1 The Fertility Clinic, University of Copenhagen. Rigshospitalet, and 2 Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Panum Institute, Denmark
3 To whom correspondence should be addressed at: The Fertility Clinic, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. e-mail: apinborg{at}rh.dk
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Abstract |
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Key words: attitudes/IVF/mothers/single embryo transfer/twins
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Introduction |
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Twin pregnancies carry additional risk to mother and child and increase the health economic costs (Wølner-Hanssen and Rydhstroem, 1998; Keith et al., 2000
). Although register-based and casecontrol studies on the outcome of IVF pregnancies have shown that singleton IVF pregnancies are at a slightly increased risk of perinatal morbidity and mortality, twin pregnancies are the main factor in the poorer perinatal outcome compared with spontaneous pregnancies (Bergh et al., 1999
; Dhont et al., 1999
; Westergaard et al., 1999
). Moreover IVF children have an increased risk of developing cerebral palsy and a higher hospitalization rate mainly due to the high twinning rate (Ericson et al., 2002
; Strömberg et al., 2002
). Hence increased concern about embryo transfer policy is being expressed and single embryo transfer (SET) is being intensively discussed in many European countries. In 1997 The Danish National Board of Health recommended that only two embryos should be transferred per treatment cycle. In Scandinavia the triplet pregnancy rate has been minimized, but overall the twin pregnancy rate has remained the same (Nygren and Andersen, 2001
). However, the multiple pregnancy rate in Helsinki University Central Hospital in Finland has been reduced from 24% in 1998 to 8% in 2001 after the implementation of elective SET as their daily practice (Tiitinen et al., 2002
).
When informing and counselling the infertile couples about the number of embryos to be transferred, knowledge of patients attitudes and expectations towards twins and SET is of great importance. Previous studies have shown that prior to treatment the attitudes towards multiple pregnancy and various pregnancy complications differ between fertile and non-fertile women. A questionnaire survey with a response rate of only 15% (582 out of 3800 couples) noted that a desire for conception of twins was expressed by 6790% (Gleicher et al., 1995). Three other studies showed that infertile women found multiple pregnancy and the associated risks more acceptable than fertile women (Leiblum et al., 1990
; Goldfarb et al., 1996
; Grobman et al., 2001
). Despite the intensive debate no studies have investigated attitudes among women with a history of infertility and experience with their own twins. Recently, the impact of patients choice for single or double embryo transfer on pregnancy and twinning rates was published by a Belgian group (De Neuborg et al., 2002
). The present study was a Danish national cohort study undertaken to advance our understanding of womens attitudes towards twins and SET, thereby promoting the counselling process and the implementation of elective SET.
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Materials and methods |
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The Danish Medical Birth Registry, which records all pregnancies and births in Denmark was used to identify all women giving birth to twins from January 1, 1997 to December 31, 1997. Since January 1, 1994 it has been compulsory to report each initiated IVF or ICSI cycle to the Danish IVF Registry in the National Board of Health (Andersen et al., 1999). The personal identification number of the women was cross-linked with the Danish IVF registry to identify the IVF/ICSI treated women. This enabled a separation of the twin mothers into two groups, namely the study population of IVF/ICSI-twin mothers and the control group of non-IVF/ICSI-twin mothers. The control group of IVF/ICSI-singleton mothers was identified in the same way. The non-IVF/ICSI-twin mothers with a history of other types of assisted reproductive treatment [ovarian stimulation with/without intrauterine insemination(IUI)] prior to their delivery, could not be identified through the IVF registry, but were identified by the questionnaire. Addresses were found through The Danish Central Population Registry (CPR). Eleven women had emigrated, one had died, and addresses of five women were not found in the CPR.
In October 2001, 1769 questionnaires were mailed to the study group consisting of all women giving birth to IVF/ICSI-twins in Denmark in 1997 (n = 266) and to the two control groups consisting of all IVF/ICSI-singleton mothers (n = 764) and all non-IVF/ICSI-twin mothers (n = 739) giving birth in Denmark in 1997. After two requests 1436 questionnaires were received resulting in an overall response rate of 81% [IVF/ICSI-twin mothers 89% (n = 236), IVF/ICSI-singleton mothers 83% (n = 634) and non-IVF twin mothers 77% (n = 566)]. The children were 34 years old when the women received the questionnaire. Women with stillborn children or children who died within the first 3 years of life also received a questionnaire. Child deaths were reported by 15 IVF/ICSI-twin mothers (in 12 cases one twin died and in three cases both twins died), eight IVF/ICSI-singletons mothers and 11 non-IVF/ICSI-twin mothers (in eight cases one twin died and in three cases both twins died). Demographic questions were addressed regarding the womans age, length of infertility, parity, the number of prior children, social position and divorce rate.
Pilot test
The questionnaire was pilot-tested in summer 2001 among 39 women giving birth in 1998 after treatment with IUI. These participants were invited to comment on the questions and the response categories and on any important theme which had not been addressed. The pilot test showed good distribution of scores across the different response categories. The statements concerning twins were finally constructed based on the written responses in the pilot test.
Questionnaire
The survey comprised several types of questions. The first section ascertained demographic information and infertility history. In addition to age, parity and social position, mothers were asked about their history of infertility and fertility treatment in relation to their delivery in 1997. Social position was measured in a standardized method including seven items about school education, vocational training and job position and categorized into six social classes I to V and VI (receiving social benefits) (Hansen, 1984). In the analyses the groups were merged into three different groups: High (I + II), medium (III + IV), and low social class (V + VI). A minor group was outside classification due to leave, sickness or unemployment.
The second and third section of the survey covered the pregnancy, delivery and childrens morbidity. In the fourth section of the survey we sought to determine patients perceptions towards twins and attitudes towards SET. This section consisted of 10 items especially designed for this research. To provide a point of comparison, the women were briefly advised on the additional risk a twin pregnancy carries to mother and child (no risk estimates were given) and informed that nearly 40% of all children born after IVF treatment are twins. In the first two items the participants were asked, both prior to pregnancy and again after their delivery in 1997, whether they found either a singleton or twins most desirable. The following items contained different statements about twins and singletons; respondents preferring twins were asked to mark the statements regarding why they preferred twins, and respondents preferring a singleton were asked to mark the statements regarding why they preferred a singleton.
After being presented with the recommendation on the transfer of only two embryos in ART from The Danish National Board of Health, the respondents were asked to rank their attitudes towards one, double or triple embryo transfer in the following three items. The response categories in these items were a five point Likert scale from (1) agree to (5) disagree. Responses of agree and partly agree were considered affirmative to the questions and responses of partly disagree and disagree were seen as a rejection. In Denmark, the first three IVF/ICSI treatments are provided free of charge in the Public Health System; in the last items the respondents were asked whether they would agree to SET, if they were offered more than the three normally reimbursed IVF/ICSI treatments. A version of the questionnaire in English is available from the first author, A.P.
Statistics
The results were analysed by SPSS (Statistical Package for Social Sciences) version 10.0. Statistical significance was defined as a probability value of P < 0.05. Differences of the means of continuous parametric data were analysed with the use of Students t-test. To compare differences of frequencies between groups, 2-analyses were used. All analyses were carried out separately for all three groups. Multivariate logistic regression analyses were performed to examine predictors of respondents wishes for twins and attitudes towards SET. IVF/ICSI-twin mothers were studied versus non-IVF/ICSI-twin mothers and in separate analyses IVF/ICSI-twin mothers versus IVF/ICSI-singleton mothers. Women who did not consider the items were excluded from the analyses. The following predicting variables were entered into the models: maternal age, parity, social position and birth weight. Mortality was not entered as a predictor, because the numbers were too small. In the analysis with IVF/ICSI-twin mothers versus IVF/ICSI-singleton mothers duration of infertility and IVF versus ICSI were also entered. The outcome measure was the wish for twins and agreement to SET. We used backwards elimination and excluded predictor variables which were not significantly associated with the outcome measure. The participants were separated into four age groups: <30, 3034, 3539 and >40 years, parity was entered as a binary variable either 0 or >1 deliveries before the delivery in 1997; infertility length was separated into three groups: 05 years, 610 years and >10 years; birth weight was separated in three groups: >2500 g, 15002499 g and <1500 g; and finally social position was separated in three groups: high, medium and low.
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Results |
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Reasons to prefer either twins or singletons are listed in Table IV. The majority of IVF/ICSI-twin mothers responded that they preferred twins as their first child because it could be their only opportunity of having two children and that twins are a joy to each other. Among the few IVF/ICSI-twin mothers, who would have preferred a singleton as their first child, the most common reason was that it is difficult for the mother to have twins. Very few of the IVF/ICSI-twin mothers would have preferred a singleton because of the additional risk in a twin pregnancy or because it is difficult for a child to be a twin. The non-IVF/ICSI-twin mothers differed from the IVF/ICSI-twin mothers as less preferred twins as their first child because twins are a joy to each other (P < 0.001) and less preferred twins because it could be their only possibility of having two children (P < 0.001). Also more non-IVF/ICSI- twin mothers preferred a singleton because it is difficult to become a mother of two children at the same time (P < 0.001).
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Discussion |
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Our results show that twin mothers in general had positive preferences towards twins and that IVF/ICSI-twin mothers were significantly more positive towards twins compared with non-IVF/ICSI-twin mothers. These results demonstrate that a majority of the twin mothers seem willing to accept eventual risks and complications together with the social and physical strain. One could argue that women, and especially women who undergo IVF/ICSI treatment, easily convince themselves of the quality of their offspring, even if there are serious or minor problems, because they love their children. Presumably more correctly, they minimize twin complications both perinatally and postnatally. This problem is illustrated in a recent paper on perspectives of patients and health care professionals on blastocyst transfer (Hartshorne and Lilford, 2002). This study showed that it is still possible to convince couples to have a blastocyst transfer, notwithstanding the fact that most recent studies have showed absolutely no superiority of day 5 transfer. The wish for a child is so strong that infertile couples are willing to try almost everything.
Women who experienced child deaths were also included in the present study. The numbers are too small to make statistical comparisons meaningful, but the crude numbers showed that most of these women in the two IVF/ICSI groups had preferred twins and were against SET. It is noteworthy however that in the non-IVF/ICSI group three out of four women had preferred a singleton.
No differences were seen between respondents and non-respondents in the IVF/ICSI-twin group (Table I). On the contrary non-respondents in the two control groups (IVF/ICSI-singletons and non-IVF/ICSI-twins) had significant poorer perinatal outcome and higher child mortality compared with respondents. The high response rate in IVF/ICSI-twin mothers, even in women with poor outcomes, could be explained by the fact that these women felt an obligation to complete the questionnaire due to the interest in the future of their offspring. Since the IVF/ICSI-twin mothers had the most positive preferences towards twins, the unequal distribution of pregnancy outcome and mortality among respondents versus non-respondents in the control groups will not alter the conclusion.
In contrast with the clinicians view of a twin pregnancy as a high-risk pregnancy and even as a complication in ART (Hazekamp et al., 2000), very few twin mothers (3.86.4%) considered the additional risks of twin pregnancies to be a problem. We think this is due to insufficient information, or women minimizing or even denying the additional risk involved in twin pregnancies. We have to clarify that this study presents women who were counselled and underwent IVF/ICSI treatment during 1996 and 1997. At that time dual embryo transfer had just replaced triple embryo transfer in Denmark. Obviously, the couples did not receive thorough information on the additional risk in twins at embryo transfer and no further risk estimates were included in this questionnaire.
Acceptance of SET was expressed by 20% of the women in both IVF/ICSI groups. Further, one quarter of the women, who initially disagreed would accept SET if they were offered more than the three reimbursed treatments given in our country. Presumably, the use of less intensive ovarian stimulation protocols (Ingerslev et al., 2001
) would facilitate agreement to SET, if patients were offered additional IVF/ICSI treatments. Further, the introduction of reimbursement of IVF/ICSI treatments prior to the second child could also advance the cause of SET.
Infertility of >5 years duration was predictive of low acceptance of SET. Even though SET in selected patients does not reduce the pregnancy rate (De Neuborg et al., 2002), the majority of these couples apparently think that SET may prolong their infertility period. Our results suggest that delivery of a child with VLBW and hence potentially higher morbidity is predictive of agreement to SET; when a woman has a VLBW infant the experienced risk will outweigh the arguments against SET. In a previous study which has illustrated the same problem, the authors found that after being confronted with actual probabilities of specified perinatal complications associated with a twin pregnancy, women were less keen to have a twin pregnancy (Grobman et al., 2001
). Risks can be expressed in two different ways; the individual risk for the woman, who undergoes IVF treatment, and the attributive risk, the number of extra twins born each year in a population due to IVF. The first risk is of interest for the women, the latter for the society. As doctors we have an obligation also to take the attributive risk into account.
Prospective randomized SET trials in younger women with good quality embryos have shown that the twin birth rate can be reduced, while maintaining an ongoing pregnancy rate of 3240% (Gerris et al., 1999; Martikainen et al., 2001
; De Neuborg et al., 2002
). In the light of the high pregnancy rates in these studies and the considerable risk of twin pregnancies, SET in selected patients should be the future goal. Our study showed that a majority of IVF/ICSI women, treated and counselled during 1996 or 1997, expressed a relatively low acceptance of SET (1724%). However, 20% of the non-accepting women would agree to SET if they were offered more treatment cycles, but to do so they wanted at least three additional treatments. The women in the present study were not fully informed of the twin risk, nevertheless, the results indicate that mothers of children with potentially higher morbidity (children with VLBW) expressed a high acceptance of SET. The impact of this study is a reduction of the twin rate by implementation of elective SET, thereby minimizing the individual health risk of each IVF/ICSI child born. In this process extensive counselling, including exact risk estimates and information on SET pregnancy rates plays an essential role. Furthermore, reasonable selection criteria for SET are required. Through the process of counselling a fair amount of congruency between the thoughts of the patient and the doctor should be obtained. Two reports comparing health economical costs in SET versus double embryo transfer (DET) have shown that SET, if long-term morbidity is taken into account, is more cost-efficient (Wølner-Hanssen and Rydhstroem, 1998
; De Sutter et al., 2002
). Reimbursement of a limited number of additional IVF/ICSI treatment cycles and treatment cycles prior to the second child would also enhance the implementation of elective SET as our daily clinical practise. Legislative initiatives including strict selection criteria may perhaps be used to facilitate this process.
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Acknowledgements |
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References |
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Submitted on June 26, 2002; resubmitted on October 23, 2002; accepted on December 5, 2002.