1 Foetal Medicine Unit, Department of Obstetrics and Gynecology, Hopital Arnaud de Villeneuve, Avenue du Doyen Gaston Giraud, 34 000 Montpellier Cedex and 2 Department of Medical Information, Hopital Lapeyronie, Avenue du Doyen Gaston Giraud, 34 000 Montpellier Cedex, France
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Abstract |
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Key words: multifetal pregnancy reduction/perinatal mortality/prematurity/triplet gestation/twins
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Introduction |
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Materials and methods |
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Management of the reduced group was as follows: as of 1993, all reductions were performed as previously described (Boulot et al., 1993b). Before 1993, two techniques were used, both performed by the same practitioner. The technique used in the initial 16 cases of our experience with MFPR was the transcervical mini-suction at 811 weeks using an echo-guided Karmann cannula no. 6 to 10 inserted through the cervix under local or general anaesthesia. Transabdominal echo-guided embryo puncture was then used in the 49 following cases. Under local anaesthesia, a 22.5 gauge needle was transabdominally inserted through the uterus wall, then into the amniotic cavity, and finally pushed into the fetal thorax at a level above the diaphragm. Then, potassium chloride solution (amount ranging from 0.5 to 5 ml) was injected, leading to the cessation of the heartbeat. Antibioprophylaxy was used in all cases. The choice of technique was based on the period at which the patients entered the study. The transcervical approach was used until 1989 and then was replaced by the other technique because of a lower miscarriage rate. The procedures were performed between 8.0 and 13.5 weeks and the mean gestational age at the time of the reduction was 9.7 ± 2.5 weeks. All pregnancies obtained were twins with typical ultrasonographic features of a dichorionic placentation. Scans were then performed monthly until the end of pregnancy. After the procedure, nearly half of the patients in the reduced group were referred to their primary care providers for the remainder of the pregnancy.
Statistics
Data are presented as means ± SD. Length of gestation was established according to the date of IVF or ovulation induction or, for cases of spontaneous gestation, on the first day of the last menstrual period, which was then verified by ultrasound examination. Durations of pregnancies are presented as number of weeks gestation. Delivery at term was after 37 completed weeks gestation. Fetal weights were reported on growth curves for singletons. The perinatal mortality rate (PMR) included deaths occurring from the beginning of the 22nd week of gestation to the seventh day after birth. The neonatal mortality rate included deaths occurring from birth to the 28th day after birth. Therefore deaths occurring during the first 7 days after birth were included in both perinatal and neonatal categories. Data were analysed using the 2-test, Fisher's exact test and the KruskalWallis test. For uniformity, infant follow-up refers to follow-up until 6 months of age for both populations.
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Results |
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Discussion |
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The main challenge in triplet pregnancies is the high rate of premature delivery, ranging from 87.5 to 91.6%, with a mean age at delivery of 33.9 weeks (Lipitz et al., 1989; Newman et al., 1989
; Seoud et al., 1991
; Albrecht and Tomich, 1996
; Berkowitz et al., 1996
; Evans et al., 1998
). The proportion of births occurring before 32 weeks reaches ~25% according to the series in the literature, while the rate of premature deliveries occurring between 24 and 28 weeks varies from 3 to 7% (Boulot et al., 1993; Berkowitz et al., 1996
; Evans et al., 1998
; Torok et al., 1998
). There was a significant decrease (P = 0.001) in prematurity in our reduced groups compared with the triplet group since pregnancies of the reduced group continued for 2.5 weeks longer on average. The mean gestational age at delivery in the expectantly managed group was 33.5 weeks, whereas for the twins resulting from reduced triplets, it was 36 weeks. Extreme premature births occurred more frequently in the non-reduced group than in the reduced group. The rate of preterm births was 2-fold higher between 24 and 28 weeks and 2.5-fold higher in the interval 2932 weeks. In another study, the rate of prematurity among twins from reduced triplets did not significantly differ from that of dichorionic twins naturally obtained or by means of assisted reproduction procedures (Macones et al., 1993
; Alexander et al., 1995
; Groutz et al., 1996
). Similar results were observed in the two other series that compare the outcome of triplets reduced to twins versus non-reduced triplets (Macones et al., 1993
; Lipitz et al., 1994
) and in our previous study (Boulot et al., 1993). For Lipitz et al. (1994), the rate of preterm births among triplets was respectively 23.8% between 25 and 31 weeks and 67.9% between 32 and 36 weeks versus 9.7% and 16.1% among reduced triplets (Lipitz et al., 1994
). For Macones et al. (1993), a higher percentage of pregnancies was delivered before 32 weeks in the non-reduced triplets (43%) compared with the reduced group (7%) (Macones et al., 1993
). In a collaborative study (Evans et al., 1998
), the prematurity rate observed among triplets managed with MFPR, mostly to obtain twins, was 3.3% in the interval of 2528 weeks and reached 7.5% between 29 and 32 weeks. These rates are consistent with our data. Similar data were reported by Berkowitz et al. (1996) on their monocentric series of 179 triplets reduced mostly to twins with 2% of reduced triplets being delivered between 24 and 28 weeks, 6% between 28 and 32 weeks and 35% between 24 and 28 weeks.
As for fetal growth, there was significant weight gain in the reduced group since the birthweights of the infants from that group were 571 g higher than in the triplet cohort. Two other similar studies found differences of nearly 450 to 700 g (Macones et al., 1993; Lipitz et al., 1994
). In our series, the percentage of fetal weights <1500 g was significantly lower among the reduced groups (6.9 versus 27.4%). We also found that the proportion of infants whose weights were under the third centile was significantly lower (P = 0.002) in the reduced group (8.7%) when compared to the non-reduced group (18.4%). In the study of Lipitz et al. (1994) the incidence of infants weighing less than 1000 g and those whose weights were between 1000 and 1500 g were respectively 1.7 versus 6.7% and 5.1 versus 19.7% in comparison with the non-reduced group. Macones et al. (1993) reported an 83% rate of expectantly managed triplets weighing less than 2500 g compared with 73% in the reduced group. This weight gain may indicate that MFPR has no detrimental effects on the growth of the remaining twins, in agreement with the findings of Torok et al. (1998), who reported that MFPR is not associated with an increased risk of intrauterine growth restriction (IUGR) unless the starting number of embryos is five or more. In this latter study, no significant difference was found in the frequency of birthweight discordance or the incidence of IUGR when 233 twins from reduced triplets were compared with a control group of 136 dichorionic twins.
Our study fails to demonstrate a significant decrease in perinatal or neonatal mortality rates among the reduced triplets despite a larger cohort of patients although the perinatal mortality rate of the non-reduced triplets was already very low (6.41%). The study of Lipitz et al. (1994) reported a decrease in the incidence of perinatal mortalityalthough it was not statistically significantin the patients undergoing MFPR (48 versus 109 per 1000 births). Macones et al. (1993) reported a perinatal mortality rate of 210 per 1000 births among expectantly managed triplets whereas it was only 30 per 1000 births in the reduced group (P < 0.001). In their series, the perinatal morbidity of twins was significantly lower when compared with the non-reduced group because the proportion of infants admitted to a neonatal intensive care unit was higher for the triplets than for the twins, as was the need of ventilatory support (respectively 84.6 versus 36.2% and 51.3 versus 14%). Similar data have been reported by others (Lipitz et al., 1994) and our group (Boulot et al., 1993a
). Our present data suggest that a reduction from triplet to twin decreases the risk of extreme prematurity, and consequently that it may reduce the risk of cerebral palsy linked to intraventricular haemorrhage. Interestingly, in a retrospective series (Khadel et al., 1998
) comparing 24 ongoing triplets and 17 triplets reduced to twins conducted over a short (3 years) and recent period, pregnancies received standardized care (births in a level III perinatal centre, fetal lung maturation). Although prematurity was lower in the reduced pregnancies group, severe prematurity (<32 weeks, and between 26 and 31 weeks) was not different. As in our study, no significant difference was observed for perinatal mortality in the two groups. Bollen et al. (1993) reported that 8% of surviving triplets suffer from neurological sequelae and this percentage may be higher because many of these infants were too young to permit full evaluation. Although MFPR decreases the number of babies going home per couple, it may increase the proportion of surviving infants without complications.
It should be noted, however, that MFPR on triplets is performed in several centres: in one study (Evans et al., 1994) 42% of the 1084 procedures performed were for reducing triplets. This rate is similar for a later expanded series including 1789 gestations out of which 759 were triplets (Evans et al., 1998
). In a French national study, 41% of 262 cases of reductions performed were on triplets (Dommergues et al., 1994
). Similar data are reported from monocentric series, with a mean rate of 40%: 44% (Wapner et al., 1990
), 43% (Salat-Baroux et al., 1988
), 26% (Dommergues et al., 1991
), 57.5% (Tabsh, 1990
), 24% (Lipitz et al., 1994
), 50% (Trimor-Trisch et al., 1993), 44% (Berkowitz et al., 1993
), and 49% in their recently expanded series (Berkowitz et al., 1996
). MFPR in triplets (resulting in twins and less often in singletons) should be considered in pregnancies with serious maternal disease (e.g. heart disease, diabetes), poor uterine conditions (bicornuate uterus, exposure to diethylstilboestrol, previous Caesarean section, previous preterm delivery) or in cases where an embryo is affected by a severe disease (neural tube defect, cystic hygroma). In the absence of worrisome factors, one might consider that the decision belongs to the well-informed couple. The results shown above indicate that reduction of triplets improves some obstetric parameters. Consequently, couples with triplets should be informed of both the benefits and risks of reduction as well as of the risks of naturally managed triplet gestation. Comprehensive psychological support should be offered to parents of multiple pregnancies, regardless of their willingness or not to reduce the pregnancy. Lack of knowledge about long-term psychological consequences of MFPR on both mothers and babies is an argument to reinforce the prevention of these undesirable pregnancies, at least for the majority of cases. In a 2 year comparative prospective follow-up study between reduced and ongoing triplets (Garel et al., 1997
), it was shown that for a majority of women, MFPR was experienced as stressful, painful and frightening in the immediate post-procedure period. However, most women had overcome these emotional difficulties 2 years later. The comparison with mothers having delivered reduced triplets indicated that psychological health and the relationship with the children were more satisfactory in the reduction group. Families with triplets had much more acute psychosocial problems than families who underwent MFPR.
Our experience and that of other teams suggest that MFPR on triplets is currently performed not only for obstetric reasons, some of which are difficult for the couples to understand despite full medical disclosure provided by obstetricians or reproductive medicine practitioners (Boulot et al., 1993a; Smith-Levitin et al., 1996
; Berkowitz et al., 1996
; Evans et al., 1998
). Additional reasons for requesting MFPR include financial and social concerns, as well as the mother's obligation to stop working and the anticipation of a poor quality of life after the birth of triplets. It should be emphasized that the aim of assisted reproduction procedures is a viable pregnancy leading to the birth of a healthy baby. In most cases of infertility, the desire for a child is best fulfilled by a singleton or twin pregnancy rather than the birth of triplets. As the main series in the literature offer similar results to our own, we believe that MFPR applied on triplets is a reasonable parental option and should be accepted if requested.
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Notes |
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References |
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Submitted on April 9, 1999; accepted on March 31, 2000.