Causes of Infertility

Introduction
Definitions
Causes
    Abnormalities of Ovulation
    Pelvic Factors
    Cervical Mucus
    Male Factor
    Genetic
Immune Problems
Recurring Pregnancy Loss
Testing in Infertility
    Post Coital Test
    Semen Analysis
    Pelvic Infection
Evaluation Process
    Evaluation of Ovulation
    Evaluation of Pelvic Factors
    Evaluation of Male Factor
Treatment
    Male Factor
    Hormone Problems
    Pelvic Factors
    Fibroid Tumors
    Unexplained Infertility
Rebound Pregnancy

InfertilityPhysician.com Home

There are many reasons why a couple may not achieve a successful pregnancy. It is important to understand that, in our opinion, infertility is not the inability to become pregnant, it is the inability to have a baby. Fortunately, for those infertile couples whose problem is recurrent pregnancy loss, the insurance companies do not agree with my definition and these couples have an easier time getting their evaluation paid for than those couples who cannot achieve a pregnancy at all.

The causes of infertility can be separated into several broad categories. Each category will be covered in a separate section of this pamphlet. These categories are: 1) Abnormalities of Ovulation (and other hormonal problems); 2) Male Factor; 3) Pelvic Factors; 4) Cervical Mucus Factors; 5) Genetic Factors; 6) Immune Problems . Some of these problems interfere with a woman's ability to become pregnant, others will interfere with her ability to stay pregnant, and some may do both.

Please understand that this pamphlet is designed to provide general information. There will always be exceptions to almost everything I say. Human beings are so variable that it is impossible to put people into neat little pigeonholes. Nonetheless, the principles I will discuss in these sections do apply to the vast majority of infertility couples.

Abnormalities of Ovulation
30 - 40% of all Infertility

At one time, about the only thing you could tell by testing was whether a woman ovulated or did not ovulate. Even then, you couldn't always be sure. The techniques that were available were the Basal Body Temperature (BBT) Chart, careful evaluation of changes in the cervical mucus, changes in the appearance of the cells of the vagina when appropriate smears were made, and the measurement of a metabolite of progesterone in the urine called Pregnanediol.

BBT charts will tell you if a woman ovulated but cannot tell you if "normal" ovulation has occurred. Many women ovulate quite normally with very bizarre looking BBT charts.

The measurement of the urinary pregnanediol could tell you if ovulation occurred. However, it is not a valid test to determine whether normal ovulation is occurring.

Changes in the cervical mucus or changes in the vaginal smear again may tell you if ovulation occurred but that is about all and they are very inaccurate and subject to numerous influences.

The ability to measure the concentration of hormones in the blood using highly accurate techniques combined with the development of ultrasound - first abdominal and now vaginal - has permitted us to study the normal menstrual cycle literally day by day. This has allowed us to determine, with a fairly high degree of accuracy, exactly what a normal menstrual cycle ought to look like. I know what the hormone levels ought to be. I know what the lining of the uterus ought to look like both before and after ovulation. I know how large the follicles should get when looked at by ultrasound and by evaluating all of these factors, I can now assess the normalcy of ovulation with a high degree of accuracy.

As a result of this, I have been able to learn that many women who ovulate do not do so normally. For many women, making this determination has been of great benefit in helping them achieve a pregnancy.

It is also true that many women with other obvious problems, such as tubal disease, male factor infertility or endometriosis may also have an abnormality of ovulation. There is evidence that a previous pelvic infection may affect future ovarian function. It has been known for many years that women with Endometriosis frequently do not ovulate normally. These are very often couples who end up seeking infertility care.

I am convinced that couples with only a single problem (unless that problem is very severe) will often achieve a pregnancy on their own. It is when a couple has multiple problems, none of which may be all that bad, that infertility results. Studies have shown that if infertile couples are followed for 5 years without therapy, approximately 50% will achieve a pregnancy. Often, treatment of the infertile couple does not achieve higher pregnancy rates, it only helps the couple achieve a pregnancy sooner.

The modern assessment of ovulatory abnormalities is now common and requires seeing the women 5 or 6 times during her menstrual cycle. The initial visit occurs early in the cycle, ideally on Day 3 (day 2, 3, or 4 is acceptable). Blood tests obtained at that time are very valuable in predicting the success of future therapies. An ultrasound obtained at that time is used to evaluate the ovaries at the time in the menstrual cycle when they are at their least active state.

Depending on the age of the woman, her history, and what other therapies she has undergone, a Clomiphene Citrate Challenge Test (CCCT) or a GnRH stimulation test may be performed. These are tests to assess "Ovarian Reserve" - a measure of the functional reserve capacity of the ovaries to produce normal eggs. (See section below)

The next important time to evaluate the menstrual cycle is at the time of ovulation. Several visits are required, often on a daily basis. Blood tests make sure that the amount of estrogen and other hormones produced are normal. This indicates that the follicle is healthy. Ultrasound is correlated with the estrogen level to make sure that the follicle has achieved full mature development and that the lining of the uterus has also developed properly. Failure to develop a normal uterine lining is a much more common cause of infertility than was formerly believed.

At this time, the cervical mucus is also checked and a post coital test is done. This is often as good a test of male fertility as the traditional semen analysis. Some studies have shown that the post-coital test is actually better than a semen analysis, at least in terms of predicting future pregnancies.

The woman is next seen shortly after ovulation to make sure that the follicle has ruptured and that the egg has actually been expelled from the ovary. Failure to observe that ovulation has actually occurred is a strong clue that the woman has endometriosis.

The last visit is later in the cycle about 1 week after ovulation. Again, hormone levels and an ultrasound are performed to evaluate the endometrium (the lining of the uterus).

The traditional way that progesterone production is assessed is to perform an endometrial biopsy, a procedure in which a small piece of the endometrium (the lining of the uterus) is removed and sent to a pathologist for evaluation. This is usually done just prior to the onset of the menstrual period. Endometrial biopsies are done in the office and can be painful, even if techniques are employed to reduce the pain.

I rarely perform endometrial biopsies in infertile women. The reason for this is simple - there is no evidence that (for the reasons a biopsy is usually done), it means anything or makes any difference in the treatment of an infertile woman. European Reproductive Endocrinologists do not do endometrial biopsies for this very reason.

If a woman produces too little progesterone during the second half of the menstrual cycle after ovulation has occurred (the luteal phase), then that woman is said to have a "luteal phase defect". Common sense says that a woman with a luteal phase defect should have trouble conceiving and for this reason, some physicians give their patients progesterone (often in the form of vaginal suppositories or cream) following ovulation.

As much as common sense says this should work, all the research that has been done clearly shows that it doesn't. There is no evidence that giving progesterone to an infertile woman increases her chances of becoming pregnant. There is also no evidence that giving women progesterone after they have conceived helps them "hold" the pregnancy. IVF is an exception to this - progesterone supplementation is mandatory.

There is evidence that endometrial biopsies to determine whether normal ovulation is taking place may have been done at the wrong time of the cycle. Some researchers now feel that if a biopsy is going to be done, it should be at the time of implantation (7-8 days after ovulation). This is still an unresolved issue. Until the argument is settled, the preceding paragraphs still hold.

Newer information indicates why progesterone therapy is ineffective. A luteal phase defect, by definition, means that the woman is producing less progesterone during the luteal phase of her cycle than normal. Studies have shown that at least 50% of women with a "luteal phase defect" as diagnosed by endometrial biopsy have normal progesterone production during the luteal phase of the cycle. The evidence indicates that the real problem is not inadequate progesterone production but an abnormal response of the endometrium to progesterone. These women have an endometrial progesterone receptor defect. The first studies showing this were published many years ago. Giving extra progesterone will not overcome this inherent abnormality in the endometrium.

Endometrial biopsies do have a role in infertility to detect endometritis (not endometriosis), a chronic inflammation of the endometrium. Endometrial biopsies are also necessary to measure endometrial integrins - a newly discovered group of molecules that make cells "sticky". This may be of value in women with unexplained infertility but the test is not covered by most insurances and is expensive.

Endometritis, if present, it will keep a woman from conceiving. It needs to be diagnosed and the endometrial biopsy is the only way.

The endometrial integrins are molecules that help cells stick to each other. There is evidence that they are necessary for the embryo to attach itself to the endometrium. Women have been identified who are infertile, have no obvious reason for their infertility and who are found to be deficient in endometrial integrins. Newer evidence also indicates that women with early stage endometriosis are also deficient in endometrial integrins. This may explain their infertility or sub-fertility. This is all new information and it will take several more years until it is sorted out. None-the-less, measuring endometrial integrins may be of benefit in women with otherwise unexplained infertility.

At each visit, the endometrium is also evaluated by ultrasound. The endometrium also goes through a series of changes during the menstrual cycle. Recent data has shown something that was suspected for a long time, namely that if the endometrium is not properly developed prior to ovulation, a pregnancy will not occur even if all other factors are normal. Many women with totally normal hormone levels will not have a normal endometrium. This is why giving progesterone does not help. Such women require special therapies to achieve a pregnancy.

This assessment is very important in women taking Clomiphene. It has been known for a long time that Clomiphene will adversely affect the cervical mucus. By the same mechanisms, Clomiphene will also interfere with the normal development of the endometrium. Ultrasound monitoring will often detect this, and, if present, requires that the woman be switched to Pergonal or a similar drug. Taking a baby aspirin every day also helps, in some cases, to overcome the adverse effects of the Clomiphene.

There is one important thing to keep in mind - no woman ovulates normally every cycle. If you were to study 100 women chosen randomly, you would find that 25 to 30% of them would ovulate abnormally in any one given menstrual cycle. The incidence is probably higher in infertile women. Therefore, if a problem with ovulation is detected, it is mandatory that the woman be evaluated in a subsequent menstrual cycle. Only in this way can you be sure that the problem you have detected and may wish to treat truly exists. A woman with a significant problem will show that problem almost everytime she is evaluated. If a woman has a problem in one cycle but is completely normal in the next cycle, then that problem probably either does not exist or is of lesser significance in terms of her overall infertility.

This is another reason why progesterone therapy is ineffective. Studies have clearly shown that women with biopsy proven luteal phase defects do not show that defect in every cycle, when multiple biopsies are done over many cycles. Furthermore, it is rare to have a woman conceive in the cycle a biopsy is done. Therefore, if a woman has a biopsy proven luteal phase defect, I have no way of knowing whether the problem was present in the cycle in which she conceived. It is apparent from all the data currently available that those women who conceived, even with a properly proven luteal phase defect, ovulated normally in the cycle of conception and any progesterone given was coincidental to the pregnancy which would have occurred anyway.

There are a number of other reasons why endometrial biopsies are unreliable (the way they are usually done). The vast majority of women who have been told they lave a luteal phase defect have not had the diagnosis established by valid means. Therefore, those women who were told they had this problem, were treated for it, and then conceived are mistaken in their belief that the therapy had anything to do with the successful pregnancy.

There is another very, very important reason why abnormalities of ovulation should be documented before therapy is begun. It has been a very common practice in infertility to give Clomiphene (Clomid or Serophene) to infertile women, often without a proven need for it. In fact, under the rules established by Aetna-USHealthcare's infertility program, a woman had to be given 3 cycles of Clomiphene by her general OB/GYN before she could be referred to a Reproductive Endocrinologist.

A recent study proved what had long been suspected and for which a great deal of indirect evidence already exists, namely that giving Clomiphene to a normally ovulating woman may actually decrease her chances of becoming pregnant! More recent data has shown that sophisticated ultrasonic evaluation of follicles generated by Clomiphene are often not normal, further supporting the fact that giving Clomiphene just because the woman is not becoming pregnant may not always be appropriate. Proving whether a woman ovulates normally or not is an essential part of the evaluation process as it will play a major role in determining which therapies are best for that couple.

Ovarian Reserve

It goes without saying that normal ovarian function is essential for a woman to become pregnant. Making the diagnosis of abnormal ovarian function is easy when a woman has significant irregular menstrual cycles, when she has stopped menstruating completely or when she shows evidence of some other obvious hormone problem.

The dilemma arises in those women in whom it is suspected but not proven that their ovaries may not be functioning normally. Until recently, we did not have good techniques for evaluating this -- now we do.

The transition from normal ovarian function to menopause as a woman ages is not an abrupt change but a gradual one. At menopause, it is not like suddenly turning off the light switch -- it is if a dimmer were used to reduce the intensity step by step.

If a woman is trying to become pregnant, particularly if she is over the age of 35, or if she has already undergone unsuccessful infertility treatment, it is critically important to determine how her ovaries are functioning. Newer data clearly shows that if the ovaries are not producing their eggs and hormones the way they ought to, the chances of a successful pregnancy are very poor -- regardless of what technique is used to try to achieve that pregnancy.

The term now used for this is "Ovarian Reserve." There are several ways to assess ovarian reserve. To understand these tests, it is important to understand how the body normally controls ovarian function.

As I have mentioned in other pamphlets, a woman is born with all the eggs she will ever have -- about 1 million at birth, 400,000 at puberty and essentially "0" at menopause. Although it cannot be definitively proven, it is generally believed that a woman ovulates her best eggs at a younger age. As she gets older, the eggs that remain in her ovaries are not the best of her eggs. These eggs don't function properly and the body has to work harder to get these eggs to ovulate.

The following explanation obviously oversimplifies what is a very complex process. However, I believe it will provide the necessary insights for you to understand exactly what is going on.

The pituitary gland produces two principal hormones that control the ovary -- FSH or Follicle Stimulating Hormone, and LH or Luteinizing Hormone. FSH can be thought of as the hormone that controls egg development and LH controls hormone production.

Your endocrine system controls itself in a manner very similar to the way your thermostat at home controls the temperature of your house. This is called "negative feedback". When you are at home, and if you are cold, you go to the thermostat and raise the temperature setting. The thermostat then sends a signal to the furnace. The furnace produces heat which raises the temperature of the house to your desired level. The thermostat senses this and turns off the furnace. Later, should the temperature of the house fall on its own, the thermostat will sense this automatically and turn the furnace on once again.

Think of your ovaries as the furnace and think of your pituitary gland as the thermostat. Just as the signal from the furnace to the thermostat is the temperature of the house, the signal from your ovary to the pituitary gland is estrogen.

As a woman ages and ovarian function declines, ovarian estrogen production will begin to fall. The pituitary gland senses this and tries to generate more estrogen. The signal it sends to the ovary is FSH. The increased production of FSH by the pituitary gland is an attempt to increase estrogen production by the ovary. Adequate estrogen production can be equated to normal egg development.

If your furnace were not functioning properly, your thermostat would have to send a stronger and stronger signal to the furnace to try to get the temperature of the house higher. So too, the pituitary gland, as the ovary fails, sends a stronger and stronger signal to the ovary.

If women are monitored very carefully as they age, the earliest sign that the ovaries are functioning abnormally and are beginning that long transition into menopause is a rising level of FSH. We take advantage of this to assess ovarian function in determining a woman's chances of subsequently conceiving.

The first test that came along that showed real value is called "Cycle Day 3 FSH". This test was almost discovered by accident. It turns out that for most IVF programs, hormone stimulation begins on cycle day 3 and many facilities routinely drew blood on their patients prior to the initiation of a cycle. This blood was then stored and analyzed at a future date.

As studies were done that correlated the cycle day 3 FSH level with the subsequent success of the IVF cycle, it quickly became apparent that those women with higher FSH levels were less likely to conceive. As more and more data became available, it became possible to segregate women into three categories -- those with a good chance of success with IVF, those with almost no chance of success and those who fell somewhere in between.

An ideal day 3 FSH is less than 10. Values between 10 and 15 fall into a gray zone. A day 3 FSH is over 15 is a poor prognostic sign.

As more and more data began to accumulate, other studies looked at different hormone levels and it quickly became apparent that the serum estradiol on day 3 is also a predictor of ovarian reserve. If a woman has a high serum estradiol level on cycle day 3 (over 75), this is also an indicator of an ovary that is not functioning properly and is also a poor prognostic sign.

In endocrinology, dynamic testing often gives better results than simply drawing a single blood test. With this idea in mind, the GnRH stimulation test and the "Clomiphene Citrate Challenge Test" have been devised. The "Clomiphene Citrate Challenge Test" was invented many years ago, whereas the GnRH test is new and probably better.

Newer studies have come up with what is probably an even better way of assessing ovarian reserve - the GnRH stimulation test. This test begins on cycle day 2 at which time an Estradiol, Progesterone, FSH, and LH levels are obtained.

The woman then begins GnRH - either Synarel or daily Lupron.

Repeat blood tests are then obtained on cycle days 3,4, and 5. (Some studies have indicated that repeat tests on only days 3 and 4 are necessary). However, eliminating the cycle day 5 hormone levels may draw erroneous conclusions from the tests.

Four different patterns of Estradiol response to the GnRH have been demonstrated.

In the most optimum response, the Estradiol level from day 2 to day 3 will increase by at least 100% or even more. Therefore, it will double. It then slowly declines over the next two days.

The second response shows no change between day 2 and day 3 but the Estradiol level then increases between day 3 and day 4 or increases between day 4 and day 5.

The third response is a slow steady increase of the Estradiol level over all 4 days.

The fourth response is a virtual flat line over all five days.

The first and second responses are what is hoped for. Published success rates with in vitro fertilization show pregnancy rates of 46% with the first response pattern and 38% with the second response pattern.

Pregnancy rates of only 16% are seen with the third response pattern and if the woman's Estradiol level shows virtually no increase over the four days of the tests (the fourth response pattern) the pregnancy rates were only 6%.

Because of the nature of this test and because it is often impossible to obtain laboratory studies on Sunday (and often on Saturday), this type of testing can only be carried out when your menstrual cycle begins either on Sunday, Monday, or Tuesday. (It may be sometimes possible to also perform the testing if your period begins on Wednesday but not if it begins on a Thursday, Friday, or Saturday).

The "Clomiphene Citrate Challenge Test" relies on the fact that Clomiphene is an anti-estrogen. Therefore, if there is any significant compromise of ovarian function and the pituitary gland is already beginning to work harder to produce more FSH, anything that tips it a little bit over will actually produce an exaggerated rise in FSH.

The Clomiphene Citrate Challenge Test (CCCT) is very easy to carry out. Baseline blood is drawn on cycle day 3.

The woman takes 100 mg. (2 tablets) of Clomiphene beginning on cycle day 5 for 5 days. Recent data suggests that brand name Clomid or Serophene should be used to make sure that the test is performed with as little room for error as possible and to insure consistent results from one physician to another. Blood is then drawn on cycle day 10. An FSH level is over 15 indicates an ovary that is failing. If the FSH is over 25, the likelihood of a pregnancy is very poor.

Because of advances in our knowledge and technology, there are several other newer studies that can also help assess ovarian reserve. The first is measuring the hormone "Inhibin". Inhibin is a hormone produced by the early developing follicles in the ovary and one of its functions is to inhibit the production of FSH by the pituitary gland. Therefore, a reduced number of healthy follicles results in a lower level of Inhibin and this is no doubt one of the factors contributing to the increase in FSH that serves as a marker for diminished ovarian reserve.

It is now possible to measure Inhibin directly and, again, a low level of Inhibin early in the cycle indicates diminished ovarian reserve.

As has been discussed elsewhere, women are born with all the eggs they are ever going to have. As the pool of eggs is used up, logic would tell you that the size of the ovary will decrease. In fact, this is the case, and another way to assess ovarian reserve is to actually measure ovarian volume. Newer ultrasound machines, such as the one we have in our office, can calculate ovarian volumes. If the volume of an ovary is less than 3 cc's, that ovary most likely has an insufficient egg pool.

Another study looked at the FSH to LH ratio on cycle day 3. The authors of this study found that if that ratio is more than 3.6 then, again, there is diminished ovarian reserve.

One of the issues currently being debated revolves around which tests should be used, is there any one definitive test, and how significant are these tests. It may be several more years before we have a definitive answer. Most of the studies suggest that the cycle day 3 FSH, the cycle day 3 Estradiol, and the cycle day 10 FSH following a Clomiphene Citrate Challenge Test are the three most important tests. However, additional studies are needed.

These tests have little "positive" predictive value. In other words, they will not tell you who will become pregnant.

However, they do have very high "negative" predictive value. If the tests results show poor ovarian reserve, that woman needs donor eggs - a poor test indicates a very low chance of conception, regardless of what infertility therapy is used.

All women over 35 and any woman under age 35 who has gone through unsuccessful infertility therapy in the past should undergo Ovarian Reserve testing.

There are several issues that must be kept in mind when discussing ovarian reserve and its impact on infertility. First, decreasing ovarian reserve is a normal part of the aging process. Although some studies have suggested that diminished ovarian reserve, as measured by the cycle day 3 FSH, is a better predictor of infertility therapy success, most Reproductive Endocrinologists would agree that age is still the number one factor that compromises a woman's ability to become pregnant. Age and diminished ovarian reserve are usually synonomous, but not always.

In looking at the success of standard infertility therapy, all other things being equal, the older the woman, the less likely she is to become pregnant. One study looked at a large number of women with unexplained infertility who were going through super ovulation using Clomid combined with IUI. This study showed that regardless of the age of the woman, 85% of the pregnancies that were achieved occurred in the first four treatment cycles. However, the actual numbers from this study showed that for women under 30, 50% were pregnant after four treatment cycles; if the woman was between 31 and 35, 40% conceived; for women between 36 and 40, 26% conceived and for women 41 and older, 24% conceived. Again, these numbers show once again that the woman's age is perhaps the most important factor, all else being equal.

It is also important to understand that these tests of ovarian reserve are not absolute. Unless the tests indicate that you are actually quite close to menopause, there will always be an occasional patient who becomes pregnant, even when the numbers say that it shouldn't happen.

As an example, a large study looking at IVF cycle cancellation rates yielded the following results. If the cycle day 3 FSH was less than 15, only 5% of the cycles had to be canceled.

If the FSH was less than 20 - 10% were canceled; less than 25 - 20% cancellation rate; and if the FSH was over 30, 40% of the cycles had to be canceled.

This particular study did not mention pregnancy rates even in those cycles with elevated FSH levels that were not canceled. However, other studies have definitely shown that the higher the FSH, the lower the pregnancy rate.

These studies also point out one other trap for the unwary - namely, that most of them deal with IVF. There are not that many studies looking at pregnancy rates in women going through standard infertility treatments such as Clomiphene/IUI or Gonadotropin/IUI. Nonetheless, what few studies are available, combined with common sense, suggests that the higher the FSH, the less likely the woman is to become pregnant.

Nonetheless, since there will be women who do conceive even when the numbers say they shouldn't, we would never arbitrarily deny therapy unless the numbers clearly indicated menopause. However, women with diminished ovarian reserve must understand that their chances of becoming pregnant are certainly less than those of women whose ovaries appear to be functioning normally.

AGE AND FEMALE INFERTILITY

Almost everyone is familiar with the concept of the "biological clock". We have known for years that a woman's fertility declines as a function of her age. This is usually because of the declining ability of the eggs to be fertilized and/or develop into a normal embryo. This decline is evaluated by the techniques mentioned in the preceding section which discusses ovarian reserve.

A number of studies have been done looking at various cultural or religious groups who never practiced contraception. These studies evaluated the likelihood of the women in that group becoming pregnant strictly as a function of their age. What these studies showed was, not surprisingly, that there is a slight decrease in fertility after the age of 30, a more significant decrease after the age of 35, and there is a major decrease after age 40. These studies, however, made no attempt to determine what individual characteristics might be affecting this decline in fertility - it was simply raw population data.

Although most of the decline in fertility after age 35, and especially after age 40, is the result of diminishing ovarian reserve, a study from Israel published in Fertility and Sterility in September 2000 clearly shows that other factors are at work.

This study looked at women over 40 going through in vitro fertilization. It is important to remember that before they would even be selected as a candidate for IVF, they would have to have normal ovarian reserve testing. This group, therefore, at least on the surface, would appear to be appropriate candidates for IVF.

What the study showed was that given their normal ovarian reserve testing, 87% of the women's ovarian response to stimulation was good enough to allow for ovum retrieval and subsequent fertilization. An 87% fertilization rate is very respectable by anyone's standards.

Despite this, the overall pregnancy rate was approximately 5% (the range was 2-7%) - far far less than you would expect in younger women. Furthermore, no women over the age of 44 became pregnant.

Another study from Germany published a number of years ago looked at pregnancy rates in women going through donor insemination. By looking at this group of women, the confounding effect of the male factor was essentially eliminated. What this study showed was that whereas in younger women (under the age of 30), you would expect most of your pregnancies to occur within the first 4 or perhaps 6 insemination cycles (numbers that are consistent with our own office results). For women over 35, it would often take 10 or 12 cycles of insemination to achieve a pregnancy.

Lastly, experimental studies in mice which have been confirmed in humans clearly show that it is a function of the eggs - not the uterus. If invitro fertilization is performed using the eggs from an old animal or an older woman and those subsequent embryos are transferred to a younger animal or woman, the success rates are poor. On the other hand, young mouse eggs transferred to the uterus of an older mouse do quite well and the same is true for the human experience.

The bottom line - there is a biological clock. The battery that runs this clock begins to deteriorate with age. Many women for a large variety of reasons do not begin to pursue their fertility until after age 35. While we will make every effort to help them achieve a pregnancy (and often we are successful), they must understand that the one thing we cannot fix is the calendar.

Pelvic Factors
50% Of All Infertility

50% of all infertility is the result of some abnormality of the woman's reproductive organs. Damage to the female reproductive tract most commonly occurs from either endometriosis, damage from a previous pelvic infection or damage from previous pelvic surgery. In fact, the most common reason for pelvic adhesions is previous pelvic surgery.

Other major but less common causes include congenital abnormalities of the uterus or tubes and DES exposure which is fortunately becoming a problem of historical interest only - at least in terms of infertility. Fibroid tumors of the uterus are quite common, though less so in women trying to conceive.

Damage to or congenital abnormalities of the reproductive organs may either keep a woman from conceiving or may predispose her to recurrent miscarriage. Sometimes, the same problem will do both, depending on its severity. Fibroids are an example of this. Smaller fibroids may cause a woman to lose pregnancies whereas very large fibroids will keep her from conceiving. The location of the fibroids is often more important than their size.

A woman who is DES exposed also has the same problem - some will lose pregnancies and others will not become pregnant.

Prior to 20 years ago, the only way to diagnosis abnormalities of the reproductive tract was to perform an X-ray called a hysterosalpingogram. We now recognize, however, that the hysterosalpingogram can be inaccurate in a substantial percentage of cases. Women thought to have a problem by hysterosalpingogram often turn out to have nothing wrong at all. If the hysterosalpingogram is performed incorrectly, it will show an abnormality when none exists. However, women can have very significant degrees of pelvic damage, particularly from endometriosis, with a totally normal X-ray.

The only way to accurately assess the status of the woman's reproductive organs is to look at them and this requires laparoscopy. Not only is laparoscopy diagnostic, but because of the advances in technology over the last 10 years or so, it has become therapeutic as well. In fact, for many types of problems, laparoscopy and laparoscopic therapy are the only treatments necessary. Problems that would have required open surgery can now be treated completely, effectively and even better by laparoscopic techniques. There are problems such as very severe endometriosis, severe tubal disease, and severe post-operative adhesions that still require open surgery.

The same is true for abnormalities of the uterus where hysteroscopy is used to both diagnose and treat problems such as fibroids inside the uterus and some congenital abnormalities as well. Many problems diagnosable by hysteroscopy may be missed by a hysterosalpingogram.

In many instances, it is necessary to use the information from both the laparoscopy and X-ray to accurately assess the problems that a woman might have. This is vitally important because the treatment that is offered depends upon knowing exactly how bad the damage is. Now that IVF is becoming routine and fairly successful as it is (30% in a good program but only 20% overall), many couples are opting to go directly into an IVF program rather than go through the surgery necessary to correct severely damaged tubes. This is true because the success rate from correcting severely damaged tubes is the same as the success rate for IVF. However, before this advice can be given to a couple, it is critically important to determine exactly how bad the damage is. I have seen many women who were prematurely pushed toward IVF when they had problems that were easily and highly treatable by traditional means.

Unfortunately, another factor that must be considered is whether or not that couple's insurance company will pay for IVF or whether they have the financial resources necessary to pay for it on their own. Many couples who are actually better candidates for IVF may be forced into undergoing corrective surgery or other therapies because that is the only treatment their insurance company will pay for.

Pelvic damage from either a pelvic infection or pelvic surgery is usually easy to diagnose and the treatment is straight forward.

Endometriosis is its own special case and has been dealt with in another pamphlet.

DES exposure is also a special case. Many women were exposed to DES but do not know it. However, the appearance of the uterus on X-ray is very typical and makes the diagnosis even when no history is available.

Most women who are DES exposed have impaired fertility. Unfortunately, there is nothing that can be done to substantially alter that situation. Nonetheless, women who are DES exposed frequently have other complicating factors such as endometriosis. Even though the DES created damage cannot be fixed, treating the other problems will allow the couple to achieve a successful pregnancy. Fortunately, DES is no longer used. At one time, it was very common to see DES exposed women with infertility problems. Now, the vast majority of DES exposed women are of the age where fertility is no longer a consideration.

Another common pelvic problem is the presence of fibroid tumors - the most common benign tumor in the female pelvis. If appropriate studies are done, probably 50% of women by the time they reach the age of 40 have one or more small fibroids. These are of no consequence and do not require treatment.

The real dilemma occurs in women with a fertility problem or in women who will, at some time in the future, wish to have a baby.

For women with significant fibroids who wish to preserve their future fertility, removal of the fibroids is the treatment of choice. This operation, called a "myomectomy", is usually quite successful in forestalling any more radical surgery. However, women undergoing myomectomy must understand that they have a 25-40% chance of needing additional pelvic surgery in the future. It is not a magic cure-all despite an attempt by some recent books and TV programs to make women believe that it is a simpler and easier alternative to hysterectomy. A myomectomy is major surgery that is at least as complicated as a hysterectomy and often more so.

A larger dilemma arises when a woman who is trying to have a baby is discovered to have fibroids. If that woman has a history of recurrent miscarriage and it seems fairly certain that the fibroids are responsible for this, then again, removal of the fibroids is the treatment of choice. This is easy when the fibroid actually projects into the uterine cavity.

Unfortunately such women are a relatively small percentage of women with fibroids. More often, women who are trying to get pregnant are discovered to have fibroids but in these women, they have never achieved a pregnancy. It can then be quite difficult to determine whether or not the fibroids themselves are playing a significant role and whether surgical removal is necessary. The location of the fibroid is important but so is the size. Large fibroids (larger than 3-4 cm in diameter) probably play a role in infertility even if they are not near the lining of the uterus.

Another significant problem that is becoming more common are those women who have small fibroids that are initially of no consequence. However, with many of the therapies currently used in infertility, most notably Pergonal or similar drugs, the very high estrogen levels achieved during the menstrual cycle stimulate these fibroids to grow. What was then a minimal problem becomes a significant problem and many of these women ultimately undergo myomectomy because the fibroids have enlarged to a significant degree.

Hysteroscopy is another important diagnostic and therapeutic tool. The hysteroscope is a smaller version of a laparoscope and permits direct visualization of the interior of the uterus. Many problems are best diagnosed and treated by hysteroscopy. The treatment of a uterine septum, a problem which formerly required open surgery, can be carried out much better and much more simply by resection through a hysteroscope. Scar tissue within the uterus can be best diagnosed and treated through a hysteroscope. Fibroids that impinge on the uterine cavity can also be resected through a hysteroscope if they are not too large, thereby sparing the woman an open surgery.

Minor degrees of pelvic damage or early endometriosis can also be treated by this technique.

A newer technique you may read about is called "Transvaginal Hydrolaparoscopy". A small laparoscope is inserted through the upper vagina and the pelvis is filled with saline to float the pelvic organs. It can be done in the office under local anesthesia. Visibility is limited but it may become a good screening technique. However, it is too new to be sure.

Pelvic damage from a previous pelvic infection is another common reason for infertility. The bacteria that causes the damage is Chlamydia. The real problem is that 90% of the infections caused by Chlamydia are clinically silent. The woman has either no symptoms or such mild ones that she does not seek out medical attention.

Fortunately, there is a blood test to detect the presence of antibodies to Chlamydia. This blood test should be a part of every infertility evaluation and if the test is positive, it indicates a high degree of probability that pelvic damage from the infection is playing a role in that couple's problem.

If a woman has a positive Chlamydia antibody, she should undergo a Hysterosalpingogram prior to any other investigations. It is important to know whether a woman has any evidence of tubal disease prior to a laparoscopy.

If the antibody is negative, the likelihood of the Hysterosalpingogram showing an abnormality is in the range of 2-3%. Therefore, the x-ray need not be done.

Cervical Mucus
5% Of All Infertility

Abnormalities of cervical mucus play a major role in approximately 5% of all infertility problems. Understand that at the time of intercourse, the semen is deposited in the upper vagina and into the mucus. The sperm then have to swim through the cervical mucus where they are then propelled through the uterus and out into the fallopian tubes.

Evaluation of the cervical mucus is done at the same time that the woman's menstrual cycle is being tracked. The cervical mucus is receptive to the sperm only at the time of ovulation. When a woman is at the time of ovulation, the cervical mucus is thin, clear, watery and very stretchable. When put under the microscope and allowed to dry, the mucus takes on the appearance of a fern leaf. This phenomenon, called "ferning" is another way to assess the quality of the cervical mucus.

There are many problems in evaluating cervical mucus and especially its relationship to infertility. First of all, there are many studies in the literature calling in to question how important abnormalities of cervical mucus truly are in causing infertility. A study published several years ago from Canada came to the conclusion that post-coital tests are a waste of time and should not be done. While I think this may be an extreme position, it is inappropriate to blame every infertility problem on cervical mucus and spend a great deal of time trying to diagnosis and treat cervical mucus problems while at the same time missing the real cause of that couple's infertility.

Another study was published in the British Medical Journal in the summer of 1998 looking at post coital tests and pregnancy rates. This was a randomized, controlled, prospective study and it showed that the post coital test had no bearing on that woman's subsequent ability to become pregnant. This is consistent with other studies which have shown essentially the same thing.

Another problem is the fact that there is no universally accepted definition as to what constitutes a normal post-coital test. While there may be a general consensus, there is no one standard and every infertility specialist has his or her own definition as to what is normal. The World Health Organization (WHO) does have a standard, but not everyone adheres to it. Many people feel that as long as there is at least 1 moving sperm seen, the test is "normal".

A normal post coital test tells me that the man is capable of having normal intercourse and is capable of depositing reasonably normal semen into the upper vagina. It tells me that the woman is capable of producing normal cervical mucus. It tells me that the sperm are capable of living in that mucus. It therefore may help to identify specific problems. However, please understand that there is no good evidence that treating cervical mucus problems per se substantially improves a couple's chances of conceiving. While there are occasional couples for whom the cervical mucus problem is the only reason for their infertility, I am very reluctant to blame a woman's infertility problem solely on poor cervical mucus. Whenever I encounter a couple with a persistently abnormal post coital test, particularly in the face of a normal semen analysis, I always look for other causes of that couple's infertility.

Nonetheless, it can be a valuable test if interpreted properly. When the woman is being tracked through her menstrual cycle, and she is near the time of ovulation, she is asked to have intercourse prior to her office visit. This, of course, creates its own problems since some men cannot perform on demand and under pressure. Ideally, the couple should be seen 6 to 10 hours following intercourse.

To perform the test the woman comes to the office and a small sample of the cervical mucus is removed. This is a totally painless procedure. The mucus is then placed on a slide and examined under the microscope.

When you look through a microscope, the area that you see is a circle and this circle is called a "microscopic field". Depending upon the degree of magnification, that field may take in a larger or smaller amount of the slide.

When looking at the cervical mucus under high magnification (a high power field) you should see at least 5 and preferably 10 or more actively moving sperm in each field for the test to be normal.

Not only must the sperm be moving, they must be moving forward with some "purpose" to their motion. Sperm that are simply moving around back and forth or only wiggling their tails may be moving but it is not a normal movement.

All these factors are taken into consideration in evaluating the normalcy of the test.

In order for the test to be truly interpretable, it must be done at the time of ovulation. Ultrasound and hormone levels are used to determine that the timing is indeed correct. The most common reason for an abnormal post coital test is simply the fact that it was not done at the proper time of the menstrual cycle.

In addition to being properly timed, you really only expect to get a normal post coital test if the husband has a normal semen analysis and the wife's cervical mucus is also of good quality. A post coital test performed in a situation where it is known that the husband has poor semen quality does have some predictive value. There is some evidence in the medical literature that a post coital test may be a better predictor of future pregnancy than the semen analysis. Certainly it is very gratifying to see a relatively good post coital test in a couple where the husband's quality is subfertile. On the other hand, a properly timed poor post coital test with a normal semen analysis and good mucus may indicate a significant problem, often suggesting significant anti-sperm antibodies.

It is also important to determine that the quality of the cervical mucus is good. Unfortunately this is done by very crude means such as looking at the mucus and seeing the quality of the fern pattern. More sophisticated tests are available on a research basis but are not available for clinical practice.

If a couple is found to have a persistently abnormal post coital test, various therapies can be tried. However, their success is still variable and no definitive answers are yet available.

We know that estrogen stimulates the production of cervical mucus. Estrogen is sometimes, therefore, given to women with poor mucus in the hopes of improving the quality of the mucus. Unfortunately, most women with poor mucus have normal estrogen levels. Furthermore, giving a dose of estrogen high enough to stimulate good mucus production would also interfere with ovulation.

Women being treated with Clomiphene (Serophene or Clomid) will occasionally develop poor mucus from the Clomiphene itself (though not as often as commonly believed). Clomiphene also interferes with the development of the endometrium as well. These women were often given estrogen along with the Clomiphene in an attempt to improve the quality of the mucus. Unfortunately, such an approach does not work.

To get around this, Pergonal is often used as a treatment for poor cervical mucus, particularly in women who need Clomiphene, and it is often very successful. Pergonal will also improve the quality of the endometrium.

Another technique that is used to bypass poor cervical mucus is Intra-Uterine Insemination (IUI) . This is probably where intrauterine insemination has its greatest usefulness and its most proven effectiveness even though most evidence does indicate that IUI improves pregnancy rates regardless of the cause so long as the woman has at least one open and relatively undamaged tube.

As I have discussed in other pamphlets, for those couples with either "unexplained infertility" or for those couples who are going through ovulation stimulation with IUI as an alternative or as a preliminary step to IVF, the question has been asked whether a normal post coital test eliminates the need for IUI. Some studies have shown a better pregnancy rate with IUI and other studies have shown that properly timed intercourse is probably just as good although most studies do tend to lean toward IUI as the better therapy.

This has more than academic importance because of the restrictions that some insurance companies place on IUI. Because of some of these restrictions, couples may be forced to choose between what is economically feasible compared to what is medically better. As an example, Pennsylvania Blue Shield has adopted the position that not only will they not pay for IUI, they will not pay for any of the drugs or monitoring during an IUI cycle. From both a medical and an economic perspective this makes absolutely no sense whatsoever. It is about as stupid a restriction as I have ever seen an insurance company impose. The numbers clearly show that Pennsylvania Blue Shield will have to pay out over twice as much money to achieve a pregnancy by denying couples IUI than they would if they agreed to pay for it.

As fewer couples are covered by Pennsylvania Blue Shield and are being switched into other plans, some of which cover IUI, this becomes a less important issue. Nonetheless, it does clearly illustrate the absurd position that some insurance companies take when it comes to the coverage they provide for infertility therapy.

In summary then, I do believe that the post coital test has value in the evaluation of the infertile couple but its importance has often been exaggerated. I believe the post coital test is important not because of its predictive value but because it may permit a better choice of therapies.

Male Factor
30-40 % Of All Infertility

Of the many tests performed on the infertile man, there are really only two that are truly meaningful - the semen analysis and the post-coital test. Our lack of understanding as to what causes male infertility is obviously the reason why we still don't have more and/or better tests. With rare exceptions, we still do not understand what affects a man's ability to produce normal semen. Once we know the cause, there will be accurate tests and also, hopefully, effective therapies.

Other tests that have been used such as the Hamster Egg Penetration Test, Immuno-Bead testing looking for immune problems, and the Hypo-Osmotic Swelling Test may be of value in selected situations but are too unreliable to be used routinely. Also, these tests are expensive and are not usually covered by insurances. Furthermore, treatment options are limited. Therefore, I feel there is little reason to waste a couples' money since the tests mentioned in this paragraph are not covered by insurance and treatment will usually be the same regardless of the results. Immunobead testing for antibodies may be of benefit in selected cases but the test must be done properly.

Because we do not understand the causes of male infertility, there is (with occasional exceptions) no therapy for the infertile man that has ever been proven to be effective. I am well aware that many men undergo numerous therapies in an attempt to improve their sperm count. Unfortunately, when these studies are done in a very scientific fashion, it is difficult, if not impossible, to prove that any of these therapies are more effective than no treatment at all. There is some recent evidence that treating men who have very low sperm counts with high doses of FSH may improve their count. However, it requires giving the FSH every other day for 6 months to know whether the therapy will work. Tamoxifen, an anti estrogen similar to Clomiphene may also work is a few isolated instances.

It has often been said that the best way to discover an infertile man is to marry him to an infertile woman.

It is also true that the best way to treat male infertility is to evaluate and treat his partner. If you study men requesting vasectomy, 25% of them will have sperm counts that are "subfertile", yet they have been able to father children. These men have been able to achieve fatherhood because their wives had no problems compromising their fertility.

This means that a man with a fertility problem can often father children if the woman herself has no significant problems. If an infertile man tries to impregnate a woman who herself has compromised fertility, that couple will not achieve a pregnancy.

Since there is usually little that can be done for the infertile man, better success can be obtained by properly diagnosing and treating the woman. In this way, pregnancies can often be achieved.

Even though there is little that can be done to treat the man himself and improve the quality of the semen he produces, newer treatments that allow us to bypass the natural reproductive processes are helping many men to achieve fatherhood. A full discussion of these techniques is beyond the scope of this pamphlet. However, I would like to mention them here so that you are aware of what is happening.

Artificial insemination was previously a common therapy for male infertility. However, to simply put a man's semen into the woman's cervical mucus is, with rare exceptions, a totally useless procedure. It has virtually no place in modern infertility therapy. However, after "enhancing" the man's semen by washing it and then carrying out a "swim up", placing that semen into the uterus (Intra-Uterine Insemination or IUI) may be an effective therapy for male infertility. However, despite many reports as to the effectiveness of intrauterine insemination, there are also some reports that cannot demonstrate any advantage and no improvement in the pregnancy rates. Nonetheless, it is often done on the theory that it cannot hurt and may help.

In-Vitro Fertilization has emerged as the "last resort" treatment for male infertility. You need far fewer sperm to fertilize an egg "in vitro" than you do naturally and it is possible to extract a few normal sperm from an infertile man for IVF. However, as with any infertility therapy, the success rate in those couples with a significant male fertility factor will be less than for couples where the husband's semen quality is normal.

There are men whose ability to produce normal sperm is so impaired that it is impossible for them to achieve a pregnancy even with IVF. It is now possible to successfully artificially fertilize an egg by taking these very abnormal sperm and literally injecting them into the egg where fertilization can then occur. This technique is call Intra-Cytoplasmic Sperm Injection (ICSI) and is the treatment of choice for male infertility when nothing else has worked.

Because of ICSI, there is no such thing as an infertile male (with very rare exceptions). Sperm can even be removed directly from the testicle and used for ICSI. This is called MESA, or Micro-Epididymal Sperm Aspiration. Unfortunately, ICSI must be done in conjunction with IVF. The cost is $10,000 or more a try which puts it beyond the reach of many couples who would benefit from it.

There are other techniques which have been used with some degree of success, but not as good as ICSI. You may still read about them in various articles. These techniques go by several names and you need to be aware of them. They are called either Subzonal Insemination (SZI or SUZI), or Zona Drilling.

HORMONE TESTING

Any man with impaired semen quality needs to have a full evaluation of his endocrine status. Although it is an uncommon cause of male infertility, various hormone problems do occur in men that can sometimes impair their ability to father a child. These problems must be looked for because when they are found, they constitute one of the few successful ways I have of treating the infertile man.

Poly-Cystic Ovary Syndrome, the most common endocrine problem in women of reproductive age, can affect men as well. PCOS is inherited as an autosomal dominant and therefore, a man can acquire the gene. If a man has a sister with PCOS and he is infertile, he should be evaluated as well. Early balding (younger than age 30) is also an indicator that the man has "PCOS". Because of the endocrine abnormalities associated with PCOS, the man's fertility could also be impaired.

PHYSICAL EXAMINATION

Any man who is producing subfertile semen should undergo a complete physical examination just as his wife is doing. Particular attention should be paid to the anatomy of the penis and testicles to make sure that no other problems exist.

Particular attention should be made to the detection of a varicocele - a varicose vein in the scrotum. Varicoceles are most commonly found on the left side but they can be bilateral and, much less commonly, are found only on the right side.

TREATMENT

When the cause of a given disease or illness is known, the treatment is usually is straightforward. Even when treatment is not available, I know enough to be able to give a prognosis. When the cause is unknown, often numerous therapies are tried in the hopes that one will be successful. Male fertility falls into this latter category.

In the vast majority of instances, as I have already said, I simply to not know what it is that causes impaired sperm production. Since I do not know why men are infertile, I cannot treat them specifically.

Occasionally, I am lucky and I can uncover a specific endocrine problem or some unusual circumstance that does lend itself to specific therapy. Unfortunately, this is the exception, not the rule.

Studies have been done looking at men requesting vasectomy, i.e. men who have (usually) proven they are fertile by fathering children. Twenty-five to thirty percent of these men have semen quality that is officially "subfertile" - yet these men have been able to father children without difficulty. The difference is their partner.

Given the fact that many "subfertile" men can father children, the implication is that if a man is subfertile and his partner is not becoming pregnant, then she too has a problem. This is why I firmly believe there is not such thing as an infertile man or an infertile women - there are only infertile couples. Just because a male factor has been identified does not mean that the wife can be ignored. She too deserves a full evaluation.

What I have also learned is that in many instances, the successful treatment of the infertile man is really the treatment of his wife. Therapies that were originally designed to treat infertile women have emerged in the last five to ten years as the main stay therapies for male infertility as well. I am referring to in vitro fertilization and the various therapies derived from it such as Pergonal stimulation with Intrauterine Insemination. If male subfertility is one of the factors in a couple's fertility problem, then going to either IVF or intrauterine insemination is often the best therapy available, depending upon what is wrong with the wife as well.

This philosophy is based on the fact that while there is usually little you can do to improve the quality of semen a man produces, there is a lot you can do to improve the quality of the semen after it has been produced. This is the underlying principle behind intrauterine insemination with sperm wash and sperm enhancement procedures.

Various types of hormone therapies have been tried to stimulate better sperm production in the men. Men have been given Clomiphene, Tamoxifen (the anti-breast cancer drug which is really very similar to Clomiphene), Pergonal, Metrodin and HCG.

The medical literature is full of "anecdotal" reports as to the success of these therapies but most properly conducted scientific studies do not demonstrate any significant improvement. None-the-less, there are men who will improve. Unfortunately it is impossible to select these men from the overall larger group who will not respond. Therefore many men are treated with the hope that a few will be helped.

There have been several reports that using large doses of FSH for six months may improve sperm counts. This requires the man to receive an injection of FSH three times a week. Given the expense of this therapy and the unwillingness of many insurance companies to pay for it, it is not something that most couples will choose.

As I have already pointed out, if significant numbers of white blood cells are found in the semen, antibiotic therapy is often prescribed although again, the evidence for its effectiveness is still not that strong.

VARICOCELE

I have put the whole discussion of varicocele in its own separate section because it is such a common problem and because it is still a very controversial one.

As I have indicated, a varicocele is a varicosity of the spermatic veins. Ten to fifteen percent of all men have varicoceles. Twenty-five to forty percent of all infertile men have varicoceles.

It has been known for many years that there is an association between a varicocele and male infertility. Whether it is a cause and effect or simply an association is unknown.

Because it is so commonly found in infertile men, it did not take very long for people to decide that perhaps treating the varicocele might improve the man's semen quality. Indeed, the initial reports were very glowing and very quickly, many men with varicoceles underwent surgical correction. The surgery itself is very similar to having a hernia repaired.

Unfortunately, as was true of most infertility studies, the early reports on the success of varicoceles were not done with control groups. Without a control group, an infertility study is meaningless. Therefore, many people felt that the success claimed for varicocele ligation was vastly overstated and the surgery began to fall into disrepute. I freely admit that for many years, I discouraged patients from undergoing this surgery because I did not believe that there was any evidence that it worked.

In the mid 1980's, a large study was published in the British Medical Journal from Melbourne, Australia. At one of the major hospitals in Melbourne, they had a large male infertility clinic and virtually all the infertile men in the Melbourne area were seen and treated at this one facility.

This infertility clinic in Melbourne accumulated a large number of men whom had undergone varicocele ligations and an equally large number of men who, for whatever reason, did not undergo this surgery. It was impossible to scientifically categorize all the problems that these men and their wives might have had. None-the-less, the results quite clearly showed that the pregnancy rates in the two groups were the same. The study could not demonstrate that there was any benefit to ligating a varicocele.

None-the-less, there were men who did show improvement in their semen quality after having undergone a ligation of their varicocele. The question really became one of how to select those men who might benefit.

The only type of medical study that really proves anything is a "prospective one." In other words, you must set up your research criteria and then go forward from that time. Looking back at data that has already been accumulated is very risky because people's memories tend to fade with time.

Finally, a prospective study looking at varicocele ligation has been done and has been published. In addition, this study was randomized. In other words, some men were initially assigned to have their varicoceles ligated immediately. The other men in the study group were not treated for a period of one year. Following that year's period of observation, if their wives had not become pregnant, they too underwent ligation of their varicoceles.

The study quite clearly shows that if a man has a varicocele and his semen quality is only mild to moderately impaired, there will be a substantial improvement in his ability to impregnate his wife. This study only included men whose sperm counts were between five and twenty million. This is in keeping with all the evidence that clearly shows that if a man's sperm count is less than five million, there is probably no therapy that is going to improve it, even if he has a varicocele.

There is another reason for ligating a varicocele even if the man's semen quality is not that much impaired. It has become evident that men with varicoceles suffer a progressive decrease in their semen quality as they age. Therefore, if a man has a varicocele, there is justification in ligating it to prevent his semen quality from getting any worse. Therefore, even though he might be able to get his wife pregnant now, if his varicocele were not treated, he might not be as fertile several years hence when they might hope for another child.

Another controversy that has arisen which must be clearly understood by any man who is infertile is how to diagnose a varicocele. Initially, all the studies and all the treatments were offered to men with clinically apparent varicoceles, i.e., those varicoceles that could either be seen or felt on routine scrotal examination.

Studies began to emerge over the past ten years or so looking at men who were subfertile who did not have an obvious varicocele. These men were then subjected to ultrasound evaluations of the spermatic veins. Men who were found to have a small varicocele detected only by ultrasound but not by physical exam were termed "subclinical varicocele." Many men with these subclinical varicoceles also underwent ligation. This further muddied the waters and made it more difficult to assess whether or not varicocele ligation has a role to play in the treatment of the subfertile man.

Most infertility specialists now feel that in order to justify the surgery necessary to correct a varicocele, it must be detectable on routine physical exam. Varicoceles that can only be detected by ultrasound do not justify therapy.

Genetic

Genetic causes are usually found when the woman has recurrent miscarriages. They are also found in couples who are unable to achieve a pregnancy at all but this is much less common.

Obviously there are no treatments for a genetic abnormality per se. However, if the husband has the problem, donor insemination is available. If the wife has the problem, donor eggs are the only effective treatment.

There are some genetic problems that are minor enough that they constitute only a relative obstacle to having a normal child. Such problems, called balanced translocations, do not affect the health of the person who has it but it does affect their ability to form a normal sperm or egg. However, if it is only a minor defect in the genetic material, the couple may still be able to have a normal child but may have to endure numerous miscarriages to achieve that goal.