Professional Documents
Culture Documents
Medicine
Clinical Embriology & Assisted Human
Reproduction
Male Infertility
Course 1
1. Couple Infertility
-affects 15% of couples in the
reproductive age
-40% of cases male factor
-40% of cases female factor
-20% of cases both
2. Men and women are equally
affected
3. Infertility affects all ethnicities
and races
1. Andrologys addressability is
rising.
2. Assisted human reproduction
techniques have substantially
evolved
(offering
solutions
even to the most severe cases
of male infertility).
3. Almost all patients with male
infertility (90%) become able
to conceive their own child
through
assisted
human
reproduction techniques.
Unexplained Infertility
- Idiopathic (modified
spermogram)
- Unexplained (normal
spermogram)
Erythromycin, Gentamicin,
Neomycin, Nitrofurantoin,
Tetracycline
Antihyperten
sive Drugs
Chemotherap
y Drugs
Busulfan, Cisplatin,
Vinblastine, etc ...
Hormones
Anabolic steroids,
Antiandrogen, Estrogen,
Progesteron derived drugs,
Testosteron
Psychotherap
y Drugs
Others
Alopurinol, Cimetidine,
Ciclosporin, Colchicine
APP
(high
fever,
acute
infections,
surgery
of
urinary
illicit drugs,
Male
infertility
can
be
the
first
sign
towards
marrow
neoplasia,
endocrinopathies,
SRY Gene
Sex-determining Region
Swyer syndrome
Female XY
Santhi Soundarajan,
1981
Indian Athletewinner
of 11 international
medals
2006- Asia Games
revoked her Silver
Medal she didnt
pass the feminine test
Sexual Differentiation in
Males
Genetic sex at fecundation
Gonadal sex (testicles or ovary) S6 ( until
then the embryo is in non-differentiation stage
of gonadal sexualisation bipotential gonads
Genital sex (genital ducts OGE) under the
influence of testosterone secreted starting
S7/s (absence of testosterone: bipotential
gonads ovary) until S8 sexual nondifferentiation of genital ducts stage
S12- genital sex distinguished at ultra-sound
Intrauterine Sexualisation
Spermatogenesis
Starts at puberty (testicular cords become
seminiferous tubules) it never ends
At Contorted seminiferous tubules level
100 mil spz/day (IN COMPARISON WITH 1
OVOCIT/month)
Hormone controlled (GnRH, LH, FSH, Testosterone,
Inhibina) and through temperature control (-2C for
man and -8C at mouse)
Testicule volume - 18cm3 (5*2*3) ! 30g -0.08% of
body weight
Spermatogeneza
Mitosis of the
spermatogonia
16 days
Up to the primary
spermatocytes
First meiosis
24 days
Second meiosis
A few hours
Spermiogenesis
24 days
Total
~64 days
For engendering
the spermatids
Up to the
completed sperm cells
Spermatogenesis
Adjustment
Male Contraception
Condom
Vasectomy the male vas deferens are severed and then
tied/sealed; reversible but a small portion can still have children
EXP- Analogue nontoxic Adjudin (substance that disrupts sperm
maturity) can be useful in blocking spermatogenesis
EXP -No hormones pill which is capable to induce a dry orgasm.
The man can still orgasm (erection is not affected) but the substance
prevents sperm production. This is administered 4-6 hours before
sexual intercourse and fertility effect is reversible after 12-24 hours.
EXP -Hormonal in study combination
Progesterone (3doses/month) reduces spermatogenesis +
Testosterone (implant changed every 4 months) maintains
potency
Hormonal treatments have side effects: nausea,
headaches, icterus.
Long term, prostate issues may appear.
In addition, disadvantage of long latency period until it
can take effect (3 months).
Coming soon!
2017
Vasalgel injection of a nontoxic polymer in
the deferent duct (local anaesthetic). 10 years
protection. Cancelling the effect is made
through the injection of a polymer dissolvent..
Testosterone Substitution
NOT IN INFERTILITY
Inactive oral; Preparations IM (esteri)
Clinical use:
IMPOTENCE Vs INFERTILITY
INFERTILITY
IMPOTENCE
(52% 40-70 years)
Cystic fibrosis
Medication
Mumps in postpuberty
Neurological illness
Trauma
High cholesterol
Toxines
Arterial hypertension
Diabetes
Evaluation of Infertility
Medical history (childhood illnesses, cryptorchidism, chronic
treatment, family medical history, illicit drugs, smoker, previous
infections, working in toxic environment)
Clinical tests (rectal exam, inguinal scars, OGE test varicocele
(left>right), epididymis, vas deferent)
Hormonal dosage (FSH, LH, PRL, Testosterone,
freeTestosterone, PRL, Estradiol, AMH)
Specific Tests (testicular ultra sound, transrectal, abdominal,
spermogram, MAR test, Halosperm)
Urine test determining of sperm cell =retrograde ejaculation
Accessory glandes markers
a. zinc, citrate or cholesterol for prostate
b. fructose, prostaglandin, bicarbonate for seminal vesicles
c. alpha-glucosidase, glycerylphosphorylcholine, L-carnitine for
epididymis
AMH in Males
Indicator of presence/functionality of Sertoli cells
Indications:
Sexual ambiguity;
Pseudohermaphroditism
Hermaphroditism
Cryptorchidism
Female testicle
Azoospermia (adult)
Prolactin in Infertility
Indications : In Men:
ginecomastia, infertility, azoospermia, exposure to pituitary gland
tumours (microadenome and macroadenome) si breast tumours
Seminoma / epididymitis
SPERMOGRAM
Spermogram Results
Values following test
Normal values
Volume: ml
Colour: opalescent
pH:
Liquefying: complete
Time to liquefy: 15min
Viscosity: normal
Concentration: mil/ml
Total no. of spz in sample: mil
Motility a+b: %
Motility a+b+c: %
1,5ml
Opalescent
7,2-8,0
Complete: distinguished drops
20 min
Normal
15 x 106 /ml or
39 x 106 in sample
32%
40%
Morfology
Values following test
Normal forms: %
Abnormal forms: %
Normal values
> 4% normal forms
(according to WHO 2010)
Leucocyte: 1%
1% leucocyte
Spermogram
Results:
MAR Test
(Mixed Antiglobulin Reaction)
Direct MAR test is done to detect antisperm antibodies of the IgA class in human semen.
The presence of antisperm antibodies can interfere with sperm function and zona binding
and the acrosome reaction.
Antisperm antibodies. The presence of antisperm antibodies which react with antigenes
present on sperm cells is considered typical and specific towards immunological infertility.
These antibodies can be found in approx. 8% of infertile men.
Limitations. Direct MAR testing can only be done on mobile sperm cells. Samples with low
concentration or low mobility can deliver a false negative result.
Interpretation reference values.
When antispermatic antibodies are present, the mobile sperm cells will tie the latex
particles forming agglutinate, in a proportion (percentage) which is correlated directly with
the severity of the immunological reaction.
Reference values:
< 10% - negativ;
10 39% - intermediary (suspicion of infertility of immunological cause);
> 40% - positive (very high probability of infertility of immunological cause).
Factors that can influence broken sperm cell DNA: some medication, toxins,
fever, smoking, drugs, infections, age, long abstinence.
AZOOSPERMIA
OBSTRUCTIVE
NON-OBSTRUCTIVE
Idiopathic
Cryptorchidism
Genetic Causes
Chromosome anomalies: present in 5-10% of men with
oligozoospermia and 10-15% of those with azoospermia; the best
known anomaly is Klinefelter syndrome (47, XXY); - for AZOO nonobstructive
Microdeletions of Y chromosome: present in 10-18% patients with
severe oligo-or azoospermia; AZF (Azoospermia Factor)cu
localisation Yq11.23 - for AZOO non-obstructive
Muatations of cystic fibrosis gene (CFTR): transmits autosomalrecessive; several mutations can determine: bilateral congenital
absence of the vas deferens (CBAVD), unilateral absence of it
without pulmonary or pancreatic manifestations (CUAVD) or
obstruction of the vas deferens; for AZOO obstructive
Transmitted to male
Deletion of the entire AZFa region leads to SCO Sertoli-Cell-OnlySyndrome and to the impossibility to collect mature sperm cells from
the testicular tissue
Complete deletion AZFb and AZFbc stopping the maturity process
of spermatogonia leads to azoospermia. The same as in the case of
complete deletion AZFa, ICSI assisted reproduction technique is not
recommended. They can be counseled by the specialist doctor,
recommending alternatives (for example sperm donors).
Deletion of AZFc region (b2/b4) is associated with clinical and
histological phenotypes and in general will be compatible with
residual spermatogenesis. Deletion AZFc can be encountered in men
with azoospermia or severe oligoazoopermia and in rare cases, they
can be transmitted to male descendants. Also, patients with AZFc
deletions can benefic from ICSI; their male children will present
AZFc deletions.
Cryptorchidism
Varicocele
Incidental -10-20%
Dilation pampiniform plexus veins
Infertility and stopping testicular growth
Affected Spermatogenesis;
Oxidative stress apoptosis
Acrozomial flaws
Clinical Use
Choosing the right assisted
reproduction method