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Home  Articles & Poetry Tell me some more about ....? Single Embryo Transfer
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Friday, 29 July 2005 |
Infertility Network UK have kindly allowed us to reproduce this article from the last issue of their magazine.
Should you wish to obtain future copies of the magazine then you can do
this by signing up for INUK membership at their website
www.infertilitynetworkuk.com
I would like to thanks Clare Brown and her team for her assistance with
this and also Siladitya Bhattacharya, Vanessa Sandison for producing
the article.
Tony.
Introduction
Many couples with unresolved fertility problems see IVF as their only
chance of having a family. Improved techniques have led to
increased success rates but the traditional practice of transferring
more than one embryo has remained unchanged. As a result, over half of
all babies born as a result of IVF are twins, triplets or higher order
multiples. Most clinics in the United Kingdom now replace 2 rather than
3 embryos at a time. While this has been effective in preventing
triplets the twin rate, at 25%, is still very high compared to a
natural incidence of 1.25%. This can lead to increased health risks for
mothers and babies.
Consequences of twin pregnancy
Advances in neonatal care have greatly reduced the risk of serious
complications in new born babies. Nevertheless, in comparison
with singletons, twins still face a six-fold increased risk of death
and permanent handicap due to cerebral palsy, chronic lung disease,
blindness, learning difficulties and behavioural disorders. Women
carrying twins are more prone to complications such as miscarriage,
high blood pressure, diabetes, premature labour, and abnormal delivery.
The resulting demands on the National Health Service are significant.
This has highlighted the need to develop a practical effective strategy
to minimise twin pregnancies.
Strategies for prevention of twins
Suggested options for the elimination of multiple pregnancies
include selective fetal reduction, single blastocyst transfer and
elective single embryo transfer (eSET). Selective fetal reduction
(reducing the number of fetuses in the womb) carries a risk of
miscarriage and poses serious ethical and legal questions. Blastocyst
transfer involves transferring fewer, but higher quality embryos which
have survived in culture up to the blastocyst stage (day 5). This
technique needs special expertise and cannot be routinely offered by
all laboratories. Failure to grow to blastocyst stage can limit the
number of embryos available for fresh and frozen transfers. A recent
analysis of all published studies has failed to show any advantage of
blastocyst transfer over conventional (day 2-3) transfer, in terms of
pregnancy rate per woman.
Elective single embryo transfer
The simplest and potentially most effective way of preventing twin
pregnancies is by choosing to replace a single embryo at a time. The
clear benefits of this strategy need to be weighed up against the
possible risk of lowering success rates. Initial studies in Belgium and
Scandinavia suggest that by using strict embryo selection criteria,
single embryo transfer can result in a pregnancy rate of 30% to 40% per
fresh treatment cycle and twin pregnancies virtually eliminated. The
outcome is enhanced by a policy of repeated transfer of thawed,
cryopreserved spare embryos leading to a cumulative pregnancy rate
comparable to that associated with DET (47% to 53%). The best way to
compare treatments is to compare them head to head in randomised
trials. These are research studies where the treatment used is selected
at random and thus evaluation is an unbiased one. In recent years a
number of randomised trials comparing single embryo transfer with
double embryo transfer have been published. Their results confirm that
single embryo transfer dramatically reduces the risk of multiple
pregnancy. Although live birth rates following a single fresh IVF
treatment are lower, subsequent replacement of a frozen embryo results
in a livebirth rate comparable with double embryo transfer. The largest
of these studies involved 661 Scandinavian women aged 36 years or less,
in their first or second cycle of IVF and possessing four or more good
quality embryos. Women were randomised to receive either: 1) 1 fresh
embryo followed by 1 frozen/thawed embryo or 2) 2 fresh embryos. The
live birth rate was 131/330 = 40% in the single embryo group and
144/331 = 44% in the double embryo group. There was a single twin
pregnancy in the single embryo group compared to 59 (36%) pregnancies
in the double embryo group. This trial showed clearly that a policy of
elective fresh and frozen SET produced live birth rates comparable to
those after double embryo transfer, but with a very low risk of
multiples. None of the trials done so far have assessed costs to the
patients or the National Health Service. More importantly, they have
not been done in an environment (such as the one in the United Kingdom)
where many couples pay for IVF. Crucially, patient acceptability has
not been evaluated.
Considerations before implementation of single embryo transfer
It is clear that in selected groups of women at risk of twins,
replacing embryos one at a time in fresh and subsequent frozen cycles
may be an effective way of eliminating multiple pregnancies without
lowering success rates. However, before clinics in the UK can consider
adopting a single embryo transfer policy, we need to consider a number
of issues. We need more data from large trials comparing livebirth
rates following replacement of all embryos (either one or two at a
time) produced from eggs collected at a single egg recovery procedure.
We also need more information about the cost per livebirth, including
costs of freezing and replacing single embryos, and patient costs. Most
importantly we do not have any data on couples' views on the
acceptability of the alternative strategies or whether in their view
single embryo transfer offers "value for money".
Any plans to move to single embryo transfer will have to tackle the
difficult issue of identifying accurate good quality embryos that have
the potential to develop into pregnancies. Treatment using single
embryo transfer is only in the presence of an and reliable embryo
freezing and thawing programme.
Single embryo transfer is not for all women. It should be reserved only
for women who are relatively young (under 38), in their first or second
IVF cycle and in possession of a number of good quality embryos.
Any decision to opt for single embryo transfer will be affected by
couples' views about potential success rates. At the moment, results of
treatment in IVF are conventionally expressed in terms of a live birth per fresh cycle,
while outcomes of subsequent frozen cycles are reported separately.
This underestimates the success of SET and may prove to be a deterrent
to couples and clinics. Expressing the outcome of treatment in terms of live birth per oocyte retrieval
may be more logical. This would include results after fresh and frozen
embryo transfer of all embryos created as a result of a single fresh
treatment cycle.
While clinicians may feel that a high twin rate in IVF is unacceptable,
couples may not share their views. Some women may actually see twins as
a desirable outcome. Others, who are paying for their treatment, may
see twins as a cost-effective option. Many are willing to take risks in
order to achieve this goal. This may be due, in part, to insufficient
information about the potential risks of a twin pregnancy.
Finances may also affect couples decisions. Those who are charged
either for multiple fresh IVF cycles (resulting in a transfer of the
single best embryo) or for freezing and thawing embryos may be
understandably reluctant to consider single embryo transfer. Elective
single embryo transfer has worked well in European settings where IVF
is subsidised. The existing system in the UK, whereby many couples pay
for IVF while the cost of neonatal care is free, is apt to discourage
couples from adopting a single embryo policy.
Legislation is a potent factor in changing practice in IVF. However, if
legislation is considered as the final step in implementing SET, this
will need to be backed up with adequate funding for multiple
treatments.
Conclusion
Twin pregnancies resulting from IVF treatment are associated with high
rates of complication for the mother and babies. There is now some
evidence to suggest that single embryo transfer, in selected women, can
eliminate twins without compromising success rates when combined with
effective methods of embryo selection and freezing. Single embryo
transfer is mainly confined to settings where financial support is
available and/or strict legislation enforced. More information from
large clinical trials are needed to demonstrate whether a policy of
single embryo transfer is effective, acceptable and financially viable
in other clinical settings.
Further reading
- ESHRE Campus Report. (2001) Prevention of twin pregnancies
after IVF/ICSI by single embryo transfer. Hum. Reprod., 16
(4): 790-800.
- Bergh T, Ericson A, Hillensjo T. et al (1999) Deliveries and
children born after in-vitro fertilisation in Sweden 1982-95: a
retrospective cohort study. Lancet., 354: 1579-1585.
- Pandian Z, Bhattacharya S, Ozturk O, Serour GI, Templeton A
(2004). Number of embryos for transfer following in-vitro fertilisation
or intra-cytoplasmic sperm injection (Cochrane Review). In: The
Cochrane Library, Issue 4, 2004. Chichester: Wiley.
- Thurin A, Hausken J, Hillensjo T, Jablonowska B, Pinborg A,
Strandell A, Bergh C.(2004) Elective single embryo transfer in IVF, a
randomized study. Abstracts of the 20th Annual meeting of the ESHRE,
Germany, June 2004., 0 -170: i60.
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