Patient-staff communication and its effect on reactions to treatment and treatment failure

Transcription

1 Patient-staff communication and its effect on reactions to treatment and treatment failure Published in: Boivin, J. (2000). Patient staff communication and its effect on reactions to treatment and treatment failure. In F. van Balen, T. Gerrits & M. Inhorn (Eds) Proceedings of Social Science Research on Childlessness in a global perspective. Amsterdam: SCO-Kohnstam Instituut. Jacky Boivin, Ph.D. School of Psychology, Cardiff University, PO Box 901, Cardiff, Wales, United Kingdom, CF11 3YG, FAX: (2920) ; TEL: (2920) ; boivin@cardiff.ac.uk Abstract In vitro fertilisation (IVF) is a stressful infertility treatment. Recent studies have found that women who do not achieve a pregnancy with IVF experience more distress during treatment than those who are successful in becoming pregnant. Although this finding supports a possible role for distress in the outcome of IVF there is an alternative explanation; namely, that those who fail at IVF are likely to have received stressful negative feedback during the cycle because their biological response to IVF, which is monitored by medical staff, is poorer. The primary objective of the present study was to examine how patient-staff communication impacts on patients' experience of their medical treatment. One issue addressed is whether stressful communication between medical staff and patients accounts for the proposed relationship between emotional distress and treatment outcome. A secondary issue addressed was whether receiving negative feedback during treatment prepares patients for a negative outcome, in other words whether 'advanced warning' lessens the distress patients experience when treatment does in fact fail. This research was funded by the Economic and Social Research Council (grant: ) 1 2

2 Introduction A number of components within the in vitro fertilisation (IVF) treatment process can be challenging for patients. These include, for example, invasive physical procedures and negative side effects, low probability of success and disruptions to daily activities. These different factors are thought to increase the strain of undergoing IVF. Another factor which has received some attention has been the feedback patients receive from medical staff as they go through the IVF process (Seibel & Levine, 1987; Boivin & Takefman, 1995). Unlike other fertility treatments, the monitoring necessary for the success of IVF allows medical staff to provide patients with feedback about the ongoing progress of their treatment cycle as it unfolds. For example, feedback concerning the progress of stimulation is provided through the results of estradiol blood tests and scans, while feedback about the success of retrieval or fertilisation is provided by the number of oocytes obtained or fertilised. We became interested in feedback for two reasons. First, our research suggested that negative feedback might be responsible for the relationship observed between treatment distress and treatment outcome. The distress of IVF is wellestablished in both retrospective and prospective studies. Several prospective studies have also shown a relationship between emotional distress during IVF and the outcome of treatment with subsequently non-pregnant women reporting more distress then pregnant women. One model proposed suggests that emotional distress somehow degrades the biological response to IVF which in turn reduces the chances of conception with this treatment (Demyttenaere et al. 1991). However, we have argued that the observed relationship between distress and biology is an artefact of the monitoring procedures involved in IVF. Our research showed that the difference in emotional distress between subsequently pregnant and non-pregnant women occurred only during those stages when medical staff had access to biological markers (i.e., estradiol level) with which they could provide feedback about the progress of IVF (Boivin & Takefman, 1995). When such markers were not available, for example, during GnRH-a administration (gonadotrophin releasing factor - analog) or the two week waiting period after transfer, group differences on distress were not observed. Feedback would be important in determining stress level as subsequently non-pregnant women would be expected to have a poorer response in terms of these biological markers, and therefore more likely to receive more negative [and distressing] feedback than those who ultimately become pregnant. Thus treatment stress and biological response could appear to be related because of their respective relationship to medical feedback. A second reason for our interest in patient staff communication was to determined whether it could prepare patients for the outcome of treatment. If patients were made aware of the precarious progress of their treatment would this knowledge affect their reactions when treatment did fail? On the one hand, telling women that treatment is not going well might help them prepare themselves mentally and emotionally for the worst and thereby reduce the intensity of their reactions when treatment failed (Lazarus & Folkman, 1984). On the other hand, because negative feedback does not predict failure with complete accuracy it may be difficult for patients to interpret it. Providing feedback would then increase distress without substantially affecting patient's response to a negative pregnancy test. In the present study these issues were examined using a daily monitoring methodology. Women rated their daily emotional reactions to IVF using a multi-item symptom inventory which also allowed space to indicate whether positive, negative or ambiguous feedback had been received from medical staff about the progress of treatment. Data from biological markers indicating patient responsiveness to treatment (e.g., estradiol levels, oocytes retrieved) were collected from medical charts at the end of the IVF cycle. Based on whether pregnancy was achieved, women were assigned to either the Pregnant or to Non-pregnant group whereas women whose treatment cycle was cancelled prematurely due to a poor response to IVF interventions were assigned to the Cancelled group. Groups were compared on the dependent measures: emotional distress, medical feedback and biological responsiveness. Method Sample The final sample consisted of 107 women about to begin an IVF cycle at a large urban hospital. The selection criteria for the study were that women: 1) were accepted into the IVF program, 2) started the IVF cycle and 3) spoke and understood English sufficiently to be interviewed and complete study materials. Of the final sample 63 did not achieve a pregnancy (Nonpregnant group), 13 achieved a pregnancy (Pregnant group) and 30 had a cancelled treatment protocol due to a poor response to treatment interventions (Cancelled group). Table 1 presents a comparison of demographic and medical variables for the patients who had a cancelled cycle versus those who continued the cycle and obtained either a positive or negative pregnancy test. While differences between the groups were generally not significant the direction of mean differences showed that couples in the Pregnant group were slightly younger, had been married and infertile for fewer years and had been in treatment for fewer years. In addition, slightly more patients in 3 4

3 the Pregnant group (42.9 %) had tried IVF in the past compared to the Nonpregnant (32.8%) or Cancelled group (36.7%) (! 2 (2)=..54, p = NS). Materials and Procedure A. Distress, feedback and biological response during treatment: The daily monitoring inventory was a modified version of the Daily Record-Keeping chart (DRK) designed for use with patients undergoing infertility treatment (Boivin & Takefman, 1995). The distress subscale of this measure contains 16 negative affective reactions (e.g., nervous, tense, pessimistic) which were averaged to produce a measure of treatment distress. Each day women rated to what extent they had experienced each of the reactions using a Likert scale which ranged from not at all to severe. The psychometric properties of the distress scale were examined in several infertility studies (Takefman et al., 1992; Boivin & Takefman, 1995; Boivin et al., 1999) and it was found that: 1) internal reliability for the subscale was high; 2) the sum of the items correlated moderately with other measures of distress; 3) the subscale total fluctuated across the treatment cycle in a manner consistent with expected changes; 4) subjects reported that the scale was neither difficult nor distressing to complete. For purposes of this study, the DRK was modified to include an item on medical feedback received during treatment. For each day, women were asked to indicate whether they received negative (-), ambiguous (+/-) or positive (+) feedback about the progress of their IVF cycle from medical staff. At the end of the IVF cycle, patients' medical charts were examined and information about their biological responsiveness to ovarian stimulation (e.g., peak estradiol level), oocyte retrieval (e.g., follicles aspirated) and embryo transfer (e.g., oocytes fertilised) was collected. Using factor analysis these variables were grouped into two factors accounting for 44.8% and 14.7% of the variance in biological data. The first factor was labelled 'Ovarian response quality' as oocytes retrieved, follicles aspirated, mature oocytes and peak estradiol level loaded highly (>.30) on this factor. The second factor was labelled 'Fertilisation and embryo quality' as oocytes fertilised, embryos transferred and number of grade A embryos loaded highly on this second factor. Information about sperm quality on the day of retrieval (i.e., count, percent motile) was also collected from medical notes. Procedure Patients were provided with a complete description of the study one to two weeks before the start of their IVF treatment cycle. Those who wished to participate signed a consent form and were then interviewed by a research psychologist. At the end of the interview patients were provided with 1) a detailed explanation on when and how to complete the daily monitoring forms, 2) the battery of pre- and posttreatment questionnaires to be completed at home. Results concerning pre- and posttreatment questionnaires will be presented in a separate study but for general information there was no difference between subsequently pregnant, non-pregnant and cancellation groups on any of the psychological variables assessed prior to treatment whereas post-treatment differences emerged between the pregnant group on the one hand and pregnant and cancelled groups on the other. Over a 22 month period, from September, 1995 through June, 1997, a total of 129 women attended a clinic appointment for IVF, met the selection criteria and were interviewed as possible candidates for this study. Of these 17.1% (22) agreed to participate but did not complete study materials. Most of these withdrew from the study because of the time commitment involved in daily monitoring (n=19). Women filled out the daily monitoring form for one complete IVF cycle, starting from the first day of GnRH-a administration until the third day following the pregnancy test (! 30 days). Each sheet of the DRK contains seven days of daily monitoring (i.e., seven columns). For each day, women filled out the day and date of treatment, and whether they received a medical intervention that day (e.g., hmg, oocyte retrieval) by using the list of treatment codes provided on the sheet. They then indicated the type of feedback they had received and the extent to which they had experienced each of the reactions listed on the scale that day. The monitoring form was completed daily and mailed weekly in the stamped, pre-addressed envelopes provided. Patients mailed the forms weekly to reduce the possibility that treatment reactions were rated retrospectively. Women were assigned to the Pregnant or Nonpregnant group on the basis of the biochemical pregnancy ("-hcg) test carried out 14 days after embryo transfer and assigned to the cancelled group if IVF was terminated prematurely. Results A. Perceptions of medical feedback during treatment Overall, patients did not report any feedback on 63.2% (SD=.22) of cycle days and reported negative feedback on fewer than 10% of cycle days (M=.054, SD=.06). As expected, there was a significant difference between groups in terms of the number of positive feedback days reported with the Nonpregnant and Pregnant groups each reporting positive feedback on! 27% of cycle days and the Cancelled group reporting positive feedback on only 16% of days (F(2, 82)=3.38, p <.05). The number of days of each type of feedback as a function of outcome group was computed using a 3"(Group) x 4 (Day) analysis of variance (ANOVA) with Day as repeated measure. Only the main effect of day was significant showing that all patients, regardless of group, reported significantly more days of positive feedback 5 6

4 and days of no feedback than days of either negative or ambiguous feedback (F(3, 249)=110.00, p <.001). were not significantly different from average scores of the Nonpregnant group at the time of the negative pregnancy test (t(71)=.72, p = NS). B. Emotional distress and negative feedback i - Comparison among outcome groups Daily distress ratings were averaged once across the 16 emotional items (e.g., nervous, tense, hassled) and once across the individual days of a specific IVF stage to produce a series of stage scores (Boivin & Takefman, 1995). Averages were computed on an individual basis because the number of days in a stage differed between women. The stages for which these averages were computed were downregulation, first five days and following days of ovarian stimulation, week one and week two of the waiting period and the three days that followed the pregnancy test. Comparison of distress scores across days of each stage showed that the average was an adequate estimate of the reactions during that particular stage. Stage scores were not computed for the day of induction, retrieval, transfer and the pregnancy test as these stages represent single days in the IVF cycle. A 2 (Group) x 10 (Stage) ANOVA with Stage as a repeated measure was computed on distress level. As shown in Figure 1, there was a significant Group x Stage interaction (F(9, 675)=5.21, p <.001). Posthoc tests revealed that the interaction was due to significant group differences on the day of the pregnancy test and the three days that followed. As expected, the Nonpregnant group reported significantly more distress on the day of the pregnancy test (t(75)=3.76, p <.001) and the days that followed (t(75)=2.75, p <.01) than did those who achieved a pregnancy. In addition, the Nonpregnant group reported slightly more distress for the retrieval and transfer stage but these differences were not significant. A significant main effect of Stage (F(9, 5.72)=p <.001) showed the retrieval and transfer stages were more stressful than other stages (except for pregnancy test day) for both the Nonpregnant and pregnant women. This analysis was repeated including the Cancelled group for the early stages of treatment: early follicular, first five days and last days of stimulation, induction and retrieval 1. A significant main effect of group (F(2, 94)=3.93, p <.001) was obtained and as illustrated in Figure 1, patients in the Cancelled group reported more distress during the initial stages of IVF compared to the two other groups. Average stage scores of the Cancelled group on the day of retrieval when treatment was cancelled 1 The ANOVA did not include the stage of retrieval because of the 22 women in the cancelled group who reached the stage of retrieval only 9 returned their DRK chart. Thus mean scores for retrieval in Figure 1 represent an n=9. ii - Comparisons among feedback days An ANOVA was computed to examine the relationship between distress level and type of feedback. The dependent variable for this analysis was distress level on each type of feedback day across all days of the IVF cycle. The three groups did not differ with respect to distress level reported in response to positive feedback (F(2, 79)=.93, NS) but the Cancelled group reported significantly more distress than the other two groups on days when no feedback was reported (F(2, 79)=2.42, p <.10). Because few Pregnant patients reported days of negative and ambiguous feedback (three and five respectively) only data from the Nonpregnant and Cancelled group was used to examine the impact of this type of feedback versus other kinds on distress level. A 2 (Group: Nonpregnant, Cancelled) x 3 (Feedback: Positive, Negative, None) ANOVA with feedback as a repeated measure was computed for patients reporting all types of feedback (n=29). A significant main effect of Feedback (F(2, 54)=20.85, p <.001) showed that negative feedback was much more distressing to patients than either positive or no feedback (see Figure 2). A significant Group x Feedback interaction (F(2, 54)=4.91, p <.001) also showed that days of no feedback or of negative feedback were more distressing for the Cancelled group compared to the Nonpregnant group. C. Negative feedback, stress and biological response The major objective of this study was to examine whether the relationship between distress and IVF outcome could be explained by the negative feedback patients received during their IVF cycle. To test this hypothesis a path analysis was carried out using three variables: overall distress during IVF, amount of negative feedback and biological response. Biological response consisted of the factor scores reflecting ovarian response and those reflecting fertilisation and embryo quality. Figure 3a and 3b presents the path model for negative and positive feedback. The numbers represent zero-order correlations for a specific path. The link of particular interest in this Figure would be between distress and the biological response variable (e.g., ovarian response or fertilisation quality). If negative feedback could mediate the relationship between stress and biological response then one would expect that the path coefficient for this link would be smaller than the zero-order correlation since the path coefficient is the correlation between distress and biological response with the effect of negative feedback covaried (or partialled from it). 7 8

5 To be considered a mediator variable several conditions must be met. The minimum requirement is that the proposed mediator, in this study feedback, is linked to the other two variables in the model (treatment distress and biological response). As shown in Figure 3a and 3b neither negative or positive feedback met this minimum requirement. Negative feedback was not related to either of the two biological response variables whereas positive feedback was not related to treatment distress. As this minimum condition was not met it was not possible to test the model. Results with ambiguous feedback are not presented as they were as was the case for positive feedback. That is, ambiguous feedback was significantly related to both ovarian response (r = , p <.05) and fertilisation and embryo quality (r = , p <.01) but was not related to treatment distress (r =.0394, p <.05). C. Impact of feedback on reactions to treatment failure One of the objectives of this study was to examine whether receiving negative feedback during the course of the IVF cycle prepares patients for an eventual treatment failure. Two multiple regression analyses were carried out using the number of days of positive, negative and no feedback as predictors for distress level the day of and three days after negative pregnancy test results. The regression for the day of the pregnancy test was significant (F(4, 51)=2.63, p <.05) as was the regression on the days after the pregnancy test results (F(4, 51)=5.72, p <.001). In both cases the only feedback variable to be significant was the number of negative feedback days reported prior to the pregnancy test day with those reporting more days of negative feedback during the cycle also reporting more distress on the day of the pregnancy test (p <.05) and three days after (p <.01). Semi-partial correlations squared revealed that number of days of negative feedback accounted for 9.0% and 11.6% of variance in pregnancy test day distress and three days after distress scores, respectively. Correlations computed between the number of negative feedback days and distress at other stages of IVF were also significant during: ovarian stimulation (r=.43), oocyte retrieval (r=.27) and embryo transfer (r=.19). Discussion Patients reported receiving negative feedback on less than 10% of cycle days and it is unclear whether this low frequency represents an objective evaluation of the amount of feedback patients were given or whether it reflects a bias against reporting this type of feedback. The fact that the Cancelled group did not report more negative feedback then other groups despite a poorer biological response may suggest that patients were indeed reluctant to report such feedback. It may be less threatening for patients to report less positive feedback, as did patients in the Cancelled group, than to report any negative feedback. This "optimistic bias" would be consistent with the finding that patients tended to react emotionally to days without feedback as they did to days of positive feedback possibly following the old adage "no news is good news". A finding of an optimistic bias would also be consistent with previous research showing that patients overestimate their chances of success prior to treatment (c.f. review, Mazure et al., 1992). Optimism may be not only a reaction to treatment but also a way of coping with the strains of initiating treatment (Collins et al., 1992) or managing uncertainty during treatment (Callan & Hennessey, 1988; Boivin & Takefman, 1996). Although few patients reported negative feedback it was still possible to evaluate its relationship to emotional distress relative to other types of feedback patients might have received. More distress was reported on days of negative and ambiguous feedback than on days of positive feedback or on days when no feedback was given. Post hoc explanations for the similarity between the different types of feedback can easily be made. When outcome was not threatened either because the feedback was positive or because none was provided then distress level remained stable. However, whenever the feedback involved concrete information which threatened the outcome of treatment, no matter how certain (negative) or uncertain (ambiguous), then patients experienced distress. This proposal would be consistent with anecdotal evidence (Seibel & Levin, 1987) which suggests that patients are "exquisitely sensitive" to negative feedback from medical staff as well as to more empirical evidence which shows that patient mood is partly dependent on whether patients successfully "pass or fail" various stages of IVF (Boivin & Takefman, 1996; Merari et al. 1992; Demyttenare et al., 1991). The predicted model between emotional distress, negative feedback and biological response could not be tested because of underlying interrelationships between these variables. Negative feedback was unrelated to biological response variables (e.g., ovarian response, fertilisation quality) whilst positive and to a lesser extent ambiguous information were related. Conversely, negative feedback was related to emotional distress whilst positive and ambiguous feedback were not. These 9 10

6 results suggest that while ratings of ambiguous and positive feedback may be grounded in actual treatment events as measured by objective biological markers, negative ratings may not. One possible explanation, in line with other proposals, is that when patients come to think back on the day's events they can more easily recall and acknowledge those medical events which do not wholly threaten their beliefs about the success of treatment. In the cognitive dissonance model (Festinger, 1957), personal beliefs (i.e., optimism about pregnancy) are thought to lead to greater distress when they conflict with external information. In order to deal with that dissonance individuals may change their personal beliefs or disregard and/or modify external information. Accordingly, negative feedback may, for the most part, be disregarded in the written form though it may still influence the emotional reactions for that day. Although ambiguous feedback causes as much distress as negative feedback its ambiguous nature may allow patients to at least acknowledge it without feeling that it completely invalidates beliefs about treatment. This cognitive bias, if it exists, poses a threat to the method we used to test the mediation hypothesis. In this study the link between emotional distress and ovarian response was marginally significant replicating earlier findings of a weak but significant relationship between stress and IVF outcome (Boivin & Takefman, 1995; Demyttenaere et al., 1991). However, if patients were reluctant to report negative events as we propose they were, then we cannot determine whether this weak effect is due to negative feedback or to a real biological link between emotional and biological variable. We originally debated the validity of using subjective (self-report) versus objective (staff reports) ratings of negative feedback. We selected self-report because of practical issues but also because it seemed emotional reactions would be dependent on patients' appraisal of the feedback they received rather than on any of its objective properties. In some ways we have confirmed this contention as patient's rating of feedback as being negative was more related to their emotional reactions then was an objective measure of the feedback (i.e., biologic response variables). Perhaps one way of circumventing this methodological problem would be to ask patients to rate the feedback on a Likert scale, for example from 'not at all good' to 'very good'. Using this method we would have a rating of how patients interpreted the feedback without actually forcing them to say that it was bad news. On the other hand it may also be possible that there is a real link between emotional distress and biological response in IVF. In other words that the predicted relationships among the variables examined simply does not exist and that distress is related to a poorer biological response. This possibility would be in line with past research (Demyttenare et al., 1992, 1998; Stoleru et al., 1997; Thiering et al., 1993). If such a relationship does exist then it is a weak one by our account and seems unlikely to be of a magnitude sufficient to influence the actual outcome of IVF especially as it would account for less than 10% of variance in outcome variability. In this study relationships between emotional distress and ovarian response were stronger than those between emotional distress and fertilisation and embryo quality. This may suggest that a good avenue of research for a potential psychological influence on the reproductive process would be follicular maturation. This finding would be in line with some work which has shown that oocytes exposed (in vivo) to stress sensitive hormones are less likely to lead to fertilisation than oocytes not so exposed (Michael et al. 1993) as well as research on vascular reactivity which may be implicated in the health of follicles (Bhal et al., 1997). Another important objective was to examine the relationship between negative feedback during treatment and reactions to treatment failure. It was found that receiving negative feedback did not lessen the emotional impact of a negative pregnancy test. In fact, this type of information was distressing when it was received during treatment and it predicted a more negative emotional response to the pregnancy test as well as the three days which followed it. Whilst it would be unethical to withhold negative feedback from patients these results show no clear emotional benefit from doing so. It may be that because negative feedback cannot predict IVF failure with complete accuracy it only serves to increase uncertainty about treatment outcome without promoting the type of anticipatory mental preparation which would benefit the patient and help them cope with a negative result (Lazarus & Folkman, 1984). The findings also showed that positive feedback was not detrimental to the well-being of patients. Many have suggested that medical staff and patients alike should be encouraged to hold more realistic expectations about pregnancy (Mazure et al., 1992; Leiblum et al. 1987) under the premise that a more optimistic approach would lead to greater disappointment if treatment failed. The results of this study suggest that such cautiousness is not warranted as patients receiving more positive feedback were as distressed as those receiving relatively less. While ambiguous information was distressing when it was received during treatment it was unrelated to reactions when treatment failed. Thus this approach, may reflect an approach of "cautious optimism" (Leiblum et al., 1987). In summary, patients showed an optimistic bias during treatment and this affected the way in which they reported on the type of feedback they received during treatment. Specifically, patients were reluctant to report negative feedback then positive and ambiguous feedback. It is proposed that this bias represents a way of coping with information that threatens patients beliefs about the anticipated success of treatment. As a result of this methodological complication it was not possible to test the mediation hypothesis that negative feedback was responsible for the weak but significant relationship between emotional distress and biological response variables especially ovarian response. Thus the question of whether this link is an artefact of 11 12

7 the monitoring process in IVF or a consequence of a real biological link between these variables remains unknown. Finally, our results show that there is no benefit of providing patients with negative feedback during treatment. This type of feedback is distressing to patients when it is received and it is linked to a poorer biological response when IVF does fail. References Bhal, P.S., Pugh, N., Chui, D., Gregory, L., Walker, S. M., & Shaw, R. W. (1997). Is follicular vascularity an index of pregnancy potential among women undergoing assisted reproduction treatment cycles. Human Reproduction, 12 (suppl.), 72. Boivin, J., Andersson, L., Shoog-Svanberg, A., Hjelmstedt, A., Collins, A. Bergh, T. (1998). Psychological reactions during in vitro fertilisation (IVF): Similar response pattern in husbands and wives. Human Reproduction, 13, Boivin, J. & Takefman, J. (1995). Stress reactions across an IVF cycle in Pregnant and Non-pregnant women using daily monitoring prospective data. Fertility and Sterility, 64, Boivin, J. & Takefman, J. (1996). The impact of the in vitro fertilization-embryo transfer (IVF-ET) process on emotional, physical and relational variables. Human Reproduction, 11, Callan, V.J. & Hennessey, J.F. (1988). Emotional aspects and support in in vitro fertilization and embryo transfer programs. Journal of In Vitro Fertilization and Embryo Transfer, 5, Collins, A., Freeman, E., W, Boxer, A.S. and Tureck, R. (1992) Perceptions of infertility and treatment stress in females as compared with males entering in vitro fertilization treatment. Fertility and Sterility, 57, Connolly, K.J., Edelmann, R.J., Bartlett, H., Cooke, I.D., Lenton, E. & Pike, S. (1993). An evaluation of counselling for couples undergoing treatment for in vitro fertilization. Human Reproduction, 8, Demyttenaere, K., Bonte, L., Gheldof, M., Vervaeke, M., Meuleman, C., Vanderschuerem, D., D'Hooghe, T. (1998). Coping style and depression level influence outcome in in vitro fertilization. Fertility and Sterility, 69, Demyttenaere, K, Nijs, P, Evers-Kiebooms, G, Koninckx, P. (1991) Coping, ineffectiveness of coping and the psychoneuroendocrinological stress responses during in vitro fertilization. Journal of Psychosomatic Research, 35,

8 Demyttenaere, K., Nijs, P., Evers-Kiebooms, G. & Koninckx, P.R. (1992). Coping and the ineffectiveness of coping influence the outcome of in vitro fertilisation through stress responses. Psychoneuroendocrinology, 19, Leiblum, S.R., Kemmann, E. & Lane, M.K. (1987). The psychological concomitants of in vitro fertilization. Journal of Obstetrics and Gynaecology, 6, Mazure, C.M., Milki, A.A., Takefman, J.E., & Lake-Polan, M. (1992). Assisted reproductive technologies: I. Medical alternatives for women and their partners. Journal of Women's Health, 1, Merari, D., Feldberg, D., Elizur, A., Goldman, J. & Modan, B. (1992) Psychological and hormonal changes in the course of in vitro fertilisation. Journal of Assisted Reproduction and Genetics, 9, Michael, A. E., Gregory, L., Walker, S. M., Antoniw, J. W., Shaw, R. W., Edwards, C. R. W. & Cooke, B. A. (1993). Ovarian 11beta-hydroxysteroid dehydrogenase: Potential predictor of conception by in vitro fertilization and embryo transfer. Lancet, 342, Seibel, M.M. & Levine, S. (1987). A new era in reproductive technologies: The emotional stages of in vitro fertilization. Journal of In Vitro Fertilization and Embryo Transfer, 4, Stoleru, S., Cornet, D., Vaugeois, P., Fermanian, J., Magnin, F., Zerah, S. & Spira, A. (1997). The influence of psychological factors on the outcome of the fertilization step of in vitro fertilisation. Journal of Psychosomatic Obstetrics and Gynaecology, 18, Thiering, P., Beaurepaire, J., Jones, M., Saunders, D., & Tennant, C. (1993). Mood state as a predictor of treatment outcome after in vitro fertilisation/embryo transfer technology (IVF/ET). Journal of Psychosomatic Research, 37,