1 Department of Obstetrics and Gynaecology, Research Institute Growth and Development (GROW), Academisch ziekenhuis Maastricht, and Maastricht University, Maastricht, The Netherlands
2 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Academisch ziekenhuis Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. e-mail: jlan{at}sgyn.azm.nl
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Abstract |
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Key words: ART quality/assisted reproduction/outcome measures/single embryo transfer/success rates
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If we agree that the goal of assisted reproduction should be maximizing a womans chance of having a healthy baby, and if at the same time we aim at reducing the greatest single risk associated with assisted reproduction, i.e. multiple pregnancy, we could decide to adopt an outcome measure that rewards efficacy (many healthy singleton babies) and penalizes unsafety (multiple embryo transfer). This would be the corrected singleton live birth rate per cycle started, i.e. the singleton live birth rate per cycle started (SLBRPCS) minus the multiple live birth rate per cycle started (MLBRPCS). For Europe, in the year 2000, this figure (SLBRPCS MLBRPCS) would vary between 3.3% for Ukraine, which reaches a delivery rate per cycle started of 15.3% at the expense of almost 40% multiples, and 12.1% for Finland, which reaches 19.7% deliveries/cycle with <20% multiples (ESHRE, 2004). The resulting parameter, SLBRPCS MLBRPCS, would be difficult to envisage however.
Several other proposals for new end-points have been made to encourage the transfer of fewer embryos, in order to diminish the number of multiple pregnancies. The implementation of these recommendations, however, is hampered by the perception that safety and efficacy are communicating vessels: by decreasing the number of embryos transferred, pregnancy rates will be reduced as well. However, it has been shown that triplets can be avoided by replacing two embryos (Staessen et al., 1995; Templeton and Morris, 1998
), and that twins can be avoided by replacing one embryo (Martikainen et al., 2001
; Gerris et al., 2002
), without significantly decreasing the overall pregnancy rate. These findings confirm that in selected groups of patients, increasing the number of embryos transferred will not improve the overall pregnancy rate any further, but only result in a higher multiple pregnancy rate (Martin and Welch, 1998
). The characteristics of patients and embryos with high implantation potential are still poorly defined. However, recent observations from the University Hospital in Helsinki (Tiitinen et al., 2003
), where elective single embryo transfer (eSET) is performed in 56% of all cycles and pregnancy rates remain over 30%, cast doubt upon very strict selection criteria. The clinics performing eSET in a substantial proportion of their patients have been shown to be capable of combining safety with efficacious treatment, which reflects a high standard of clinical quality.
In spite of the convincing observations on pregnancy rates after elective single and double embryo transfers, from the annual reports on the year 2000 of European (ESHRE, 2004), American (MMWR, 2003
) and Australian registries (AIHW, 2003
), it can be concluded that in a substantial number of patients, three or more embryos are still transferred. However, the data from these registries do not confirm the assumption of the communicating vessels: pregnancy rates tend to be low in countries in which many embryos are transferred, and the highest pregnancy rates are found where the number of embryos per transfer is low (Figure 1). This inverse relationship between efficacy and safety cannot be explained by differences in patient populations, which are very similar in developed countries, but rather is due to differences in laboratory expertise (in culturing and selecting embryos) and clinical skills (in ovarian stimulation leading to an adequate number of embryos and optimal endometrial receptivity). Only top-level clinics (where treatment efficacy is guaranteed) are able to decrease the number of embryos transferred without compromising their pregnancy rate, and to vouch for safety in this way.
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References |
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Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Vercruyssen M, Barudy-Vasquez J, Valkenburg M and Ryckaert G (2002) Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme. Hum Reprod 17,26262631.
HFEA. (2004) Human Fertilisation and Embryology Authority, Code of Practice, accessible at www.hfea.gov.uk.
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