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Assisted Reproduction Techniques and Multiple Births
Table 2: Cumulative Pregnancy Rates—Single- versus
thawed embryo in this trial did not receive the transfer because
Double-embryo Transfer
the embryos did not survive the thaw. An assessment of a clinic’s
cryopreservation program is clearly crucial when contemplating
Assumptions for Analysis
elective SET.
Drop-out rate after each cycle 40%
Pregnancy rate—SET 25%
Extrapolation to the United States
Pregnancy rate—DET 25%
SET twin rate 2%
The results of studies such as that detailed above cannot be extrapolated
DET singleton rate 70%
to the situation in the US. Fertility treatment is expensive, and in the US
DET twin rate 29%
prospective parents usually foot most of the bill. This means that seeking
DET triplet rate 1%
invasive medical treatment for infertility is often the last option for the
SET = single-embryo transfer; DET = double-embryo transfer.
majority of couples in the US and, in consequence, the women seeking
infertility treatment are significantly older than in other parts of the
world. In addition, the infertility of these women is likely to be more
women, the benefit of the transfer of multiple embryos on pregnancy severe, as they will have been trying to get pregnant for a greater period
rates peaks at two. The average number of embryos transferred of time and will have already tried other less expensive options.
during ART procedures has dropped from around four across all This population is very different from that investigated in studies such as
age groups in 1995 to around 2.5 in women less than 35 years of the Scandinavian experience, and is not ideal for SET. This was
age and 3.5 in women aged 41–42 years in 2004. The result has quite clearly demonstrated in a more recent European study that found
been the avoidance of triplets without a significant drop in the that in unselected patients the pregnancy rate obtained with SET is half
overall pregnancy rate; however, there has been no real improvement that of DET.
13
in the incidence of twins, which remains at around 25%. Reducing
the rate of twinning would require a shift from double-embryo The recognition that multiple gestations are an undesirable outcome of
transfer (DET) toward elective single-embryo transfer (SET). Evaluating ART has led many countries to enact strict laws governing how many
the corresponding effect on pregnancy rates is vital.
9
embryos can be transferred per cycle. In the UK, for example, a maximum
of two embryos can be transferred in women under the age of 40 years.
Success Rates of Single-embryo Transfer In Belgium, SET is obligatory in good-prognosis patients. The result of this
A number of studies, mainly in Europe, have attempted to look at the policy is not only fewer multiple births, but also fewer live births per IVF
success rates of SET—with fresh embryos as well as with frozen–thawed cycle. Figures for 2000 indicate that in the US
1,2,14
—where there is no
embryos—versus DET. In summary, the studies indicate that high success federal legislation on the practice of assisted reproduction—31% of IVF
(i.e. delivery) rates in good-prognosis patients can be achieved with SET cycles led to babies being delivered compared with 19.4% in the UK and
if the transfer of an additional frozen–thawed embryo is included. 16.4% in the rest of Europe.
In a large (661-patient) multicenter trial in Scandinavia,
12
the aim was to Individualized Care
demonstrate equivalence of live birth rates between the two strategies. According to the American Society for Reproductive Medicine
A further hypothesis was that the multiple birth rate would be lower in (ASRM), elective SET is not appropriate clinical care for all patients. Its
the SET group. Women younger than 36 years who had at least two guidelines state: “Strict limitations on the number of embryos
good-quality embryos underwent either: transferred, as required by law in some countries, do not allow treatment
plans to be individualized after careful consideration of each patient’s
• transfer of a single fresh embryo and, if there was no live birth, own unique circumstances.” This means that the ultimate decision
subsequent transfer of a single frozen–thawed embryo; or remains with patients and physicians. However, while allowing for
individualization of patient care, this also means that the decision on
• a single transfer of two fresh embryos. how many embryos to transfer may be subject to bias such as economic
pressures and insurance circumstances. The US does transfer more
Pregnancy resulting in at least one live birth occurred in 42.9% of the embryos than Europe.
DET group compared with 38.8% of the SET group. Rates of multiple
births were 33.1 and 0.8%, respectively. The study showed that the Another necessary consideration is that while physicians regard multiple
live birth rate in the SET group was not substantially lower than in births as an unwanted outcome, not all patients do. In fact, for many
the DET group, although equivalence could not be declared according to patients the relative risk of having twins will be hugely offset by specific
the definition (the upper limit of the 95% confidence interval (CI) for the potential benefits. There is even a potential medical benefit from
difference in live birth rates should not be >10%). However, the multiple twinning: there is a distinct possibility that the delay in any second
birth rate was much lower in the SET group. The live birth rate after only conception may result in additional loss of fertility, with the net loss of a
fresh embryo transfer was, however, significantly lower in the SET group. potential second child.
The price of the higher live birth rate in the DET group was a high
multiple-birth rate. Typically, patients who seek IVF treatment are considered to be highly
motivated, and the general impression is that these patients end
It is important to note that 17% of the women eligible for a frozen– treatment only if they have become pregnant or run out of funds.
28 FERTILITY TREATMENT REVIEW
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