Letter to the editor |
Multiple birth risks associated with IVF and extended embryo culture: USA, 2001
1 President, 2 Immediate Past President, 3 President-Elect, 4 Vice-President and Research Committee Chairman, Society for Assisted Reproductive Technology
5 To whom correspondence should be addressed. Eric S.Surrey, M.D., 799 E. Hampden Ave, #300, Englewood, C0 80113, USA. E-mail: Esurrey{at}colocrm.com
Sir,
We reviewed the manuscript by Kissin et al. (2005)
with great interest. The authors suggest variations in live birth and multiple pregnancy rates across various patient groups who underwent embryo transfer with cleavage stage embryos on day 3 or blastocyst stage embryos on day 5 without significant differences. The authors analysed the data according to the day of embryo transfer and whether or not supernumerary embryos were frozen. There are several issues which make interpretation of the conclusions somewhat challenging. The authors have lumped all multiple pregnancies together in their analysis which makes an accurate evaluation of the outcomes difficult. There is no question that all multiple pregnancies are associated with a higher risk than that associated with singleton pregnancies, and that the goal of practitioners of assisted reproductive technologies should be to achieve a single healthy pregnancy. It would also be appropriate to state that the relative risks of twin versus high order multiple pregnancies are significantly different. The authors have concluded that a day 3 versus day 5 embryo transfer has no impact on multiple pregnancy despite the fact that fewer embryos were transferred with day 5 transfer. This conclusion may not be valid at all if either day 3 or day 5 transfer is associated with reduced likelihood of high-order multiples as compared to twins. In order to greatly enhance the value of this work, and given the ready accessibility of the data, we would strongly recommend that additional analyses differentiating twin and high order multiple pregnancy rates be incorporated into the tables. The current data set also does not provide specific information on implantation rates. The absence of this parameter makes interpretation of the effect of a differing stage of embryo transfer on multiple pregnancy rates difficult to interpret. This potentially could result in a significant alteration of the conclusions derived from this manuscript.
The data analysed from 2001 would have reflected practice guidelines published in 1999 which recommended that no more than two embryos be replaced in good prognosis patients in an effort to decrease the incidence of high order multiple pregnancies (Practice Committee of ASRM, 1999). These guidelines have had a major impact on reducing the incidence of high order multiple pregnancy, as has been demonstrated by Jain et al. (2004). It is important to note that within the USA, guidelines for the number of embryos to be transferred which recommended discussion of single embryo transfer in good prognosis patients were not published until September 2004 (Practice Committees of ASRM and SART, 2004) well after the data set included in this manuscript. It is important to note that, though the authors stress the importance of single embryo transfer, this manuscript does not provide information as to which patient groups, or either developmental stage or quality of embryos to be transferred, would achieve this goal with any degree of efficiency. It is interesting to note that in an analysis published as recently as October 2004, Pandian et al. (2004) in writing for the Cochrane data base felt that, based on the current literature, there was insufficient available evidence to recommend that single embryo transfer be the preferred approach for all patients undergoing IVF.
This manuscript clearly does not represent a definitive analysis of the relative benefits of day 3 versus day 5 embryo transfer in that the indications for these two procedures vary between clinics. There are those programmes that solely perform day 3 transfer, solely perform day 5 transfer, or perform blastocyst transfer based on clinic-specific criteria typically based on embryo quality and patient history. In spite of relatively large numbers of embryos transferred, it is virtually impossible to compare these two groups in the absence of data derived from equivalent patient groups.
We are concerned that the authors have relied upon the presence of supernumerary embryos available for cryopreservation as an indication of embryo quality. While there is some evidence for this relationship, in reality, there is no information regarding embryo quality for either of these groups which clearly can play a role in cycle outcome as well as the decision to consider day 3 versus 5 embryo transfer. Decisions about cryopreservation are also made for a variety of reasons that do not necessarily reflect embryo quality. Clearly differences in laboratory techniques as well as patient selection and internal laboratory protocol play a major role
The labelling of patients undergoing day 3 transfer without cryopreservation as a ‘worst prognosis group’ is curious. The pregnancy rate for this group is markedly higher than that described by most investigators when describing patients with poor prognosis—a descriptor which is typically attributed to women with poor ovarian response, advanced maternal age, poor embryo quality, or multiple implantation failures. None of these characteristics is used in the current analysis. The statistic presented in this manuscript is clearly not representative of outcomes for poor responders as defined within the clinical community and should not serve as a basis for policy regarding transfer recommendations in this patient group.
References
Jain T, Missmer S and Hornstein M (2004) Trends in embryo-transfer practice and in outcomes of the use of assisted reproductive technology in the United States. New Engl J Med 350,1639–1645.
Kissin DM, Schieve LA and Reynolds MA (2005) Multiple-birth risk associated with IVF and extended embryo culture: USA, 2001. Hum Reprod 20,2215–2223.
Pandian Z, Bhattacharya S, Ozturk O, Serour GI and Templeton A (2004) Number of embryos for transfer following in-vitro fertilization or intra-cytoplasmic sperm injection. Cochran Database Syst Rev 4: CD002416.
Practice Committees of American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology (1999) Guidelines on Numbers of Embryos Transferred. American Society for Reproductive Medicine, Birmingham, AL.
Practice Committee of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology (2004) Guidelines on the numbers of embryos transferred. Fertil Steril 82,773–774.[CrossRef][Medline]
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