1 Aberdeen Fertility Centre, Aberdeen Maternity Hospital, Foresterhill, Aberdeen AB25 2ZL, UK
2 To whom correspondence should be addressed. e-mail: s.bhattacharya{at}abdn.ac.uk
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Abstract |
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Key words: IVF/patient information/provision of information/randomized controlled trial/single embryo transfer
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Introduction |
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These considerations have led to a move towards strategies for reducing multiple pregnancies in order to improve the safety of assisted reproduction. Evidence from observational studies suggests that, where a number of embryos are available, transferring two embryos may provide pregnancy and live birth rates comparable with those achieved by replacing three (Templeton and Morris, 1998). As a consequence, most IVF units in the UK and the rest of Europe have moved from a three-embryo to a two-embryo transfer (DET) policy. Although this has dramatically reduced the incidence of triplets, it has had little impact on twin rates, which remain close to 25% in most IVF units. While opinions regarding the acceptability of a twin pregnancy as one of the normal outcomes of assisted reproduction may vary, twins are associated with a 5-fold increased risk of perinatal mortality compared with singletons, as well as greater perinatal morbidity and long-term health problems (Dhont et al., 1999
). This inevitably aggravates the emotional burden on parents and leads to increased costs for them as well as for the health service.
The challenge facing providers of IVF treatment is to find a means of decreasing the rate of multiple pregnancy which is acceptable to couples undergoing treatment, many of whom are funding their own IVF cycles. The obvious way of reducing the risk of twin pregnancy is to perform elective single embryo transfer (eSET) in couples with a good prognosis, i.e. those more at risk of twins. A randomized controlled trial has demonstrated that cumulative pregnancy rates after SET in this group compare favourably with those achieved following DET, with very significant reduction in twinning rates (Martikainen et al., 2001; Tiitinen et al., 2001
). It is also likely that although more embryo transfers may be required to achieve the same live birth rate, the cost per child born using eSET could be the same or lower than that using DET (Wolner-Hanssen and Rydhstroem, 1998
; DeSutter et al., 2002
). While further trials are needed to establish the effectiveness of such a policy (Ozturk et al., 2001
), the success of these proposed trials will depend on whether clinicians as well as couples are in a state of equipoise. This implies that they are willing, in principle, to consider a policy of eSET as an alternative to DET and, even more crucially, the couples are willing to be randomized to either of these treatment options.
In recent times, there has been an increasing recognition of the need to increase patient participation in clinical decision making (Royal College of Obstetricians and Gynaecologists, 1998; General Medical Council, 2001
). Traditionally, views about the potential risks of multiple pregnancies in IVF have been polarized, with health professionals adopting a more conservative stance than that of consumers (Pinborg et al., 2003
). Couples undergoing IVF treatment often tend to focus on their individual circumstances and may not necessarily take into account the wider social and financial implications of multiple pregnancy. Many find the associated risks acceptable, and some consider a twin pregnancy a desirable outcome (Goldfarb et al., 1996
; Pinborg et al., 2003
).
The aim of our study was to compare the effect of alternative ways of providing information about risks associated with twin pregnancy on the acceptability of a hypothetical policy of eSET among couples undergoing IVF. The hypothesis was that facilitating access to detailed information about the risks associated with twin pregnancy would increase couples acceptance of an eSET policy.
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Materials and methods |
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Couples were contacted by means of an initial letter from the research nurse conducting the trial. Those who consented were randomized into one of three groups at the time of their first IVF clinic appointment. Couples were randomized on a 1:1:1 ratio into a control group (standard clinic information pack about IVF), a leaflet group (extra written information about twin pregnancies) and a discussion group (as in the leaflet group + short discussion with a nurse). Allocation was made by the research nurse by opening consecutive, numbered, sealed, opaque envelopes. The computerized randomization schedule was prepared by one of the authors (S.B.) who was not involved with recruitment. It was not possible to blind either the staff or the patients to the nature of the intervention.
Couples in group 1 (control) received no information other than that routinely given to all couples attending for IVF. Couples in group 2 (leaflet group) received, in addition, an extra information sheet addressing specific potential problems associated with twin pregnancy. This single-page document used a question/answer style to highlight maternal and fetal/neonatal risks in twin pregnancies (including prematurity and long-term handicap) and included published results of outcomes following eSET. It drew on epidemiological studies (including results of randomized trials where available) from the literature and was put together by the research team comprising two medical and two nursing staff. The information sheet was piloted on patients before the start of the trial. Those allocated to group 3 (discussion group) received, in addition to the two sources of information described above, a 10 min discussion with a member of the nursing staff who went over the information contained in the information sheet. While specific questions asked by the couple were answered, no fresh information other than that in the twin information sheet was volunteered.
The primary outcome was the acceptability to couples of a hypothetical policy of eSET. Secondary outcomes measured couples knowledge of the risks associated with twin pregnancy in the context of IVF.
Data were collected by means of a questionnaire completed jointly by the couple after their clinic visit. This was completed at home and mailed back to the IVF unit. Questionnaires were anonymized but coded to allow tracing of non-responders. Non-responders were contacted initially by letter and then by telephone and reminded to send in completed questionnaires.
The first section of the questionnaire explored the sources of information couples used. The male and female partners were asked to complete this section separately as it was assumed that they might not have used the same sources. The subsequent parts of the questionnaire were completed by the couple together, as treatment decisions would have to be agreed by both partners. Couples were then asked to consider and rate their perception of complications associated with treatment. Next, their views on the optimum number of embryos for replacement were sought. The final section focused on eSET and the acceptability of this policy to couples under different circumstances.
The questionnaire was devised to take 1015 min to complete. It was piloted initially with other members of staff and then, after making a number of adjustments, on 10 couples attending for treatment. A final pilot of another 10 couples showed good understanding and high rates of completion of the questionnaire.
A previous survey within the same IVF unit showed that 20% of the couples undergoing IVF were prepared to consider an eSET policy (S.Bhattacharya, personal communication). In order to show a 30% increase in acceptability between the control group and each of the two experimental groups (i.e. from 20 to 50%), 58 patients were required in each group in order to provide 90% power at the 5% significance level. Data analysis was by intention to treat, using SPSS for Windows version 11 (SPSS Inc., Chicago, IL), and GraphPad Instat Version 3.01 (GraphPad Software Inc., CA). Students t-test and 2 tests were used where appropriate.
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Results |
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Discussion |
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Despite widespread awareness of the need to increase patient participation in clinical decision making, the clinical debate about moving towards eSET (Gerris, 2000) has so far failed to engage consumers. To our knowledge, this is the first prospective randomized trial to examine the effect of alternative means of information provision on decision making in infertility, although similar exercises have been performed in other clinical areas (Graham et al., 2000
; Kennedy et al., 2002
).
The study was confined to couples in their first cycle of treatment. One of the problems encountered in this trial was the failure to recruit a proportion (72/272 or 25%) of all eligible couples. Due to our inability to collect data from those who withheld consent for this study, it is difficult to establish whether participants differed significantly from non-participants. Analysis of an anonymized version of the clinic database suggests that participants had a shorter mean duration of infertility than the total eligible cohort. This may, to a small extent, limit the generalizability of the findings.
A further weakness of this study concerns potential bias associated with the face to face discussions, which were conducted by all eight nurses within the IVF unit. Efforts were made to minimize individual variation by ensuring that all of them followed a standard protocol which required them not to volunteer information outside the contents of the information leaflet except in response to specific questions from the couple. It can also be argued that involving a number of different nurses could actually enhance the generalizability of the study. In designing the trial, a substantial difference (30%) in acceptability rates was chosen as the basis for the power calculation. This reflected the clinical perception that a minimum of 50% of all couples would need to favour the prospect of an eSET before this policy could either be evaluated in the context of a randomized controlled trial (Ozturk et al., 2001) or be implemented in everyday practice.
We aimed to capture the opinions of the couples as opposed to individual opinions of the male and female partners, as we felt that decisions in IVF have to be taken jointly by couples. It is therefore likely that individual variations in opinions have not been picked up by our questionnaire.
In counselling subfertile couples about the number of embryos to be transferred, appreciation of the nature and magnitude of the risks posed by twin pregnancy is crucial. Approximately two-thirds of couples in this study were able to predict the likelihood of twins in IVF correctly. Nearly all were aware of the higher risks associated with twins; two-thirds indicated a preference for a single baby, although fewer than 10% felt that they would be deterred by the prospect of having twins. This is in contrast to data from some previous studies that suggest that despite being well educated about risks of multiple pregnancies, couples with infertility frequently desire twins and triplets (Leiblum et al., 1990; Gleicher et al., 1995
; Goldfarb et al., 1996
). Other workers (Grobman et al., 2001
) have found that women undergoing fertility treatment are unaware of the risks of perinatal complications associated with multiple gestations and are willing to reconsider their views on the basis of newly acquired knowledge. In our cohort of couples, levels of knowledge about twins and acceptability of eSET were comparable in the three randomized arms, suggesting that alternative methods of information provision had a minimal effect on either knowledge levels or risk perception in this cohort. Couples were more concerned about perceived treatment failure than iatrogenic complications such as ovarian stimulation and multiple pregnancy.
Most couples in our study favoured the transfer of two embryos, which is the existing policy in our IVF unit. This acceptance of the status quo has been noted in previous studies on hospital patients. Only a third of couples in any of the three randomized groups felt that reducing the number of twins by an SET policy was acceptable if it meant slightly reduced pregnancy rates. This is similar to the findings from Denmark reported by Pinborg et al. (2003) in a population of women with IVF/ICSI pregnancies. There was a degree of conflict between couples perceptions of what was appropriate in principle and what they actually wanted for themselves. For instance, while only 6% of couples in the control group felt that three embryos should be replaced in principle, nearly a quarter of them declared a preference for three-embryo transfer in their own treatment. There was also a non-significant gradient in preference for a three-embryo transfer in the three randomized arms (23 versus 15 versus 10%).
In general, attitudes towards eSET were negative in all three groups, and seemed independent of the methods of information provision. Even an assurance of similar rates of success (as compared with DET) convinced just over 80% of couples about the acceptability of eSET. A fixed charge irrespective of the number of treatment cycles would encourage just over half of all couples in each group to consider eSET. Couples convictions were deep and unaffected by external factors such their own funding status or the possibility of bearing the costs of neonatal care.
In conclusion, it seems that manipulating the content of information or the method in which it is presented does not change couples attitudes to either the risks posed by twin pregnancy in the context of IVF or the role of eSET in eliminating them.
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Acknowledgements |
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References |
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Submitted on October 23, 2003; resubmitted on January 2, 2004; accepted on January 22, 2004.