS (partial ejaculatory duct obstruction)
Antisperm antibody evaluation
Hormonal analysis
Physical examination for
varicocele,toxins,environment,chemorad,orch
itis
Semen quality
Sperm density
Severe oligospermia
(< 5 million per mL)
Motility
Azoospermia
Sperm centrifuged to verify azoospermia
Postejaculation urine (retrograde ejaculation)
Hormonal evaluation
Testicular biopsy (testicular failure)
TRUS (ejaculatory duct obstruction)
Decreased
Antisperm antibodies
Physical examination for varicocele
Medical Treatment
-may be effective in the following cases:
• Hypo-gonadotropic hypogonadism may be
treated with FSH/LH preparations
• Combination of human chorionic gonadotropin
(hCG) and FSH therapy for 6—24 months results in
testicular growth in almost all and spermatogenesis
in 80—95% of patients without undescended testis
• Coital infertility e.g. sympathomimetic drugs
such as pseudo-ephedrine, vibrator and
electrojaculation for anejaculation and
sympathomimetic drugs
• Clomiphene citrate which is a selective oestrogen
receptor modulator (SERM) has also been used
successfully in patients with the adult onset form of
idiopathic hypogonadotropic hypogonadism
• Chronic prostato-vesiculitis is associated with
impaired semen parameters, elevated ROS and
increased DNA fragmentation. It is diagnosed by the
finding of pyospermia; ≥106 peroxidasepositive
white blood cells (WBCs) per millilitre of ejaculate.
Surgical Treatment Of Infertility
• Vas reversal
• Varicocele Surgery
• Surgical Sperm Retrieval
Varicocele
• Dilatation of the pampiniform plexus of
spermatic veins
• Incidence 12% of men in the general
population
• 25-35%with infertility
• 90% left sided, 10% on right
• NB- renal cell carcinoma
Grading of varicocele
I palpable during valsalva
II palpable on standing
III visible on standing
Bag of worms
Indications of Treatment?
• In the context of male factor infertility two
indications for treatment;
• Patients with grade II/III varicoceles associated with
a reduction in ipsilateral testicular volume
• ?Abnormal semen parameters in subfertile men
including oligozoospermia <20x 106/ml, poor
motility <50% progression, abnormal sperm
morphology
Indications Surgical Sperm Retrieval
• Nonobstructive azoospermia(NOA)
• Obstructive azoospermia not amenable to
reconstruction as in CBAVD
• Coital infertility due to anejaculation
• PESA
• TESA
• MESA
• TESE
• Micro TESE
• Azoospermia - The patient produces semen
containing no sperm
• Oligozoospermia - sperm concentration is low,
less than 15 million per ml
• Asthenozoospermia: < 32% motile
spermatozoa
• Teratozoospermia: < 4% normal forms
• Oligoasthenoteratozoospermia (sometimes
referred to as OATS) – combination of the
above
• Necrospermia - all sperm are dead
• Pyospermia or leucospermia - presence of
large number of white blood cells in the
semen, often associated with an infection
Prognostic factors for male infertility
• duration of infertility;
• primary or secondary infertility;
• results of semen analysis;(Conc. & Morph)
• age and fertility status of female partner
Summary
• Male infertility should be treated in a
specialized unit
• Assisted conception techniques have
revolutionized management
• Obstruction is a treatable cause of male
factor infertility
• Even those with primary testicular failure can
achieve paternity
THANK YOU