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In-vitro fertilisation and risk of multiple pregnancy
RESEARCH LETTERS
40
Ozkan Ozturk, Allan Templeton
30
There is concern about the medical, social, and economic consequences of multiple pregnancy after in-vitro fertilisation (IVF). The most effective way to limit the risk of such a pregnancy is to replace only one or two embryos simultaneously. This strategy, however, is thought to reduce pregnancy rates. We analysed the rates of multiple pregnancies and live-births in all clinics in the UK in relation to their elective two-embryo transfer (ETT) policies. Our results suggest that replacement of two embryos eliminates the chance of triplets without affecting overall success rates.
Livebirth rate (%)
In-vitro fertilisation and risk of multiple pregnancy
20
r=⫺0·05
10
0 0
Lancet 2002; 359: 232–232
The aim of assisted reproduction is to increase the chance of pregnancy. However, multiple pregnancies often arise as a result of the simultaneous transfer of more than one embryo during in-vitro fertilisation (IVF). Although the need to minimise the frequency of this iatrogenic complication is recognised, debate has primarily focused on how to achieve such a result without compromising overall live-birth rates.1,2 Since we are unable to reliably predict whether or not implantation of an embryo will occur, or whether the endometrium will be receptive, some researchers feel that reduction in the number of embryos transferred might adversely affect treatment outcome.2 Findings of an analysis of individual IVF cycles logged in a national database indicate that elective transfer of two embryos, when more than four are available, results in a reduced number of triplets without affecting live-birth rate.3 Our aim was to ascertain the validity of this finding in individual clinics, through assessment of data published by the Human Fertilisation and Embryology Authority (HFEA).4 Since 1991, the HFEA has had a statutory duty to collect information about IVF treatments and their outcomes from all licensed clinics in the UK. In 2000, they published details of 27 230 IVF or intracytoplasmic sperm injection (ICSI) treatment cycles done between April, 1998, and March, 1999. Data were presented in the form of live-birth rates, number of singleton, twin, and triplet births, and proportion of treatment cycles in which a choice was made to transfer two embryos instead of three. Of 74 licensed clinics, livebirth rates for all age groups were available from 64, and 63 centres reported multiple pregnancy rates. 0·5
Individual clinic values
60 80 100 20 40 Proportion of elective two-embryo transfers (%)
Figure 2: Elective two-embryo transfer and overall live-birth rates per embryo transfer Cases weighted by number of patients from each clinic.
We used SPSS (version 9.0.1) for analysis of data. We used the square root transformation for triplet birth rates, to satisfy the assumption of normality. The strength of association between birth rates and proportion of elective two-embryo transfer (ETT) cycles was tested with Pearson correlation coefficient to show an ecological correlation based on cliniclevel data. We noted a positive association between proportion of ETT cycles and singleton birth rates (correlation coefficient 0·32, p=0·01), and a negative association between ETT and triplet births (p=0·009, figure 1). We did not see a correlation between ETT and overall live-birth rates (p=0·66, figure 2). Additionally, no significant correlation was evident between ETT and twin-birth rates (⫺0·18, p=0·15). Thus, previously expressed concerns2 about two-embryo transfer seem unsubstantiated. Our findings indicate that individuals who work in IVF units that do more frequent ETTs are more likely to achieve singleton births than triplets, without compromising success rates. Our results lend support to the recommendations made by the British Fertility Society and the Royal College of Obstetricians and Gynaecologists, which state that two-embryo transfers should be the norm.5 Transfer of two embryos does not guarantee a singleton birth, however, as twins are still possible. A policy of elective singleembryo transfer, aimed at reducing the number of twins born to the same rate that arises naturally, is being investigated. Future work should concentrate on this area. Contributors O Ozturk designed the study, collected and analysed results and wrote the manuscript. A Templeton initiated and conceptualised the report, identified the key areas of discussion based on the results of data analysis, and reviewed the manuscript.
0·4 Triplet birth rate*
Individual clinic values
Conflict of interest statement None declared.
0·3
1
0·2
2 3
0·1
r=⫺0·33 4
0
5
0
20
40
60
80
100
Proportion of elective two-embryo transfers (%) Figure 1: Elective two-embryo transfer and triplet birth rates *Square root transformed. Cases weighted by number of patients from each clinic.
232
Templeton A. A check on limiting multiple births. Lancet 2000; 355: 1999–2000. Craft I, Gorgy A, Podsiadly B, Venkat G. Limiting multiple births. Lancet 2000; 355: 1103–04. Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med 1998; 339: 573–77. Human Fertilisation and Embryology Authority (UK). The patients’ guide to IVF clinics. London: HFEA, 2000. Murdoch AP. How many embryos should be transferred? Hum Reprod 1998; 13: 2666–70.
Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen AB24 3DB, UK (O Ozturk MRCOG, A Templeton FRCOG) Correspondence to: Dr Ozkan Ozturk (e-mail: [email protected])
THE LANCET • Vol 359 • January 19, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
40
Ozkan Ozturk, Allan Templeton
30
There is concern about the medical, social, and economic consequences of multiple pregnancy after in-vitro fertilisation (IVF). The most effective way to limit the risk of such a pregnancy is to replace only one or two embryos simultaneously. This strategy, however, is thought to reduce pregnancy rates. We analysed the rates of multiple pregnancies and live-births in all clinics in the UK in relation to their elective two-embryo transfer (ETT) policies. Our results suggest that replacement of two embryos eliminates the chance of triplets without affecting overall success rates.
Livebirth rate (%)
In-vitro fertilisation and risk of multiple pregnancy
20
r=⫺0·05
10
0 0
Lancet 2002; 359: 232–232
The aim of assisted reproduction is to increase the chance of pregnancy. However, multiple pregnancies often arise as a result of the simultaneous transfer of more than one embryo during in-vitro fertilisation (IVF). Although the need to minimise the frequency of this iatrogenic complication is recognised, debate has primarily focused on how to achieve such a result without compromising overall live-birth rates.1,2 Since we are unable to reliably predict whether or not implantation of an embryo will occur, or whether the endometrium will be receptive, some researchers feel that reduction in the number of embryos transferred might adversely affect treatment outcome.2 Findings of an analysis of individual IVF cycles logged in a national database indicate that elective transfer of two embryos, when more than four are available, results in a reduced number of triplets without affecting live-birth rate.3 Our aim was to ascertain the validity of this finding in individual clinics, through assessment of data published by the Human Fertilisation and Embryology Authority (HFEA).4 Since 1991, the HFEA has had a statutory duty to collect information about IVF treatments and their outcomes from all licensed clinics in the UK. In 2000, they published details of 27 230 IVF or intracytoplasmic sperm injection (ICSI) treatment cycles done between April, 1998, and March, 1999. Data were presented in the form of live-birth rates, number of singleton, twin, and triplet births, and proportion of treatment cycles in which a choice was made to transfer two embryos instead of three. Of 74 licensed clinics, livebirth rates for all age groups were available from 64, and 63 centres reported multiple pregnancy rates. 0·5
Individual clinic values
60 80 100 20 40 Proportion of elective two-embryo transfers (%)
Figure 2: Elective two-embryo transfer and overall live-birth rates per embryo transfer Cases weighted by number of patients from each clinic.
We used SPSS (version 9.0.1) for analysis of data. We used the square root transformation for triplet birth rates, to satisfy the assumption of normality. The strength of association between birth rates and proportion of elective two-embryo transfer (ETT) cycles was tested with Pearson correlation coefficient to show an ecological correlation based on cliniclevel data. We noted a positive association between proportion of ETT cycles and singleton birth rates (correlation coefficient 0·32, p=0·01), and a negative association between ETT and triplet births (p=0·009, figure 1). We did not see a correlation between ETT and overall live-birth rates (p=0·66, figure 2). Additionally, no significant correlation was evident between ETT and twin-birth rates (⫺0·18, p=0·15). Thus, previously expressed concerns2 about two-embryo transfer seem unsubstantiated. Our findings indicate that individuals who work in IVF units that do more frequent ETTs are more likely to achieve singleton births than triplets, without compromising success rates. Our results lend support to the recommendations made by the British Fertility Society and the Royal College of Obstetricians and Gynaecologists, which state that two-embryo transfers should be the norm.5 Transfer of two embryos does not guarantee a singleton birth, however, as twins are still possible. A policy of elective singleembryo transfer, aimed at reducing the number of twins born to the same rate that arises naturally, is being investigated. Future work should concentrate on this area. Contributors O Ozturk designed the study, collected and analysed results and wrote the manuscript. A Templeton initiated and conceptualised the report, identified the key areas of discussion based on the results of data analysis, and reviewed the manuscript.
0·4 Triplet birth rate*
Individual clinic values
Conflict of interest statement None declared.
0·3
1
0·2
2 3
0·1
r=⫺0·33 4
0
5
0
20
40
60
80
100
Proportion of elective two-embryo transfers (%) Figure 1: Elective two-embryo transfer and triplet birth rates *Square root transformed. Cases weighted by number of patients from each clinic.
232
Templeton A. A check on limiting multiple births. Lancet 2000; 355: 1999–2000. Craft I, Gorgy A, Podsiadly B, Venkat G. Limiting multiple births. Lancet 2000; 355: 1103–04. Templeton A, Morris JK. Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl J Med 1998; 339: 573–77. Human Fertilisation and Embryology Authority (UK). The patients’ guide to IVF clinics. London: HFEA, 2000. Murdoch AP. How many embryos should be transferred? Hum Reprod 1998; 13: 2666–70.
Department of Obstetrics and Gynaecology, University of Aberdeen, Aberdeen AB24 3DB, UK (O Ozturk MRCOG, A Templeton FRCOG) Correspondence to: Dr Ozkan Ozturk (e-mail: [email protected])
THE LANCET • Vol 359 • January 19, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.