1 Departments of Obstetrics and Gynaecology, 2 Medical Psychology, 4 Epidemiology and Biostatistics, University Medical Centre St Radboud Nijmegen, 3 Clinical Psychology, University of Nijmegen and 5 Department of Health Psychology, University of Tilburg, The Netherlands
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Abstract |
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Key words: anxiety/depression/in-vitro fertilization/model/pregnancy
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Introduction |
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The role of psychological factors in IVF/ICSI outcome has still to be established. As this knowledge is a prerequisite for adjuvant psychological interventions, the question has a major clinical relevance. Several statistical models have been published using combinations of biomedical factors in relation with IVF outcome. The model of Templeton is well known: it is based on a large database and includes the factors age, duration of infertility, number of previous unsuccessful IVF attempts, tubal indication for fertility treatment and number of previous pregnancies as independent predictors (Templeton et al., 1996). Others (Stolwijk et al., 1996
) identified two factors, i.e. at least two preceding gestations and age, to be significant in predicting IVF outcome. It was also demonstrated that both models have limited external validity (Stolwijk et al., 1996
; Smeenk et al., 2000
). A possible reason for the limited validity of the presented models is that they are based only on stable variables. Some studies, however, indicate that the success of assisted reproductive treatment may also be dependent on variable factors, such as a woman's distress level at the time of treatment (Boivin and Takefman, 1995
; Facchinetti et al., 1997
; Demyttenaere et al., 1998
). The main objective of the current study, conducted at three Dutch hospitals, was to clarify the additional role of pre-existing anxiety and depression on IVF/ICSI results, controlling for known predictors.
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Materials and methods |
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Of the 359 invited patients (313 in Nijmegen, 46 in Breda), 68 declined or were excluded. Reasons indicated by patients were: lack of time (n = 23), already participating in another study (n = 7), emotional burden of the treatment (n = 7) and unknown (n = 5). Twelve patients were excluded because of missing data, and 14 because of language difficulties. Thus, the remaining group consisted of 291 (81%) patients.
The demographic and gynaecological variables studied are derived from the model of Templeton: age, duration of infertility, number of previous pregnancies and infertility diagnosis. In addition to `tubal' factor (as diagnosed in Templeton's model), other infertility diagnoses were included. Since only the first cycle of each patient was included, number of previous unsuccessful IVF attempts was not included as a predictor.
Anxiety was measured by means of the Dutch version of the State and Trait Anxiety Inventory (STAI) [Spielberger et al., 1970; Vanderploeg et al., 1980 (Dutch version)], a scale showing satisfactory reliability and validity. Trait anxiety refers to a general tendency of an individual to be anxious, whereas state anxiety refers to the anxiety level of an individual at a given moment. Both measures include 20 items, the score for each item ranging from 1 to 4, with higher scores indicating greater anxiety. Thus, total scores range from 20 to 80. In our sample the coefficient alpha for state anxiety was 0.94, and that for trait anxiety 0.91.
Depression was measured by means of the Dutch version of the Beck Depression Inventory (BDI) [Beck and Beamesdeerer, 1976; Bouman et al., 1985 (Dutch version)], being one of the most widely used instruments for assessing intensity of depression and for detecting depression in the general population. This reliable and valid measure (Beck et al., 1988) includes 21 items, the score for each item ranging from 0 (low) to 3 (high). Thus, total scores range from 0 to 63. In our sample the coefficient alpha was 0.86. Because of high levels of curtosis and skewness on the BDI scale, square roots were taken from the scores and used in the analysis (Tabachnick and Fidell, 1996
).
The outcome measures were the number of follicles, number of embryos and pregnancy status. The number of follicles was defined as the number of follicles (9 mm) present on transvaginal ultrasound, on the day of human chorionic gonadotrophin (HCG) administration. Pregnancy was defined as a positive urinary pregnancy test 15 days after embryo transfer. In this analysis, attention was focused on the women who reached embryo transfer because the aim was to compare all stages of treatment, including the implantation phase.
All statistical analyses were performed by means of the SPSS program. Multiple logistic regression analysis was used to analyse the variables related to pregnancy. The first step was, by using a backward conditional stepwise procedure, to find biomedical variables from Templeton's model related to treatment outcome in the current sample. The second step was to add psychological variables to this block of variables, again in a stepwise backward procedure. Linear logistic regression techniques were used to compare outcome variables between groups, and t-tests were used to compare groups on baseline parameters.
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Results |
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Among the original group of 291 women, 237 (81.4%) reached embryo transfer. Reasons for not reaching embryo transfer were cancellation by patient (n = 4), poor response (n = 19), risk of ovarian hyperstimulation syndrome (n = 5) or total fertilization failure (n = 26). The group who did not achieve embryo transfer (n = 54) was the same age (P = NS) as the group who did achieve embryo transfer. In addition, no differences in state anxiety (P = NS), trait anxiety (P = NS) and depression (P = NS) scores were found. Sample characteristics with respect to demographic and psychological variables of the group that reached embryo transfer are shown in Table I.
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Discussion |
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In addition, an independent relation of `age' and `number of previous pregnancies' with the probability to become pregnant was found, and this is consistent with previous findings (Stolwijk et al., 1996). Other variables presented previously in a model (Templeton et al., 1996
) did not show any significant relationship with treatment outcome, stressing once more the limited external validity of the Templeton model.
Our data are also in agreement with those of a previous study (Facchinetti et al., 1997) in which effects of state anxiety, and not trait anxiety, on assisted reproductive treatment outcome were found. Others (Demyttenaere et al.. 1992
) also found a negative influence of state anxiety on IVF outcome, but did not publish any data on trait anxiety. In another study (Thiering et al., 1993
), significantly lower success rates for IVF were found in depressed versus non-depressed women, but no predictive value of the anxiety could be demonstrated. Several authors, however, found no relationship between the emotional status of women and the outcome of assisted reproduction treatment (Boivin and Takefman, 1995
; Harlow et al., 1996
; Slade et al., 1997
; Ardenti et al., 1999
).
Although the current study had good power, and was multicentre in design, our recommendation would be to reproduce the findings in a larger patient group and to validate the model in another population. Moreover, with the number of co-variables being limited to those found in the Templeton model, and the fact that logistic regression cannot establish the exact relationship among variables, causal inference should be made with caution. Finally, the possibility of selection bias cannot be excluded, as some patients indicated `stress' as a reason not to participate.
The mechanism of the distress effect on pregnancy rates is still unknown. Subtle disturbances of the cycle may play a role, these being caused by minor endocrinological alterations (Demyttenaere et al., 1989, 1994
; Psech et al., 1989
). In a prospective study in women undergoing IVF, an increase during state anxiety treatment was established, parallel to increases in serum prolactin and cortisol concentrations (Harlow et al., 1996
). Depression was found to be associated with an abnormal regulation of LH (Meller et al., 1997
).
Some studies suggest promising results of psychological interventions on pregnancy rates (Sarrel and DeCherney, 1985; Domar et al., 1990
, 2000
). However, further prospective research is needed in order to obtain a better understanding of the mechanisms involved and to provide an evidence base for effective stress reduction interventions aiming at better pregnancy rates.
In conclusion, the current study shows that, in addition to some well-known biomedical variables, state anxiety may have an independent contribution to explaining the variability in pregnancy rates. This effect is probably strongest in the implantation phase of the cycle. These findings are particularly important because in contrast to, for example, the factor of age, psychological factors may well be sensitive to interventions, thus increasing the chance of improving treatment results. In view of the current results, psychological factors should be taken into consideration in patient counselling.
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Acknowledgements |
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Notes |
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References |
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Submitted on December 29, 2000; accepted on April 4, 2001.