ORIGINAL ARTICLE

Obstetric and neonatal outcome of multifetal

pregnancy reduction

Abdel Baset F. Mohammed a,*, Ibrahim Farid b, Badreldeen Ahmed c,

Ehab Abdel Ghany c

a Departments of Obstetrics and Gynecology, Minia University, Egyptb Departments of Obstetrics and Gynecology, Zagazig University, Egyptc Women’s Hospital, Hamad Medical Corporation, Qatar

Received 27 October 2014; revised 14 January 2015; accepted 25 January 2015

KEYWORDS

Multifetal pregnancy reduc-

tion;

Obstetric and neonatal

outcomes

Abstract Objective: To evaluate obstetric and neonatal outcomes of multifetal pregnancy reduc-

tion (MFPR) in patients with higher order multiple pregnancies (HOMP) compared to those man-

aged expectantly.

Methods: Forty patients with HOMP (quadruplets or more) were included. Seventeen patients

were reduced and 23 patients were non-reduced as per patient’s choice. Obstetric and neonatal out-

come measures were compared.

Results: The mean gestational age at the procedure was 12.8 ± 0.9 weeks. Five cases out of fif-

teen were reduced to triplets and 10 cases were reduced to twins. The mean total volume of KCL

used was 5.4 ± 1.3 ml and the mean number of attempts was 1 ± 0.4. The most frequent compli-

cations were maternal anxiety and abdominal pain (29.4%). The procedure failed in two cases due

to abdominal pain and maternal distress. The differences regarding preterm labor, gestational age at

delivery, mode of delivery and neonatal birth weight were statistically significant. This was in favor

of MFPR procedure.

Conclusion: MFPR procedure seems to be good and acceptable option for patients with HOMP

but not totally safe.

� 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-

nd/4.0/).

1. Introduction

The incidence of multifetal pregnancies has increased over the

last few decades – largely a result of assisted reproductive tech-

nology (ART) (1,2). This is significant as the rates of fetal and

maternal complications are higher in multifetal pregnancies,

with this risk increasing with the number of fetuses. This trend

has necessitated the development of fetal reduction to manage

* Corresponding author. Mobile: +20 00974 55458229.

E-mail address: abdu163@hotmail.com (A.B.F. Mohammed).

Peer review under responsibility of Middle East Fertility Society.

Production and hosting by Elsevier

Middle East Fertility Society Journal (2015) xxx, xxx–xxx

Middle East Fertility Society

Middle East Fertility Society Journal

www.mefsjournal.orgwww.sciencedirect.com

http://dx.doi.org/10.1016/j.mefs.2015.01.0011110-5690 � 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Middle East Fertility Society.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Mohammed ABF et al. Obstetric and neonatal outcome of multifetal pregnancy reduction, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.01.001

multifetal pregnancies, in order to improve perinatal survival

and reduce maternal risk. Although fetal reduction techniques

have emerged to be effective in improving pregnancy out-

comes, this has been an area of great controversy where ethical

and legal issues have not been clearly addressed (3).

Fetal reduction may be indicated in various circumstances.

In selective termination, (one or more) anomalous fetuses in a

multifetal pregnancy are terminated. In contrast, multifetal

pregnancy reduction (MFPR) reduces the number of fetuses

in gestation in order to improve the chances of healthy survival

in the remaining conceptuses and to reduce the hazards to the

mother (4). Apart from optimization of outcome, fetal reduc-

tion may be conducted for social reasons based on the patient’s

request.

Pregnancy outcome is improved when higher-order multife-

tal pregnancies [HOMP] are reduced (5). Fetal reduction has

been shown to decrease the incidence of miscarriage, prematu-

rity and low-birth-weight infants. However, fetal reduction

intervention also has inherent risk, with recent series citing

an overall pregnancy loss rate of 4.7% (6). This retrospective

study was conducted to evaluate the obstetric and neonatal

outcomes of MFPR procedure in patients with HOMP com-

pared to those managed expectantly in a local tertiary unit.

2. Patients and methods

This retrospective study was conducted in the Feto-Maternal

Unit (FMU), Women’s Hospital, Hamad Medical Corpora-

tion in Qatar after being accepted from the local research com-

mittee. The study population included all women with HOMP

(quadruplets or more) conceived after ART (ovulation induc-

tion, intra-uterine insemination or in vitro fertilization) during

the period from 2002 to 2012. Women included in this study

were identified using the FMU electronic database. Case

records were reviewed regarding demographic and clinical data

and details of MFPR procedure. Prior to the procedure

patients were counseled and all possible risks were explained

to them. According to patient choice, they were categorized

into those who underwent procedure (reduced group;

n= 17) and those who declined (non-reduced group;

n= 23). A written informed consent was obtained from all

patients who underwent the procedure.

Prior to the procedure, an ultrasound examination was per-

formed to know the number of embryos with heartbeats, to

determine the chorionicity, to establish the relationship of

the gestational sacs to each other and to determine which of

the fetuses are most accessible to needle insertion.

The procedure was performed trans-abdominal (TA) by

injection of 2–3 ml of potassium chloride (2 meq/ml) into the

fetal thorax using a 22 gauge spinal needle under ultrasound

guidance. Potassium chloride was injected slowly so as not

to dislodge the needle tip. The cardiac activity is carefully

observed for at least 2 min and if cardiac activity persists, more

potassium chloride is injected. Asystole was usually seen with-

in 1–2 min of injection of potassium chloride and total proce-

dural time is typically less than five minutes. Additional fetuses

could be reduced with the same needle puncture or, more com-

monly, with a separate needle stick.

The procedure was performed between 12 and 14 weeks of

gestation. Out of the 17 cases, 16 of them were done at the

beginning of the second trimester, and the last one was done

in the first trimester. Selection of fetuses to be reduced was

not based on genetic evaluation, but mainly on chorionicity

and ease of procedure. The fetus (es) reduced are those that

are most easily accessible, usually those closest to the anterior

uterine wall and/or the fundus while those above the cervix

were avoided. Procedures were done by FMU team, not by

single operators.

After the procedure, the patients were observed for one

hour for pain, leaking, bleeding or any other complication

related to the procedure. A repeat ultrasound was performed

one hour after the procedure to confirm asystole in the reduced

fetus (es) and cardiac activity in the non-reduced fetus (es).

All patients were scheduled for ultrasound examination for

fetal well-being and cervical length assessment 2 weeks after

the procedure. Regular follow-up in FMU had been squealed

for them. Maternal data, sonographic findings and MFPR

procedure details were entered into a computer database.

Different outcome measures were compared between the

two groups including miscarriage (pregnancy loss before

24 weeks of gestation), early preterm delivery (prior to

32 weeks of gestation) and median gestational age at delivery.

Data were statistically analyzed. Chi-square, Fischer’s exact

and Mann–Whitney U-tests were used as appropriate to exam-

ine the significance of differences between the two groups for

pregnancy outcomes. Significance was assumed at P < 0.05

and two-tailed P-values are reported.

3. Results

Forty patients with HOMP (quadruplets or more) were identi-

fied and included in this study. Reduced pregnancies (n = 17)

were compared to non-reduced (n = 23) ones regarding differ-

ent outcome measures. All patients underwent the procedure

completed the follow-up in our hospital and included in the

analysis. The demographic and clinical data of patients are

reported in Table 1. There were no significant differences

between the two groups regarding demographic and clinical

data. The range of fetal sacs in both groups was 4–7 in reduced

group and 4–6 in the non-reduced group.

The details of MFPR procedure including the order of ges-

tation, number of viable fetuses at presentation, gestational

age at presentation, timing of the procedure and end number

of fetuses are shown in Table 2. The mean gestational age at

the procedure was 12.8 ± 0.9 weeks. Five cases out of fifteen

were reduced to triplets and 10 cases were reduced to twins.

The method used for MFPR, number of attempts, total vol-

ume of KCL used and possible complications associated with

the procedure were reported in Table 3. The mean total vol-

ume of KCL used was 5.4 ± 1.3 ml and the mean number of

attempts of the procedure was 1 ± 0.4. The most frequent

complications were maternal anxiety and abdominal pain

which occurred in 5 patients (29.4%). The procedure failed

in two cases; the first case after 2 attempts due to abdominal

pain and maternal distress and the second one after only one

attempt due to abdominal pain. Multifetal pregnancy increases

the mother’s risk of developing pregnancy complications.

Table 3 also demonstrates the maternal complications encoun-

tered during pregnancy after MFPR procedure.

Different obstetric outcome measures were compared

between the two groups (Table 4). The differences regarding

incidence of preterm labor, median gestational age at delivery,

2 A.B.F. Mohammed et al.

Please cite this article in press as: Mohammed ABF et al. Obstetric and neonatal outcome of multifetal pregnancy reduction, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.01.001

mode of delivery and neonatal birth weight were statistically

significant. This was in favor of MFPR procedure. Order of

gestation and maternal pain and anxiety were critical in affect-

ing outcome. The number of patients with HOMP underwent

MFPR procedure in our unit was increasing over years. This is

clearly shown in Fig. 1.

4. Discussion

Fertility treatments have contributed significantly to the

increase in multifetal pregnancies especially with low quality

fertility care. The first approach to this problem should be pre-

vention, and strategies to limit multifetal pregnancies, especial-

Table 1 Demographic and clinical data of patients.

Parameter Reduced group (n = 17) Non-reduced group (n = 23) p value

Maternal age (years)

Mean ± SD 34 ± 2.2 33 ± 1.3 NS

Range 18–40 22–40

Nationality

Qatari 5 (29.4%) 10 (43.5%)

Non-Qatari 12 (70.6%) 13 (56.5%) NS

Parity

<5 14 (82.4%) 16 (69.6%)

>5 3 (17.0%) 7 (30.4%) NS

Duration of infertility (Years) 3.5 ± 2.2 3.1 ± 1.5 NS

ART technique

Clomid + Gonadotropins 6 (35.3%) 7 (30.4%)

IVF 8 (47%) 11 (47.8%)

IUI 3 (17.7%) 5 (21.8%) NS

Order of gestation (Range) 4–7 4–6 NS

Antepartum complications

Gestational diabetes 2 (11.7%) 5 (21.7%)

Pre-eclampsia 3 (17.6%) 3 (13%)

PPROM 2 (11.7%) 7 (30.4%)

Cervical cerclage 1 (5.8%) 3 (13%)

Antepartum hemorrhage 2 (11.7%) 2 (13%)

Postpartum hemorrhage 2 (11.7%) 3 (13%) NS

N. Number NS. Non-significant ART. Assisted reproduction technique IVF. In-vitro fertilization IUI. Intrauterine insemination P. Probability

PPROM. Preterm premature rupture of membranes.

Table 2 Order of gestation, number of viable fetuses, gestational age at presentation and end number of fetuses and timing of MFPR

procedure (n= 17).

Serial N Treatment type Gest. sacs (n) Viable fetuses (n) GA at presentation (weeks) GA at procedure (weeks) N of sacs after MPR

1 IVF 5 5 12 14 2

2 IVF 7 7 6 13 + 5 2

3 Clomid + Gn 4 4 6 12 & 14 (2 trials) Failed

4 IUI 4 4 7 12 3

5 IVF 6 5 7 14 Failed

6 IVF 5 4 9 14 2

7 IUI 7 7 7 10 & 11 (2 trials) 3

8 Clomid + Gn 4 4 9 12 2

9 IVF 7 7 7 12 + 5 3

10 Clomid + Gn 4 4 13 13 2

11 IUI 4 4 12 12 + 5 2

12 Clomid + Gn 4 4 12 13 + 1 2

13 IVF 6 6 11 + 12 12 & 13 (2 trials) 2

14 IUI 4 4 11 + 6 12 + 3 2

15 IVF 6 5 8 12 + 1 3

16 Clomid + Gn 4 4 12 13 3

17 Clomid + Gn 4 4 5 12 + 5 2

Mean ± SD 4.1 ± 1.2 3.9 ± 1.2 9.6 ± 3.6 12.8 ± 0.9 1.8 ± 1.0

n. Number GA. Gestational age MFPR. Multifetal Pregnancy Reduction Gn. Gonadotrophin IVF. Invitro Fertilization IUI. Intrauterine

Insemination.

Outcomes of multifetal pregnancy reduction 3

Please cite this article in press as: Mohammed ABF et al. Obstetric and neonatal outcome of multifetal pregnancy reduction, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.01.001

ly HOMP, should be practiced by all physicians who treat

women for infertility (7).

Multifetal pregnancy reduction should be considered for

any pregnancy with three or more fetuses, as there is good evi-

dence that it improves pregnancy outcome for survivors. But it

must be emphasized that this still is fraught with dangers to

pregnancy and not always accepted when compared to single-

ton pregnancy resulting from good quality fertility care. In

fact, an International Federation of Gynecologists and Obste-

tricians (FIGO) Committee Report stated that, ‘‘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 preg-

nancies arise, it may be considered ethically preferable to

reduce the number of fetuses rather than to do nothing’’ (8).

The rate of MFPR Procedure increased steadily in

Women’s hospital, Hamad Medical Corporation over the last

few years since the establishment of FMU at 2002 as a com-

mon sequel of overly aggressive infertility therapy, increased

patient and physician awareness of the availability of the pro-

cedure and lack of guidelines appears to have contributed to

more aggressive infertility treatments and more subsequent

MFPR procedures. Recently, local Hospital guidelines on fer-

tility care were developed but still not well implemented and

not reflected on prevention of HOMP.

All patients included in this study had suffered from infer-

tility for a significant time ranging from one to four years.

Table 3 The method used for MFPR, number of attempts, volume of KCL used and possible complications associated with the

procedure.

Case N Method used KCL volume (ml) N of

attempts

Reason

of failure

Procedure related

complications

Maternal complications

1 TA 4 1 Nil Preterm labor

2 TA 5 1 Nil APH 26 weeks

3 TA Unknown 2 Maternal distress Maternal pain – failed Miscarriage 15 weeks

4 TA 5 2 Nil Severe PET, IUGR in twin who

shares the placenta with the reduced twin

5 TA 4 1 Painful procedure Maternal pain – failed Severe PET, PPH

6 TA 4 1 Nil PPROM and preterm labor

7 TA 6 2 Maternal pain Severe hyper emesis

8 TA 4 1 Nil Nil

9 TA 10 1 Nil GDM, preterm labor

10 TA 3 1 Nil PET

11 TA 3 2 Nil IGTT

12 TA 4 2 Miscarriage 17 weeks

13 TA 4 2 Maternal pain exhaustion PPROM, APH, preterm labor

14 TA 3.5 1 Nil Nil

15 TA 3 1 Nil Preterm labor

16 TA 3 1 Nil Preterm labor 24 weeks

17 TA 3 1 Maternal pain Nil

N. Number TA. Transabdominal PPROM. Preterm premature rupture of membranes APH. Antepartum hemorrhage PPH. Postpartum

hemorrhage PET. Pre-eclampsia GDM. Gestational diabetes IGTT. Impaired GTT. IUGR. Intrauterine growth restriction.

Table 4 Obstetric outcome measures in the two groups.

Parameter Reduced group (n= 17) Nonreduced group (n = 23) P value

Miscarriage (<24 weeks)

N% 2 (11.7%) 3 (13%)

GA 16 ± 2.5 17.3 ± 3.5 NS

Preterm labor 10 (58.8%) 20 (87%) <0.001

GA at time of delivery

Median 35.6 ± 2.5 31.6 ± 1.9 <0.01

Range 26–39 24–35

Mode of delivery

Normal Delivery 5/17 (29.4%) 0

Cesarean section 10/17 (58.8%) 20/23 (87%) <0.001

Neonatal birth weight 1916 ± 320 1320 ± 280 <0.05

IUGR 3 (17.6%) 6 (26.1%) NS

Cerebral palsy 1 (5.8%) 3 (13%) NS

Neonatal mortality 2 (11.7%) 1 (4.3%) NS

N. Number P. Probability IUGR. Intrauterine growth restriction GA. Gestational age.

4 A.B.F. Mohammed et al.

Please cite this article in press as: Mohammed ABF et al. Obstetric and neonatal outcome of multifetal pregnancy reduction, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.01.001

The patients and their husbands have three difficult options to

choose; Termination of the pregnancy and start a new one

which is an unlikely choice for a couple who has suffered years

of infertility and is probably going through great emotional and

financial expenses. A second choice is to continue the HOMP,

accepting the high possibility of having a miscarriage or a very

preterm delivery and the increased risk for perinatal mortality

and morbidity. The third option is the MFPR, where the num-

ber of fetuses is reduced in order to lower the likelihood of pre-

term delivery and optimize the chance of a successful outcome.

In a multichorionic pregnancy, the fetus (es) reduced are

those that are most easily accessible, usually those closest to

the anterior uterine wall and/or the fundus. The fetus above

the cervix is avoided whenever possible because of a hypo-

thetical increased risk for infection or uterine irritability if that

fetus was reduced. However, if a fetus has a lagging crown

rump length, a significantly smaller sac, markers of aneu-

ploidy, or an obvious anomaly, then that fetus is preferentially

reduced since these findings are associated with adverse preg-

nancy outcome (miscarriage, fetal aneuploidy) (8,9). In this

study, MFPR was not done selectively, as we do not have

the ability of genetic testing. It was based on chorionicity

and ease of the technique.

The majority of centers, which perform the technique, uti-

lize TA approach with intra-thoracic injection of potassium

chloride under ultrasound guidance (10,11). All procedures

in our unit were performed utilizing TA approach. A trans-cer-

vical or a trans-vaginal approach can be used, but both have

been associated with increased post-procedural pregnancy loss

rates when compared with the TA approach; therefore, these

approaches are usually reserved for situations in which the

TA approach is not technically feasible (9).

Maternal pain and anxiety were the main complications

related to the procedure in this study. It was noted in five

patients and the procedure was abandoned to another session.

The procedure failed in two patients because of this pain. The

procedure was done without local anesthesia or sedation. This

may be a favorable option to avoid maternal pain and anxiety

and increase chance of success of the procedure. Other compli-

cations encountered were not related to the procedure but

related to the risks of multifetal pregnancy.

Regarding the timing of the procedure, sixteen of our

patients had the procedure done at the beginning of the second

trimester and one was done in the first trimester. The literature

reviews say fetal reduction in most centers is performed

between 10 and l4 weeks’ gestation. Before 10 weeks it is tech-

nically more difficult because of the small size of the fetuses

and greater distance from the maternal abdominal wall to

the fetuses. If fetal reduction was performed too late the risk

of preterm labor may be higher (12). To verify it, Lynch and

Berkowitz (13) in 1993, after reporting two hundred completed

cases say there is no advantage in delaying the procedure

beyond the l2th week of gestation, because if all fetuses are

alive and are of appropriate size at that time, spontaneous loss-

es are not likely in the next few weeks. Moreover the later in

pregnancy the termination is not recommended, the more

probable it is that fetal resorption will be incomplete, and

may be the rare chance, that maternal disseminated intravascu-

lar coagulation will develop.

The results of the present study suggest favorable obstetric

outcomes after MFPR procedure in terms of incidence of pre-

term labor, median gestational age at delivery, mode of deliv-

ery and neonatal birth weight. This was in agreement with

previous studies and meta-analysis (6,13–19). However, the

risk of miscarriage before 24th gestational week following

MFPR has been a controversial issue. While an earlier study

reported that risk of miscarriage was increased after the proce-

dure (20), a more recent review reported similar risk of preg-

nancy loss before 24 weeks for reduced and non-reduced

pregnancies (21). Our findings are in accordance with the latter

report and with a recent study mostly with similar results (22).

Available data on MFPR, do not support an increase in the

risk of miscarriage before 24 weeks when MFPR is performed

by experienced operators and when compared with those who

declined the procedure. It is suggested that the resorbing dead

fetoplacental tissue rather than the procedure itself could cause

increased risk of pregnancy loss before 24th gestational week

following the procedure (20).

Since a favorable obstetric outcome is reported in our study

when compared to those who declined the procedure, it

appears that the mechanism causing the spontaneous loss of

one embryo did not affect the growth of remaining embryos

and pregnancy outcome. A uterine factor causing embryonic

loss is unlikely to be present in this situation. The presence

of a uterine factor could be expected to cause the loss of other

remaining embryos as well (21).

The management of multifetal pregnancy is difficult. While

fetal reduction is a possible management option, it should not

be utilized as a safety net in fertility treatment. Prevention of

HOMPs must be the primary objective. In addressing complex

medical issues such as fetal reduction, knowledge of the rele-

vant ethical and legal implications besides medical skill compe-

tency are important. Nevertheless, while knowledge makes for

good medical practice, it is the upholding of compassion,

fidelity and humanity as common denominators across time

and cultures that should be the ethical aspirations of health

professionals (3,23).

This study has limitations in terms of small number of

patients as HOMP is rare and fetal reduction for a couple suf-

fered from infertility for long time is a difficult choice. Another

limitation also is the absence of control group from singleton

or twin pregnancy for comparison regarding pregnancy

outcome.

Figure 1 Number of MPR procedures over the years.

Outcomes of multifetal pregnancy reduction 5

Please cite this article in press as: Mohammed ABF et al. Obstetric and neonatal outcome of multifetal pregnancy reduction, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.01.001

In conclusion, MFPR procedure seems to be good and

acceptable option for patients with HOMP but not totally safe.

Patients should be thoroughly counseled before the procedure.

Local hospital guidelines should be implemented to limit the

number of embryos transferred and avoid occurrence of

HOMP in the first place. A large randomized controlled study

is recommended.

Conflict of interest

The authors report no conflict of interests.

Acknowledgments

The authors thank all members of Fetomaternal Unit, WH,

HMC; Dr Najat Kenyab, Dr Najah Saleh, Dr Zeina Al Man-

souri, Dr Sawsan Al Obaidy, Dr Abdallah Al Ibrahim, Dr

Mariam Bleushi.

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Please cite this article in press as: Mohammed ABF et al. Obstetric and neonatal outcome of multifetal pregnancy reduction, Middle East Fertil Soc J (2015), http://dx.doi.org/10.1016/j.mefs.2015.01.001