An Overview of Temporal Trends in Multiple Births After Assisted Reproductive Technology in the USA

Judy E Stern


Expert Rev of Obstet Gynecol. 2013;8(4):357-368. 

In This Article

Can we Achieve SET?

Our goal is to arrive at highly successful SET.[68] In the USA, one program has instituted SET using a combination of patient education and mandatory SET for good prognosis patients.[69] The education phase of this project involved actively teaching patients about the risks of multiple as opposed to singleton delivery. Education alone helped encourage many patients to choose SET. The study also described a mandatory SET policy that was put in place for patients aged ≤37 years with good prognosis by program criteria. Five years after initiating the mandatory SET program, clinical volumes had not declined and the patients who had mandatory transfer of one embryo had a fresh live birth rate of 64.4% and a total reproductive potential rate of over 80% with a multiple birth rate of 3.4%.[70] It should be noted, however, that since SET was recommended for only a selected group of patients, the clinic's overall rate of multiple delivery, though approximately half of what it had been before the policy, was still 18.3%.

The most difficult patients to move to SET are those of advanced age or poor prognosis in whom a substantial proportion of embryos will not implant. As stated previously, ASRM's recommended number to transfer for women over 38 years of age remains three to five on day 3 although it has been reduced to two to three on day 5.[27] Studies have reviewed cycle parameters that predict improved pregnancy rate in older patients and these generally include retrieval of more oocytes and availability of embryos for cryopreservation.[71–73] In patients with positive predictive factors, fewer embryos can be transferred to achieve pregnancy but it is rare to electively transfer a single embryo in this age group. Nevertheless, in one recent study of over 1200 fresh cycles to women 36–39 years of age, some received SET and some double embryo transfer with little difference in delivery rates between the groups.[74] Availability of embryos for freezing and good quality embryos improved delivery rates and when used for subsequent frozen cycles, the addition of frozen embryo transfer actually resulted in the SET group having higher cumulative delivery rates. More recently, Steinberg et al. assessed national CDC data and suggested that SET be encouraged for patients up to 37 years.[75] In another study of women aged 40–44 years, Niinimaki et al. found that even for these older patients, if carefully selected for SET, delivery rates comparable to those following transfer of two embryos are possible.[76] In all these studies, multiple birth rates in the SET groups were significantly lower than in the double embryo transfer groups, however, all studies selected their patients for SET. At this time, the only proposed strategies for those patients in this age group who do not meet such selection criteria are use of newer techniques, such as preimplantation screening and metabolomics mentioned above for embryo assessment.

Multiple other factors may enter into the adoption of SET. Patients have been shown to worry about program delivery rates and the ability of a clinic to cryopreserve their embryos but many also have a lack of knowledge about the value of SET.[77] Patient desire for twins and their lack of risk aversion to this outcome have also been mentioned.[78] Some patient concerns, as previously discussed, can be overcome by good live birth rates and a well designed education program[69] although it may be important to tailor the educational message to a patient's particular wishes and fears.[79] The method by which education is presented can also affect patient acceptance of SET and visual images such as those that can be presented on DVDs may be better than printed material in the form of brochures.[80] Nevertheless, education alone may not suffice and payment plans such as those that include all transfers from a single retrieval can help patients accept a single embryo in the first cycle.[81,82] Despite best efforts, some educational programs may not encourage patients in this direction.[83]

Some countries have made substantial progress in increasing SET usage. Japan, which preforms the greatest number of ART cycles of any country in the world,[84] provides an excellent example. Twin rates in Japan rose steadily from the 1980s until 2003 attributable to the increased use of ART over that time period.[85] These multiple pregnancy rates began to drop in 2004. Ooki demonstrated that increased use of SET resulted in the change in multiple birth rate from a high of close to 20% in the 1990s to a rate of approximately 5% in 2009.[86]

Some have suggested mandating the use of SET. Several European countries have legislated a reduction in embryo transfer number with a goal of reducing the number of multiples.[87–90] Sweden, for example, now has the highest proportion of SET cycles.[91] As discussed above, however, it is understood that SET is not universally optimal for use in all patients. Reduced implantation rates with increasing age is still a factor necessitating transfer of more than one embryo in older women if delivery rates are to remain at current levels.[87]

A few countries in Europe such as Germany, Switzerland and Austria have laws restricting the number of embryos inseminated and discarded as well as those transferred. Such laws, unfortunately, may not take age or prognosis into consideration and in some cases, they are so restrictive of clinic practice that they can effectively increase the number transferred and associated multiple birth rates.[91] In Germany, some restrictions result from the historical legacy of eugenics that translates into a hesitation to engage in embryo selection.[92] Other restrictions, as in the case of a 2004 Italian law, arise from moral or religious issues surrounding the implications of embryo discard. Whether these laws increase or decrease multiple delivery is still being debated. There is at least one report that the Italian law limiting insemination and transfer of excess embryos neither decreased pregnancy rate nor increased multiple birth rate; however, overall pregnancy rates both before and after the law went into effect were low in this study (~12–14% live birth rate for women aged <35 years) and this may have affected the accuracy of the analysis.[93] Turkey enacted legislation in 2010 that reduced the number transferred but did so in an age-sensitive manner with SET for women aged <35 years in their first or second cycle and two transferred for all others. A recent study on this case revealed only minor changes in pregnancy rate (live birth rate was not reported) with significant reduction in multiple birth rate.[94]

Laws that are prompted by an agenda of preventing embryo discard may not take pregnancy and live birth rates or even multiple birth rates into consideration. Enactment of such laws may result in fewer embryos transferred but might equally lead to practices such as the one at the program mentioned at the start of this article that was visited in 1984 that required transfer of 12 embryos in one cycle. Similarly, laws developed out of fear that we are choosing one embryo over another and thus deciding which will survive and which will be discarded can result in forbidding preimplantation genetic screening and other methods that might increase the use of SET.[92] The mixing of the embryo transfer debate with the debate on these volatile ethical issues may thus hurt rather than help the cause of reducing multiples. Such laws may even lead to higher multiple birth rates with higher risks. At the present time, many US states are considering legislation that could take us down this path. Time will tell the outcome of the debates over legislation of this sort, but laws developed in such an atmosphere must be considered with extreme caution when considering the effect on multiple birth; they are certainly no guarantee of improvement.