Azoospermia
What is Azoospermia (Nil Sperm)?


Azoospermia is one of the most severe forms of male
factor infertility. It is a condition in which a man has
no sperm in his ejaculate. In order to transport sperm
outside of the body, it mixes with ejaculate (semen) at
certain places throughout the male reproductive system.
Sometimes, due to blockages or sperm production
problems, sperm does not mix with ejaculate, and
therefore cannot leave the body. This is why so many men
with azoospermia find it difficult to have children.
There are actually two types of azoospermia:
Obstructive Azoospermia:
Obstructive azoospermia accounts for 40% of all cases of
azoospermia. It occurs when a blockage in your duct
system prevents your sperm from mixing with your semen.
These obstructions may be present in your vas deferens
or epididymis.
Non-Obstructive Azoospermia: Non-obstructive azoospermia accounts for 60% of all cases of azoospermia. It occurs when there is a problem with the actual production of sperm within your body. It is often the result of hormonal imbalances

How sperms develop:
When boy becomes of 14 years of age then L.H. & F.S.H.
hormone secretion from pituitary increases. The rise in
these hormones leads to proliferation of sperm forming
cells (Germ Cells) in the testis. These germ cells start
multiplying under the effect of above-mentioned
pituitary hormones along with assistance of other
hormones as testosterones, Growth hormones,
Androstenidione, insulin like growth factor-I, Thyroids
hormone, paracrine hormone & growth factors. Under the
control of above-mentioned hormones germs cells divide &
transformed into primary spermatocytes. Then further
maturation of primary spermatocytes to spermatids & then
finally into mature spermatozoa (i.e. normal sperms)
occurs under the control of above-mentioned hormones.
After few weeks of progressive maturation inside the
testis these sperms become normally motile & develop the
capacity to fertilize the ovum. This total sperm cycle,
from first stage to final stage of normal mature sperms
is of three months. Thus to produce normal sperms testis
should have normal sperm producing germ cells & normal
regulating hormones. Any major hindrance in the
development of these spermatozoa will lead to absent
sperm production resulting into nil sperm..
Causes of Azoospermia:
The various causes of Azoospermia are as follows :
Hormone Disorder:
The various endocrine (Hormone) disorder leading to
azoospermia are as follows
(i) Hormone deficiency of pituitary gland as L.H.,
F.S.H., Prolactin, thyroids hormone, hypothalmic
deficiency of GnRH, Pituitary gland failure,
Hypopituitarism, Idiopathic hypopituitarism, Kallman
syndrome, Isolated hypogonadotropic hypogonadism, Drugs,
toxins, Idiopathic hypogonadotropic hypogonadism & due
to many more causes.
(ii) Obstruction in the outflow of semen (Sperms) from
testis to outside through urethral opening. Many times
the production of sperms in testis is absolutely normal
but these sperm are unable to come out due to
obstruction in the out flow tract leading to absent
sperms in the semen. The various causes of obstruction
are absent vas deferens, absent seminal vesicle,
posttraumatic, post surgical ligation of vas deferens.
After some infections, as chlamydial, gonococcal
urethritis. It may also be due to post tubercular
epididimo-orchitis. The sperm may also not come out of
testis if the are imotile due to any of the following
causes as imotile cilia syndrome, kartagener syndrome
cystic fibrosis & many other rare diseases.


(iii) Absence of germ cells in testis also called
sertoli cell only syndrome. In this there are no germs
cells i.e. sperm forming cells in the testis. For you
knowledge, I wish to inform you that in testis germ cell
come to testis from neural cord area of the body during
neural cord area of the body during development of
fetus. So in some fetuses this migration of sperm cells
do not occurs leading to testis only having testosterone
forming & sertoli cells. Thus this condition is called
sertoli sell only syndrome it is a developmental defect.
(iv) Maturation Arrest (. Spermatid arrest): of primary
spermatocytes to secondary spermatocyte, spermatids or
to mature spermatozoa. Due to may local, systemic,
hormonal growth factor deficiency or due to idiopathic
factor. The various paracrine hormones and growth
factors are essential for normal development i.e.
maturation of one germ cells to multiplication of
ultimately production of multiple mature, normal &
motile sperms. Many other factor as infection,
varicocele, drugs, chemotherapy may also lead to
maturation arrest. The other causes may by
developmentally defective germs cells & spermatocyte. So
that they did not have inherent capacity of developing
into a mature & motile sperms.
4) Testicular disorders (primary leydig cell
dysfunction), Chromosomal (Klinefelter syndrome and
variants, XX male gonadal dysgenesis), Defects in
androgen biosynthesis, Orchitis (mumps, HIV, other
viral, ),Myotonia dystrophica, Toxins (alcohol, opiates,
fungicides, insecticides, heavy metals, cotton seed
oil), Drugs (cytotoxic drugs, ketoconazole, cimetidine,
spironolactone)
5)
Varicocele (Grade 3 or more severe): A varicocele is a
varicose vein in the cord that connects to the testicle.
(A varicose vein is one that is abnormally enlarged and
twisted.)
Varicocele decreases sperm productions by elevating
temperature of the testis, may produce higher levels of
nitric oxide chemical in the testis which blocks sperm
production, varicocele damages sperms directly & lastly
varicocele decrease the oxygen supply to testis.

6) Drugs (e.g. spironolactone, alcohol, ketoconazole,
cyclophosphamide, estrogen administration, sulfasalazine)
7) Presence of Antisperm antibody. These Antisperm
antibodies bind with sperms & either make them less
motile, totally immotile or even dead which is called
necrospermia
8) Trauma
9)
Environmental toxins
10) Viral orchits
11) Granulomatous disease as tuberculosis, sarcoidosis
of the testis
12) Defects associated with systemic diseases, Liver
diseases, Renal failure, Sickle cell disease, Celiac
disease
13) Neurological disease as myotonic dystrophy
14) Development and structural defects, Germinal cell
aplasia, sertoli cell only
syndrome, Cypt-orchidism
15) Androgen resistance
16) Mycoplasma infection
17) Cystic fibrosis patients often have missing or
obstructed vas deferens (the tubes that carry sperm) and
hence a low sperm count.
18) Klinefelter syndrome patients carry two X and one Y
chromosomes (the norm is one X and one Y), which leads
to the destruction of the lining of the sperm forming
germ cell in the testis.

19) Environmental Assaults: Over exposure to
environmental assaults (toxins, chemicals, infections)
can cause nil sperm either by direct suppression of
sperm production or on the hormone. Some chemicals that
affect sperm production men are: Oxygen-Free Radicals,
Estrogen emulation pesticidal chemicals (DDT, aldrin,
dieldrin, PCPs, dioxins, and furans), plastic softening
chemicals like Phthalates, hydrocarbons (ethylbenzene,
benzene, toluene, and xylene)
20) Exposure to Heavy Metals: Chronic exposure to heavy
metals such as lead, cadmium, or arsenic may affect
sperm production and may cause nil sperms in otherwise
healthy men. Trace amounts of these metals in semen seem
to inhibit the function of enzymes contained in the
sperms, the membrane that covers the head of the sperm.
20) Radiation Treatment: Over-exposure to radiation & xrays affect any rapidly dividing cell, so cells that produce sperm are quite sensitive to radiation damage. Cells exposed to significant levels of radiation may take up to two years to resume normal sperm production, and, in severe circumstances, may never recover.

21) Misuse of substances: There are a number of banned
substances that can have potentially lethal effects on
sperm production. Taking anabolic steroids, for example,
to increase performance in sports such as weight
lifting, can dramatically alter both the motility and
the health of the spermatozoa. Other banned substances,
such as cocaine, marijuana and heroin can reduce sperm
production & may make a man infertile.
22) HGH Deficiency
Diagnosis of Cause of Nil Sperm Count

For correct diagnosis of cause of nil sperm count, we
need detail history & physical examinations then certain
relevant investigations are required.
History & Physical Examinations: First step in proper
treatment is accurate diagnosis of cause of nil sperm
count. So we first try to find out cause. We take
detailed history, thorough drug history, and general
physical examination, examination of testis, epididymis
& testicular veins & sperm carrying duct examinations.
These examinations give idea about whether testis is
normally developed or not & how is its function. After
that depending on likelihood of particular, cause
relevant tests are done. All testing facilities are
available at our centre. Thus you may consult us at our
centre & at same time you may get all tests done. The
time taken in getting all the reports ready is 36 hours.
So if you are from out of Delhi, you may come here for
two days.
Investigation & Diagnosis: For completes diagnosis of
causes of azoospermia (nil sperms) one or more of the
following tests may be required as:
1) Complete male hormone profile: This profile includes
all the male hormone tests which affect testicular
development, growth & other genital organ development as
well as genital functions. L.H., F.S.H., Testosterone,
prolactins, thyroids test,
2) Antisperm antibody
3) USG or Doppler study of scrotum & testis
4) Semen culture sensitivity
5) Semen fructose
6) Fine Needle Testicular Biopsy of the testis to look
for evidence of spermatogenesis & testicular structure.
8) Human Sperm-Zona Pellucida Binding Ratio
9) Human Sperm-Zona Pellucida Pentration test
10) Genetic Studies
11) FNAC Testis


12) Egg penetration test
13) Molecular genetic studies done in some special cases
14) Chromosome analysis i.e. Karyotype (chromosome
analysis)
15) Assessment of androgen receptor
16) Combined Pituitary hormone tests is performed when
needed
17) Immunobead test
18) MRI head, Hemogram, test for systemic diseases.
19) Olfactory test is done to find out kallman's
syndrome
At our
center facility for all the above tests are available.
Treatment of Azoospermia:
After the
finding out cause of azoospermia treatment is started
depending on the cause found.
The various
treatments are as follows:
Correction of the Cause: First of all we try to find out
the primary cause of nil sperms by above mentioned
investigations. Then we correct the basic defect i.e.
correction of hormone disorder & other defects. We also
give following treatment for permanent cure of low sperm
count & motility disorder.
1) Correction of Hormone deficiencies: Once the hormone
disorder is found then it is corrected by any of the
below medicines. Usually sperm count normalizes in three
month time with proper hormone treatment.
2) Gonadotropin Therapy: Gonadotropins are most potent
natural stimulators of sperm production in the testis.
Once we start gonadotropin therapy, these gonadotropins
stimulates the sperm producing cells in testis. Under
the stimulating influence of gonadotropins dormant sperm
forming cells which were not producing any sperms, they
start dividing & produce multiple immature sperm cells
with in three to four weeks. These are further matured
in next two to three month into mature sperms under the
influence of gonadotropin treatment. Thus in more than
90% cases sperm production can be normalized in three to
four months time if it is started in properly selected
cases of nil sperms. Gonadotropin therapy is most
successful of all the available treatment for nil sperms
till now. In many cases of nil sperm count, when all
other treatment has failed even in those cases
gonadotropin therapy is effective. Thus treatment of nil
sperms with gonadotropin results in pregnancy soon.

3) Repronex.
4) Bravelle
5) Ovidrel
6) Gonadotropin-releasing hormone (Gn-RH) analogs
7) Growth hormone therapy in many cases where somatropin
deficiency is found
8) In cases of Antisperm antibody induced cases
treatment is sperm washing followed by intrauterine
insemination, steroid use or intra-cytoplasmic injection
of sperms (ICSI).
8) Growth Factor, Mineral & Micronutrient Therapy
9) Free Radial Scavengers: These are drug to reduce the
free damaging oxidative radical in the testis. For your
information every minute lot of oxidant radicals are
generated inside the testis which damages sperm forming
cells. These special antioxidant drugs scavenge these
damaging oxidative free radicals thus leading to
production of normal sperms by the testis. In many study
these free radical scavengers have been found to be
very-very effective in normalizing sperm count.

11)
carnititine supplimentation increases the production of
sperm, with normalization of sperm count in three
months.
13) Bromocriptine. This medication is for men who has
elevated levels of prolactin, then this hormone rise
decreases the sperm production
14) Correction of thyroid hormone
15) Correction of congenital adrenal hyperplasia
17) Zinc
19) Antibiotics
23) Hgh
26) AIH
27) Certain Newer Drugs has been found very effective
28) Surgery: Depending on the surgery may be a treatment
option for nil sperm count due to blockade of the tract
from testis to the tip of penis (i.e. obstructive
azoospermia). Surgery is also the treatment of choice
for significant varicocele. Similarly surgery may be one
of the treatment options for many endocrine tumours. Surgical reconstruction When obstruction in transport of
sperm from testis to outside is diagnosed, it is treated
by surgical reconstruction. All this surgical treatment
facility is provided by our expert micro surgeon. In
this obstruction segment is bypassed by surgical
anastomosis.
29) But there are many cases of azoospermia in which
inspite of best treatment sperm production either does
not improves or is impossible. In these cases we do fine
needle testicular biopsy in which sometimes we may get
some normal sperms or even spermatids. These
spermatocytes or sperms are then injected in ovum
leading to formation embryo. These embryos are ten
transferred into uterus leading to achievement of
pregnancy.


30) But in some cases inspite of all efforts no sperm
can not be produced. In such cases we advise artificial
insemination by semen from donor. In this normal semen
is taken from sperm i.e. semen bank. This is one of the
very successful method of treatment with minimal cost
involvement.
31) Test
tube baby is also delivered with our efforts by use of
intra-cytoplasmic sperm injection (ICSI), then transfer
of embryo to uterus of mother.
32) Semen Bank: Facility for good quality sperm is semen
bank in also available. At our center we have facility
for all the testing & treatment facility required for
low sperm count to achieve pregnancy.
33) Assisted reproductive technology (ART)
ART has revolutionized the treatment of infertility.
Each year thousands of babies are born in India as a
result of ART. Medical advances have enabled many
couples to have their own biological child.
The most common forms of ART include:
a)
In vitro fertilization (IVF). This is the very
effective ART technique. IVF involves retrieving mature
eggs from a woman, fertilizing them with a sperm from
sperm bank in a dish in a laboratory and implanting the
embryos in the uterus three to five days after
fertilization.
b)
Surgical sperm aspiration. This technique
involves removing sperm from part of the male
reproductive tract such as the epididymis, vas deferens
or testicle. This allows retrieval of sperm if blockage
is present.


c) Intracytoplasmic sperm injection (ICSI). This
technique consists of a microscopic technique
(micromanipulation) in which a single sperm is injected
directly into an egg to achieve fertilization in
conjunction with the standard IVF procedure.
34) Varicocele ligation
A varicocele is an abnormal tortuosity and dilation of
veins of within the scrotum. It can be surgically
treated - which might help fertility in some cases.
At our center we have facility for all the testing &
treatment facility required for nil sperm count to
achieve pregnancy.
Response of Treatment: By above treatment many patients
are cured in three to four months times. But if we
diagnose that this problem is not curable in such
cases we tell the patient that your problem is incurable
& suggest them other available options as test tube
baby, ICSI, AIH etc..
Treatment
Treatment for
Azoospermia
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