Coping style and depress!on level influence outcome in in vitro fertilization

Transcription

1 FERTILITY AND STERILITY VOL. 69, NO. 6, JUNE 1998 Copyright (#1998 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A. Coping style and depress!on level influence outcome in in vitro fertilization Koen Demyttenaere, M.D., Ph.D.,*t L. Bonte, M.Sc.,* M. Gheldof, M.Sc.,* M. Vervaeke, M.Sc., C. Meuleman, M.D., D. Vanderschuerem, M.D., Ph.D., and T. D'Hooghe, M.D., Ph.D. University Hospital Gasthuisberg, Leuven University Fertility Center, Leuven, Belgium Objective: To examine the influence of depression levels and coping on 1VF outcome in women, taking into account the cause of infertility. Design: Prospective clinical study. Setting: A university hospital. Patient(s): Ninety-eight women undergoing IVF treatment. Intervention(s): Psychometric tests were administered at the first visit (day 3) of the investigated treatment cycle. Main Outcome Measure(s): Achievement of pregnancy. Results: The nonpregnant group reported increased expression of negative emotions. In the subgroup with a female indication for IVF, increased depressive symptomatology (correlated with increased expression of negative emotions) was associated with lower pregnancy rates (prs), whereas in the subgroup with a male indication for IVF, increased depressive symptomatology (correlated with decreased expression of negative emotions) was associated with higher PRs. Conclusion(s): Expression of negative emotions predicts depression levels and outcome in IVF. The cause of infertility should be taken into account when investigating the relation between psychologic functioning and outcome in IVF. (Fertil Steril 1998;69: by American Society for Reproductive Medicine.) Key Words: IVF, coping, depression, infertility Received July 22, 1997; revised and accepted February 20, Reprint requests: Koen Dernyttenaere, M.D., Ph,D., University Hospital Gasthuisberg, Department of Psychiatry and Leuven University Fertility Center, Herestraat 49, 3000 Leuven, Belgium (FAX: ). * Department of Psychiatry, University Hospital Gasthuisberg. t Department of Psychiatry, Katholieke Universiteit Leuven /98/$19.00 PII S (97) Whether psychologic characteristics influence fertility or the outcome of infertility treatment remains a matter of debate, and the available data are the result of different approaches. First, it often has been suggested that unexplained infertility equals "psychogenic infertility," but this stems from an outdated way of defining psychogenic infertility or functional infertility with the use of an exclusion criterion (i.e., the absence of detectable organic causes). Second, anecdotal data suggest that both major stressors (e.g., war, confinement in a concentration camp and admission to an intensive care unit) and minor stressors (e.g., starting college and the so-called first-kiss amenorrhea) can provoke amenorrhea. Third, some epidemiologic studies suggest that a history of depressive symptoms and previous long-term use of antidepressants or tranquilizers significantly increase the relative risk (adjusted for age, sedentary lifestyle, and cigarette smoking status) for infertility (1, 2). Fourth, the few studies available in the literature that have used standardized psychometric tests to assess stress, anxiety, or depression levels provide contradictory results (3-7). Only one prospective study investigated the effect of chronic stress levels (trait anxiety) on conception rates in natural cycles of normally fertile women; it demonstrated that a higher initial trait anxiety level significantly predicts a lower pregnancy rate (PR) (3). The results of studies concerning the effect of stress levels during IVF are contradictory. Some studies have demonstrated that higher trait anxiety levels or higher depression levels result in a lower PR per IVF cycle and increase the likelihood that a woman will abandon further IVF attempts (4, 5). These studies also showed that higher present state anxiety levels 1026

2 during different stages of the IVF treatment cycle predict a negative outcome (4, 6). Other studies, however, have failed to find a relation between chronic stress levels and IVF outcome (6, 7). These discrepancies could result from methodologic flaws. In a study by Boivin and Takefman (6), retrospective assessment of stress levels during the luteal phase of an IVF cycle (as measured 2-3 weeks after the IVF cycle) demonstrated higher stress levels than assessment during the IVF cycle; that is, there was an important discrepancy between the prospective and retrospective ratings (6). This finding suggests that women may suppress or downplay their stress during treatment as a way of coping with the emotional strain of waiting to find out whether they will become pregnant. It has been shown that positive thinking is the most common coping strategy used during IVF (8). It also was demonstrated that patients with infertility usually present with suppressed stress levels because they tend more than other patients to give socially desirable answers because they are afraid of being denied further treatment (9). We suggest that this mechanism of "suppressed" stress could explain, at least in part, the contradictions found in the literature concerning the relation between stress and IVF outcome. Stress can be considered a "healthy" reaction (i.e., it is healthy to feel stressed in stressful situations), and it is a person's style of coping with stressful situations that seems to be important in maintaining health. Moreover, self-reports on personal coping style are not influenced by social desirability because there are no "good" or "bad" answers (10). Another methodologic problem found in the literature on the relation between stress and IVF treatment outcome is the fact that patient populations are comprised of couples with different causes of infertility, and a woman's reaction to male factor infertility and female factor infertility may be different (11). The first goal of the present study was to assess a woman's depressive symptomatology and coping style and to investigate the relation between these psychologic variables and IVF outcome in a prospective manner. Because a woman may react differently depending on the perceived cause of the infertility, our second goal was to investigate the relation between these psychologic variables and IVF outcome in a subgroup of couples undergoing IVF for female factor infertility and a subgroup of couples undergoing IVF for male subfertility. MATERIALS AND METHODS Patients The study sample consisted of 98 women who were about to begin a trial of IVF at the Leuven University Fertility Center. A total of 125 consecutively seen women were referred to the study, and 98 women agreed to participate. The mean (_+ SD) age of the women was 29.7 _+ 3.5 years, and that of the men was 31.5 _+ 4.5 years; the mean (_+ SD) duration of infertility was years. It was the first 1VF attempt for 55 women, the second for 22 women, the third for 13 women, and the fourth for 8 women. All the couples presented with primary infertility. In most cases, IVF was performed for multiple indications. Male subfertility (sperm count of <20 X 106/mE or motihty of <50%) was present in 59 men, mechanical infertility in 20 women, endometriosis in 34 women, and ovulatory dysfunction in 44 women. Because one of the aims of the study was to investigate whether the perceived cause of infertility influences psychologic functioning and outcome, two subgroups were created: in one group (n = 52 couples) the main indication for IVF was male subfertility (excluding female mechanical infertility), and in another group (n = 39 couples) the main indication for IVF was female subfertility (excluding male subfertility). The 7 couples who were not included in a subgroup had a combination of severe male subfertility and female mechanical infertility that resulted in equal attribution of cause. Ovarian stimulation was performed after pituitary desensitization using the GnRH agonist buserelin (Suprefact; Hoechst AG, Frankfurt, Germany) in a short or long protocol. The mean (_+ SD) of injected ampules of hmg was 24.7 _+ 9.4; the estradiol concentration increased from 242 _+ 175 pg/ml on day -6 to 2,229 _+ 935 pg/ml on day 0 (oocyte retrieval). The numbers of retrieved, mature, and fertilized oocytes were 12.9 _+ 7.1, , and , respectively. No embryo was transferred in 13.2% of the women, one was transferred in 9.9% of the women, two were transferred in 15.4% of the women, three were transferred in 59.3% of the women, and four were transferred in 2.2% of the women. Of the 98 women who completed the study, 23.5% (n = 23) became pregnant during the investigated IVF cycle, whereas the remaining 76.5% (n = 75) did not achieve a pregnancy. Pregnancy was determined by /3-hCG levels in blood tests performed 14 days after ET and by positive ultrasonographic findings at 7 weeks of pregnancy (ongoing pregnancy was the investigated end point). The Ethical Committee for Biomedical Trials of the University Hospitals Gasthuisberg approved this study. Materials A Dutch-validated translation of the Zung Depression Scale was used to assess depressive symptomatology (12). This is a widely used self-rating scale in which an index score (a standardized transformation of the raw score) of <50 is considered to be within the normal range, a score of >50 to indicate mild depression, a score of >60 to indicate moderate depression, and a score of >70 to indicate severe depression (12). The Utrechtse Coping List, a well-validated questionnaire derived from the Westbrook Coping Scale, was used to FERTILITY & STERILITY 1027

3 Psychometric characteristics (Zun9 Depression Scale an0 Otrechtse Gopin9 List) of the 98 investi9atecl women. Psychometric characteristic Score (mean + SD) Zung Depression Scale 52.5 _+ 9.8 Utrechtse Coping List Active coping 17.8 _+ 2.9 Palliative coping _ 3.3 Avoiding 15.2 _+ 3.2 Social support seeking _ 3.7 Depressive coping _ 2.6 Expression of negative emotions Comforting ideas 13.6 _+ 2.4 assess coping style. Seven coping mechanisms (active coping, palliative coping, avoiding, social support seeking, depressive-regressive coping, expression of negative emotions, and comforting ideas) are scored (13). The validity of the seven subscales of the Utrechtse Coping List has been confirmed by several studies, and most professionals in psychology or psychiatry agree that the terms used in the Coping List are valid (14). The internal consistency (Crohnbach's c0 for the different Utrechtse Coping List scales ranges from The test-retest reliability in female students for active coping, palliative reactions, avoiding reactions, social support seeking, depressive-regressive coping, expression of negative emotions or anger, and comforting ideas is 0.76, 0.43, 0.76, 0.64, 0.70, 0.74, and 0.64, respectively (6-week interval) (14). Female standard population scores are for active coping, for palliative coping, for avoiding, for social support seeking, for depressive coping, 6-8 for expression of negative emotions, and for comforting ideas (14). Both questionnaires were administered in the infertility clinic at the first visit (day 3-5) of the treatment cycle studied. Data Analysis Data analysis was performed with the use of the Statistical Package for the Social Sciences (SSPS Inc., Chicago, IL). Data are expressed as means _+ SD. Pearson's correlation coefficients, t-tests, the X 2 test, and linear regression analysis (stepwise forward procedure) were used for statistical analysis. RESULTS Psychologic Variables in the Total Study Group The psychometric characteristics of the investigated sample are given in Table 1. The scores for the different coping mechanisms all were comparable with those of a standard population. However, the mean Zung Depression Scale score was high; 54.1% of the women had Zung scores higher than the cutoff score suggestive of mild depressive symptomatology (score 50), 19.4% had Zung scores higher than the cutoff score suggestive of moderate depressive symptomatology (score 60), and 2% had Zung scores higher than the cutoff score suggestive of severe depressive symptomatology (score 70). Comparison of the Zung Depression Scale score and the coping mechanisms on the Utrechtse Coping List revealed that a higher Zung score was correlated with higher depressive-regressive coping (r = 0.50, P <0.001) and with lower active coping (r = -0.26, P <0.005). Within the Utrechtse Coping List, higher active coping was correlated with increased use of comforting ideas (r = 0.39, P <0.001). Higher palliative coping was con'elated with higher avoiding (r = 0.26; P = 0.004), higher social support seeking (r = 0.24, P = 0.008), and greater use of comforting ideas (r = 0.33, P = <0.001). Higher social support seeking was correlated with greater expression of negative emotions (r = 0.32, P = 0.001). Higher depressive coping was correlated with increased expression of negative emotions (r = 0.33, P <0.001). The Zung Depression Scale score was negatively correlated with the woman's age (r = -0.22, P = 0.01), the duration of infertility (r = , P = 0.04), and the number of previous IVF attempts (r = -0.17, P = 0.05). Somatic Variables and IVF Outcome in the Total Study Group There were no statistically significant differences between the women who became pregnant and those who did not in terms of age (t-test = 1.53), duration of infertility (t-test = 0.49), or number of previous IVF attempts (t-test = -0.25). There also were no statistically significant differences between these two groups in terms of the number of injected ampules of hmg (t-test = 0.81), the estradiol concentrations on day -6 (t-test = 0.72) and day 0 (t-test = ), the number of retrieved oocytes (t-test = ), or the number of mature oocytes (t-test = ). The mean (-+ SD) number of fertilized oocytes and transferred embryos was higher in the women who became pregnant than in those who did not ( versus 4.3 _+ 3.9; t-test = 2.00, P = 0.05 and versus 2.1 +_ 1.2; t-test = 3.22, P = 0.002, respectively). Psychometric Variables and IVF Outcome in the Total Study Group The first goal of this study was to investigate whether the psychometric characteristics assessed at the beginning of the studied IVF cycle were different in the women who became pregnant and in those who did not. Table 2 illustrates the results of the Student's t-test analysis comparing the group means of the psychometric variables as a function of preg Demyttenaere et al. Coping, depression, and IVF outcome Vol. 69, No. 6, June 1998

4 Psychometric variables (Zung Depression Scale and Utrechtse Coping List) in the total study group (n = 98) according to IVF outcome. IVF outcome Psychometric variable Not pregnant (n = 75) Pregnant (n = 23) t-test P value Znng Depression Scale score Utrechtse Coping List Active coping score Palliative coping score Avoiding score Social support seeking score Depressive coping score 1.8 _ _ Expression of negative emotions score _ Comforting ideas score Note: The scores are given as means SD. nancy group. Higher palliative coping and decreased expression of negative emotions was found in the women who became pregnant (P = 0.03) compared with those who did not (P = 0.01). Palliative Coping, Comforting Ideas, and IVF Outcome in the Total Study Group A linear regression analysis (stepwise forward) that included the Zung Depression Scale score and the seven coping mechanisms of the Utrechtse Coping List as independent variables and pregnancy as the dependent variable was performed. It revealed that decreased expression of negative emotions and increased palliative coping predicted a higher PR (total R 2 = 0.34;f = 6.16; P = 0.003; partial R 2 = 0.24 and 0.11, respectively). This means that 34% of the variance in becoming pregnant or not becoming pregnant is explained by palliative coping and the expression of negative emotions. To investigate further the clinical importance of these two coping mechanisms in predicting outcome, a "midsplit" was performed for both of them (i.e., the total group of patients was split into two subgroups, above or below the median value). This midsplit also was performed to investigate whether somatic variables (e.g., number of retrieved oocytes) were different in these two subgroups. The patients were divided into two groups according to whether their score for the expression of negative emotions was >6 or -<6. The PRs in the two groups were 14.9% (7 of 47) and 31.3% (16 of 51), respectively (X a = 3.69, P = 0.05). There was no statistically significant difference in the number of injected ampules of hmg (t-test = -1.16), the number of retrieved oocytes (t-test = 0.98), the number of mature oocytes (ttest = 1.14), the number of fertilized oocytes (t-test = ), the number of transferred embryos (t-test = -0.79), patient age (t-test = -0.91), duration of infertility (t-test = -0.79), or the number of previous IVF attempts (t-test = 1.28) in the two groups. The patients were divided into two groups according to whether their score for palliative coping was >17 or --<17. The PRs in the two groups were 29.8% (17 of 57) and 14.6% (6 of 41), respectively (X 2 = 3.06, P = 0.07). There was no statistically significant difference in the number of injected ampules of hmg (t-test = -0.23), the number of retrieved oocytes (t-test = -0.40), the number of mature oocytes (t-test = -0.66), the number of fertilized oocytes (t-test = 0.66), the number of transferred embryos (t-test = ), patient age (t-test = 0.57), the duration of infertility (t-test = 1.17), or the number of previous IVF attempts (t-test = -1.37) in the two groups. Among the women who received -->3 embryos at ET, the PR was 21.4% (6 of 28) in those with greater expression of negative emotions and 53.8% (14 of 26) in those with lesser expression of negative emotions (X 2 = 6.07, P = 0.01). Thus, within the group of women who had the highest "somatic" chance of pregnancy (i.e., those who received -->3 embryos at ET), the midsplit further increased the difference in the predictive value of the expression of negative emotions. Psychometric Variables and the Cause of Infertility The mean (+ SD) Zung Depression Scale score was comparable in the women who were undergoing IVF because of female subfertility (n = 39) and those who were undergoing IVF because of male subfertility (n = 52) ( versus 51.4 _+ 10.0; t-test = 0.87, P = 0.39). The coping mechanisms also were comparable in these two groups, with the exception of depressive coping, for which the mean (_+ SD) score was higher in the women with female subfertility (12.7 _+ 2.6 versus 11.0 _+ 2.4; t-test = 3.15, P = 0.002). Patient age, duration of infertility, the number of previous IVF attempts, the number of retrieved oocytes, the number of mature oocytes, the number of fertilized oocytes, and the number of transferred embryos were not significantly different between the two groups. FERTILITY & STERILITY 1029

5 Psychometric variables (Zung Depression Scale and Utrechtse Coping List) in the subgroup of women with a female indication for IVF (n = 39) according to IVF outcome. IVF outcome Psychometric variable Not pregnant (n = 32) Pregnant (n = 7) t-test P value Zung Depression Scale score 54.7 _ _ Utrechtse Coping List Active coping score 17.7 _ _ Palliative coping score 18.3 _ _ Avoiding score 15.8 _ _ Social support seeking score 14.8 _ _ Depressive coping score _ Expression of negative emotions score Comforting ideas score 13.7 _ _ Note: The scores are given as means +_ SD. The PR was not significantly different in the two groups: it was 17.9% (7 of 39) in the group with female subfertility and 26.9% (14 of 52) in the group with male subfertility (Fisher's exact test: odds ratio = 0.59; 95% confidence interval = ). Psychometric Variables and Outcome in the Group with Female Subfertility Among the patients who were undergoing IVF for female subfertility, age, the duration of infertility, the number of previous IVF attempts, and the number of transferred embryos (mean _+ SD) were not statistically different between those who became pregnant and those who did not (t-test = -0.82, -0.58, -0.84, and -1.11, respectively). The psychometric characteristics of the women who became pregnant (n = 7) and those who did not (n = 32) are listed in Table 3. A higher Zung Depression Scale score (t-test = 2.87, P = 0.01) and greater depressive coping (t-test = 3.78, P = 0.003) were associated with a lower PR. In the group of women with female subfertility, the Zung Depression Scale score was positively correlated with depressive coping (r = 0.58, P <0.001) and with the expression of negative emotions (r = 0.35, P <0.03) and was negatively correlated with active coping (r = 0.55, P <0.001) and with comforting ideas (r = -0.34, P <0.03). Psychometric Variables and Outcome in the Group with Male Subfertility Among the patients who were undergoing IVF for male subfertility, the duration of infertility and the number of previous IVF attempts were not significantly different in those who became pregnant (t-test = 0.92) and those who did not (t-test = 0.47). However, in the nonpregnant group, the mean (+ SD) patient age was significantly higher ( versus 27.9 _+ 2.8 years, respectively; t-test = 2.04, P = 0.05) and the mean (-+ SD) number of embryos transferred was significantly lower ( versus 2.9 _+ 0.2, respectively; t-test = -3.29, P = 0.002) than in the pregnant group. The psychometric characteristics of the pregnant (n = 14) and nonpregnant (n = 38) groups are listed in Table 4. A higher Zung Depression Scale score (t-test = -2.77, P = 0.009) and greater depressive coping (t-test = -2.70, P = 0.01) and palliative coping (t-test = -2.31, P = 0.03) were associated with a higher PR. In the group of women with male subfertility, the Zung Depression Scale score was positively correlated with depressive coping (r = 0.43, P = 0.001) but negatively correlated with the expression of negative emotions (r = -0.24, P = 0.04). The Zung Depression Scale score was not significantly correlated with active coping (r = 0.14, P = 0.15) or with comforting ideas (r = 0.03, P = 0.42). DISCUSSION The psychometric test results demonstrate that the coping styles of the women participating in our IVF program were comparable to those of a standard population, but that the depression levels as assessed by the Zung questionnaire were high: 54.1% of the women had mild depressive symptomatology and 19.4% had moderate to severe depressive symptomatology. These depression scores are in accordance with those in the published literature, in which the reported prevalence of depression in patients with infertility is high (usually twice that of control patients). However, the findings depend on the specific psychometric test used. In two studies that used the Center for Epidemiological Studies Depression Scale, which has a poor sensitivity of 64%, depression was found in 25% of women being treated with IVF and 25.8% of women attending an infertility clinic compared with 13.2% of control patients awaiting a routine 1030 Demyttenaere et al. Coping, depression, and IVF outcome Vol. 69, No. 6, June 1998

6 Psychometric variables (Zung Depression Scale and Utrechtse Coping List) in the subgroup of women with a male indication for IVF (n = 52) according to IVF outcome. IVF outcome Psychometric variable Not pregnant (n = 38) Pregnant (n = 14) t-test P value Zung Depression Scale score _ Utrechtse Coping List Active coping score Palliative coping score _ _ Avoiding score Social support seeking score 15.2 _ _ Depressive coping score Expression of negative emotions score Comforting ideas score 13.4 _ _ Note: The scores are given as means -+ SD. gynecologic examination (5, 15). In one of these studies, the severity of the depressive symptomatology also was assessed with the Beck Depression Inventory, which indicated that 36.7% of the women attending the infertility clinic were depressed compared with 18.4% of the control patients (15). These reports confirm that infertility and its treatment are experienced as extremely stressful situations. Although affected women have coping skills comparable to those of the general population, they are more frequently depressed. As expected, a higher depressive-regressive coping style was positively correlated and a higher active coping style was negatively correlated with the Zung Depression Scale score, suggesting that active coping is a more effective coping mechanism and depressive-regressive coping is a less effective coping mechanism, at least in preventing high depression scores in the total study group (n = 98) (10). Our results also demonstrate that the depression scores decreased as patient age, the duration of infertility, and the number of previous IVF attempts increased. This could suggest that women progressively adapt to the idea of remaining childless and gradually come to accept their infertility. The literature on the relation between the duration of infertility and the number of IVF attempts and depression is not conclusive. Several studies indicate that the most anxiety-provoking times for couples are during their first and final attempts to become pregnant, the first because of the fear of the unknown and the last because of its finality in determining their chances of producing biologic offspring (16, 17). This is in accordance with our findings. We speculate that most of the couples who participated in our study did not regard the present IVF cycle as their last one. Another study, however, found an opposite nonlinear relation between the duration of infertility and depression: women with a 2- to 3-year history of infertility had significantly higher depression scores than women with a < 1-year or >6-year history of infertility (15). The latter study comprised patients with infertility, but not all of them were treated with IVF. The first goal of the present study was to investigate the relation between a woman's depressive symptomatology and coping style and the outcome of IVF treatment. In the total study group, two coping mechanisms differentiated between the women who became pregnant and those who did not. Palliative coping was higher in the pregnant group than in the nonpregnant group, and the expression of negative emotions was lower in the pregnant group than in the nonpregnant group, suggesting that palliative coping is a more effective coping mechanism and the expression of negative emotions is a less effective coping mechanism, at least in terms of becoming pregnant with IVF treatment. These findings are clinically important because they result in a twofold increase in the chance of conception. A midsplit of the palliative coping score revealed that women with a higher than median score had a 29.8% chance of conception and those with a lower than median score had a 14.6% chance of conception. A midsplit of the expression of negative emotions score revealed that women with a lower than median score had a 31.3% chance of conception and those with a higher than median score had a 14.9% chance of conception. Because other variables that influence outcome (e.g., age, number of fertilized oocytes, and number of transferred embryos) were not significantly different in the midsplit subgroups, it could be the implantation mechanism that is influenced most by the woman's coping style. Because a mind-body program that teaches relaxation responses (which is a way of improving palliative coping) as well as cognitive-behavioral interventions (focusing on negative distortions and on negative emotions such as guilt or anger) is effective in reducing stress levels, perhaps it should be offered to infertile patients entering an IVF program. However, future studies are needed to prove whether such an FERTILITY & STERILITY 1031

7 approach also increases PRs (18). We know of only one small study of patients with unexplained secondary infertility in which PR was higher in the subgroup of patients who received psychotherapeutic counseling in addition to standard medical treatment compared with the subgroup of patients who received only standard medical treatment. However, no psychometric assessment was performed in this study (19). The second goal of this study was to investigate the relation between depressive symptomatology, coping style, and IVF outcome while taking into account the cause of infertility. We found that depression scores of the women with a female indication for IVF were comparable to those of the women with a male indication for IVF. This is in accordance with other published studies, in which equivalent depression scores have been found in couples with female factor infertility and those with male factor infertility (15). The finding that the women with a female indication for IVF had greater depressive coping than the women with a male indication for IVF is at least in partial accordance with the literature. Previous research has indicated that female partners of couples with male factor infertility tend to express anger toward their husbands, whereas female partners of couples with female factor infertility express depressive symptoms (20). The analysis of coping style, depressive symptomatology, and IVF outcome within the subgroups of women with a female or a male indication for IVF produced several unexpected results. First, we observed a complex relation between the Zung Depression Scale score and the outcome of IVF. In the total study group (n = 98) there was no statistically significant difference in the Zung score between the women who became pregnant and those who did not. However, in couples who were undergoing IVF for female subfertility, a higher Zung Depression Scale score was associated with a lower PR. The opposite was true in couples who were undergoing IVF for male subfertility. In these couples, a higher Zung Depression Scale score was associated with a higher PR. A more detailed post hoc analysis of the correlations between coping style and Zung Depression Scale score resulted in two unexpected findings but contributed to a better understanding of the apparent contradiction because this analysis suggested that the coping mechanisms that influence the Zung score are different in the subgroups with different causes of infertility. This suggests that the Zung Depression Scale score has a different content in each subgroup. First, active coping and comforting ideas (which are believed to be protective coping mechanisms against depression) are negatively correlated with the Zung Depression Scale score (r = and r = -0.34, respectively) in the group of women with a female indication for IVF. However, they are not significantly correlated with the Zung Depres- sion Scale score (r = and r = 0.15, respectively) in the group of women with a male indication for IVF. Second, the expression of negative emotions is positively correlated (r = 0.35) with the Zung Depression Scale score in the group of women with a female indication for IVF but negatively correlated (r = -0.24) with the Zung Depression Scale score in the group of women with a male indication for IVF. These apparently contradictory findings can be interpreted within the theoretic framework of the "coping-ineffectiveness of coping" construct that we described previously: when faced with a stressful situation (i.e., infertility and infertility treatment), an individual makes a primary appraisal (What is the possible danger or harm of the stressor [the infertility problem] for me?) and a secondary appraisal (How can I use my coping skills to protect myself against the stressor?). The depression score then can be seen as the ineffectiveness of coping (10, 21). It also should be remembered that the expression of negative emotions is positively correlated with the Jenkins Activity Scale (0.27), which contains elements of aggression and anger, and is positively with correlated the turning-against-objects scale (0.24) of the Defense Mechanisms Inventory (14). Women with a high expression of negative emotions hence will show elements of aggression and anger against the perceived cause of the problem, and this varies depending on the cause of the infertility. If the woman attributes the cause of the infertility to herself (female indication for IVF), general protective coping mechanisms (active coping and comforting ideas) are helpful in preventing depressive symptomatology and the expression of negative emotions worsens her psychologic situation (the expression of anger against the cause of the problem [i.e., herself] increases depressive symptomatology because anger will be turned into guilt). In contrast, if the woman attributes the cause of the infertility mainly to her partner (male indication for IVF), general protective coping mechanisms (active coping and comforting ideas) are not helpful in preventing depressive symptomatology and the expression of negative emotions protects her because anger will be directed toward her partner (the expression of anger against the cause of the problem [i.e., the male partner]). Guilt about one's own fertility problem increases depressive symptomatology, whereas anger about a partner's fertility problem decreases depressive symptomatology. The coping mechanisms that contribute to the Zung Depression Scale score thus are different in the female partners of couples with genuine female subfertility and in the female partners of couples with mainly male subfertility. To the best of our knowledge, an investigation of the relation between coping mechanisms and the Zung Depression Scale that takes into account attribution aspects (i.e., who is to blame?) has not been published previously. We speculate that these different "contents" of the Zung Depression Scale could 1032 Demyttenaere et al. Coping, depression, and IVF outcome Vol. 69, No. 6, June 1998

8 have different somatic effects (and hence different influences on treatment outcome). This explanation is in accordance with the previously mentioned finding that the female partners of couples with male factor infertility tend to express anger toward their spouses, whereas the female partners of couples with female factor infertility tend to express depressive symptoms (20). This observation also may explain why the literature on the influence of stress (anxiety or depression levels) on fertility has reported contradictory findings when the cause of infertility is not taken into account. This observation is in accordance with our clinical experience that one of the strongest taboos in subfertile couples is discussing the cause of the subfertility problem. It is remarkable that couples so seldom address this subject or express these negative feelings and emotions. It is our clinical experience that the decision making in infertility treatment (when to start IVF and, especially, when to stop it) is particularly difficult in couples with male subfertility. The cause of the subfertility lies with the man, but the woman has to undergo invasive therapy. If the woman holds on until she becomes pregnant, she can "hide" the man's problem; if she does not hold on, she makes the man's problem even more apparent. The man often does not dare insist on another IVF trial because his spouse has to suffer, but he does not insist on stopping treatment because that means withholding a child from his spouse. The present investigation risks placing an additional burden on the woman because it suggests that the woman's psychologic adaptation to the stress of the infertility and the infertility treatment can influence the outcome of the treatment. We are aware that our approach, which was to evaluate couples with strictly male factor or female factor infertility, inadvertently perpetuates the myth that women, directly or indirectly, are the main source of infertility problems. It is remarkable that the literature on the link between male fertility and male psychologic functioning is almost nonexistent. In conclusion, the present study demonstrates that the expression of negative emotions is negatively correlated with outcome during IVF. It also shows that the cause of infertility should be taken into account when investigating the relation between psychologic variables and IVF outcome. Protective mechanisms (e.g., active coping and comforting ideas) usually are protective against depressive symptomatology only when the indication for IVF is female subfertility and not when the indication is male subfertility. Moreover, the expression of negative emotions is positively correlated with depressive symptomatology when the indication for IVF is female subfertility (emotions are transformed into guilt directed against the woman herself), but is negatively correlated with depressive symptomatology when the indication for IVF is male subfertility (the emotions are transformed into anger directed toward the male partner). These findings can explain why the correlation between the Zung Depression Scale score and the outcome of IVF is different in couples who have a female or a male indication for IVF. A higher Zung Depression Scale score is correlated with a lower PR rate when the indication for IVF is female factor infertility but with a higher PR when the indication for IVF is male factor infertility. References 1. Lapane KL, Zierler S, Lasater TM, Stein M, Barbout MM, Hume AL. Is a history of depressive symptoms associated with an increased risk of infertility in women? 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New York: Springer Verlag, FERTILITY & STERILITY 1033