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A. Toth, M.D.
Obstetrician, Gynecologist, & Pathologist
Paths to Parenthood:
Antibiotic Therapy and Its Options and Follow-ups
For patients and doctors alike, the quest to overcome infertility is a passionate one involving not only a struggle on the physical plane but also a struggle on the emotional plane. Each month without a pregnancy brings another wave of depression-as if a small death has occurred-and prompts another round of the same frustrating questions: Why wasn't the therapy effective? What can be done now? What is the prospect for success in the future? And each new step in therapy, whether it goes in the same direction as a previous step or in a different direction entirely, inspires fresh hope, which, in turn, calls for renewed commitment.
The prospect of creating a baby is so exciting that it compels both patients and their doctors to consider every means of restoring fertility, from the simplest to the most complicated. Weighing against that consideration, however, are very pressing limits in time, energy, and circumstances. Each couple brings its own combination of biological factors to an attempted pregnancy, and each couple that fails to achieve a pregnancy spontaneously develops its own set of decision-making criteria for getting help.
As I've stated before, fertility therapy is based on meticulous, systematic detective work. Individual leads may have to be followed from all possible angles, and individual problem-solving strategies may have to be tried again and again before a proper diagnosis is attained, reproductive health restored, and an actual pregnancy achieved. Many infertility patients and doctors understandably lack the patience to pursue this work for long periods of time, maybe years, against ever-diminishing odds. This is especially true of female patients over the age of thirty-five (approximately 50 percent of all infertility patients), who legitimately believe they can't spare much time for therapy.
It almost always takes several years for a situation causing infertility to develop in the reproductive system of a man or a woman. Restoring the health of that system, which is the best way to guarantee a healthy pregnancy and a healthy baby, also takes time: thinking time, acting time, and waiting time. Any responsible infertility treatment program requires a carefully constructed master plan that incorporates these time factors and determines the types of therapy to try first, second, and so on. Such a plan inevitably assumes a pyramidal shape, with the broadest range of appropriate therapies for a given patient at the bottom, and gradually narrows-in pace with diagnostic discoveries and/or trial-and-error experiences-to the "last resort" therapies at the top.
Antibiotic treatment, in my estimation, is the proper "first block, first tier" therapy in any pyramid plan to reverse infertility. It is the easiest and least expensive therapy; it has the least significant possible side effects; and if it doesn't eventually reverse infertility, it definitely contributes to the safety and success of all other infertility treatments. Nevertheless, it can, in some cases, take a year and a half for antibiotic therapy to result in a pregnancy: approximately four months to clean the reproductive system and nine to fourteen months for the micromilieu in the genital tract to recover so a healthy pregnancy can take place spontaneously, At the top of the pyramid, by contrast, is the complex and expensive strategy known as in vitro fertilization.
Ideally, every pyramid plan to reverse infertility should be undertaken step by step, exploiting the full possibilities of each therapy before moving on to the next, more advanced and more risky therapy. There are certain situations, however, when patients must make wrenching judgments about whether to commit themselves to the full plan. Most in vitro programs, for example, won't accept a woman over forty years old, and so I am obliged to ask my female patients who are thirty-eight or thirty-nine, "Do you feel you can afford to stay with me until your fortieth birthday?" It's a decision only they can make, and only after they have reached an understanding of all the options available to them in a full plan for reversing infertility. If they do answer no, however, I still encourage them to go through microbial testing and antibiotic therapy to improve their chances for success with in vitro fertilization.
In this chapter, I'll examine how antibiotic therapy works in conjunction with-or in place of-other therapies to restore fertility. For the sake of convenience, I have divided this discussion into three sections, reflecting the three main categories of alternative therapies. In ascending order of complexity, these categories are: (a) fertility drugs, (b) surgery, and (c) assisted reproduction (which includes artificial insemination and in vitro fertilizations).
Essentially, fertility drugs are used to compensate for hormonal imbalances in the male or female reproductive system. The biggest challenge facing specialists who administer drug therapy is to determine the proper drug dosage for each individual patient. If the dosage is too high, it may trigger negative side effects, such as overstimulation of the reproductive system and continued infertility.
The major drugs prescribed for both women and men are clomiphene, Pergonal, and human chorionic gonadotropin, or HCG. Other fertility drugs prescribed solely for women include progesterone supplements, Danocrine, and Parlodel. Obviously, fertility drugs work differently for men than they do for women, so let's consider each gender separately.
Clomiphene When a woman's reproductive system is basically functional but needs stimulation-either she is ovulating erratically, or she is not ovulating at all-clomiphene is the drug treatment of choice. Clomiphene acts through the hypothalamus and pituitary glands to stimulate gonadotropin release, which in turn facilitates regular ovulation. Gonadotropin also facilitates the ovary's output of progesterone during the luteal phase, so the fertilized egg can remain securely implanted in the uterine lining.
Specific clomiphene treatment programs, like treatment programs for any fertility drug, vary greatly from individual to individual. A hypothetically valid treatment might be a daily oral dose of 50 milligrams for five days, beginning around the fifth day of the patient's monthly cycle, during the first several months of treatment. If no pregnancy occurs after three months, then the dose is usually increased for the following three months-a process that may continue until the dose is as high as 150 milligrams. Any time after that first unsuccessful month, the attending doctor may also decide to supplement the clomiphene dosage with HCG or a combination of Pergonal and HCG.
Clomiphene in low doses is a relatively harmless and complication-free medication, but when the dose reaches 100 or 150 milligrams per day for a five-day period, the patient often develops ovarian cysts. Therefore, many physicians recommend sonographic evaluation during each of several low-dosage months prior to initiating a renewed cycle with a higher dose. If the monthly sonogram shows that a patient's ovaries are free of cysts, then her clomiphene dose for the following month can be increased.
A postcoital mucus examination should also be performed for all clomiphene users during the first month and any subsequent month when the dose is increased. Clomiphene tends to have a negative effect on the cervical mucus, and thus, several months of frustration can be avoided if a poor postcoital test is documented at the very beginning and steps are taken to avert future complications.
To document the effectiveness of clomiphene on a patient's reproductive system, another very useful test is the endometrial. biopsy, which the fertility specialist should perform during the second part of the patient's cycle in order to establish whether the stimulation is adequate. If a favorable luteal phase is indicated by the biopsy, then there is no need to increase the patient's clomiphene dose or administer a more powerful medication.
Pergonal. A much stronger drug that works directly on the ovaries in place of the system's naturally generated hormones is Pergonal. It encourages the production of multiple eggs-an event known as superovulation-thus increasing the odds of both fertilization and a multiple pregnancy (in the case of multiple pregnancy, the chances are between 1 and 8 percent).
Pergonal is a very potent drug, and its effect on a given individual's reproductive system is highly unpredictable. Each month a patient takes Pergonal, her system's response to the drug must be closely monitored with blood tests, ultrasound scans, and mucus examinations, necessitating several visits to the fertility specialist's office.
My most common treatment regimen involving Pergonal is as follows:
In a given month, the patient takes 50 milligrams of clomiphene on days 2, 3, and 4 of her cycle in order to initiate ovarian stimulation.
Each day from day 5 to day 9 of her cycle, the patient receives 150 units of Pergonal intramuscularly.
During the next few days in her cycle, the patient is monitored closely with sonographic examinations. If the sonography does not show adequate ovarian stimulation by day 10, I administer Pergonal for two additional days and repeat the sonography. Pergonal administration is continued until the sonography reveals a sufficient ovarian response, at which point I give the patient an HCG injection to facilitate release of the egg.
HCG. HCG stimulates egg maturation as well as the rupture of the egg follicle-an event that not only sends the egg on its journey to the uterus but also triggers production of progesterone, a hormone that enables the uterine lining to receive and support the egg. Most often, the patient receives an HCG injection as the final component of a clomiphene or Pergonal based treatment program. The moment of injection is carefully calculated so that the HCG performs its mission at the best possible time, which is approximately thirty-six hours later.
Progesterone Supplements. Progesterone in the form of pills, injections, or suppositories is often prescribed for inadequate luteal-phase function when it is feared that low natural progesterone levels may result in miscarriage.
Danocrine. Danocrine is the most common medication used to treat endometriosis, which can forestall egg development altogether. Unfortunately, being a powerful anabolic steroid, it can also cause negative side effects (including facial hair growth or muscle enlargement) in over half of the women who use it.
Parlodel. Commonly known as bromocriptine, Parlodel is used to suppress prolactin-a normal pituitary hormone that markedly elevates during pregnancy, causing engorgement of the breasts and preparation for lactation. If an excessive prolactin secretion exists prior to the onset of pregnancy, it may interfere with successful ovulation or egg implantation.
Parlodel is administered all through the monthly cycle in daily, divided doses of 2.5 milligrams. During this time, the blood prolactin level is frequently checked to make sure the desired effect is achieved.
Although I advocate giving priority to antibiotic therapy over any kind of fertility drug therapy, I do not deny that fertility-drug therapy all by itself may enable a woman to conceive and give birth to a live baby. Nor do I deny that fertility drug therapy is sometimes required to make this happen. I only object to the frequent practice of turning to fertility-drug therapy first, thereby seeking to override a health problem instead of trying to cure it.
Assuming, as I do, that bacterial infection causes or aggravates up to 50 percent of reproductive maladies, then it only makes sense to look for bacterial infection before going any further, especially since eradicating such an infection involves much milder medications and a much simpler treatment program. At best, antibiotic therapy alone can clear the way for a natural, safe, and comfortable pregnancy and the birth of an infant free of bacterial contamination. At the very least, antibiotic therapy increases the odds that other, subsequent treatment programs will be successful- they won't spread or intensify an already entrenched bacterial infection, their effectiveness won't be compromised or nullified by it, and they won't bring into the world a bacteria-ridden child.
Because my laboratory is a popular referral center, I have had the chance to follow the protocols of hundreds of my colleagues who deal with infertile couples. Consequently, I have been informed of several treatment regimens involving fertility drugs of which I cannot approve. There are four common situations involving clomiphene prescription that particularly bother me:
Many couples who consult a gynecologist after years of infertility are simply given clomiphene and sent home with the reassurance that the drug can improve their fertility.
Many couples are automatically given clomiphene for secondary infertility following the birth of a live baby.
Many couples are automatically given clomiphene after a second pregnancy ends in miscarriage, the first pregnancy having produced a live baby.
In cases of couples in which the woman has one malfunctioning fallopian tube, clomiphene is frequently prescribed to ensure ovulation in the ovary facing the working tube. While this increases the short-term likelihood of conception, it does not address the issue of the blocked tube.
In all four of these situations, no attempt is made by the specialist to elucidate in any detail what the cause (or causes) of the couple's previous problems may have been. In the third situation, the specialist is apparently just assuming that the lining of the uterus is too weak to maintain the pregnancy. In the fourth situation, the infectious cause of the blocked tube is ignored and no attempt is made to document whether the uterine cavity and the contralateral tube are free of harmful bacteria.
While fertility drugs are geared toward rectifying a particular problem in the genital tract and, therefore, a specific difficulty in the reproductive process, antibiotics have a pervasive effect. A given course of antibiotic treatment eliminates harmful bacteria throughout the genital tract so the entire reproductive process can run more smoothly.
To illustrate this important distinction, let's consider reproductive health problems at different locations in the female genital tract, starting at the beginning point with a very widespread and basic problem: a vaginal milieu that is too acidic. The academic approach is to blame the acidity for killing sperm and to recommend a baking-soda douche. This relatively homespun medication will certainly make the vaginal milieu temporarily more alkaline after each application, during which time sperm entering the vagina can survive longer. My challenge to this approach is, why not get rid of the acidity once and for all? It is quite likely bacteria are causing the acidity; so to reverse the condition permanently rather than merely to attempt overcoming it for a while, I would advise a more efficacious strategy: first, establish the presence of infectious bacteria; then, destroy those bacteria with the appropriate antibiotic regimen.
Let's move farther up the female reproductive system to a more complicated problem. Suppose a postcoital specimen of cervical mucus reveals only dead or sluggish sperm. Typically, the mucus is diagnosed as hostile, and Pergonal or estrogen is prescribed to stimulate or supplement the body's natural production of estrogen. More estrogen makes the cervical mucus more copious, diluting the concentration of any hostile agents, such as sperm antibodies or infectious bacteria. The hope is that. the dilution all by itself will weaken the power of the hostile agents to harm sperm so extensively. Again, I beg to differ with this therapeutic approach. Why not take the eminently sensible precaution of checking the mucus for infectious bacteria? If the underlying problem does prove to be bacteria, it can be solved more simply and successfully with the right antibiotics.
The same argument applies to problems in the upper reproductive tract. In the uterus, luteal-phase defect may be treated-at various stages in the cycle-with clomiphene, Pergonal progesterone supplements, and/or HCG. The basic effect of each of these drugs is to throw the uncooperative uterine lining into overdrive. By contrast, antibiotic therapy stands a good chance of eliminating the problem without risking the potentially dangerous consequences of forcing events that are not occurring naturally. Aside from tissue irritation and swelling, adverse side effects from fertility drugs might include actually jeopardizing, rather than enhancing, the system's ability to carry out a healthy pregnancy.
As for the ovaries, any of the drugs I just mentioned may be prescribed to stimulate ovarian function artificially; indeed, the problems fertility specialists most commonly treat with drugs originate in the ovaries. In my own practice, I've discovered that biopsies taken from malfunctioning ovaries frequently indicate bacterial infection. This fact alone makes me even more confident in my recommendation that antibiotic therapy should be a patient's first choice, before resorting to more toxic medications. It may turn out that this first choice is the only therapeutic choice a patient will have to make.
For some women, drug treatment may indeed prove to be the final answer to reversing an infertile situation caused by poor ovarian function, but that happy ending does not come without risks. The ovary is particularly vulnerable to bad side effects from fertility drugs, including hyperstimulation syndrome (during which the ovary may grow from the size of an almond to the size of a fist or even larger), ovarian-cyst formation, bleeding disorders, and ovarian rupture, which can lead to all sorts of pelvic disasters.
While drug-related complications rarely become this serious, they are well worth avoiding altogether and that is why I so strongly advocate seeing what antibiotic therapy can do first. Maybe it won't go all the way to restoring fertility, at least within the desired time frame, but maybe it will help fertility drugs perform more safely and effectively. That's what happened with Sharon, who endured eight miscarriages between 1984 and 1988 before she became my patient at the age of thirty-four.
Sharon's first miscarriage ended her only spontaneous pregnancy. The remaining seven miscarriages occurred while she was undergoing different courses of drug therapy administered by other fertility specialists. The first four of these failed pregnancies were stimulated with clomiphene; the last three, with Pergonal. The therapeutic goal had always been the same: to stimulate her ovaries so they would produce eggs, nourish them to maturity, release them at the proper time, and finally, keep up a steady supply of progesterone to the uterine lining.
When I first examined Sharon, shortly after her eighth miscarriage, she was ovulating very irregularly. She was also panic stricken at the prospect of suffering premature menopause. "I'm willing to do anything," she told me. "I'm not afraid of trying something more radical."
Ironically, I felt Sharon's situation called for something much simpler. It was obvious to me that her drug treatments and the subsequent pregnancies had steadily eroded the health of her ovaries, and I suspected a progressively worsening bacterial infection might be primarily responsible for her troubles.
Sharon and her husband both tested positive for anaerobic bacteria: three different types in her and two in her husband, with one shared anaerobe. I immediately put them on ten days of intravenous antibiotic therapy. Each received a combination clindamycin-gentamicin course: four doses of 900 milligrams of clindamycin were administered daily using an ambulatory pump system in a continuous infusion; the gentamicin level was adjusted on the basis of repeated blood sampling so the level of medication in the bloodstream remained in a therapeutic range.
As fate would have it, Sharon's therapy did not bring back normal ovulation after three months, at which time she was desperate to have a child. Despite this disappointment, I was sufficiently pleased with the improved hormonal function of her ovaries to think Pergonal could now be beneficial.
I started Sharon's treatment regimen with clomiphene given from day 2 through day 4 of her cycle. Then the Pergonal injections began-150 units daily for a five-day period. At the end of that period, sonography showed her ovaries were still not adequately stimulated, so Pergonal injections were given for an additional three days. On the thirteenth day of her cycle, a second sonogram documented three well-formed eggs, two in the right ovary and one in the left ovary. An HCG injection was administered, and the couple was instructed as to the best timing for sexual intercourse. The very first month brought about a pregnancy, and nine months later, in June of 1989, Sharon gave birth to a healthy daughter.
I sincerely believe that if we'd let nature take its course for two or three years after the antibiotic therapy, Sharon would have become pregnant spontaneously, and her pregnancy would have been a similarly fortunate one. A fertility drug, however, enabled Sharon and her husband to have their child at the time that was best for them. And antibiotic therapy, I am sure, provided much better circumstances in which that drug could do its intended job.
Because the same hormones that induce egg development in a woman also induce sperm development in a man it is not surprising that specialists use the same fertility drugs to rectify both male and female hormonal imbalances. For men, however, there is really only one reproductive problem that may respond favorably to fertility-drug treatment: a low sperm-count (oligospermia) due to insufficient hormone production by the pituitary gland.
Other male reproductive problems that often appear together with a low sperm count are poor sperm motility (that is, the sperm do not move as swiftly or efficiently as they should) and/or poor sperm morphology (the sperm have structural irregularities that impede their ability to swim or impregnate an egg). Sometimes these two problems clear up as a side effect of increasing the sperm count. Overcoming them directly, whether or not the patient has a low sperm count as well, is best considered in the context of artificial insemination and in vitro fertilization. (See my discussion of assisted reproduction, below.)
When fertility specialists detect a low sperm count in a patient who does not have a varicocele, they can't help suspecting the pituitary gland is at fault, since the hormonal output of the pituitary gland raises the testosterone level in the testicles, which, in turn, stimulates the manufacture of sperm. Fertility drugs attempt to compensate for a presumably malfunctioning pituitary gland by working directly on the testicles to boost the testosterone level.
When the problem is mild, many doctors rely on clomiphene. Typically, a patient will be put on a three- to six-month course of 25 milligrams a day for twenty-five days per month. On occasion, clomiphene can stimulate a man's sperm production, but I don't know of a single case where administering clomiphene to a man has been solely responsible for reversing a couple's infertility.
In more serious cases (for example, when the sperm count is especially low, or when a low count is accompanied by abnormally small testicles), treatment with HCG and Pergonal is often administered. The HCG stimulates testosterone production. A patient may be given two or three injections a week for five to six months until his testosterone level is acceptable. At that time, Pergonal is usually added to the patient's regular HCG injections in order to escalate his sperm production. In general, however, there is a very low rate of response.
In my own practice, I am very reluctant to use fertility drugs to create a higher sperm count. Many of my cases have indicated that a patient's low sperm count does not necessarily or entirely result from poor pituitary performance (a condition that is difficult to prove and easy to assume); instead, a low count may be due exclusively or primarily to bacterial infection in the testes, or congenital in nature and resistant to any therapy.
What I've said before bears repeating: fertility drugs are quite potent and can easily throw a reproductive system out of whack; therefore, antibiotic therapy-which is very promising and far less toxic-should take precedence.
At any rate, I could never justify artificially increasing the number of sperm a man produces without first making sure his reproductive system isn't contaminated by bacteria. Otherwise, I would only be increasing the chances for him to infect or re-infect his partner.
Any form of surgery on the male or female genital tract to enhance the possibility of reproduction is, to my mind, a definite second-tier strategy. No matter what good it may accomplish. or how certain a therapist may be that it is the only solution, reproductive surgery is a radical and risky invasion of a highly delicate system. Before any kind of reproductive surgery is undertaken, the system must at least be free of bacterial infection. Otherwise, surgery could inadvertently cause the infection to spread, either by means of the procedure itself or by means of the structural changes it creates. Assuming the system does prove to be infected and the infection is cleared, then if it's at all possible and appropriate, surgery should be delayed until it can be determined whether the newly bacteria-free system is also a newly fertile one.
In examining drug therapies, we started with a woman's point of view. Since we've just considered low sperm count and since this problem lies behind 80 percent of the cases involving surgery on the male reproductive system, we'll begin the examination of surgical therapies from a man's point of view.
Approximately 10 percent of all men and 40 percent of men who visit fertility clinics have a swollen (or varicose) vein on their left testicle. As I mentioned in Chapter 2, this kind of vein, a varicocele, can impede sperm production by raising the temperature in the testicles.
The standard treatment for varicoceles is surgery, in which the vein is cut and stitched. A less conventional but increasingly popular surgical procedure is called balloon occlusion. A silicone balloon, inserted into the vein through a catheter, is left there to block off the blood supply. Although this latter approach is quicker, easier, and less painful, it is also riskier; the balloon may loosen and float elsewhere in the body, causing serious blood clots. In either case, there's at least a 15- to 20-percent chance that a varicocele will recur.
For those who are afraid of surgical intervention, a newly invented testicular-cooling device is available. This device is best described as a pair of modified jockey shorts with a coolant circulating in the fabric that intimately surrounds the testicles. The device can lower the testicular core temperature to the desired level. Thus, if a man can accept the discomfort of wearing the device for a three-month period, he may be able to avoid surgery, except if he desires a longer-lasting correction of his infertile situation.
In my opinion, varicocele surgery is performed far too soon in many cases and far too often in general. Usually, it's the first, if not the only, course of action advised. The operation may well yield a satisfyingly fast solution for the varicocele itself, but is it the best possible way to restore the couple's fertility? In other words, is it in the best interest of the patient, his partner, and even the child they may bear?
I think not. First, the man's genital tract should be cleared of bacterial infection. This step alone may take care of the existing infertility problem, which may or may not be low sperm production. Assuming antibiotic therapy does not take care of that problem, then, and only then, would I advise surgery. Surgery before clearing up any possible infection is irresponsible for reasons I've already stated: if surgery provides a bacterially contaminated man with more and/or better-functioning sperm, then he is all the more capable of passing along his infection to his wife and, through her, to their yet-to-be-born child.
A varicocele may be the sole cause of a couple's infertility if the man has never fathered a child and if the two partners are otherwise healthy. Let's say the couple has produced a child within the past couple of years, however-a very common scenario. Faced with this history, I would not automatically assume the man's varicocele is to blame for their current infertility, and I would argue against an operation to correct it unless all other possible causes were ruled out. In my opinion, it is far more likely the couple's infertility is the result of a growing bacterial infection in the woman's reproductive tract dating from her previous pregnancy.
The varicocele condition no doubt plays a role in the scenario I've just mentioned. The elevated temperature in the scrotum increases the amount of harmful bacteria in the man's system, intensifying his contamination of his partner so much that she becomes incapable of sustaining another pregnancy. I find it extremely difficult to believe, however, that a varicocele condition by itself could have affected the quality and quantity of the man's sperm adversely enough in only two years to render conception impossible.
Accordingly, whenever I interview a patient with a varicocele condition, I always look for signs of secondary infertility in the couple's history:
Did the woman notice any change in her period after the birth of her previous child?
Did she experience any pain or discomfort in her genital tract or in her abdominal region in general?
Did she develop any of the major PMS symptoms? (See Chapter 5.)
Is the couple's child frequently sick or ill-behaved?
If I can establish a reasonable case for secondary infertility through history taking and culture studies, I put off any consideration of varicocele surgery until antibiotic therapy has been given every chance to restore the health of each partner's reproductive system.
Antibiotic therapy alone worked for Bernard and Carol. They came to me in the summer of 1989, after they had been trying unsuccessfully for several months to conceive a second child (their daughter was two years old at the time). After I reviewed the questionnaire and examined Bernard, the three of us discussed their therapeutic options. I explained that I suspected bacterial infection as the prime culprit. In addition to the presence of a varicocele on Bernard's testicle, their reproductive history included Carol's having several bouts of vaginitis shortly after giving birth.
Carol and Bernard agreed to be cultured, and I found chlamydia in both of them. They immediately consented to the six-week antibiotic regimen my laboratory recommends for a chlamydia genital-tract infection. That treatment consists of 100 milligrams of doxycycline three times daily for three weeks, followed by 333 milligrams of erythromycin four times a day for three weeks.
As soon as I was satisfied that both Carol's and Bernard's reproductive systems were uncontaminated, I advised them to try unprotected intercourse again. In two months, Carol was pregnant, and right now, that pregnancy is in its fourth, trouble-free month.
Many couples have come to me after a varicocele operation has failed to restore their fertility. In February 1986, Jeanette read about my antibiotic therapy in a popular magazine and encouraged her husband, Carl, to join her in consulting me. A year previously, another specialist attributed their primary infertility to Carl's varicocele. Carl had it surgically corrected, but they remained infertile. A second specialist advised Prednisone-a cortisone-like drug-as therapy for sperm antibodies. This tactic didn't help either.
I tested Carl and Jeanette for bacteria and found five anaerobes and chlamydia in Carl and four matching anaerobes and chlamydia in Jeanette, plus sperm antibodies. Evidently her prior therapy succeeded in suppressing her antibodies only temporarily. For the chlamydia infection, I prescribed three weeks of doxycycline followed by erythromycin; for the anaerobic bacteria, I continued the treatment with two additional weeks of Flagyl, 500 milligrams four times daily. By June 1986, Jeanette was free of bacterial infection. By October, the sperm antibodies had disappeared. Over the next two year she had two normal pregnancies resulting in two healthy sons.
My hesitancy to advise surgery for varicoceles stems from a fundamental preference to avoid such a traumatic procedure as surgery, no matter what form it may take, unless it is absolutely necessary. This is not to say varicocele repair can't make a critical difference in a couple's ability to have a child; many times, it can. The experience of Gail and Evan, two of my current patients, offers a good illustration.
As soon as Gail and Evan were married, Gail became pregnant. Three months later, she miscarried; they remained childless for the next five years. I diagnosed Gail as having luteal phase defect associated with endometriosis. Evan had a varicocele and a very low sperm count. In this case, I suspected both partners were suffering from bacterial infection but that Evan's varicocele was, by now, directly responsible for his low sperm count. First, I tested them for bacteria and found mycoplasma and three anaerobes in each culture. Next, I placed them on a three-week doxvcycline course (100 milligrams three times daily) followed by a two-week Flagyl course (500 milligrams four times daily). When I was finally convinced both partners were free of bacteria and that Gail's reproductive system was fully restored to health, I recommended surgery for Evan's varicocele. One year after the surgery, Gail delivered a seven-pound boy.
For women, recent advances in surgical procedures to correct genital-tract problems have achieved miracles. In the late 1960s, the advent of microsurgery-operations featuring microscopes and microscopic knives, forceps, needles, and threads-enabled specially trained surgeons to perform all sorts of delicate repairs they couldn't do, or couldn't do nearly as well, before, including excising small adhesions and reshaping intricate malformations in the uterus, the fallopian tubes, and the ovaries. Beginning in 1979, their work was made even more effective by the introduction of microsurgery via laparoscopy, in which surgical instruments or even laser beams are passed through thin operating tubes under laparoscopic visualization.
But while reproductive surgery has become vastly more far-reaching and sophisticated, it still remains invasive and potentially dangerous. And while, in some cases, it can make the difference between being fertile and being infertile, it is among the last steps to be considered, not the first.
Too often, the reverse happens. Aside from the small number of unscrupulous doctors who steer their patients toward surgery for the money it will bring, there are many doctors who are so fascinated with the new technological advances that they advise immediate surgery for every applicable situation, knowing it will "do the trick" quickly and impressively. Many patients, all too eager to believe that their uncooperative bodies, like broken-down machines, can be fixed with tools, accept this advice without question.
Given the inherent danger and expense of surgery, not to mention its capacity to spread infection, I recommend opting for a medical approach whenever possible. My feeling in this matter is especially strong if the reproductive problem seems to be attributable to adhesions in the peritoneal cavity or around the Fallopian tubes-the situations for which surgery is most commonly prescribed. Most adhesions of this type are caused by bacterial infection ascending from the vagina.
Since most patients diagnosed as having pelvic adhesions can't recall an episode that could be considered the beginning of the process, it is logical to assume their adhesions developed as the result of bacterial irritation over an extended period of time. It is also logical to assume the same bacterial irritation is still actively working against the local tissue. Therefore, I believe such cases require broad-spectrum antibiotic therapy directed primarily against anaerobic bacteria.
In October of 1987, Joy decided the time was right to conceive a child with her present husband, Ralph. Having had genital-tract problems during a previous marriage, she wanted to be sure everything was OK before she and Ralph stopped using condoms, so she went to a fertility specialist in Boston, where they'd just moved. She told the specialist that she had had an induced abortion in 1983. In the months that followed, she had experienced progressively worse pains in the abdomen, which had been attributed at the time to PID and had been treated with oral drugs.
After listening to Joy's history, the Boston specialist performed a laparoscopy and discovered a group of fairly large adhesions behind the uterus and a few fine adhesions around the right Fallopian tube and ovary. He proceeded to burn away the adhesions with laser surgery. Since no pregnancy occurred afterward, however, a friend convinced her to see me for a second opinion; and so, in January 1988, she made the trip to my Manhattan laboratory.
When Joy told me her complete reproductive history, I theorized her first husband had been the source of a bacterial infection that had spread through her genital tract during her pregnancy and had caused the PID she had experienced after that pregnancy was aborted. Fortunately, she was able to provide me with a videotape of the laparoscopy that her Boston specialist had performed. When I saw the adhesions, my theory turned into a tentative conclusion. I believed a bacterial infection had created those adhesions and, since no broad-spectrum antibiotic was given following surgery, that the harmful bacteria were still present in her reproductive system.
Joy's culture did, in fact, reveal two anaerobes. Ralph's culture revealed none. I advised Joy to undergo ten days of intravenous clindamycin and gentamicin medication (administered by pump so she could go about her normal daily routines). When the ten days were over, I performed a "second look" laparoscopy. Comparing her present condition with the condition I had seen previously on the videotape, I realized that the pelvic damage she had sustained from her infection was beyond repair. At this point, both her fallopian tubes were badly involved in a complicated web of adhesions, and when we attempted to perfuse the tubes with a marker dye, the delicate fingers at the ends of the tubes were so swollen they refused to pass the dye.
I concluded that the surgery performed by Joy's previous specialist had only accelerated her infection. Now, the best recommendation I could make for Joy was to pursue in vitro fertilization. On her second attempt, she became pregnant, and today, she and Ralph are the proud parents of twin girls.
Not all adhesions in a woman's reproductive system are caused by bacterial infection. Some are the result of advanced endometriosis; others may be scars from previous surgery (like an appendectomy or an operation on the bowels). While these latter types account for a very small percentage of adhesions, surgery is advisable if such adhesions do seem to be responsible for a couple's infertility. Before surgery, however, the patient should be checked for bacterial infection, and any existing infection needs to be eradicated. If this isn't done, when the adhesions are surgically severed or burned, blood oozing from the adhesions will provide a fertile milieu for spreading bacteria, and new, bacteria-caused adhesions may form as soon as a week or two later. The problem is much worse, of course, if the original adhesions were full of bacteria in the first place.
Today, many specialists prescribe ten days of doxycycline treatment after reproductive surgery. From the standpoint of proper antibiotic therapy in such a situation, this treatment is woefully inadequate. The only safe, healthy, and reliable approach to a bacterial infection of any kind anywhere in the female or the male genital tract is to get rid of the infection first; then, move on to whatever other measures need to be taken to facilitate a pregnancy.
So far, we've examined treatments for restoring the reproductive health of both the male and the female partner so they can go about having a baby in a natural way. Occasionally, however, an infertility problem can't be solved. When couples face this dilemma, they may need outside help in getting a pregnancy started.
There are two major categories of assisted reproduction: artificial insemination and in vitro fertilization. I'll address each one separately in the light of what antibiotic therapy can do.
Although artificial insemination is commonly thought to be a twentieth-century, ultrascientific approach to overcoming infertility, it's actually one of the oldest recorded techniques in history. Egyptian papyruses mention it. So does the Talmud. But for millennia (as far as we know), it took only one form: the transfer of freshly released sperm into the vagina.
Historical evidence also suggests artificial insemination was used in only two situations. Sometimes, the would-be father was too inhibited to ejaculate inside or in sight of the would-be mother. More often, the woman was unable to conceive by the man in the normal manner and was forbidden or unwilling to have intercourse with anyone else, which necessitated a non-intimate arrangement with another male. In either case, semen was collected outside her body and quickly injected into her-by reed, tube, or plunger.
These reasons for artificial insemination continue to exist; but modern breakthroughs in identifying the causes of infertility, in collecting and storing sperm, and in administering sperm into a woman's reproductive system have greatly increased the range of potential applications for artificial insemination. Still, as always, the most commonly prescribed treatment for dealing with male-factor infertility problems, artificial insemination today is also helpful in working around certain female-factor infertility problems and in making it possible for a couple to conceive a child at a time of their choosing, regardless of whether the father is present or capable at that particular time.
First, let's look at male-related issues. Aside from impotence or a performance problem, the main reasons a man may have difficulty impregnating his partner-according to most doctors-are a low sperm count, poor sperm motility, and/or poor sperm morphology. Given these conditions, the man's sperm can be specially processed and artificially inseminated so their chances of fertilizing an egg are greatly enhanced.
The principal form of sperm processing to compensate for a low sperm count is called sperm washing. The ejaculate, suspended in a culture medium, is spun in a centrifuge, which separates the sperm itself from the seminal fluid. The concentrated sperm are then injected into the woman's genital tract.
In cases of poor sperm motility or morphology, a swim-up process is used, whereby sperm (unwashed or washed) literally swim up a tube of culture medium. The best swimmers-the ones that reach the top of the tube first-are captured and inseminated.
For women, the major infertility problem currently overcome by artificial insemination is the presence of hostile cervical mucus. In this situation, the sperm is injected directly into the uterus (a process known as intrauterine insemination, or IUI), thus bypassing the cervix altogether. If the uterine milieu is also hostile to sperm, then sperm can be injected directly into the fallopian tubes (a process known as intratubal insemination, or ITI). These different placement options are also serviceable in cases of a woman's partner having a low sperm count, poor sperm motility, or poor sperm morphology. Sperm that are injected directly into the uterus or the Fallopian tubes have a far shorter distance to swim to the eggs.
Perhaps the most beneficial modern-day advance in artificial insemination has been the ability to freeze sperm so they can be used at a later date. Some couples choose to freeze a sample of the male partner's sperm so the female partner has the opportunity to conceive his child no matter what happens-an extended separation, an event that might render the male physically incapable of fathering a child (such as a severe groin injury or the effects of chemotherapy), or even his death. Other couples, who can't conceive because of problems with the male partner’s sperm or who don't want to risk reproducing some genetic defect in the male partner's line, choose among frozen and "typed" sperm specimens donated to a sperm bank by other men.
I am entirely sympathetic to the use of artificial insemination in these latter situations involving insurmountable barriers in time and circumstance. I also feel it is a justified treatment whenever a man has an intransigent performance problem but can still masturbate to a climax or whenever the volume of semen is so small it gets completely lost in the walls of the vagina. Otherwise, I think fertility specialists misunderstand and abuse artificial insemination more than any other single therapy.
As I've already discussed in this chapter, antibiotic therapy alone may reverse an infertile situation that is apparently caused by a low sperm count, poor sperm motility, or poor sperm morphology. If, in fact, testicular infection is playing havoc with sperm production, the right combination of antibiotics will knock the infection out. In any event, antibiotic therapy will strip the sperm of any harmful bacteria they may be carrying into the woman's genital tract, and such an infection in itself may well be the real cause of the couple's infertility. Hostile cervical mucus can also be successfully treated with antibiotic therapy, and it should be treated instead of merely avoided.
Unfortunately, the process of washing sperm does not remove any harmful bacteria that may be adhering to them. Artificially inseminating a woman with washed sperm that have not been tested for bacteria-and treated if necessary-is, in my opinion, courting disaster. Using IUI or ITI to bypass hostile cervical mucus without first making every attempt, beginning with antibiotic therapy, to render that mucus hospitable, is, I believe, similarly dangerous.
At best, with no other problems to be managed besides insufficient or poorly performing sperm, artificial insemination has about a 20-percent chance of causing a pregnancy. This is not a high enough success rate to warrant the current emphasis on artificial insemination within the profession. At worst, it can wind up giving the recipient a bacterial infection that endangers her health, any subsequent pregnancy, and the well-being of any child or children that she brings into the world. In aiming for the best, a fertility program involving artificial insemination must, first involve testing and, if appropriate, therapy to make sure there are no harmful bacteria attached to the sperm or preexisting in the woman's reproductive system.
In Vitro Fertilization
Simply speaking, in vitro (Latin for "in a glass") fertilization is a three-step process:
Eggs are surgically removed from the ovary.
Eggs are fertilized with sperm in a special culture dish.
Fertilized eggs are surgically placed in the uterus, where it is hoped they will implant so a normal pregnancy can begin.
As practiced, however, in vitro fertilization is anything but simple. It's a very complicated, uncertain, and expensive process, and the specific form it takes can vary considerably from case to case.
A woman who is unable to produce healthy eggs may require heavy doses of fertility drugs ahead of time. If the man's sperm are poor performers, the woman's eggs may need to be drilled (a recently developed form of microsurgery known as partial zona dissection) to make sperm penetration easier in the culture dish. For couples who, apparently, have no one serious reproductive problem but still can't conceive, gamete intrafallopian transfer (or GIFT) may be advised. This is an extremely sophisticated microsurgical procedure in which the eggs and the sperm are mixed together inside the Fallopian tube so fertilization has a better chance of occurring "naturally."
In vitro fertilization can definitely be a godsend for women whose Fallopian tubes are completely dysfunctional or missing (although a tube compromised by bacterial infection can often regenerate within six to ten months after antibiotic therapy). Generally, however, in vitro fertilization is prescribed fat more frequently than it should be. Many conditions that prompt specialists to recommend it, such as sperm-antibody problems, endometriosis, or a dry cervical milieu, can be corrected fairly easily with other, less costly and less time-consuming therapies. And the success rate for in vitro fertilization is discouragingly low. On a national average, 65 percent of in vitro patients fail to get pregnant; a mere 27 percent end up giving birth to a live baby.
Why, then, is in vitro fertilization such a popular therapy! The most plausible reason is that in vitro fertilization enables both patients and their doctors to bypass months and maybe even years of experimentation with other therapies. The body is causing complications? Let's try something else altogether! The "bad" reason is that in vitro fertilization involves a great deal of money. Many patients truly believe that the more money they spend on their infertility problem, the greater the chance they have of solving it. Some doctors are all too willing, to encourage this belief for their personal benefit or for the benefit of their clinic.
Assuming in vitro fertilization is essential for a couple to have a child, prior antibiotic therapy can raise the odds that it will be successful. Failed attempts at in vitro fertilization can often be attributed to bacterially infected eggs or to a bacterially infected uterine lining, which proves incapable of holding onto the fertilized egg after it is surgically inserted. Antibiotic therapy can eliminate these problems, plus it can help the entire reproductive system to function more efficiently throughout the pregnancy. In my own practice, antibiotic therapy always precedes in vitro fertilization, and I am extremely proud to say that my antibiotic-treated patients' success rate for in-vitro-related pregnancy and live birth is slightly more than twice the norm.
For Ronnie, in vitro fertilization was, quite appropriately, the last-resort strategy in a long, complex, and exhausting case. Ronnie was a DES baby, and I suspect her genital-tract contamination came from her mother. After Ronnie married Ted in 1979, she relied on the Dalkon shield IUD for birth control and began suffering pelvic pains within the very first month of use.
Looking back, I believe these pains signaled the onset of a serious bacterial infection. I can't be certain whether this infection came from bacteria in Ted's seminal fluid-bacteria that used the IUD as an opportunistic device to "wick" farther into Ronnie's system or whether it came from her own vertically transmitted bacteria, which were pushed into her upper reproductive system when the IUD was inserted. Whichever way the infection developed, Ronnie didn't have any idea what was happening. At the end of her first year of marriage, she went off birth control to have a baby, and the result was an ectopic pregnancy.
Ronnie and Ted sought my help five childless years later, and I reconstructed much of the history I have just recited from the information they gave me during our first conference. Certain that an infected fallopian tube (due to PID) was the direct cause of her ectopic pregnancy, I evaluated Ted and Ronnie for bacterial contamination and found three shared anaerobes in their cultures.
If a woman has had one ectopic pregnancy, she faces a five to eight times greater likelihood of having another ectopic pregnancy in the remaining tube because it, too, is apt to be infected. To reduce this risk for Ronnie and Ted, I put both of them on a two-week course of intravenous clindamycin and gentamicin. Afterward, I performed a hysterosalpingogram to help determine the health of Ronnie's remaining tube. According to the evidence, the tube still had a chance of functioning properly. Therefore, I advised Ronnie and Ted to resume their attempt to achieve a pregnancy, but I also recommended we follow Ronnie's progress closely if and when a pregnancy began.
Two months later, Ronnie reported to my laboratory five days after she missed her period. I decided to perform a beta subunit (BSU) pregnancy test. The beta subunit is part of a pregnancy hormone produced by the placenta, the concentration of which doubles every two or three days during pregnancy. Pregnancies conceived in a Fallopian tube do not initially thrive as well as normal pregnancies, and thus a delay in BSU production is the most sensitive indicator of a misplaced pregnancy. Two tests of Ronnie's blood conducted one week apart revealed an unusually low rise in the level of BSU, and so I advised a sonogram to see where the fetus was positioned.
Sadly, this pregnancy, too, was ectopic, despite the fact that we'd considerably reduced the risk. A laparotomy (a surgical operation through the abdomen) was unable to save Ronnie's remaining tube, but it did reveal the full extent of the damage caused by her pelvic infection. It was now apparent both tubes had been rendered irreversibly incapable of delivering a fertilized egg to the uterus.
I advised another set of culture studies for Ronnie and Ted, and when one anaerobe reappeared in both samples, I put them on a second, two-week course of intravenous therapy. Then they entered an in vitro fertilization program. They conceived in their first trial, and subsequently Ronnie delivered healthy twins.
Many patients seek my help when in vitro fertilization has failed to work for them. Beverly and Philip consulted me after two unsuccessful in vitro trials. Both of Beverly's tubes were irreparably blocked, so this last-tier, last-block therapy was their only hope. Beverly got right to the point in our first interview: "We're counting on you to make in vitro work."
After hearing Beverly and Philip's history, I could deduce that bacteria attached to Philip's sperm (which were still "good performers") had infected Beverly and that the infection had developed into PID. This disease had not only ruined her tubes, but it was also preventing her from sustaining a pregnancy begun by in vitro fertilization. When I tested them and found two anaerobes and chlamydia in each culture, I prescribed ten days of intravenous antibiotic therapy.
Normally, I would counsel couples in such a situation to let six months pass after bacteria have been cleared from their systems before trying in vitro fertilization again. But because Beverly was already forty-two years old, I suggested only a three-month wait. The first trial worked, and nine months later, I delivered a healthy boy.
Later, Beverly wrote me a note saying, "'My husband and I especially appreciated the fact that you listened carefully to us and took a more thorough history than we had encountered elsewhere. You really gave thought to what we were telling you, and had a positive, activist, scientific approach that worked for us." I quote her letter because it draws attention to the most important aspect of any infertility therapy-particularly one that involves such a complicated process as in vitro fertilization: namely, the need to enlist a couple's cooperation in examining their past and present reproductive experiences closely and critically so the best possible therapeutic program can be devised to meet their particular situation.
The final case I'd like to share in this chapter illustrates a fairly frequent and always happy occurrence in my practice: the discovery that in vitro fertilization, previously claimed to be the one and only potential solution to a couple's infertility problem, is, instead, not necessary at all. Germaine and Stan tried for three years to have a child without ever conceiving. None of the fertility specialists they consulted could find anything wrong with them. Each specialist eventually gave up testing and suggested in vitro fertilization, which, unfortunately, is a common prescription when the cause of a couple's infertility can't be identified.
By the time friends referred Stan and Germaine to me, they had been through three unsuccessful attempts at in vitro fertilization. At this point, they were understandably pessimistic about their chances of success a fourth time around. Germaine confessed to me, "We hadn't planned on re-applying for in vitro, but then we heard about your therapy. We decided it was worth seeing if it would make a difference."
I tested both of them and found the same three anaerobes in Germaine's cervical culture and Stan's semen. After ten days of intravenous antibiotic treatment, I tested them again, and the anaerobes were gone. At thirty-four, Germaine was still relatively young. I advised them to put off the next in vitro trial at least six months so her reproductive system would have plenty of time to recover from any damage the infection may have caused. Because they wanted to take advantage of a sudden vacation opportunity, they wound up postponing that next trial two additional months. While they were on vacation, they achieved pregnancy spontaneously. That was two years ago. Today, they have two children: a fifteen-month-old daughter and a six-week-old son.
I can't prove beyond any shadow of a doubt that antibiotic treatment made it possible for Germaine and Stan to have a baby. At the moment, given all the uncertainties that surround the whys and wherefores of pregnancy in general, let alone the specific mysteries of cases like the one I just described, medical science doesn't offer any means for establishing such proof. What I can say with complete conviction, however, is that antibiotic treatment is the only fertility therapy that works to restore the natural health of male and female genital tracts, and if the reproductive systems of both would-be parents are free of bacterial infection, each is much better equipped to function as it was designed to function.