Genetics
Perhaps surprisingly, much of male infertility is thought to be due to genetics. With the human DNA sequence completed by the Human Genome Project in April 2003, more conditions of male infertility caused by genetics will be discovered in coming years. Some known genetic causes of problems with male fertility include (among many others):
- Klinefelter syndrome: two sex X chromosomes in addition to the Y (XXY)
- Kallmann syndrome: pituitary production of LH and FSH is low or absent
- Kartagener syndrome, primary ciliary dyskinesia, immotile cilia syndrome: these are structural problems in the microscopic tubes in the sperm tail
- Congenital bilateral absence of the vas deferens (CBAVD): changes in the gene responsible for cystic fibrosis cause the vas deferens on both sides to be absent
- Androgen insensitivity syndrome: the receptor that binds to testosterone is altered
- 5-a-reductase deficiency: the enzyme that converts testosterone to the more active form dihydrotestosterone is altered
- Persistent Müllerian duct syndrome: female organs develop in the male embryo
- Changes in the deleted in azoospermia (DAZ) gene: alterations in a gene on the Y chromosome involved in making sperm
Azoospermia
Azoospermia refers to the condition where no sperm are found in the ejaculate. Azoospermia is different than anejaculation, where the man does not ejaculate. Azoospermia with a low ejaculate volume (typically less than one milliliter) may be caused by:
- Obstruction of the ejaculatory ducts emptying semen into the urethra. This may be treated by using surgery to open the ejaculatory ducts, or if surgery is not possible or unsuccessful, to extract sperm directly from the testis or epididymis for IVF.
- Retrograde ejaculation of sperm into the bladder. Rather than being propelled forward during ejaculation, sperm goes backwards into the bladder. This may be treated by medicines to strengthen the bladder neck, or retrieving sperm from the bladder for artificial insemination or IVF.
- Conditions like CBAVD which cause problems in development of the prostate and seminal vesicles. These may be treated by extracting sperm directly from the testis or epididymis for IVF.
Azoospermia with a normal semen volume may be caused by obstruction of the epididymis or vas deferens ("obstructive azoospermia", OA) or to problems with spermatogenesis ("non-obstructive azoospermia", NOA). A doctor can distinguish between obstructive and non-obstructive azoospermia with approximately 90% accuracy by measuring testis size and FSH. Biopsy of the testis is occasionally necessary to determine whether azoospermia is obstructive or non-obstructive.
A man may be born with obstructive azoospermia or he may have had a vasectomy, injury or infection as a cause later in life. The treatment of obstructive azoospermia is to correct the obstruction with microsurgery if possible. If surgical reconstruction is not possible or successful, sperm is extracted from the testis or epididymis. As it is immature, sperm extracted from the testis or epididymis must be used in IVF, typically with intracytoplasmic sperm injection (ICSI).
Like obstructive azoospermia, non-obstructive azoospermia may be present from childhood, or acquired later in life due to injury or infection. A man with non-obstructive azoospermia may be treated with medicine to stimulate spermatogenesis, requiring three months or more of treatment. If sperm is not found in the ejaculate after treatment, or if the couple prefers immediate treatment, sperm is extracted from the testis for IVF.
A surgeon may use many different ways of extracting sperm from the testis, including open surgery, microsurgery, using a needle to aspirate draw out sperm, and retrieving sperm from the testis or epididymis. All choices are possible with obstructive azoospermia, as large numbers of sperm are present in the testis. Non-obstructive azoospermia limits a surgeon's choices. In order to obtain enough sperm, a surgeon may use microsurgery, open surgery, or multiple needle punctures from the testis.[9]
Extracted sperm may be frozen for later use with IVF. Advantages of freezing sperm include that the couple may choose a date for the extraction procedure, the female partner may be present for the extraction, and the couple will know whether sperm was able to be extracted before IVF is done. There is no difference in the success of IVF with frozen sperm or sperm extracted on the day of IVF.
Hormones
Failure of the pituitary to release LH and FSH causes failure of the testis to produce testosterone and sperm. This condition is diagnosed by low testosterone accompanied by relatively low LH levels. The most extreme example of pituitary failure is Kallmann syndrome, which may be treated with HCG and recombinant FSH, often requiring lengthy treatment periods of a year or more. Milder forms of pituitary problems are common, and may be treated with clomiphene citrate if the pituitary is responsive.
Failure of the Leydig cells in the testis to make testosterone results in low levels of testosterone accompanied by very high levels of LH as the negative feedback of testosterone on the pituitary is decreased. Treatment is surgical extraction of sperm if possible, as the body is already providing its own hormonal stimulation.
Testosterone therapy is not used for male fertility. Although the blood levels of testosterone rise with external application of testosterone, negative feedback on the pituitary and the resulting fall in LH causes the very high levels of testosterone in the testis to fall. For this reason, scientists have studied external testosterone for male contraception.
High levels of the female hormone estradiol may impair male fertility; this condition can be treated with medications such as anastrozole (Arimidex). High levels of sex hormone binding globulin may also lower the amount of effective testosterone, referred to as “bioavailable” testosterone. If the total or bioavailable testosterone is too low, clomiphene citrate may be used to increase the production of testosterone in the testes.
Varicocele Because it is outside of the body, the testis is cooler than other organs, a condition that is important to sperm survival; conversely, heat is toxic to sperm production. The cords transporting blood to and from the testis are arranged in a radiator-like “counter current heat exchange.” A common cause of male fertility is varicose veins in the scrotum that heat the testis and disrupt sperm production. Varicose veins in the scrotum are called a varicocele. Until the 1990s, doctors argued whether varicoceles were important to male fertility, and if treating them helped. It was discovered that treating varicoceles that were neither felt nor visible to the naked eye was not helpful, but that varicoceles that could be felt or were visible damaged sperm production, and that male fertility improved with treatment. Treating a varicocele usually involves an outpatient surgical procedure called a “varicocelectomy,” which may be done with the surgeon using magnifying lenses or the operating microscope to preserve the tiny arteries carrying blood to the testis. A varicocele may also be treated by an experienced interventional radiologist.
Childhood conditions Sperm production in the pre-adolescent boy is inactive until he reaches puberty. If the testis does not descend in the scrotum, a condition called cryptorchidism, early sperm cells may be permanently damaged. Early treatment of cryptorchidism by surgery to bring the testis into the scrotum, called orchidopexy, is important to preserve a male's later fertility. Other childhood conditions that may affect future fertility include:
- Mumps orchitis: mumps involving the testis. Treatment is prevention of mumps, or if it occurs, treating as best as possible the episode of mumps.
- Testis torsion: the testis twists on itself. Treatment is surgical untwisting of the testis as soon as possible.
- Testis trauma: injury significant enough to disrupt the inside of the testis. If the outer sheath of the testis is ruptured, treatment is surgical repair.
The immune system
White blood cells in the semen release toxic chemicals that may affect sperm function. Antioxidants and anti-inflammatory medication may help prevent sperm damage by excessive white blood cells in the semen.
If the man's body is producing antibodies to his own sperm, “antisperm antibodies,” steroids may be used to desensitize the immune system. Intrauterine insemination with washed sperm may be used , but IVF with ICSI may be necessary to treat antisperm antibodies.
Problems with erections and ejaculation
Difficulty with erection of the penis becomes increasingly likely as a man ages. Many treatments are available to treat erectile dysfunction. Problems with ejaculation may be due to injury to the nerves controlling ejaculation, such as in spinal cord injury, or disease of the nerves by conditions like diabetes. Anejaculation (a condition where a man cannot ejaculate) may be treated by collection of sperm with vibratory stimulation of the penis or stimulation of the nerves using a procedure called electroejaculation, or by surgical extraction of sperm from the testis or epididymis and IVF.
This is a great piece to highlight the issues which a man can suffer. Thank you. My partner has/had high sperm antibodies and they told us that we needed ICSI IVF and assumed it was because of some unknown trauma at some point in his life.
I did my own research & we had a go at 'alternative' methods - acupuncture, a male pre-natal vitamin and antioxidants. When tested the antibody count had reduced significantly from about 80% to about 15%. However, the doctors were sceptical and said it may be a fluke or a lab error. We since however have had 2 natural pregnancies.
Therefore I was very pleased to see you have a category of immunology as a possible cause of male infertility as I dont think doctors necessarily give this sufficient focus and jump straight to ICSI-IVF.
What I would add is that I have not known steroids be recommended or prescribed (we spoke to five different REs) - the only thing I have read is that they arent used as the risks (bone damage) are considered too great. So is this some other sort of lower dose steroid that you are referring to?
Posted by: MARPSJR | 09/23/2010 at 06:21 AM