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A. Toth, M.D.
Obstetrician, Gynecologist, & Pathologist
Breaking the Circle:
The Fertile Future
To use a very appropriate metaphor, antibiotic therapy for reproductive health problems is still in its infancy. The child is growing and gathering strength, but it's too young to stand on its own. It continues to need a great deal of support, attention, and development. Assuming it prospers as it should, I believe it will be an exceptional gift to the world-one that holds the promise of breaking a vicious circle of pain, poor health, and infertility now being passed from one generation to another as well as from one sexual partner to another.
Fifteen years ago, I was just beginning to prescribe antibiotics for the treatment of mycoplasmal infections, and I was virtually alone in doing so. At that time, routine testing procedures for chlamydia or anaerobic bacteria didn't even exist. Medical science has come a long way since then. Now virtually all fertility specialists who request my consultation in a case include the request for culture studies for mycoplasma, chlamydia, and anaerobic bacteria in their patient's work-up, and follow my recommended antibiotic regimen in treating organisms that my experience has shown to be harmful to the reproductive process.
Nevertheless, there remain many mysteries about bacteria and bacterial infection that need to be solved. And there remains the challenge of ensuring that all culture studies meet the same standards of thoroughness and reliability and that all treatments for bacterial infection are sufficiently far-reaching and powerful.
Whatever direction the medical community takes in fostering the effective growth of antibiotic therapy, it is only one of two "parents." The other parent is the non-medical population. Breaking the circle of problems I've described in this book requires that people in general take it upon themselves to become better informed about reproductive health issues, particularly about the damage bacterial infections can cause, and that they assume more responsibility for maintaining their own well-being. This responsibility includes getting tested for bacteria and, if appropriate, conscientiously completing antibiotic therapy.
To a certain extent, the advent of AIDS in recent years has helped alert people to the potential dangers of careless sexual relations. No longer are most sexually active adults quite so willing or able to wait for a palpable problem to develop before they think about reproductive health care. More men use condoms. More women insist their male partners use condoms. More couples avoid intercourse altogether until some degree of mutual commitment has been made.
Unfortunately, concern about AIDS has also had an adverse impact on popular attitudes toward responsible reproductive health practices. Many people so deeply mourn the demise of the "free sex" atmosphere associated with the 1960s and 1970s that they idealize promiscuity. They feel AIDS is the only barrier to sexual freedom, but in doing so they forget the many other dangers of irresponsible sex. Such public attitudes keep us from paying more attention to the seriousness of such STDs as bacterial infection.
Another problematic outcome of the current focus on AIDS is that health conditions not perceived as immediately life threatening tend to be ignored. Few realize bacterial infection can, in fact, lead to an early death. Considering that the government and other funding institutions are so slow to finance research into a disease as horrifying as AIDS, it is little wonder they are even slower to provide grants for the study of "lesser" reproductive health problems, such as those caused by bacteria.
Ideally, I would like the federal government to declare bacterial infection in the reproductive system a major public health issue and to authorize, say, five billion dollars to facilitate appropriate research and therapy. This sum is approximately equal to the sum this country will pay in a few years' time for treating pelvic inflammatory disease and its most serious complication, ectopic pregnancies. It does not come close, however, to including the total cost of infertility-reversing procedures.
For a few moments, let's assume my dream comes true. What research needs to be done? What therapeutic programs should be implemented?
ANTIBIOTIC THERAPY: RESEARCH CHALLENGES
Often my patients-or non-medical people who have heard about my work-say to me, "Antibiotic therapy for reproductive health problems is so simple and so effective, and it makes so much sense. Why doesn't every doctor or clinic offer it?" The only answer I can give them is that conventional approaches to health care are slow to change in the absence of repeated scientific proof that a change is warranted.
For all its success in short-term, double-blind studies and in the laboratory of human experience, the type of antibiotic therapy I advocate is still new and, therefore, still in the process of proving itself. We know antibiotic therapy works, but until we know more about how and why it works, it will continue to be categorized as an experimental therapy.
How, then, would I allocate the research half of my hypothetical five-billion-dollar federal grant? What specific research goals do I feel most need to be met in order to make antibiotic therapy for reproductive health problems universally accepted, available, and even mandatory in certain situations?
First, we must design studies that will yield a more precise identification and characterization of every type of bacteria that can be found in the human reproductive system. At present we can only single out a small percentage of bacteria that by association are suspected of causing reduced fertility or interference with the course of the pregnancy and the health of the newborn. In time, I believe we will find that many more are implicated.
A detailed mapping should be made to identify the bacterial flora present in the genital tracts of truly fertile couples (i.e., apparently harmless bacteria) and the bacterial flora present in the genital tracts of those couples who experience infertility or troubled pregnancies (i.e., apparently harmful bacteria). For each harmful bacterium we find, we must establish clear answers to two basic questions: What is its autogenic (that is, self-generated) role? What kind of immune response does it elicit?
After obtaining the answers to these questions, we can proceed to the second important phase of research: studying each bacterium in reference to its involvement in specific reproductive health problems. These problems are the ones I've described in earlier chapters of this book: localized infections, hormonal imbalances, functional interference in the genital tract, miscarriages, and so on.
Right now, following strict scientific standards, we can make only an anecdotal connection between bacteria and many of these problems. We can say, for example, "Fran had a chlamydia infection, and later, she miscarried." But what, exactly, was the physiological nature of the link between these two facts? Why did the chlamydia in Fran's system evolve beyond being a mere opportunistic cohabitant to become an outright pathogen? Did it function in concert with other types of bacteria in her system? What else was happening in her system during the same period of time? Did any of these events contribute to the infection or the miscarriage?
The results of this second phase of research will establish scientific proof that bacteria do, indeed, have a cause-and-effect role in the development of reproductive health problems. Without such a scientific basis, antibiotic therapy for such problems can't be institutionalized, however successful the therapy may be in practice. And without institutionalization, there will continue to be a dearth of testing centers technologically sophisticated enough to isolate harmful bacteria-a situation that currently imposes a severe limit on the potential widespread use of antibiotic therapy.
Unfortunately, research into bacterial infections in the reproductive system and their response to antibiotic therapy can never be conducted according to the rigid clinical standards that apply to most other forms of medical research. These standards include completing double-blind studies (studies during which neither the volunteers nor the administrators know who's taking a placebo) at least two years in length. It would be inhumane to ask infertility patients-especially women who are in their late thirties or early forties-to remain on a placebo for two years. Under the circumstances, I believe most scientists will accept considerably shorter studies, as long as they are otherwise well designed and well implemented.
Of course, many reproductive health specialists have already become enthusiastic prescribers of antibiotic therapy. They have been converted to this therapy by the positive results of dozens of short-term, double-blind studies conducted over the past ten years within the medical system (that is, in the context of clinical research, which is not as strict as academic research). Among these studies has been the six-month PMS-related study I supervised in 1986 (see Chapter 5). In the future, we must have repeated proof of these studies, as well as new studies altogether to confirm what we now only suspect and to uncover what now lies beyond our suspicions.
ANTIBIOTIC THERAPY: A PREVENTIVE APPROACH
Once science verifies and articulates the major role played by bacteria in triggering reproductive health problems, the human race can enter into an exciting new era of reproductive health care. Today, the type of broad-spectrum antibiotic therapy I recommend for my patients is relatively unknown. Even if it were better known, most testing centers are ill-equipped to facilitate it, and most doctors are not trained to take adequate patient histories in order to detect possible bacterial infections. As a consequence, when antibiotic therapy is administered these days, it's usually to treat diseases and maladies that have already caused considerable damage. In the future, when antibiotic therapy has gained widespread acceptance and availability, it can be aimed mainly at preventing diseases and malfunctions before they ever have a chance to develop.
In essence, the prophylactic prevention of bacterially related reproductive health problems requires the administration of different antibiotic treatment regimens at different periods in every individual's life. Specifically, bacterial testing would become routine procedure for both males and females at birth, at puberty, prior to marriage, and prior to attempting a pregnancy (women would also be routinely tested after giving birth). In addition, bacterial testing would be a standard procedure whenever an individual experienced any genital-tract pain or problem. If such testing revealed the presence of harmful bacteria, then the appropriate course of antibiotic treatment would be given.
At this point, let us review those symptoms or circumstances that I believe would indicate the possible presence of harmful bacteria in a patient's genital tract at the time of his or her birth. Chief among such symptoms and circumstances are:
A premature or postdated pregnancy
Early rupture of the amniotic membranes
The existence of an intrauterine infection in the mother during pregnancy
A pregnancy complicated by toxemia or preeclampsia
An intrauterine infection called chorioamnionitis
A low birth weight or growth retardation, especially when inflammation of the placenta can be histologically documented
Severe postpartum infection in the mother, particularly endometritis
The only-child syndrome, when it can be established that secondary infertility in the mother may have had an infectious origin, in which case the harmful bacteria were probably present in her system before she gave birth to her only child
Conception soon after a miscarriage, without the mother having been properly treated with antibiotics
Besides these warning signals, I also think doctors in the future will suspect possible bacterial infection whenever they encounter a patient whose mother delivered by cesarean section. In my opinion, the great majority of cesarean sections not indicated by a genuine size discrepancy between the mother and the infant may be performed either because the uterus failed to respond to natural hormonal stimulation or because the labor contractions were too strong to enable a poorly implanted placenta to supply the infant with oxygen during the delivery process. Both of these conditions could be due to bacterial infection in the mother's uterine lining prior to implantation.
In the future, doctors will probably also be suspicious of a lengthy labor in their patient's birth history. Bacteria in the mother might have compromised the myometrial contractibility. In such a situation, the infant is worse off passing through an infected birth canal after the protective membranes are broken than being delivered by cesarean section. In my own practice to date, I've had to reverse my originally negative attitude toward cesarean section because I realized it often has the potential of rescuing a baby from the serious bacterial contamination that could result if he or she were left inside the mother during a lengthy labor. I have also become more and more convinced that it is prudent to treat an intrauterine baby exposed to potential infection during the course of the pregnancy itself. Since the early 1980s, I have managed patients who were in early premature labor with antibiotics: orally at first; later, intravenously. The side effects of these antibiotics for the baby are negligible; and the fact that pregnancies so treated go to term even after membranes have ruptured testifies to the value of such management.
Any of the above-mentioned indicators of possible bacterial infection at the time of a patient's birth should warrant immediate bacterial testing. Should the presence of potential pathogens become apparent, case-appropriate antibiotic treatment should be given. Ideally this testing and treatment will occur as soon after a patient's birth as possible.
Because the pediatric community at present does not officially accept that genital-tract infections can be vertically transmitted, there is no body of information that would enable me to project whether any bacterial testing or antibiotic treatment for children is likely to become a part of future reproductive health care. The need to develop this information through research is urgent. For all we know at this point, it may be possible for bacteria to multiply and turn destructive in an individual's genital tract even before puberty or before any history of sexual intercourse. In a female child, bacteria may be proved capable of ascending to the ovaries; in a male child, to the epithelium in the testes.
If periodic medical intervention-perhaps at milestones in a child's physical development could detect such dangers and prevent them from happening, then it should become routine. Of course, now as well as in the future, if a child actually exhibits any symptoms of trouble in the genital tract, bacterial testing and, possibly, antibiotic treatment are definitely advisable.
Assuming there are no relevant problems after a child's birth, the next routine testing for bacterial infection should occur at puberty, while the patient is still a virgin. As discussed in previous chapters, hormonal changes associated with puberty can, I believe, suddenly spur the growth of vertically transmitted bacteria that have lain dormant in the individual's genital tract up until that stage of his or her life. A female victim of such bacterial growth may remain asymptomatic, or she may develop menorrhagia, dysmenorrhea, vaginitis, and/or a host of ovarian-cystic conditions. A male victim may also remain asymptomatic, or he may develop urethritis and/or prostatitis.
In my ideal future, for all women during and after puberty, bacterial testing would be added to the routine gynecological testing most clinics now offer. For all men during and after puberty, semen analysis in general, including bacterial testing, would become routine for the first time in history.
Exactly how routine bacterial testing should be in an individual adult's life-that is, how often he or she needs to be tested is conjectural right now, pending further research. Based on what we do know so far, a bacteria-free adult who is celibate shouldn't need frequent bacterial testing- nor should a bacteria-free adult who has a monogamous relationship with a bacteria-free partner. A sexually active adult with multiple partners, however, should be tested whenever he or she changes partners (the optimum situation, of course, is for both new partners to be tested together). As I've already mentioned, I would advise making culture testing for bacteria-followed, if applicable, by antibiotic treatments a prerequisite for a marriage license.
Once during a public interview I was asked if I would condone the routine administration of (for example) a three-week Vibramycin course prior to an attempted conception for any couple living in a geographical area where testing procedures are not readily available. My unequivocal answer was, "Yes!" In fact, I would probably give this regimen in combination with erythromycin or Flagyl for a five- to six-week duration. Having worked with these antibiotics for the last decade, I know that their side effects are insignificant and are capable of being tolerated with only minor discomfort. Until the time when testing procedures are universally offered and available, I believe that routine pre-conceptional, antibiotic therapy would prevent innumerable miscarriages or troubled pregnancies. Speaking for myself as a doctor in such a situation, I am quite willing to take the blame for administering antibiotics without thorough testing when the potential return is so precious.
In my dream scenario of the future, I would also like to see bacterial testing and treatment become a routine first-step procedure in preconception child planning and an early follow-up procedure for women after giving birth. Although it would be difficult to make these procedures mandatory, they could be tied to hospital admission and discharge. Better yet, they could become standard practice in a whole new network of pregnancy clinics that would evolve to facilitate every stage of a pregnancy from a couple's first intention to reproduce to the final postpartum care of the mother and newborn.
My notion of pregnancy clinics in the future is not at all farfetched. Obstetrics today, which technically confines itself to the actual delivery of a child, is turning into an increasingly high-risk profession. More, and more, we're learning that many complications, with which an obstetrician must deal, including the ones we've examined in this book, are predetermined at conception or even earlier. Given the rising rate of problem pregnancies, the litigious nature of our society, and the distorted expectation among many would-be parents that modern technology can guarantee perfect babies, obstetricians today must pay exorbitant malpractice-insurance premiums. I project the escalating bacterial contamination of the general population is bound to bring all these matters to a head very soon, provoking major alterations in how medical specialists define their responsibilities and how medical care is extended to prospective parents and their babies.
THE ANTIBIOTIC FUTURE: POSSIBLE IMPLICATIONS
The timetable for personal bacterial testing and treatment I have just outlined, along with the establishment of pregnancy clinics, promises to create stronger bridges among different existing fertility therapies. For example, I predict bacterial testing and treatment will become an integral part of in vitro fertilization. In my own laboratory, where the two therapies are already linked, it is an enormous joy to help a woman who has been through numerous unsuccessful in vitro cycles finally achieve an in vitro pregnancy after a two-week clindamycin and gentamicin course. I also believe future research will demonstrate that bacterial infections initiate infertility problems in the immune system; thus, bacterial testing and treatment will merge with immunological fertility therapy.
Because it stretches across a patient's life span, the timetable I've outlined strongly suggests that antibiotic therapy to maintain reproductive health will become a multidisciplinary option. As individuals go through different physical and emotional changes and consult different kinds of specialists, they will repeatedly encounter the possible prescription of bacterial testing and antibiotic therapy. It will be a treatment regimen associated with pediatrics, gerontology, and even psychiatry as well as gynecology, obstetrics, and urology.
The institutionalization of bacterial testing and antibiotic therapy could also have profound side effects on the attitudes and behaviors of the general population. Knowing how infectious bacteria are spread and how to prevent their spread, individuals may become more circumspect in their sexual lives, in their choice of marriage partners, and in their approach to family planning. In the future, potential parents will not only strive to achieve a particular pregnancy but will also have the utmost concern for maintaining their genital-tract purity, in order to allow themselves the freedom to reproduce at will.
Tricky ethical issues may arise. For example, infected people who are unable to reproduce may be able to sue the partners who infected them. A new component may have to be added to rape cases, since the rapist may actually transmit an infection to his victim that renders her infertile. Publicity campaigns to encourage cooperation with reproductive health programs may have to be launched and ways found to persuade individuals and groups to engage in socially responsible sexual and reproductive conduct.
Even the most vigorous efforts, however, are bound to fall short of the goal of entirely eradicating reproductive bacterial infection from the population. Some people will continue to be troubled by infection-related fertility problems. Thus, couples considering the termination of a pregnancy through abortion - particularly if it is the woman's first pregnancy - may want to take this factor into account when making their decision. Because bacterial infection compromises fertility in a progressive manner, first pregnancies often produce the healthiest offspring. Each successive pregnancy may yield weaker children, so the termination of any pregnancy may mean taking the chance that later pregnancies may be more difficult or produce less healthy children.
REPRODUCTIVE HEALTH: WHAT YOU CAN DO NOW
Until reproductive health is recognized by the medical establishment and the federal government as a major public health issue, thereby ensuring better, more concerted efforts at research, consumer education, and consumer protection, infertile couples must make their own way through the vast, intimidating wilderness of fertility specialists and therapies. To make this quest less perilous, nothing is more important than information.
When a man and a woman suspect that they are suffering from infertility, the first thing they should do is read about infertility on their own. Fortunately, many widely available books offer comprehensive and reliable basic information on infertility and are written in layperson’s language. My advice is to read several of these books and make notes.
However fast-paced recent scientific developments in the field of infertility have been, the major tests and treatments have not changed much, and they're likely to remain the same for years to come. The more you learn about these tests and treatments - why they are prescribed, how they are administered, and what the results may be - the more potentially successful your campaign to overcome infertility will be. You will be able to talk more constructively with fertility specialists, develop more reasonable expectations regarding what different therapies can do for you, and cooperate more effectively in giving specific therapies their best chance of working.
When you feel you are fairly well informed about the different types of fertility specialists and what they do, then gather as much information as you can about the specialists who practice in your area. Consult friends and local professional groups for recommendations, and interview several specialists before making a final decision about which one to retain. It will cost money to shop around in this manner, but it will be money very well spent, given what a mistake in judgment may cost you.
The relationship between an infertility patient and a fertility specialist is uniquely intimate, requiring a great deal of mutual trust and respect. It makes far more sense to spend time and money up front finding the best specialist for your physical and emotional needs than to waste time and money over several months or even years on a specialist who ultimately proves to be inappropriate.
Here, to get you started, are some, sources of information regarding infertility and fertility specialists:
American College of Obstetricians and Gynecologists Resource Center
409 Twelfth Street, SW, Washington, DC 20024
National professional organization for obstetricians and gynecologists; offers printed materials regarding reproductive health and infertility plus information about contacting obstetricians and gynecologists across the nation
American Fertility Society
2140 Eleventh Avenue, South, Suite 200, Birmingham, AL 35205
National organization of fertility specialists; offers printed materials regarding infertility
American Urological Association
1120 North Charles Street, Baltimore, MD 21201
Offers printed materials regarding urology and male reproductive health -plus information about contacting urologists across the nation
Planned Parenthood Federation of America
810 Seventh Avenue, New York, NY 10019
Offers information about contacting affiliated groups across the nation, which can supply information about local fertility specialists, clinics, and resource centers
5 Water Street, Arlington, MA 02174
(617) 662-1016/(617) 643-2424
Self-help organization for infertile couples, offers printed materials regarding infertility plus information about contacting affiliated groups across the nation, which. can supply information about local fertility specialists, clinics, resource centers, and support groups
As a general rule for choosing a specialist, I would suggest going to a large fertility clinic. There, you will find a number of specialists whom you may interview, all of whom have had the benefit of each other's counsel and quality control.
I particularly recommend fertility clinics affiliated with teaching institutions. Because of the very active communication and loan network among teaching institutions, their fertility clinics are most likely to utilize the very latest information, instruments, and techniques in their therapies.
Before or during your initial interview of a specialist, here are some very basic questions to which you need answers:
In what areas of medicine is the specialist certified: obstetrics and gynecology, urology, reproductive endocrinology?
What specific reproductive health problems does the specialist treat?
What tests, procedures, medications, and treatments does the specialist offer? What is the average total cost and total time span of different types of therapies?
How many patients has the specialist treated? What is the specialist's overall rate of success for different therapies (interpreted as the percentage of live births among the total number of couples treated)?
With what types of patients does the specialist usually work? What, for example, is the average age of the specialist's patients?
Does the specialist personally handle all aspects of a patient's case?
Who else may become involved in a patient's case? What are the qualifications of that individual (or those individuals)? What might be the extent of such involvement?
Is the specialist readily available for consultation? Are there certain times of the day or days of the week that the specialist is more (or less) likely to be available?
How does the specialist handle the patient's insurance?
Some answers may immediately disqualify particular specialists. For example, they may not offer services that you want, or their prices may be too high. Other answers may not mean much to you because you don't yet know enough about your particular infertility problem to interpret their relevance. Nevertheless, it's critical to get all the advance information you can so you can monitor progress in your case and anticipate possible problems, alternatives, and needs.
Be sure to pose the same questions to each specialist you interview. This will give you a more accurate basis for comparing one with another. And it's in the context of such a comparison that many of the individual answers you've accumulated will acquire more significance.
Above all, pay attention to how sensitively and thoroughly each specialist frames his or her responses. Try to assess whether one specialist inspires your confidence more than any of the others, or whether he or she seems to have a more knowledgeable approach to infertility problems or an approach that is more compatible with your own ideas and feelings.
Once you finally decide upon a specialist, make sure at all times during your doctor-patient relationship that you have a clear sense of how your case is progressing and some idea of what to expect a month down the line, three months down the line, a year down the line. Your specialist should provide you with a systematic plan for making progress in treating your infertility. If such a plan is lacking or if your patience is exhausted, then you should seek help elsewhere. For, all you know, you may be dealing with someone who has, in fact, quite legitimately run out of ideas. Remember it's never too late to get a second opinion or change specialists if you feel you're in a rut-for example, repeating the same therapy over and over, always experiencing the same type of failure, and never having a reason to believe the future holds anything different. I offer only one cautionary note, for those patients who have been treated for infectious bacteria with antibiotics. It is good to keep in mind that the period of greatest fertility following a negative culture study is not the following month. As several months pass by, the individual's fertility improves; and it may be approximately six to ten months before optimal restoration of the reproductive process is achieved, provided there is no pre-treatment structural damage. The explanation for this time lag is probably the fact that once bacterial infections are eliminated, the immune system requires time to restore the local environment to normal.
Before you change specialists, it's critical to get all the information you can about your case from the specialist you're leaving. Insist upon receiving copies of every test the specialist has performed, and check to see that these copies are dated and include all relevant information. Such documents are extremely helpful to any future specialist you may consult and can save you a great deal of time, money, and frustration.
BRINGING ABOUT THE FERTILE FUTURE
Just as infertile couples critically need information, the field of infertility treatment critically needs informed consumers. Today, too much energy is expended on reversing or overcoming problems that may never have materialized in the first place if the patients presenting the problems had been more enlightened about, and responsible for, their own reproductive health. The more effort an individual can contribute to his or her own well-being, the more effort medical science can devote to making progress on promising treatment breakthroughs like antibiotic therapy.
When infertility problems or other reproductive health problems do arise, informed patients can save their specialists, not to mention themselves, a great deal of time if they already have a good, general background knowledge relative to their situation. They can also make far more intelligent choices among the specific treatment options they are offered.
The future of antibiotic therapy for reproductive health problems hinges on the public's becoming more aware of why that therapy is so promising and on individual patients' actively seeking that therapy from their specialists. Left to its own devices, without the watchdog influence or intelligent decision making of an informed public, institutionalized reproductive health care has pretty much confined itself to the treatment of outright infertility-a very advanced reproductive health problem-and has become relatively fixated on complex, high-risk, and expensive assisted-reproduction technologies (like in vitro fertilization) that try to work around infertility problems instead of correcting them.
I believe we need to identify and attack reproductive health problems much earlier, much more directly, and much less dangerously than we do now. Most important of all, I believe we need to identify and attack reproductive health problems more successfully than we do now. I am convinced antibiotic therapy has the capacity to satisfy all these needs.
It is, indeed, possible that the near future will bring about substantial government support for antibiotic therapy and that the general population will have the information and the means to live much healthier lives and produce much healthier offspring. If this support doesn't materialize, it is highly probable that the near future will at least bring about laws to curb escalating reproductive health care costs and educate the public about such preventive reproductive health strategies as bacterial testing and antibiotic treatment. What's absolutely certain is that the near future will bring about increasing public discussion of reproductive health care in general and antibiotic therapy in particular. We owe that discussion to the next generation-and to every generation that follows.