Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic

Abstract

BACKGROUND: Little is known about the prevalence of specific depressive and anxiety disorders in women before a new course of assisted reproductive technology treatment. Few studies have adopted the proper psychiatric diagnostic procedures. METHODS: All consecutive women visiting the assisted reproduction clinic of a university-affiliated medical centre, with the intention of starting a new assisted reproduction treatment course, were recruited. A psychiatrist made a diagnosis of psychiatric disorders using a structured interview, the Mini-International Neuropsychiatric Interview (MINI). RESULTS: Of a total of 112 participants, 40.2% had a psychiatric disorder. The most common diagnosis was generalized anxiety disorder (23.2%), followed by major depressive disorder (17.0%), and dysthymic disorder (9.8%). Participants with a psychiatric morbidity did not differ from those without in terms of age, education, income, or years of infertility. Women with a history of previous assisted reproduction treatment did not differ from those without in depression or anxiety. CONCLUSIONS: Depressive and anxiety disorders were highly prevalent among women who visited an assisted reproduction clinic for a new course of the treatment. Demographic features and a history of previous assisted reproduction treatment were not risk factors for these psychiatric morbidities in the assisted reproduction clinic.

Introduction

Many studies have reported that depression and anxiety are highly prevalent among infertile women (Golombok, 1992; Beutel et al., 1999; Lok et al., 2002). It has been postulated that these psychiatric symptoms may either be the cause of infertility or the consequence of it, or both (Greil, 1997). Depressive and anxiety disorders deserve much clinical attention because they greatly affect the patients' quality of life (Wilson and Kopitzke, 2002). Despite the importance of psychiatric morbidities, we still know little about the prevalence of specific psychiatric disorders in women who come to assisted reproduction clinics for help before undergoing assisted reproduction treatment. Most, if not all, previous studies have adopted questionnaires in the assessment of their patients' psychiatric status (Newton et al., 1990; Domar et al., 1992; Demyttenaere et al., 1998; Lukse et al., 1999; Oddens et al., 1999; Matsubayashi et al., 2001; Anderson et al., 2003). Questionnaires, however, can only reveal the prevalence of psychiatric symptoms. Previous studies have shown that self-ratings, although a useful tool for assessing the severity of depressive symptoms, are not ideal for identifying the existence of major depression as a disorder (Prusoff, 1972; Carroll, 1973). To obtain a more accurate understanding of psychiatric morbidity among women before assisted reproduction treatment, studies using proper and structured psychiatric diagnostic procedures are needed.

The purpose of the current study was to evaluate the prevalence of psychiatric disorders in pre-assisted reproduction treatment women in an assisted reproduction clinic using a structured diagnostic interview performed by a board-certified psychiatrist. It is hoped that clinicians working at assisted reproduction clinics can understand their patients better through an awareness of their psychiatric condition. As a consequence, clinicians may be able to provide more comprehensive care for their assisted reproduction patients.

Materials and methods

Participants

The present study is a part of the Mood, Distress, and Assisted Reproductive Technique (MD-ART) project. The aim of the MD-ART is to assess the bi-directional relationship between emotional distress and assisted reproduction procedures: that is, how emotional distress influences the outcome of assisted reproduction treatment and how the treatment affects mood. The MD-ART participants were recruited from consecutive new patients who visited the Endocrine and Reproduction Outpatient Clinic at the Taipei Veterans General Hospital, a university-affiliated medical centre in Taipei, Taiwan, from December 2002 to May 2003. No referral is required to attend this clinic. The inclusion criteria were: (i) the main reason for the visit was to undergo a new course of assisted reproduction treatment [artifical insemination with the husband's semen (AIH), IVF or ICSI]; and (ii) an agreement to participate in the research after we presented ourselves as a research team outside the assisted reproduction team, and explained the purposes of the research. The exclusion criterion was a previous course of assisted reproduction treatment that had not completely come to an end. The participants might or might not have received assisted reproduction treatment before. During the recruiting period, there were 166 women fulfilling the inclusion criteria. Of these, 112 subjects agreed to participate, a participation rate of 67%. We assured the participants that their individual data were confidential, even to the assisted reproduction team. Since all the participants were still under evaluation for the upcoming assisted reproduction treatment, they had not yet received hormone treatment.

Psychiatric diagnosis

After subjects had given informed consent, their demographic data were collected. A board-certified psychiatrist then conducted a standardized structured diagnostic interview according to the Mini-International Neuropsychiatric Interview (MINI) 5.0.0 edition (Sheehan et al., 1998). The MINI is a standardized diagnostic instrument for the diagnosis of Diagnostic and Statistical Manual, 4th edn (DSM-IV; American Psychiatric Association, 2000) and International Classification of Diseases (ICD)-10 psychiatric disorders (World Health Organization (1992)). It consists of standardized, structured, closed-end questions throughout its diagnostic procedure. The DSM-IV and ICD-10 criteria were reframed into standardized questions in MINI. The interviewers read literally these close-ended questions as verbatim as possible to the interviewees. Psychiatric diagnosis was made according to the number of affirmative replies to the specific questions. Studies have shown that the MINI is a valid and reliable diagnostic tool. Inter-rater and test–retest reliabilities were high among the majority of disorders. Validities with other lengthy structured diagnostic interviews, including the Composite International Diagnostic interview CIDI and Structured Clinical Interview for DSM-IIIR SCID, were also high (Lecrubier et al., 1997; Sheehan et al., 1997). Research has also shown that the MINI can be used successfully as a gold standard of psychiatric diagnosis in multi-centre clinical trials and epidemiology studies (Gabarron et al., 2002; Wojnar et al., 2003). To reduce the time of the interview, we excluded alcohol abuse and dependence, substance use disorders, psychotic disorders, and antisocial personality disorder, because these disorders are beyond the scope of the present study and are considered to be of negligible frequency in our sample. Only current diagnoses were made.

Psychological assessments

The participants also filled out the Hospital Anxiety and Depression Scale (HADS). The HADS is a self-administered rating scale composed of 14 questions, seven for anxiety and seven for depression, yielding a total score, an anxiety score, and a depression score, respectively. By focusing on psychological symptoms of anxiety and depression, the HADS avoids the confounding effect of physical symptoms in detecting anxiety and depression among subjects with somatic illness (Zigmond and Snaith, 1983). The HADS has been successfully used to screen emotional disorders in subjects with a variety of diseases, including infertile women (Herrmann, 1997; Juang et al., 1999; Matsubayashi et al., 2001). Similar to the study of Matsubayashi et al. (2001), we adopted a total HADS score of >12 as a threshold value. In both the anxiety score and depression score, we used a threshold value of >9 to identify participants with high anxiety and high depression respectively.

Statistical analysis

The Statistical Package for Social Sciences for Windows program was used for statistical analysis. Descriptive statistics of frequency, the Student's t-test, χ²-test, and linear regression were used for comparisons when appropriate. P<0.05 was considered statistically significant.

Results

A total of 112 women were enrolled in this study. The mean±SD age of the participants was 33.79±4.93 years old (range 24–45). The demographic data and clinical characteristics of these participants are presented in Table I.

Table II shows the prevalence of psychiatric disorders in our sample. Forty-five participants had at least one psychiatric diagnosis. The prevalence of any psychiatric disorder was 40.2%. The respective prevalence of major depression and dysthymia was 17.0% and 9.8%. The frequency of having any mood disorders was 26.8%, and the frequency of any anxiety disorder was 28.6%. Among all the psychiatric diagnoses, generalized anxiety disorder (GAD) was the most frequent (prevalence = 23.2%), followed by major depressive disorder (17.0%), and dysthymic disorder (9.8%). Co-morbid mood and anxiety disorders were common. About 15.2% of our participants had both mood disorders and anxiety disorders.

The mean±SD total HADS score of all the participants was 11.3±6.1 (median = 11). The mean±SD anxiety score was 6.7±3.5, median = 7), and the mean depression score was 4.6 (SD = 3.1, median = 4). Forty per cent of our participants had a total HADS score >12. Twenty-three per cent had an anxiety score of >9, and 5.0% had a depression score >9. In linear regression, the HADS score did not correlate with either age (P=0.33) or years of education (P=0.48).

When comparing demographic characteristics between participants with a psychiatric disorder and those without, we could not find any significant difference in age, education, income, or any other feature. The comparison of demographic data between the two groups is shown in Table III. When comparing the HADS scores between participants with and without a psychiatric disorder, the differences were significant. The mean total HADS score was 14.2±6.2 for our participants with any psychiatric diagnosis, 15.3±5.8 for participants with any mood disorder, and 14.5±6.5 for participants with any anxiety disorder, which were all significantly different from the mean for 9.4±5.3 of participants without any psychiatric disorder (all P<0.01).

Fifty of our participants had received assisted reproduction treatment before they came to our clinic for help, while 48 participants were totally new to assisted reproduction. As shown in Table IV, none of the HADS scores were significantly different between participants with previous assisted reproduction treatment and those without. The frequencies of depressive disorders or anxiety disorders were also similar between these two groups.

Only three of our participants had consulted a psychiatrist before they came to the assisted reproduction programme. Among the 45 participants whom we found to have a psychiatric disorder in this study, the frequency of psychiatric service utilization was 6.7%.

Discussion

In the present study, we found that the prevalence of psychiatric disorders among women preparing for a new course of assisted reproduction treatment was as high as 40.2%. That is, about two out of five of the participants had a psychiatric disorder. More than a quarter (26.8%) of all these participants had depressive disorders, and even more (28.6%) had anxiety disorders. The prevalence of psychiatric disorders was not affected by demographic features or a history of previous assisted reproduction treatment. Our results from a verified standardized structured diagnostic interview have provided further evidence to support some of the previous questionnaire-based research which found high frequencies of anxiety and depression in assisted reproduction clinics (Domar et al., 1992; Demyttenaere et al., 1998; Lukse et al., 1999; Oddens et al., 1999; Matsubayashi et al., 2001; Anderson et al., 2003). However, these studies using questionnaires could not distinguish between major depression and dysthymic disorder, nor could they differentiate between specific anxiety disorders.

The extraordinarily high prevalence of GAD (23.2%) in our assisted reproduction clinic is noteworthy. Anderson et al. (2003), using the HADS, also found that about a quarter of the infertile women attending the clinics had a high level of anxiety. According to DSM-IV (American Psychiatric Association, 2000), the 1 year prevalence of GAD is ∼3% in the community. In a similar study that also adopted the MINI in a headache clinic, the frequency of GAD was only 5% (Juang et al., 2000). Recently, Jackson et al. (2001) showed that the prevalence of anxiety disorders among general medical outpatients was ∼11%. Therefore, it is unlikely that the sampling bias of a clinical population alone can explain the high prevalence of GAD in our results. The high prevalence of GAD among our participants suggests that a possible link may exist between GAD and participation in assisted reproduction clinics. It is possible that GAD is associated with infertility or with the intention to receive assisted reproduction treatment, either as a cause or as a consequence. More research is needed to determine the role of GAD in the ART process.

The DSM-IV-TR also concludes that the point prevalence of MDD in adult women in the community varies from 5 to 9%, and that the point prevalence of dysthymic disorder is ∼3% (American Psychiatric Association, 2000). In Jackson et al.'s clinical sample, the prevalence of major depression was 6%. Studies that adopted MINI in their survey seemed to find slightly higher rates of depression. Dubini et al. (2001) adopted MINI in a survey of an Italian community and found the prevalence of major depression to be 8%. In a primary care setting in Spain, the prevalence of depressive disorders (major depression plus dysthymia) was 20.2% in all patients and 26.8% in women by MINI (Gabarron et al., 2002). In comparison with these data from the community or other clinics, our participants at an assisted reproduction clinic before assisted reproduction treatment did show a high prevalence for major depression (17.0%) and dysthymia (9.8%). The presence of such a high rate of depression among women in an assisted reproduction clinic should arouse much clinical attention and awareness.

The HADS scores of our participants may provide information in addition to the results of diagnosis. The HADS scores may help in the comparison with different research results. Our findings based on the HADS scores were comparable to other studies that also adopted the HADS (Matsubayashi et al., 2001; Anderson et al., 2003). Since the HADS is filled out by the participants, the results may be less biased by the psychiatrist. Furthermore, the HADS has excluded the physical symptoms of anxiety and depression in order to avoid their confounding effects in subjects with somatic illness. Therefore, the HADS scores may be used to examine whether some physical symptoms confound the relationship between infertility and psychiatric conditions.

Table V summarizes studies of pre-assisted reproduction treatment psychiatric morbidity that have adopted rating scales or other verified instruments. Our finding of a high prevalence of depressive disorder lies within the higher range of these estimations from questionnaire-based studies. Anxiety was explored much less frequently in previous studies. The prevalence of anxiety disorder in the present study was similar to, although slightly higher than, that found by Anderson et al. (2003).

Rating scales and self-administered questionnaires are designed to evaluate the severity of psychiatric symptoms. Research has shown that they are not very good instruments in determining the existence of psychiatric disorders (Prusoff, 1972; Carroll, 1973). The threshold values of these rating scales also greatly affect the estimation of anxiety and depression. The threshold values used in previous studies varied greatly, yielding a very wide range of estimations. As shown in Table V, the threshold values of the BDI have been set at 8, 9, 10, 18 and 20 in different studies. A score of 20 in the BDI or a depression score of 10 in the HADS is a very strict criterion for depression. A high threshold values may underestimate the prevalence of psychiatric disorders, whereas a low threshold values may overestimate. Since the MINI has been used as a gold standard of psychiatric diagnosis in some studies (Gabarron, 2002; Wojnar, 2003), our results from the MINI provide standardized information of psychiatric diagnosis that have not been shown by previous questionnaire-based studies.

Some patients with anxiety and depression may lack insight into their psychiatric condition. Consequently, it is possible that estimation based on the subjects' self-assessment of whether or not they are depressed may underestimate these psychiatric disorders. Furthermore, participants in assisted reproduction treatment may try to impress the clinicians at the assisted reproduction clinic as good patients (Wilson and Kopitzke, 2002). The effort to be a good patient, although a proper way to cope with the stress of an assisted reproduction treatment, may prevent participants from revealing psychological distress to their clinicians. Since we provided confidentiality to our subjects, it is possible that our participants may have been more willing to disclose their emotional distress. Further research is needed to determine whether these methodological variables lead to different results.

Cultural factors may play some role in the mood of infertile women. In traditional Eastern culture, the family is usually valued more than the individual. The meaning of an individual's life often includes the extension of the family by giving birth to offspring. Infertile women in the East may suffer from more stress than those in the West. Further research is needed to determine whether the prevalence of anxiety and depression is also high in the assisted reproduction clinics of the West.

Only three (6.7%) of our participants who had a psychiatric disorder had consulted a psychiatrist for their emotional distress before they came to the assisted reproduction clinic. In comparison with the high frequency of participants who had a psychiatric disorder in our sample, disproportionately few of them utilized mental health care services. We do not offer counselling services or self-help groups to the clients of assisted reproduction treatment at our hospital. However, even in those centres that offer a counselling service, the utilization rate has been low (Boivin et al., 1999). Moreover, a counselling service is unnecessary for most of the women undergoing assisted reproduction treatment (Boivin et al., 1999). Clinicians need to find a way to identify who is at risk of a psychiatric disorder and who needs mental health services. Psychiatric referral based on the assisted reproduction clinicians' judgement may be insufficient. One study found that among the assisted reproduction patients not referred to psychiatrists, 24% had a psychiatric disorder and 33% had psychological dysfunction (Guerra et al., 1998). More research is needed to establish methods to screen the smaller proportion of subjects who have psychiatric disorders in order to establish a proper referral to the counselling service.

The present study is limited by the low number of cases included. Caution should be taken in interpreting some data from such a small number of participants. We were also limited by our recruiting period. We did not recruit subjects during an entire year, so we do not know whether there is a seasonal variation of mood among the participants attending the assisted reproduction clinic. However, the changes in weather and the amount of sunshine in Taiwan are mild. There are few reports of seasonal affective disorders in Taipei, Taiwan. The study is also limited by the lack of data on the husbands of these women and their families. The spouses may have influenced the mood of the women who were about to undergo assisted reproduction treatment. A previous study showed that psychological reaction response was similar in both husbands and wives during IVF (Boivin et al., 1998), although the husbands were less depressed (Beutel et al., 1999). The interaction between the couple deserves further investigation. We are also limited by the fact that we do not have data of the MINI diagnosis in community or primary care settings in Taiwan for comparison. Although MINI is a validated and standardized diagnostic instrument, it is still possible that MINI tends to result in slightly higher rates of depression than previous diagnostic tools. We do not know to what extent our results were biased by MINI. We also failed to include a re-confirmed diagnosis by a second psychiatrist. However, due to the high inter-rater and test–retest reliabilities of the MINI (Sheehan et al., 1998), the lack of a second interview should be acceptable.

In conclusion, we found in the present study that the frequencies of depressive and anxiety disorders were high in women who were preparing to undergo a new course of assisted reproduction treatment. Nonetheless, very few women had visited psychiatric clinics for help. The most conspicuous finding is the high frequency of GAD in our participants. Whether GAD plays some role in infertility or in the suffering during the assisted reproduction process deserves more attention in the future. In addition, we also found that psychiatric morbidity was not affected by the woman's age, education level, husband's age, husband's education level, income, years of marriage, years of infertility, or a history of previous assisted reproduction treatment. Based on these findings, we suggest that clinicians offering assisted reproduction treatment to their patients should be aware of the high prevalence of psychiatric morbidity among this group.

References

Author notes

1Department of Psychiatry and 2Department of Obstetrics and Gynecology, Taipei Veterans General Hospital 3National Yang-Ming University School of Medicine, Taipei, Taiwan and 4Department of Psychiatry, Tri-Service, Geneva Hospital, Taipei, Taiwan