Seminars in Fetal & Neonatal Medicine 15 (2010) 306e312

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Seminars in Fetal & Neonatal Medicine

journal homepage: www.elsevier.com/locate/siny

Epidemiology of multiple pregnancy and the effect of assisted conception

Mairead Black*, Siladitya Bhattacharya
Department of Obstetrics & Gynaecology, University of Aberdeen, School of Medicine, Aberdeen Maternity Hospital, Aberdeen AB25 2ZL, UK

s u m m a r y
Keywords: Multiple pregnancy is one of the greatest perinatal challenges facing clinicians today. In a society of rising
Assisted reproductive technology expectations among fertility and maternity service users, the potential for adverse outcomes associated
Epidemiology
with multiple pregnancy is a source of concern. This article examines the impact of assisted conception
Fertility treatment
Maternal morbidity
on the incidence of multiple pregnancies and associated complications. It explores some of the reasons
Multiple pregnancy for the strong association between assisted reproductive technology and multiple pregnancies and
Perinatal morbidity and mortality suggests possible ways of addressing this continuing problem.
2010 Elsevier Ltd. All rights reserved.

1. Introduction assisted reproductive technology or ART implies any procedure

Between 1970 and 2003, twinning increased by 50% and triplets
by 400% in England and Wales,1 mirroring similar trends in the
USA.2 Higher maternal age has been a contributory factor, but it is
the liberal use of assisted reproduction technology (ART) which is
responsible for this rise in multiple pregnancy rates. ART relies on
ovarian stimulation3 to produce multifollicular ovulation and
replacement of multiple embryos is common following in-vitro
fertilisation (IVF). The need to maximise treatment success has led
to a culture of acceptance of multiple pregnancies, including high
order multiples. The rise in ART-related multiple births, including
a high proportion of preterm deliveries, has led to an increased
demand for intensive neonatal care services resulting in consider-
able unease among clinicians, funders and regulators.4
National guidance on reducing the number of IVF embryos from
three to two has led to a reduction in triplet pregnancies in the
UK,5,6 and encouraged future efforts to promote single embryo
transfer (SET) in order to reduce twin rates.7 Given that countries
such as Belgium and Sweden have beneted from an elective SET
strategy,8,9 the case for actively preventing multiple pregnancies in
ART has been the subject of enthusiastic debate in recent years.10e12
An electronic search using Ovid MEDLINE (from 1950) was
conducted to identify relevant published literature in the English
language. Reference lists of identied studies and review articles
were checked for cross-references. The latest search was done on
14 April 2010, using multiple pregnancy, twin, high-order,
trend, prevention, fertility treatment and articial reproductive
technology as search terms. Throughout this article, the term
* Corresponding author. Tel.: 44 01224 550590; fax: 44 01224 559948.
E-mail address: mairead.black@abdn.ac.uk (M. Black).
involving ovarian stimulation and/or IVF, unless stated otherwise;
twins imply dizygotic twins, unless specied otherwise.
The aim of this review is to describe trends in twin and higher
order multiple pregnancies, discuss the inuence of fertility treat-
ment on multiples, outline the risks associated with multiple
pregnancy and consider strategies for reducing multiples in ART.13
2. Trends in multiple pregnancy
Time trends in multiple pregnancy tell a remarkable story of
changes in reproductive behaviour and their consequences. Early
records from Sweden suggest that rates of multiple pregnancy in
the late 18th century were higher than those seen today, peaking at
17 per 1000 maternities.14 During the 20th century, twin preg-
nancies appeared to be in decline until the early 1970s,15 but the
last three decades have seen a reversal in this trend.16 On the other
hand, the incidence of high order multiples has remained constant
during most of the 20th century, showing a clear rise1 from the
early 1980s. Recent data on multiple pregnancy rates in the UK
report a current rate of 15.5 per 1000 maternities or 1.5% (Fig. 1).13
In the USA, multiple birth rates in 1999 were approximately 30
per 1000 birth births, having doubled over a 20 year period
(Fig. 2).17 More recent data suggestive an ongoing increase with
rates of 32 per 1000 in 2006.18 While the rates of both twin and
higher order multiple pregnancies have increased with ART use, it
is the latter which has seen the steepest rise in the last four decades
(Fig. 3). From 1972 until 1999, the rate of triplet births increased 6-
fold and quadruplets 12-fold,19 with the former rising 50-fold in
women aged >44 years. The difference between US and European
multiple pregnancy rates is explained by differences in the way
fertility treatments are delivered.

1744-165X/$ e see front matter 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.siny.2010.06.004
 M. Black, S. Bhattacharya / Seminars in Fetal & Neonatal Medicine 15 (2010) 306e312 307

Multiples per 1000 maternities - England and Wales Triplet Birth Rates
16
180
14

12 160

Num ber per 100,000 m aterni ti es

10 140

8 All Multiples per 1000 maternities

120
6 England and Wales
100
4 US
80 Finland
2
60
0
1938
1942
1946
1950
1954
1958
1962

1966
1970
1974
1978
1983

1987
1991
1995
1999
2003
40

20
Figure 1. Rate of all multiple births in England and Wales per 1000 maternities since
1938.1 0
86-90 91-95 96-2000 01-'05

Between 1998 and 2001, triplet and higher order multiple birth Figure 3. Graph of changes in higher order birth rates globally. Data from Simmons
et al.5 (England and Wales; includes higher order multiples), Russell et al.17 and Martin
rates in England and Wales fell by 25%, a substantial fall in such
et al.18 (USA), and Perinatal Statistics in the Nordic Countries; Multiple births 1975e2006
a short time.5 This was thought to reect guidance set out by the (2009) (Finland).
Human Fertilisation and Embryology Authority (HFEA) limiting the
number of embryos transferred during IVF in women aged <40
years from three to two.20 The twin rate continued to rise during maternal age is evident in that 62% of all multiple pregnancies were
this period but at a slower rate (Fig. 3).1 born to women aged >30 years in 2008 compared with 51% in
1938.13 In the USA, these age-related changes were also noted, with
increase in maternal age being thought to contribute to a 10% rise in
2.1. Effect of maternal age spontaneous high order multiples from 1971 to 1997 (Fig. 4).24

The association between advanced maternal age and sponta- 2.2. Iatrogenic inuences
neous dizygous twinning has been shown to be strongest at 37
years.21 The decline in multiple pregnancies seen in the early 1970s Around 1.5% of all UK births are due to either IVF or donor
was probably a reection of the relative youth of the mothers insemination.25 The proportion of births in the UK due to non-IVF
involved.22 Although higher maternal age is associated with fertility treatment involving controlled ovarian stimulation is more
reduced fertility, the recent trend towards delaying planned preg- difcult to quantify, as these data are not collected nationally. The
nancies has not prevented the total fertility rate in England and number of babies born in the UK following IVF rose by 8% between
Wales from rising to 1.97 pregnancies per woman between 2001 2006 and 2007. In 2007 almost 37,000 IVF cycles were performed in
and 2008.13 The number of live births in women aged >40 years has the UK with an overall live birth rate of 23.7% and a multiple birth
doubled compared to those in the previous decade (Fig. 3).13 The rate of 23%.26
average maternal age in 2007 was 29.3 compared to 26.3 in married In the USA, almost 55,000 infants were born following 138 198
women in 1970.23 The combined effect of delayed child-bearing IVF procedures in 2006, giving a live birth rate of 36%, with 31%
and high uptake of fertility treatment at relatively advanced being multiple pregnancies.27 In 1991, 22% of all US high order
multiple pregnancies resulted from ART, rising to 38.7% in 1996.
Extrapolating from these data, it would appear that >50% of all
Multiple rate/ 1000 maternity
40
Multiple Births per 1000 Maternities - England and
35 Wales
Multiple Pregnancy/ 1000

30
80
25 England and Wales 70
per 1000 births

60
20 US 50
15 40
Australia
30
10 20
Czech
5 Republic(twins) 10
Finland 0
0
38
42
46
50
54
58
62
66
70
74
78
83
87
91

95
99
03

1970- 1980- 1990- 2000-

19

19
19
19
19
19
19
19
19
19
19
19
19
19
19
19
20

1979 1989 1999 2008 Year

Decades
Age of mother at birth - Under 20 Age of mother at birth - 20-24
Figure 2. Changes in multiple birth rates (all modes of conception) internationally. Age of mother at birth - 25-29 Age of mother at birth - 30-34
Data from Ofce for National Statistics13 (England and Wales), Russell et al.17 and Age of mother at birth - 35-39 Age of mother at birth - 40-44
Martin et al.18 (USA), Imaizumi30 (Czech Republic and Slovakia); Births, Australia, Age of mother at birth - 45 and over
Australian Bureau of Statistics, Report No. 3301.0 (2008) and 3301.46 (1999) (Australia);
Perinatal Statistics in the Nordic Countries; Multiple births 1975e2006 National Institute Figure 4. Multiple pregnancy rates according to maternal age categories in England
for Health and Welfare (2009) (Finland). and Wales since 1938.1
308 M. Black, S. Bhattacharya / Seminars in Fetal & Neonatal Medicine 15 (2010) 306e312
ART-conceived offspring are born as multiples.28 Ovulation stimu-
lation without IVF, used as treatment of ovulatory disorders or in
conjunction with intrauterine insemination (IUI) for a variety of
causes of infertility, contributed a steady 40% of all high order
multiple pregnancies in the USA throughout the early 1990s.24
Data on ART use collected by the European Society of Human
Reproduction and Embryology (ESHRE) demonstrate huge Europe-
wide variations in multiple pregnancy rates.29 Overall, the inci-
dence of IVF/intracytoplasmic sperm injection (ICSI) multiple
pregnancies have decreased from 22.7% in 2004 to 21.8% in 2005.
The Czech Republic reported the highest proportions, with 10% of
all IVF births being triplets and 1.5% quadruplets in 1997. Previously
it had been one of the few countries to remain relatively unaffected
by the impact of ART, with stable multiple birth rates over the
preceding two decades.30 Greece also reported a high incidence of
higher order multiple pregnancies following IVF, with 35.5% being
twins in 1997 and 24.8% in 2005. Their triplet proportion halved
during this time, from 2.7% to 1.3%. One likely explanation for this is
that the proportion of women receiving four or more embryos per
transfer fell from 42% to 15%, while transfer of single embryos
increased from 9.1% to 13.3%. Countries which have more recently
joined the ESHRE reporting system have demonstrated a remark-
ably high multiple pregnancy rate, including 5.7% triplets in Albania
and 33% twins in Lithuania in 2005, although the absolute numbers
of deliveries following IVF are still very small.29
In the USA, data since 1998 show that while the odds of high
order multiple births following ART (excluding ovulation induc-
tion) are decreasing, rise in the overall numbers of treatments
means that the absolute number of high order multiples has not
fallen. The Society for Assisted Reproductive Technology/American
Society for Reproductive Medicine guidance on transfers of two
rather than three embryos or more in IVF31 has resulted in an 8%
decrease in triplet rates since 1998, whereas twin births rates are
up by 65%.
Globally, a picture of ART events (excluding ovulation induction/
hyperstimulation) and success is drawn due to the International
Committee for Monitoring Assisted Reproductive Technologys
(ICMART) analysis of data from its member countries which are in
excess of 50. Its report in 2002 revealed overall twinning rates of
25% and triplet rates of 2.5%.32 It was also noted that whereas the
number of cycles sharply increased that year, delivery rates rose
only mildly, and a slight fall in number of embryos transferred per
cycle was complemented by a similar decline in multiple births.
2.3. Other inuences
Whereas maternal age and mode of conception have a signi-
cant effect on multiple pregnancy rates, other factors are also rec-
ognised to play a role in twinning.
Geographical and ethnic inuences on multiple pregnancy rates
have been reported.22,32 The latitude of a region can cause a varia-
tion of up to two-fold in twinning rates in the resident pop-
ulation.22 Nigeria had one of the highest dizygotic pregnancy rates
prior to the introduction of ART internationally.33 Dizygotic twin-
ning rates may also be inuenced by diet and endogamy.22
Although race appears to impact on multiple pregnancy rates, it
is unclear as to whether this is a reection of access or attitudes
towards fertility treatment.17 Both high parity and increased height
have been linked with multiple pregnancy, and while the reason for
this is not proven,22 higher circulating levels of FSH have been
suggested as an explanation.21 This is in keeping with the mecha-
nism thought to link higher maternal age with multiple pregnan-
cies. Maternal family history is also known to increase risk of
dizygotic twinning.34
3. Effect of multiple pregnancies on women
Maternal and perinatal complications of multiple pregnancy are
well-documented.35,36 The impact on maternal well-being may
receive minimal attention in the media, and as a result may be less
appreciated by would-be parents.
The physiological changes of pregnancy are exaggerated in
a multiple pregnancy, with hyperemesis and anaemia being
common problems.37
Maternal morbidity and mortality are increased in multiple
pregnancy. Thromboembolism, pre-eclampsia and obstetric hae-
morrhage, which are among the top ve causes of maternal death
in the UK, are all more common in women with multiple preg-
nancies.38,39 These women are at higher risk of miscarriage,
gestational diabetes, pre-eclampsia,37,40,41 operative vaginal
delivery and caesarean section.37 The overall relative risk of
maternal death is also higher in women with multiple pregnancies
as compared with those carrying singletons,42 although the abso-
lute risks are low in the developed world. Quality of life in parents
can be signicantly impaired following a multiple birth, when
compared with families of singletons.43 This is likely to be related to
higher levels of maternal emotional stress following births of twins
and triplets.44,45
4. Fetal risks of multiple pregnancy
Multiple pregnancy puts offspring at signicantly increased risk
of prematurity,46 particularly extreme prematurity (birth before 29
weeks gestation).35 The prognosis for these very preterm infants is
poor, with a very low chance of intact survival if born before 26
weeks.10,47 The risk of cerebral palsy in twins has been estimated at
four times that of singletons,48 and even moderate prematurity is
associated with long term educational49 and behavioural prob-
lems50 and infant death.51
Multiple gestations pose a number of unique challenges, such as
discordant growth abnormalities, intrauterine demise, preterm
premature rupture of the membranes, or premature delivery of one
or both twins.52 At a more complex level, multiples sharing a single
placental circulation are associated with additional problems in
their diagnosis and management, including twinetwin transfusion
syndrome. All measured adverse outcomes of pregnancy, including
mortality, are more likely in multiples compared with singleton
pregnancies, and associated risks increase in higher order multi-
ples.35 Due to the rarity of higher order pregnancies, it is perhaps
not surprising that twins have been found to contribute more to the
burden of prematurity and low birth weight babies than triplets.53
Low birth weight and prematurity are even more common
following ART.27
5. ART and multiple pregnancy
Multiple pregnancies following ART originate from pharmaco-
logical stimulation of the ovaries, with the aim of producing
multiple oocytes per cycle. Controlled ovarian stimulation is
combined with either IUI of prepared sperm or alternatively oocyte
retrieval and IVF. Although IVF was initially performed in natural
cycles without drugs, results were poor and there was a gradual
acceptance that higher numbers of oocytes and fertilised embryos
produced better pregnancy rates.54
Currently, treatment using non-IVF ovarian hyperstimulation
with or without concomitant IUI is associated with a greater risk of
high order multiple pregnancies than treatment with IVF.55
However, absolute numbers of multiple pregnancies are highest
following IVF,56 due to the much larger volume of IVF currently
offered. The contribution of each type of fertility treatment to
 M. Black, S. Bhattacharya / Seminars in Fetal & Neonatal Medicine 15 (2010) 306e312
multiple pregnancy rates has been estimated in the USA at 20% of
twins, 40% of triplets and 71% of quadruplets due to ovulation
induction; 16% of twins, 45% of triplets and 30% of quadruplets due
to IVF-related procedures.31 These data were collected following
the 1999 introduction of the revised SART/ASRM guidelines, rec-
ommending no more than two good quality embryos to be
transferred per IVF cycle in women aged >35 years, and if further
adequate embryos were available, they were to be frozen. Initial
data following this change in guidelines showed a slight decrease in
triplet and higher order pregnancy rate, whereas the twin rate
continued to rise.57
In relation to ovulation induction and IUI, women most at risk of
multiple pregnancy of high order are younger, those with seven or
more follicles, and those in the rst cycle of hyperstimulation.58 A
large case series of patients undergoing ovulation induction with or
without IUI revealed that those most likely to have a high order
pregnancy are those aged <32 years, highest total number of
follicles and highest peak estradiol levels on the day of human
chorionic gonadotrophin injection.59 Recent reports conrm that
age continues as a barrier to IVF success. In women using fresh
embryos from their own eggs, success rates of 45% in women aged
<35 years compares with 7% in those aged >42 years.60 Both live
birth rates and multiple pregnancies are less likely in women with
a longer duration of infertility, and with multiple previous attempts
at IVF.61
In the UK, a survey of all births during one week in 2003
revealed that of the multiple pregnancies following fertility treat-
ment, 16.7% resulted from clomiphene citrate (CC) therapy (7.3% of
all CC pregnancies), 5.6% from ovulation induction with IUI and
almost three-quarters from IVF (26% of all IVF/frozen embryo
transfer pregnancies).56
As may be expected, the vast majority of IVF twins are dizygotic,
resulting from two separately fertilised eggs. Background mono-
zygotic pregnancy occurs in 0.42% of the general population.62
Studies have shown a monochorionic rate of 2% in IVF twins28
and have suggested a slightly higher rate than expected naturally
following ovulation induction63 and IUI.64 Recently, the use of
blastocyst transfer in an attempt to improve embryo selection has
raised concerns regarding the possibility of increased monozygotic
pregnancies.65 Further study has suggested that no such increase
occurs.62 Ultimately, the majority of ART multiple pregnancies are
not at risk of the complications unique to those sharing a placental
circulation, including twinetwin transfusion syndrome. However,
by virtue of the requirement of assistance to conceive, these
pregnancies are to older women, who are more likely to have
comorbidities or a poor reproductive history.
After years of debate and gradual reduction in number of
embryos transferred as per national policies, Swedish guidelines
from the National Board of Health and Welfare nally changed in
2003 to state that elective SET should be the norm in IVF, unless
multiple pregnancy risk was thought to be low. In the year
following this policy change, when 67.4% of all embryos transferred
were single, multiple birth rates were lowered by more than two-
thirds to just 5.7% with a live birth rate which did not appear to
have been adversely affected.9
5.1. Risks of ART
Data on singleton pregnancies following ART have suggested
increased risk of prematurity, low birth weight,66 fetal malforma-
tion and cerebral palsy compared with those spontaneously con-
ceived.67e70 Research on the effect of ART itself on twin outcomes is
somewhat limited. For some time, results suggested that twins
conceived following IVF were less likely to encounter adverse
outcomes compared with spontaneously conceived twins.68 More
309
recent work suggests that this impression was merely due to the
protective effect of dizygosity, and that ART per se does not reduce
risk of adverse outcomes.71 A systematic review of the literature in
2005 concluded that overall risks were not signicantly increased
by mode of conception in twins72 whereas others have suggested
no overall increase in fetal abnormalities either.73
The risk of prematurity in IVF twins is higher than that of
spontaneous conceptions,28,74e76 particularly affecting delivery
before 32 weeks.75 Twins conceived through IVF or intra-Fallopian
gamete transfer are more likely to be of low birth weight than
spontaneously conceived twins,74 contrary to the ndings of
a previous study.77 A retrospective study of neonatal inpatient
admissions showed signicantly higher admission rates in ART
twins compared with spontaneous conceptions, along with
increased risk of perinatal death.74 The incidence of cerebral palsy
in ART twins is not signicantly different from that in spontane-
ously conceived twins.70 Higher rates of hospital admission and
their associated costs are cited as one of many economic reasons to
promote SET.78
A systematic review of neonatal outcomes following alternative
strategies for embryo transfer conrmed that transferring fewer
embryos resulted in increased birth weight and reduced prema-
turity.79 A retrospective study comparing perinatal outcomes
following SET and double embryo transfer (DET) revealed signi-
cantly reduced birth weight, increased preterm birth and stillbirth,
and a 10-fold increase in multiple pregnancy rates after DET.80
6. Economic implications
Multiple pregnancies generate higher health service costs than
singletons e mainly due to the need for more intensive antenatal
monitoring and higher risk of maternal and fetal complications.81
There is a high risk of operative delivery and the large proportion
of preterm deliveries generates signicant neonatal and infant
healthcare costs.82 Data from follow-up studies in ART-conceived
infants indicate that IVF multiples incur higher National Health
Service costs (compared with IVF singletons) at one year of age.83
With regards to preventative strategies, elective SET is more
cost-effective than DET in terms of costs during pregnancy84 as well
as up to six months postpartum.85 This is mainly related to the
increased costs of antenatal and peripartum care as well as
neonatal and post-neonatal costs in preterm multiples.
7. Limiting the complications and prevention of multiple
pregnancies
It can be argued that twin pregnancy is not necessarily an
undesirable outcome in the eyes of subfertile patients and some
fertility clinicians looking after them. Many who wish more than
one child may prefer to have twins rather than undergo multiple
ART attempts at additional cost.86 Yet, the compelling evidence for
increased maternal and perinatal risks associated with twins, as
well as concerns about long term handicap in ART-conceived
multiples, has prompted most practitioners to accept the fact that
there is an urgent need to prevent multiples in ART.95
High order multiple pregnancies commonly arise following
aggressive gonadotrophin stimulation of ovaries, with increased
follicle number and higher peak serum estradiol levels corre-
sponding with increased risk.87 Effective strategies to reduce the
incidence of multiple pregnancy associated with ART require
creation of, and strict adherence to, protocols within monitored and
legislated practice.
310 M. Black, S. Bhattacharya / Seminars in Fetal & Neonatal Medicine 15 (2010) 306e312
7.1. Prevention in IUI
Efforts to achieve unifollicular ovulation are crucial in anovu-
latory women treated with ovulation induction with or without IUI.
Strategies to do so may involve early cancellation of treatment
cycles if multiple follicles develop. In women with unexplained
infertility undergoing ovulation induction/IUI to further enhance
their chances of conception, the situation is more complex as these
women are ovulatory and the aim is to encourage more than one
follicle to grow. Care to ensure that no more than two follicles
develop, a low threshold for cycle cancellation, aspiration of excess
follicles prior to ovulation, or even conversion of the procedure to
IVF have been suggested. A cut-off of three pre-ovulatory follicles
had been recommended as an acceptable number in which high
order multiple pregnancy could be avoided88 but this cannot
reduce the incidence of twin or triplet pregnancy.61 The key
difference between IVF and ovulation induction/IUI is that in IVF,
the number of embryos transferred can be reduced in high risk
women in an attempt to reduce multiple pregnancy rates. There is
little opportunity to exercise the same degree of control in ovula-
tion induction/IUI87 and therefore less scope for limiting multiples.
7.2. Prevention in IVF
Where there is a choice of embryos, replacement of three
embryos instead of two results in an increased risk of triplets
without a signicant increase in live birth rates.61 Recent rando-
mised controlled trials comparing live birth and multiple preg-
nancy rates following SET versus DET conrm a reduction in live
birth rates per embryo replacement procedure but a virtual elimi-
nation of twins.89e92 The reduction in pregnancy rate associated
with eSET does not appear to persist following subsequent transfer
of a frozen embryo, so that cumulative pregnancy rates are not
signicantly less than those of DET.89,93 If carefully chosen, couples
at high risk of multiple pregnancy may therefore benet from
eSET.94
The lower live birth rate per transfer associated with eSET may
be mitigated by efforts to maximise chances of successful implan-
tation of a single embryo. These include transfer of cleavage-stage
embryos with good prognostic signs such as symmetric blastomere
sizes, absence of multinucleation and minimal cytoplasmic frag-
mentation.95 More recently the advantage of replacing a single
blastocyst has been recognised.96,97 This technique involves pro-
longed culture of embryos until day 5 or 6 before transfer e
signicantly longer than the traditional 2 or 3 days. Blastocyst
transfer is particularly successful in women with a number of good
quality embryos developing on day 3. Limitations of this strategy
include the fact that the process of self-selection can potentially
leave no embryos for transfer and fewer embryos for cryopreser-
vation.96 As eSET involves replacement of only one embryo,
ensuring availability of facilities for cryopreservation of spare
embryos potentially suitable for replacement in future cycles is
a vital part of the treatment process (see HFEA website).
8. Conclusion
Multiple pregnancy must be viewed as a complication of fertility
treatment. As the global twinning rates continue to rise primarily
due to use of ART, we are now seeing a slow decline in high order
multiple births. Although the risk of multiple birth may be highest
following ovulation induction or superovulation, actual numbers of
multiple pregnancy are higher following IVF due to the ever-
increasing number of treatment cycles performed. Clinicians and
patients should always be aware of the need for a dynamic
approach to these treatment cycles, adopting strategies to minimise
risk of multiple pregnancy, such as cycle cancellation during
ovulation induction. The opportunity for almost complete control
over risk of multiple pregnancy afforded by IVF should make this
procedure a major focus of future efforts to limit the extent of the
multiple pregnancy problem. In an attempt to make elective SET an
acceptable norm, integrating recent developments in improving
SET implantation rates, such as blastocyst culture, into everyday
practice may hold the key to securing a substantial reduction in
multiple pregnancies. Ongoing efforts to improve, extend and
implement ART legislation will play a vital role in ensuring
continued achievements in minimising high order multiple births,
but also to enable an eventual change in direction of twinning rates.
Unless widespread legally binding changes are made in favour of
elective SET, the onus will be on clinicians, fertility nurses, patient
groups, the HFEA and parties overseeing funding, to guide practice
in order that a long term reduction in multiple pregnancy rates may
be achieved. Further research to convince sceptics of its benets
will also play an important role.
Practice points
 Strict protocols aimed at minimising the risk of multiple
pregnancy in ART should be used.
 Elective SET including single blastocyst transfer should
be promoted in IVF.
 Ovulation induction in anovulatory women should aim
for monofollicular development.
 When used as part of IUI treatment, ovulation induction
cycles should be carefully monitored by ultrasound.
Cycle cancellation or conversion to IVF should be
considered in the presence of exaggerated ovarian
response.
Research directions
 True impact of non-IVF fertility treatment on multiple
pregnancy rates.
 Exploration of barriers to the uptake of SET.
 Effectiveness of IVF versus ovulation induction and IUI
in terms of optimising live birth and minimising
multiple birth.
 The use of financial or alternative incentives to
encourage SET.
 Economic benefits of alternative SET strategies.
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