ART Success rates - all that glimmers
ART Success rates - all that glimmers
by Sam Thatcher MD, PhD
Reprinted with permission from the American Infertility 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.
- 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.
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.
- 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.
- 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.
- 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.
- 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.
- 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
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
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
Sam Thatcher MD, PhD
Center for Applied Reproductive Science
Johnson City, Tennessee