Female Infertility

Ovulation is a precise and elaborate system, arranged around four epic events in a woman's reproductive life: her development in utero; her childhood; her prime reproductive years; and menopause, when the door closes to the reproductive cycle. When a woman is infertile, something has gone wrong during one of the first three epochs.

In Utero Development

Sometimes a woman is born infertile. As a female fetus grows inside her mother's womb, some small flaw may occur in the cell groups that cluster into specific bits of tissue. The possibility of error is easy to imagine when we consider that every fragment of the human body, every limb and eyelash, comes from a single pair of fused cells.

Sometimes the cell groups that construct the various organs misread the architect's blueprint. Instead of one vagina, they make two. Instead of one tiny cervical canal, they build two. Where the plan calls for a single roomy uterus, they put up a wall and divide it into two compartments. Sometimes the builders forget to put in an ovary or a fallopian tube.

When the baby is born she looks perfect. No one would know of the few little mistakes on the inside. At least not immediately. These kinds of flaws usually remain completely unnoticed until the baby grows up and enters her prime reproductive years.

Childhood

Most of the time the cell engineers do a flawless job. Generations of exquisitely formed female babies testify to their skill. Once a baby girl is born, however, she is subject to an onslaught of travail from the outside world. If she is lucky, threats to her reproductive function are held at bay throughout childhood. However, even a well protected child can innocently stumble into trouble. It could be something as simple as falling off a bicycle. If the hard metal frame jams between her legs, her reproductive organs may be damaged. Straddle injuries can be serious for both boys and girls. Much more traumatic is sexual abuse, an event more common than we ever believed possible. Such acts against a child are usually kept secret. The child victim may feel shame and guilt, and almost never speaks of the crime. The moral implications are only part of the picture.

A little girl has neither emotional nor biological defenses against sexual abuse. Her body has not yet developed the cervical mucus that defends the pelvic cavity against infection. Such an infection may go by unnoticed and subside spontaneously; but it can completely destroy the girl's reproductive organs. The psychological ramifications also may indirectly affect her future fertility. Children who are abused sexually may be so contaminated by the experience that their adult lives are forever haunted by memories and guilt, stress patterns that one way or another can make pregnancy impossible.

Fortunately, most little girls do not encounter such physical or sexual abuse and come through these years unscathed. Their biological time clocks, which have been quiet through the days of childhood, begin to wind up around age ten. Both hands start to sweep erratically around the clock face, stalling here, jumping there. The system seems to be going haywire. Then quite suddenly the hands sweep together at twelve o'clock high, and the girl begins to menstruate. From that moment on, the clock precisely ticks off the cycle of ovulation, and thus begins the third major epoch of her reproductive life. How smoothly the clock starts off plays an important part in the girl's fertility. A quick, easy startup usually means that ovulation will be regular throughout her lifetime.

The Reproductive Years

With the onset of menstruation it is possible for a woman to have a child. This critical epoch is also the time when most fertility problems arise. Something may have happened during fetal development or childhood, but most causes of infertility arise in adult life.

Fertility problems in adult women are divided almost equally into two fairly distinct categories. The first category, called ovulatory failures, has to do with ovulation the production and release of eggs. Any disturbance in the hormonal axis can cause the system to misfire. Nowadays such problems are almost always treated with the new fertility drugs.

The second major category of problems involves "mechanical" failures, in which the reproductive organs themselves are damaged. For various reasons, scar tissue or endometriosis can build up all over the organs. Not so long ago these kinds of problems were considered hopeless. Thanks to advances in twenty first century medicine, microsurgery often can successfully free the tubes and ovaries, making pregnancy possible for thousands of couples.

A third, less frequently seen, group of problems involves the route traveled by sperm as they swim from the vagina through the cervix and uterus, and into the tubes. Problems here may go all the way back to the dim hours of fetal development. Some of these problems can be corrected with clever surgical reconstruction of the reproductive structure.

At least half the fertility problems in women are related to egg production and release. The egg may not mature properly; or if it does grow, it may not release from the ovary on schedule. The operation of the ovaries is overseen by the hormonal system. If this system is even slightly disturbed, ovulation won't occur.

The hormonal system has two major components: hormones sent by the hypothalamus pituitary control center and hormones made by the ovaries themselves. Errors in either part of the system may interfere with egg production.

Birth Control Pills. Some errors occur spontaneously in the timing mechanism of the hormonal system. Others are perpetrated by that ingenious culprit, the birth control pill. Every helpful modem invention is said to have at least one drawback. We are only beginning to recognize some of the drawbacks of the pill. One that physicians see almost daily is temporary infertility after a woman stops the pill.

Birth control pills work by interfering with the hormonal axis. Because the control center receives a constant signal each day to limit its work load, it does not send FSH and LH hormones to the ovaries. The cells that operate the control center become lazy and dull; they go to sleep at the switch.

The result? When a woman stops taking the pill, the cells grumble and grouse and try to catch another forty winks. Ovulation does not occur in the first month, or the next. Sometimes it does not resume for several months. Time is needed for the cells that run the control center to fully reawaken and take command of the system. Generally, this condition, called postpill anovulation (no ovulation) or oligo ovulation (occasional ovulation), cures itself within six to twelve months.

How quickly the system wakes up depends largely on how easily the woman's periods began when she entered puberty. If she had an instant startup then, she will usually quickly recover her normal cycle. However, if she had a slow startup in youth, birth control pills may have a profound effect on her system.

Serious problems can arise if a woman has delayed pregnancy until her thirties. At that point, she can't afford to wait an extra year for the cell staff to wake up at the control center. Older women, and women whose systems refuse to wake up after a year, need extra help. The control center can be booted into action with fertility drugs. At the Omega Institute, we have found that about 25 percent of patients over twenty seven years of age who sufer postpill anovulation need this extra initiation. For the rest, the system usually fires up on its own without medical interference.

Other contraceptives also can affect a woman's future fertility. IUDs have been known to cause secondary pelvic infections, which result in scar tissue around the reproductive organs, so this form of contraception also has some risk to fertility. Abortion does not seem to affect future fertility, unless the procedure is carelessly performed and infection sets into the pelvic cavity. However, each time a foreign object is introduced into the uterus, there is a chance of infection, and repeated abortions increase the risk.

Polycystic Ovarian Disease (PCO). The most common cause of serious ovulatory problems is a disorder called polycystic ovarian disease. Researchers dispute the exact origin of the disease, but most investigators agree that the ovaries misread the LH/FSH signal from the pituitary and send back the wrong response along the feedback loop. Scientists are uncertain whether the original flaw lies in the control center or in the ovaries themselves. Some believe heredity may play a role.

Regardless of which came first, the result is the same: ovaries clogged with cysts, and few or no ovulations each year. As with most problems involving hormones, the disease runs in gradations, all the way from very mild to extremely severe. About 75 percent of the time women with PCO respond well to a three month course of therapy with superfertility drugs. The pregnancy rate is about 35 to 40 percent. In some women, however, the system is completely resistant to drug therapy.

Emotional Disturbances. Few scientists today believe that psychological problems directly cause infertility, but this is still a prime area for research. Too many indicators point to emotional involvement to discount such a possibility. The lower brain (hypothalamus), which is the major thrust behind the reproductive system, can be overpowered by the higher brain (central nervous system). The hypothalamus is sensitive to psychological trauma, which can severely deplete the messenger chemical that it sends to the pituitary gland.

We know that certain drugs, particularly the psychiatric class of tranquilizers and mood modifiers, can override the hypothalamus and disturb the hormonal axis. Usually as soon as the drug is stopped the axis returns to normal. Illness and stress also can interfere with hormone production, and thus temporarily stop ovulation.

The deemphasis on psychological factors as a cause of infertility is a result of two events. First, it represents something of a backlash against the insensitivity of physicians over the past few decades to the plight of infertile women. Thousands of women were told that their inability to conceive was strictly in their heads. Modem science has shown that the vast majority of these women probably had undiagnosed physical problems that caused their infertility. Second, science has been so successful that 90 percent of all cases of infertility today can be accurately diagnosed, compared with only 40 percent ten years ago. Most of the leading researchers in the field are so impressed with these advances that they believe that new, even more sophisticated diagnostic techniques will eventually be able to identify a physical cause for the remaining 10 percent.

While psychological factors are not often considered a cause of infertility, they frequently are a result. One of the most important discoveries to come out of modem fertility research is the recognition of an infertility stress syndrome. Infertility creates enormous psychological stress for both partners, and the stress increases as the couple goes through the workup and subsequent treatment. Stress can create problems in the marital relationship and make existing problems worse. For these reasons, professional psychological evaluation is part of many fertility workups today.

The benefit of this counseling is twofold: Couples receive support to help them cope with stress, and scientists gain some insight into stress factors that may, in fact, be putting so much pressure on the couple that treatment cannot succeed. This new knowledge and experience may ultimately help us learn why some couples, for unknown reasons, cannot conceive.

Modern Treatment. Twenty years ago almost no medical treatment was available for women who were infertile because of ovulatory failure. Some physicians tried what is known as the rebound technique. If a woman took large doses of estrogen orally, the control center in the brain, detecting the excess in tile bloodstream, would completely shut down the ovaries. When she stopped taking the estrogen supplement, the brain would react powerfully to the sudden hormonal absence from the bloodstream and throw an extra boost of FSH and LH to the ovaries to force them back into production. This new, high energy startup would sometimes result in temporary ovulation.

Ovulation is a very precise mechanism. The rebound technique, which involved a general flooding of the system with estrogen to see if anything happened, did not begin to deal with the complexity of the problem. What was needed was a drug that would directly manipulate the control center, forcing it to issue correct instructions to the ovaries. That drug was finally made available in the early 1960s when clomiphene citrate came onto the market. Since that time clomiphene (Clomid, Serophene) has been the leading fertility drug in the world . Clomiphene acts directly on the hypothalamus, forcing it to boost the pituitary, which in turn drives the ovaries to produce and release eggs.

Clomiphene can induce ovulation in nearly 80 percent of all women with ovulatory failure. When clomiphene fails, other, extremely potent fertility drugs can be tried; these drugs have severe potential side effects, and must be carefully monitored.

Mechanical problems involve the frailties of the reproductive organs, particularly the egg's transport system. Fallopian tubes may be damaged on the inside or the outside. Even a web of scar tissue tying down the tube can keep it from picking up the ovum. Blockages inside the tube prevent the union of sperm and egg; partial blockages can entrap a fertilized ovum and cause a dangerous tubal (ectopic) pregnancy that cannot implant in the uterus.

The other reproductive organs may also be severely damaged by scar tissue. All the organs should slide naturally and smoothly againt one another. Rubbery adhesions on the outside literally paralyze the organs. These are only a few examples of mechanical problems. A woman is not born with these kinds of problems; she catches them.

The Role of Infection. Scar tissue is most often caused by infections inside the pelvic cavity. Such infections, primarily venereal disease, are the major factor behind the rising incidence of infertility in women. Pelvic inflammatory disease (PID) accounts for roughly 20 percent of fertility problems in women, and this is a rapidly climbing statistic.

Almost all pelvic infections are venereal in origin, meaning simply that they are transmitted sexually. Women today become sexually active earlier, often in their early teens, and may have a number of different partners during their lifetime. Having multiple partners increases the risk of being exposed to infection.

When a woman contracts even a relatively minor venereal disease for example, condylorna (venereal warts) or herpes virus the tough barrier of mucus in the cervix, which normally protects the pelvic cavity, may be destroyed. Through this open portal, a bacterial infection such as Streptococcus or gonorrhea can travel freely through the uterus and into the fallopian tubes. The body's immune system quickly responds to the invasion. An army of white blood cells swarms over the bacteria and literally eats them up. As the white blood cells destroy the invaders, they excrete a collagen protein that resembles steel mesh. This is scar tissue.

Rapid treatment can stop massive damage, but it doesn't take much scarring to interfere with pregnancy. For example, the fallopian tubes are very susceptible to gonorrheal infection and may become permanently damaged after a single "small case of gonorrhea." About 25 percent of women with any form of gonorrhea will have significant tubal damage that results in infertility. (Interestingly, because gonorrhea seldom reaches the ductal system in men, it is not a significant cause of male infertility.)

New diagnostic tests have led to the discovery of other organisms dangerous to women. Some of the so called nonspecific infections ignored in the past have proved to be quite specific. One hard to identify organism called chlamydia can invade and silently destroy the fallopian tubes within a few days. Today chlamydia has far outstripped gonorrhea as the most widespread of all sexually transmitted diseases. Scientists are working hard to develop better detection methods for this elusive organism.

Infection is not the only creator of scar tissue. Even a minor surgical procedure in the abdomen can cause severe scarring in women, particularly if the operation was complicated by infection. Another major cause of pelvic adhesions is endometriosis, dubbed the "careerwoman's disease," since it is more likely to occur in women who have never had children. Both endometriosis and pelvic inflammatory disease are sometimes called pelvic adhesive disease (PAD), a general term for adhesions in the pelvis of any origin.

Endometriosis. This is a painful and destructive disease in which tissue identical to the endometrial lining of the uterus begins to grow in the interior of the abdomen. Somehow, endometrial cells implant on the outside of the uterus, on the ovaries or bowel, and continue to grow just as if they were inside the uterus, steadily spreading through the pelvic cavity. Every month, under the influence of hormones, blood flows from this misplaced tissue, just as it does from the uterus. Since the blood cannot escape through the vagina, as it would in a normal menstrual period, it flows into the pelvic cavity, creating scar tissue that ties down the reproductive organs.

No one knows for certain how this tissue gets into the abdomen in the first place. For a while scientists held that some of the endometrial lining, instead of being fully expelled during menstruation, backed up through the fallopian tubes into the abdominal cavity. Recently, however, researchers have learned that some women who have their tubes tied still develop endometriosis.

If the endometrium can't back up out of the tubes, how does it implant itself? One idea is that endometriosis is a birth defect. During fetal development the cell engineers that build the reproductive system misplace tiny endometrial cells in the abdomen, much like carpenters lay down their tools in the wrong place and forget to take them home. The cells may lie dormant for many years, then sometime after puberty they begin to grow. This neat idea fills several gaps in the old theory. For example, if the error in the blueprint is inherited, it could explain why endometriosis tends to run in families.

Whatever its origin, even a small amount of endometriosis in the wrong place can interfere with fertility. It is a painful disease, especially in early stages when the cells are tender and burgeoning.

For some reason, endometriosis seldom attacks the flowerlike fimbria that picks up the egg. Nor does it harm the delicate cilia. Thus, if the endometriosis can be cleared up, usually with a combination of fertility drugs and new microsurgical techniques, a woman has a good chance for pregnancy. After proper treatment of the less severe forms, about 60 to 70 percent of women are able to become pregnant. Whether a woman can conceive following treatment for the more advanced stages of the disease depends on how much damage has been done to the reproductive organs.

Twenty first Century Medicine. Surgical advances have made possible the correction of hopelessly blocked and damaged fallopian tubes. Fifteen

years ago the microscope was matched to surgery for the first time, and surgeons were no longer limited to what they could see with their own eyes. With 10 or 25 power magnification, miraculous repairs could be made on delicate, nearly invisible structures. Surgeons could eradicate problems that had never been seen before, such as small adhesions around the fallopian tubes or "invisible" implants of endometriosis. Surgeons can today rebuild a fallopian tube, because they can match up, and neatly stitch together, the three separate layers of the tube.

No longer do the surgeon's needle and thread drag and tear at tissue, suggesting the need for finer equipment. Today microsurgeons use' needles smaller than eyelashes to rebuild reproductive organs. The needle is made by lasers that drill a hole down the length of the steel lash; a technician inserts a thread into the hole and presses the union together, so that needle and thread are One slender strand.

The precision of lasers makes them a natural tool for use in medical surgery. Lasers combined with microsurgery can clear obstructions, rebuild tubes, and free reproductive organs from massive sheets of adhesions. This is done without damage to the surrounding tissue, little bleeding, few sutures, and in half the operating time of conventional surgery.

Menopause

As a woman approaches menopause, the fourth epoch event in her reproductive life, the door begins to close on her childbearing years. The precise, bright countenance of her reproductive mechanism flickers and ultimately fades.

Middle age, which has little effect on male fertility, puts an end to a woman's childbearing years. Our changing views about parenthood have made age a critical issue in the rising incidence of infertility in women. Many women are now postponing childbearing until their late twenties and thirties. They gain the advantage of personal and professional growth, and their children in turn benefit from more mature, stable parents. But the flip side of this gain is that a woman's finely tuned reproductive system functions best between the ages of eighteen and twenty eight, when ovulation is most regular. Also her ova, which are present at birth, are as old as the rest of her body, and older eggs begin to deteriorate and lose some of their capability for fertilization. If her husband has a slightly lowered sperm count, together they may be infertile.

Any one of these factors may be involved when a woman finds herself unable to have a child, and each of these components is fully described in the chapters that follow. But an infertility problem may lie with a man as well. We know today that men, for a variety of reasons, have as high an incidence of infertility as women. And in 20 percent of couples, both partners have a problem. Many women have undergone major surgery for tubal reconstruction only to discover later that their husbands were infertile.