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.