Chapter 3: How Antibiotic Therapy Works to Ensure Fertility

How Antibiotic Therapy Works to Ensure Fertility

Typically, when people go to a fertility specialist, they're prepared to be patients in the most literal sense of the term. They assume their task will be to wait patiently in fear, hope, and bewilderment while the specialist performs inscrutable tests on them and, ultimately, deciphers what's wrong with their reproductive system. When people come to me, their role is not a passive one at all. Instead, they join me as active partners in a detective case.

Much of the territory I want my patients to explore is predictable, given their reason for consulting me. Therefore, I can set them on the trail even before we meet. I've designed a detailed questionnaire to elicit any medical or family history relevant to a couple's current status of infertility, and I ask that the questionnaire be completed ahead of time so we can review it together during the first appointment.

The most important group of questions-for both the man and the woman-concerns previous marriages and/or relationships. I ask them to establish the order and extent of their individual sexual experiences with different partners and the kinds of birth control they practiced prior to their own sexual union.

In the woman's case, I am particularly interested in learning about any previous infectious events related to her genital tract, such as vaginitis, cervicitis, PID, abdominal pain, or STD. I want to know whether she ever perceived any changes in her menstrual period-for example, she may have observed a difference in the color, pattern, or quantity of the menstrual flow, or there might have been a delay in the onset of a period, which could be interpreted as a short-lived pregnancy. I also ask her about obstetric events or premenstrual symptoms during any previous relationships. Once this past history has been covered, the woman is directed to provide similar information regarding her current relationship.

In the man's case, I am likewise interested in both the past and the recent health status of his genital tract. The questions posed to him cover the full range of male-related problems from relatively common events, such as changes in the nature of the ejaculation, a burning sensation when urinating, urethral discharge, prostatitis, epididymitis, or testicular infection, to less common and more potentially serious conditions, such as undescended testicles, hydrocele, varicocele, or venereal disease.

Finally, the questionnaire bids the man and the woman to focus on the specific time period during which they've been trying without success to achieve a pregnancy together. They are asked more specific questions about any methods they may have used in their marriage to avoid a pregnancy as well as about their sexual practices, any previously performed infertility tests, and any medications or procedures they've tried in an effort to reverse or overcome their infertility.

Among all these latter questions, I am especially interested in knowing the length of time the man and the woman have been attempting to have a baby. Speaking strictly as a physician, I've observed that if an infectious cause does lie behind a couple's infertility, then the longer they've tried to conceive, the more extensive the infection-related damage is likely to be in the woman's reproductive tract. Speaking as a human being, I've learned from my patients that a lengthy, frustrating trial for pregnancy can destroy the spontaneous desire for intercourse and leave in its place a pre-planned performance schedule mechanically timed to coordinate with ovulation. With this unfortunate side effect in mind, I rely a great deal on tact and humor to make our doctor-patient collaboration and, I hope, their sexual response to each other during this time as pleasant and casual as possible.

My patients may be uncomfortable or embarrassed about answering the questions I've mentioned so far, and they may not understand what, specifically can be learned from individual answers, but at least the questions themselves seem relevant to their goal. They realize we need to discuss such sexual matters openly, and so my tact-and-humor formula usually works right away to make this discussion easier.

Other questions take my patients completely by surprise. For example, I may ask a male or female patient:

• Are you an only child? A first, second, or third child? A last child?

• Were you born prematurely? Were you born by cesarean, section? How long was your mother in labor?

• Were you often sick as a child? Did you have frequent bouts with tonsillitis? Enlarged adenoids? Recurring ear infections?

• Where did your mother and father come from? Where did your grandparents come from?

• What is the reproductive history of your siblings?

I might ask a woman who has already borne a child whether she experienced a noticeable personality change after the delivery. I might ask a man who has fathered a child in a previous relationship whether his former partner exhibited a noticeable personality change after the delivery or whether the relationship started to suffer seriously a few months following the birth of a particular child. What could the answers to these questions possibly have to do with the patient's or couple's infertility?

In this chapter, I'll examine the reasons behind all these questions-both the predictable and the unexpected-by reviewing actual cases from my practice. I'll consider how and why individuals become involved in my antibiotic treatment program, what they experience as a result of that program, and why it makes sense as a first-step strategy for preventing and reversing infertility.

LYNN: A FRESH START

No matter how paramount the problem of infertility may be in their lives, most people won't discuss it in a social setting unless they find themselves in the company of a fertility specialist. When Lynn and I first met informally in 1980, she was emboldened by years of frustration to share with me her disastrous reproductive history. It was a history she assumed was behind her, for she had ceased to menstruate the year before, at age thirty-seven, and three different specialists had told her she had suffered ovarian failure. In short, she considered herself a victim of premature menopause.

Lynn's health troubles began in 1969, when she married Richard. Prior to the marriage, Richard had been bothered by frequent episodes of nonspecific urethritis, a common inflammation of the urinary tract that, in hindsight, was probably not treated adequately. After the marriage, Lynn also began to have similar problems: lower-urinary-tract infections and vaginal irritations. She immediately became pregnant but lost the baby after four months due to a premature rupture of membranes. No fertility workup was performed; her doctor simply urged the couple to try again. In 1970, they conceived once more, but Lynn miscarried within a few weeks.

Following the failure of her second pregnancy, Lynn had her first fertility workup, which resulted in a rather broad diagnosis of luteal-phase defect-that is, a delayed development of the uterine lining. She was given progesterone, a typical medication for this condition, and was told her chances of bearing a child full term would subsequently be much better.

The strategy appeared to work: in 1972, after an eight-month pregnancy, Lynn gave premature birth to a boy. Recalling this pregnancy for me, she mentioned that her baby was conceived while she was on a short course of tetracycline for a skin problem. She remembered going to Florida shortly afterward and being forced to discontinue the tetracycline because it made her skin too sensitive to the sun. This seemingly insignificant detail stuck in my mind.

In the hospital, during her recuperation from the delivery, Lynn developed a serious infection in her uterus (endometritis). She was treated with antibiotics (ampicillin and cephalothin) and then sent home with the baby. Right after her next period, she became pregnant again. However, since neither Richard nor Lynn wanted a second child so soon, Lynn had an induced abortion.

A year later, Richard and Lynn conceived another child but lost it at fifteen weeks. Fertility specialists attributed this particular miscarriage to an incompetent cervix and advised her to get a stitch in her cervix to improve her chances of holding a fetus full term. She chose not to get the stitch. "There was no guarantee it would do any good," she explained. "Plus it would mean having to remain in bed for most of the pregnancy, which I didn't think I could manage." Instead, she opted for a heavy regimen of fertility drugs, including clomiphene and progesterone.

Over the next four years, from 1975 through 1979, Lynn had five more miscarriages. The last two pregnancies (her tenth and eleventh) were so short in duration that they could be detected only by biochemical analysis. At this point, her doctor warned her she was failing to ovulate and her menstruation was shrinking away. He prescribed Pergonal, one of the most potent fertility drugs available. Four months before we met, she had stopped taking Pergonal. She had not had a period-or sexual intercourse with her husband-since then.

Aside from all the emotional and physical pain Lynn had suffered throughout the previous ten years, something else profoundly disturbed me about her story. I couldn't reconcile its various elements: the rationale behind individual diagnoses, the sequence of diagnoses, the repeated occurrences of infection in her reproductive system, the timing of her one successful pregnancy, and the ultimate conclusion that she had irretrievably lost her reproductive powers. I finally said to her, "Why don't we look into this matter a little further?" Weary though she and her husband were, of tests and treatments, they responded positively to my suggestion.

The first thing I did was perform culture studies for each partner: two apiece to ensure accuracy. Both times, Richard's semen and a biopsy from Lynn's uterine lining tested positive for chlamydia. This discovery implied it was indeed highly possible, as I'd suspected, that Lynn's reproductive difficulties were tied directly to bacterial infection.

At my recommendation, Lynn came into the hospital for a laparoscopy (a visualization of her ovaries via a telescope-like instrument); and what we learned completely contradicted the grim diagnosis of ovarian failure that had so depressed her. In fact, she had plenty of eggs-they just weren't being released from the ovary as they should be.

In June of 1981, I prescribed a broad-spectrum antibiotic drug program for Lynn and for Richard. Lynn received 100 milligrams of doxycycline twice a day for six days intravenously in the hospital followed by three weeks of the same dosage orally as an outpatient. Richard took 100 milligrams of doxycycline orally twice a day over the same time period. Meanwhile, I advised them to continue abstaining from intercourse until we had clear evidence their individual bacterial infections were completely eradicated.

Right after the treatment ended, an ecstatic Lynn phoned me to say she had resumed menstruating. An endometrial biopsy following this announcement showed her uterine lining was in good condition, possessing what is known in medical terms as perfect phase.

Enormously heartened by Lynn's progress, I said to her, "OK, go home and start having sexual intercourse with your husband." It took a few weeks before they were able to overcome two years of mutual avoidance, but in October of 1981, Lynn conceived again. To everyone's joy, after an uneventful, nine-month pregnancy, she gave birth to a healthy girl.

Looking back over the history of this case, I interpret Lynn's and Richard's reproductive problems as follows. Because Lynn had never experienced any genital-tract problems prior to her marriage and because her husband had, I reasoned that Lynn's postnuptial history of cystitis, vaginitis, and infection of the uterine lining and ovaries came from exposure to Richard's seminal fluid. Most likely, chlamydia entered Richard's seminal fluid during the time of his premarriage genital-tract infections and was never completely eliminated by the medication administered for those infections. The subsequent infection of his wife was an ascending one; that is it began in the lowest part of her genital tract and progressed to higher and higher structures without obstructing the fallopian tubes.

The fertility workup conducted by the first specialist Lynn consulted yielded a diagnosis of a deficient uterine lining with perfectly maintained ovarian function and normal hormonal levels. Fertility workups later in her history pointed to luteal phase defect plus a deficient hormonal supply from the ovaries, indicating that the ovaries, at this point, were now malfunctioning. Reviewing the histological slide I prepared from her specimen at the time of the laparoscopy, I saw clear evidence of bacterial infection, and ultimately, I had no doubt that her failing ovaries were being suppressed by chlamydia.

I was now able to envision mentally how a spreading bacterial infection had led to Lynn's series of miscarriages. I propose that her one pregnancy resulting in a live child, her son, was facilitated by the tetracycline she was taking when the child was conceived. In addition to clearing her skin condition, it also worked-without anyone's knowledge at the time-to suppress the chlamydia in her reproductive system, rendering her more capable of bearing a child. I further propose that the tetracycline treatment was not extensive enough to ensure a trouble-free pregnancy, and so she delivered prematurely. Whether or not the young child's chronic episodes of asthma, bronchitis, ear infection, and tonsillitis were due to intrauterine exposure to microbes is only hypothetical, but from my point of view, it could be of significant relevance.

Lynn's health history displays the whole spectrum of ways bacterial infection can spread through the female genital tract and interfere with every single step in the reproductive process. In fact, this one case is so impressive that it single-handedly triggered my interest in studying habitual aborters and the relationships between ongoing bacterial infections and simultaneously deteriorating fertility. But the fascinating scope of Lynn's case doesn't stop there. Her history also reveals a potentially strong link between bacterial infection and PMS.

Following the restoration of her normal menstrual cycle, Lynn reported that several troublesome premenstrual problems she had experienced during most of her married life had now changed for the better or had completely disappeared. Specifically, she no longer suffered so severely from breast tenderness, bloating, depression, or hostility, and she was much more enthusiastic about sexual intercourse. Analyzing her premenstrual symptoms closely, I found them to be the same symptoms that many of my own patients and medical literature in general associate with PMS. Five years passed before I could launch my first organized study into the effects of antibiotics on certain cases of PMS, but it was Lynn's case that prompted me to ask about PMS symptoms in every subsequent consultation. In Chapter 5, I will talk more about PMS and antibiotic therapy.

TREATING DIFFERENT TYPES OF INFECTIONS

As far as Lynn is concerned, antibiotic therapy restored to health a reproductive system that had been compromised by a bacterial infection in the ovaries. Just as often in my practice, however, antibiotic therapy has reversed infertility caused by a bacterial infection somewhere else in a woman's reproductive system. The female genital tract is compartmentalized into a lower genital area, comprising the labia, the vagina, and the lower cervix, and an upper genital area, comprising the uterus and the Fallopian tubes. Infections serious enough to cause-or foster-infertility can occur at several critical points along this tract.

Rita, a twenty-nine-year-old woman, came to me because of an ongoing vaginal irritation (vaginitis). She also suffered from a chronic infection of the Bartholin's gland, which is located just under the small labia and is supposed to lubricate the vaginal entrance. Both conditions made sexual intercourse intolerably painful and, therefore, thwarted her sexual satisfaction as well as her desire to have a baby.

The Bartholin's-gland problem presented the bigger treatment challenge. In cases like Rita's, we count heavily on antibiotic therapy to locate and destroy the precise bacterium that is causing the inflammation. Otherwise, surgery has to be considered. This involves opening up the infected gland and allowing the pus to drain from it over a period of time-a much more painful. expensive, and time-consuming procedure.

Rita was referred to me by a colleague and had already received three courses of oral antibiotics plus a month's supply of vaginal creams. Nothing seemed to help. As a first step, I conducted bacterial testing on both Rita and her husband, Jerry. The only meaningful isolate in both Rita's vaginal fluid and Jerry's seminal fluid was an anaerobe, streptococcus, which I decided to treat with Flagyl, a commonly used antibiotic. A two-week course of 500 milligrams four times daily was prescribed for both partners. As a result, Rita experienced temporary relief of her symptoms. A month later, I requested repeat culture studies. Unfortunately, the bacterium had reappeared. And even before the culture reports were available, Rita's symptoms had flared up again.

When I first met Rita, I was just beginning to try out a portable infusion pump for ambulatory treatment of PID. My purpose was to enable patients to live at home while they were on medication instead of having to remain in the hospital. The pump had a small reservoir containing a day's supply of clindamycin and gentamicin, the two most potent drugs for treating PID. It featured plastic tubing that carried the antibiotic solution to the patient's lower arm, where a venous catheter was inserted into a vein. On the whole, it was a fairly cumbersome apparatus, and during treatment courses, the catheter had to be changed several times. The drugs themselves can have dangerous side effects, so we had designed a very close monitoring system to follow the patients who were using it.

At that time, I had never heard of using intravenous treatment to alleviate the types of problems Rita and her husband had. But I was so frustrated with the stubborn perseverance of the anaerobic bacteria in both partners' reproductive system despite the oral regimens that I prescribed ten days on the intravenous pump for both of them. The results were-spectacular. Rita's Bartholin's duct healed, her vaginitis disappeared, and follow-up cultures on both her vaginal fluid and Jerry's semen were negative for the anaerobe.

After resuming a normal intercourse pattern, Rita achieved pregnancy within four months. In retrospect, I can't help but be convinced that Rita's problems were due to an anaerobic bacterial contamination. Since she had been completely asymptomatic until entering marriage, I also believe that the original anaerobic infection came from Jerry's seminal fluid.

Now let's consider cervical infections. Because the cervix functions as the mechanical and immunological barrier between a woman's lower and upper genital tracts, it is especially vulnerable to bacterial infection, and any infection that takes hold there is highly likely to result in infertility. This is precisely what happened in the case of Keith and Becky, a couple in their early thirties who had tried for eight years to have a baby and had failed to conceive even once.

Before consulting me, Becky had undergone a laparoscopy and several hysterosalpingograms (X-ray examinations of the Fallopian tubes). None of these procedures indicated any problem that would inhibit reproduction. There was, however, a persistent abnormal finding in her previous chartings. The postcoital test, which evaluates the survival of sperm in the cervical mucus, was repeatedly noted, by three different infertility specialists, to be poor or marginal at best. Vaginal douching with baking soda failed to improve sperm survival in her cervical mucus, and three cycles of intrauterine artificial insemination did not overcome her infertility.

The first thing I did after reviewing their individual and combined reproductive histories was to analyze Keith's semen and Becky's cervical mucus. Both showed high concentrations of mycoplasma and anaerobic bacteria-specifically, two anaerobes were shared, and Keith had one additional anaerobic bacterium.

In the spring of 1988, after a combined course of oral doxycycline did not improve the postcoital test and did not eradicate the anaerobic organisms, I put Becky and Keith on two weeks of intravenous clindamycin and gentamicin. Subsequently, I tested them again for mycoplasma and anaerobic bacteria. This time, the results were negative, and a postcoital test was excellent in all respects. In August of 1988, Becky became pregnant, and nine months later to the day I delivered a healthy boy.

My summary of Keith and Becky's case is that a chronic cervical infection with local antibody formation resulted in their infertility. Following the antibiotic therapy, we tested Becky's cervical mucus and her blood for antisperm antibodies, and they were negative. If, as in this case, only the cervix is contaminated and the immune system is not yet involved, antibiotic therapy can usually result in pregnancy within a few months. If infection is documented in both the cervix and the uterine lining, however, especially with antisperm antibodies already detected, patients may have to wait six to ten months after antibiotic therapy before a pregnancy can be expected. In my opinion, this extended time is necessary for the complete cessation of antibody production.

THE ISSUE OF VERTICAL TRANSMISSION

In the cases I've reviewed so far, information provided by my patients relating directly to their sexual and reproductive history enabled me to suspect what culture studies confirmed that bacteria had been continuously exchanged between one partner and another during intercourse and had eventually created an infection virulent enough to cause infertility. Often in such cases, I can deduce from the initial interview precisely how the bacteria spread.

For example, if a woman first develops vaginal irritation after marrying a man who had recurrent bouts with STDs during his bachelor days, it's logical for me to posit that she picked up infectious agents from her husband. If a woman taking birth control pills tells me that she always avoids sexual intercourse during menstruation, then I can assume with reasonable surety that any infection she may have contracted while taking the pills has not spread above her cervix. If an infertile woman has previously borne a child, I know one strong possibility is that bacterial infection, transmitted to the woman at the time of conception, ascended through her reproductive system and intensified.

But how do I explain the apparent presence of bacterial infection in the reproductive tract of a woman who by every indication has no history of sexual contact or reproduction at all? The only explanation lies in vertical transmission, the passage of bacteria from parent to child during fetal development, and/or the birthing process itself.

The scientific community unanimously agrees that bacteria can be transmitted to the ear canal, nasal passages, oral cavities, and gastrointestinal tract by way of the newborn's swallowing the genital-tract fluid of the mother. Speculation that the baby's genital tract is another body orifice that can be colonized by the mother's bacteria is compelling but far more complicated to verify. Assuming, as I do, that this transmission does indeed occur, then it is perhaps the most mysterious aspect of bacterial infection in the reproductive system, and the effort to shed some light on that mystery accounts for the more surprising questions I ask my patients.

Irene was a virgin. Her mother brought her to me because she had been suffering erratic menstrual periods, with profuse bleeding and unusually long bleeding times, since she was sixteen-about a year and a half after menarche. I was as positive as I could be from appearances, examination results, and interview material that she had led a very wholesome and sheltered life and, at the age of eighteen, had yet to experience physical intimacy with a man. When I accepted her as a patient, the fact that there were situations where bacteria could be transmitted vertically was just beginning to be acknowledged. Faced with the enigma of Irene's symptoms, I said to myself, Let me begin by investigating her family history.

Irene, it turns out, was an only child. Her mother's menstrual periods had ceased at the relatively young age of thirty-seven, an event that was written off as premature ovarian failure and menopause. Irene's father had been the victim of episodic prostatitis for most of his life. I conjectured that the source of both parents' health problems was bacterial infection. Specifically, I theorized that the bacteria had been passed from the father to the mother and had ascended to the mother's upper genital tract during the course of her pregnancy with Irene, rendering her infertile thereafter.

As for Irene herself, I suspected even before testing her that her menstrual troubles were due to an infection resulting from prenatal exposure to her mother's bacteria. Sure enough, the bacteria culture revealed five different anaerobic bacteria in her vaginal tract. I prescribed a ten-week program of oral antibiotics-. three weeks, of Vibra-Tabs, followed by three weeks of erythromycin, followed by two weeks of Flagyl and another course of erythromycin. Within one month after completing the last antibiotic course, her specific menstrual irregularity disappeared, and she resumed a normal menstrual pattern.

While taking Irene's history during our initial consultation, I learned that a previous specialist had recommended birth control pills to alleviate her perplexing menstrual difficulties. She followed this advice but found the pills emotionally upsetting. So did her mother, a conservative woman and protective parent who kept complaining to the specialist, "My daughter's a virgin. Why in heaven's name should she be put on birth control pills?" Fortunately, Irene stopped taking the pills after a few months (as a substitute, her specialist prescribed a dilation and curettage-D and C-to alleviate cramps and Danocrine for possible endometriosis). Had she remained on the pills, her condition would have been superficially indiscernible, making her feel her troubles had been eliminated while, in reality, the bacteria present in her genital tract would have continued to proliferate.

This case has an especially rewarding coda. Two years after I treated Irene's infection, she was astute enough to return to my laboratory with her fiancee, Tom, so that he, too, could be checked for possible bacterial contamination. Tom's test revealed no such problem. After their marriage, they conceived during the first month they stopped using condoms. One day shy of the due date, Irene gave birth to a healthy girl. A chain of infection passing from parent to child-for who knows how many generations-is now broken.

As convincing an example of vertical transmission as Irene's case may be, it was impossible to prove she actually picked up infectious bacteria from her mother. I couldn't insist that her parents come in for bacteria cultures. At any rate, her mother had had a hysterectomy many years before, so obtaining the culture I needed from her would have been impossible, and her father's strict religious beliefs prevented him from discussing his daughter's situation, much less becoming actively involved in it.

Even assuming Irene's mother had not had a hysterectomy, and both parents had volunteered to be tested, and the resulting cultures had contained the same kinds of anaerobic bacteria, it's purely a matter of speculation that the parents' bacteria found their way into the child's reproductive system. Current technology does not enable us to trace a literal parent-child link between one group of bacteria and another or to observe bacteria in the process of moving from mother to child before or during birth. Nevertheless, the circumstantial evidence- supporting vertical transmission is overwhelming.

As it happens, my very first private patient in the United States wound up contributing to that body of evidence. Barbara was already pregnant when I took over her case in the summer of 1976. I was covering for a colleague of mine on an extended vacation. At six and a half months' gestation, Barbara was hospitalized with premature labor. We couldn't halt her labor with the methods available to us then (intravenous alcohol, sedation, and bed rest), so we soon were forced to deliver a tiny female child, Alice, who spent the next three weeks in the hospital's intensive-care unit before going home.

Alice was destined to be an only child. Later, Barbara consulted me about chronic vaginal irritation dating from the time Alice was born. I cultured Barbara and discovered chlamydia in her vagina. In 1988, Alice herself, now twelve years old, came to my laboratory. She had just begun menstruating, and her vaginal discharge was disturbingly copious and odd smelling. Although she was a virgin, she, too, tested positive for chlamydia.

In my opinion, the only sensible explanation for Alice's infection is that she had harbored chlamydia in her reproductive system since contracting it from her mother, most likely in the womb itself during the turbulence attending her mother's premature labor. Twelve years later, the onset of Alice's sexual maturity triggered changes in her vaginal milieu that were favorable to the chlamydia bacteria and caused them to flourish to the extent that they gave her the localized symptoms I've already mentioned.

In the interest of scientific accuracy, I must repeat that vertical transmission of bacteria from the genital tract of the mother to the genital tract of the child is technically a theory, not an established fact. Patients concerned about their individual fertility problems are understandably, if lamentably, reluctant to involve family members in such a highly sensitive area of their lives. Within the limits of my own practice, which is large and cosmopolitan, I have been able to obtain matching cultures from only six mother-virgin-daughter pairs and only one complete family unit: a father, a mother, and their virgin daughter, who all tested positive for chlamydia. I consider myself lucky to have achieved this much progress.

Yet, as a scientist, I must also admit I support the vertical transmission hypothesis because it reconciles so many diverse phenomena that crop up in the histories of infertile people. Hundreds of successful diagnoses and treatments have stemmed from my belief in this hypothesis, and that fact alone explains why I initially ask my patients the more surprising questions cited at the beginning of this chapter-questions having to do with the reproductive health history of the patients' parents and siblings and the circumstances surrounding the patients' birth.

Let's suppose, for example, a woman develops amnionitis in the sixth month of her pregnancy. In other words, the amniotic fluid that surrounds the baby and protects the baby from infection is itself contaminated with bacteria. The baby already has some kind of immune system working, the specific organs being the bronchial tree, the nasal pharynx, the lymphatic tissues, the ear canal, the prostate in a male, and the cervix in a female. All of these organs are suddenly at risk for infection.

Possibly the mother we are discussing will go into early labor at this point. If so, chances are good she will be given paralyzing agents to prolong her pregnancy, which may leave the baby soaking in the infected fluid for weeks or even months to come. Whatever the labor and delivery situation, the baby may be born with any number of immunological maladies-manifest or not-that could indicate bacterial infection in the reproductive system as well: chronic coughing, bronchitis, postnasal drip, allergies, oversized tonsils or adenoids, an enlarged prostate, an irritated cervix.

If the baby is fortunate enough to be saved from bacterial infection by way of the amniotic fluid, he or she is subject to infectious exposure from the second the membrane ruptures. If a cesarean section is performed on the mother, the risk of the baby becoming infected during the birth process is very low. In a vaginal delivery, the risk of infection is, in my estimation, very high-and increases the longer the labor lasts.

So we see why I ask my patients how long their mother was in labor and whether there were any complications surrounding their birth. After conducting some family research of her own, one patient, Andrea, responded, "My mother went into labor, then stopped, then was stimulated with Pitocin. The membrane at this stage had already broken. After another hour, she was told to go to sleep for the night. I wasn't born until late the following day." Andrea herself had been plagued with tonsillitis, colic, and ear infections as a child and had developed vaginitis during puberty. When I cultured her, I found a high level of mycoplasma.

Taking all this data into account, I felt the final picture strongly suggested that Andrea was infected with mycoplasma from her mother, whose pregnancy with Andrea may have been complicated by mycoplasmal infection. By the time Andrea was finally ready to have a child of her own, the mycoplasma inside her reproductive system. had long since caused an infection that prevented her from conceiving. The antibiotic therapy I prescribed wiped out the mycoplasma, the infection disappeared, and she became pregnant shortly afterward.

If my patient or either of my patient's parents (or my patient's partner or either of his or her parents) is an only child, then I know it's possible I'm dealing with a family history of secondary infertility due to bacterial infection. I'm also alert to the possibility of vertical transmission if I learn my patient's siblings (or his or her partner's siblings) have had childless or one-child marriages. But what could I hope to gain from a patient's answer to the question, "Where are your parents from?" or "What is your ancestry?"

Essentially, I'm trying to investigate the origin of my patient's physical being as thoroughly as I can, so I can be all the more confident about my diagnosis of his or her reproductive health problem and about the potential efficacy of solving that problem with broad-spectrum antibiotic treatment. Perhaps one or both of my patient's parents were from an extremely inbred community or cultural group, in which ease the chance of vertical transmission of bacteria or the chance of vertical transmission of a genetic condition predisposing the recipient to bacterial infection is much greater.

It is my impression, based on my own experience and research into the matter, that patients who can trace their descent to tropical, tribal areas, like the South Pacific or Africa, are far more likely to be heavily laden with vertically transmitted bacteria in general than patients whose families come from temperate, nontribal areas. I also believe (again, based on my own experience and research) that descendants of people who were incarcerated in concentration camps fall into a more contaminated category.

This entire line of inquiry is clearly controversial. It must be pursued however-with extra sensitivity and scrupulosity, to be sure-if we are to accept the possibility that infectious bacteria can be transmitted vertically to the child's reproductive tract.

THE ISSUE OF "PERSONALITY CHANGE

Not all of the questions that surprise my patients are aimed at tracing vertical transmission. Some are concerned with establishing horizontal (or sexual) transmission, which can reveal itself in many unsuspected ways. The questions of this type that raise the most eyebrows among my patients deal with postpregnancy personality changes.

When I ask a female patient who has previously given birth whether she noticed any change in her personality after the delivery, I am trying to decipher whether she might have begun experiencing PMS at that time. If she admits having noticed a personality change and the change corresponds to the type of troublesome emotional patterns commonly associated with PMS, then I can hypothesize that her pregnancy spurred the development of a serious bacterial infection that caused her to develop PMS and perhaps, secondary infertility as well.

When I ask a male patient whether he witnessed any change in his partner's personality, or in that of any prior partner after she gave birth, I am attempting to find out whether she might have developed PMS at that time, which could indicate that the two of them exchanged infectious bacteria during the course of their sexual relationship. I usually pose this question without explaining in advance why I'm asking it, so 1 don't prejudice the response. As a result of this strategy and of the professional knowledge that lies behind my questioning, I can sometimes appear to be psychic.

Recently, I was conducting an initial interview with a patient, Paul, who said he had previously been involved in a four-year marriage that produced one male child before ending in divorce. As soon as I heard this, I said to him, "Am I correct in assuming your first wife went into a severe depression after delivering your son?" He was clearly taken aback. "How did you know that?" he asked. I told him it was just a guess. Then I went on to inquire, "Is it fair to say that about six months later, you were fighting all the time, and your marriage was going on the rocks?" Speechless, he nodded.

Ultimately, I collected enough data from my interview with Paul to justify a preliminary conclusion that his ex-wife had developed PMS after her pregnancy-and, therefore, possibly harbored a bacterial infection in her reproductive system. Then Paul mentioned that his son from that marriage is a "problem child," subject to all sorts of infectious diseases and the ill-tempered behavior that often goes with them. This additional information only corroborated my suspicion that bacteria were transmitted through the family. I wasn't surprised in the least when I subsequently discovered high levels of chlamydia in Paul's semen.

Only in recent years has PMS been acknowledged as a legitimate physical illness with potentially devastating emotional consequences. Given the lack of popular understanding concerning PMS, it's little wonder so many cases of it are never recognized as such by their victims or their mates. The consequences of such ignorance can be enormous, for identifying PMS is frequently an important step toward identifying even more serious conditions, including infertility. I'll return to the subject of PMS in Chapter 5, where I'll also examine other reproductive health problems short of infertility that can be successfully managed with high-powered antibiotic treatment.

ANTIBIOTIC TREATMENT TO RESTORE FERTILITY - WHAT TO EXPECT

By discussing the questions-common and uncommon-I ask my patients, I hope that I have provided some insight into the range of issues that need to be examined before I can determine (a) the most probable cause of a patient's infertility and (b) the specific antibiotic therapy most likely to alleviate or eliminate that cause. Now it's time to consider what my patients want to know about antibiotic treatment programs in general.

Here are the questions I most often encounter from my patients or prospective patients, accompanied by my responses:

What symptoms may indicate I have a bacterial infection in my genital tract?
The most important point to remember concerning this issue is that a bacterial infection harmful enough to interfere with fertility does not necessarily announce itself in ways you can feel or observe. In my experience, vertically transmitted bacterial flora in particular is scarcely ever symptomatic. Therefore, the procedure I recommend is to begin your self-examination by considering whether you might be in a high-risk category for congenital reasons.

Here are some questions to ask yourself (and, perhaps, members of your family or a family physician):

1. Am I an only child? Why?

2. Were there miscarriages before and/or after my birth?

3. Was I born prematurely?

4. Did my mother have any unusually severe infection around the time I was born?

5. Did my mother try to get pregnant for a long time before I was born? Were my parents trying to overcome any infections during this period?

If a bacterium transmitted at birth remains in the genital tract of the adolescent, usually that person's very first sexual partner will pick it up and develop symptoms from it. In a male partner, the most common symptom of such a sexually transmitted infection is a burning sensation when urinating or soreness in the urinary tract and, later, prostatitis. A female partner might develop what is commonly labeled a yeast infection (vaginitis).

If you are a woman and you experienced a vaginal infection or repeated episodes of cystitis around puberty-and prior to any history of sexual intercourse-then this may be a symptomatic warning sign of vertically transmitted bacterial infection. Whatever your age now, you should definitely arrange to be cultured for bacteria.

If you are a DES-exposed child, I also recommend being tested for the presence of infectious agents in your genital tract. The drug known as DES (diethylstilbestrol, a synthetic estrogen) was widely administered during the 1950s to pregnant women who had a history of miscarrying. The drug did, indeed, work to prevent miscarriage, but tragically for the individuals it helped to bring into the world, it caused a high rate of infertility, which fertility specialists often attribute to anatomical malformations in the reproductive system.

The reason I advise bacteria testing for DES-exposed children is not that I suspect any possible adverse effect of DES itself. I believe the infertility problem many of them experience results from the same condition for which the DES was given to their mothers; a bacterial infection causing a tendency to miscarry. The DES ingested by the mother maintained the child artificially inside an infected uterus until birth, a situation that, in my opinion, would almost certainly have resulted in heavy bacterial contamination of the child by way of vertical transmission. I have treated numerous DES-exposed women whose spontaneous abortions had been written off by previous specialists as the effects of a DES-related malformed uterus (the so-called T-shaped uterus) or an incompetent cervix. In every single case to date, a strong course of antibiotic therapy has yielded a normal pregnancy.

After identifying all factors that might suggest vertical transmission of bacterial infection, look for indicators of possible sexual transmission. Consider your history of sexual partners and sexual activities in conjunction with any unusual physical symptoms you may have experienced in the genital or pelvic area.

For men, episodes of urethritis, prostatitis, or gonorrhea are especially suspect for asymptomatic bacterial infection. For women, the most telling indicators are chronically recurring vaginitis (yeast infection) or repeated flare-ups of PID. Any deviation from "normal" menstruation is also suspicious: for example, a time when the menstrual flow suddenly became lighter, heavier, or more odorous or when the cycle itself became irregular or studded with midcycle bleeding. Menstruation that turns into brown staining almost always suggests endometritis or ovarian infection. Other functional problems that can be associated with bacterial infection are ovarian-cyst formation, a rapidly developing luteal-phase defect, or the skipping of ovulation altogether (anovulatory cycle).

Women also need to review their history of birth control. IUD users, past or present, are in a high-risk category for bacterial infection. Women who use barrier-type birth control, such as condoms or diaphragms, should be concerned if any sudden change in pelvic function occurs after they discontinue use. Ideally, a woman experiencing such a symptom should immediately refrain from sexual intercourse and go for testing.

In cases of secondary infertility, the course of the first pregnancy frequently provides clues that mandate the search for bacteria. In general, the longer it took to conceive the child, with all fertility parameters being normal, the higher the chance the secondary infertility is bacteria-related. Other abnormalities surrounding a first pregnancy that may indicate bacterial infection are unusual bleeding, prematurity, postdatism, an incompetent cervix, intrauterine growth retardation of the fetus, an exceptionally long labor without an oversized fetus, a cesarean section performed for reasons besides size differentials, and postpartum infections of the mother or the newborn.

So far, we've been considering mild bacterial infections. Severe bacterial infections in the female genital tract invariably cause clinically discernible symptoms, including pain, fever, localized tenderness, an elevated sedimentation rate, a high white-cell count in the blood, and/or copious vaginal discharge. A more subtle, but still manifest symptom is an emotional and sometimes, physical disturbance during the weeks preceding a period, which could betoken PMS. (See Chapter 5 for a more specific discussion of PMS symptoms.)

Assuming I don't notice any specific symptoms and I can't account for possible bacterial infection by reviewing my family or sexual history, when should I consider being checked for bacterial infection in my genital tract?
The ideal situation is for a man or woman to be cultured shortly after puberty and definitely before sexual intercourse begins. Of course, this scenario requires parents who are informed about the possible causes and effects of bacterial infection. Whether or not you had this experience, your approach to testing should be preventive rather than strictly curative.

I recommend yearly examination of seminal fluid for sexually active men and yearly examination of vaginal and cervical cultures for sexually active women. In the woman's case, these tests could be administered as additions to the annual checkup now recommended by the American College of Obstetricians and Gynecologists.

Following satisfactory results, it would be wise to determine the genital-tract flora of every new partner before engaging in sexual intercourse. If sexual intercourse causes local irritation or if you and your partner intend to have a child together, then in my opinion, a bacterial study is mandatory-the sooner, the better.

Is antibiotic therapy ever useful for just one person as opposed to a couple?
Assuming the individual being treated is or may become sexually active, my answer is unequivocally no.

Is every fertility specialist willing to consider and prepared to offer antibiotic therapy as a possible treatment for reversing infertility?
This is a question you must pose to individual specialists. Each doctor offers his or her own repertoire of treatments, according to the areas in which he or she feels the most knowledgeable and the most skilled. My broad-spectrum antibiotic therapy is relatively new in the field, and so not every fertility specialist has yet given it a sufficient amount of consideration or incorporated it into his or her practice. I am very gratified to see, however, the high rate at which more and more specialists are turning to broad-spectrum antibiotic therapy as a first step in restoring fertility.

About how much does antibiotic therapy cost?
Since there are no pretest guarantees regarding how much antibiotic therapy may cost you, let's take the most extreme case. Assuming your antibiotic testing calls for intravenous treatment (instead of no treatment at all or orally administered treatment) as well as a full complement of pre- and post-therapy culture studies, the final cost could be as high as three thousand dollars per person.

The majority of cases by far do not cost nearly as much. But even the top possible cost of three thousand dollars is, a small price to pay if you take into account that antibiotic therapy could prevent years of frustration, the total loss of spontaneous reproduction, the need for much more expensive therapies (like fertility-drug treatments or in vitro fertilization), the delivery of a premature infant, and the cost of caring for a premature or seriously infected infant in a high-risk nursery.

About how long does it take to make a diagnosis? To complete the antibiotic treatment itself? When can I resume having intercourse?
If we reasonably assume from our first look at a culture that bacterial infection may be a contributing cause of infertility, the final testing for specific organisms will take about a month. The prescribed antibiotic therapy, if given orally (which is most often the case), will take from six to eight weeks. The post-therapy testing will take another month, and only thereafter do I advise resuming unprotected intercourse-that is, intercourse without a condom.

I must add that it can take up to ten months before a pregnancy is realized. While a bacterial infection is rife in a woman's reproductive system it causes certain immunological changes, and such changes always take time to reverse themselves.

Can I pursue other types of testing or treatment for infertility while I am undergoing antibiotic therapy?
Generally, I advise my patients not to pursue other tests or treatments while they are undergoing antibiotic therapy. In the first place, other tests or treatments might neutralize or work against antibiotic therapy or render the results of the therapy inconclusive. Some tests or treatments involving invasive instruments might even spread an existing bacterial infection farther into the reproductive system. In the second place, antibiotic therapy-in my experience-has a good chance of working all by itself to restore fertility, in which case other tests and treatments are unnecessary.

In addition to refraining from unprotected sexual intercourse during antibiotic therapy, should I avoid any other activities, circumstances, or substances?
I recommend a regular diet with minimal alcohol intake. Certain tetracycline drugs that may be used in antibiotic therapy make patients sensitive to sun exposure, and because most antibiotics make the user more prone to fatigue than usual, one should minimize strenuous exercise.

Are there any negative side effects or aftereffects with antibiotic therapy?
Most of the antibiotics used in this kind of therapy can cause minor, short-term episodes of nausea, dizziness, and fatigue. Among all the antibiotics that can be used, very few produce any major side effects. In some gastrointestinal tracts, certain antibiotics may induce serious diarrhea, which ceases as soon as the patient is taken off the offending antibiotic.

Extremely high concentrations of antibiotics have the potential of damaging the kidneys or nerve endings in the ear, but this kind of dangerous situation is avoided entirely if antibiotic levels in the bloodstream are carefully monitored. This precaution always accompanies antibiotic therapy as I apply it.

Assuming both my partner and I are cleared of any bacterial infection and remain faithful to each other, might there ever be a need to repeat antibiotic therapy?
If a monogamous relationship exists and if you do not practice anal intercourse, manipulation of the genital canals with foreign objects, or oral intercourse, then your genital tract and that of your partner should remain functional and clean with out the need for future testing. If an infectious symptom does recur under these circumstances, then it does not indicate reinfection but, rather, the incomplete treatment of the previous infection, in which case you should go back for testing.

If you are unable to achieve a pregnancy within a reasonable amount of time after antibiotic therapy and there is no other apparent cause for infertility, then I recommend culture studies be repeated after six months. If the same bacteria show up again, I advise repeating the antibiotic therapy.

To Chapter 4: Paths to Parenthood: Antibiotic Therapy and Its Options and Follow-ups