Many different factors can ultimately contribute to a man's infertility, and it's important for a medical health professional to ask the right questions in order to determine this diagnosis. Proper evaluation of the man in an infertile couple includes a detailed questionnaire (known as a medical history), which looks for clues as to what may be causing the infertility. Questions about childhood and current illnesses or surgery, previous and current medications and family patterns of fertility are important. Has the man been able to get a previous partner pregnant? Has there been a pattern of recurring miscarriages? These and other questions are relevant.
Semen Testing
Semen testing is a critical part of the evaluation of the man but unfortunately it does not tell the whole story. A standard semen test will report the volume of the fluid, the number of sperm in it, the percentage of sperm moving (motility), how fast the sperm are swimming (progressive motility) and what percentage of sperm appear normal or abnormal (morphology). Sperm testing is typically performed with one or two days of abstinence. There is a wide range of “normal” when it comes to sperm counts. Sperm counts can vary dramatically from one test to another, from one season to another, and from one lab to another. At least two tests are recommended to get an idea of where the fluctuating results trend. There is a wide range of patterns of semen tests that are seen with normally fertile men. There is an equally wide range of patterns of semen tests that are seen with infertile men. It's often very difficult for a doctor who is not experienced in evaluating semen tests to make an accurate prediction of whether a man is truly normally fertile based on the results of one semen test.
Advanced Testing
When all the results of a standard semen test are normal, there still can be a hidden problem with the sperm quality that may be preventing the sperm from successfully fertilizing the egg, or may be resulting in early miscarriages. More advanced testing is required to discover such a hidden problem of sperm quality. There are a variety of tests that attempt to predict sperm quality. Strict Morphology is a test where sperm are examined at very high power magnification to determine what percentage of sperm look perfectly normal. Most normal men will only have less than 15 to 20 percent normal, and in fact, many men will be able to successfully cause a pregnancy with less than the standard cut off for normal of 14 percent. If the level is severely low, then it likely is predicting poor quality.
Another test is the hamster egg penetration test, in which the patient’s sperm are mixed in a dish with specially prepared hamster eggs. Normal donated sperm is also mixed with different hamster eggs and the amounts of sperm that penetrate the eggs are compared between the patient and the normal donor. It is thought that if the patient’s sperm do not penetrate the hamster eggs well, they may not be able to penetrate human eggs effectively. This test, like the Strict Morphology test, is not a perfect predictor of sperm function and even with abnormal results, patients may go on to get their wives pregnant naturally. However, more often than not, when the test is very abnormal, there is a problem with the sperm. The computerized semen analysis (CASA) uses a computer scanner to measure different characteristics of how sperm swim, how straight, for example. It is thought that the characteristics of how the sperm are moving may correlate to how well the sperm may function.
An increasingly popular test looks at what percentage of the sperm’s DNA is packaged in a fragmented way. It is thought that if there is a high percentage of fragmentation then natural conception and even intrauterine insemination is unlikely to work. It is also thought that a high percentage of fragmentation may be the cause of recurrent miscarriages in some couples.
Like with all these tests, there are always exceptions where patients with abnormal results still get their wives pregnant naturally. Some treatments can improve abnormal findings in this and the other tests. Alternatively, in-vitro fertility with intracytoplasmic sperm injection (ICSI) can increase the chances of the sperm fertilizing the egg and establishing a pregnancy successfully even when these tests are abnormal.
Other tests that may be performed on the semen include culture for bacterial infection. A few labs offer evaluation of the level of reactive oxygen species in the sperm. These are chemicals that can degrade sperm. They may come from the environment, infection, inflammation, smoking, or other conditions affecting the testicles like varicose veins of the testicles (varicoceles). In cases of severe infection or injury to the testicles, or even surgery on the testicles or vas deferens (vasectomy), antibodies against the sperm can arise. These can be tested with an antisperm antibody test on the sperm (not the blood). It there are a lot of antibodies bound on the sperm, the sperm will not be able to penetrate the egg on its own.
Hormone Testing
Hormone testing is another important part of the evaluation of the man. This is blood testing and it is best performed in the morning when the man’s reproductive hormones are typically surging. Testosterone and Follicle Stimulating Hormone (FSH) are two important indicators of the function of the man’s testicles. Testosterone is made primarily in the man’s testicles and a small amount in his adrenal gland. If there is a problem with the testicle, the testosterone may be low. Many more men with infertility have low testosterone than men with normal fertility. However, the majority of men with infertility still have normal testosterone levels because the testicles can sustain testosterone production better than they can sustain sperm production when there is s problem.
Evaluation of the Pituitary Gland
FSH is the hormone that is produced by the pituitary gland, which stimulates the testicles to produce sperm. The pituitary gland is a grape size structure that hangs from the mid-portion of the brain just behind the eyes. When the testicles receive this hormone, they make sperm which then releases a signal back to the pituitary telling it to stop releasing so much FSH. This signal is called inhibin. If there is a problem with the testicle, there won’t be normal or in some cases any sperm production and there will be less inhibin signal released and as a result, the pituitary gland will release higher than normal amounts of FSH. Therefore, a higher than normal FSH is a signal that low or even no sperm counts are due to a problem with the testicle working as opposed to a blockage or a lack of stimulation.
There can, on the other hand, be a problem with a lack of stimulation. In this situation, the pituitary or the hypothalamus, which is a part of the brain above the pituitary that controls it, is not releasing adequate levels of hormones such as FSH, so that the testicles are simply not getting enough stimulation to make sperm. In this case, if the pituitary can be stimulated to release more FSH or if an injection of FSH is given to the patient, the testicles will usually produce more sperm. If the FSH is already high, injecting more FSH is not likely to help. Prolactin is a hormone which is produced at low levels by the pituitary gland. If there is a tumor of the pituitary gland, there may be an excess secretion of prolactin which will suppress the signals to the testicles to produce testosterone and sperm. A high prolactin level is an indication to look for a pituitary tumor with an MRI of the brain. Sometimes pituitary tumors do not secrete prolactin but cause the FSH and testosterone to be low. This hormonal pattern can be a tip off to check an MRI of the brain.
Excessive estrogen can prevent the pituitary from releasing the normal stimulation to the testicle for sperm and testosterone production. High estrogen or estradiol can be detected on blood testing. Estrogen levels may be higher in obese men, and weight loss can improve this cause of low testosterone and infertility. Medications can be used to decrease the production of estrogen that occurs in the fat of these men which usually increased testosterone levels and may improve fertility. Testosterone is mostly produced in the testicle. The amount of testosterone in the testicle is about 100 times more concentrated than the amount in the blood stream. Only one percent of the concentration that the sperm are exposed to is flowing though the circulation to reach the pituitary gland.
When the pituitary received that much lower concentration, it then stops sending the signal to the testicle to make more testosterone. This signal is called Luteinizing hormone (LH). If a man is given testosterone, whether it's injected or through a topical gel or patch, the concentration that gets into his blood is about the same as the concentration that the pituitary is used to receiving but only one percent of that the sperm need. Nonetheless, the pituitary is tricked into stopping the signal to simulate the testicle and additionally it is tricked into stopping the signal to stimulate the sperm production.
As a result, very little LH and very little FSH is released. Without normal levels of LH, very little testosterone is produced inside the testicles and sperm production which relies on FSH as well as high testicular levels of testosterone 100 times higher level of testosterone is shut down. Testosterone supplements shut down sperm production they do not improve it. Thyroid abnormalities—either too much or too little can result in impaired fertility as well and this may be screened for with blood testing.
