Risk factors for psychiatric disorders in infertile women and men undergoing in vitro fertilization treatment

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1 Risk factors for psychiatric disorders in infertile women and men undergoing in vitro fertilization treatment Helena Volgsten, M.Sc., a Agneta Skoog Svanberg, Ph.D., a Lisa Ekselius, Ph.D., b Orjan Lundkvist, Ph.D., a and Inger Sundstr om Poromaa, Ph.D. a a Department of Women s and Children s Health, and b Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden Objective: To identify risk factors associated with depression and anxiety in infertile women and men undergoing in vitro fertilization (IVF). Design: Prospective study. Setting: A university hospital in Sweden during a 2-year period. Patient(s): 825 participants (413 women and 412 men). Intervention(s): Primary Care Evaluation of Mental Disorders (PRIME-MD), based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), as the diagnostic tool for evaluating mood and anxiety disorders, and fertility history and outcome of IVF treatment collected from the patients medical records. Main Outcome Measure(s): Risk factors associated with depression and anxiety disorders. Result(s): A negative pregnancy test and obesity were the independent risk factors for any mood disorders in women. Among men, the only independent risk factor for depression was unexplained infertility. No IVF-related risk factors could be identified for any anxiety disorder. Conclusion(s): A negative pregnancy test is associated with an increased risk for depression in women undergoing IVF, but no risk of developing anxiety disorders is associated with the pregnancy test result after IVF. Pregnancy test results were not a risk factor for depression or anxiety among men. (Fertil Steril Ò 2010;93: Ó2010 by American Society for Reproductive Medicine.) Key Words: Depression, anxiety, women, men, infertility, in vitro fertilization, risk factors Undergoing in vitro fertilization treatment (IVF) is considered to be a multidimensional stressor. The treatment itself may evoke anxiety, and the unpredictable outcome of IVF treatment may induce a depressive mood (1). We previously reported that approximately 30% of infertile women and 10% of infertile men undergoing IVF fulfilled the criteria for a depressive and/or anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) (2). The prevalence of depressive disorders among infertile women was almost twice that of the general population, although the prevalence rates of anxiety disorder were similar (3 5). One study found that approximately 37% of infertile women had depressive symptoms on the Beck Depression Inventory (BDI), which was twice rate of the control group (6). At onset of IVF, 19.4% of infertile women have Received August 22, 2008; revised October 10, 2008; accepted November 2, 2008; published online December 31, H.V. has nothing to disclose. A.S.S. has nothing to disclose. L.E. has nothing to disclose. O.L. has nothing to disclose. I.S.P. has nothing to disclose. Supported by research grants from the Swedish Research Council, project K X , the Council for Working Life and Social Research, project , the Family Planning Foundation, and the Foundation of Caring Sciences, Uppsala University. Reprint requests: Helena Volgsten, M.Sc., Department of Women s and Children s Health, University Hospital, Uppsala, Sweden (FAX: þ ; helena.volgsten@kbh.uu.se). been estimated to have moderate to severe depressive symptoms and 54% as being mildly depressed according to the Zung Depression Scale (7). Before IVF, 11.6% of women reported depressive symptoms according to the BDI; the frequency increased to 25.4% after failed IVF (8). However, it must be emphasized that the prevalence rates of depression and/or anxiety disorders among infertile women undergoing IVF in the present study are similar to what has been found in unselected gynecologic outpatients, where 30.5% had any psychiatric disorder and 10% had major depression (9). Hence, compared with patients in gynecologic practice, depression and/or anxiety disorders do not appear to be more common in infertile women. However, compared with a population-based study of pregnant women in the second trimester, the prevalence rates of depression and/or anxiety disorder are higher in infertile women. The prevalence of any depressive disorder in pregnant women was 11.6%, and the prevalence of any anxiety disorder was 6.6% (10). Risk factors for depression and anxiety in the general population include low socioeconomic status, smoking, drug and alcohol abuse, and being single and unemployed (11 12), which is fairly consistent with risk factors for psychiatric disorders in a population-based sample of pregnant women (13). A history of depressive disorders is another risk factor for depression in the general population (14). Prospective studies of risk factors for psychological problems in infertile women 1088 Fertility and Sterility â Vol. 93, No. 4, March 1, /10/$36.00 Copyright ª2010 American Society for Reproductive Medicine, Published by Elsevier Inc. doi: /j.fertnstert

2 TABLE 1 Fertility factors and outcome of IVF treatment for women with or without any psychiatric disorder. Women Any psychiatric disorder (n [ 127) diagnosis (n [ 286) No. oocytes at retrieval Fertilization rate (%) ET, n (%) Yes 115 (90.6) 245 (86.3) No 12 (9.4) 39 (13.7) No. of embryos at ET No. of frozen embryos after ET Positive 35 (27.6) 101 (35.3) Negative 92 (72.4) 185 (64.7) Ultrasound findings, n (%) Clinical pregnancy 27 (21.3) 88 (30.8) Biochemical 3 (2.4) 8 (2.8) Empty gestational sac 5 (3.9) 5 (1.7) Miscarriages, n (%) Extrauterine pregnancy 0 1 (0.3) Miscarriage < wk 12 1 (0.8) 12 (4.2) Miscarriage > wk (0.3) Live birth rate, n (%) Yes 26 (20.5) 74 (25.9) No 101 (79.5) 212 (74.1) Mode of delivery, n (%) Vaginal 22 (84.6) 54 (73.0) Caesarean section 4 (15.4) 20 (27.0) Note: ET = embryo transfer. undergoing treatment are scarce (1). Compared with the general population, it can be assumed that other risk factors are of importance as IVF couples by definition are in stable relationships and presumably avoid smoking and alcohol use to a greater extent. Our prospective study identified risk factors for depressive disorders and anxiety disorders in infertile women and men undergoing IVF. MATERIALS AND METHODS Study Population From April 11, 2005, to April 13, 2007, all female and male partners in consecutive couples undergoing IVF or intracytoplasmic sperm injection (ICSI) treatment at the Centre of Reproduction at Uppsala University Hospital, Sweden, were approached for participation in the study. Study exclusion criteria were [1] inability to read and understand the questionnaire because of language difficulties and [2] couples undergoing cycles with gamete donation (i.e., oocyte and sperm donation). Furthermore, patients already evaluated during an earlier IVF treatment during the study period were not approached to participate. A detailed description of the study population has been presented elsewhere (2). In summary, 545 couples comprising 1090 eligible women and men were approached to participate in the study. Overall, 862 (79.1%) participants filled out the patient questionnaire and consented to a telephone interview. The response rates were 439 (80.5%) and 423 (77.6%) among women and men, respectively. Among participants who filled out the patient questionnaire, 452 (52.4%) women and men indicated a positive response to one or more of the key questions for mental disorders and also consented to a follow-up telephone interview. Of these, 26 (5.9%) women and 11 (2.6%) men could not be reached by telephone within the stipulated 21-day period. Hence, a telephone interview was conducted in 415 cases; the study sample wherein a possible confirmation of a psychiatric diagnosis could be made consisted of 825 participants (413 women and 412 men). The Centre of Reproduction is a public clinic, and three IVF treatments are offered free of charge to infertile couples. The waiting list for IVF/ICSI is approximately 3 months. Couples who are referred for IVF treatment from areas outside Uppsala County are pretreated at the referring clinic. The pregnancy test (human chorionic gonadotropin [hcg] in urine) is assessed at home by the woman 16 to 19 days after oocyte retrieval. Fertility and Sterility â 1089

3 TABLE 2 Associations between sociodemographic, fertility data, and any mood disorder in women. Women Any mood disorder (n [ 108) diagnosis (n [ 286) Adjusted odds ratio Positive 27 (25.0) 101 (35.3) ref Negative 81 (75.0) 185 (64.7) 1.68 a <35 71 (65.7) 183 (64.0) ref R35 37 (34.3) 103 (36.0) BMI (kg/m 2 ), n (%) <30 91 (85.0) 257 (92.8) ref R30 16 (15.0) 20 (7.2) 2.21 a Nonsmoker 100 (92.6) 273 (95.5) ref Smoker 8 (7.4) 13 (4.5) Previous pregnancy, n (%) No 67 (62.0) 208 (72.7) ref Yes 41 (38.0) 78 (27.3) <36 73 (67.6) 176 (61.5) ref R36 35 (32.4) 110 (38.5) Male 31 (28.7) 86 (30.1) ref Female 40 (37.0) 85 (29.7) Unexplained 37 (34.3) 115 (40.2) Note: BMI ¼ body mass index. a P<.05, multiple logistic regression based on 384 patients; 10 were missing data. Psychiatric Assessment Diagnoses of psychiatric disorders were assessed by use of the PRIME-MD (Primary Care Evaluation of Mental Disorders). The original PRIME-MD system, which is fully described elsewhere (15), consists of two components: a 1-page patient questionnaire and a 12-page clinician evaluation guide, which is a structured interview guide to be followed when evaluating the responses on the patient questionnaire. A modified form of the PRIME-MD patient questionnaire, containing 24 questions, was used for this study. The PRIME-MD system evaluates the presence of 20 possible psychiatric disorders, of which this study focused on depressive disorders (major depressive disorder, dysthymia, partial remission of major depressive disorder, and minor depressive disorder) and anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social phobia, and anxiety not otherwise specified). Study Design On the day of oocyte retrieval, each eligible participant was asked for consent to participate in the study and to complete and return the PRIME-MD patient questionnaire. To confirm a diagnosis, a telephone interview using a computerized version of the clinical evaluation guide was conducted with the screen-positive women and men. The telephone interview was conducted 21 days after screening (i.e., after the pregnancy test had been performed). Sociodemographic data were collected by asking the participants to fill in a separate questionnaire with questions on socioeconomic factors. The fertility history and outcome of IVF treatment were collected from the patients medical records after all of them had participated in the study. The study was approved by the independent ethics review board at Uppsala University, Sweden. Statistical Analyses Continuous variables were compared by the use of an independent t-test and are displayed as mean standard deviation (SD). Frequencies were compared between groups by chisquare tests. Demographic data, fertility history, and treatment outcome were compared between participants with any psychiatric disorder and those with no psychiatric diagnosis; the latter group consisted of screen-negative patients 1090 Volgsten et al. Risk factors for psychiatric disorders Vol. 93, No. 4, March 1, 2010

4 TABLE 3 Associations between sociodemographic, fertility data, and major depression in women. Women Major depression (n [ 45) diagnosis (n [ 286) Adjusted odds ratio Positive 9 (20.0) 101 (35.3) ref Negative 36 (80.0) 185 (64.7) 2.23 a <35 29 (64.4) 183 (64.0) ref R35 16 (35.6) 103 (36.0) Nonsmoker 40 (88.9) 273 (95.5) ref Smoker 5 (11.1) 13 (4.5) 3.28 a Previous pregnancy, n (%) No 24 (53.3) 208 (72.7) ref Yes 21 (46.7) 78 (27.3) 2.17 a <36 31 (68.9) 176 (61.5) ref R36 14 (31.1) 110 (38.5) Male 11 (24.4) 86 (30.1) ref Female 20 (44.4) 85 (29.7) Unexplained 14 (31.1) 115 (40.2) a P<.05, multiple logistic regression based on 331 patients. and screen-positive patients in whom no psychiatric diagnosis was established during the telephone interview. Multiple logistic regression analysis (16) was used to calculate adjusted odds ratios (OR) and (CI) for risk factors of psychiatric disorders (any mood disorder or any anxiety disorder). Variables with P%.25 in the univariate analyses were included in the multiple logistic regression analyses (17) with the exception of age, smoking, duration of infertility, cause of infertility, and the result of the pregnancy test. These variables were forced into the model as they are factors of clinical importance (17) for the IVF treatment and possible risk factors for depression in participants undergoing IVF. The following variables were dichotomized and assessed in the univariate analyses: female or male age at the time of IVF treatment (<35 or R35 years), body mass index (BMI) in kg/m 2 at the first visit (dichotomized according to recommendation by the World Health Organization as normal and overweight BMI <30 or obese BMI R30), smoking recorded at the first visit to the clinic (nonsmoking, i.e., no daily smoking, or smoking one or more cigarettes per day), socioeconomic status (professional employee or laborer, according to Swedish socioeconomic indexes), economic status (reported by the patients as good, acceptable, or bad was dichotomized as good or acceptable), and native language (Swedish as first language or first language other than Swedish). Fertility history variables such as previous pregnancy, previous miscarriage (including extrauterine pregnancies), and parity were categorized as yes/no. The remaining fertility variables were categorized accordingly: duration of infertility recorded at the first visit to the clinic (<36 or R36 months) and previous IVF/ICSI (first or repeated IVF/ICSI treatment). The cause of infertility was categorized as female factors (including tubal factor, endometriosis, anovulation, and other factors), male factors (including combined male and female factors), or unexplained factors (including no evaluation). The cause of infertility was then dichotomized as explained (female/male factor) or unexplained; as the result did not differ from the first categorization, those three categories were kept in the analyses. The outcome of IVF was assessed as a positive or negative pregnancy test after started treatment (cycle). The pregnancy test result was confirmed at ultrasound during gestational week 7 to 8 and was categorized as clinical pregnancy or biochemical (including empty gestational sac). All statistical analyses were performed with SPSS 15.0 (SPSS, Inc., Chicago, IL). Two-sided P<.05 was considered statistically significant. RESULTS Study Population More women than men had any psychiatric disorder: 127 (30.8%) of 413 women and 42 (10.2%) of 412 men (OR Fertility and Sterility â 1091

5 TABLE 4 Associations between sociodemographic, fertility data, and any mood disorder in men. Men Any mood disorder (n [ 38) diagnosis (n [ 370) Adjusted odds ratio Positive 11 (27.0) 122 (33.0) ref Negative 27 (73.0) 248 (67.0) <35 19 (50.0) 197 (54.0) ref R35 19 (50.0) 168 (46.0) Nonsmoker 35 (92.1) 355 (95.9) ref Smoker 3 (7.9) 15 (4.1) Socioeconomic status, n (%) Professional employee 14 (41.2) 176 (52.4) ref Laborer 20 (58.8) 160 (47.6) <36 22 (56.8) 236 (65.4) ref R36 16 (43.2) 125 (34.6) Female 8 (21.0) 120 (32.4) ref Male 12 (31.6) 111 (30.0) Unexplained 18 (47.4) 139 (37.6) 3.41 a Previous IVF/ICSI, n (%) No 25 (65.8) 285 (77.0) ref Yes 13 (34.2) 85 (23.0) a P<.05, multiple logistic regression based on 356 patients; 52 were missing data. 3.91; 95% CI, ). Any mood disorder was the most prevalent psychiatric disorder, with 108 (26.2%) women and 38 (9.2%) men. Major depression, the most prevalent mood disorder, was present in 45 (10.9%) women and 21 (5.1%) men. Any anxiety disorder was prevalent in 61 (14.8%) women and 20 (4.9%) men. According to the subjective evaluations of economic status, fewer women with a psychiatric disorder rated their economic status as good in comparison with women with no psychiatric diagnosis. Outcome of Treatment The overall treatment outcome in the study population of 413 women was 136 (32.9%) positive pregnancy tests, resulting in a live birth rate of 100 (24.2%). Fertility factors and outcome of IVF treatment for women with or without any psychiatric diagnosis are presented in Table 1. There were no differences in fertilization factors such as number of oocytes retrieved, fertilization rate, number of frozen embryos, or treatment outcome (pregnancy test result) between women with or without any psychiatric disorder. Risk Factors for Any Mood Disorder When risk factors for any mood disorder were analyzed separately, previous pregnancy and obesity were statistically significantly associated with any mood disorder among women in the unadjusted analysis. Multiple logistic regression revealed an independent association with a negative pregnancy test. In the adjusted logistic regression, obesity also remained an independent risk factor for any mood disorder in women (Table 2). Women with major depression (n ¼ 45) more often had a negative fertility history than women with no psychiatric diagnosis. Previous extrauterine pregnancy was more prevalent in women with major depression (n ¼ 5, 11.1%) than in women with no psychiatric diagnosis (n ¼ 8, 2.8%, P<.008). Although the study was not designed to address the impact of major depression on treatment outcome, it was apparent that women with major depression had the most negative outcomes after IVF treatment of all women in the study. The pregnancy rate for women with major depression (n ¼ 9, 20.0%) was statistically significantly lower compared with women with no psychiatric diagnosis (n ¼ 101, 35.3%). Multiple logistic regression showed a negative pregnancy test, previous pregnancy, and smoking were independent risk factors for major depression in women (Table 3). The live birth rate for women with major depression was 8.9% (n ¼ 4) compared with a live birth rate of 25.9% among women with no diagnosis (n ¼ 74; OR 3.57; 95% CI, ; P<.02) Volgsten et al. Risk factors for psychiatric disorders Vol. 93, No. 4, March 1, 2010

6 TABLE 5 Associations between sociodemographic, fertility data, and any anxiety disorder in women. Women Any anxiety disorders (n [ 61) diagnosis (n [ 286) Adjusted odds ratio Positive 20 (32.8) 101 (35.3) ref Negative 41 (67.2) 185 (64.7) <35 43 (70.5) 183 (64.0) ref R35 18 (29.5) 103 (36.0) Nonsmoker 56 (91.8) 273 (95.5) ref Smoker 5 (8.2) 13 (4.5) Native language, n (%) Swedish 55 (90.2) 273 (95.5) ref Not Swedish 6 (9.8) 13 (4.5) Previous pregnancy, n (%) No 38 (62.3) 208 (72.7) ref Yes 23 (37.7) 78 (27.3) <36 46 (75.4) 176 (61.5) ref R36 15 (24.6) 110 (38.5) Male 20 (32.8) 86 (30.1) ref Female 19 (31.1) 85 (29.7) Unexplained 22 (36.1) 115 (40.2) Note: Multiple logistic regression based on 347 patients. The only independent risk factor for any mood disorder among men was unexplained infertility factor (Table 4). Treatment outcome after IVF did not affect the risk of having any mood disorder in men. Risk Factors for Any Anxiety Disorder Among women, no independent IVF-related or other risk factors for any anxiety disorder were detected, and the pregnancy test result was not associated with the risk of being diagnosed with any anxiety disorder in women (Table 5). The unadjusted analysis found several risk factors for any anxiety disorder in men, such as age, obesity, smoking, other native language, and previous IVF/ICSI treatment (Table 6). However, the number of men with any anxiety disorder in the current study was limited, and a multiple logistic regression was not performed. DISCUSSION This is the first study to describe risk factors for depressive disorders and anxiety disorders in women and men undergoing IVF treatment. Independent risk factors for any mood disorders in women were a negative pregnancy test and obesity. Among men, the only independent risk factor for depression was unexplained infertility. For any anxiety disorder no IVFrelated risk factors could be identified. A negative pregnancy test after IVF treatment was associated with an increased risk of any mood disorder, in particular major depression, among women. As the pregnancy test is taken at home by the woman, a negative test result will be revealed for the couple outside the fertility clinic. Therefore, it is clinically important to continue to observe couples who have negative pregnancy tests. It has been suggested in previous studies that infertile couples need to be informed before IVF that the outcome can result in an unsuccessful treatment (18). We recommend that all couples should have a mandatory appointment for follow-up already booked at the start of IVF. In case of treatment failure, the follow-up visit should be made within a few weeks after the pregnancy test result to a specialized midwife or mental health professional. Not only is unsuccessful treatment associated with an increased risk of depression, a failed treatment may also cause an increase in preexisting depressive symptoms, which are unlikely to diminish shortly after treatment (18). An unsuccessful first treatment is a less favorable starting point for the next treatment cycle and may be a risk for later development of clinical depression (19), although our study was unable to substantiate this assumption in women. Clearly, it Fertility and Sterility â 1093

7 TABLE 6 Associations between sociodemographic, fertility data, and any anxiety disorder in men. Men Any anxiety disorder (n [ 20) diagnosis (n [ 370) Unadjusted odds ratio a Positive 5 (25.0) 122 (33.0) ref Negative 15 (75.0) 248 (67.0) <35 6 (30.0) 197 (54.0) ref R35 14 (70.0) 168 (46.0) 2.73 b BMI (kg/m 2 ), n (%) <30 15 (75.0) 333 (91.7) ref R30 5 (25.0) 30 (8.3) 3.70 b Nonsmoker 17 (85.0) 355 (95.9) ref Smoker 3 (15.0) 15 (4.1) 4.17 b Native language, n (%) Swedish 16 (80.0) 355 (95.9) ref Not Swedish 4 (20.0) 15 (4.1) 5.91 b <36 9 (47.4) 236 (65.4) ref R36 10 (52.6) 125 (34.6) Female 4 (20.0) 120 (32.4) ref Male 7 (35.0) 111 (30.0) Unexplained 9 (45.0) 139 (37.6) Previous IVF/ICSI, n (%) No 11 (55.0) 285 (77.0) ref Yes 9 (45.0) 85 (23.0) 2.74 b Note: BMI ¼ body mass index; 22 patients were missing data. a Univariate analyses. b P<.05. is important for the IVF team to identify couples with mood disorders and ensure that adequate treatment is initiated before further IVF treatment. However, it must be emphasized that a positive pregnancy test is not a cure for depression; one out of four women was still depressed in spite of a positive pregnancy test after IVF. In women with any anxiety disorder, this is even more obvious as the treatment outcome was not associated with risk for anxiety disorders. In women with anxiety disorders, the pregnancy test result, whether positive or negative, will merely be another cause for anxiety. This assumption is further corroborated by studies indicating that fear of miscarriage still may be present after a positive pregnancy test (19). Obesity (BMI R30) was another risk factor, independent of a negative pregnancy test, for any mood disorder in women. Obesity is a major health concern, and its prevalence has tripled in many Western countries since the 1980s (20). Obesity is associated with depressive and anxiety disorders (21 22). Given the increasing prevalence of obesity in the population, there is a strong probability that obesity and depression will occur together. For this reason, treatment of both disorders needs to be addressed in these women (23). Clearly, obese women undergoing IVF are at increased risk for depression during the treatment course, not only because of the obesity but also as the obesity in itself is associated with increased risk of treatment failure (24). Obesity may negatively affect the live birth rate after IVF (25), and weight reduction before the onset of IVF has been shown to be efficient for improving treatment outcome (26). Information about the negative effects of obesity is important, and many clinics recommend weight reduction before IVF. Couples undergoing IVF need to be counseled and advised regarding their individual lifestyle changes (27). The cause of infertility has been suggested to affect the mood of infertile patients and has to be taken into account when couples undergo IVF (7). In our study, unexplained infertility was an independent risk factor for any mood disorder 1094 Volgsten et al. Risk factors for psychiatric disorders Vol. 93, No. 4, March 1, 2010

8 in men undergoing IVF but not for women. This finding was consistent with a previous study where unexplained infertility was not associated with depression among women (6). The cause of infertility among men appeared to influence their willingness to participate in our study: the men who declined to participate more often had male factor infertility than the men who participated (2). However, the number of men with any mood disorder in our study was limited, so the results of the logistic regression must be interpreted with caution. A number of sociodemographic risk factors for anxiety disorders in men were identified in the univariate analyses. However, because of the limited number of cases, multiple logistic regression was not performed. Clearly, there is a need for further studies to establish the risk factors for any anxiety disorders in men undergoing IVF. Common risk factors for psychiatric disorders in the general population, such as low socioeconomic status, unemployment, and being unmarried (11 12), were not associated with depression or anxiety in our study population, most likely because patients accepted for IVF must be in stable relationships. Employment status, which could have affected the risk of mood disorders, was not originally included in the study questionnaire and could not be assessed in the logistic regression analyses. Another limitation of the current study was that a history of depression could only be reported by women and men who had had a psychiatric disorder diagnosed (2), not by all participants in the study population; therefore, this variable could not be used in the statistical analyses. Other factors such as vulnerability or personality traits must be taken into account to identify patients at risk for depression before IVF (1, 28). Although the number of women with major depression in our study was limited, it is difficult to ignore that women with major depression had the most negative outcome after IVF treatment of all women in the study, with a live birth rate of 8.9%. The final assessment of the psychiatric diagnosis was made when the pregnancy test result was known to the woman, which most likely influenced the risk of depression at that time point and consequently decreased the rate of positive pregnancy tests (20.0%) in this group. However, it is unlikely that the time-point of assessment biased the live birth rate. A review of the literature indicates that mood disorders may be associated with decreased pregnancy rates (29), although there is great controversy in the field. An association between anxiety and/or depression and lower pregnancy rates has been suggested (7, 30 32), but other studies have failed to indicate any association between anxiety and/or depression and negative pregnancy rates (33 35). Few studies have addressed the association of mood disorders and live birth rate as the end point. Klonoff-Cohen et al. (36) found that live birth rate was negatively influenced by baseline stress before IVF, but de Klerk et al. (37) did not. Clearly, there is a need for further studies to establish the association between depressive disorders such as major depression and unsuccessful outcomes after IVF. The results of our study suggest that a negative pregnancy test after undergoing IVF is an independent risk factor for any mood disorder in women. These women need to be identified before the onset of the next IVF treatment (18). Anxiety disorders appear to be less influenced by the pregnancy test result. In men, unsuccessful treatment was not associated with a risk for either depression or anxiety. Women with major depression had a statistically significantly lower live birth rate than women with no psychiatric diagnosis. These findings underscore the need to identify women with risk factors for depressive disorders before they undergo further IVF treatment and to offer them adequate treatment. Acknowledgments: The authors thank all the infertile women and men who participated in this study. REFERENCES 1. Verhaak CM, Smeenk JM, Evers AW, van Minnen A, Kremer JA, Kraaimaat FW. Predicting emotional response to unsuccessful fertility treatment: a prospective study. J Behav Med 2005;28: Volgsten H, Skoog Svanberg A, Ekselius L, Lundkvist O, Sundstrom Poromaa I. Prevalence of psychiatric disorders in infertile women and men undergoing in vitro fertilization treatment. Hum Reprod 2008;23: Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, et al. 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