The outcome of multiple pregnancy

The outcome of multiple pregnancy

Pat Doyle

Epidemiology Unit, Department of Epidemiology and Population Sciences,London School of Hygiene and Tropical Medicine, Keppel Street, London

WC IE 7HT, UK

The incidence of multiple pregnancy and delivery has increased dramaticallyover the past 10-15 years in many developed countries of the world. Datafor England and Wales show that between 1980 and 1993 the twin maternityrate increased by ~25% and the triplet and higher order maternity ratemore than doubled. Similar trends have been reported elsewhere. Themajority of these increases have been linked to the use of ovarian stimulantsand assisted reproduction techniques, and multiple pregnancy must beconsidered to be one of the most important adverse outcomes in currentmethods of infertility treatment. Obstetric complications associated withmultiple pregnancy include prenatal screening problems and increasedincidence of pregnancy-induced hypertension, antepartum haemorrhage,preterm labour and assisted or surgical delivery. Neonatal problems includelow birthweight and increased prevalence of congenital malformations.Compared with singletons, neonatal mortality was seven times higher intwins and >20 times higher in triplets and higher order births in Englandand Wales in 1991. Survivors also suffer higher rates of cerebral palsy andother neurological impairments. Most studies of pregnancies and babiesresulting from assisted reproduction have demonstrated similar, if not higher,risks of adverse obstetric and neonatal outcomes for multiple births comparedwith national expectations. A poorer outcome in multiple pregnancy, especi-ally in triplet and higher order pregnancy, supports the replacement of twogood quality embryos in assisted reproduction treatment cycles.Key words: assisted reproduction/multiple maternity/multiple pregnancy/trends

Introduction

In the treatment of infertility, ovarian stimulation and the replacement of multipleembryos increase the probability of pregnancy. These techniques also increasethe risk of multiple pregnancy. Although many infertile couples may welcomemultiple pregnancy as a way of achieving their desired family, many are unawareof the complications and poorer outcomes associated with them. Data fromthroughout the world now show that multiple pregnancy, especially triplet and

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Figure 1. Trends in multiple maternities in England and Wales, 1971-1993. (A) All multiple maternities. (B)Twin maternities. (C) Triplet and higher order maternities. (D) Numbers of twin, triplet and quadruplet plusmaternities. These data include maternities where still births occurred. (Office of Population Censuses andSurveys, FM1.)

higher order pregnancy, is one of the most important adverse effects of ovarianstimulation and assisted reproduction treatment. This paper discusses the impactof infertility treatments on national trends in multiple births, and considers themajor short- and long-term health consequences of multiple birth.

National trends in multiple maternities

The incidence of deliveries with more than one baby (multiple maternities) hasincreased dramatically over the past decade in many countries. There have beenreports of increasing multiple maternities in the USA (Luke, 1994; Jewell andYip, 1995), Canada (Millar et al, 1994), Belgium (Derom et al, 1993), TheNetherlands (van Duivenboden et al, 1991), France (Tuppin et al, 1993) andTaiwan (Chen et al, 1992). In England and Wales, the downward trend evidentfrom the early 1950s slowed and began an upward course in the early 1980s inall maternal age groups except the under 20s (Botting et al, 1987). Thisincreasing trend has continued into the 1990s (Figure 1A) (Office of PopulationCensuses and Surveys, Series FM1). The proportion of multiple maternitiesincreased from 9.8 per 1000 in 1980 to 12.7 per 1000 in 1993. Most of thisincrease is made up of twin maternities, because they are the most commonmultiple pregnancy (Figure IB). Triplets and higher order maternities remain

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relatively rare, but they showed an even more dramatic change within the timeperiod, increasing from 1.5 per 10 000 in 1980 to 3.7 per 10 000 in 1993 (Figure1C). Changes in the numbers, rather than rates, of multiple maternities are shownin Figure ID. In 1980 there were 6308 twin, 91 triplet and five quadruplet orhigher order maternities in England and Wales. This increased to 8302 twin, 234triplet and 13 quadruplet or higher order maternities by 1993.

Contribution of ovarian stimulation and assisted reproductiontreatment to national multiple birth rates

Although some of the increase in multiple births can be attributed to nationalincreases in age at childbirth, the majority is associated with treatments forinfertility. An accurate assessment of the impact of infertility treatment is difficultin the absence of complete national treatment data, but estimates have been madeusing hospital birth series, drug sales records and multiple birth registers. A UKstudy of 156 triplet, 12 quadruplet and one quintuplet delivery occurring in 1989found that 31% were conceived naturally, 34% were the result of ovarianstimulation and 35% of the mothers had undergone in-vitro fertilization (IVF)or gamete intra-Fallopian transfer (Levine et al., 1992). Using national data onmultiple maternities and fertility drug sales in France, Tuppin et al. (1993)estimated that between 1985 and 1989 50% of all triplet deliveries resultedfrom treatments with ovulation-inducing agents and 26% from other assistedreproduction techniques such as IVF. Similarly, data from the East FlandersProspective Twin Study have confirmed the close association between fertility-enhancing drugs, other reproductive technologies and multiple pregnancy (Deromet al, 1993).

National registers of assisted reproduction have reported proportions of multiplepregnancies ranging between 15 and 27% (Lancaster, 1992; Logerot-Lebrumet al., 1995). Correspondingly, the proportions of multiple birth babies lie between30 and 40% of all babies born following assisted reproduction treatment.

Obstetric complications

Multiple pregnancy carries extra risk for both mother and babies, and greatermonitoring of the pregnancy is required. Prenatal screening poses particulardifficulties. Apart from the technical problems of invasive procedures such asamniocentesis, the couple may have to cope with severe dilemmas when facedwith discordancy for abnormality (Nielson, 1992). Recent work has shown thatserum-free a-human chorionic gonadotrophin concentrations can be successfullyadjusted to produce standards for use in twin pregnancies (Wald and Densem,1994), but difficulties remain for prenatal screening in higher order pregnancies.

The incidence of pregnancy-induced hypertension is greatly increased inmultiple pregnancies, and both pre-eclampsia and eclampsia are more common

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(Chamberlain, 1991; Douglas and Redman, 1994). In a study of births followingassisted conception in the UK, 23% of women with a multiple pregnancy wereadmitted to hospital because of hypertension compared with 13% of motherswith singleton pregnancies (Beral et al, 1990). Similarly, bleeding duringpregnancy is more common in multiple births: 22% of the women with a multiplepregnancy in the above study were admitted to hospital because of bleeding atsome time during their pregnancy compared with 17% of mothers of singletons(Beral et al, 1990). These rates are generally higher than would be expected inthe general population (Tan et al, 1992). Growth retardation can occur at anytime during a multiple pregnancy, but is more likely to appear in the third trimesterwhen fetal demands on the placenta are greatly increased (Chamberlain, 1991).

It is of very great significance that preterm labour resulting in low birthweightis the most important determinant of perinatal and neonatal mortality. Nationaldata show median gestational durations of 40 weeks for singletons, 37 weeksfor twins and 33 weeks for triplets (Chamberlain, 1991), and the incidence ofpreterm delivery (<37 completed weeks of gestation) follows a clear upwardtrend with increasing plurality. The UK register of babies resulting from assistedconception found preterm delivery rates of 13% for singletons, 57% for twinsand 95% for triplets and higher order pregnancies (Beral and Doyle, 1990).These figures are significantly higher than expected using national rates, whichwere 6% for singletons and 38% for twins (Office of Population Censuses andSurveys). Similar results have been reported from other registers of assistedreproduction (Lancaster, 1992).

Surgical and assisted delivery is common in all multiple pregnancies, but thereis evidence that rates are higher in pregnancies following assisted reproductiontreatment. Only 13% of twin and 2% of triplet and higher order pregnanciesexperienced a normal vaginal delivery in the UK series (Beral et al, 1990). Ina comparative study of IVF versus naturally conceived pregnancies in Finland,62% of IVF multiple pregnancies were delivered by Caesarean section comparedwith 41% of naturally conceived multiple pregnancies (Gissler et al, 1995).

Neonatal outcome

Congenital malformations

There is good evidence that babies from multiple pregnancies have a higherprevalence of reported malformations at birth than singletons. Neural tube defectsand structural malformations of the gastro-intestinal tract are increased in twinscompared with singletons (Doyle et al, 1991). The study of malformations inassisted reproduction treatment babies is hampered by low statistical power toassess relatively rare outcomes and the incomplete nature of national congenitalmalformation registry data for comparison. Meta-analysis of data from severalassisted reproduction registers is required to investigate whether assisted reproduc-tion and other infertility treatments are associated with risks of congenitalmalformation over and above those expected, in both singleton and multiple births.

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4.4

2.9

0.8

2.4

6.1

14.2

22.8

3.9

6.3

33.0

19.3

75.6

10.6

15.1

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Table I. Mortality multiplicity of birth, England and Wales, 1991"

Mortality Singleton Twin Triplet and higherbabies babies order babies

Stillbirth rate (late fetal deaths per 1000 totalbirths)

Early neonatal mortality rate (deaths in first 6 daysper 1000 live births)

Late neonatal mortality rate (deaths at ages 7-27completed days per 1000 live births)

Post-natal mortality rate (deaths at ages >28 daysbut <1 year per 1000 live births)

Infant mortality rate (deaths at age < 1 year per1000 live births)

"Office of Population Censuses and Surveys, Series DH3, No. 26.

Low birthweight

Median birthweights in the UK are ~3300 g for singletons, 2500 g for twins,1800 g for triplets and 1500 g for quadruplets and above (Botting et al, 1990),and the proportion of low birthweight babies (<2500 g) rises with increasingplurality. In the UK MRC/IVF register data, 12% of singletons, 55% of twinsand 94% of triplets or higher order babies were of low birthweight. After makingallowance for differences in maternal age and parity, there is some evidence thatthese proportions are higher than expected compared with national data (Beraland Doyle, 1990; Tan et al, 1992).

Mortality

Early fetal death in the form of 'vanishing sacs' is a fairly common occurrencein a multiple pregnancy following assisted reproduction treatment. An ultrasoundstudy of 38 triplet pregnancies found that 50% experienced spontaneous reductionof at least one embryo (Manzur et al, 1995). It is likely that a similar phenomenonoccurs in naturally conceived pregnancies, and multiple conception rates areprobably much higher than the detected multiple pregnancy and correspondingmultiple maternity rates. Late fetal death is increased in multiple pregnancy, withthe stillbirth rate being over three times higher in twins (14.2/4.4 = 3.2) than insingletons and over four times higher in triplets and higher order births (19.3/4.4 = 4.4) m England and Wales in 1991 (see Table I and Figure 2, Office ofPopulation Censuses and Surveys, Series DH3). Neonatal deaths (0-27 days)show the greatest disparity by multiplicity, the twin rate being seven times andthe triplet plus rate >20 times (86.2/3.7 = 23.3) the singleton rate. Despite theirrelative rarity, multiple births make a large contribution to overall mortality rates.In England and Wales, multiple births made up 2.5% of all births, but 8% of allstillbirths, 19% of all neonatal deaths and 7% of all postneonatal deaths in 1991(Office of Population Censuses and Surveys, Series DH3). Mortality of multiple

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Figure 2. Mortality by multiplicity of birth: England and Wales, 1991.

births resulting from assisted reproduction treatment generally follows this patternof increasing risk with increasing plurality (Lancaster, 1992), although there isa tendency for the rates to be non-significantly higher than expected on the basisof national rates (Beral and Doyle, 1990).

Morbidity

The vast majority of excess mortality in multiple births is attributable to alow birthweight resulting from premature delivery (Chamberlain, 1991). Lowbirthweight is also a major risk factor for infant and childhood morbidities suchas cerebral palsy, mental retardation and cataract. Two recent studies of theincidence of cerebral palsy reported dramatically increased risks in multiplebirths: twins had risks approximately five times higher and triplets 17 timeshigher that in singletons (Petterson et ai, 1993), and the risks of producing atleast one child with cerebral palsy was estimated to be 1.5% for twin, 8% fortriplet and almost 50% for quadruplet pregnancies (Yokoyama et al, 1995). Theprevalence of cerebral palsy in babies resulting from infertility treatments is notknown, but results such as this make long-term follow-up studies imperative.

Conclusion

A dramatic increase in the numbers of multiple births in developed countries hasstimulated interest in the progress and outcome of such pregnancies. As well asconsiderable health risks, the social, psychological and financial impact of

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multiple births, especially higher order multiple births, has been highlighted(Botting et al, 1990; Levine et al, 1992; Gissler et al, 1995). Treatment forinfertility has improved dramatically over the past 15 years, but it is now wellrecognized that a balance has to be struck between offering a technique whichhas a reasonable chance of success whilst keeping the proportion of multiplepregnancies low. Methods of fetal reduction have been shown to be safe andeffective in reducing higher order pregnancies (Evans et al, 1994), but thepsychological and ethical issues surrounding the technique remain problematicand the avoidance of these pregnancies must be a priority. The Human Fertilizationand Embryology Authority of the UK recommend the replacement of up to threeembryos per IVF cycle (four in exceptional circumstances), and the Royal Collegeof Obstetricians and Gynaecologists (RCOG; London, UK) has recommendedabandonment of ovarian stimulation cycles if multiple mature follicles are present(RCOG, 1990). Recent trials on the replacement of two good quality embryosfor specific groups of women reduced triplet pregnancy rates but did notsignificantly depress pregnancy rates (Nijs et al, 1993; Staessen et al, 1993;Kodama et al, 1995), and there is recent evidence that the replacement of fewerembryos in assisted reproduction treatment cycles in the USA has been followedby a general decline in the number of higher multiple pregnancies (Evans et al,1995). The availability of large amounts of patient and treatment data wouldallow a statistical investigation of risk factors for multiple birth in assistedreproduction treatment, with the ultimate aim of tailoring treatment regimes todifferent types of patient. Pooling of data both nationally and internationally forthis purpose is to be recommended.

References

Beral, V. and Doyle, P. (1990) Births in Great Britain resulting from assisted conception, 1978—87. Br. Med. J., 300, 1229-1233.

Beral, V., Doyle, P., Tan, S.L. et al, (1990) Outcome of pregnancies resulting from assistedconception. Br. Med. Bull., 46, 753-768.

Botting, B.J., MacDonald-Davies, I. and MacFarlane, A. (1987) Recent trends in the incidence ofmultiple births and associated mortality. Arch. Dis. Childhood, 62, 941-950.

Botting, B., MacFarlane, A. and Price, F. (1990) Three, Four or More: A Study of Triplet andHigher Order Births. HMSO, London, UK.

Chamberlain, G. (1991) Multiple pregnancy. Br. Med. J., 303, 111-115.Chen, C.J., Lee, T.K., Wang, C.J. et al., (1992) Secular trend and associated factors of twinning

in Taiwan. Ada Genet. Med. Gemelloi, 41, 205-213.Derom, C , Derom, R., Vlietinck, R. et al., (1993) Iatrogenic multiple pregnancies in East Flanders,

Belgium. Fertil. Steril., 60, 493-496.Douglas, K.A. and Redman, C.W. (1994) Eclampsia in the United Kingdom. Br. Med. J., 309,

1395-1400.Doyle, P., Beral, V., Botting, B. and Wale, C.J. (1991) Congenital malformations in twins in

England and Wales. J. Epidemiol. Community Health, 45, 43-48.Evans, M.I., Dommergues, M., Timor-Tritsch, I. et al, (1994) Transabdominal versus transcervical

and transvaginal multifetal pregnancy reduction: international collaborative experience of morethan one thousand cases. Am. J. Obstet. Gynecol., 170, 902-909.

Evans, M.I., Littman, L., Louis, L.S. et al, (1995) Evolving patterns of iatrogenic multifetal

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pregnancy generation: implications for aggressiveness of infertility treatments. Am. J. Obstet.GynecoL, 172, 1750-1755.

Gissler, M., Silvero, M. and Hemminki, E. (1995) In-vitro fertilization pregnancies and perinatalhealth in Finland 1991-1993. Hum. Reprod., 10, 1856-1861.

Jewell, S.E. and Yip, R. (1995) Increasing trends in plural births in the United States. Obstet.GynecoL, 85, 229-232.

Kodama, H., Fukuda, J., Kambe, H. et al. (1995) Prospective evaluation of simple morphologicalcriteria for embryo selection in double embryo transfer cycles. Hum. Reprod., 10, 2999-3003.

Lancaster, P. (1992) International comparisons of assisted reproduction. Assist. Reprod. Rev., 2,212-221.

Levine, M.I., Wild, J. and Steer, P. (1992) Higher multiple births and the modern management ofinfertility in Britain. Br. J. Obstet. Gynaecol, 99, 607-613.

Logerot-Lebrum, H., De Mouzon, J., Hatchelot, A. and Spira, A. (1995) Pregnancies and birthsresulting form in vitro fertilization: French national registry, analysis of data 1986-90. Fertil.Steril., 64, 747-756.

Luke, B. (1994) The changing pattern of multiple births in the United States: maternal and infantcharacteristics, 1973 and 1990. Obstet. GynecoL, 84, 101-106.

Manzur, A., Goldsman, M.P., Stone, S.C. et al., (1995) Outcome of triplet pregnancies afterassisted reproductive techniques: how frequent are the vanishing embryos. Fertil. Steril., 63,252-257.

Millar, W.J., Wadhera, S. and Nimrod, C. (1994) Multiple births: trends and patterns in Canada,1974-1990. Health Rep., 4, 223-250.

Neilson, J.P. (1992) Prenatal diagnosis in multiple pregnancies. Cum Opin. Obstet. GynecoL, 4,280-285.

Nijs, M., Geerts, L., Van Roosendaal, E. et al., (1993) Prevention of multiple pregnancies in anin-vitro fertilization program. Fertil. Steril., 59, 1245-1250.

Office of Population Censuses and Surveys. Birth Statistics. HMSO, London, UK, Series FM1,Nos. 1-22.

Office of Population Censuses and Surveys. Mortality Statistics, Perinatal and Infant: Social andBiological Factors. HMSO, London, UK, Series DH3, No. 26.

Petterson, B., Nelson, K.B., Watson, L. and Stanley, F. (1993) Twins, triplets, and cerebral palsyin births in Western Australia in the 1980s. Br. Med. J., 307, 1239-1243.

Royal College of Obstetricians and Gynaecologists (1990) Guidelines on Assisted ReproductionInvolving Superovulation. RCOG, London, UK.

Staessen, C , Janssenswillen, C , Van den Abbeel, E. et al., (1993) Avoidance of triplet pregnanciesby elective transfer of two good quality embryos. Hum. Reprod., 8, 1650-1653.

Tan, S.L., Doyle, P., Campbell, S. et al., (1992) Obstetric outcome of in vitro fertilizationpregnancies compared with normally conceived pregnancies. Am. J. Obstet. GynecoL, 167,778-784.

Tuppin, P., Blonde], B. and Kaminski, M. (1993) Trends in multiple deliveries and infertilitytreatments in France. Br. J. Obstet. Gynaecol., 100, 383-385.

van Duivenboden, Y.A., Merkus, J.M. and Verloove-Vanhorick, S.P. (1991) Infertility treatment:implications for perinatology. Eur. J. Obstet. GynecoL Reprod. Biol., 42, 201-204.

Wald, N.J. and Densem, J.W. (1994) Maternal serum free a-human chorionic gonadotrophin levelsin twin pregnancies: implications for screening for Down's syndrome. Prenat. Diagn., 14,717-719.

Yokoyama, Y, Shimizu, T. and Hayakawa, K. (1995) Prevalence of cerebral palsy in twins, tripletsand quadruplets. Int. J. Epidemiol., 24, 943-948.

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Simpson: I have a comment just for the record. I think the difficulty in screeningin multiple gestations is less that of being able to perform amniocentesis, whichis now fairly simple with good ultrasound, but the lack of efficiency. It is difficultif not impossible to screen for Down syndrome because algorithms were notprepared for the detection of trisomies and neural tube defects in multiplegestations. For example, if a 5% rate in the detection of a neural tube defect inmultiple gestation is accepted, then only 40% of cases are detected. In order toachieve the 80% obtained in singleton gestations, we would have to performamniocentesis on 20% of cases. Thus, the greater problem is lack of detectionefficiency.My specific question relates to your thoughts about the US, where most patientsare paying for IVF out of their own pockets at a rate of about US $5000 to$10000 per treatment. Another $2000 or $3000 is added for ICSI. Given this, itis difficult to demand restriction on the number of embryos that are transferred,even though one can argue that if there are multiple order gestations, the familywould eventually never be able to pay all the bills. Thus, society would beinvolved.Perhaps a middle ground could be devised. Because pregnancy success is afunction of maternal age, one might transfer more embryos in, say a 35 to 38year old woman than in a younger woman. In the absence of a flexible policy,i.e. with a policy of restricted transfer, preimplantation genetic diagnosis to verifythe normalcy of embryos would probably be instituted. Thus, at least in theUSA, there would be a potential financial downside to restricting embryos. Howwould you respond to our side of the Atlantic?Doyle: I think that is a very good point about infertile couples desiring multiplebirths. But they have to be made aware, and most clinics do make people aware,of the long-term costs. The monetary costs of the treatment are an importantissue of course, but what are the long-term health costs? Having a child withsevere prematurity with a so called normal child is very costly to that familyand they should know the risk. My talk was based largely on national data.Whether risks are higher in ART is not known, but the idea about cost has to belong-term cost and not just financial cost. The other issue about changingtreatment algorithms according to the type of woman: her age, her diagnosticproblem, and so on to maximise the probability of producing a live birth, butminimising the chance of multiplicity, seems entirely appropriate. With goodenough data, clinicians could work out suitable schedules for specific groups ofpatients.Zeilmaker: I very much appreciated one of your last remarks, namely that tripletsshould be avoided at all costs. In this regard, I would like to make a smallcomment on the table you presented. The percentage of triplets of all pregnancieswas about four in your table, and it was a bit lower in another table presentedearlier. If we could calculate the number of triplets on the basis of pregnanciesonly originating from transfers of three or more embryos, that percentage would

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be much higher. In Rotterdam, we calculated that about 10% of all pregnanciesoriginating after transfer of three embryos were triplet pregnancies, which led tothe decision that never more than two embryos can be transferred. So our doctorshave to tell the women that if you get a pregnancy after transfer of 3 embryosyou have a 10% chance of getting a triplet. This is of course totally unacceptable.We have analysed the effect of age in Rotterdam, and up to the age of 38 therisk of producting a triplet is the same when three embryos or more are transferredand the patient becomes pregnant. We have to be careful with transfers evenwith patients of advanced age.Doyle: I appreciate your comment and I think the figures you quote illustratehow treatments have improved. I have data only from 1978 to 1987, whensuccess was much lower. We had data on numbers of embryos transferred andthe plurality of pregnancy, showing a clear link, but nowhere near as high asyou have just quoted. However, the data are rather old, and you are referring totreatments using new ovarian stimulation methods.Diedrich: Is fetal reduction a solution to avoid triplet deliveries?Doyle: This is out of my field, but I have read the literature. Data that have beenpublished show low risks for both mother and remaining fetus, but there is muchliterature about the psychology and the short- and long-term psychological aspectsof the procedure.Camus: With a fetal reduction in a triplet pregnancy, the outcome to expect isthat of a twin pregnancy. The obstetrical outcome is similar to the obstetricaloutcome of control twin pregnancies.Devroey: We have reported that perinatal morbidity is lower after reduction oftriplet pregnancies to twin pregnancies.Anonymous: How many pregnancies are lost when fetal reduction is performed?Camus: Several studies report that pregnancy loss after embryo reduction oftriplets to twins is about 10%. There is a similar take-home baby rate in reducedand non-reduced triplet pregnancies but the perinatal morbidity is significantlyless after embryo reduction.Nygren: I have three comments. First, the question of fetal reduction is verymuch dependent on which society you live in. In Scandinavia where we havebeen traditionally very liberal to abortion as part of a treatment schedule, fetalreduction is not acceptable. We do it occasionally, but it would never be 'part ofa system'. That would endanger the whole abortion law in my country.Secondly, yes, the women would like to have two eggs. My question is: wouldit be possible to say, yes you will have two eggs, but one at a time? If the otherone is frozen, how many are lost?Thirdly, most multiple pregnancies in my country arise not from IVF anymore,but originate from ovarian stimulation alone. We have issued guidelines nowthat ovulation must not be induced if you have more than three follicles of 18mm or more present.Devroey: With women less than 37 years of age, the implantation rate will be20% when one embryo is replaced. Secondly, we must make guidelines aboutovulation induction: any gynaecologist can convert from ovulation induction to

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IVF when he sees that there are too many follicles. I think that could be asolution to that problem.Ron-El: Vanishing twins are accepted to occur with a frequency of 18 to 20%.So we are lucky that triplets go spontaneously to twins in around 50% of thecases. In our programme, we are hardly trying to convince the patients to reducethe triplets to twins. The overall pregnancy loss in recent reports is between 3and 5% and this is also the range in our series.Tarlatzis: An interesting presentation at the 1995 IFFS meeting in Montpellierfrom Salat-Baroux showed a prospective study comparing perinatal outcome innon-reduced triplets and reduced triplets. Perinatal outcome was significantlybetter when the triplets were reduced in this prospective study.Diedrich: Is a lower success rate more acceptable than to reduce a tripletpregnancy?Doyle: If you choose embryos carefully, there is no reduction in success rate.There are ways around the problem. Again, I am not a practitioner, but recentreports, using only good-quality embryos, look very promising. Two-good qualityembryos, or even one good-quality embryo, has quite a good chance ofimplantation.Liebaers: Transferring only two good-quality embryos does not reduce the rateof twins, but does reduce the rate of higher multiples. If we want to reduce therate of twins, we should transfer one. Another issue is whether we get the samesuccess rate by using frozen embryos in subsequent cycles. That question wasnot answered.

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