Reduction of multifetal pregnancies to twins does not increase obstetric or perinatal risks

A.J. Antsaklis1, P. Drakakis, G.P. Vlazakis and S. Michalas

1st Department of Obstetrics and Gynaecology, Department of Fetal Maternal Medicine, Universityof Athens Medical School, `Alexandra' Maternity Hospital,Athens 115 28, Greece


    Abstract
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Selective reduction in cases of multiple fetuses is used more often nowadays due to the increased number of multiple pregnancies resulting from assisted reproduction. In this retrospective study, we investigated whether twin pregnancies derived from fetal reduction carry a higher obstetric and perinatal risk compared to standard twin pregnancies. We found that the rate of miscarriage was 10.6% in the reduction group (n = 158) compared to 9.5% in the controls (n = 135). Mean gestational age at delivery was 35.7 weeks in the reduction group versus 35.1 weeks in the control group. Mean neonatal weight at birth was 2.260 g (800–3.750 g) in the reduction group compared to 2.240 g (540–3.360 g) in controls. Perinatal mortality rate was 49.3{per thousand} after reduction and 42.0{per thousand} in the control group. There was no statistically significant difference in any of the above parameters. Therefore, multifetal pregnancy reduction to twins does not appear to increase obstetric or perinatal risks.

Key words: multifetal reduction/multiple pregnancies/obstetric outcome/perinatal outcome


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Most multifetal pregnancies are problematic gestations either because of the high number of fetuses or because of the presence of genetic disease in one fetus. Multiple gestations have become more commonplace, reflecting the increasing usage of assisted reproductive technologies.

Despite the use over quite a long period of prenatal diagnosis, many associated medical, ethical and legal questions are still unresolved (Antsaklis et al., 1984Go). The selective reduction of multiple fetuses is routinely performed in Prenatal Medicine Centers, but its effects on the evolution of pregnancy are still under consideration (Melgar et al., 1991Go; Porreco et al., 1991Go; Berkowitz et al., 1993Go). Nevertheless perinatal morbidity and mortality remain high in multiple gestations, due mainly to premature births but also to early miscarriages, late abortions and increased rates of fetal growth retardation (Boulot et al., 1990Go).

In this study, we have investigated a few of the points that remain unresolved. We considered whether pregnancy outcome was determined by the initial number of embryos implanted into the uterus or by the final number of fetuses growing in it in order to determine the role played by the reduced quantity of embryonic and placental tissue.


    Material and methods
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Our study population included 158 patients who underwent embryonic reduction to twins from January 1992 till May 1996 in the Fetal Maternal Medicine Clinic of Alexandra University Hospital in Athens, Greece. All of them had delivered during the course of this study.

In this retrospective study, we wished to determine pregnancy outcome, so outcome measures included the rate of miscarriage, the mean gestational age at delivery and neonatal weight.

All of the 158 patients had followed an in-vitro fertilization (IVF)–embryo transfer programme. There were 108 triplet pregnancies, 38 quadruplet, seven quintuplet, three hextuplet, one heptuplet and one octuplet pregnancy. We considered only fetuses with cardiac activity before the procedure. The reduction to twin pregnancies occurred between the 9th and 11th weeks of amenorrhoea, although it has since been shown that selective multifetal pregnancy reduction even at a later stage (around the 20th week) is associated with a favourable perinatal outcome (Hartoov et al., 1998Go). The method used was transabdominal intracardiac injection of 1–3 ml of potassium chloride. One week after reduction an ultrasound was performed. Blood coagulation tests were not performed routinely.

The control group consisted of 135 twin pregnancies conceived either naturally or after assisted reproduction which were followed up in our Clinic for various reasons without being a selective group.

The vast majority of patients in both groups were primiparous.

Statistics
Data were compared with the {chi}2-test or z-test for proportions where appropriate.


    Results
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
In our study we assessed miscarriage rate, gestational age at birth, mean neonatal weight, perinatal mortality rate and proportion of Caesarean sections, both in the study group and in the control group (Table IGo).


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Table I. Outcome of twins obtained by selective reduction of higher order pregnancies compared with control twin pregnancies
 
When we compared patients who had reductions of triplets and quadruplets (n = 146) in the 10th week of gestation with those in the 11th, no significant difference was observed in miscarriage rate, mean gestational age at delivery, mean neonatal weight at birth or perinatal mortality rate. Therefore, all the patients were considered as one group, as was the case with other studies (Groutz et al., 1996Go).

The miscarriage rate (earlier than week 26 of gestation) for both fetuses was 10.6% in the reduction group, and occurred at a mean gestation week of 21.3 weeks, i.e. >10 weeks after the reduction. In the control group, the miscarriage rate was 9.5% (P > 0.05).

In the reduction group delivery occurred at a mean gestational age of 35.7 weeks, compared with 35.1 weeks for the control group (P > 0.05). In the reduction group 43% of patients delivered at 37 weeks or beyond, 69% of the deliveries were beyond 34 weeks, 26% were between 28 weeks and 34 weeks and only 4.5% were before 28 weeks. In the control group, 46% delivered beyond 37 weeks (P > 0.05), with 62% of the deliveries beyond 34 weeks, 35% between 28 weeks and 34 weeks and 3% before 28 weeks.

In the reduction group the mean neonatal weight at birth was 2.260 g (ranging from 800 to 3.750 g), while in the non-reduction group, twins had a mean weight of 2.240 g (ranging from 540 to 3.360 g) (P > 0.05).

The perinatal mortality rate was 49.3{per thousand} in the reduction group, that is 14 neonates out of 284 that were born died in the early neonatal period (within 7 days). The cause of perinatal death was prematurity (n = 7), sepsis (n = 2), respiratory distress (n = 2), spina bifida (n = 1), haemorrhage (n = 1) and gastroschisis (n = 1). Seven patients had intrauterine deaths after the 26th week of pregnancy. In the control group, six fetuses died in the uterus after the 26th week and 10 in the early neonatal period because of prematurity. The overall perinatal mortality rate was 42.0{per thousand} (P > 0.05).

A total of 83% of patients in the reduction group and 84% in the non-reduction group underwent Caesarean section.

No patients in the reduction group had any evidence of consumptive coagulopathy during follow-up.


    Discussion
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
An increased number of multifetal pregnancies is an inevitable consequence of ovarian stimulation regimens (Loutradis and Drakakis, 1995Go). There is a tendency, nowadays, to transfer a smaller number of embryos (a maximum of three) in order to reduce the incidence of unwanted multifetal pregnancies.

Reduction procedures in multifetal gestations are inevitable since it has been established that the obstetric outcome for triplets or a higher number of fetuses is significantly worse than that for singleton or twin gestations (Newman et al., 1989Go; Petrokovsky et al., 1989; Collins and Bleyl, 1990Go; Lipitz et al., 1994Go; Manzur et al., 1995Go). The exact number of fetuses that should be left in the uterus is uncertain. Although singletons have longer gestations and lower morbidity compared to twin gestations, the latter are more feasible for the vast majority of multifetal pregnancy reductions since the number of fetuses left should be greater than the final number desired (Dommergues et al., 1991Go; Evans et al., 1992Go).

At the start of this study, one question was whether premature delivery was related to the initial number of embyros implanted or the final number of fetuses growing in the uterus. Our study suggests that, since there was no statistically significant difference in gestational age at delivery between control twins and twins obtained by reduction, prematurity is a consequence of the number of fetuses in the uterus and is not related to the amount of placental tissue left after the reduction.

Both groups of patients had the same obstetric outcome according to perinatal mortality, gestational week at delivery, weight of neonates at birth and miscarriage rate. Many years of practice has made the technique of multifetal pregnancy reduction a very safe procedure.

Some studies have shown a constant decreased weight at birth in the reduction group (Alexander et al., 1995Go), other studies found a difference in the mean gestational age at birth (Meglar et al., 1991) and some studies found both (Groutz et al., 1996Go; Sebire et al., 1997Go). None of these results were observed in our study. Similarly, the rate of miscarriage (10.6%) was in the lower regions of the range reported in the literature (4–33%) (Berkowitz et al., 1988Go). It must be noted that early abortions, premature births and fetal growth retardation are not prevented by fetal reduction (Boulot et al., 1990Go).

The number of Caesarean section in both groups was rather high and in the majority of cases it was due to the patient's decision. This was influenced by the amount of effort required to achieve a pregnancy by assisted reproduction.

In a reduction procedure, both the medical aspect and the psychological cost must be considered. Sadness and guilt may persist for a long time in some patients, although the majority tolerates the procedure well. The vast majority of patients seems to reconcile the concept that the termination of one or more fetuses preserves the lives of those remaining (Kanhai et al., 1994Go; Garel et al., 1995Go, 1997Go; Schreiner-Engel et al., 1995Go). The religious faith of the parents may lead to a denial of reduction (Lipitz et al., 1994Go). Although selective reduction has enabled many patients to continue successfully an otherwise high risk pregnancy, the legal issue and ethical aspects are unresolved (Check et al., 1993Go; Evans et al., 1996Go). Ethical consideration must be remembered in order to prevent abuse of this procedure.


    Notes
 
1 To whom correspondence should be addressed Back


    References
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Alexander, J.M., Hammond, K.R. and Steinkampf, M.P. (1995) Multifetal reduction of high-order multiple pregnancy: comparison of obstetrical outcome with nonreduced twin gestations. Fertil. Steril., 64, 1201–1203.[ISI][Medline]

Antsaklis, A., Politis, J., Karagianopoulos, G. and Kaskarelis, D. (1984) Selective survival of only the healthy fetus following prenatal diagnosis of thalassemia major in binovular twin gestation. Prenat. Diagn., 4, 289–296.[ISI][Medline]

Berkowitz, L.R., Lynch, L. and Chitkara, U. (1988) Selective reduction of multifetal pregnancies in the first trimester. N. Engl. J. Med., 318, 1043–1047.[ISI][Medline]

Berkowitz, L.R., Lynch, L., Lapinski, R. and Bergh (1993) First trimester transabdominal multifetal pregnancy reduction: A report of two hundred completed cases. Am. J. Obstet. Gynecol., 169, 17–21.[ISI][Medline]

Boulot, P., Hedon B., Pelliccia, G. et al. (1990) Obstetrical results after embryonic reductions performed on 34 multiple pregnancies. Hum. Reprod., 5, 1009–1013.[Abstract]

Check, J., Nowroozi, K., Vetter, B. et al. (1993) The effects of multiple gestation and selective reduction on fetal outcome. J. Perinat. Med., 21, 299–302.[ISI][Medline]

Collins, M.S. and Bleyl, J.A. (1990) Seventy-one quadruplet pregnancies: Management and outcome. Am. J. Obstet. Gynecol., 162, 1384–1392.[ISI][Medline]

Dommergues, M., Nisand, I., Mandelbrot, L. et al. (1991) Embryo reduction in multifetal pregnancies after infertility therapy: obstetrical risks and perinatal benefits are related to operative strategy. Fertil. Steril., 55, 805–811.[ISI][Medline]

Evans, I.M., Littmann, L., King, M. and Fletcher, J.R. (1992) Multiple gestation: The role of multifetal pregnancy reduction and selective termination. Clin. Perinatol., 19, 345–357.[ISI][Medline]

Evans, M.I., Mark, P.J., Quintero, R.A. and Fletcher, J.C. (1996) Ethical issues surrounding multifetal pregnancy reduction and selective termination. Clin. Perinatol., 23, 437–451.[ISI][Medline]

Garel, M., Starck, C., Blondel, B. et al. (1995) Psychological effects of embryonal reduction. From the decision making to 4 months after delivery. J. Gynecol. Obstet. Biol. Reprod. Paris, 24, 119–126.[Medline]

Garel, M., Starck, C., Blondel, B. et al. (1997) Psychological reactions after multifetal pregnancy reduction: a 2-year follow-up study. Hum. Reprod., 12, 617–622.[ISI][Medline]

Groutz, A., Yovel, I., Amit, A. et al. (1996) Pregnancy outcome after multifetal pregnancy reduction to twins compared with spontaneously conceived twins. Hum. Reprod., 11, 1334–1336.[Abstract]

Hartoov, J., Geva, E., Wolman, I. et al. (1998) A 3-year, prospectively-designed study of late selective multifetal pregnancy reduction. Hum. Reprod., 13, 1996–1998.[Abstract]

Kanhai, H., De Haan, M., Van Zanten, L. et al. (1994) Follow up of pregnancies, infants, and families after multifetal pregnancy reduction. Fertil. Steril., 62, 955–959.[ISI][Medline]

Lipitz, S., Reichman, B., Uval, J. et al. (1994) A prospective comparison of the outcome of triplet pregnancies managed expectantly or by multifetal reduction to twins. Am. J. Obstet. Gynecol., 170, 874–879.[ISI][Medline]

Loutradis, D. and Drakakis, P. (1995) Multiple pregnancies after assisted reproductive techologies (ART). Syllabus of the 3rd ESHRE Campus Symposium, November, pp. 10–11.

Manzur, A., Goldsman, M.P., Stone, S.C. et al. (1995) Outcome of triplet pregnancies after assisted reproductive techniques: How frequent are the vanishing embryos? Fertil. Steril., 63, 252–257.[ISI][Medline]

Melgar, A.C., Rosenfeld, D.L., Rawlinson, K. and Greenberg, M. (1991) Perinatal outcome after multifetal reduction to twins compared with nonreduced multiple gestations. Obstet. Gynecol., 78, 763–767.[Abstract]

Newman, R.B., Harner, C. and Miller, C. (1989) Outpatient triplet management: a contemporary revue. Am. J. Obstet. Gynecol., 161, 547–555.[ISI][Medline]

Petrokovsky, B. and Vintzileos, A. (1989) Management and outcome of multiple pregnancies of higher fetal order: Literature review. Obstet. Gynecol. Surv., 44, 578–588.[Medline]

Porreco, P.R., Burke, M.S. and Hendrix, M.L. (1991) Multifetal reduction of triplets and pregnancy outcome. Obstet. Gynecol., 78, 335–339.[Abstract]

Schreiner-Engel, P., Walther, N.V., Mindes, J. et al. (1995) First-trimester multifetal pregnancy reduction: Acute and persistent psychologic reactions. Am. J. Obstet. Gynecol., 172, 541–552.[ISI][Medline]

Sebire, N.J., Sherod, C., Abbas, A. et al. (1997) Preterm delivery and growth restriction in multifetal pregnancies reduced to twins. Hum. Reprod., 12, 173–175.[ISI][Medline]

Submitted on March 18, 1998; accepted on January 27, 1999.