Male Sub-fertility: Causes, Effects and Treatments

Introduction
Subfertility is a common problem affecting nearly 10 -15 % of couples attempting to conceive a baby even though they’ve had frequent sexual intercourse for a year or longer. In up to one third of people having problems in getting pregnant, the issues are related to male reproductive system.[1][3]
Definition
Male sub fertility is any condition in which the man negatively affects the ability of initiating a pregnancy with his partner. Most commonly, those issues arise when the male is unable to deliver or produce fully-functioning sperm.[2]
Prevalence of Male Subfertility
Prevalence of subfertility among male varies depending on the definition.

Some reports show that worldwide “between 3% – 7% of all couples / males alone have an unresolved problem of subfertility. [14]
Some other couples, has involuntary childlessness in a range of 12% to 28% at least one year: [14]
Sub fertility issues affect one in seven males in the UK.[15]nearly half of fertility issues occurred with the male in UK.[13]
Male subfertility counts to 25% of infertile peoples In Britain. [14]
Nearly 10% of peoples expecting children are sub fertile in in Sweden. Of these peoples one third of the man has the problem. [8]

The Causes of Male Subfertility
Male Subfertility is driven by many causes, such as hormonal imbalances, physiological problems structural defects and other abnormalities in the reproductive system, and psychological and/or behavioral problems and illness or even trauma. [13]
The most common problems of male sub fertilityrelate with the production and development of sperm. Sperm may be abnormally shaped, not develop normally or not making movements properly. Or, even though having normal sperm in structural of functional, it may be produced in abnormally low count which is called as oligospermia.[1]
When delivering the sperm, an Obstruction may lead to sub fertility by blocking sperm from its normal passage. It can be caused by a various factors, like prior surgery (includingvasectomy),[1] inflammation or development problems and repeated infections. Any part of the male reproductive pathway can be obstructed, avoiding normal transport of sperm from the testicles to the urethra.
Hormonal Problems
A small percentage of male subs fertile are caused by hormonal issues.Hormones produced by thepituitary glandare responsible for stimulating the testicles to make sperm. So, when these hormone levels are severely low, low sperm production and development can be result.

The gonadotrophic-releasing hormone (GnRH)[3] stimulatesthe hormonal pathway which stimulates testosterone synthesis and so on the sperm production. An inadequaterelease of GnRH results in low levels of testosterone production and a failure in sperm production.
The pituitary can fail to produce adequate Lutenizing hormone (LH)[3] and follicle stimulating hormonewhich is called as FSH, which help to stimulate the testes and from that, the testosterone/sperm production.In testosterone and sperm production, these hormones, LH and FSH are very important in the hormonal pathway.
Also the sex-hormone balance of a male can be interrupted by some other hormones and some chemical compounds which are produce by himself[13]

Physical Problems
Many physical problems can cause male sub fertility. These issues will direct affect on sperm production of male body or interruption in the pathway which sperm travel from the testes to the penis and then the female body. These issues are normally identified by a low sperm count and sometimes using the abnormal sperm shape.
Varicoceles
Varicoceles are the most common correctable cause of male Subfertility:The dilated scrotal veins are present in 16% of all male but are most seen in sub fertile male – 40 percent. They interfere with sperm development by fail to give a proper blood supply to testis. Varicocoeles can be result in low sperm count and abnormal sperm morphology which cause sub fertility. Varicoceles are easily identified by physical examination because the veins feel especially like a bag of worms. They can also be able to be enlarged and twisted enough to be seen in thescrotum.[8][9]

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Damaged Sperm Ducts: 7% of sub fertile male cannot deliver sperm from their testicles to out using their penis. This pathway can be blocked by a various conditions: A genetic or developmental abnormalities can be result in obstruction or cause not having of one or both tubes which needed importantly to transport the sperm from the testicles to the penis to pass the female. Scarring from tuberculosis or some STDs can block the epididymis or tubes. An elective or accidental vasectomy may interfere with tube continuity.[3][8]
Retrograde ejaculation
Retrograde ejaculation is another physiological phenomenon which can be result in male subfertility.
When semen pushes backwards into the bladderthan out thepenis, retrograde ejaculation occurs. This is caused by nerve failure and muscles in the bladder neckto close during orgasm. It can be occur as result from some diseases acting on the nervous system, though out a previous surgery or medications. Cloudy urine after ejaculation mainly helps in identifies this condition. In some cases, diminished or “dry” ejaculation with orgasm may also help to identify this condition.[3][8]
Torsion it is a common issue affecting sub fertility that can be caused by a supportive tissue abnormality which can be result in the testes to twist inside the scrotum which is identified by extreme swelling. Torsion pinches the blood vessels that supply the testes shut which causes testicular damage. When both testes twist, it can be a severe condition which can then results in permanent subfertility if emergency surgery is not to be done to untwist the testes.[3]
Infection and Disease:
Typhoid, influenza, tuberculosis, brucellosis, gonorrhea, Mumps, syphilis and smallpox can lead to testicular atrophy. A low level of sperm count and low sperm motility are characteristic of this condition. Also, high FSH levels and other hormonal issues are indication of testicular damage. Some STDs like gonorrhea can cause sub fertility by blocking the epididimis or tubes. These situations are usually treated with hormonal replacement therapy and surgery.[13]
Genetically Problems
Genetics issues have a major contribution to sub fertility. Abnormalities inchromosomalnumbers in the cells and structural issues such as deletions of the relevantY chromosomepresent in normal males can be also interfering with fertility.
E.g.

Klinefelter’s Syndrome: Is a genetic condition in which is created by additional X chromosome. Physiological symptoms may include peanut-sized testicles which are small than normal size and having enlarged breasts. Most of these males who have genetic issues will suffer with subfertility.

Behavior Problems.
Some bad behavior pattern also can lead to male sub fertility. # Smoking-significantly decreases the sperm count, volume, quality and sperm cell motility. [13] # Prolonged usage of drugs like marijuana and other recreational drugs. # Chronic alcohol abuse. # Anabolic steroid use- causes testicular shrinkage and then the sub fertility. # Inadequate vitamin C and Zinc in the diet. # Tight underwear-A common reason which increases scrotal temperature and results in decreased sperm production. # Exposure to environmental facts and toxins such as mercury,benzene, boron ,pesticides, lead and heavy metals, paint, radiation, radioactivesubstances. # In some cases excessive stress can also be result in male sub fertility.
#Strenuous riding[4] Improving or simply change some pattern of these behaviors can help in sub fertility.
Medication
Some medications which are sing to treat conditions like arthritis, digestive problems, infections,and even cancer can affect sperm production. Also medication for hypertensionand depression can also be affect on male sub fertility.[13]
Diagnosing male Sub fertility
Diagnoses can be done using a complete history and physical examination and is usually followed by blood andsemenanalysis.
From a sample of semen obtained through masturbation, it can check the factors like concentration, movement, volume, count, and structure of spermatozoa.
The low values in any of the above factor can also indicate a problem with the development of male reproductive system or delivery of sperm which require some further testing.
In atransrectal ultrasound, which mean an imaging test that places a probe into therectum safely to beam high-frequency sound waves to nearbyejaculatory ducts. This test can check whether these structures of male reproductive system are either abnormally developed or obstructed withcysts,calcificationsor other obstructions.
Atesticular biopsyis useful to be done when a semen analysis results gives very low count of sperm or either no sperm. This test is done under general or regionalanesthesia through a small cut in the scrotum or using a needle which is inserted through the skin over the testicle for microscopic evaluation. The biopsy is important to be done in two ways. First, it is to determine the cause of sub fertility, and, if necessary, to get sperm sample for use in assisted reproduction.
A hormonal profile is also an important evaluation to test sperm-producing ability. The pituitary hormones like follicle-stimulating hormone (FSH) which is responsible in stimulating testicles in sperm production. High levels of follicle-stimulating hormone may indicate that the pituitary is over producing the hormones to stimulate the testicles which they are not responding.[13]
Treating Male Subfertility
The treatment using for male subfertility bases on specific issue. Unfortunately, no treatment will be available for some cases. But more often, there is a mix of medications, Simple lifestyle changes, assisted reproductive techniques (ART), also the surgical approaches are available as treatments for the male subfertility.
Some treatment ways are –
Minor outpatient surgery (varicocelectomy) is used more frequently to rearrange dilated scrotal veins (varicoceles), which may help in develop sperm concentration, sperm movement, and its structure. An obstruction causing sub fertility can also be surgically corrected for some extend. [1][3]
Intrauterine insemination (IUI) means placing the sperm directly into theuterusvia acatheter close to thefallopian tubes where fertilization occurs. IUI can be a successful solution in avoid the sperm movement problems and sperm count problems like immunologic subfertility or retrograde ejaculation, and some other causes.
Taking place the fertilization in a laboratory Petri dish, which means outside the body, is called as vitro fertilization (IVF). There, the male sperms are joined with egg of a female partner .When using IVF, the ovaries should be overly stimulated. Fertility drugs are normally used for that which is facilitating the retrieval of multiple mature eggs. Soon after 2 to 3 days of incubation, this fertilized egg (embryo) is inserted in the uterus of female partner which result the normal pregnancy.[8]
When a male with sub fertility and the semen quality is poor or low in volume, a different treatment method is used which is called as Intracytoplasmic sperm injection (ICSI). The method is to inject a good quality single sperm directly in to an egg of female partner. Once it is fertilized, it can place inside in female uterus.[1]
Treating Hormonal Problems
Medication:pituitary hormone deficiency can be corrected with using the drugs such as clomiphene or gonadotropin If Lutenizing hormone (LH) or follicle stimulating hormone (FSH) levels are abnormally low but both the pituitary gland and hypothalamus gland are functional properly, using the drugs likeclomiphene citrate (Serophene, Clomid) which helps to stimulate the hypothalamus and helps to release GnRH withregular intervals. When the pituitary is not functioning properly and not produce the necessary sex hormones, hormonereplacement therapy can be used which is usually works in about 4 months. Injecting of hCG (human chorionic gonadotropin) helps to the increase LH levels and it helps in production of testosterone and sperm by stimulating the testes.
In case of unresponsive to hCG , a combination of LH and FSH which is called as the Pergonal drug is used to stimulate spermproduction.
The drug Parlodel (bromocriptine) can correct hyperprolactinemia.[3] Cortisone replacement therapy is used to stimulate the pituitary.
Testosterone replacement therapy is highly effective for males with low testosterone levels.
Treating Physical Problems:
Varicocele[8][9]
Varicoceles are most often treated by microsurgery. Surgical treatments improve the semen in 70% of male and results in pregnancy in 60% of couples. Surgery relates the interruption of the damaged testicular veins.
Blocked Ducts:
The sperm travelling pathway which is, from the testicle to the penis, can become interfere or blocked by several factors. In situations like voluntary or accidental vasectomy, the testicle and vas deferens should reconnect by using a vasectomy reversal.In situations like congenital absence of the vas deferens, a male’s sperm can be retrieved using three methods.

Micro Epididymal Sperm Aspiration (MESA)- Which is getting a sperm sample proximal to the tubal obstruction using fine surgical techniques. [8]
Percutaneous Epididymal Sperm Aspiration (PESA)- which is using a small needle to aspirate spermfrom a location proximal to the tubal obstruction.
Testicular Sperm Biopsy (TESE)-Which is using a small biopsy of testicular tissue. [13]

Treating Psychological/Physical Problems [1][13]
Pharmacological treatment: More commonly related to use of medications which helps to restore erections. Severaldrugs are currently used to treat. Sildenafil (Viagra) is normally taken orally to increase penile bloodflow which is highly effective. Caverject is a drug which is effective highly to cause anerection in penis after injected directly to it.
Mechanical Treatment is also effective butmore cumbersome Treatment which uses a vacuum erection device and a constriction ring. The penis get into an erection by the vacuum from the. The constriction ring helps to maintain the erection by blocking blood fromexiting the spongy bodies of the penis.
Surgical Treatment can be used in restore erectile capacity of penis. In these treatments, repairing or correcting the vascular damage/blockage or use of implants is used to restore erectile capacity.Arterial and venous reconstructive surgery helps moderatelyeffective and can obtain to restore a male’s erection ability of the penis.
As treatments for premature ejaculation squeeze technique can be used effectively.When using squeeze technique, male is stimulated continually until they reach orgasm and after that, his partner squeezes his frenulum. With using this technique, longer sexual intercourse becomes possible. Another treatment option for premature ejaculation is to collect the ejaculate which is used for fertilizing an egg of female partner by using artificial insemination.
As treatments for ejaculatory incompetence behavioral therapy can be used for some extend.When using behavioral therapy, ejaculation of a male can be stimulated by using both manual stimulation from insertion of penis into the vagina of his partner and masturbation together. If this method is failing to success, an ejaculate which takes through masturbation can be used in artificial insemination with a female egg and overcome the sub fertility of male.
References

“Men’s Health – Male Factor Infertility”. University of Utah Health Sciences Center. 2003-04-01.
Brugh VM, Lipshultz LI (2004). “Male factor infertility”.
Hirsh A (2003). “Male subfertility”.
“The Vicious Cycling: Bicycling Related Urogenital Disorders”. Leibovitch I, Mor Y (2005).
Agarwal A, Prabakaran SA, Said TM (2005). “Prevention of Oxidative Stress Injury to Sperm”. Journal of Andrology 26
Robbins WA, Elashoff DA(2005). “Effect of lifestyle exposures on sperm aneuploidy”. Cytogenetic and Genome Research
Ji G, Long Y, Zhou Y, Huang C, Gu A, Wang X (2012). Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility.
“Infertility in men”. Retrieved 2007-11-21.
Costabile RA, Spevak M (2001). “Characterization of patients presenting with male factor infertility in an equal access, no cost medical system”.
Masarani M, Wazait H, Dinneen M (2006). “Mumps orchitis”. Journal of the Royal Society of Medicine
Hwang K, Walters RC, Lipshultz LI (February 2011). “Contemporary concepts in the evaluation and management of male infertility”.Nature Reviews Urology
“Men’s Health – Male Factor Infertility”. University of Utah Health Sciences Center. 2003-04-01.
Web site – http://www.ncbi.nlm.nih.gov/pubmed/?term=male+infertility
Himmel, W.; Ittner, E; Kochen, MM; Michelmann, HW; Hinney, B; Reuter, M; Kallerhoff, M; Ringert, RH (1997). “Voluntary Childlessness and being Childfree”
NICE fertility guidance.

Acknowledgment
I would like to offer an especial thank for Dr. K.D. Mahinda (Department of Physiology) for spending his valuable time and for giving his precious advice to make my effort more effective. And I also thank every other person who helped me in this effort.