How common is male infertility?
In 60% of cases, a male factor contributes to a couple’s infertility. That’s why it makes sense to evaluate the man as well as the woman when a couple is facing infertility.
Sperm takes three months to produce and mature and so there can be a four to six month delay between the time a man starts treatment and when he will see resulting changes in the sperm. Because the evaluation of the woman may also take several months, we recommend that a comprehensive semen analysis be performed as soon as the woman starts treatment. If necessary, the male partner can also immediately begin treatment. When the treatment of both partners happens at the same time, there is no unnecessary, additional delay.
CAUSES Of Male Infertility
Just like people can have varicose veins in the legs, a man can have dilated veins in the scrotum. When the blood doesn’t drain properly, the veins dilate (or enlarge). This extra blood that pools in the scrotum, raises the temperature and negatively impacts sperm production. The good news is that this is a common cause of male infertility and may be corrected with minor outpatient surgery.
The most highly trained specialists will perform this surgery microscopically to preserve the arterial supply and lymphatics. An incision is made about one inch above and to the side of the penis ( a subinguinal incision), avoiding the abdominal muscles. This procedure, referred to as a “microscopic subinguinal varicocelectomy,” means less post-operative pain for the patient.
Seminal Fluid Abnormalities
The semen may be very viscous (thick), making it difficult for the sperm to move into the woman’s reproductive tract. Sometimes we “wash the sperm”, which means that we separate the moving sperm from the dead sperm and surrounding debris, process it, and place it directly into the uterus with a small tube. This is called intrauterine insemination (IUI).
Ductal System Problems
There can be a number of problems with the ducts that carry sperm. For instance, a man can be born missing ducts on either or both sides of the vas deferens (the duct that conveys sperm from the testicle to the urethra). There can be an obstruction at the point where the delicate tubular structure drains the testes. Or there can be an obstruction higher up in the more muscular vas deferens. Additionally a man can have blockages which occur as a result of a repair of a hernia or hydrocele or from scar tissue due to an infection.
Sperm must travel through the ejaculatory ducts as they go from seminal vesicles to the urethra. If these ducts are blocked, the sperm can’t get through.
The first treatment option is repairing or unblocking the ducts. If that is not possible, the sperm can be harvested (removed by a physician) for insemination. When sperm is harvested, physicians can usually only harvest low numbers, so this procedure must be used in conjunction with advanced reproductive techniques in order to attempt a pregnancy.
It is possible for a man to develop antibodies to his own sperm. This can occur because of testicular trauma, testicular infection, large varicoceles, or testicular surgery. Sometimes, there are unexplained reasons for this occurrence.
The antibodies have a negative effect on fertility, but the reason isn’t clear. Most likely, the antibodies cause the sperm to have trouble penetrating the partner’s cervical mucous and making their way to the uterus. It may become more difficult for the sperm to bind with the external membrane, shell, of the egg, or to fuse with the eggs themselves.
Can the antibodies be treated? Yes, but that treatment is controversial and the side effects problematic. To avoid complicated side effects, often the first level of treatment is intrauterine insemination. If the couple is planning in-vitro fertilization (IVF) and antibodies are present, the sperm can be injected directly into the egg (ICSI) instead of using the conventional IVF procedure which may be affected by the antibodies.
Difficulties with Erections and Ejaculations
In about five percent of couples with infertility, the problem is partially due to difficulties related to intercourse. This includes the inability to obtain or maintain an erection, premature ejaculation, lack of ejaculation, retrograde (or backward) ejaculation, lack of appropriate timing of intercourse, and excessive masturbation. Many men may have difficulty with erections under the pressure of trying to achieve conception. Interestingly, the most common problem is infrequency of intercourse. Studies have shown that five out of six previously fertile couples having intercourse four times per week will conceive over six months, while only one out of six will conceive if they have intercourse once per week during the same period . In most of these situations, the problem can be solved when these couples learn the technique of self-insemination.
When the sperm-producing part of the testicles can’t make an adequate number of mature sperm, it is called testicular failure. It can happen for any number of reasons: the testicle may lack the cells needed to divide and become sperm, the sperm can’t complete their development or there are too few sperm to travel through the ducts into the ejaculated fluid. Genetic abnormalities, hormonal factors, or varicoceles, the veins in the scrotum, may cause this situation.
The good news is that even if your testes are producing very little sperm, the sperm can be harvested and, using advanced reproductive techniques, pregnancy can be attempted.
Cryptorchidism, a condition where a baby boy is born without the testes fully descending into the scrotum, is a possible cause of testicular failure. The testes are very sensitive to temperature and if they do not descend into the scrotum prior to adolescence the body’s heat will stop them from producing sperm. They will also have a higher rate of malignancy. The current recommendation is that at approximately one year of age, if the testes have not descended by themselves, this is corrected surgically.
Cryptorchidism can be a factor in male infertility. 19 percent of men with one testis in this condition will have fertility issues. 50 percent of men with cryptorchidism in both testes will have normal fertility. This may be due either to something inherent in the testes which made them unable to descent or to damage done by not having the testes brought down in time.
Even fairly common drugs may have a negative effect on sperm production and/or function. Some of those include:
- Ketoconazole (an anti-fungal)
- Sulfasalazine (for inflammatory bowel disease)
- Spironolactone (an anti-hypertensive)
- Calcium Channel Blockers (anti-hypertensives)
- Allopurinol, Colchicine (for gout)
- Antibiotics: Nitrofuran, Erythromycin, Gentamicin
- Methotrexate (cancer, psoriasis, arthritis)
- Cimetidine (for ulcer or reflux)
The following drugs can cause ejaculatory dysfunction:
- Antipsychotics: Chlorpromazine, Haloperidol, Thioridazine
- Antidepressants: Amitripltyline, Imipramine, Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft)
- Anti-hypertensives: Guanethidine, Prazosin, Phenoxibenzamine, Phentolamine, Reserpine, Thazides
The testicles need pituitary hormones to stimulate them to make sperm. If these hormones are absent or severely decreased, the testes cannot produce sperm to maximum capacity. It is important to note that men who take androgens (steroids) for body building, either by mouth or injection, shut down the production of hormones for sperm production.
If you’re a male with infertility problems it is important to run blood tests in order to understand your hormonal profile. A hormonal profile will rule out some serious medical conditions, provide more information on the sperm-producing ability of the testes, and inform the physician on the possibility of future hormonal treatment.
Men may have infections of their reproductive tract. These may include infections of the prostate (prostatitis), of the epididymis (epididymitis), or of the testes (orchitis).
After puberty, in rare cases, viruses can result in absolute and irreversible infertility. Bacterial infections or sexually transmitted diseases can cause blockages of the sperm ducts. In these cases, sperm production may be normal but the ducts carrying them are blocked.
Active bacterial or viral infections may also have a negative effect on sperm production or function. White blood cells, the body’s response to infection, can also have a negative effect on sperm membranes, making them less hearty.
When excessive white blood cells (more than one million/cc) are found in a semen specimen, we recommend having cultures performed on the specimen. These cultures include tests for commonly asymptomatic, sexually-transmitted diseases: mycoplasma, ureaplasma, and Chlamydia. Also, a general genital culture is usually taken. If the infection and the white blood cells are persistent, antibiotics may be considered.
Ejaculate isn’t sterile and most men will test positive for two organisms. That’s why it’s important to be judicious in treating non-sexually-transmitted organisms found on cultures.
This is an area of active research. At this point it is recommended that all men receive basic genetic testing, measuring the number of chromosomes and looking at the blocks of genetic material. Screening for the genes that can cause cystic fibrosis is sometimes suggested. There are tests for specific genetic abnormalities on the male chromosomes that can cause azoospermia. If a son were to inherit this, he may have the same problem.
Cigarette smoking significantly affects semen quality. A regular smoker has a 23% decrease in sperm density (concentration) and a 13% decrease in sperm motility (ability to move). To a lesser extent, smoking causes toxicity to the fluid ejaculated with the sperm (seminal plasma). And when sperm from non-smokers were placed in the seminal plasma (hormonal) of smokers, the sperm were adversely affected (had significantly decreased viability).
Smoking affects the hypothalamic-pituitary-gonadotropic axis, most commonly affecting levels of estrogens. Other problems are secretory dysfunction in the Leydig Cells, which are in the testes and produce testosterone. Most worrisome is that there is evidence that suggests that paternal smoking may also be associated with congenital abnormalities and childhood cancer, though the relative risk in most studies is less than two.
Marijuana often causes a decreased average sperm count, a change in the movement of the sperm (motility), and compromised size and shape (normal morphology). It affects the hormonal axis (HPG), causing decreased plasma testosterone. It may also have a direct negative effect on the Leydig Cells.
Even infrequent cocaine use causes decreased sperm count, motility, and normal morphology. These effects can be found in men who have used cocaine in the two years preceding their initial semen analysis. Cocaine also decreases the ability of sperm to penetrate the cervical mucous, making it difficult for them to enter the uterus.
Anabolic Steroids (male hormones)
The use of anabolic androgenic steroids has reached almost epidemic proportions. Nearly seven percent of 12th-grade males use or have used them to build muscle mass and improve athletic performance. These male hormones suppress normal testosterone production. This decreases the intratesticular testosterone level. This may cause severely diminished spermatogenesis or complete absence of sperm (azoospermia). These steroids cause a persistent depression of the hypothalamus and pituitary, which may be irreversible even when the steroids are stopped.
Moderate alcohol use does not affect male fertility. However, excessive alcohol use affects the hormonal axis and negatively affects the gonads. It may cause associated liver dysfunction and nutritional deficiencies, which are also detrimental for sperm production.
Most vaginal lubricants, including K-Y Jelly, Surgilube, and Lubifax, are toxic to sperm. Couples should avoid their use when trying to achieve a pregnancy. There are lubricants which are specifically formulated for use when trying to conceive.
Male Infertility TESTING
The most important first step in any man’s evaluation is the semen analysis. The semen analysis allows us to identify problems to be addressed in order to maximize the quality of the man’s semen. This may reduce the need for more complicated interventions for the female partner. It will also allow us to rule out significant medical problems that may contribute to poor analysis results.
Semen is the fluid that a man ejaculates. It is produced at several different sites in the body. The sperm within the semen are the cells that actually fertilize the egg. While it is most important to assess the sperm, they account for only 1% to 2% of the semen volume. Problems with the surrounding fluid may also interfere with the movement and function of the sperm. Therefore, both the sperm and the fluid must be tested.
There is no specific, magic number of sperm in the semen analysis of men whose partners will get pregnant. The partners of some men with a very poor semen analysis may conceive easily. The partners of some men with an excellent semen analysis may experience difficulty. However, men with good semen analysis results will, as a group, conceive at significantly higher rates than those with poor semen analysis results. The semen analysis will help determine whether there is a male factor involved in the couple’s sub-fertility. In those cases, we will recommend an evaluation. There are certain findings of the semen analysis which suggest specific potential problems. For example, an increased white blood cell count may indicate infection or inflammation. However, other abnormalities in many of the main parameters are non-specific. For example, there are a number of different causes for a decreased sperm count or diminished sperm movement. Some of these causes have other serious medical implications, others don’t. A thorough evaluation helps determine the cause of an abnormal semen analysis.
Standard Semen Analysis Tests
Almost all laboratories will conduct tests and report on the following information, using values established by the World Health Organization:
- Concentration (sometimes referred to as “the count”): This is a measurement of how many million sperm there are in each milliliter of fluid. There are various techniques for obtaining this number. Some prove to be more accurate than others. Average sperm concentration is more than 60 million per milliliter (>60 million/cc). Counts of less than 20 million per milliliter (<20 million/cc) are considered sub-fertile.
- Motility (sometimes referred to as “mobility”): This describes the percentage of sperm that are moving. Fifty percent or more of the sperm should be moving.
- Morphology: This describes the shape of the sperm. The sperm are examined under a microscope and must meet specific sets of criteria for several sperm characteristics in order to be considered normal. Most commercial laboratories will report WHO morphology (use World Health Organization criterion). Thirty percent of the sperm should be normal by these criteria.
- Volume: This is a measurement of the volume of the ejaculate. Normal is two milliliters (two ccs) or greater. The volume may be low if a man is anxious when producing a specimen, if the entire specimen is not caught in the collection container, or if there are hormonal abnormalities or ductal blockages.
- Total Motile Count: This is the number of moving sperm in the entire ejaculate. It is calculated by multiplying the volume (cc) by the concentration (million sperm/cc) by the motility (percent moving). There should be more than 40 million motile sperm in the ejaculate.
- Standard Semen Fluid Tests: Color, viscosity (how thick the semen is), and the time until the specimen liquefies should also be measured. Abnormalities in the seminal fluid may adversely affect the sperm. For example, if the semen is very thick, it may be difficult for the sperm to move through it and into the woman’s reproductive tract.
Additional Semen Analysis Tests
- Forward Progression: This describes how well the sperm that are moving are making progress. Only when the motility (percent moving) is combined with the forward progression is an accurate picture of sperm movement obtained. Unfortunately, this is often not tested by commercial laboratories. A man’s motility may be normal and the fact that the sperm are moving sluggishly or almost not at all will be overlooked if the forward progression is not recorded separately.
- Kruger Morphology: This is a more detailed evaluation of the morphology. Slides are specially stained and the sperm examined microscopically under high-power magnification. The sperm must meet a stringent set of criteria that evaluate the shape and size of the head, midpiece, and tail in order to be considered normal. A Kruger test helps determine which of the available advanced reproductive techniques may be most appropriate and successful.
- Anti-Sperm Antibodies: Some men may produce antibodies to their own sperm. These antibodies may decrease fertility rates in a number of ways. They may impede the movement of sperm through a woman’s cervical mucous, inhibit the binding of a sperm to the egg, and/or inhibit its penetration into the egg. Men who are most at risk for developing antibodies are those with previous testicular and epididymal infection, trauma, surgery, or large varicoceles. The presence of these antibodies is often not predictable from other semen parameters or from the man’s history.
- White Blood Cells: The semen may contain a high number of white blood cells, which may be an indication of either infection or inflammation. White blood cells are considered significant if more than one million are found in each milliliter of the ejaculate.
White blood cells cannot be differentiated from other round cells normally found in the semen (debris and immature sperm) without special staining. If more than one-million round cells are found in the ejaculate, a portion of the ejaculate should be specially stained to look for an increased number of white blood cells.
If the white blood cell count is elevated, semen cultures should be performed on a subsequent specimen. Unfortunately, the semen culture cannot be performed on the original specimen as it must be the first step performed on the specimen in order to keep it sterile.
In certain situations, specialized tests are needed. These depend on the findings at the time of the analysis and can often be performed on that specimen.
- Spun Specimen: Even if no sperm are seen on the test slide, the sperm count may still not be zero (there may be very low numbers of sperm in the ejaculate). This has very important implications as it may determine if the couple can conceive using advanced reproductive techniques. This must be assessed by spinning down the specimen so all of the sperm are concentrated in a pellet on the bottom of the tube and then examining the pellet beneath the microscope.
- Viability: Sperm may be alive, but not moving. A specialized staining technique is used to determine what percentage of the sperm are alive and is indicated when the motility (percent moving) is less than thirty percent.
- Fructose: In men with no sperm or very low numbers of sperm in the ejaculate, it is important to determine whether the sperm are not being produced at all, or whether they are being produced but are blocked from “getting into” the semen. A fructose test can help differentiate between these two problems.
- Post-Ejaculatory Urinalysis (PEU): Some men ejaculate all or part of the sperm backward into the bladder. This can be detected by having a man ejaculate and immediately afterward urinate into a separate cup. The post-ejaculatory urine is then centrifuged to see if any sperm are present.
- Expertise: Semen testing is a sophisticated and technical field. An improperly performed or incomplete semen analysis may miss significant problems. Unrecognized problems may unnecessarily delay a man’s treatment. Unlike many other lab tests which are mechanized, a semen analysis relies completely on the expertise of those performing it. Be sure the lab has sophisticated protocols and well-trained, specialized technicians.
- Timing:In order to get accurate results, the specimen must be processed within one hour of collection. If not, the measurement of the movement of the sperm may be extremely inaccurate. With any lab you use, make sure that the analysis is performed on site and not shipped elsewhere for evaluation.
- Thoroughness: As a semen analysis is being performed, certain findings may indicate the need for additional tests. Ideally, you should use a laboratory that has the capability to do complete initial testing as well as the flexibility to do the appropriate follow-up testing on the same specimen.
- Comfort and Convenience: In order to maximize your results, it is important that you are as relaxed as possible. Ideally, the specimen should be collected at the laboratory itself in a comfortable room that is meant specifically for that purpose.
Male Infertility TREATMENT
The purpose for all of this testing is to arrive at a treatment plan that can improve your fertility. More than 50% of men will have a treatable cause of male factor infertility. These factors include varicoceles (dilated veins in the scrotum), infections, hormonal abnormalities, abnormalities in the seminal fluid, ductal blockages, and difficulties with erections and ejaculation. When these conditions are treated, either through medication (hormones or antibiotics) or surgery (varicocelectomy, vasal reconstruction, repair of a blocked ejaculatory duct), a man will often see a significant improvement in his semen analysis.
If the specialist believes that sperm might indeed exist, even after sperm production has been maximized but still can’t be found in the ejaculate, he may suggest one of the following advanced techniques:
In 44% of cased where no sperm was found, this technique may be able to find even a single sperm through advanced processing techniques. These sperm may then be used in in-vitro fertilization (IVF) with intracytoplasmic sperm insertion (ICSI). ESSM involves a specially trained andrologist processing the specimen, then dividing it into minute amounts. They then spends multiple hours looking through the entire semen specimen for any moving sperm. If sperm are found, they are placed on a specialized device, and frozen in a minuscule quantity of fluid so that they can be easily found when needed for insertion into an egg.
In those cases where appropriate interventions have been tried and where the ESSM did not locate sperm in the ejaculate, there may be the possibility of harvesting sperm directly from the testes. In 43-68% of azoospermic men there may be small number of sperm, which have been produced in the testis, but exist in such small quantities that they do not reach the semen. An in-office procedure called Sperm Mapping can determine if there are sperm producing areas in the testes, and where they are. If sperm are found on the sperm mapping, then the couple can proceed with in-vitro fertilization and an open sperm retrieval procedure, called micro-TESE (Testicular Sperm Extraction).