Multifetal pregnancy reduction (MFPR)
MFPR refers to an intervention in which the number of fetuses in a
multifetal gestation is reduced by terminating one or more fetuses.
The first reports of MFPR came from France by Dumez and Oury in 1986
explaining first-trimester selective abortion for pregnancies involving
more than 3 fetuses, or an abnormal cotwin. 12 Evans
et al13 reported their MFPR experience and argued it
to be ethically justified because it met the criterion of least harm and
more potential good. Berkowitz14 and later
Wapner15 described a surgical approach to improve the
outcomes. Methods have included predominately transthoracic injection of
Potassium Chloride (KCl), but also transcervical embryo aspiration,
mechanical disruption of the fetus, air embolization, and
electrocautery.
American College of Obstetricians and Gynaecologists (ACOG) Committee
Opinion16 on MFPR recommends that obstetricians should
be knowledgeable about medical risks of multifetal pregnancy, potential
benefits of MFPR and complex ethical issues inherent in the decision for
reduction. Nondirective patient counseling should be offered to all
women with multifetal pregnancies by a multidisciplinary team including
maternal-fetal medicine specialists, neonatologists, child development
specialists, mental health professionals, etc. and informed consent
taken. Patient should be referred in time and without judgement to fetal
therapy center. Obstetrician should respect patients’ autonomy and that
”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.”
The consensus views arising from the 50th RCOG Study Group recommend
that selective reduction should be discussed in all higher-order
pregnancies.17 An International Federation of
Gynaecology and Obstetrics(FIGO) Committee Report18stated ”multiple pregnancy of an order of magnitude higher than twins
involves great danger for the woman’s health and also for her fetuses,
which are likely to be delivered prematurely with a high risk of either
dying or suffering damage” and ”where such pregnancies arise, it may be
considered ethically preferable to reduce the number of fetuses rather
than to do nothing”.
MFPR is performed between 11 and 14 weeks as the risk of spontaneous
reduction has by then passed19 and fetus are
sufficiently large to allow for the detection of gross structural
anomalies and markers of aneuploidy including thick nuchal translucency
or absent nasal bone to guide the selection of the fetus(es) for
reduction. Pregnancies conceived by IVF and ICSI are known to be
associated with a higher incidence of aneuploidy as well as structural
anomalies, some centers now offer routinely chorionic villous sampling
(CVS) before the MFPR. Evans20 reported about 85% of
their patients followed the protocol of CVS followed by MFPR the next
day. In pregnancies with sonographically normal fetuses, 3.1% of women
had a fetus with an abnormal karyotype. FISH detected 90% of aneuploidy
while the remaining 10%, virtually were confined placental mosaicisms
for other chromosomes.21
There are no absolute contraindications to MFPR, however, cases as a
mother with HIV or active hepatitis, extreme obesity with poor
visualization of the fetus warrant special consideration.
The fetus(es) selected for MFPR is generally the one that is most
accessible to needle insertion and furthest away from the cervix.
However, if a fetus has a structural anomaly, markers of aneuploidy or
lagging crown-rump length or a substantially smaller sac then that fetus
is preferentially chosen for reduction so as to leave behind apparently
healthy fetuses. Most commonly, the procedure is performed using a
transabdominal percutaneous technique under ultrasound guidance. A
transcervical or a transvaginal approach can be used if performed
before10 weeks or transabdominal route is not technically feasible.
However, recent studies have confirmed that these routes have been
associated with higher postprocedural pregnancy loss
rates.22
MFPR is performed most commonly by giving an intracardiac injection of
KCl (1.5 g in 10mL) into the targeted fetus using a 20 gauge needle
resulting in fetal asystole. Additional fetuses can be reduced by the
same puncture if next desired fetus is accessible or else a separate
second puncture may be required to complete the procedure. An ultrasound
examination is performed one hour after the procedure to confirm
asystole in the reduced fetus(es) and cardiac activity in the nonreduced
fetus(es).
A finishing number of two has become standard practice, as the perinatal
outcome of twin pregnancies is considered acceptable and it still leaves
an option of ST if discordant fetal abnormalities are detected at
mid-trimester scan later.
Data from observational studies23,24 show consistently
that perinatal and obstetric outcomes particularly preterm birth (PTB)
rates, improve significantly after MFPR. International Registry analysis
of 3513 patients undergoing MFPR, in 11 centers showed overall loss
rates were correlated strongly with starting and finishing numbers.
Stone et al24 reported outcomes of 1000 consecutive
cases of MFPR at Mount Sinai Medical Centre (1999-2006). Post-procedure
pregnancy loss rate was 4.7% and it correlated with the starting number
when reduced to twins (> 5: 12.1% loss; 4: 5.8%
loss; 3: 4.5% loss), but that the rate of PTB did not differ with
starting number. The lowest loss rate occurred in the patients reducing
from twins to a singleton (2.1%), likely it is basically the background
spontaneous loss rate of twin pregnancies.25,26Reduction to a singleton was also associated with higher birth-weights
and lower rates of preterm deliveries.
Evidence of improved perinatal and obstetric outcomes after reduction of> 4 fetuses is undisputed, convincing data has
emerged for triplets as well in various meta-analysis.
A 2017 meta-analysis27 including 24 studies
(1999-2015) compared triplets reduced to twins with expectantly managed
triplets. The risk of pregnancy loss before 24 weeks was similar in both
groups (7.4 versus 8.1%, OR 0.87, 95% CI 0.52-1.42). Reduction to
twins was associated with a 60% reduction in early PTB (<32
weeks: OR 0.30, 95% CI 0.22-0.41; <28 weeks: OR 0.40, 95% CI
0.22-0.71) which resulted in a significant reduction in neonatal
mortality. Other adverse pregnancy outcomes as gestational diabetes
reduced by nearly 70% and hypertensive disorders by 60%. Mothers of
reduced triplets had a lower rate of Caesarean deliveries (61.4%)
compared with the non-reduced triplets’ (90.5%) cohort. Nonreduced
triplets delivered significantly earlier, with a consequent higher
prevalence of major morbidities.28 Twins from reduced
triplets didn’t follow the true growth curves of spontaneous twins, and
instead, retain their suboptimal growth potential as triplets, secondary
to early placental processes or retained fetoplacental material after
MFPR.
Papageorghiou et al29 calculated that seven (95%CI
5-9) reductions needed to be performed to prevent one early PTB, while
the number of reductions that would cause one miscarriage was
26(95%CI14-193) in their systematic review.
Another meta-analysis30 separately assessed outcomes
of trichorionic triamniotic triplet pregnancies (TCTA, n=501) and
dichorionic triamniotic triplet pregnancies (DCTA, n=200) versus those
electively reduced to twins (TCTA n=666;DCTA n=49). In TCTA gestations,
MFPR was associated with a substantial reduction in PTB <34
weeks (17.3 versus 50.2%), without a substantial increase in the rate
of miscarriage (8.1 versus 7.4%). In DCTA pregnancies, only a modest
reduction of PTB ( 51.9% to 46.2%) was observed with selective
reduction of the triplet with the separate placenta while miscarriage
rate increased from 8.5 to 13.3%. The numbers were small to draw any
confident conclusion.
Morlando 31 presented a systemic review of MFPR
outcomes. Out of 331 DCTA triplets, the miscarriage and PTB rates were
8.9% and 33.3% respectively with expectant management. The miscarriage
rate was 14.5% with a reduction of MC pair, 8.8% with a reduction of
one fetus of the monochorionic pair, and 23.5% with a reduction of the
fetus with a separate placenta. Severe PTB rates were 5.5%, 11.8%, and
17.6% respectively. The highest rate of fetal loss was observed where
monochorionic pair was left behind reflecting losses secondary to
complications of monochorionicity. Hence, they concluded expectant
management in DCTA triplets, is a reasonable choice when a liveborn
infant is a top priority irrespective of the possible presence of
handicap. The benefit of fetal reduction is a decrease in the rate of
severe PTB thereby minimize risks of long-term sequelae.
Presently enough evidence exists that even when chorionicity is taken
into consideration, reducing triplets to twins does reduce the rate of
PTB with probably no significant increase in the miscarriage rate.
A recent retrospective review32 of large contemporary
cohort comparing pregnancy outcomes of DCDA twin pregnancies reduced to
singletons (n = 250) with ongoing (nonreduced) twin pregnancies (n =
605) showed in univariate logistic regression analysis, MFPR was
associated with higher mean gestational age at delivery (39 versus 36.7
weeks), reduction in PTB <37 weeks (18 versus 54%) and
<34 weeks (7 versus 17%) as well as reduction in birth weight
<5th percentile (9 versus 22% ). Other
adverse outcomes including preeclampsia (4 versus 17%), PPROM (6 versus
19%), gestational diabetes (5 versus 9%) also showed improvement with
MFPR. No significant increase in unintended pregnancy loss <24
weeks (2.4 versus 2.3 %) was reported.