Department of Anatomy and Human Biology, The University of Western Australia, Nedlands, W.A. 6907, Australia
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Abstract |
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Key words: infertility/IVF/prospective study/psychosocial stress
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Introduction |
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Psychosocial stressors originate in the social relationships or arrangements between individuals and are mediated through psychological processes. For couples involved in IVF and related programmes there are numerous psychosocial stressors to cope with, including: their infertility, the inconvenience of daily injections and blood samples, the perception of low success rates, the wait for results, and financial pressures. These are on top of the psychosocial stressors associated with everyday life. It has been suggested that differences in the ability to cope with stress could have implications for conception rates after treatment (Demyttenaere et al., 1992; Merari et al., 1992
) although there have been relatively few studies in this area.
An individual's ability to cope with stress is conditioned by their past experience and also by their current social environment (Lazarus, 1975). Thus, lifestyle factors, such as previous reproductive history, socio-economic status and work commitments, could influence the ability of women to cope with infertility treatment, and the relationship of these factors to treatment outcome is largely unknown. Personality characteristics, such as proneness to anxiety or depression, also determine one's ability to cope with stress (Spielberger et al., 1970
) and a number of studies have already suggested an association between depression and less favourable treatment outcome (Demyttenaere et al., 1992
; Thiering et al., 1993
). Therefore the purpose of the present study was to assess the role of anxiety proneness (trait anxiety), mood states, and specific lifestyle factors on outcome of IVF and GIFT treatment.
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Materials and methods |
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The questionnaire sought information on general demographic characteristics, aspects of lifestyle and psychological status, and included two standard psychometric tests; the StateTrait Anxiety Inventory (STAI; Spielberger et al., 1970) and the Bi-polar Profile of Mood States (POMS; McNair and Lorr, 1982
). The STAI is comprised of two separate scales; the State scale which measures the degree of anxiety at a particular given time and the Trait scale which assesses the tendency of an individual to respond to stressful circumstances with raised anxiety. The POMS measures six bipolar subjective mood states; one pole measures the positive or desirable aspects of the dimension while the other pole refers to the more negative and less desirable aspects. The six POMS scales are: composedanxious, agreeablehostile, elateddepressed, confidentunsure, energetictired and clearheadedconfused.
Details of reproductive characteristics were abstracted from records held within the clinic. Approximately 12 months after the entry of the last participant an outcome measure was determined for each participant in terms of whether they were pregnant or not pregnant and the number of treatment cycles undertaken to achieve pregnancy. Since IVF and GIFT cycles were sometimes interchanged and occasionally punctuated by frozen embryo transfer cycles, all treatments commenced were included when calculating the number of cycles to pregnancy. Some women withdrew from treatment or transferred to other clinics before pregnancy. In these cases, the number of cycles was censored at the time of withdrawal; that is the women were not pregnant at that time beyond which their status was unknown. For all analyses, a successful pregnancy was defined as a positive fetal heart beat detected by ultrasound at 8 weeks post oocyte collection.
Statistical analysis
The cumulative probability of pregnancy after successive treatments was estimated by product-limit analysis which takes into account the presence of censored observations. The separate effects of different variables (each one transformed into a two-level factor) on the cumulative pregnancy rate, were tested with Wilcoxon and log-rank tests for homogeneity. The Wilcoxon test is more sensitive to differences across the strata at earlier time periods than that of the log-rank statistic which lends more weight to late time differences. Eighteen potentially prognostic fecundity, lifestyle and psychological variables were investigated. These were previous pregnancy history, age, body mass index, education, work status, socio-economic status, smoking habit, and level of tea, coffee and alcohol consumption, and also the psychological test scores from the POMS (six items) and STAI (two items).
Cox's proportional hazards regression was used to determine the best predictors of time to pregnancy for the sample. In constructing the multivariate model the influence of fecundity (previous pregnancy, age) and lifestyle (work status, education, socio-economic status, smoking habit, tea, coffee and alcohol consumption), variables on time to pregnancy were first examined. These variables were entered into a model and those not contributing to the fit of the model were backwards eliminated. Previous pregnancy history remained as the only significant predictor of time to pregnancy. Previous pregnancy history was then included in a second model along with the psychological test scores. The psychological test scores were entered into the model as continuous variables and those that did not contribute significantly to the fit of the model were backwards eliminated. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated from the Cox regression equation for each variable included in the final model. The analyses were performed using the PHREG procedure of SAS (Release 6.04; SAS Institute Inc., Cary, NC, USA).
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Results |
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Table I shows the mean pre-treatment scores for the STAI and the POMS, separately for first-time IVF participants and repeat treatment women. For comparison, published normative scores are also given. Mean psychological scores on all measures were not significantly different between new patients and women who had undergone previous treatment. Mean scores were also comparable to published population norms except for the POMS agreeablehostile scale where the study group reported significantly less favourable scores (P < 0.025, two-sample t-test).
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Product-limit statistics were used to investigate the separate effects of different stress and lifestyle variables on the number of treatments to success and the results are summarized in Table II. Taken alone, previous pregnancy history, work status, the POMS agreeablehostile scale and trait anxiety were significantly associated with the number of treatment cycles to pregnancy. Twenty-five women had had a previous pregnancy in the current relationship, and after five treatment cycles the cumulative probability of pregnancy for this group of women was 77.8% compared with 19.6% for women without a pregnancy (Figure 1
). The probability of pregnancy was lower for the first five treatment cycles for women in full-time paid employment compared with women working part-time or employed in home duties (Figure 2
). Figure 3
shows women that who scored towards the agreeable pole of the POMS agreeablehostile scale experienced a higher success rate than more hostile women across all treatment cycles. For trait anxiety, characteristically anxious women experienced a lower probability of pregnancy during later treatment cycles than non-anxious women (Figure 4
). No other variables were significantly associated with time to pregnancy.
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Discussion |
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Facchinetti et al. recently reported a reduced pregnancy rate after one treatment cycle for women who worked `outside the home' (Facchinetti et al., 1997). In the present study, women in full-time employment had a reduced pregnancy rate for their first five treatment cycles, and these findings are supportive of a role for stress in treatment outcome. It is possible that full-time employment, or working `outside the home', while undertaking IVF treatment, creates a number of additional stressors that patients must cope with. These could include such things as difficulty in arranging leave from work, financial considerations, added time pressure, worry or embarrassment over work colleagues' knowledge of personal issues, and added discomfort due to the stimulatory drugs. It should be noted, however, that work status failed to significantly predict outcome in the multivariate Cox analysis and thus this finding should be interpreted with caution.
Also supportive of a stressoutcome relationship was the finding, in both univariate and multivariate analyses, that a hostile mood was associated with a decreased probability of pregnancy after successive treatment cycles. The question arises whether more `hostile' women are physiologically less responsive to treatment or whether treatment itself is compromised by hostile attitude. It is interesting to note that the clinic provides an information sheet to prospective patients that states: `your co-operation in all aspects (of treatment) mentioned is vital to the success and smooth running of the programme.' Hence, it is possible that the association between hostile mood and decreased chance of pregnancy may have been due to subtle differences in timing or management of routine clinic events. Regardless of actual mechanisms, however, this finding could have important implications for patient counselling and management.
Trait anxiety refers to the tendency of individuals to respond to stressful situations with elevated anxiety (Spielberger et al., 1970) and thus, measurement of trait anxiety can be considered an index of ability to cope with stressors. We postulated that highly trait anxious women would be less likely to achieve pregnancy through assisted reproductive technology because they would be less able to cope with the stressors of treatment. The results showed that, at least initially, higher trait anxiety was associated with reduced risk of pregnancy. However, the multivariate regression analysis revealed that the risk of pregnancy actually increased for trait anxiety scores in the highest quartile and this finding is more difficult to interpret.
Few previous studies have addressed the role of trait anxiety in treatment outcome. Demyttenaere et al. found a positive correlation between trait anxiety level and number of treatment cycles amongst women conceiving in a donor insemination programme (Demyttenaere et al., 1988). However, they did not take into account women who failed to achieve pregnancy. Merari et al. reported mean trait anxiety, assessed in the early follicular phase, to be similar for unsuccessful women and women who conceived following one IVF cycle (Merari et al., 1992
), but the levels of anxiety in that study were higher than for normal women and for the women in our study. A recent study reported a trend towards lower trait anxiety in women who became pregnant after one treatment cycle but this was not significant on univariate analysis and multivariate analysis was not applied (Harlow et al., 1996
). Our study is the first to include multivariate analysis in a prospective study of trait anxiety and fertility treatment outcome after several treatment cycles.
The level of trait anxiety reported by women in this study was within the normal range and consistent with the findings of a number of other studies (Brinsmead et al., 1986; Shatford et al., 1988
; Thiering et al., 1993
; Boivin and Takefman, 1995
). An examination of other lifestyle and treatment characteristics for the very highly anxious women failed to reveal any major differences that could account for the increased pregnancy rate observed. According to Spielberger and Rickman highly trait anxious women are more likely to use the psychological defence mechanisms of repression and denial to minimize state anxiety (Spielberger and Rickman, 1990
). Thus, it could be postulated that these women have a different psychoneuroendocrine stress response pattern that positively influenced treatment outcome. However, further research is required to explore this unexpected but interesting finding.
As well as trait anxiety, state (transient) anxiety was measured in both the POMS and STAI scales. However, in contrast to trait anxiety, neither state scale appeared to have any association with pregnancy rates. This is not an unexpected finding since the women completed the scales after acceptance into the programme and prior to any treatment. Other workers have shown that this time may not demonstrate the anxieties of treatment, but rather, reflect feelings of relief regarding the decision to undertake IVF and general high expectations of success (Callan and Hennessey, 1988; Thiering et al., 1993
). The normal scores found for most other mood states measured in the present study would tend to support this notion.
Clinically depressed women have previously been reported to have lower pregnancy rates for the first six to seven IVF treatment cycles (Thiering et al., 1993). In our study, however, the pregnancy rate was increased for women scoring towards the depressed pole on the POMS elateddepressed scale. It must be noted, however, that the POMS scale used in our study was not designed to distinguish clinical conditions. Furthermore, the scale is generally regarded as a measure of transient mood state and, as such, it may be altered by a subsequent change in psychosocial environment. A plausible explanation for the present results, therefore, is that at the time of completing the questionnaire, before entry into the treatment programme, some women were excessively `elated' at the prospect of resolving their fertility problems through IVF. As indicated above, many new IVF participants frequently enter the programme with unrealistic expectations of success (Callan and Hennessey, 1988
; Reading, 1989
; Slade et al., 1997
). However, failure of treatment can lead to severe depression (Baram et al., 1988
; Dennerstein and Morse, 1988
; Slade et al., 1997
). In our study, ~77% of women were new participants and so a high level of `elatedness' might have been expected. For these women, the actual demands of the treatment cycle may have had a major negative impact on their subsequent emotional state, and their chance of pregnancy. It is noteworthy that in the Thiering et al. study (Thiering et al., 1993
), the association between depression and treatment outcome was less predictive for new participants than for repeat treatment women.
Our finding of a higher pregnancy rate for women with a previous pregnancy in their current relationship confirms that of Haan et al. who demonstrated that the results of treatment are dependent on the couple's previous history rather than on the female partner's history alone (Haan et al., 1991). Recently, Molloy et al. found the cumulative pregnancy rates for GIFT and IVF to be higher for the first three treatment cycles, in women who had previously had pregnancies through assisted reproductive technologies (Molloy et al., 1995
). These authors suggest that the association between previous pregnancy and treatment outcome may relate to differences in oocyte/embryo quality. Unfortunately this factor could not be assessed in our study.
In conclusion, the present study demonstrates an important link between lifestyle and personality characteristics, ascertained before treatment, and the outcome of IVF and GIFT procedures. The findings that full-time work and more hostile mood states are associated with reduced pregnancy rates, in the study group, conform to the original hypothesis that psychosocial stress reduces successful treatment outcome. The findings that trait anxiety and depression are also related to treatment outcome further emphasizes the importance of psychosocial factors but indicates that these relationships are complex. But whatever the actual direction of psychosocial stress and treatment outcome relationships and their underlying mechanisms of action, the present study could have important implications for overall patient management. Although the limited sample size of the present study reduces the ability to generalize the results to other assisted reproductive treatment clinic populations, if these findings are confirmed in other, similar studies, the role of psychosocial support programmes in infertility treatment needs to be more actively investigated.
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Acknowledgments |
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Notes |
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References |
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Submitted on November 2, 1998; accepted on February 15, 1999.