Most male infertility specialists classify problems with sperm production into two main categories: obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). Azoospermia means the absence of sperm in the ejaculate. The typical man has 100–300 million sperm in the ejaculate but the results of a semen analysis are highly variable, and the only condition on a semen analysis that makes natural conception completely impossible is azoospermia or the complete absence of any sperm in the ejaculate on at least two semen analysis performed by a high volume lab.
Obstructive azoospermia is caused when there is a plumbing problem that does not allow the sperm to get from the testis to the penis. This condition is also referred to as a post-testicular cause of azoospermia as the sperm production in the testis is fine but the transport system for allowing the sperm to leave the body is abnormal.
The most common cause of this is when a man has had a vasectomy and the vas deferens, which carry sperm from the testicles to the urethra during ejaculation, has been divided for contraception. Other causes are scarring from sexually transmitted infections, midline congenital cysts, which block the vas deferens from emptying into the urethra, narrowing of the opening of the penis from the foreskin (phimosis), and congenital conditions such as cystic fibrosis or a variant of it that result in abnormal formation of the male reproductive tract leading to malformation or lack of the vas deferens.
Natural conception may be possible for the vast majority of men who have undergone a vasectomy through the procedures vasovasostomy and vasoepididymostomy. Link to slide 14 Another option for men who have had a vasectomy or who have another form of obstructive azoospermia is a testicular sperm extraction (TESE) procedure. This procedure is typically done in the office under local anesthesia. After fully anesthetizing the scrotal skin, a small incision is made either with a scalpel to expose the testicular tissue or a needle is used to aspirate the seminiferous tubules (testicular tissue) to obtain sperm.
For men who have an obstruction where the vas deferens empty into the urethra at the ejaculatory ducts, a procedure called a transurethral resection of the ejaculatory ducts (TURED) can relieve this blockage and result in the flow of sperm through the natural channels. Narrowing of the foreskin can be treated with a circumcision and scarring from sexual infections can often be treated endoscopically (with a scope through the urethra in the operating room with a patient under general anesthesia).
Cystic fibrosis (CF) is a common pulmonary disease that has important reproductive consequences. Nearly all men (95%) with cystic fibrosis (CF) do not develop all or part of the vas and epididymis on both sides, a condition called congenital bilateral absence of the vas deferens (CBAVD). Although these transportation tubes are missing, sperm is still produced (spermatogenesis) in each testis. In fact, sperm production is normal in 90% of men with CF and CBAVD. CBAVD accounts for about 8% of all cases of obstructive azoospermia.
The exact cause of CBAVD is not known, but it is thought that the same gene mutations that cause the lung and pancreas problems with CF likely cause the failure of these ducts to form. Interestingly, 1–2% of infertile men who do not have signs of lung disease or digestive problems so commonly seen in CF have CBAVD. It is thought that CBAVD is based on similar genetic patterns found in typical CF but involves milder mutations that cause only the CBAVD and not the typical full blown picture of CF. As a result of this it is important that any man with CBAVD be evaluated by testing for CF. CBAVD does not affect sexual performance or ability to make love. n fact, most people are unaware that they have CBAVD until they are unable to conceive and seek care from a male reproductive expert. When considering parenting it is advisable for men with CF to consult a male reproductive expert.
Non-obstructive azoospermia is a set of disorders where there is abnormal production of sperm. While the etiology of non-obstructive azoospermia is multifactorial, all of these conditions have either decreased or absent sperm production.
Non-obstructive azoospermia can be further sub-divided into pretesticular and testicular causes. Causes of pretesticular non-obstructive azoospermia are hypogonadotropic hypogonadism (a problem with the pituitary where it does not make the hormones necessary for spermatogenesis or adequate testosterone production), hypothyroidism, use of certain medications, elevated estradiol, Kallman’s syndrome, and certain rare types of pituitary tumors. All of these conditions result in a disruption of the hormonal conditions necessary for normal spermatogenesis. These conditions are typically treatable through oral or injectable medications.
Testicular causes make up the majority of the cases of non-obstructive azoospermia. Broadly defined, a testicular cause is any process that disrupts spermatogenesis and originates at the level of the testicle. Varicoceles, link to slide 10 or varicose veins in the scrotum, are a common cause of disruption in spermatogenesis at the level of the testicle, but rarely result in azoospermia. Bilateral undescended testicles or cryptorchidism, testicular cancer, gonadotoxins (substances such as radiation, chemotherapy, and certain industrial chemicals that are toxic to the testes or gonads), immunologic insults to the testicles, such as post-pubertal mumps orchitis (a mumps infection of the testicle in a man who has already reached puberty), Sertoli-cell only syndrome (absence of sperm cells in the testis), maturational arrest (where all of the sperm can only reach a certain, incomplete stage of development), and many genetic syndromes such as Klinefelters (presence of an extra X chromosome in a man so they have XXY instead of XY) comprise the main testicular causes of azoospermia.
Regardless of the cause of non-obstructive azoospermia, the treatment approach is the same. In fact, we often cannot find the exact cause of non-obstructive azoospermia in the majority of cases. Most of these cases are caused by a combination of genetic factors that we are just beginning to understand.
The University of Utah offers one of the top andrology laboratories in the world investigating human sperm production and conditions, such as azoospermia, and has been at the forefront of many of these research developments for many years. Douglas T. Carrell PhD, HCLD, directs is the laboratory director for the andrology program.
Treatment of non-obstructive azoospermia begins with semen analyses and a male endocrine profile (blood work). If a man has a low bioavailable testosterone (<155 ng/dl) (note: this is very different from the total testosterone that many labs check), we typically start him on clomiphene citrate or clomid. The man remains on this drug for four months, and we repeat another semen analysis. One in nine men will have sperm return to the ejaculate after having their testosterone brought back within the normal range through medication. Even if a man does not have sperm return to the ejaculate, normalizing his testosterone through medication doubles the chances of finding sperm on a surgical sperm extraction procedure called microsurgical testicular sperm extraction (microTESE).
If a man has an adequate bioavailable testosterone on initial diagnostic testing or if he has had it corrected for at least four months and remains azoospermic, we typically recommend microsurgical testicular sperm extraction (microTESE). Sperm is found approximately 70% of the time in the microTESE procedure. For men with non-obstructive azoospermia, we typically do not recommend fine needle aspiration or biopsy prior to microTESE as many studies have shown that microTESE yields the highest sperm retrieval rate and causes the least amount of damage to the testis. If all of the sperm from the first microTESE are used in subsequent in vitro fertilization attempts, repeat microTESE procedures are possible. However, if the first microTESE is unsuccessful, repeat procedures result in only a 7-10% success rate.
Douglas T. Carrell, Ph.D.Locations
|Andrology & IVF Laboratories||(801) 581-3740|
Specialties: Andrology, Reproductive Endocrinology & Infertility, In Vitro Fertilization