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| Journal of the New Zealand Medical Association,
01-April-2005, Vol 118 No 1212
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Responsible IVF treatment in New Zealand is the preferential
transfer of a single embryo
Andrew Murray, John Hutton, John Peek
In vitro
fertilisation (IVF) was first undertaken in New Zealand in 1983, 5 years after
the first IVF baby, Louise Brown, was born in England. Since then, IVF has
become an increasingly common treatment. The treatment has improved with better
drug regimens; simpler oocyte retrieval techniques; fertilisation by
intracytoplasmic sperm injection (ICSI); and better methods of culture,
cryopreservation and transfer of embryos.
Many factors affect the success of an IVF treatment
including particularly the number of embryos transferred, and whether these are
replaced fresh or after cryopreservation.1,2
In the early 1990s, before there were good cryopreservation
techniques, it was common to transfer three embryos (see Table 1). However, as
IVF became responsible for a significant proportion of triplet pregnancies, the
average number of embryos transferred fresh was reduced, particularly in
Northern Europe, Australia, and New Zealand (see Table 1). Even in 2001, one in
seven replacements were of three or more embryos, however this was usually in
the setting of repeated IVF failures or advanced maternal age.
Table 1. Number of fresh embryos replaced per transfer
in all Australian and New Zealand IVF
clinics3,4
As the number of treatments has increased, and the success
of IVF has improved, the impact of transferring even two embryos in a majority
of cycles has become more visible.
A comparison of the IVF births with all the births reported
in New Zealand for 1992 and for 2002 is shown in Table 2. Given the growth in
the number of treatments and current success rates, we estimate there will be,
in 2004, at least 100 IVF twin births in New Zealand, and these will represent
at least 10% of all twin pregnancies and births.
Table 2. Comparison of all births and IVF births in New
Zealand (NZ) in 1992 and
2000refs:3,5–7
*Estimate
based on combined Australian and New Zealand rates.
The second major factor affecting the success of IVF is the
age of the woman. Younger women who have two embryos replaced are more likely to
have twins than older women undergoing IVF—the numbers of all IVF births
and twin births from the transfer of two fresh embryos at the Fertility
Associates Ltd clinics in Auckland, Wellington, and Hamilton between 2000 and
2002 is shown in Table 3 according to the age of the woman.
Table 3. Number of transfers of two fresh embryos at
all Fertility Associates Ltd clinics between 2000 and 2002, and the consequent
number of total births (>20 weeks), and number of twin births
Outcome of twin pregnancies after IVFTwin pregnancies have long been
known to be associated with an increased risk of serious obstetric and perinatal
complications when compared with singleton
pregnancies.7 In addition, IVF singleton
pregnancies have more complications than naturally conceived singleton
pregnancies.8 Therefore, as expected, twins
born after IVF have a higher rate of complications compared to even natural
binovular twins.9–11
At National Women’s Hospital, Auckland, between 1996
and 2001, 126 of 1136 multiple births (11%) were conceived following
IVF—these pregnancies and births were all much more complicated than twin
pregnancies not associated with fertility treatment, and had poorer infant
outcomes.9
In comparison to singleton
births,12–15 the risks of complications
for either the mother or the infants of having IVF twins are generally always
increased—commonly three-fold but sometimes up ten-fold. The stillbirth
and neonatal death rates are increased at least three
times.16
A Swedish Register study
has found an increased risk of cerebral palsy in
children after assisted conception, mainly
because of the high rate of
twins17. IVF twins also cause more
stress for the mother.18
In a recent European study comparing IVF singleton
pregnancies and births with those of IVF twins, the medical cost per IVF twin
pregnancy was more than five times higher than per singleton pregnancy, at
€13,469 and €2,550,
respectively.19
Preliminary analysis of New Zealand data suggests a similar
differential between singleton and twin births (W Gillett, personal
communication, 2004). Thus, the additional hospital cost of the 100+ twin births
after IVF in New Zealand is currently estimated at >NZ$2,000,000 per annum.
There are also other non-hospital costs that continue, such as those for the
care of children with disabilities consequent upon being born
prematurely.
Single embryo transferTheoretically,
the only way to minimise the chance of a multiple pregnancy after IVF is to
always transfer only a single embryo. Unfortunately, there is no prospective
randomised study to compare the outcomes of single and double embryo
transfer—such a study involving some IVF units in Australia and New
Zealand was discontinued this year because of the difficulty in recruiting
adequate numbers of couples willing to be randomised between single and double
embryo transfer.
There are, however, several published retrospective studies
that demonstrate that multiple pregnancies can be significantly reduced by
transferring only a single embryo in selected populations without significantly
affecting the overall pregnancy
rate.20–23 In one study, despite an
increase of single embryo transfers from 11% to 56%, a relatively stable mean
pregnancy rate of 34.0% (range 28–42%) was maintained while the multiple
pregnancy rate was reduced from 25% to 7.5%.22
Thus, it was concluded that, in selected populations, a
single embryo transfer policy could be adopted without significantly affecting
the pregnancy rate. Interestingly, the mean birthweight of singleton births in
one study was significantly higher after single embryo transfer than with
singleton births after the transfer of two embryos—this suggests there may
even be superior implantation and developmental potential after a single embryo
transfer.23
Transferring only one embryo, rather than two, will usually
result in one more embryo being available for cryopreservation. When these extra
frozen embryos are subsequently thawed and transferred, the cumulative pregnancy
rate may approach that for double embryo transfer. We have modelled the chance
of pregnancy in women aged <36 yr who are having their first or second IVF
cycle with the assumption that the chance of pregnancy from a good quality
frozen embryo will be about half that of a fresh embryo.
The cumulative chance of pregnancy from one fresh embryo and
a second frozen embryo, if not pregnant with the fresh embryo, is 40% compared
to 48% if both embryos had been transferred fresh. The proportion of twin
deliveries would fall from 36% to under 2%. In the single embryo transfers, the
small incidence of twins arises from identical twins.
Selecting single embryo transferWhilst
the transfer of a single embryo is a theoretical solution to the problem of
multiple pregnancy; in practice, a woman’s age, and whether she has had a
pregnancy previously are factors which also need to be considered. An older age
at treatment, embryos of lower quality, nulliparity and previous unsuccessful
IVF attempts are not only associated with lower pregnancy rates, but also a
lower chance of multiple pregnancy (see Table 3).
Currently, in New Zealand, there is a strong preference to
transferring two embryos; and few women with two or more good quality embryos
elect to transfer a single embryo, and cryopreserve the others. One factor that
has been discouraging couples from electing the transfer of a single embryo has
been funding. Since late 2000, public funding of IVF in New Zealand has been
restricted to only one cycle in a couple’s lifetime, and consequently most
couples have chosen to have two embryos transferred. However, the Minister of
Health has recently announced the public funding of a second cycle of IVF for
those who do not become pregnant from their first cycle. The extra funding is
linked with introduction of a single embryo transfer policy in recognition of
the risks and costs of twins, and of improvements in IVF pregnancy rates that
make this feasible.
Broader social issuesAnecdotal observation and research
shows many infertile couples do not see any problem with having twins, and
indeed regard twins as a bonus for the completion of their family with one cycle
of IVF treatment.24
Women alter their dietary and social habits to minimise an
already small risk of handicap to their infant—such as by the addition of
a folate supplement and the avoidance of alcohol, smoking and caffeine—yet
they elect the transfer of two embryos, with, comparatively, a very high risk of
handicap, or other serious adverse outcome.
However, we acknowledge that lifestyle precautions are easy
and inexpensive, while reducing the perceived chance of pregnancy carries a high
opportunity cost. Although there is media publicity about the adverse outcomes
of IVF twin pregnancies, (such as Courtney Cox’s IVF twin pregnancy), more
education about the benefits of the transfer of a single embryo is
required.
The move to elective single embryo transfer has engendered
widespread debate on the best means of measuring success for IVF programmes. One
candidate is the birth of a single child at 37 weeks or more gestation
(BESST—Birth Emphasising Successful Singleton at
Term).25 Although measures such as BESST have
their shortcomings26,27, they do signal a new
era in IVF where improved pregnancy rates allow a growing focus on the quality
of a pregnancy, not just the chance of a pregnancy.
SummaryThe current data about IVF birth
outcomes suggests that responsible IVF in New Zealand now requires a policy of
selective single embryo transfer in higher risk groups to minimise the number of
twin births with their relatively high rate of complications for both mother,
infants, and society.
Author information:
Andrew Murray, Senior Lecturer, Department of Obstetrics and Gynaecology,
Wellington School of Medicine, University of Otago, Wellington (and Fertility
Associates Ltd, Wellington); John Hutton, Professor of Reproductive
Endocrinology and Infertility, Department of Obstetrics and Gynaecology,
Wellington School of Medicine, University of Otago, Wellington (and Fertility
Associates Ltd, Wellington); John Peek, Group Operations Manager, Fertility
Associates Ltd, Auckland
Correspondence:
Andrew Murray, Department of Obstetrics and Gynaecology, Wellington School of
Medicine, PO Box 7343, Wellington. Fax (04) 385 5943; email amurray@wnmeds.ac.nz
References:
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