One of the biggest concerns of couples involved in an infertility work up relates to the status of the male partner's sperm evaluation. While the thorough evaluation of sperm and sperm function should be given high priority in any infertility evaluation, we have found from our web page interactions with patients that often times the couple are told very little related to test results in this area. Or, in other cases, we hear of couples being told about "high numbers" of "abnormal" sperm, or "low" numbers of "good" sperm with little additional information about what those results mean to their chances for conception. Other very concerned couples have sent us copies of original semen analysis reports, having been told of "problems". On review, many of these reports have been printed with very out of date data related to what "normal" fertility test results should be in a fertile man. While there is no substitute for the evaluation of semen and sperm testing results by a highly trained and specialized professional, the truth is that many modern laboratories and even some very well qualified physicians have not kept totally abreast of our changing understanding of sperm function, and our new and evolving views of "fertile" sperm test results.
In our laboratory, we arrived at our "normal" values for sperm test results by closely watching the fertility course of the many, many patients that we have tested and followed over the years. If 60% of our male patients with sperm counts of 20 million/ml (considered "low" by many laboratories) are able to produce pregnancies without medical assistance, should a count of 20 million be considered "infertile"? In the 40% of men unable to produce a pregnancy with a count of 20 million/ml, they may indeed have a fertility problem. The point is that there are no absolutes in the area of sperm evaluation. This is true between different laboratories, and even within the same laboratory.
It is our opinion that sperm test results should not be presented to patients by way of a five minute telephone conversation. Instead, we feel each couple is entitled to sit in consultation with their physician or nurse or Laboratory Director and be advised of the specific results, and how those results compare to the results of known fertile males tested in that laboratory. Couples should also ask and be told about how the "Normal" ranges for the individual laboratory were established. There are, of course, many more things to be elicited from the laboratory, but we feel this to be a good starting point.
Male Reproductive Semen and Sperm Testing
The Fertility Institutes have Board Certified, Male Reproductive MEDICAL (Urologist/Andrologist) AND LABORATORY (Embryologist/Andrologist) Specialists Available At Each Location, Including MEXICO. We provide all advanced male reproductive semen and sperm testing in-house and with our affiliated laboratories worldwide.
Laboratories performing sperm "counts", in general, vary in the details that they provide the physician requesting the "count". A general sperm count as part of a fertility evaluation should include the total density or count (20 million per ml or above), and the motile density (8 million per ml or higher). The motile density is perhaps the most important part of the semen analysis, as it reports the total number of sperm thought capable of progressing from the site of sperm deposition to the site of fertilization. This value is essential in both allowing a determination regarding whether or not a semen analysis is "normal", as well as in providing prognostic information should advanced reproductive medical assistance be required. (Numbers in italics are what "normal" values should be.)
Definitions of "abnormal" counts:
Oligozoospermia: Sperm count less than 20 million/ml
Hypospermia: Semen volume < 1.5 ml
Hyperspermia: Semen volume > 5.5 ml
Aspermia: No semen volume
Pyospermia: Leukocytes (germ fighter cells) present in semen
Hematospermia: Red blood cells present in semen
Asthenozoospermia: Sperm motility < 40%
Teratozoospermia: > 40% of sperm seen are of abnormal form
Necrozoospermia: Nonviable ("dead") sperm
Oligoasthenozoospermia: Motile density < 8 million sperm/ml
Sperm Morphology (Shape and Appearance)
The evaluation of sperm size, shape and appearance characteristics should be assesed by carefully observing a stained sperm sample under the microscope. The addition of colored "dyes" (stains) to the sperm allow the observer to distinguish important normal landmarks (characteristics) as well as abnormal findings. Several methods of staining sperm are used, and the method employed should be one with which the examiner is comfortable and experienced.
Several different shapes or forms of human sperm have been identified and characterized. These forms fall into one of four main categories: normal forms, abnormal head, abnormal tail and immature germ cells (IGC), as follows:
Normal sperm have oval head shapes, an intact central or "mid" section, and an uncoiled, single tail.
Many different sperm head abnormalities may be seen. Large heads (macrocephalic), small heads (microcephalic) and an absence of identifiable head are all seen in evaluations. Tapering sperm heads, pyriform heads (teardrop shape) and duplicate or double heads have been seen. Overall (gross) abnormalities in appearance may be termed "amorphous" changes.
Coiling and bending of the tail are sometimes seen. Broken tails of less than half normal length should be categorized abnormal. Double, triple and quadruple tails are seen and are abnormal. Cytoplasmic droplets along the tail may indicate an immature sperm.
Immature germ cells (IGC's)
White blood cells (WBC's, germ fighters) in the semen should rarely be seen. It is very difficult to distinguish between an immature germ cell and a WBC. Because the presence of WBC's in the semen (pyospermia) can be a serious concern, if a report of "many IGC's" is delivered, it becomes very important to assure that these cells are not, instead, WBC's.
Sperm "Motility" (Movement)
Sperm motility studies identify the number of motile (moving) sperm seen in an ejaculate specimen. Here again, as in many other sperm studies, many laboratories use "normal" values that are out of date and inaccurate. Many labs will assess sperm motility upon receipt of the specimen, and again at hourly time intervals for four to twenty four hours. It is well known that sperm motility is a temperature dependent sperm function, so the handling and processing of specimens is critical. It is for this reason that we, except in very rare instances, require that specimens be evaluated only in a laboratory such as our own, where we are able to tightly control laboratory conditions. We have found the repeated testing of sperm over time for motility adds little to the evaluation of motility over the initial sperm motility assessment. Sperm are known not to survive well for extended periods of time in semen, and in nature, sperm very rapidly leave the semen to enter the cervical mucus. Many laboratories consider "normal" sperm motility to be 60% or greater. Our own studies, in agreement with many others have found men with 40% or greater sperm motility to be "normal". Motility characteristics:
Decreased sperm motility. If found to be present, exam should be repeated to assure that laboratory conditions did not cause the problem. Frequent causes: abnormal spermatogenesis (sperm manufacture), epididymal sperm maturation problems, transport abnormalities, varicocele. These conditions should all be looked for if sperm motility is repeatedly "low".
A total absence of moving sperm. It is vital, if sperm are seen, but are not moving, to carry out studies (vital stains) to see if the sperm seen are alive. It is possible to have sperm with normal reproductive genetics that are deficient in one or several of the factors necessary to produce motility. We have achieved several successful pregnancies emploting microinjection of healthy, non motile sperm directly into the egg (ICSI).
Chemical and Biochemical Semen Characteristics
Semen acid-base balance (pH)
The pH of semen is measured using a specially treated paper blot that changes color according to the pH of the specimen that it is exposed to. The pH of normal semen is slightly alkaline ranging from 7.2 to 7.8. Prostatic secretions are acidic while the secretions of the seminal vesicles are alkaline. Therefore, alterations in pH may reflect a dysfunction of one or both of these accessory glands. The pH of semen has not been generally found to have a major influence on a man's fertility potential.
Color and Turbidity
Semen is normally translucent or whitish-gray opalescent in color. Blood found in semen (hematospermia) can color the semen pink to bright red to brownish red. The presence of blood in semen is abnormal and should be reported. The presence of particles, nonliquified streaks of mucus or debris requires further evaluation.
Semen is normally produced as a coagulum. The specimen will ususally liquify within 30 minutes. The failure to liquify within one hour is abnormal. Excellent methods for correcting this problem in the laboratory are available.
Nonliquefaction and excessive viscosity are two separate conditions. Viscosity is measured after complete liquefaction has occured. Viscosity is considered "normal" if the liquefied specimen can be poured from a graduated beaker drop by drop with no attaching agglutinum between drops. The role of hyper (excessive) viscosity is being studied, but it seems possible that htis condition may interfere with the ability of sperm to travel from the site of deposition into the cervix or uterus.
Computer Assisted Semen Analysis (CASA)
The use of computer asisted semen analysis has advanced the ability to study and understand sperm function as it relates to human infertility. The major advances have been in the ability to more accurately determine sperm concentration (counts) and motility (movement). Generally, sperm are "looked" at by a computerized digitizing tablet through a microscope. The computer has been "taught" by the laboratory personnel what sperm look like, and how they move. When the computer then "sees" a sperm under the microscope, it is able to draw a digitized picture of each individual sperm, including the speed and path this sperm takes while moving under the microscope. A great deal has been learned about the normal and abnormal "micro"characteristics of sperm employing this method. The method is, however, not foolproof. The computer is only as intelligent as it's programmer. Small changes in the computer program can alter the sperm calculations significantly. The computers must constantly be monitored and updated. In our laboratories, all grossly abnormal CASA assays are always verified by both a repeat analysis as well as with a "hands on" human second look opinion. We feel that any abnormal sperm count must be verified by a manual counting and assesment method.
Sperm Penetration Assays (SPA, "Hamster Tests")
There have been many attempts made to develop a Laboratory test that will accurately predict the ability of a human sperm to fertilize a human egg. Dr. Aitken and his group many years ago demonstrated a correlation between sperm movement characteristics and sperm fertilizing ability as evaluated by the zona pellucida-free hamster egg penetration test. In this test, the species specific barrier to penetration (not fertilization) is removed from the ova (eggs) of the hamster. These oocytes are then exposed to prepared sperm from the man being tested. There is some feeling that if a man's sperm are able to penetrate the hamster eggs in the laboratory, there is a higher likelihood that his sperm will ultimately be able to fertilize a human egg if so exposed. This test is not uniformly accepted, due to the high false negative (no penetration of the hamster egg, but wife gets pregnant anyway) rate and the sometimes seen false positive (penetrates the hamster egg but does not fertilize human eggs in vitro) rate of this test. Our experience has been that good performance in the hamster test can provide some limited reassurance of the likelihood that a man's sperm will be able to achieve fertilization if given the chance. If men fail the hamster test, we rely upon in vitro fertilization with ICSI. This protocol has provided us with excellent success rates in men whose sperm function remains questionable. It should be noted that most men that fail the hamster test, are able to achieve normal fertilization with ICSI. For a detailed explanation of the "hamster test" click here.
The postcoital test (also known as the Huhner test or the Sims-Huhner test) is a valuable office test that should be carried out in selected patients early in their infertility evaluation. While this is a very popular and widely used test, there are no widely accepted normal values for the interpretation of this test. Simply, the postcoital (after intercourse) test evaluates the women's cervical mucus at the time of ovulation and how the mucus interacts with her husband's sperm as ovulation is about to occur. The couple is instructed to avoid sexual intercourse for two days prior to the exam. When evidence of impending ovulation is detected (LH testing, hormone blood tests, ultrasound, etc.) the couple is instructed to have intercourse and then present to the office 6 to 10 hours later (standard test). At this time, a small drop of mucus is painlessly removed from the endo (inner) cervix, and this drop is examined under the microscope. A favorable result would find many sperm in thin watery mucus, with good forward, active motion through the mucus. If the initial test is good, a second delayed exam (18-24 hours after intercourse) may be required if infertility persists. If the initial test is poor, a repeat exam carried out 2-3 hours after intercourse may be needed. The timing of the postcoital exam is very important. If carried out too soon after intercourse, sperm that appear normal at that time may later die, giving a false sense of security. Patients should assure that the test timing is appropriate, and that they are not just being squeezed in to a busy schedule at a convenient time. A normal test largely excludes the cervix as a contributor to any fertility problem.
Sperm Washing and Freezing
Sperm "washing" techniques have been applied to treat a wide variety of sperm and semen disorders, as well as to prepare "normal" sperm for intrauterine insemination in the treatment of some female disorders. What is being "washed" in a sperm washing procedure are the various constituents of semen and the remainder of the ejaculate not deemed necessary to achieve fertilization of the egg. An ejaculate is not a sterile specimen and may contain both aerobic (oxygen dependednt) and anaerobic bacteria. In addition cellular debris from the vas deferens, the prostate, the seminal vesicles and thr urethra may be present. All of these components are "washed" from the specimen in the sperm wash procedure.
Antisperm antibodies have been well documented in the scientific literature as having the potential to cause impairment of fertility in humans. Sperm antibodies are detectable in either the male or female partner in approximately 10% of infertile couples. While these antibodies may be present, they may not be ultimately implicated as the cause of the infertility, making the search for antibodies in infertile couples both important and frustrating for the physician.
Antibodies, in general, are biochemical "time-bombs" that develop in the immune systems of all normal human beings. They are there to protect us from foreign "invaders" (viruses, bacteria, foreign objects, etc.) that would otherwise have the potential to attack and harm vital parts of the body. A newborn infant is supplied with a temporary supply of vital antibodies from the mother. This supply may be initially be replenished and transmitted from breast milk from the mother. Ultimately, antibodies to harmful outsiders develop slowly and reliably over time as a growing human is exposed to more and more "coughs, clods and flu's" from the outside world. Vaccines are a way to trick the body into producing long term protective antibodies without the body having to first suffer the disease. Antibody protection can, on occasion, "short circuit". In these instances, the abnormal function of the antibodies can lead to a variety of diseases. Some common examles are certain forms of severe arthritis, lupus, diabetes, and in reproduction, premature menopause (ovarian failure) and antisperm antibodies.
What happens in many immunologic disorders is the immune system that is normally ONLY supposed to make antibodies to protect from harmful threats begins to see "normal" tissue as a threat. In the case of arthritis, the immune system mistakenly decides that a person's bone joints have become a threat and begins to attack the joints. This persistent immune attack leads to an eventual painful destruction of the involved joints. In the case of antisperm antibodies, either the man begins to see his own sperm as a foreign "threat" or his female partner, whose immune system is supposed to tolerate sperm as non-threatening, begins to lose this tolerance and produces a destructive antibody that may damage the sperm and make it incapable of performing it's egg penetration and fertilization duties.
Antisperm antibody testing is complex, as at least three different antibodies can have a damaging effect on sperm. Each of these antibodies must be specifically looked for in the investigation of the male and female. A new test, due for release to laboratories in early 2001 is able to determine biochemically if sperm have been damaged by any cause within the male reporiductive tract, making them incapable of fertilizing the egg. This new assay promises to make our ability to assess sperm function much more accurate. Initial use of this investigation assay has shown it to be nearly 100% accurate in determining is a sperm can fertilize an egg without help, either naturally or with in vitro fertilization, of if intervention in the fertility laboratory with ICSI will be required.
Advanced Sperm Testing Procedures
Many of the following tests are found useful at The Fertility Institutes in our investigations of males who have demonstrated "problem" results on earlier semen analysis. These tests are not performed routinely in the initial testing of sperm, but are employed to help further understand the nature and extent of a possible sperm or semen "problem".
Hypo-Osmotic Swelling (HOS) Test
This fairly simple and relatively inexpensive test is based on the semipermeability (ability to allow fluid or elements to pass through it's membrane) of the intact sperm cell. A live sperm cell will "swell" when placed in a solution that is "hypo-osmotic", expanding the cell's volume. This test is easy to score and provides valuable information on the integrity and behavior of the cell membrane of the sperm tail.
Zona-Free Hamster Oocyte Test
In the past, this was one of the most widely used accessory tests in the evaluation of advanced sperm function. The fusion between human sperm and the hamster oocyte (egg) is nearly identical to that occuring with the human egg. Fusion with the vitelline membrane of the oocyte is normally initiated by the healthy sperm's plasma membrane that lies over a special section (equatorial segment) of the sperm head in a sperm that has prepared itself for normal fertilization. This test relies upon the ability of sperm that are tested in the laboratory to undergo the necessary reactions to fertilize an egg. Because the sperm prepare themselves in a slightly different manner in the laboratory than in the body, false negatives (fail in the hamster test but normally fertilize the partner's human egg) have been reported. This test may be used as a screen to asist in determining which men may need the assistance of "ICSI" fertilization by our embryology team. Due to the very high fertilization success rates routinely seen with assisted fertilization (ICSI), a standard move to ICSI has replaced the costly hamster evaluation. This has resulted in our ability to reliably achieve excellent fertilization and pregnancy rates in couples affected by even VERY low sperm counts and / or motility.
Reactive Oxygen Species And Male Infertility
Reactive oxygen species in the sperm result from the metabolism of oxygen by the sperm cell. These species include superoxide anion, hydrogen peroxide and nitric oxide. The detection of excess amounts of these chemicals in the sperm combined with abnormally high concentrations of certain enzymes may indicate that the involved sperm are immature, damaged or abnormal. Excess levels of reactive oxygen species can produce oxidative damage to important components of the sperm. Sperm normally maintain levels of "anti" oxidant systems to protect the sperm cell. If the presence of high levels of oxidants are present, the cell's defenses may be overwhelmed, and cellular damage may result. Chemiluminescent testing in the laboratory can detect excess levels of reactive oxygen species.
Zona Pellucida Binding Tests
When a normal sperm binds to the zona pellucida of a healthy egg, the sperm normally undergoes an "acrosome reaction" that releases components that lead to normal fertilization. This process may be approximated in the laboratory by exposing the sperm being tested to the dissected zona pellucida of human eggs obtained from non-fertilized human eggs. The zona pellucida of such an egg is split in half. Sperm from the man being tested are exposed to one half of the split zona pellucida, while sperm from a man known to have "normal-fertile" sperm are exposed to the other half. A comparison of the performance of the sperm of the two men is carried out to ascertain the functional binding capacity of serm of the man being tested.
Sperm antibodies in semen belong almost entirely to two classes of antibodies; IgA and IgG. IgA antibodies are probably more important sources of sperm problems than IgG. IgM antibodies, because of their large molecular size, are rarely seen in semen. Of import, it has been found in the IVF labortory that unless 50% or more of the sperm have antibodies coated on them, there is little chance that the sperms function will be significantly impacted. That is, problems are rarely encoutered from antibody levels lower than 50%.
Sperm Chromatin Structure Assay (SCSA)
Until several years ago the belief among most reproductive specialists was that if a man had live sperm then they were suitable for use with IVF / ICSI and if the female partner didn't get pregnant or a miscarriage ensued then it was probably an egg quality issue. Several studies had implied that the conventional sperm parameters (count, motility and morphology) as measured on a routine semen analysis had no bearing on success when ICSI was used. Many couples pursued egg donation after failed IVF attempts because the husband's semen parameters were relatively normal and yet conception hadn't occurred. Some of these same couples were still unable to conceive even with the "better quality" donor eggs leaving both the doctors and the couples frustrated and perplexed. Some couples then went on to use both egg donors and surrogates thinking it was both an egg quality and implantation issue, again without success. The only commonality was the husband's sperm. In 2005, a relatively new concept was introduced to clinical practice; sperm quality was dependent on the amount of damage to the sperm DNA or DNA fragmentation. Simply put, DNA is arranged in a double helix or ladder configuration with side rails and rungs. If the rungs are broken, then the ladder is unsteady and won't function properly. What has recently been shown in several studies is very interesting and in some ways unexpected. Sperm DNA fragmentation has little or nothing to do with the parameters that we measure on the routine semen analysis. It has little to do with the shape of the sperm or whether the sperm are moving. It is a completely independent variable. Men with otherwise normal semen analyses can have a high degree of DNA damage and men with what was called very poor sperm quality can have very little DNA damage. More importantly what has also been demonstrated is that the degree of DNA fragmentation correlates very highly with the inability of the sperm to initiate a birth regardless of the technology used to fertilize the egg such as insemination, IVF or ICSI. Sperm with high DNA fragmentation may fertilize an egg and embryo development stops before implantation or may even initiate a pregnancy but there is a significantly higher likelihood that it will result in miscarriage. By testing for sperm DNA fragmentation, many cases of formally "unexplained" infertility can now be explained. Many of those couples who have been previously unable to conceive with what would be considered extreme measures have been diagnosed with high sperm DNA fragmentation and treated. It is now very clear to see that having this information about the quality of the sperm can be tremendously helpful to couples and their physicians. There are several ways to test for sperm DNA fragmentation; the most widely used and statistically robust test is called the Sperm Chromatin Structure Assay or SCSA. The patient semen samples are frozen and shipped in a liquid nitrogen container to the SCSA reference laboratory in South Dakota. The sperm are thawed out and a stress is applied (low pH). The sperm are then labeled with a special orange colored dye that only attaches to the ends of broken DNA within the sperm cell. If the DNA is intact then no dye will attach to the sperm. A machine called a flow cytometer is used to analyze ten thousand sperm from the sample. The sperm are passed single file by a beam of light that hits the dye inside the sperm cell and reflects light at a specific wavelength causing the sperm to appear either orange (damaged) or green (normal). A computer counts the percentage of green versus orange-labeled sperm and software allows for creation of a graphic plot of the percent of damaged sperm giving an index known as the DNA fragmentation Index (DFI). The data from thousands of patients has been analyzed and correlated with the patient's clinical outcomes and references ranges were compiled. A normal sample has less then 15% of the sperm with DNA damage. Men with poor fertility potential have greater then 30% of their sperm damaged. A DFI Between 16% and 29% is considered good to fair fertility potential but becomes poorer as it approaches 27%. These numbers are thresholds meaning that above 30% the outcome for most couples was failure to have a birth even though only 30+ percent of the sperm were damaged. Under 15% most couples achieved success. The logical questions that arose were: what about the rest of the undamaged sperm in the sample? Why don't those sperm work? What causes sperm DNA fragmentation? Can the DNA fragmentation be reduced and the sperm improved? If so, How? DNA fragmentation can be thought of as a marker for other types of damage to the sperm. It is a kin to seeing the tip of the iceberg. Apparently, in semen samples with greater then 30% DNA fragmentation, other abnormalities are occurring with the non-fragmented sperm that the SCSA doesn't measure and that is why samples used with DFIs above this level do not usually result in births. The causes of high DNA fragmentation are those same causes of male factor infertility that we have known about for years such as chemical/toxin exposure, heat exposure, varicocele, infection, age, smoking, testicular cancer, radiation, and anything that increases the free radical levels in the semen among a list of many other things. It is very important to understand that sperm DNA fragmentation can change with time and it can be improved in many cases. The goal of a male factor evaluation is to seek out the causes of poor sperm quality and try to correct them so conception can occur naturally or to improve the sperm quality for IVF and maximize the chances of success. In situations where DFI can't be improved there is evidence to suggest that removing the sperm directly from the testicle via biopsy and using it with ICSI may lead to better outcomes then using poor quality ejaculated sperm. Other options include counseling patients regarding the use of donor sperm either by insemination or fertilizing a portion of the eggs harvested for ICSI with donor sperm and a portion with the patient's sperm, once again to maximize odds. The clinical utility of the SCSA is readily apparent. All men with an abnormal semen analysis are candidates for this test as well as men with normal semen analyses who have failed IVF for unexplained reasons. Those couples using egg donors or surrogates may also benefit from screening prior to going thru the procedures because the effort and costs are so great. Men with poor DFI should have a male factor evaluation including a physical examination by a male reproductive specialist. These new concepts have a significant implication on how we practice and what we recommend to couples but we must bear in mind that this test does not have a predictive values of 100% as healthy babies have been born from men with high DFI but this is fairly uncommon. Decisions concerning this advanced testing are carried out for all males presenting with sperm analysis abnormalities at the Fertility Institutes. Where SCSA is felt to be potentially helpful in resolving a problem or answering a clinical question, arrangements to obtain the test are carried out. From Resolve 2006, Dr. P. Werthman, Urologist with the Fertility Institutes.
Azoospermia (No Sperm) and Related Syndromes
Zero Sperm Counts and Genetic Links
What has become evident at our Centers over the last several years is that our ability to diagnose and successfully treat severe male infertility problems has surpassed our ability to understand the basic causes of these problems. In the recent past, it was considered that nearly 20% of men with extremely low or "zero" sperm counts had no known medical reason for their fertility problems. Most recently, major advances in molecular biology and genetics have provided the "reasons" for severe infertility (very low or zero sperm counts) in many men whose fertility problems were previously poorly understood. We now know that 20-30% of men with such low (under 10 million/ml) or zero sperm counts have a now identifiable genetic cause for their problem. While we are now able to assist many, many men previously thought to be "hopelessly" infertile achieve pregnancy, it remains very important to not only treat these men, but to provide such couples with genetic information related to the problem causing the low or zero count. This is important because many of these genetic characteristics may potentially be passed along to children conceived with the help of modern male infertility treatments. Genetic disorders that would previously not have been able to be "passed along" due to the male's infertility are now being retained in the "gene pool" as a result of new procedures that overcome most of these previously untreatable male conditions.
Congenital Absence of the Vas Deferens
Congenital absence of the vas deferens (CAVD) is a syndrome in which a portion or all of the reproductive ducts (including the epididymis, vas and seminal vesicles) are missing. This causes an obstruction to the passage of sperm. These sperm, which are being produced normally in the testicle become "trapped" in the testicle for lack of a pathway to the ejaculate. CAVD may be associated with several diseases, including cystic fibrosis (CF) and malformations of the kidneys (renal malformations). 65% of men with CAVD will have a detectable genetic mutation in one of the cystic fibrosis genes, and 15% will have a missing or misplaced kidney. This does not imply that the man has or will develop cystic fibrosis but it means that he could be a carrier of the gene. If his spouse is also a carrier, this means that there is a 25% chance of a child born to them having cystic fibrosis. It is a standard treatment policy in our Centers that all couples in which the man has CAVD undergo cystic fibrosis carrier testing of both the man and his spouse/partner. Once the genetic testing is completed (testing takes about 10 days), an in vitro fertilization cycle may be planned for the wife, and a "MESA" (microsurgical epididymal sperm aspiration) procedure planned for the man to obtain viable sperm. These sperm may then be gently, microsurgically inserted inside the eggs of the wife (ICSI) that have been obtained from an aspiration carried out through the vagina. The resulting embryos may then be placed into the uterus of the female to establish a pregnancy. Success rates remain very high with this technique, even in men with "zero" sperm counts.
Y Chromosome Microdeletions
The human genome consists of 23 pairs or 46 chromosomes. There are 44 autosomes and two sex chromosomes. The sex chromosomes are called "X" and "Y". Each genetically normal human has two sex chromosomes. A woman has "X" and "X" (2X) and a man has one "X" and one "Y". The reproductive gametes (eggs and sperm) get one or the other of each partner's sex chromosomes. Because women have 2 "X" chromosomes, each of her eggs will have an "X" sex chromosome. Because men have one "X" and one "Y" chromosome, half of their sperm will carry the "X" chromosome and half will carry the "Y" chromosome. It can therefore be soon that men are responsible for sex determination. If an "X" egg is fertilized by an "X" sperm, an "XX" female will result. If an "X" egg is fertilized by a "Y" sperm, an "XY" male will result.
If the "Y" chromosome from the sperm that fertilizes the "X" egg carries a small mutation or deletion affecting sperm production in part of it's genetic make-up, a male child resulting from a pregnancy may have the same sperm production problem. We have found that 10-13% of men with an absent, or "zero" sperm count will have a mutation or deletion on the "Y" chromosome. We have also detected "Y" chromosome microdeletions in men with low, but not zero counts. We offer a very sophisticated blood analysis (test) to determine if these genetic conditions are present before undertaking therapy that will lead to pregnancy.
Klinefelter's Syndrome is a genetic disorder characterized by infertility, abnormal male breast tissue development (gynecomastia) and small, firm testes. It is the most common cause of azoospermia (no sperm production). Klinefelter's Syndrome is caused by an abnormal number of sex chromosomes. Whereas a normal male genetic make-up includes one "X" chromosome and one "Y" chromosome, in patients with Klinefelter's Syndrome, an extra "X" chromosome is present, resulting in three (XXY) sex chromosomes. Thought at one time to be hopelessly infertile, it has been found that these men can have small amounts of sperm production occuring within the testicle. Our Center has successfully recovered sperm in men with this disorder who have gone on to father normal, healthy children. It is important that all men with very low or absent sperm counts be tested for Klinefelter's Syndrome before offering IVF and ICSI.
Donor Sperm Bank Options
For patients requiring donor sperm samples, we offer the selection of specimens from the nation's leading registered sperm banks. This selection includes samples from "designer" sperm banks specializing in specimens from men with specific backgrounds and physical and intellectual traits desired by some patients.
Written by Jeffrey Steinberg, MD