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A 3 year, prospectively-designed study of late selective multifetal pregnancy reduction

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A 3 year, prospectively-designed study of late selective multifetal pregnancy reduction
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  Human Reproduction  vol.13 no.7 pp.1996–1998, 1998 A 3 year, prospectively-designed study of late selectivemultifetal pregnancy reduction J.Hartoov 1 , E.Geva 2 , I.Wolman 1 , L.Lerner-Geva 3 ,J.B.Lessing 2 , R.Amster 1 , A.Amit 2 and A.Jaffa 1,4 1 Ultrasound Unit and  2 IVF Unit, Lis Maternity Hospital,Tel Aviv Sourasky Medical Center and  3 Department of ClinicalEpidemiology, The Chaim Sheba Medical Center, andSackler Faculty of Medicine, Tel Aviv University, Israel 4 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel AvivSourasky Medical Center, Tel Aviv 64239, Israel The aim of our study was to evaluate the pregnancyoutcomes of late selective multifetal reduction (MFPR). Weperformed a 3 year, prospectively-designed study in which28 patients underwent MFPR at a mean gestational age of 20.2  3.9 weeks (range 14–29 weeks). The indications forMFPR included: multiple gestation (  3) (57%), structuralanomaly (29%), and chromosomal abnormality (14%).The procedure was performed using ultrasonographically-guided intracardiac injection of potassium chloride. Themean gestational age at delivery was 36.6    2.2 weeks(range 31–40 weeks). Nine patients (32%) delivered before36 weeks of gestation. The mean birth weight was 2370  614 g (range 1510–3250 g). Discordancy was evident infour twins (14%), and intrauterine growth retardation infour pregnancies. One case (3.5%) presented with oligo-hydramnios, and one with pregnancy-induced hyperten-sion. One case of late abortion due to passive cervicaldilatation 4 weeks after the MFPR was observed. Pro-cedure-related amnionitis followed by late abortionoccurredinonecase.Atotalof57%ofthepatientsdeliveredvaginally and 43% delivered by Caesarean section. Weconcluded that late selective MFPR is associated withfavourable perinatal outcome. Late MFPR may facilitatethe detection of structural and chromosomal anomaliesprior to the procedure, and the accomplishment of selectivereduction of the affected fetus. Key words:  in-vitro fertilization/late fetal reduction/multifetalpregnancies Introduction High-order multifetal pregnancies constitute an iatrogeniccomplication of ovulation induction and assisted reproductivetechniques (ART). These pregnancies are characterized by ahigh incidence of maternal complications and disappointingperinatal outcome. Such pregnancies are, therefore, bestavoided by judicious use of ovulatory agents, and by limitingthe number of embryos transferred in in-vitro fertilization(IVF) treatments. However, when multiple pregnancies occur1996  ©  European Society for Human Reproduction and Embryology despite appropriate precautions, selective multifetal pregnancyreduction (MFPR) appears to be an efficacious method for theimprovement of MFPR perinatal outcome (Ayers  et al. , 1991;Timor-Trisch  et al. , 1993; Evans  et al. , 1994a, b).Over the last decade clinical evaluation of MFPR hasfocused largely on the risks and benefits of the procedure:(i) pregnancy outcome, i.e. gestational age at delivery, birthweight, antepartum complications; (ii) procedure-related preg-nancy loss and (iii) fetal reduction methods (Ayers  et al. , 1991;Yovel  et al. , 1992; Timor-Trisch  et al. , 1993; Evans  et al. ,1994a, b; Groutz  et al. , 1996; Silver  et al. , 1997; Sebire et al. , 1997).Recently, late selective termination in twin pregnancies forfetal structural anomaly and chromosomal abnormality hasbeen found to be an effective and safe therapeutic approach(Lipitz  et al. , 1996; Lynch  et al. , 1996). We describe our 3year experience with late selective MFPR regarding pregnancyoutcome that includes perinatal morbidity and mortality. Materials and methods  Patients We conducted a prospectively-designed study that comprised all lateMFPR performed between April 1994 and April 1997. Late MFPRwas chosen in order to obtain the results of the prenatal screening,including:‘tripletest’ (maternalserum α -fetoprotein,humanchorionicgonadotrophin and unconjugated oestriol), ultrasonographic evalu-ation and amniocentesis prior to the procedure, thus allowing thereduction of an affected fetus if diagnosed as such.The study population comprised 28 patients: 16 patients (57%)with multiple gestation (  3), eight (29%) with structural anomaly(four neural tube defect, two cardiac malformation, one skeletalmalformation, one polycystic kidney), and four patients (14%) withchromosomal abnormality (Down’s syndrome: three; Marfan’s syn-drome: one). Among the 28 patients, four conceived spontaneously,eight after ovulation induction treatment, and 16 conceived after in-vitro fertilization (IVF) treatment. The mean maternal age was 34.5  4.4 years (range 25–42 years). The mean gravidity and parity were2.4  2.1 (range 1–9) and 1.6   0.7 (range 1–3), respectively.  Embryo reduction The Israeli law demands Institutional Committee approval for preg-nancy reduction. When MFPR is performed beyond 24 gestationalweeks, only Distinct Superior Committees (including two specialistsin obstetrics and gynaecology, a specialist in genetics, a specialist inpaediatrics and a social worker) may approve the procedure.All pregnancies were reduced by a transabdominal, ultrasound-guided, procedure using an intracardiac injection of potassiumchloride. All procedures were performed in a similar manner asdescribed elsewhere (Evans  et al. , 1994a, 1996). All procedures wereperformed by a single operator (J.H.). Exclusion criteria for the  Late multifetal pregnancy reductionTable I.  Characteristics of the study group according to number of fetusesreduced2  →  1 3  →  2 4  →  2 Total n  9  n  15  n  4Maternal age 33.7   5.4 34.4   3.9 37.5   3.5 34.5   4.4(years)Gestation age at 35.8   3.2 34.4   3.9 37.5   3.5 36.6   2.2delivery (weeks)Birth weight (g) 2150  530 2527  420 1377  39 2370  614Numbers are mean  standard deviation.There were no significant differences. procedure included fetuses with monochorionicity. Monochorionicitywas diagnosed if two consecutive ultrasonographic examinations atthe first trimester revealed the absence of separating membranes(Monteagudo  et al. , 1994). Statistical analysis Statistical analysis was performed using SPSS-PC (version 6.1, SPSS,Chicago, 1996). Probability of     0.05 was considered statisticallysignificant. Continuous variables were compared using independent t  -test and paired  t  -test analysis when appropriate. Non-parametricanalyses and  χ 2 were used for categorical variable comparisonsand trends. Results The MFPR were performed at a mean gestational age of 20.2  3.9 weeks (range 14–29 weeks). The mean gestationalage at delivery was 36.6    2.2 weeks (range 31–40 weeks)(Table I). Nine patients (32%) delivered prior to 36 weeksgestation, three with preterm premature rupture of membranes,and six with premature contractions that did not respond totocolysis. The mean birth weight was 2370    614 g (range1510–3250 g). No significant difference was found betweenthe twin and high-order pregnancies with regard to gestationalage at delivery and birth weight. However, when MFPR wasperformed on a quadruplet pregnancy, the birth weight wassmaller (1737    39 g). Discordancy (  20%) was found infour twins (14%), two after MFPR from quadruplets, and twoafter MFPR from triplets. Intrauterine growth retardation(IUGR) was observed in four pregnancies. One case (3.5%)was found to have pregnancy-induced hypertension (PIH), andone was found to have oligohydramnios.One case of late abortion due to passive cervical dilatation4 weeks after the MFPR was observed. Procedure-relatedamnionitis followed by late abortion occurred in one case (onequadruplet pregnancy that was reduced to twins at 19 weeks’gestation). No evidence of coagulopathy was found in any of the patients following the procedure.Fifteen (57%) patients were delivered of neonates vaginallyand 12 patients (43%) underwent Caesarean section. Discussion The use of assisted reproduction techniques is associated withan increased number of multifetal pregnancies. When multiplepregnancy occurs, fetal reduction would appear to be a reason-able solution. The incidence of structural and chromosomal1997anomalies is reported to be higher among multiple pregnancies(Cameron  et al. , 1983; Rodis  et al. , 1990). The improved,prenatal diagnostic modalities provide us with the possibilityof earlier diagnosis, and selective reduction of the abnormalfetus. To the best of our knowledge only a few studies havereported the perinatal outcome of late selective reduction of twin pregnancies (Evans  et al. , 1994a, b; Lipitz  et al. , 1996;Lynch  et al. , 1996). Hence, we had the opportunity to presentthe perinatal outcome of a 3 year prospectively-designed studyof late selective MFPR, that was performed after completionof screening for structural and chromosomal abnormalities.Prenatal screening included triple test, ultrasonographic evalu-ation and amniocentesis, thus facilitating reduction of anaffected fetus, if such a diagnosis was made.Earlier MFPR after chorionic villous sampling (CVS), unlikeamniocentesis, cannot be used to diagnose structural problemssuch as neural-tube defects. In addition, a woman with CVSshouldhave herserum α -fetoproteinmeasuredand/or adetailedassessmentshouldbecarriedoutat18–20weeksofgestation,toscreen for neural-tube defects in the fetus (Stranc  et al. , 1997).Our study is characterized by the following: (i) the procedurewas performed not only on twin pregnancies, but also on high-order pregnancies, and (ii) the procedure was performed inonly one centre and by one operator.The mean gestational age of MFPR was 20.2    3.9 years,similar to that reported by Lynch  et al.  (1996) (19.7    2.7),and lower than that reported by Lipitz  et al.  (1996) (24.1   1.9), both for twin pregnancies. The mean gestational age atdelivery was 36.6    2.2, similar to that reported for lateselective twin reduction (Lipitz  et al. , 1996; Lynch  et al. ,1996) and early MFPR (Evans  et al. , 1994a,b; Groutz  et al. ,1996). A total of 32% of the patients delivered before complet-ing 36 weeks of gestation, similar to the report by Lipitz  et al. (1996) (31%). On the other hand, Lynch  et al.  (1996) observedthat preterm labours (40%) were significantly more commonwhen termination was performed at or after 20 weeks. Evans et al.  (1994b) observed an even higher rate of preterm labour(46%) for early MFPR. Lynch  et al.  (1996) found that IUGRwas present in 30% of the reduced twins before 20 weeks of gestation, and 48% in the reduced twins at or after 20 weeksof gestation. Silver  et al.  (1997) reported birth weights of 1959  784 g and 1714  557 g in 18 early MFPR to twins.The discordancy rate was found to be 28%. We observed amean birth weight of 2370    614 g with discordancy andIUGR rates of 14% each. In our previous study we found asimilar birth weight for quadruplets and triplets that werereduced to twins at 12 weeks gestation (Groutz  et al. , 1996).As opposed to the described reports, our results are favourablefor late selective MFPR.After the procedure, one case of late abortion in a twinpregnancy was observed. These results concur with otherstudies of late twin reduction (Lipitz  et al. , 1996; Lynch  et al. ,1996). Evans  et al.  (1994b), in an international collaborativestudy of second-trimester, selective terminations for fetalabnormalities in twin pregnancies, reported significantly moremiscarriages when the procedure was performed after 16 weeksgestation, compared to before 16 weeks gestation. For earlyMFPR, they found that the overall pregnancy loss rate was  J.Hartoov  et al. 12%, and the miscarriage rate was negatively correlated withthe initial fetal number (8% for triplets and 23% for sextupletsor higher) (Evans  et al. , 1996).Caesarean sections were performed on 43% of the patients.This high rate may be explained by twin pregnancy (non-vertex-presenting twin), malpresentation and premature labour,advanced maternal age, and pregnancy following long-standinginfertility.We concluded that late selective MFPR is associated witha favourable perinatal outcome. Late MFPR may facilitate thedetection of structural and chromosomal anomalies prior tothe procedure and accomplishment of selective reduction of the affected fetus.In view of our recent report (Geva  et al. , 1998) suggestingthat early MFPR may be an additional risk factor for peri-ventricular leukomalacia in premature newborns, and ourfavourable results with late MFPR, a larger, prospectivecomparison between the two procedures is warranted. References Ayers, J.W.T., Petersen, E.P., Knight, L. and Peterson, S. (1991) Incorporationof transvaginal embryo reduction (TVER) with an aggressive IVF/GIFT/ ZIFT program to optimize pregnancy outcome.  Fertil. Steril .,  56,  51–73.Cameron, A.E., Edwards, J.H., Derom, R.  et al.  (1983) The value of twinsurveys in the study of malformation.  Eur. J. Obstet. Gynaecol. Reprod. Biol.,  14,  347–351.Evans, M.I., Dommergues, M., Timor-Tritsch, I.  et al.  (1994a) Transabdominalversus transcervical and transvaginal multifetal pregnancy reduction:international collaborative experience of more than one thousand cases.  Am. J. Obstet. Gynecol .,  170,  902–909.Evans, M.I., Goldberg, J.D., Dommergues, M.  et al.  (1994b) Efficacy of second-trimester selective termination for fetal abnormalities: internationalcollaborative termination for fetal abnormalities: international collaborativeexperience among the world’s largest centers.  Am. J. Obstet. Gynecol.,  171, 90–94.Evans, M.I., Dommergues, M., Wapner R.J.  et al.  (1996) International,collaborative experience of 1789 patients having multifetal pregnancyreduction: a plateauing of risks and outcomes.  J. Soc. Gynecol. Invest  .,  3, 23–26.Geva, E., Lemer-Geva, L., Stavorovsky, Z.  et al.  (1998) Multifetal pregnancyreduction - a possible risk factor for periventricular leukomalacia inpremature newborns.  Fertil Steril.,  69,  845–850.Groutz, A., Yovel, I., Amit, A.  et al.  (1996) Pregnancy outcome after multifetalpregnancy reduction to twins compared with spontaneously conceivedtwins.  Hum. Reprod  .,  11,  1334–1336.Lipitz, S., Shalev, E., Meizner, I.  et al.  (1996) Late selective termination of fetal abnormalities in twin pregnancies: a multicenter report.  Br. J. Obstet.Gynecol.,  1212–1216.Lynch, L., Berkowitz, R.L., Stone, J.  et al.  (1996) Preterm delivery afterselective termination in twin pregnancies.  Obstet. Gynecol.,  87,  366–369.Monteagudo, A., Timor-Tritsch, I.E. and Sharma, S. (1994) Early and simpledetermination of chorionic and amniotic type in multifetal gestations in thefirst fourteen weeks by high-frequency transvaginal ultrasonography.  Am. J. Obstet. Gynecol .,  170,  824–829.Rodis, J.F., Egan, J.F., Craffey, A.  et al.  (1990) Calculated risk of chromosomalabnormalities in twin gestations.  Obstet. Gynecol.,  76,  1037–1941.Sebire, N.J., Sherod, C., Abbas, A.  et al.  (1997) Preterm delivery and growthrestriction in multifetal pregnancies reduced to twins.  Hum. Reprod  .,  12, 173–175.Silver, R.K., Helfand, B.T., Russell, T.L.  et al.  (1997) Multifetal reductionincreases the risk of preterm delivery and fetal growth restriction in twins:a case-control study.  Fertil. Steril .,  67,  30–33.Stranc, L.C., Evans, J.A. and Hamerton, J.L. (1997) Chorionic villus samplingand amniocentesis for prenatal diagnosis.  Lancet  ,  349,  711–714.Timor-Tritsch, I.E., Peisner, D.M., Monteagudo, A.  et al.  (1993) Multifetalpregnancy reduction by transvaginal puncture: evaluation of the techniqueused in 134 cases.  Am. J. Obstet. Gynecol.,  168,  799–804. 1998 Yovel, I., Yaron, Y., Amit, A.  et al.  (1992) Embryo reduction in multifetalpregnancies using saline injection: comparison between the transvaginaland the transabdominal approach.  Hum. Reprod.,  7,  1173–1175.  Received on December 3, 1997; accepted on April 8, 1998 
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