Assisted Reproductive Technology

A Physician's View of Art Procedures and Legal Policy

John Rinehart, M.D., Ph.D., J.D.
Director, Division of Reproductive Endocrinology and Infertility
Evanston Northwestern Healthcare

Introduction

Ask any practicing physician about the legal system and how it impacts his or her practice and he or she will immediately talk about malpractice. Fear of a malpractice suit will make a perfectly sane physician act insanely. Possibly if physicians were convinced that regulation would result in the best patient care and that the reward for accepting regulation was a reduction in malpractice claims, most physicians would agree to increased regulation immediately. There would be great comfort for a physician if that physician felt that by following the accepted regulatory guidelines, then he or she could reduce the risk of being sued. However, physicians fear that regulation will lead to a loss of control over patient care and that this would result in compromised patient care. Yet, medicine is changing, and some of these changes lend themselves to regulation or, perhaps more importantly, will require regulation to protect patients.

The thrust of this paper is that technology-driven, fundamental changes in how medicine, and especially artificial reproductive technology (ART), is practiced are occurring. These changes commercialize the practice of ART. This alteration in the manner by which ART is practiced requires that ART be placed under the same regulatory requirements as any business. This paper will first explore the changing relationship between doctors and patients and the changes in medical decision making. This will be followed by investigating how these changes have already altered ART practices and where these changes are leading. The paper will examine the changing nature of the patients and how this impacts the practice of ART. The nature of both the business of ART and the business of law will briefly be examined, as well. With the above as background, areas of the practice of ART will be examined to determine the need and the nature of regulation. Each aspect of this will explore how the legal system could impact the regulation of ART. There are two important questions that need to be addressed for each area of consideration: (1) What needs to be regulated?; and (2) What can be regulated?

Clinical Decision Making

The legal system has not chosen to regulate the daily clinical decision making in medicine. There are strong arguments in favor of this decision, but these are not the purpose of this paper. However, as the nature of medicine changes, the legal system may wish to consider regulating the enforcement of clinical guidelines established by medical institutions. The strength of this argument depends upon how distant the practice of medicine becomes from the traditional patient-physician model.

One change occurring in medicine is the use of evidence-based medicine (EBM) for clinical decision making. EBM relies heavily upon statistical evaluation and technology. Traditional medical education and decision making, in contrast, was based upon an apprentice system. Physicians completed medical school where basic information was learned. The reward for doing well in medical school was the ability to get a "good" residency. A "good" residency tended to be one where a large number of diversified patients were seen. Furthermore, the "attending" physicians were those physicians who had distinguished themselves by publishing and being a part of "academic" medicine. Learning was to occur "at the bedside" of medical patients and "at the table" of surgical patients. The more volume a resident was able to do, the better the learning experience.

There are a number of problems with this system. This type of learning requires that there be a large volume of patients with diversified disease processes so that the resident sees as much pathology as he or she can in the time allotted. The education came at the hands of the attending physician, and it was assumed that whatever the attending said was true. This system relied heavily upon the attending physicians being accurate. Whatever misperception the attending held was then subsequently passed on to all those whom he or she trained. A mentor once commented, when told by a resident that the resident did what he was doing "because he had always done it that way," that doing something wrong for ten years did not make it right.

Furthermore, relying upon one's own experience limits the number of observations. Importantly, the human mind is not a data recorder. People tend to remember exceptions or distortions of reality. This type of learning is commonly practiced among physicians in the form of swapping "war stories." After a while, the uncommon becomes the common. This problem is manifested in ART in the form of treatment of independent pregnancies. For example, for couples trying to conceive, after the first year of unprotected intercourse, roughly 85% will be pregnant. At this point, if they are unable to conceive, the couple is termed infertile. After two years of trying to conceive with unprotected intercourse, the overall pregnancy rate is 93%. Thus, another 7% conceive during the second year of trying with no intervention at all. Therefore, if 15% remain after one year, and 8% remain after the second year, the pregnancy rate expressed for no treatment during that second year is 7/15 or 46.7%. Suppose a physician treated all of his patients with Vitamin C if the patient had failed to conceive after one year. Suppose the physician records this data and publishes it as the effect of Vitamin C for infertile patients with the claim the Vitamin C treatment has a 46.7% pregnancy rate. Is this accurate? No! The proper study is to randomly divide the patients into two comparable groups and to treat one group with Vitamin C, to treat the second group with placebo, and then to compare the results after one year. More commonly, suppose a physician treats all of his patients with infertility over the age of 38 with six cycles of clomiphene citrate. Suppose a few of his patients get pregnant. Has he really helped this group of patients? Probably not as age-related fertility is not helped by clomiphene citrate and may actually be harmed by it. Thus, learning by remembering cases leads to a bias in the interpretation of the results of treatment.

Finally, the apprentice method of learning does not allow for changes in medicine. Physicians change their methods of diagnosis and treatment very slowly because they tend to believe what they were taught over what they read. Furthermore, once out of training, the daily demands of practice limit the amount of time a physician has to learn.

Medicine has attempted to apply the scientific method to the practice of medicine. EBM is a recent manifestation of this application of the scientific method to the practice of medicine. The scientific method follows a set of steps that establish a process by which to define the physical world. The process requires observation and description of something. A hypothesis is formulated from these observations about the nature of the thing in question. The hypothesis is used to predict other physical phenomena or to predict future events. The accuracy of the hypothesis is then tested by experimental methods. EBM tries to objectify medical decision making by establishing a hierarchy of the available information (i.e., literature and clinical experience) based upon the degree of predictability of the information. It relies upon organizing the medical literature in a hierarchy such that decisions are based upon the most statistically sound evidence available at that time. Statistically sound means that there is a high degree of predictability. Studies that are randomized, prospective, and placebo-controlled are given the most credence because they have the highest degree of predictability. Case studies are given the least weight. The physician is then responsible for applying the best evidence in diagnosing and treating the patient in question. For some patients, this will mean that the evidence is very sound, and the predictions about treatment effect and risks will be very accurate. For other patients, there will be very little sound evidence, and the predictions will be less accurate with more risk for the patient that the treatment may not work.

The ability to practice EBM relies upon technology. Medical literature is now digitalized and stored in large data banks that are readily available to almost every clinician. Search engines permit clinicians and researchers to identify all relevant information quickly and to organize this information into desired categories. This same process permits rapid review and publication of research so that physicians can remain current. Data can now be analyzed using highly sophisticated statistical methods because the data is digitalized. Recent software programs for data analysis allow many people without a sophisticated background in statistics to evaluate relevant data. Gone are the days of spending hours in the library "stacks" trying to find references or of using arcane tools to apply simple statistical theory to the data.

One value of this readily available body of information is that it allows a physician to determine how he or she performs compared to the community at large. For example, the national reporting of success rates by the Centers for Disease Control and Prevention (CDC) for ART programs permits both physicians and patients to compare the pregnancy rates for various programs. Large data bases, such as MDCONSULT or pubmed.com, permit physicians to reference questions as they arise in their daily practice. The effect is to create a virtual community that provides physicians with exposure to the most up-to-date information. The same virtual community links physicians over the Internet, allowing for discussion of clinical problems so that, instead of the learning taking place at the bedside with an attending and a few other physicians in training, today's physicians can draw upon the resources of an enormous number of experts and colleagues in a matter of minutes.

The American Society of Reproductive Medicine (ASRM) has endorsed EBM. ASRM's journal, Fertility and Sterility, encourages using EBM. The journal classifies all research by EBM categories and, through editorials, has encouraged physicians to use the EBM approach to clinical decision making. However, the reality of the difficulty of actually doing this is seen by the lead articles in the December 2006 issue of Fertility and Sterility. Managing editors of journals face a continuous problem of not having enough quality research submitted. Each month, the deadline comes due, and the editors must find enough articles to publish the journal. This pressure allows for the publication of many articles that otherwise would not be published. Furthermore, it is extremely difficult to conduct the best research - whether due to ethical, financial, or practical reasons. Additionally, the review process is conducted by invited reviewers - many of whom are sympathetic to the plight of the researcher or are not adequately trained in the statistics required to be a critical reviewer. The result is seen in the articles published in the December 2005 issue of Fertility and Sterility about the role of laparoscopy in the management of endometriosis. There is a great deal of controversy among physicians regarding the use of laparoscopy in the present setting of in vitro fertilization (IVF)-dominated infertility treatment. The essence of this debate was framed in the lead article by Littman et al.¹ The authors state in the abstract that this is a retrospective case study, which is not the highest level of evidence required by the principles of EBM. Furthermore, this study has a small number of patients enrolled and does not describe certain critical methodological processes. The conclusion, however, states that the use of laparoscopy for the treatment of certain cases of IVF failed endometriosis may be appropriate. Four articles follow this one, and all of them have varying degrees of confirmation or criticism of the conclusions put forth by these authors. The reader is left unsure as to how to proceed with the treatment of a patient because the strength of the research is weak, the authorities cannot agree, and the default is to put the burden on the patient's shoulders by relying upon "informed consent" - as if that excuses the fact the experts cannot agree. Dr. Adamson, in his comment on the lead paper, starts his final paragraph by stating that the "relative benefits and costs need to be understood and explained to patients..."² Thus, the reality is that many questions relevant to ART are complex, thereby limiting the ability to obtain the highest level of statistical probability and, thus, making it difficult to know what the true best course of treatment should be.

Given these serious limitations within the field of medicine, it is unrealistic to think that the legal field would be able to provide adequate regulation if it were to try to determine specific treatment protocols. Requiring the development of protocols would be a realistic goal for the legal system but as this example demonstrates, even the best attempts will not eliminate the statistical uncertainty of medicine.

The Changing Character of Reproductive Endocrinology

Reproductive endocrinology (REI) has undergone a dramatic change since the 1970s, resulting from the introduction of IVF. This change has made REI sensitive to business demands, and, thus, REI, as practiced today, is more like a business than an academic profession. REI was recognized as a distinct subspecialty in the early 1970s, long before human IVF was a reality. REI was an academic-, research-, and surgery-based subspecialty. The academic setting provided numerous controls over the practice of REI. The programs were housed within academic departments within hospitals and medical schools. Any capital expenditure required approval after extensive review. Research was required for academic promotion, and teaching was expected. Both of these activities advanced the technical capabilities of REI. Research was regulated by institutional review boards (IRBs) and by the oversight of deans of research, department chairmen, and division directors. Virtually nothing happened in a vacuum, and deviations were rare enough that, when they did occur, they created a national scandal. This environment protected patients to a large degree - especially once IRB and patients' rights policies were established. This protection was enhanced by the National Institutes of Health, which exerted control and, thus, provided a form of regulation by controlling funding for entire institutions. There are notable exceptions in this system, and abuses of this system, many of which have been addressed and corrected, certainly occurred. But this system did provide a large amount of regulation with very little inducement for personal financial gain.

The introduction of IVF changed most of this. As acknowledged by Dr. M. Soules,³ ART has been detrimental to academic reproductive medicine. The field of REI has become the field of infertility, and rather than describe oneself as a reproductive endocrinologist, many physicians, trained as REIs, refer to themselves as infertility experts. The core therapeutic intervention in REI, now infertility, is IVF. IVF is highly successful, performed quickly compared to the previous infertility surgery, and with a much lower complication rate. IVF can be performed in an office setting and, thus, is removed from all regulation that occurs with hospital-based procedures. The financial rewards are far superior for infertility experts to practice in a private-practice setting than to practice in the traditional, academic, institution-based reproductive endocrinology. The result is that many physicians practicing REI now practice in private practices, and few remain in academic settings. As Dr. Soules summarized, this has made the practice of REI much more business-like than ever before.⁴ Dr. Soules noted that, as a private practitioner, he felt that he provided better continuity of care and more efficient care to his patients than when he practiced in an academic setting. He also noted that he spent more time focusing on the business aspects of medicine and worried about the ability to remain current with the medical literature. While some disagree with certain points made by Dr. Soules,^5,6 others suggest that there can be a marriage of private and academic infertility practice.⁷ None of these authors argues against the business-like nature of infertility practice. Quite to the contrary. They all readily admit to the financial incentives IVF provides and, thus, indirectly admit to the change in the practice of REI from an academic practice to a private practice.

Dr. Soules voiced a major concern that the transition from academic to private practice creates for physicians practicing ART. That concern involves the difficulty of remaining academically current. Physicians are required to obtain continuing medical education credits to remain licensed, but there is no mandatory program to ensure that physicians remain competent in their area of practice. Recertification is now required to maintain board certification, but this can be accomplished through reading the literature without any real evaluation of physician competence. Thus, there is no real way to monitor physician competence once outside of the academic-hospital setting. Requiring some form of meaningful competency training could ensure that minimum basic skills were retained by the practicing physician.

The move of REI from the institutionalized, academic practice to private practice results in at least two regulatory consequences. First, the inherent regulatory processes that attend institutionalized, academic medicine are removed. Second, the private practice of REI becomes more business-like. Whereas, it is difficult to regulate the practice of medicine directly, it is an accepted process to regulate business. Therefore, the practice of REI should expect more regulation as a business distinct from regulation of the practice of medicine.

Regulating IVF Laboratories

Regulation of medical laboratories exists and affects IVF labs just like any other medical laboratory. Regulations are designed to improve the accuracy of test results, and to protect both patients and workers from foreseeable infectious and environmental hazards. Regulation of medical laboratories began in the 1940s in an attempt to improve the accuracy of test results. This was accomplished by implementing quality improvement programs and proficiency testing, which became a mission for the College of American Pathologists (CAP).⁸ The regulation of medical labs was greatly increased with the passage of the Clinical Laboratory Improvement Act of 1967 (CLIA). CLIA required minimum performance standards for labs engaged in interstate commerce. There was considerable question as to whether these regulations actually did accomplish their goal of improving the accuracy of clinical results.⁹ Largely due to public awareness made possible by the press, there was an attempt to improve the accuracy of clinical test reporting through the passage of CLIA 1988. CLIA 1988 applied to all clinical labs, as well as to physician-operated labs.

Furthermore, CLIA 1988 divided testing into three levels of complexity determined by the risk of harm to the patients, as well as both the complexity and accuracy of the test in question. CLIA 1988 requires stringent personnel requirements, quality improvement, quality assurance, and proficiency testing for tests of moderate-to-high complexity. One result of this legislation was to reduce dramatically the number of tests that were done in physician-operated labs. One publication reported that physician-operated lab testing dropped from 2.7 billion per year to 294 million.¹⁰ The practice of infertility utilizes laboratories for manipulation of gametes (i.e., IVF laboratories), for endocrine assays (e.g., estradiol, FSH, etc.), and for andrology assays (i.e., sperm analysis). Both andrology and endocrinology labs fall under CLIA 1988. However, one major exception for IVF labs is that CLIA does not regulate embryology labs. Embryology labs have been excluded because they have been deemed to be practicing medicine and, as such, do not fall under CLIA. Altering the classification of embryology procedures to those covered by CLIA would immediately increase the level of regulation required to maintain an IVF lab.

All health care facilities are subject to Occupational Safety and Health Administration (OSHA) regulations. These regulations are designed to provide a safe environment for healthcare workers especially as applied to safety measures that prevent infectious diseases. They also cover the handling of hazardous materials, which is relevant for medical laboratories. Along similar lines, in 2005, the Food and Drug Administration (FDA) implemented 21 CFR 1270, 1271, designed to minimize the transmission of certain tissue-born infectious diseases, such as Creutzfeldt-Jakob disease. Yet, it remains to be seen if it will, in fact, have the desired effect. The requirements from this legislation have a direct effect upon IVF and, in particular, upon third-party reproduction. The regulations require a significant increase in the amount of infectious disease testing that is done for an IVF cycle where there is a third party to the procedures.

There are guidelines published by ASRM¹¹ for both andrology and embryology laboratories. These guidelines require such laboratories to undergo certification or accreditations by CAP/ASRM, the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO), or the New York State Tissue Bank Program (NYSTB), and requires that such labs be in compliance with all federal and state regulations. Furthermore, embryology laboratories are considered manufacturers of transplantation products (i.e., gametes and embryos) according to the FDA's proposed Cell/Tissue Transplantation regulations.¹² However, the embryology laboratories are not required to follow most of the guidelines. Nevertheless, the recent implementation of federal transplantation regulations does alter this somewhat, but the embryology portion of the laboratories is not required to follow the guidelines. Mandating quality control and quality assurance programs would ensure a minimum level of competence for embryology laboratories.

Changes in the laboratory practice of ART suggest that regulation is now possible. When IVF was first started, the laboratory practice was largely academic and research based. Research Ph.D.s and their assorted postdoctoral and doctoral candidates performed much of the work that was done in the IVF laboratories. Laboratories developed their own media, instruments for micromanipulations, quality control measures, and quality assurance indicators. All labs had an associated animal colony for testing media, and the media was made on-site. The research done by the pioneers in human IVF established a more standardized approach for the embryology lab. Media became commercially available, as did most of the instruments used for micromanipulations. The use of cryopreserved animal embryos allowed programs to use biologic quality testing without the necessity of maintaining an animal colony. The net effect of this on the practice of human IVF embryology has been to standardize much of what is done within the embryology labs and has permitted less-trained individuals to perform most of the daily work done in embryology labs. The standardization and simplification of media preparation and instrument manufacturing have created a number of small companies that sell the various components used in the IVF lab. Thus, today's embryology labs are more akin to commercial medical labs than to older, academic-based research labs. Assuming this is true, a strong argument can be made that CLIA should now cover embryology labs just as it does andrology and endocrine labs.

Requiring regulation of ART labs may not actually improve the overall outcome. One problem with requiring conformity to standards is that the performance is directed toward the norm and not the excellent. This is a type of "regression to the mean," or, in common parlance, "dumbing down." If standards are constantly being revised based upon research then, the norm continues to improve. But without a research structure, the system becomes stagnant. This problem was addressed by Dr. Smith.¹³ The report by Smith compared live-birth rates among ART labs without accreditation to those with accreditation by either CAP or ASRM. The live-birth rate was chosen because this was deemed to be the desired outcome. The report demonstrated that, for patients under the age of 35, the live-birth rate per cycle for all laboratories reporting their results was 28.7%, but, for those programs accredited by CAP or ASRM, the rate was 26.7%. These results are not statistically significant, but they make the point that regulation of laboratories does not ensure any improvement in outcome if the outcome is live-birth rate. While accreditation may not improve pregnancy rate, it does allow minimum standards to be established, which protects those individuals who would otherwise chose programs not meeting even minimum standards. Dr. Smith, in response to a letter to the editor by Dr. David Adamson, past president of the Society for Assisted Reproductive Technology (SART), emphasizes that real progress in improved success rates in IVF were related to developments in new technology that derived from research centers first published in the late 1970s and 1980s.¹⁴ Thus, laboratories are easily regulated, and this regulation establishes minimum standards for patient care. But this regulation does not seem to improve the outcome for IVF. Without significant research, progress, in the form of improved patient care, is slow.

The Changing Nature of Patients

Just as the nature of medicine has been changing due to advances in technology, so too has the nature of the patient changed. Patients today are much better informed, as they have numerous resources at their disposal for researching their infertility issues. This advance in technology has empowered patients and, thus, placed them at less risk of harm than ever before. The more informed a patient becomes, the less the fiduciary duty the physician has to the patient and the more on equal footing each is to negotiate treatment. This becomes much more like a contract and, thus, again more business-like than in many other areas of medicine. Patients today have vastly more information available to them, and they are no longer part of a small, exclusive community of IVF patients. It has been estimated that more than 2 million IVF children have been born worldwide. In the United States, the CDC has reported that there are more than 100,000 IVF procedures done each year.¹⁵ If one "googles" IVF, one will find that such a search returns more than 3 million "hits." Most patients will listen to their physician and then do a web search for more information about their fertility issues. Many physicians will advise patients to utilize the web to gather information, and most physicians maintain websites that have information they have selected for their patients. These sites also serve as advertising for the physicians' practices. The 2004 report from the U.S. Department of Commerce found that 62% of all U.S. households have a computer and 55% have Internet access.¹⁶ The increased use of the Internet and the amount of medical information available on the Internet caused the American Medical Association (AMA) to voice concern about the quality and veracity of this information.¹⁷ In 2000, the AMA published guidelines for the information contained on Internet sites.¹⁸ One emphasis concerned the quality of the content of the websites. This concern was evaluated by Huang et al.¹⁹ after reviewing the content of 263 websites on infertility drawn from the SART directory. Hospital-based sites accounted for 58 of those sites - or 25%. The authors established criteria for evaluating the websites based upon the AMA recommendations. They concluded that most websites failed to meet the guidelines published by the AMA. As there is no overarching, independent editorial review of web content, patients cannot ascertain the accuracy of website information. One solution devised by the United Kingdom to assist patients in evaluating websites was the DISCERN project. This National Health Service project developed an instrument that patients could use to evaluate the veracity of web content.²⁰ One useful regulation would require U.S.-based websites to include such an instrument on the site so that patients would readily be able to evaluate the content for accuracy and truthfulness as they browsed the site.

Regulation in the Form of Mandated Fertility Coverage

There are 13 states that mandate some insurance coverage for infertility services. Illinois has an excellent mandate in that it provides for coverage sufficient to ensure that the couple has a statistically reasonable chance of conceiving.²¹ Other states have varying amounts of mandated coverage with some providing for more coverage (e.g., Massachusetts) and most providing for far less coverage.

The ability to utilize ART requires that the patient is able to pay for these procedures. Most causes of infertility require the use of multiple cycles of treatment to maximize the chance of success. There remains a wide range in the ability of patients to afford ART. The first is the obvious factor of the socio-economic structure of society. Many patients could benefit from treatment and would be excellent parents, but, because of their income level, they simply cannot afford ART. However, a second factor has to do with state-determined mandated insurance coverage. Most states do not have mandated infertility coverage. However, at the other end of the spectrum, Massachusetts requires extensive infertility coverage. When a patient has some mandated benefit that has a ceiling of coverage, the patient becomes a consumer of services on a budget. The net effect could be to make the patient a key regulatory agent in terms of how he or she chooses to spend that money. Illinois is a good example of a state with excellent-but-not-unlimited insurance coverage for ART.²² The statute provides infertility coverage for most forms of treatment up to and including four cycles of IVF. The statute has exclusions such as for employers employing fewer than 25 employees and employers that are certain religious organizations (e.g., the Catholic Church). The practical aspect of this is that patients keep track of their benefits. If they do not achieve a pregnancy quickly, they are far more likely to switch practices or treatments. For example, a patient who has age-related infertility might be more willing try one cycle of IVF with her own oocytes rather than a person who may have no coverage and, thus, who may opt to go directly to donor oocytes. However, under this regulatory coverage regime, couples that are unsuccessful after two or three cycles will switch treatment to the use of donor oocytes for the last cycle of IVF. The effect of mandated coverage is an increased utilization of fertility services but a reduction in the number of embryos transferred per transfer and an increase in the number of couples achieving parenthood.²³ Legislatures could tie benefits, through the use of regulations, to limits on the number of embryos transferred, qualifications of the person performing the procedures, and performance standards. This would establish a minimum standard of care without directly regulating the clinical practice of ART.

The Business of ART

ART has become big business. In a 2002 publication, Collins estimated that there were approximately 350,000 cycles of IVF performed in 48 countries. Collins also estimated that the average price for an IVF cycle would be about $10,000 in 2002 with about 35,000 IVF cycles being performed, resulting in an estimated yearly price tag of $350 million. The price of IVF does not accurately reflect what the healthcare industry actual pays for IVF nor does it reflect what patients, as consumers, pay. The charges for an IVF cycle are not what the physician actually receives when IVF is a covered charge as happens in some coverage-mandated states, such as Illinois. Nonetheless, the business of ART involves hundreds of millions of dollars, where most patients are the direct consumers. This is unlike most healthcare payments where the employer or the government is the actual consumer, in terms of payment, and the patient is the beneficiary. Thus, patients are in a unique position to regulate ART through the power of the pocketbook.

The Business of Law

Regulation usually involves either lawyers or congressmen where there exists an area that requires regulation to protect patients or society. One factor contributing to the cost of medicine and the business-like nature of medicine has to do with the business of law. The legal profession has undergone many changes just as the practice of medicine has. Part of this has to do with technology, and part has to do with the fact that, as with IVF, there is money to be made in the practice of law.

Tort litigation has been targeted as one significant contributor to the high cost of healthcare. Tort litigation is present in ART but certainly not to the extent that it is in obstetrics, which is the field from which REI derives its origins. Thus, REIs feel lucky that they do not have to pay the same hefty malpractice premiums that their obstetric colleagues pay. However, malpractice litigation does affect ART, and it does contribute to the cost of IVF. A report published in 2002 by the Department of Health and Human Services²⁴ described how the legal system impacts the rising cost of healthcare, and it estimated that between $60 billion and $108 billion could be saved by eliminating "defensive medicine." Not included in the cost of defensive medicine is the harm caused by ordering unnecessary tests with their acknowledged "false positive" rate. False positives require further testing and sometimes intervention - both of which carry risks to the patient that are not justified by any benefit.

The purpose of the tort system is to provide financial compensation when a person has been unjustly injured. Most critics do not contest this purpose. The area of contention is the "pain and suffering" portion of the awards. It is not the purpose of this brief paper to address this in any detail, but a few points are salient. The tort system does make the medical system at least ask the question of whether a standard of care was met for the patient. Unless physicians are willing to accept stringent regulation, this is the best "watch dog" available. The high cost of litigating malpractice cases provides some minimum screening in an attempt to limit cases to those that have merit.

There is some debate within the State of Illinois as to whether there really is a serious malpractice problem. Professor Vidmar prepared a report for the Illinois State Legislature in which he questioned some of the most publicized concerns about the medical malpractice problem in Illinois.²⁵ The establishment of "caps" on "pain and suffering" probably will not solve the problem, as this just encourages plaintiffs' attorneys to find more defendants. Finally, the present tort system does not solve the problem of improved patient care or, in the area of ART, improved outcomes.

There can be no doubt that there are considerable sums of money being spent on legal fees in the tort system. But largely overlooked are the huge sums being spent on contracts. Most physicians have a lawyer that they deal with frequently concerning a variety of legal issues. Standardization of informed consent, disposition of genetic material, and negotiations with healthcare payers cost physicians - and, thus, the healthcare system - an enormous amount of money. This adds to the cost of doing business and promotes the legal profession. Legislation to standardize the required forms would reduce significantly the cost of legal fees.

Clinical Practice: Establishing Standards of Care

Clinical standards of care are a sword. On the one edge, the patient is protected from practices that fail to meet a minimum quality of care. On the other edge, they tend to reduce practice to the lowest common denominator. Most patients do not want to be treated by the average physician; they want the expert - the superstar. Most physicians do not want to be the average physician. They have been selected because of their intellectual competitive prowess, and this behavior is reinforced in their training. Clinical standards of care need to be set by the various colleges and need to be based upon care-based, evidence-based models. Both the American College of Obstetricians and Gynecologists (ACOG) and ASRM have clinical guidelines. Two questions arise concerning these guidelines. One question concerns the quality of these guidelines. Recent guidelines are established using EBM and, thus, have the highest quality available given existing knowledge. The second question concerns how the guidelines can be adjusted so that they continue to improve patient care as new knowledge is obtained. The movement of academic physicians to private practice removes the traditional manner in which new ideas were developed and new research was conducted so that advances can be made toward improving patient care. Especially concerning is the possibility that basic research will suffer because private-practice physicians are more concerned with the efficiency of practice than with discovering and implementing new concepts. Most private practices, composed of a limited number of physicians, cannot sustain Ph.D.-level research with funds from within their own corporation.

Clinical guidelines have become a part of clinical medicine. The Institute of Medicine has defined clinical guidelines as "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances."²⁶The guidelines serve a broader function because they are constructed in such a way as to provide for a minimum standard of care with considerations of cost. The idea is to provide a scientific basis for clinical decision making that maximizes efficiency and minimizes patient risk. The major risk from guidelines is that the information may be incorrect or only a minimum standard. One reason for this is the fact that the information necessary to make proper guidelines may not be available. Also, guidelines are often influenced by opinions of those responsible for making the guidelines. The patient suffers if the guidelines are inferior. Practitioners also suffer from flawed guidelines if these are used to establish a standard of care for malpractice litigation. Recently, Haagen et al.²⁷ evaluated barriers to physician adherence to guidelines for the use of intrauterine insemination as recommended by the Dutch Society of Obstetrics and Gynaecology. The authors found that physician knowledge and positive attitudes about the guidelines was adequate. The authors also found that one major reason why guidelines were not followed centered around the physicians' "self-efficacy regarding communication with patients during the decision-making process about appropriate subfertility care."²⁸ Thus, while physicians may agree in principle with guidelines, adherence to them in day-to-day practice might vary considerably based upon a number of factors.

Legislation requiring practices to follow practice guidelines would improve quality of care. This idea has enormous opposition in the medical community and, thus, is very unrealistic. However, mandating coverage for infertility with a cap on benefits could indirectly accomplish the same results. First, consumers would shop for their care, and, as a result, physicians would have an incentive to meet practice guidelines. More importantly, insurance carriers could establish guidelines for payment. One example of this already exists in Illinois. HMO Illinois, the Blue Cross/Blue Shield HMO in Illinois, requires certain testing to be performed before it will authorize payment for a cycle of IVF. The HMO requires an evaluation of the uterine cavity, via either a hysterosonogram or a hysterosalpingogram, a semen analysis, and day three hormonal evaluation, as well as other routine obstetric screening tests. It also reviews the indications for IVF. Authorization for payment is dependent upon meeting certain established guidelines that still permit the physician wide latitude in clinical decision making for the patient. Other payers are even more restrictive in their approval, so significant "regulation" is placed upon the patient and physician through the control of authorization for payment. This system does not deny outright the patient's ability to have procedures as any patient is free to agree to a procedure that the physician feels is warranted. That freedom, however, costs the patient the actual cost of the procedure and places the patient in a position where the patient is the direct consumer of the healthcare services. The effect forces the patient to do a limited cost-benefit analysis before agreeing to any medical procedure.

Advertising

Advertising is regulated by the Federal Trade Commission. However, ASRM has published guidelines for advertising directed toward ART. The goal of the guidelines is to ensure that advertising presents accurate pregnancy statistics to couples seeking treatment. The guidelines make the point that using the CDC ART clinic-specific data is not a valid way to compare programs; thus, the guidelines prohibit the use of these data for advertising. In reality, these comparisons are frequently made in written press ads, radio ads, and web-page ads. Furthermore, patients access the CDC website and make the comparisons. The guidelines also require the ads to clearly specify how pregnancy rates were determined.

New Technologies

ART has consistently developed and implemented new technologies. The regulation of the development of new technologies had been controlled by the academic nature of ART when ART was first emerging. Once ART moved away from academic centers, its regulation disappeared such that, now, new procedures can be developed and implemented without regulation. Examples of this are the commercial offering of elective sex selection through the use of IVF with pre-implantation genetic diagnosis (PDG) and oocyte freezing for elective preservation of fertility. The concern is that, as newer genetic manipulations become available, couples will seek to use PGD to create "designer babies." This problem presents a very difficult ethical dilemma for ART. Parents will want to provide their potential children with any advantage they can, as that is just good parenting. But is it acceptable to manipulate embryos in an attempt to achieve a potential benefit? The actual lifetime outcomes from these manipulations will not be known for decades, and in the meantime, thousands of individuals might be affected. Also, should an elite group of people, who can afford the elective use of PGD, be permitted to enhance their children? But most pressing are the questions of who gets to decide and should government intervene with regulation. What congressman is willing to put his political life on the line on either side of this argument in an attempt to draft legislation that would regulate parents' right to provide their child with an advantage? While the reality of eugenics is extremely complicated, and while the actual ability to create designer children is limited at present, the paradigm is extremely important given the uncertain ability that might be developed to manipulate desired characteristics through PGD.

An area that had created concern is the use of information derived from PGD. This information could be used by a number of agencies and eventually become discriminatory. Recent passage of the Health Insurance Portability and Accountability Act and similar legislation has restricted the transfer of all medical information and, thus, provided regulation for the distribution of genetic information.

Clinical Outcome: Embryo Transfer

The number of embryos permissible to transfer provides an excellent example of how difficult it really is to control and regulate ART. The success rate of any individual embryo surviving to the stage of a normal, healthy live-born child has increased dramatically during the last 25 years. The survival was so low in the early stages of ART that it was customary to transfer a high number of embryos. Also, early in the development of ART, the ability to cryopreserve embryos was either nonexistent or had a very low success rate. Thus, excess embryos were either discarded or frozen with a low expectation of success. Recent developments in cryobiology have provided excellent success rates for cryopreserved embryos. Similar recent developments in the design of culture media have increased the success of each embryo to survive to delivery. Therefore, today, it is not unreasonable to suggest that there should only be single embryo transfers with cryopreservation of excess embryos and, thus, use of these in successive cycles until a pregnancy ensues. Nevertheless, this is not being done, and there is no suggestion that this will be done anytime in the near future. The need to limit the number of embryos transferred is so well documented that it no longer deserves discussion.²⁹ The need derives from the creation of multiple-gestational pregnancies with the transfer of more than one embryo. Twin gestations and beyond (i.e., triplet gestations, quadruplet gestations, etc.) increase numerous risk factors for both child and mother. ASRM has acknowledged this for years and has published guidelines that would restrict the number of embryos transferred.³⁰ Every REI pays lip service to this concept. But all REIs transfer more than a single embryo.³¹ There are a number of reasons for this. First, patients demand it. The success rate per cycle is significantly lower if only one embryo is transferred rather than two. Couples do not perceive twin gestations as a risk. Thus, the patient demand is high for the transfer of multiple embryos. Second, physicians accept the transfer of more than one embryo in order to maintain a competitive pregnancy rate for their programs. The facts that ART is a business and that, in many states, the patient is a consumer require ART programs to achieve as high a success rate as they can. Programs with lower success rates will be forced out of business as patients select the program with the highest success rate. High success rates do not accurately reflect the actual quality of the ART program, but they are the only measuring stick that patients presently have to judge the quality of ART programs. Third, the embryologist cannot accurately determine which embryo has the highest chance of success. As new techniques for determining embryo quality evolve, the ability of the embryologist will improve, so that transfer of a single embryo will provide a very high chance of success. Finally, the physicians performing the ART procedures are not the physicians providing obstetric care for the patient. The effect of these and many other factors is that no program in the United States is presently routinely practicing single embryo transfers, and most have an average number of embryos transferred greater than 2.0 in their high-probability category of patients. Mandating a limit to the number of embryos transferred, as has happened in the United Kingdom, would solve much of this problem.

Third-party Reproduction

The area of third-party reproduction is an example of how regulation can work. The value of regulation in the area of third-party reproduction is that it provides for the care of the children that result from ART procedures. Perhaps this is one reason why there is legislation regarding parental rights and responsibilities for third-party reproduction. Illinois has passed the Gestational Surrogacy Act, which regulates third-party reproduction as it relates to the establishment of parental rights and responsibilities.³²

While the Surrogacy Act is a major move forward, there still remain a number of questions that require resolution. For example, it is unclear as to the legal status of human embryos. This seems remarkable given that there are thousands of cryopreserved embryos and that these can be used by the couple who created them or can be donated to other people desiring parenthood. The status of human embryos constantly challenges the courts in divorce proceedings, as well as in other legal controversies. Some states, such a Louisiana, have addressed the legal status of human embryos, declaring then juridical persons.³³ Most states have not defined the legal status of embryos, so there continues to be difficulties with how the courts are to rule when disputes arise concerning human embryos. The ability of posthumously conceived children remains an area lacking attention from state legislatures. Again, some states, such as Virginia,³⁴ have addressed the issue of posthumously conceived children. However, most states have not addressed this issue, or, if they have, they have not considered the time frame in question with cryopreserved genetic material.

Genetics and Stem Cells

The practice of ART encompasses genetic testing and the potential to create stem cells and human clones. The reality of the clinical practice of ART is that most ART centers perform PGD, but very few are involved in stem cell research and human cloning. The ability of most centers to offer PGD raises concerns about genetic manipulation of human embryos to produce designer babies for controversial medical indications. A very simple example concerns the ability to perform purely elective gender selection using PGD. ASRM has published an ethics bulletin concerning sex selection in ART and has denounced the practice of elective gender selection using ART and PGD.³⁵ Nonetheless, any woman desiring to gender select can have an early karyotyping done either through chorionic villous sampling or amniocentesis, and chose to abort a fetus of an undesired gender. When a Chicago practice advertised that it would perform PGD for elective gender selection, there was nationwide protest of this procedure, and the center subsequently retracted the offer.

Technology may soon exist that would permit manipulation of pre-implantation human embryos, and this could result in couples being able to genetically enhance their children. The extent of the freedom to choose these technologies has not been addressed by any legislative body. The assumption is that the present legal atmosphere protects patient autonomy. Children that result from ART are not protected as they are not viable when the manipulations are being done. Therefore, it is hard to imagine that the legal system would chose to regulate the use of PGD to create designer babies if that technology becomes available.

The emergence of stem cell research and cloning has produced incredible controversies and conflicts. This paper will not attempt to discuss this except to note that the conflicts typify the conflict between the law and medicine. The legal system, by constitutional design, protects minority interests. Medicine deals with treating and attempting to cure as many persons as possible. This dichotomy defies resolution.

Conclusion

ART is more like a business than many other areas of medicine. This derives from the fact that, in most states, ART is paid for by the patient and not through employer-provided health insurance. ART, as a business, succumbs to the common problems of business, such as competition. ART, as business, thus, needs regulation. There already exist a number of regulations and restrictions placed on the practice of ART. Most of this regulation involves the laboratory aspect of ART. Direct regulation on the practice of ART would be difficult to enact due to the constitutionally protected right to reproduce. Indirect regulation can be effectively achieved through the regulation of the business of ART through the commerce clause. Certain aspects of ART can be directly regulated, such as any new device or drug used in the treatment of ART. Malpractice litigation remains the only indirect regulation on practice standards, but the efficacy on this type of regulation is questionable. Certain aspects of ART need federal regulation, now, such as the number of embryos to transfer. A comprehensive approach to the treatment of infertility proposed by the federal government would provide patients with both the means to pursue treatment and protection in the form of risk reduction. The healthcare system could benefit from this if it standardized payment. The healthcare system would also benefit if the standards set and the regulations required could be used as defense to malpractice litigation.

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¹² Id. at 1736.
¹³ A. L. Smith, College of American Pathologists and American Society of Reproductive Medicine Accreditation of Assisted Reproductive Technology (ART) Laboratories Is Associated with a Decrease in Take Home Baby Rates of Reporting ART Laboratories, 73 FERTILITY & STERILITY 173-74 (2000).
¹⁴ A. L. Smith, Letter to the Editor, 74 FERTILITY & STERILITY 850 (2000).
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²¹ 215 ILCS 5/356m (2005).
²² Id.
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³⁰ Practice Committee, Society for Assisted Reproductive Technology, & American Society for Reproductive Medicine, Guidelines on the Number of Embryos Transferred, 82 FERTILITY & STERILITY 773-74 (2004).
³¹ Centers for Disease Control & Prevention, Clinic-specific Data Giving Average Number of Embryos Transferred per Transfer, available at, http://www.cdc.gov/ART/ART2003/index.htm (last visited Dec. 12, 2005).
³² Illinois Gestational Surrogacy Act, 750 ILCS 47/10 (2005).
³³ LA. R.S. 9:121 (2005).
³⁴ VA. CODE ANN. § 64.1-71 (2005).
³⁵ The Ethics Committee, American Society for Reproductive Medicine, Preconception Gender Selection for Nonmedical Reasons, 82 FERTILITY & STERILITY Supp.1: S232-S235 (2004).

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