Best Practice & Research Clinical Obstetrics and Gynaecology xxx (xxxx) xxx

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Reduction of multiple pregnancy: Counselling

and techniques
Mercede Sebghati, MBBS, MRCP, Specialist Registrar, Obstetrics
& Gynaecology a,
Asma Khalil, MBBCh, MD, MRCOG,MSc (Epid), DFFP, Professor
of Fetal Medicine and Obstetrics a, b, c, *
a
Fetal Medicine Unit, St George's University Hospitals, Blackshaw Road, London, UK
b
Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University
of London, Cranmer Terrace, London, UK
c
Twins Trust Centre for Research and Clinical Excellence, UK

a b s t r a c t
Keywords:
Multiple pregnancy The incidence of multiple births has risen in the last few decades.
Fetal reduction This rise is mainly due to the widespread use of assisted repro-
Multifetal pregnancy reduction duction techniques mainly as a result of increasing maternal age at
Bipolar cord coagulation conception.
Radiofrequency ablation Twin and higher-order multiple pregnancies are associated with
Intra-fetal laser ablation
increased risk of perinatal, as well as maternal, mortality and
morbidity compared to singleton pregnancies. There can also be
psychosocial and socioeconomic implications for women and their
families. In this chapter, we aim to discuss the risks associated with
multiple pregnancies, the pros and cons of fetal reduction, the
current techniques used in clinical practice, and how to approach
counselling parents, enabling them to make informed decisions.
© 2020 Published by Elsevier Ltd.

* Corresponding author. Fetal Medicine Unit, St George's University of London, London, SW17 0RE, UK.
E-mail address: akhalil@sgul.ac.uk (A. Khalil).

https://doi.org/10.1016/j.bpobgyn.2020.06.013
1521-6934/© 2020 Published by Elsevier Ltd.

Please cite this article as: Sebghati M, Khalil A, Reduction of multiple pregnancy: Counselling and
techniques, Best Practice & Research Clinical Obstetrics and Gynaecology, https://doi.org/10.1016/
j.bpobgyn.2020.06.013
2 M. Sebghati, A. Khalil / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (xxxx) xxx

Multiple pregnancies and the associated risks

In 1980, 10 women per 1000 giving birth in England and Wales had multiple births, compared with
16.1 women per 1000 in 2015 [1,2]. Over the last thirty years, the incidence of multiple gestations has
risen, mainly as a result of assisted reproduction techniques, such as IVF, and use of ovulation induction
drugs, whose increased prevalence is a result of increasing maternal age at conception.
National guidelines have recommended reducing the number of embryos transferred, depending on
maternal age and number of IVF cycles [3]. Furthermore, controlled use of ovulation induction drugs
has been recommended to reduce the numbers of higher-order multiple pregnancies. Despite this,
mixed chorionicity higher-order multiples have continued to show a relative increase, likely secondary
to gonadotrophin use and embryo splitting [4,5].
Multiple pregnancies are associated with a significantly higher risk of perinatal mortality and
morbidity, preterm birth and an increased pregnancy risk of maternal complications such as hyper-
tensive disorders, gestational diabetes and postpartum haemorrhage [6]. Triplet, quadruplet and
higher-order multiple pregnancies present even higher risks than twin pregnancies [7].
Discordant fetal anomalies and selective growth restriction can give rise to a clinical dilemma in
the management of multiple pregnancies. Monochorionic specific complications such as twin-twin
transfusion syndrome (TTTS) and twin-anaemia-polycythaemia-sequence (TAPS) can pose added
complications to these pregnancies. Compared with singleton pregnancies, multiple pregnancies are
associated with an approximately five-fold increased risk of stillbirth and a seven-fold increased risk
of neonatal death. These adverse outcomes are primarily due to complications of prematurity [8,9].
These risks are further increased in higher-order multiples, with a third of triplets predicted to be
delivered before 32 weeks [10], giving rise to cerebral palsy, chronic lung disease, developmental
delay and death [8].
Multiple pregnancies are also associated with social, financial and economic implications for the
parents, with higher levels of stress, poor quality of life and higher divorce rates observed in parents of
multiples [11e13].

Multifetal pregnancy reduction

Multifetal pregnancy reduction is a procedure that reduces the total number of fetuses by one or
more in a multiple pregnancy. Over the past 25 years, data from around the world have shown that
pregnancy outcomes are improved by reducing the number of fetuses in multiples [14].
Fetal reduction can also ameliorate the socio-economic challenges of multiple pregnancies for
families. Patient choice may be guided by their socio-economic status, medical history, fertility, parity
and fetal well-being.
Selective termination applies to those pregnancies affected by discordant fetal anomalies, or with
severe fetal growth restriction, with the aim to improve the prognosis of the normal fetus [15]. Table 1
outlines the indications for fetal reduction and selective termination.
A Cochrane review published in 2015 concluded that there are no randomised control trials to
inform the risks and benefits of fetal reduction procedures in multiple pregnancies. It is important to
highlight that the current available evidence is drawn from non-randomised studies, which can be
associated with the risk of bias [16].

Table 1
Indications for multifetal reduction/selective termination.

Indications for multifetal reduction/selective termination

Uncomplicated triplet/quadruplet or higher-order multiple pregnancy

Discordant anomaly or aneuploidy
Advanced twin to twin transfusion syndrome (Quintero stage IV)
Severe early onset selective fetal growth restriction
Twin reversed arterial perfusion
Advanced twin anaemia polycythaemia sequence (stage IV)

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Trichorionic triamniotic (TCTA) triplet pregnancy

Triplet pregnancies not only pose the dilemma of expectant management versus selective reduction,
but also whether these should be reduced to twins or singletons. A recent systematic review found that
fetal reduction in TCTA triplets to twins is associated with a significantly lower risk of preterm birth (17.3%
vs. 50.2% in expectant management) without significantly increasing the risk of miscarriage (8.1% vs.
7.4%) [17]. Chaveeva et al. in a retrospective study found that in TCTA triplet pregnancies, the rates of
miscarriage and preterm birth in those expectantly managed are approximately 3% and 35%, respectively,
compared to a higher rate of miscarriage and lower rate of preterm birth (7.3% and 13.1%) in those
reduced to twins. Those reduced to singletons had a further increase in miscarriage risk (11.5%), but a
further reduction in preterm birth (8.7%). Therefore, fetal reduction to twins or singletons progressively
reduces the rate of preterm birth but also progressively increases the risk of miscarriage [10] (Fig. 1).
A meta-analysis comparing the outcomes of 796 triplets that underwent reduction to twins and 899
expectantly managed triplets found that reduction was associated with delivery at a later gestational age,
a 60e70% reduction in early preterm delivery, reduction in neonatal mortality, higher birthweight, lower
incidence of hypertensive disorders of pregnancy, lower rates of antenatal hospitalisation and lower rates
of Caesarean delivery. It is generally accepted that multifetal pregnancy reduction of triplet pregnancies
to twins results in improved pregnancy outcomes when compared with non-reduced triplets [18].

Dichorionic triamniotic triplet pregnancies

Dichorionic Triamniotic (DCTA) triplet pregnancies are complicated by a monochorionic pair, which
not only carry extra risks of monochorionic specific complications but can also give rise to technical
challenges during selective reduction/termination. Morlando et al. concluded that conservatively
managed DCTA triplets carried a miscarriage risk of 8.9%, and a third suffered from early preterm
delivery. Reduction of the monochorionic pair increased the miscarriage rate to 14.5% but reduced the
preterm delivery rate to 5.5%. Reduction of one of the monochorionic twins or the triplet with the
separate placenta yielded a miscarriage and preterm birth rate of 8.8% and 11.8%, and 23.5% and 17.6%,
respectively [19]. Chaveeva et al. found that the rate of miscarriage increased with the number of fe-
tuses reduced (9% expectant, 13% reduction to 2, 17% reduction to 1), but the rate of preterm birth
decreased with the number of fetuses reduced (67% expectant, 13% reduction to 2, 9% reduction to 1), as
demonstrated in Fig. 1 [10].

Monochorionic triplet pregnancies

Monochorionic triamniotic (MCTA) and monochorionic monoamniotic (MCMA) triplets are

exceedingly rare. TTTS, TAPS, selective fetal growth restriction, and fetal loss often complicate these
pregnancies. Due to the rarity of the condition, very limited literature is available for these pregnancies.

Fig. 1. Risk of miscarriage and preterm birth following embryo reduction in triplets according to chorionicity and number of fetuses
reduced.

Please cite this article as: Sebghati M, Khalil A, Reduction of multiple pregnancy: Counselling and
techniques, Best Practice & Research Clinical Obstetrics and Gynaecology, https://doi.org/10.1016/
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One study reported the outcomes of selective fetal reduction in MCTA pregnancies but included
only two such pregnancies. Both underwent radiofrequency ablation to two fetuses at 13 weeks'
gestation and resulted in live births at 36 and 38 weeks’ gestation [20].

Twin pregnancies

As compared with singleton pregnancies, twin pregnancies are associated with a significantly
higher risk of perinatal, as well as maternal, mortality and morbidity. Selective reduction/termination
can be offered and considered in the presence of obstetric or maternal indications, such as discordant
fetal anomaly, severe selective fetal growth restriction, advanced TAPS or TTTS stage or severe maternal
cardiac disease. Fetal reduction of twins in the absence of obstetric or maternal indications remains
controversial. In the presence of maternal request for psychological or social reasons, adequate
counselling should be offered regarding the risks and benefits of the procedure [21] with consideration
given to the short and long-term psychological impact.
Vieira et al. compared the outcomes and loss rates in dichorionic twin pregnancy following selective
reduction with those managed expectantly. The researchers have concluded that the twin pregnancies
which were reduced had a higher gestational age at delivery and lower rates of preterm birth and
pregnancy complications, without an increased risk of pregnancy loss. Additionally, the risks of having
Caesarean delivery, pre-eclampsia, preterm premature rupture of membranes (PPROM) and low
birthweight (less than the fifth and tenth percentiles) were found to be lower in the twin pregnancies
reduced to singletons compared to ongoing twins (Fig. 2) [22].
Similarly, Gupta et al. found a decreased rate of preterm birth (10% vs. 43%, p < 0.001) and small for
gestational age fetuses (23% vs. 49%, p < 0.001) in those reduced to singletons. However, they did not
find a significant difference in preterm birth less than 34 weeks [23].

Fetal reduction e the procedure

Clinicians should be familiar with local and national guidelines and legal requirements, as well as
the risks and benefits of selective reduction versus expectant management [21]. Multiple methods
have been reported for fetal reduction in multiple pregnancies, which is determined by the chorio-
nicity, and the expertise of the clinician. Determining the chorionicity is therefore crucial and is best
established in the first trimester by ultrasound examination.

Fig. 2. Pregnancy outcomes and loss rates following elective twin pregnancy reduction.

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Fetal reduction is commonly performed at 12e13 weeks’ gestation. This will allow time for most
spontaneous miscarriages to occur and for first trimester ultrasound to be performed in order to rule
out major fetal abnormalities, observe for markers of aneuploidy (such as increased nuchal trans-
lucency) and calculate the risk of common chromosomal abnormalities.
An assessment of fetal anatomy of all fetuses is undertaken prior to the procedure in order to identify
obvious structural abnormalities or markers of aneuploidy. By the end of the first trimester, many major
fetal anomalies can be detected [24]; however, some anomalies are only apparent following the second
trimester scan. Prenatal testing in the form of amniocentesis or CVS can be performed when a genetic
condition is suspected. Correct sampling and labelling of fetuses is paramount, and diagnostic error due
to incorrect matching of genetic test results with the fetus, or sampling error has been reported in
0.6e0.8% of twins and up to 1.2% of higher-order multiple gestations [25].

Timing of fetal reduction

The timing of selective reduction in twin pregnancy influences the risk of miscarriage and/or
preterm birth. Fetal reduction in the second trimester carries a higher rate of miscarriage and preterm
birth (7% and 14%, respectively), compared to the first trimester. Women who are diagnosed with a fetal
anomaly following the second trimester scan can be given the option of a selective reduction in the
third trimester, if the law permits, to reduce the risk of losing the entire pregnancy [26]. The pros and
cons of each option should be considered (prematurity, loss rate, parental stress, availability of a fetal
medicine specialist to perform the procedure in the event of preterm labour, and risk of complications
associated with the specific anomaly).
One study compared cases of selective reduction in dichorionic twin pregnancies performed be-
tween 11 and 14 weeks of gestation with those performed between 15 and 23 weeks. This study
concluded that second trimester reduction of twins is associated with an increased rate of prematurity
compared to late first trimester fetal reduction [27].

The procedure

Fetuses with features of aneuploidy or those with a significantly smaller crown-rump length (CRL)
are preferentially chosen for selective reduction. In the case where all fetuses appear structurally
normal, the decision is generally based on the technical aspect of reduction with the most accessible
fetus, which is closest to the anterior abdominal wall or furthest from the cervix.

Intra-thoracic potassium chloride

In pregnancies not complicated by monochorionicity, selective feticide is performed by an intra-

thoracic or intra-cardiac injection of potassium chloride, under ultrasound guidance. Fetal asystole is
usually confirmed within 1 min of injection. Ultrasound examination is performed after the procedure
to confirm the presence of cardiac activity in the remaining fetus/fetuses. This has a 99.5e100% success
rate with minimal maternal complications [28]. Following the procedure, a degree of cramping or
leaking of amniotic fluid from the sac of the reduced fetus can be expected; however, vaginal bleeding
is uncommon and therefore patients should be advised to flag any bleeding which requires clinical
assessment in view of the potential procedure-related risk of miscarriage.

Selective reduction in monochorionic pregnancies

In monochorionic pregnancies, the placenta has various vascular anastomoses that may give rise to
twin-to-twin transfusion syndrome (TTTS) and which are responsible for acute inter-fetal transfusions
that occur when one twin dies in utero. Neurological injury to the surviving co-twin is believed to occur
when it suffers acute severe hypotension when blood is shunted into the dying twin through placental
anastomoses. The resulting cerebral hypoperfusion and hypoxia can subsequently cause a spectrum of
cerebral injury [29]. In monochorionic pregnancies, therefore, the use of intra-thoracic injection of
potassium chloride is contraindicated.

Please cite this article as: Sebghati M, Khalil A, Reduction of multiple pregnancy: Counselling and
techniques, Best Practice & Research Clinical Obstetrics and Gynaecology, https://doi.org/10.1016/
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Other techniques of fetal reduction which can be performed in monochorionic gestations are dis-
cussed below. Unlike fetal reduction in dichorionic twin pregnancies, selective termination in mono-
chorionic pregnancies requires ablation of blood flow in the umbilical cord to prevent an acute inter-
twin transfusion [29].

Bipolar cord coagulation (BPC)

Ultrasound guided Bipolar cord coagulation is commonly performed, where a 10-F disposable trocar
is inserted into the amniotic sac of the targeted fetus (Fig. 3). Cord occlusion is achieved using 3 mm
bipolar forceps under continuous ultrasound guidance. The umbilical cord is grasped with bipolar
forceps, and coagulation is performed for 30 s at a power setting of 30e50 W. Cessation of blood flow is
confirmed using Colour Doppler after the procedure [30]. The survival rate of the co-twin is approx-
imately 80%, and the risk of premature rupture of the membranes and preterm birth prior to 32 weeks
is 20% [31].

Radiofrequency ablation (RFA)

Radiofrequency Ablation (RFA) involves generating changes in alternating current at very high
frequencies (200e1200 kHz) between the tines of a needle. As the electrical current alternates in
various directions between the tines, tissue ions become agitated as they attempt to align with the
electrical field. Frictional heat is then produced, resulting in very high tissue temperatures that cause
tissue coagulation and necrosis.
A 17-gauge radiofrequency needle is inserted percutaneously under continuous ultrasound guid-
ance into the intrafetal portion of the umbilical cord (Fig. 4). Once the position is confirmed, all three
tines are applied, and radiofrequency energy is used to generate an average temperature of 110 Celsius
in all three times for 3 min [32].
One study compared the outcomes of RFA and BPC methods for selective reduction in complicated
monochorionic (MC) twin gestations. They concluded that both methods were equal in terms of the
overall survival of the remaining twin and of the rate of adverse perinatal outcome [31].

Fetoscopic and intrafetal laser ablation

Intrafetal laser is a relatively new technique described in 2014, which has been used in mono-
chorionic pregnancies and involves ultrasound guided laser ablation of the pelvic vessels of one of the
monochorionic fetuses (see Fig. 5). Following Ultrasound assessment, a transverse section of the lower

Fig. 3. Bipolar cord coagulation using bipolar forceps.

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Fig. 4. Radiofrequency ablation technique.

fetal abdomen is obtained, and colour flow Doppler is used to visualize the internal iliac arteries and
intra-abdominal umbilical vein. Local anaesthesia is administered to the maternal skin, subcutaneous
tissues and myometrium. An 18-gauge needle is introduced to the fetal abdomen with the tip being
adjacent to the pelvic vessels (Figs. 6 and 7) A laser fibre is then inserted into the needle and advanced
to a couple of millimetres beyond the tip of the needle. Laser coagulation is performed. This subse-
quently results in hyperechogenicity of tissues in the lower abdomen and cessation of blood flow in the
iliac arteries and umbilical vein. Fetal heart activity continues for several minutes. After a period of rest
for about 60 min, a further ultrasound examination is carried out to confirm the death of one mono-
chorionic twin and survival of the other fetus (es). This technique has a co-twin death rate of 46%
within 2 weeks following the procedure, likely secondary to bleeding into the placenta of the dead
fetus [33].

Fig. 5. Intrafetal laser ablation.

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Fig. 6. Intrafetal laser ablation displaying the insertion of the needle into the pelvic vessels.

Fig. 7. Laser ablation of pelvic vessels.

Novel techniques

Microwave ablation (MWA) is a novel approach in fetal procedures. Two cases of mono-
chorionic diamniotic twins have been reported in the literature that underwent MWA for se-
lective fetal reduction. MWA was used to deliver energy through a coaxial antenna. The antenna
was centred in the abdomen of the abnormal fetus close to the insertion of the umbilical cord,
and single microwave energy application was delivered. In both cases, MWA was technically easy,
and ultrasound evidence of tissue coagulation was seen immediately after the beginning of en-
ergy delivery [34].
High intensity focused ultrasound aims to bring a non-invasive technique into fetal therapy. Tar-
geted ultrasound energy is transmitted through the abdominal wall and uterus through a transducer

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placed on the women's abdomen to cause vessel occlusion. Currently, this method is limited to very
small numbers of TRAP sequence and TTTS cases; however, due to a high number of incomplete
vascular occlusions, it has not yet been proven to be superior to other methods [35].

Ethics of patient counselling

The management of multiple pregnancies can be challenging. Non-directive patient counselling

should be offered to all women with higher-order multiple pregnancies and should include a discus-
sion of the risks unique to the pregnancy, the option to continue or reduce the pregnancy, and the likely
implications for each option. Resources for providing such counselling can include maternalefetal
medicine specialists, neonatologists, mental health professionals, child development specialists, sup-
port groups and clinicians with procedural expertise in multi-fetal pregnancy reduction. Informed
consent should be obtained by fully discussing risks and benefits associated with any intervention
versus risks and benefits of expectant management.
Obstetricians should respect patients’ autonomy regarding whether to continue or reduce a multi-
fetal pregnancy. Only the patient can weigh the relative importance of the medical, ethical, religious
and socioeconomic factors and determine the best course of action for her unique situation [21].
Patients being counselled regarding multifetal pregnancy reduction should be made aware of the
possibility of prenatal testing for aneuploidy and genetic anomalies before the reduction is performed.
The results of such tests may assist patients in making their decisions.

Summary

Readily available use of assisted reproduction techniques and ovulation induction drugs in the last
few decades has led to a rise in the number of twin and higher-order multiple pregnancies. Multiple
pregnancies are associated with higher risks of maternal complications as well as preterm birth and
disability associated with prematurity. Risks of multiple pregnancies to both the mother and fetuses
should be discussed as soon as possible, and the options of conservative management or reduction of
one or more fetuses along with the risks and benefits of both options should be discussed. Women
should be supported in making an informed decision. The technique employed to perform fetal
reduction depends on the chorionicity, the level of expertise and availability of equipment in the
clinical setting. The timing of selective termination in twin pregnancy influences the risk of miscarriage
and/or preterm birth.

Practice points

 Multiple pregnancies are associated with a higher risk of perinatal morbidity and mortality
compared to singleton pregnancies
 Twin pregnancies with discordant fetal anomaly or discordant growth restriction as well as
higher-order multiple pregnancies should be referred to a fetal medicine unit
 Patients should be counselled regarding the risks associated with multiple pregnancies,
options available to them and the risks and benefits of each option
 Fetal reduction is performed with the aim of improving pregnancy outcome for the remaining
fetus (es)
 In dichorionic twin pregnancy, selective feticide is performed by ultrasound-guided intra-
cardiac or intrafunicular injection of potassium chloride or lignocaine, preferably in the first
trimester
 Selective feticide in monochorionic twins can be performed by cord occlusion, intrafetal laser
ablation or radiofrequency ablation (RFA)
 Non-directive patient counselling should be offered to all women with higher-order multifetal
pregnancies and should include a discussion of the risks unique to multifetal pregnancy as
well as the option to continue or reduce the pregnancy

Please cite this article as: Sebghati M, Khalil A, Reduction of multiple pregnancy: Counselling and
techniques, Best Practice & Research Clinical Obstetrics and Gynaecology, https://doi.org/10.1016/
j.bpobgyn.2020.06.013
10 M. Sebghati, A. Khalil / Best Practice & Research Clinical Obstetrics and Gynaecology xxx (xxxx) xxx

Research agenda

 Data from randomised controlled trials informing risks and benefits of fetal reduction pro-
cedures in multiple pregnancies
 Research into psychological sequelae in parents undergoing multifetal reduction
 Future comparative studies into outcomes of each fetal reduction technique to determine
which method is associated with the best pregnancy outcome

Declaration of competing interest

The authors have no conflicts of interest.

Acknowledgements

We thank Miss Morvarid Zadehkoochak for her contribution of creating the illustrations.

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techniques, Best Practice & Research Clinical Obstetrics and Gynaecology, https://doi.org/10.1016/
j.bpobgyn.2020.06.013
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Please cite this article as: Sebghati M, Khalil A, Reduction of multiple pregnancy: Counselling and
techniques, Best Practice & Research Clinical Obstetrics and Gynaecology, https://doi.org/10.1016/
j.bpobgyn.2020.06.013