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NIL sperms (Azoospermia)

What is Nil Sperms 
Causes of Nil Sperms 
Investigations & Diagnosis of Nil Sperms 
Treatment of Nil Sperms 
Response of Treatment 

What is Azoospermia (Nil Sperm):  Azoospermia is called when there is no sperm in semen. This type of semen disorder is found in approximately 3% of infertile men i.e. absent sperm. You should know that testis has two separate functions

(i)                   Production of normal sperms in semen which needed for pregnancy & normal fertility.

(ii)                 The other function of testis is production of male hormones i.e. testosterone & others. So in most patients with nil sperms though semen has absent sperms still production of male hormones remains normal.

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 Nil Sperms: The various causes of  nil sperm 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 Nil Sperms:

 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.

10) Coenzyme ubique: These drugs improve the nutritional status of the testis. Thus sperm forming cells get enough nutrient which helps in fast generation of sperms in good number with good motility & fertilizing capacity.

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 dono r. 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..

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(Note: Name & Place mentioned in the testimonials have been changed by the patient to hide the identity but treatment response mentioned by him/her is real.)

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