To the Editor:
Dr. David Meldrum proposes a revision of the clinic-specific Society for Assisted Reproductive Technology (SART)/Centers for Disease Control and Prevention (CDC) reporting format to better reflect the current practice of in vitro fertilization (IVF) by combining the outcomes of fresh and frozen embryo transfers in the numerator while making transfer procedure the denominator of choice (1). I concur with the first but disagree with the second part of his proposal, making transfer the preferred denominator without regard to the number of retrievals contributing embryos to the transfer. In addition to accuracy, a reporting system needs to be readily accessible to potential consumers.
With accumulation of eggs from multiple retrievals for a single transfer, this metric fails to differentiate between two distinct scenarios: A) one live birth from one transfer and one retrieval; B) one birth from one transfer following, say, four retrievals (2). Both scenarios generate 100% delivery rate per transfer, but the delivery rate per retrieval is 100% for scenario A but only 25% for scenario B. Such a reporting system would be misleading and leave patients vulnerable to exploitation by volume-driven clinics.
In the case of high responders, a single retrieval may lead to more than one live birth from sequential frozen embryo transfers (FETs), thus elevating the delivery rate per retrieval above 100% unless all births after the first one are censored—a crucial point the author does not address.
For consumers, the only numerators that matter are live births and multi-fetal births, while the obvious denominator for the former is ovum retrieval. Egg retrieval defines assisted reproduction in addition to being the most invasive as well as one of the most expensive steps of IVF. An average infertility patient cannot juggle the multiple numerators (pregnancies, live births, singleton live births) and denominators (cycle starts, retrievals, and transfers) in the current reports (3). Live birth per retrieval (“take-home baby rate”) remains the single most relevant and consumer-friendly measure of success.
For several years now I have presented patients with age-specific live-birth rates per retrieval regardless of whether the embryos are transferred fresh or frozen (http://abivf.com/solutions/results/). As illustrated below, this format lends itself to a summary graphic representation, which can be grasped at a glance:
Age-specific IVF live-birth rates per retrieval for women using their own eggs and live-birth rate per retrieval for women of all ages using donor eggs: Alta Bates IVF Program 2006-2011. [Click on figure for larger view.]
The principles of such reporting are: 1. a retrieval cycle is entered in the denominator only after the outcome of the first transfer is known; 2. only the first birth is counted in the numerator for each retrieval; 3. retrievals that yield no eggs or embryos are included in the denominator; 4. if the transfer includes embryos from multiple retrievals, the birth is credited only to the earliest retrieval without a prior birth; 5. retrievals without a birth at the end of the reporting period may later be credited with a birth from a subsequent FET.
Unbeknownst to me, a similar format was described by Dr. Howard Jones Jr., who named it Total Reproductive Potential (TRP) of a treatment cycle (4). Clinic-specific TRP can be calculated from the data currently submitted to SART (5). TRP reporting lowers the incentive to transfer more fresh embryos than advisable for competitive reasons. The TRP-based format works best with a time interval of 2 to 3 years, which reduces the random variation that plagues smaller programs in the current system.
TRP reports need not replace the national CDC compilations, which describe the overall scope of assisted reproduction and provide data for research. There is little reason for SART and CDC to publish essentially identical reports. I would urge SART to adopt a patient-friendly TRP-based reporting format specifically designed for IVF consumers rather than providers.
Ryszard J. Chetkowski, M.D.
Alta Bates IVF Program, Berkeley, California
1. Meldrum DR. Pregnancies and deliveries per fresh cycle are no longer adequate indicators of in vitro fertilization program quality: how should registries adapt? Fertil Steril 2013;100:620-1.
2. Cabo A, Garrido N, Crespo J, Remohi J, Pellicer A. Accumulation of oocytes: a new strategy for managing low-responder patients. Reprod Biomed Online 2012;24:424-32.
3. Paulos JA. Innumeracy: mathematical illiteracy and its consequences. New York: Hill and Wang, 2001.
4. Jones HW Jr, Jones D, Kolm P. Cryopreservation: a simplified method of evaluation. Hum Reprod 1997;12:548-53.
5. Stern JE, Hickman TF, Kinzer D, Penzias AS, Ball GD, Gibbons WE. Can the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) be used to accurately report clinic total reproductive potential (TRP)? Fertil Steril 2012;97:886-9.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.10.047
The authors respond:
The author has raised a concern addressed in response to a previous letter (1). There is broad agreement on the need for transparency regarding the number of retrievals done before a transfer. These oocyte/embryo accumulation cycles are being increasingly applied to poor responders, as it has been reported that this approach enhanced the cumulative pregnancy rate by 50% (2). Even in states or countries that cover the costs of in vitro fertilization (IVF), dropout from further treatment after a failed intensive stimulated cycle commonly exceeds 50%. Couples are simply unable to cope with failure, which has a profound effect on their ultimate chance of success. By avoiding the dropouts from further treatment, an improved outcome may be achieved (2). This approach commonly involves minimal stimulation with the goal of retrieving fewer oocytes of better quality and is also being evaluated for couples having embryos of poor quality. The patients for whom this accumulation strategy is being applied differ fundamentally from those receiving a usual level of stimulation followed by fresh or delayed transfer. I have therefore argued that these cycles should be reported separately (1).
The current registry structure has discouraged minimal stimulation cycles with the plan of a single initiated cycle per embryo transfer (ET), as those results would drag down an IVF center’s overall results. I have proposed that minimal stimulation cycles, such as modified natural cycles should also be reported separately (3).
The author has pointed out that total pregnancy potential (TPP) would be an excellent indicator of what the couple can expect from a single retrieval. An additional important advantage is that TPP would encourage elective single embryo transfer (eSET). Particularly with the newer vitrification technique for cryopreservation, TPP following eSET will be substantially higher for many patients compared with the transfer of two fresh embryos. The Society for Assisted Reproductive Technology (SART) has indicated at their recent annual meeting that TPP is one of the items being strongly considered for the registry, probably gathered over a 2-year period. They have also indicated the likelihood that minimal stimulation and accumulation cycles will be reported separately.
The author has argued that reporting of success rates per initiated cycle is not necessary as the retrieval is the most expensive and invasive procedure and that giving too many numerators and denominators for success is confusing. Those points are true, but Federal legislation requires reporting per initiated cycle (3). I do agree that delivery per retrieval and per transfer are the most important indicators on which couples should focus. However, cancelled stimulations carry economic, time, and emotional tolls as well, and not including all cycle starts could encourage higher cancellation rates aimed at enhancing outcomes. It is true, however, that the greatest emotional toll comes with failed ET (4), which could be reduced by cancellation and modification of the stimulation or the entire approach based on a poor response. While it is true that the SART report does not have to be identical to that of the Centers for Disease Control (CDC), it is best not to confuse patients by having a substantially different format for each.
If minimal stimulation and accumulation cycles are separated out, that will allow each group of couples to have a more accurate estimate of their expected success. Combining them all together would be misleading for all three groups. The main question that remains is what the patients will see when they first access results for a particular IVF clinic. Since outcomes for women of other ages are irrelevant for a particular couple, I would propose that when a patient chooses a clinic to view, the first field would be a filter for her age group. Then the results for minimal stimulation, accumulation cycles, and regular stimulation cycles would come up for her specific age group for that clinic. The couple can then see results for the specific treatment approach that has been recommended. Transparency and accuracy for the individual couple will be maximized, in line with the original intent of the Federal legislation. The only disadvantage would be that for some smaller programs; results in individual age categories can show wide variations. It could be emphasized at the beginning of the report that any comparison among clinics is better made with the category of women under age 35, where results are more consistent, and by examining a clinic’s success rates over multiple years if available. As always, it must be strongly emphasized to those viewing the report that abundant caution must be exercised with any attempt at comparing one clinic against another due to potential differences in the populations of patients treated.
The author has pointed out that if results from fresh and frozen ETs are to be combined, multiple successful ETs could raise the calculated success rate in some patients, even to greater than 100%. At the recent SART annual meeting it was indicated that the first ET, whether fresh or frozen, would be the most likely denominator. For the calculation of TPP, the first birth would logically be the final item for the numerator. In each case, the success rate per retrieval will be reported. For example, for a birth following 4 retrievals, the success rate would be 100 divided by 4, or 25%. For those accumulation cycles, the patient should also be able to view her expected success rate per ET. There should be very few regular stimulation cycles that are converted mid-stream to an accumulation strategy, particularly when IVF practitioners understand that success will be divided by the number of retrievals.
A revamping of the SART and CDC registries gives a wonderful opportunity to solve multiple deficiencies in the present reporting system, and electronic formatting provides the opportunity for customizing results and markedly improving transparency. We hope that a new registry structure will no longer discourage methods of treatment and investigations aimed at providing more cost-effective, safer, and effective IVF therapy, while at the same time giving couples a better estimation of the level of success they can expect with a specific mode of treatment.
David R. Meldrum, M.D.
Reproductive Partners Medical Group, Redondo Beach, California
1. Meldrum DR. Reply of the authors. Fertil Steril 2013 Oct;100(4):e31-2. doi:10.1016/j.fertnstert.2013.08.037. Epub 2013 Aug 29.
2. Cobo A, Garrido N, Crespo J, Jose R, Pellicer A. Accumulation of oocytes: a new strategy for managing low-responder patients. Reprod Biomed Online 2012;24:424-32.
3. Meldrum DR. Society for Assisted Reproductive Technology/Centers for Disease Control IVF Registry 2.0. Fertil Steril, 2013.
4. Hammarberg K, Astbury J, Baker H. Women’s experience of IVF: a follow-up study. Hum Reprod 2001;16:374-83.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.10.046