Letters to the editor |
The difference in pregnancy rates between elective single embryo transfer (SET) compared to double embryo transfer is dependent on the implantation rates of embryos being transferred. Using mathematical modeling to determine when SET becomes a viable option
School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia 5001, Australia
1 To whom correspondence should be addressed. E-mail: jeremy.thompson{at}adelaide.edu.au
Sir,
The article by van Montfoort et al. (2006)
concludes that undertaking single-embryo transfer in unselected patients will halve the pregnancy rate compared with double-embryo transfer. Their conclusion was derived following a randomized controlled trial (RCT) of single-embryo transfer versus double-embryo transfer. They also concluded that only in selected patient groups, which have a good prognosis of pregnancy establishment following IVF, would a less drastic effect of single-embryo transfer on pregnancy rate be observed compared with double-embryo transfer. Although we congratulate van Montfoort and colleagues on undertaking an RCT on this subject, we believe that the conclusion is inaccurate, because of their lack of consideration of the impact of the implantation rate of embryos on both the pregnancy rate and the proportion of twin pregnancies.
There is a dramatic relationship between pregnancy rate and twinning rate with embryonic implantation rate. Using the concept of ‘e’ for embryo contribution to pregnancy and ‘r’ for contribution of patient at transfer to pregnancy, as outlined in McMillan (1998), and based on binomial independence of embryo survival, improving the quality of the embryos being transferred and/or the management of patients undergoing embryo transfer, an exponentially increased risk of twin pregnancies occurs with an exponentially decreased advantage to improving the pregnancy rate under double-embryo transfer. From such modelling, we would predict a 10% twinning rate when single-embryo transfer and double-embryo transfer pregnancy rates are 21 and 40%, respectively, in the same population, as described by the van Montfoort et al. (2006) study. This is lower than the observed 21% twinning rate in their study. We would further predict that by increasing the quality of embryo and patient management to where the pregnancy rate for single-embryo transfer is 
35% (which has been achieved in many units), the equivalent double-embryo transfer pregnancy rate would be 50% (i.e. a 40% increase) and the twinning rate doubled to a theoretical 21%. This demonstrates that the twinning rate increases more dramatically than pregnancy rate when improvements are made to the implantation potential within an IVF unit that continues to perform double-embryo transfer.
Other modelling suggests that survival of human embryos in double-embryo transfer is not independent, such that the transfer of two embryos enhances the survival of each other (Matorras et al., 2005). If this is true, then transfer of two embryos will only further exacerbate the twinning rate. This could explain why our expected twinning rate underestimated the observed value in the van Montfoort et al. (2006) study.
Rather than declaring that single-embryo transfer will halve pregnancy rates compared with double-embryo transfer and that single-embryo transfer is appropriate only in good-prognosis patient groups, we recommend that single-embryo transfer be adopted when in either any or all patient groups the overall implantation rate of embryos is such that there is a rapidly declining advantage to the pregnancy rate and a rapidly increasing twinning rate when double-embryo transfer is applied. Mathematical models can help predict such shifts and can be utilized in assisted reproduction treatment (ART) units to make decisions about which patient groups should be treated with single-embryo transfer or double-embryo transfer. Furthermore, ART units should seek to continually increase the implantation rate of embryos across all patient groups, by improving laboratory systems and patient management, in an effort to decrease the requirement for double-embryo transfer.
References
Matorras R, Matorras F, Mendoza R, Rodriguez M, Remohi J, Rodriguez-Escudero FJ, Simon C. (2005) The implantation of every embryo facilitates the chances of the remaining embryos to implant in an IVF programme: a mathematical model to predict pregnancy and multiple pregnancy rates. Hum Reprod 20:2923–2931.
McMillan WH. (1998) Statistical models predicting embryo survival to term in cattle after embryo transfer. Theriogenology 50:1053–1070.[CrossRef][Web of Science][Medline]
van Montfoort APA, Fiddelers AAA, Janssen JM, Derhaag JG, Dirksen CD, Dunselman AJ, Land JA, Geraedts JPM, Evers JLH, Dumoulin JCM. (2006) In unselected patients, elective single-embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial. Hum Reprod 21:338–343.
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