(The following is an article by Dr. Thatcher prepared for the American Fertility Association)

A fact that makes reproductive medicine unique is a specific and quantifiable end point— a healthy baby. Each infertile couple and each and every assisted reproduction technology (ART) program are vitally interested in success rates. The stakes are high. Truly, success breeds success. A well-placed report of a center’s superior success rate can ensure survival in a competitive market and can be translated into substantial financial rewards and acclaim.

At one point in the mid 1980’s, over 50% of the over one hundred ART programs had not yet reported a pregnancy. In fact, the high failure rate and the large numbers of attempts generated a sizable financial windfall. Program growth depended on the number of attempts, not pregnancy rate. It was a new technology that offered hope to many, success to few. The low success rates were tolerated. Then, there emerged centers that appeared “to do” IVF better, patients became discriminatory and competition stiffened. Relatively low success rates coupled to the high cost of the procedure led to increased public scrutiny of the IVF procedure and ART programs. In the beginning, if either the cost of ART had been less, or the success rates greater, the need for reporting and regulation would probably never have arisen. Presently, there are many good programs and many more similarities than differences in success rates.

There have been several attempts at “industry” self-regulation. The primary example in the U.S. is the Society for Assisted Reproductive Technology (SART), in conjunction with the American Society of Reproductive Medicine (ASRM) joining forces with the Center for Disease Control (CDC). There are many flaws in the evaluation of ART success rates worldwide and especially, in the US. Make no mistake; a successful pregnancy outcome is still paramount. Perhaps it is the American way of “more is better,” and certainly the CDC reporting of center specific results, that has put the stamp of propriety on this approach, but is this the whole story? What is meant by “success”; what is truth in reporting? What is the risk-benefit of ART; its real cost? A fundamental question remains; can medical care be quantified? Is the physician-patient relationship only a Norman Rockwell magazine cover of the past?

The major caveats in the assessment of specific clinic success revolve around outcome reporting and patient management. There are many ways to evaluate, or in some cases obscure, ART success rates.

1. Acceptance-exclusion criteria - Even a modestly skilled clinician is generally able to determine which patient will have the greatest chances of success with IVF. Often extensive expensive pre-admission testing is employed as a “screening” mechanism. Who really benefits in the long run from this testing? A clinic may include the patients with the best chances of success and exclude the more difficult and less promising patients. Does this mean that the patient with a decreased chance of success should be excluded to keep the success rates high? Should a clinic with an open acceptance policy be penalized? An example was a 39 year old patient who was rejected from an IVF program and openly told to return when she was 40 so that their statistics would not be endangered.
    
2. Terminology - The most important statistic for the couple presenting for assisted reproduction is the chance of beginning cycle of therapy and ending with a single healthy baby. While this “take home baby rate” may be a legitimate reporting value, it may be more related to the individual couple than to the quality of the ART program. If a patient does not reach embryo transfer, it is most often a result of significant alteration in egg or sperm quality. This may not be predicted in advance and while different approaches in subsequent cycles may improve chances of pregnancy, success may not be related to the IVF center. A young healthy patient with tubal disease has an excellent chance of progressing from stimulation to follicle aspiration and from clinical pregnancy to delivery. Cycle start and embryo transfer rate should be almost equal. Abortion rate is probably no greater than the general population, so clinical transfer to delivery should also be nearly equal. However, the older patient with multiple etiologies of her infertility may have a much greater rate of cycle cancellation and pregnancy loss before delivery. After transfer there may be a higher the risk of miscarriage. The above differences are not due to the center performing ART, but to the difference in couples accepted into their program and little can be changed to alter success rate.

   It would seem that the acid test of the ART laboratory is the success rate from transfer to clinical pregnancy. A very important statistic to use for ART program comparison is the implantation rate. Implantation rate is calculated as clinical pregnancy rate divided by the number of embryos transferred. These statistics remove the bias of centers that transfer large number of embryos. Too few centers have a large enough database that each couple can be compared to others with very similar medical histories. Approximations are made by age and reason for infertility. It would be great to be able to answer the question “what are MY chances of a pregnancy?” Overall, it matters less as to how statistics are presented, than that they are discussed, compared in detail, and in advance with each individual couple.

3. Embryo transfer rate - It is very difficult for a center, and for the infertile couple, not to choose the option that gives the highest chance of pregnancy. The media extravaganza over the McCauley septuplets has led some to believe that they too can successfully carry multiple pregnancies. This is compounded by some ART centers, which may subscribe to the adage that there is no such thing as bad publicity and view multiple gestations as prowess. Although some couples have dread of multiple pregnancies, other look on it as a mark of achievement and still others desire a pregnancy so intensely as to be blinded to the risk. Many couples clearly profess their preference of twins and naively underestimate the risk of pregnancy-induced hypertension, gestational diabetes, premature labor and birth, and cesarean section. The total health care costs of a multiple pregnancy rivals the total cost of assisted reproduction. Have undue medical, social, and financial risks been taken in the name of success rates? There is a clear, direct, positive relationship between the number of embryos replaced, the chances of pregnancy, and the chance of multiple pregnancy. Many centers, especially in women over age 35, transfer more than 3 embryos. Several countries have mandated the limits of embryo replacement to 2 or 3 embryos.
    
4. Blastocyst transfer - The ability to prolong the culture from 2-3 to 5-6 days has been a significant scientific achievement and a new milestone for embryology. It is unclear whether this truly increases the overall cycle success rate. Most programs are relatively stringent in their acceptance criteria for the technique. Most require a relatively large number of eggs to start and the attrition rate is high. Fewer patients reach transfer than with conventional day 3 transfer. Blastocyst transfer has allowed the best quality embryos to be transferred and therefore the relative pregnancy rate to increase. Some have referred to blastocyst transfer as a day 5 pregnancy test. By reducing the number of embryos transferred, multiple pregnancy can be reduced. However, many programs still transfer 3 blastocysts with the inherent risk of triplets and a very high rate of twinning. Unfortunately, blastocyst transfer also has been use for a marketing ploy.
    
5. Sales promotions - Coupon clipping, 3 for 2, and “money back guarantees” are an American way of life. What is their purpose? It is certainly not to increase value, but to increase sales. Initially the ASRM issued a negative statement on these “deals”, but more recently this stand has been relaxed. Often programs using these incentives have stringent acceptance criteria and the option is offered to those with the greatest likelihood of pregnancy in the first cycle. Usually there is an administrative charge, “all returned except…” and medications are not included. The real beneficiary of such programs is the IVF center. The proposition still remains attractive, but let the buyer beware.
    
6. Research protocols - This is a largely unrecognized practice more commonly utilized in academic centers. Patients that have relatively low chances of success are removed from the reported statistics under the present reporting guidelines. This may allow the development of new treatment strategies, or it may be used as a loophole to escape fair reporting.
    
7. Cost is an absolute barrier to therapy for many couples. Some couples with a good prognosis for pregnancy must stop short of realization of their goal for financial reasons. It is common for lifestyles to be altered and discretionary income entirely allotted to ART. In some cases, house are mortgaged, vehicles sold, or retirement accounts depleted in order to pay for a single ART cycle. A few states have mandated coverage and insurance companies may be slightly more tolerant than in the past, but often ART is grouped with contact lenses, breast augmentation and sex change operations. The Universal Declaration of Human Rights proclaims a couple’s right to found a family. Infertility is just as crippling as other better recognized diseases. There is nothing elective about infertility, nor should there be about its treatment.

   Consider, if an IVF cycle costs 50% less at center A with the same success rates as Center B, Center A is in principle, twice as successful as Center B. There seems to be little relationship between what the centers charge and their success rates. Unfortunately, the price structures of ART programs reflect “what the traffic will bear”, rather than actual cost. Should a reproductive embryologist earn the same as a sports superstar, or that of a superb grade school teacher?

   An interesting exercise would be to record the entire revenue generated by an ART center and divide it by the number of successful pregnancies. Our ranking of most successful centers might be quite different.

8. Fraud - All centers want to be viewed favorably. Statements about pregnancy rates sometimes represent factual data, sometimes a projection, or possibly even a hope. Unfortunately, it is not unheard of for a center to knowingly misrepresent itself. In some instances, the line of legality has been crossed leading to governmental investigation and sanction. It is virtually impossible to police this aspect of ART. Reporting policies can be legislated, but not ethics.

In conclusion, there remains no doubt about the effectiveness of ART in establishing pregnancies. Often, success is achieved at the end of a long arduous journey, when all other methods have failed. For each individual couple the chances are either 0 or 100%. Of course success is important; it may even be everything. But, there should be a clarity in thought between success and success rate. In some cases, success may be translated as acceptance of infertility, election of childless living or adoption.

Over the last several years, pregnancy rates have significantly improved and most centers and couples are enjoying the benefits of greater chances of success. The two largest obstacles that we now face are not pregnancy rate, but access to therapy and limitation of number of embryos transferred and thus multiple pregnancy rates. Both could be easily solved in a cost-effective way by universal coverage by insurance of infertility and assisted reproduction and by limiting the number of embryos replaced to two.

In reality, there is probably little that separates most ART centers. No center can guarantee a pregnancy. No center can precisely predict chances of success. Should we not start to downplay the business and mechanistic side of ART and concentrate on sound, individualized, cost-effective patient care in well-respected and proven centers? In the final analysis, there can be no substitute for an informed consumer, frank conversation, and a sound doctor-patient relationship.

Sam Thatcher MD, PhD
Center for Applied Reproductive Science
Johnson City, Tennessee
October 1999

Also see success rates at C.A.R.S.

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