Hum. Reprod. Advance Access originally published online on August 19, 2004
Human Reproduction 2004 19(11):2439-2441; doi:10.1093/humrep/deh446
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What is the most relevant standard of success in assisted reproduction?
The value of cryopreservation on cumulative pregnancy rates per single oocyte retrieval should not be forgotten
1 Department of Obstetrics and Gynaecology, Helsinki University Central Hospital and 2 STAKES National Research and Development Centre for Welfare and Health, Helsinki, Finland
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, PO Box 140, 00029 HUS, Finland. Email: aila.tiitinen{at}hus.fi
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Abstract |
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 Top Abstract IntroductionThe value of cryopreservation...Implementation of eSET in...ConclusionsReferences |
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The most relevant standard of success in IVF has been discussed widely. An optimal standard should reflect both the risk aspects and the effectiveness of the treatment. The most important parameter for the couple is the ultimate cumulative delivery rate per started cycle. Even if the long-term follow-up of the treatment cycles is difficult in practice, we would stress that more emphasis should be given to embryo freezing, in order to maximize the efficiency of the IVF/ICSI cycles. The contribution of embryo cryopreservation in elective single embryo transfer cycle programmes may result in a cumulative delivery rate of >50%. In Finland, the implementation of single embryo transfer has been possible with good cryopreservation programmes. The effect of this strategy has been seen in a decrease in the proportion of twin deliveries after assisted reproduction, being 13.9% for 2002, as well as a reduction of the proportion of multiple births in the nationwide Medical Birth Registry.
Key words: assisted reproduction technologies/cryopreservation/eSET/standard of success
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Introduction |
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TopAbstractIntroductionThe value of cryopreservation...Implementation of eSET in...ConclusionsReferences |
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There has been a recent debate in Human Reproduction on defining the most relevant standard of success in IVF. An optimal standard of success reflects all risk and safety aspects of the technology, but at the same time it should consider the effectiveness of the treatment (Land and Evers, 2004
; Min et al., 2004; Pinborg et al., 2004). We agree that it is difficult to have IVF registries where all the details and long-term outcomes of treatment cycles are reported. However, we think it should be remembered that it is important to take into account the effect of all embryos achieved during a single oocyte retrieval procedure (Pinborg et al., 2004). This means that we should calculate the cumulative delivery rate per stimulated cycle after all embryo transfers, fresh and frozen, have been performed. This strategy also highlights the importance of cryopreservation programmes when implementing elective single embryo transfer (eSET) strategies. |
The value of cryopreservation in eSET programmes |
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TopAbstractIntroductionThe value of cryopreservation...Implementation of eSET in...ConclusionsReferences |
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The number of cryopreservation cycles has been quite constant in Europe during recent years. More than 45000 frozen embryo transfers (FETs) per year are performed, with a mean pregnancy rate of 16.6% (ESHRE, 2004
). In 2000, the number of FETs in relation to fresh transfers in Finland was higher (38.4%) than in other countries (mean 16.4%, range 0.6–38.4%) (ESHRE, 2004). According to Finnish IVF statistics, 39.9% (3030 out of 7587) of all embryo transfers in 2002 were FETs and 32.7% (412/1259) of assisted reproduction technology (ART) deliveries came from FET (STAKES, 2004). In spite of the high number of FET cycles, the clinical pregnancy rate per ET is very acceptable, 20.8%, which means that the patients are not highly selected cases for cryopreservation.
The outcome in FET cycles can be improved, and SET in frozen–thawed cycles also has to be considered. During the years of our recent study, the amount of SETs in frozen–thawed cycles increased from 28 to 66% and the implantation and pregnancy rates improved, from 13.5 to 30.0% and from 20.3 to 36.9%, respectively (Hyden-Granskog and Tiitinen, 2004). During the same period, multiple delivery rates have decreased from 21.8 to 7.9%. We want to suggest that when defining the standard of success in an ART programme, the quality of cryopreservation methods should be covered.
The contribution of embryo cryopreservation following IVF/ICSI provides further possibilities of pregnancy in addition to transfer in the fresh cycle. The contribution of cryopreservation to pregnancy has been reported to increase the baby take-home rate by 5.2% (Kahn et al., 1993) to 11% (Wang et al., 1994) or even 19% (Bergh et al., 1995). We analysed in a follow-up study all ETs carried out at our clinic during 1998–1999 (Tiitinen et al., 2001). Following eSET (127 cases), the pregnancy per ET was 38.6% and after double embryo transfer (DET) it was 40.0%. The contribution of embryo cryopreservation in eSET cycles resulted in the cumulative delivery rate of 52.8% per oocyte retrieval after fresh and frozen transfers. After increasing the proportion of eSET cycles yearly, we still have deliveries in >50% of eSET cycles (Hyden-Granskog and Tiitinen, 2004).
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Implementation of eSET in Finland |
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TopAbstractIntroductionThe value of cryopreservation...Implementation of eSET in...ConclusionsReferences |
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Finland has answered the challenge to lower the number of twin pregnancies while maintaining good overall pregnancy rates. This has been performed by gradually proceeding with the eSET policy in our country. In a prospective randomized study carried out in three large clinics in Finland, 144 couples were randomized for eSET or DET (Martikainen et al., 2001
). The twin pregnancy rate in the DET group was 39%, while in the eSET group there was one pair of monozygotic twins (4.2%). The cumulative pregnancy rate per patient after the transfer of fresh and frozen embryos was 47.3% in the eSET group and 58.5% in the DET group, respectively. According to the preliminary data, the price of the ‘extra’ IVF/ICSI treatment necessary in the eSET group is less than the estimated costs for the antepartum care of twin pregnancies. This means that eSET combined with embryo cryopreservation is a very cost-effective treatment mode.
There are examples of increased use of eSET which have resulted in a reduction of multiple pregnancy rates. The twin pregnancy and twin delivery rates have decreased below 10% (Tiitinen et al., 2003; Söderström-Anttila et al., 2003; Martikainen et al., 2004), while the pregnancy and delivery rates have remained nearly unchanged. In the infertility clinic of Helsinki University Central, the number of eSETs increased from 11 to 60% during 1997–2003, and during this time the clinical pregnancy rate per ET was quite stable at 34.1% (range 30.3–39.8%). The multiple pregnancy rate decreased from 25% to 
7%, while the mean number of embryos per ET decreased from 1.8 to 1.2 in 2003.
The number of fresh IVF/ICSI cycles in Finland has stabilized at 4500 cycles per year. According to Finnish IVF statistics, the proportion of SETs has increased since 1997, being near to 40% in 2002 (Figure 1). The effect of the increasing use of eSET can already be seen with the decrease in the proportion of multiple deliveries after ART in Finland (Figure 1).
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Conclusions |
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TopAbstractIntroductionThe value of cryopreservation...Implementation of eSET in...ConclusionsReferences |
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Correct counselling is very important, as some infertile couples are known to desire multiple pregnancies. Good counselling should include realistic information, not only on the risks of twin gestation but also on later burdens with a multiple birth. Since we began performing eSET, the attitude of the patients has changed. After careful counselling, most of the couples want to minimize the risk of a twin pregnancy. If only one embryo is transferred, it does not mean that the other embryos are discarded; they are only stored for later use. Of course, it has to be remembered that some of the embryos will not survive the freezing–thawing process, and we might lose some pregnancies. This risk can be minimized with improvements in cryopreservation and thawing methods.
Our experience confirms the significance of eSET as a method to reduce the proportion of multiple pregnancies resulting from ART. The increased use of eSET can already be seen to be reducing the number of twin deliveries following ART in Finland and as a reduction of the proportion of multiple births in the Finnish Medical Birth Register (Figure 2).
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In Finland, the initiative for reducing the number of transferred embryos came as a result of the IVF clinics taking on the responsibility for the safety of the ART. The decrease in multiple deliveries results in an improvement of the perinatal health of the IVF children and the well-being of the families, but it is also important to consider the overall beneficial health economic impact (Gerris et al., 2004
). We encourage all IVF clinics to develop their cryopreservation programmes in order to introduce eSET effectively into their ongoing IVF/ICSI programmes.
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References |
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Bergh C, Josefsson B, Nilsson L and Hamberger L (1995) The success rate in a Swedish in-vitro-fertilization unit: a cohort study. Acta Obstet Gynecol Scand 74, 446–450.[Web of Science][Medline]
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Submitted on June 18, 2004; accepted on July 12, 2004.
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