Abstract
STUDY QUESTION
In women undergoing fertility treatment, do those with polycystic ovary syndrome (PCOS) have a higher prevalence of symptoms of anxiety and depression and lower body appreciation than women without PCOS?
SUMMARY ANSWER
Having PCOS was not associated with symptoms of anxiety and depression but was associated with somewhat lower body appreciation.
WHAT IS KNOWN ALREADY
PCOS has been associated with a higher chance to develop mental health problems, like anxiety, and body image concerns. The International Guidelines on PCOS recommend that all women with PCOS should routinely be screened for anxiety and depressive disorders. In most studies in this field, the comparison group included healthy women without fertility problems.
STUDY DESIGN, SIZE, DURATION
We conducted a cross-sectional survey study between May 2021 and July 2023, using an online questionnaire. We informed women about this study at fertility clinics in the Netherlands through posters and leaflets and on the websites of the Dutch patient organizations Freya and Stichting PCOS.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This study included women with infertility, with and without PCOS, who were undergoing fertility treatment. Women completed two assessment tools: the Hospital Anxiety and Depression Scale (HADS) and the Body Appreciation Scale-2 (BAS-2). Primary outcomes were clinically relevant symptoms of anxiety (score ≥ 11) and depression (score ≥ 11), and BAS-2 scores. Secondary outcomes were mean anxiety and depression scores and anxiety and depression scores of 8 and higher. Dichotomous outcomes and continuous outcomes were analysed using logistic and linear regression analyses adjusted for age, BMI, and duration of infertility.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 1025 women currently undergoing infertility treatment participated, of whom 502 (49.0%) had PCOS and 523 (51.0%) had other infertility diagnoses. We found self-reported clinically relevant symptoms of anxiety in 33.1% of women with PCOS and in 31.0% of women with other infertility diagnoses (adjusted OR: 0.99, 95% CI 0.74–1.31). Clinically relevant symptoms of depression were reported in 15.5% of women with PCOS versus 14.5% of women with other infertility diagnoses (adjusted OR: 1.04, 95% CI 0.71–1.50). Women with PCOS reported slightly less body appreciation (adjusted mean difference: −1.34, 95% CI −2.32 to −0.36).
LIMITATIONS, REASONS FOR CAUTION
Results are based on self-report and may have been affected by sampling bias.
WIDER IMPLICATIONS OF THE FINDINGS
Although guidelines recommend screening women with PCOS, feelings of anxiety and depression can be present in any woman undergoing fertility treatments. We advise fertility clinics to be aware of women’s mental health issues and to offer support accordingly, as a part of routine care.
STUDY FUNDING/COMPETING INTEREST(S)
This study did not receive specific funding. All authors report no conflict of interest related to the current research.
TRIAL REGISTRATION NUMBER
This study was pre-registered at OSF: https://osf.io/qbeav.
Keywords: polycystic ovary syndrome, anxiety, depression, infertility, body image, fertility treatment
Introduction
Polycystic ovary syndrome (PCOS) is a common endocrinological disorder affecting approximately 8–13% of women in their reproductive years. It is characterized by a variety of symptoms, including irregular menstrual cycles, excess androgen levels, and ovarian cysts (Teede et al., 2018). PCOS can have significant health implications, with potential long-term consequences such as infertility, insulin resistance, and increased risk of type 2 diabetes and cardiovascular diseases (Behboudi-Gandevani et al., 2016; Zhao et al., 2016).
Women diagnosed with PCOS were found to have high prevalence of self-reported mental health issues, including anxiety, depression disorders, and reduced levels of body appreciation (Deeks et al., 2011; Alur-Gupta et al., 2019; Davitadze et al., 2023). A systematic review and meta-analysis (Cooney et al., 2017) found that 43% of women with PCOS reported anxiety symptoms and 37% reported depressive symptoms, in contrast to healthy controls without PCOS, who reported a prevalence of 10% for both anxiety and depressive symptoms. These significant differences in prevalence between women with PCOS and healthy controls align with findings from other meta-analyses (Barry et al., 2011; Dokras et al., 2011; Dokras et al., 2012; Veltman-Verhulst et al., 2012; Wang et al., 2021).
Based on the findings of previous research, the International Guideline on PCOS recommends the routine screening of anxiety and depression in all women diagnosed with PCOS. Additionally, it emphasizes the importance of healthcare professionals recognizing the potential adverse impact of PCOS on body image (Teede et al., 2023). Considering that a substantial portion of PCOS diagnoses occur within fertility clinics, it seems crucial to raise awareness of mental health challenges in these clinical settings. Such awareness is important due to the potential impact of these challenges on a woman’s ability to conceive and the subsequent effects during pre- and postnatal periods.
Previous studies have shown that specific PCOS symptoms, like hirsutism, acne, and higher BMI are associated with anxiety, depression, and body image concerns (Benson et al., 2009; de Niet et al., 2010; Bazarganipour et al., 2014; Lin et al., 2021). Furthermore, infertility and/or involuntary childlessness after desire for a child are associated with mental health issues (Kitzinger and Willmott, 2002; Lechner et al., 2007). Studies investigating mental health problems in couples dealing with infertility have reported prevalence rates ranging from 23% to 76% for anxiety symptomatology and 11% to 56% for depression symptomatology in women experiencing infertility, with rates varying based on the severity of symptoms and the research method used (Chen et al., 2004; Volgsten et al., 2008; Pasch et al., 2016). These findings underscore the significant distress associated with infertility.
Comparing anxiety, depression and body appreciation in infertile women with and without PCOS will contribute to understanding the role of infertility on mental health within women with PCOS. Only three small case-control studies compared anxiety and/or depression between infertile women with and without PCOS (Shi et al., 2011; Li et al., 2017; Basirat et al., 2019). The results were mixed, as some studies observed differences while others did not. Consequently, there remains a knowledge gap regarding whether the observed elevated prevalence of anxiety, depression, and body image concerns in women that come to fertility clinics, can be attributed to PCOS itself or to the psychological burden of infertility.
The present study aims to compare the prevalence of symptoms of anxiety and depression, and to evaluate body appreciation between women with PCOS and women with other infertility diagnoses who are undergoing treatment at Dutch fertility clinics. Additionally, the research aims to investigate potential associations between specific patient characteristics and the presence or absence of anxiety or depressive symptoms to gain a better understanding of the impact of individual patient factors on mental health outcomes among infertile women with and without PCOS.
Materials and methods
Study design and participants
This study is a cross-sectional survey study using a web-based questionnaire. Ethical approval for this study was obtained by the Medical Ethical Committee of the Amsterdam UMC, location AMC on 19 December 2019 (MEC No. 19.549). The study was registered in the OSF Register, DOI https://osf.io/qbeav.
Women were invited to participate in this study through two Dutch patient organizations: Freya, for couples experiencing fertility problems, and Stichting PCOS, for women with PCOS. Additionally, 28 Dutch fertility clinics assisted in recruiting participants by displaying posters and leaflets. The web-based questionnaire was accessible via internet-links or QR codes. Collection of data occurred between May 2021 and July 2023.
Inclusion and exclusion criteria
Women were included in the analyses if they were older than 18 years of age, experiencing infertility and were currently undergoing treatment at a fertility clinic. In the questionnaire, women were asked to confirm whether they had medically verified diagnosis of PCOS or other infertility diagnosis.
Women were excluded if they reported they were, at time of entering the questionnaires, pregnant, peri- or post-menopausal (including premature ovarian failure) or had no ovaries.
Measurements
All data were collected by self-report through a web-based questionnaire. This questionnaire collected demographic data like age, height, weight, nationality, education, and employment status. It inquired about medically confirmed PCOS, other infertility diagnoses, if any, and requested participants to specify the fertility problem, if applicable. Furthermore, the questionnaire focused on various reproductive health topics, such as the participants’ desire to have children, the duration of the child wish (in this study this is also referred to as the duration of infertility), pregnancy history, and ongoing fertility treatments. It collected data on the presence of ovaries, polycystic ovaries, (male) partner sperm quality if present, contraceptive use and menstrual cycle regularity and investigated co-morbid conditions such as diabetes, eating disorders, anxiety, depression, as well as medication use. Only if women reported a PCOS diagnosis, they were asked about the presence of hyperandrogenism symptoms (i.e. hirsutism, acne, and alopecia).
Subsequently, participants were asked to complete two validated self-report surveys: the Dutch version of the Hospital Anxiety and Depression Scale (HADS) (Zigmond and Snaith, 1983) and the Body Appreciation Scale-2 (BAS-2) (Tylka and Wood-Barcalow, 2015). The HADS is a validated 14-item questionnaire with seven questions assessing anxiety symptoms and seven assessing depressive symptoms. Each question is scored on a scale from 0 to 3, resulting in a total score ranging from 0 to 21 for both subscales. Higher scores correspond to increased levels of anxiety or depression, categorized as: no symptoms (scores 0 to 7), potential presence of depression or anxiety (8 to 10), or suspected manifestation of depression or anxiety disorder (11 to 21) (Herrmann, 1997). A score of 8 or higher signifies the presence of anxiety and/or depression symptoms. In this study, scores of 11 or higher are regarded as an indication of clinically significant anxiety or depression symptoms, as previously described in other studies (Benson et al., 2009; Cinar et al., 2011). The 10-item BAS-2 assesses body appreciation in three facets: body acceptance, body respect and care, and resistance to media-promoted appearance ideals. All items are rated on a 5-point scale ranging from 1 (never) to 5 (always), with higher scores indicating greater levels of body appreciation.
Data handling
Data were collected using the LimeSurvey web-based questionnaire tool (Version 2.6.7), which ensures complete anonymity of participants. Once data collection was completed, the data were transferred to an SPSS file, saved on secure servers of the Amsterdam UMC.
Outcomes
The primary outcomes of this study were: (i) the proportion of participants with HADS-anxiety scores of 11 or higher, indicating clinically relevant symptoms of anxiety, (ii) the proportion of participants with HADS-depression scores of 11 or higher, indicating clinically relevant symptoms of depression, and (iii) the mean BAS-2 scores, reflecting participant body appreciation.
The secondary outcomes were the proportion of participants with HADS-anxiety and depression scores of 8 or higher, indicating the presence of anxiety and/or depression symptoms and the mean scores on the HADS-anxiety and depression scales. We choose these secondary outcomes to enable a meaningful comparison of our study with other research in the literature that has used these cutoff values.
Statistical analysis
Analyses were performed using SPSS software (IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY, USA: IBM Corp; 2021). Participants were categorized based on the presence of PCOS or other infertility diagnoses. Baseline characteristics were compared using ANOVAs for continuous variables and chi-square tests for categorical variables. BMI was computed from self-reported height and weight. To compare anxiety, depression, and body appreciation between women with PCOS and those with other infertility diagnoses, generalized linear regressions were used for continuous outcomes and binary logistic regressions for binary outcomes. The analyses were adjusted for age, BMI, and duration of infertility and included testing interactions. We performed exploratory analyses to assess whether other baseline variables including education, previous pregnancies, fertility treatment type, and antidepressant use were associated with depression, anxiety, and/or body appreciation.
We performed an additional subgroup analysis stratifying BMI into <25 kg/m2 and ≥25 kg/m2 for the primary outcomes. To examine the relationship between mean anxiety, depression, and body appreciation scores we calculated bivariate correlation and we used linear regression adjusted for diagnosis, both with bootstrapped confidence intervals. We conducted a sensitivity analysis on the primary outcomes in which we excluded women who did not meet the Rotterdam criteria for PCOS based on their questionnaire responses. The Rotterdam criteria (The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004) include the presence of at least two of the following: (i) menstrual irregularity (oligomenorrhoea or amenorrhea), (ii) the presence of polycystic ovaries, and (iii) indicators of hyperandrogenism (i.e. hirsutism, acne, and alopecia). Continuous data were assessed for normality and expressed as mean ± SD, categorical data were expressed as frequencies and proportions. A two-sided P-value lower than 0.05 was considered statistically significant.
Results
A total of 1107 women undergoing treatment at a fertility clinic provided self-report data. Of these, 40 women were excluded due to pregnancy, and 42 due to being menopausal. Consequently, 1025 women were included in this study: 502 with PCOS and 523 without PCOS (referred to as women with other infertility diagnoses; Fig. 1). No data were missing for demographic information and HADS questionnaire, 22 participants had missing data for the BAS-2 questionnaire (10 women with PCOS and 12 women with other infertility diagnoses).
Figure 1.
Flowchart of inclusion of women in the present study.
Demographics
The mean (±SD) age of women with PCOS was 30.8 years (±3.7) versus 33.4 (±3.8) in women with other infertility diagnoses (P < 0.001; see also Table 1). Women with PCOS had higher mean BMI (26.7 ± 5.7 kg/m2) than women with other infertility diagnoses (24.9 ± 3.4 kg/m2; P < 0.001). Consequently, a larger proportion of women with PCOS was also classified as overweight (i.e. BMI ≥25 kg/m2 55.4% versus 40.0%, P < 0.001). Compared to women with other infertility diagnoses, women with PCOS had lower educational levels, a shorter duration of infertility (28.8 ± 19.4 versus 35.4 ± 19.2 months, P < 0.001) and had less often been pregnant (41.2% versus 50.1%, P = 0.004).
Table 1.
Descriptive statistics of women with polycystic ovary syndrome (PCOS) and women with other infertility diagnoses.
| PCOS (N = 502)* | Other infertility diagnoses (N = 523)* | P-value | |
|---|---|---|---|
| Age (years) | 30.8 ± 3.7 | 33.4 ± 3.8 | <0.001 |
| (range: 20.0–42.0) | (range: 21.0–43.0) | ||
| BMI (kg/m2) | 26.7 ± 5.7 | 24.9 ± 4.3 | <0.001 |
| (range: 16.8–51.4) | (range: 16.4–40.9) | ||
| BMI ≥25.0 (kg/m2) | 278 (55.4) | 209 (40.0) | <0.001 |
| Nationality | 0.630 | ||
| Western European | 490 (97.6) | 507 (97.1) | |
| Other | 12 (2.4) | 15 (2.9) | |
| Highest level of education | 0.003 | ||
| Primary and secondary education | 30 (6.0) | 24 (4.6) | |
| Secondary vocational education | 151 (30.1) | 108 (20.7) | |
| Higher professional education | 200 (39.8) | 243 (46.5) | |
| University education | 121 (24.1) | 148 (28.3) | |
| Employment status | 0.873 | ||
| Employed | 480 (95.6) | 499 (95.4) | |
| Unemployed | 22 (4.4) | 24 (4.6) | |
| Diagnosis other than PCOS | – | N.A. | |
| Unexplained infertility | 266 (50.9) | ||
| Male infertility | 106 (20.3) | ||
| Other diagnoses | 72 (13.8) | ||
| Unknown | 79 (15.1) | ||
| Reduced sperm quality in partner | 103 (21.4) | 177 (35.8) | <0.001 |
| Type of treatment in fertility clinic | <0.001 | ||
| Ovulation induction (OI) | 139 (27.7) | 12 (2.3) | |
| Intrauterine insemination (IUI) | 39 (7.8) | 129 (24.7) | |
| IUI with OI | 39 (7.8) | 52 (9.9) | |
| Gonadotrophins | 87 (17.3) | 8 (1.5) | |
| IVF/ICSI | 112 (22.3) | 275 (52.6) | |
| Other | 29 (5.8) | 324 (4.6) | |
| Unknown | 57 (11.4) | 23 (4.4) | |
| Duration of infertility in months | 28.8 ± 19.4 | 35.4 ± 19.2 | <0.001 |
| Previous pregnancy | 207 (41.2) | 262 (50.1) | 0.004 |
| Number of pregnancies | 1.8 ± 1.2 | 1.9 ± 1.3 | 0.666 |
| Regular menstrual cycle | 85 (16.9) | 455 (87.0) | <0.001 |
| Number of periods in the past 12 months | 7.9 ± 3.7 | 12.3 ± 1.9 | <0.001 |
| Use of contraceptives in the past 12 months | 51 (10.2) | 48 (9.2) | 0.595 |
| Polycystic ovaries | 335 (66.7) | 137 (26.2) | <0.001 |
| Both ovaries still present | 494 (98.4) | 510 (97.5) | 0.314 |
| Hyperandrogenism (acne, hirsutism, alopecia) | 440 (87.6) | – | N.A. |
| Women meeting the Rotterdam Criteria | 456 (90.8) | – | N.A. |
| Medical history of diabetes | 16 (3.2) | 10 (1.9) | 0.194 |
| Medical history of anxiety disorder | 83 (16.5) | 71 (13.6) | 0.185 |
| Medical history of depression | 94 (18.7) | 96 (18.4) | 0.879 |
| Use of antidepressants | 15 (3.0) | 26 (5.0) | 0.105 |
| Medical history eating disorder | 26 (5.2) | 17 (3.3) | 0.124 |
Data are N (%) or mean±SD.
Current fertility treatment for women with PCOS more commonly included Clomid, Letrozole, and gonadotrophins, whereas women with other infertility were more likely to receive IUI or IVF/ICSI.
Consistent with the characteristics of PCOS, women with PCOS had a lower prevalence of regular menstrual cycles (16.9% versus 87.0%, P < 0.001), fewer menstrual cycles in the past year (7.9 ± 3.7 versus 12.3 ± 1.9, P < 0.001), and a higher prevalence of polycystic ovaries (66.7% versus 26.2%, P < 0.001). Signs of hyperandrogenism (i.e. hirsutism, acne, and alopecia) were found in 87.6% of women with PCOS. Based on self-reported data, 90.8% of the women who reported to have PCOS met the Rotterdam criteria, requiring the presence of at least two of the following: menstrual irregularity (oligo- or amenorrhea), polycystic ovaries, and signs of hyperandrogenism. For the other 9.2%, the Rotterdam criteria were ambiguous, for example, some women registered regular cycles that may have been due to their treatment at that moment and hyperandrogenism was only determined based on physical signs (hirsutism, acne, and alopecia) and therefore likely underreported. Slightly more women diagnosed with PCOS (16.5%) reported a medical history of anxiety disorder compared to women with other infertility diagnoses (13.6%), although this difference was not statistically significant (P = 0.185). Both groups had similar rates of diagnosed depression disorder (18.7% versus 18.4%). Antidepressant use was slightly lower in women with PCOS (3.0%) compared to those with other infertility diagnoses (5.0%), but this difference was not statistically significant (P = 0.105). No statistically significant differences were found in medical history of diabetes and eating disorders.
Anxiety, depression, and body appreciation
We performed exploratory analyses of baseline variables, including education, previous pregnancies, fertility treatment type, and antidepressant use. These variables had no impact on the model performance, nor on the relevant associations with other variables for the outcomes depression, anxiety, or body appreciation and were therefore excluded from the regression analysis.
Anxiety
The prevalence of clinically relevant anxiety symptoms (scores ≥11) was 33.1% in women with PCOS and 31.0% in women with other infertility diagnoses (adjusted OR: 0.99, 95% CI 0.74–1.31; Table 2). Rates for anxiety scores of 8 or higher were 56.8% for PCOS and 53.5% for other infertility diagnoses (adjusted OR: 1.06, 95% CI 0.82–1.39).
Table 2.
Comparison of the HADS-anxiety, HADS-depression, and BAS-2 scores between women with polycystic ovary syndrome (PCOS) and women with other infertility diagnoses.
| PCOS (N = 502) | Other infertility diagnoses (N = 523) | Unadjusted odds ratio (95% CI) | P-value | Adjusted* odds ratio (95% CI) |
Adjusted* P-value |
|
|---|---|---|---|---|---|---|
| HADS-A score ≥ 11 | 166 (33.1) | 162 (31.0) | 1.10 (0.85–1.43) | 0.473 | 0.99 (0.74–1.31) | 0.923 |
| HADS-A score ≥ 8 | 285 (56.8) | 280 (53.5) | 1.14 (0.89–1.46) | 0.298 | 1.06 (0.81–1.39) | 0.662 |
| HADS-D score ≥ 11 | 78 (15.5) | 76 (14.5) | 1.08 (0.77–1.52) | 0.652 | 1.04 (0.71–1.50) | 0.854 |
| HADS-D score ≥ 8 | 170 (33.9) | 168 (32.1) | 1.08 (0.83–1.40) | 0.553 | 1.02 (0.77–1.36) | 0.900 |
| Unadjusted mean difference (95% CI) | P-value | Adjusted* mean difference (95% CI) |
Adjusted* P-value |
|||
|---|---|---|---|---|---|---|
| HADS-A mean score | 8.7 ± 4.2 | 8.3 ± 4.2 | 0.38 (−0.13 to 0.90) | 0.145 | 0.24 (−0.31 to 0.79) | 0.396 |
| HADS-D mean score | 6.2 ± 4.0 | 6.0 ± 3.9 | 0.20 (−0.28 to 0.68) | 0.417 | 0.18 (−0.33 to 0.70) | 0.488 |
| BAS-2 | 33.0 ± 8.3 | 35.7 ± 7.6 | −2.72 (−3.70 to −1.73) | <0.001 | −1.34 (−2.32 to −0.36) | 0.007 |
Data are N (%) or mean ± SD. HADS-A, Hospital Anxiety and Depression Scale for Anxiety; HADS-D, Hospital Anxiety and Depression Scale for Depression; BAS-2, Body Appreciation Scale-2.
Adjusted for age, BMI, and duration of infertility.
Mean anxiety scores were comparable (adjusted mean difference: 0.24, 95% CI −0.31 to 0.79). Longer duration of infertility was associated with higher levels of clinically relevant anxiety (P = 0.005) while older age was associated with lower levels of anxiety (P < 0.001), and BMI was not significantly associated (Supplementary Table S1). We found no evidence of interactions between age, BMI, or duration of infertility and the presence of PCOS on anxiety score.
Subgroup analysis on BMI (BMI <25 and ≥25 kg/m2) did not indicate differences in clinically relevant anxiety between groups (Table 3).
Table 3.
Subgroup analyses for BMI <25 kg/m2 and BMI ≥25 kg/m2.
| BMI <25 kg/m2 | PCOS (N = 278) | Other infertility diagnoses (N = 209) | Unadjusted odds ratio (95% CI) | P-value | Adjusted* odds ratio (95% CI) | Adjusted*P-value |
|---|---|---|---|---|---|---|
| HADS-A ≥ 11 | 86 (30.9%) | 68 (32.5%) | 0.93 (0.63–1.37) | 0.707 | 0.84 (0.56–1.26) | 0.398 |
| HADS-D ≥ 11 | 48 (17.3%) | 35 (16.7%) | 1.04 (0.64–1.67) | 0.880 | 0.99 (0.60–1.63) | 0.954 |
| Unadjusted mean difference (95% CI) | P-value | Adjusted* mean difference (95% CI) |
Adjusted* P-value |
|||
|---|---|---|---|---|---|---|
| BAS-2 | 30.7 ± 7.9 | 32.8 ± 7.8 | −2.11 (−3.53 to −0.69) | 0.004 | −1.85 (−3.32 to −0.39) | 0.013 |
| BMI ≥25 kg/m2 | PCOS (N = 224) |
Other infertility diagnoses
(N = 314) |
Unadjusted odds ratio (95% CI) | P-value | Adjusted* odds ratio (95% CI) |
Adjusted* P-value |
|---|---|---|---|---|---|---|
| HADS-A ≥ 11 | 80 (35.7%) | 94 (29.9%) | 1.30 (0.90–1.87) | 0.158 | 1.21 (0.82–1.80) | 0.340 |
| HADS-D ≥ 11 | 30 (13.4%) | 41 (13.1%) | 1.03 (0.62–1.71) | 0.910 | 1.10 (0.64–1.90) | 0.729 |
| Unadjusted mean difference (95% CI) | P-value | Adjusted* mean difference (95% CI) |
Adjusted* P-value |
|||
|---|---|---|---|---|---|---|
| BAS-2 | 35.8 ± 7.8 | 37.6 ± 6.9 | −1.79 (−3.05 to −0.53) | 0.005 | −1.66 (−3.02 to −0.31) | 0.016 |
Data are N (%) or mean±SD. PCOS, polycystic ovary syndrome; HADS-A, Hospital Anxiety and Depression Scale for Anxiety; HADS-D, Hospital Anxiety and Depression Scale for Depression; BAS-2, Body Appreciation Scale-2.
Adjusted for age and duration of infertility.
Depression
The prevalence of clinically relevant depressive symptoms (scores ≥11) was 15.5% in women with PCOS and 14.5% in women with other infertility diagnosis (adjusted OR: 1.04, 95% CI 0.71–1.50; Table 2). The prevalence of depression scores of 8 or higher was 33.9% and 32.1% (adjusted OR: 1.02, 95% CI 0.77–1.36) for PCOS versus other infertility diagnoses. Mean depression scores were similar in both groups (adjusted mean difference: 0.18, 95% CI −0.33 to 0.70).
Longer duration of infertility was associated with higher levels of clinically relevant depressive symptoms (P < 0.001), while no association was found with age and BMI (Supplementary Table S1). We observed no indication of interaction between age, BMI, or duration of infertility and presence of PCOS on depression scores.
Subgroup analysis on BMI (BMI <25 kg/m2 and BMI ≥25 kg/m2) did not indicate differences in clinically relevant depression between groups (Table 3).
Body image
Mean Body Appreciation-2 scores were 33.0 (±8.3; range: 10–50) in the PCOS group and 35.7 (±7.6) in women with other infertility diagnoses, indicating slightly lower body appreciation in women with PCOS (adjusted mean difference: −1.34, 95% CI −2.32 to −0.36; Table 2).
Older age was associated with higher body appreciation scores (P < 0.001), while higher BMI and longer duration of infertility were associated with lower body appreciation scores (respectively P = 0.000, P < 0.001; Supplementary Table S1). We found no evidence suggesting that the presence of PCOS modified the relationship between BAS-2 scores and age, BMI, or duration of infertility.
In subgroup analysis on BMI (BMI <25 kg/m2 and BMI ≥25 kg/m2) the differences in BAS scores between groups remained (Table 3).
Correlations amongst all outcomes
A moderate to strong positive correlation was observed between anxiety and depression scores (r = 0.70, 95% CI 0.67–0.73 and beta coefficient of 0.66, 95% CI 0.61–0.70 with a R2 of 49%; see Supplementary Table S2). An R2 of 49% implies that about half of the variability in anxiety scores can be explained by depression scores and vice versa. Moderate negative correlations were found between anxiety and body appreciation scores (r = −0.46, 95% CI −0.41 to −0.51 and beta coefficient of −0.45, 95% CI −0.66 to −0.34 with a R2 of 21%), as well as between depression and body appreciation scores (r = −0.50, 95% CI −0.45 to −0.55 and beta coefficient of −0.49, 95% CI −0.57 to −0.41 with a R2 of 25%), with similar patterns in both subgroups.
Sensitivity analysis
We conducted sensitivity analyses on the primary outcomes in which we excluded the women that did not meet Rotterdam Criteria based self-report (Supplementary Table S3). These findings were similar to the original analyses: Clinically relevant levels of anxiety were reported by 33.8% of women with PCOS and 31.0% of those with other infertility diagnoses (adjusted OR: 1.03, 95% CI 0.77–1.38). Clinically relevant levels of depression were reported by 15.1% of women with PCOS and 14.5% of women with other infertility diagnoses (adjusted OR: 1.00, 95% CI 0.68–1.48). Mean Body Appreciation-2 scores were 32.7 (±8.2) in the PCOS group and 35.7 (±7.6) in women with other infertility diagnoses (adjusted mean difference: −1.57, 95% CI −2.58 to −0.57).
Discussion
The present study evaluated the prevalence of self-reported symptoms of anxiety, depression, and body appreciation in women with infertility, both with and without PCOS, who were seeking care at Dutch fertility clinics. We found that women with PCOS reported comparable rates of anxiety and depressive symptoms to women with other infertility diagnoses. Yet, women with PCOS reported slightly lower body appreciation scores. In both groups, we found that longer duration of infertility was associated with higher levels of clinically relevant symptoms of anxiety and depression and lower body appreciation, while higher BMI was only associated with lower body appreciation. Additionally, older age was associated with more positive outcomes (i.e. lower clinically relevant anxiety and higher body appreciation). Exploratory analyses found no association between the mental health outcomes and other baseline variables, including education, previous pregnancies, fertility treatment type, and use of antidepressants.
The prevalence of anxiety and depression we found in women with PCOS, assessed via the HADS questionnaire, is consistent with other studies using the same tool (Benson et al., 2009; Moran et al., 2010; Barry et al., 2011; Cinar et al., 2011; Deeks et al., 2011; Moran et al., 2012; Asik et al., 2015). However, these studies primarily used healthy individuals as control group, lacking direct comparisons among women experiencing infertility, and therefore cannot be directly compared with our study. A limited number of studies have directly compared anxiety and/or depression between infertile women with and without PCOS (Shi et al., 2011; Li et al., 2017; Basirat et al., 2019). Li and colleagues and Shi and colleagues observed elevated levels of both anxiety and depression in these comparisons, while Basirat and colleagues did not find such differences. Discrepancies with our results might be explained by smaller sample sizes in other studies and the use of different screening methods. Additionally, it should be noted that the aforementioned studies were conducted in China and Iran. There is evidence suggesting variations in both the prevalence and phenotypic characteristics of PCOS across diverse ethnical populations and geographical regions (Zhao and Qiao, 2013). Differences between ours and previous findings could possibly be attributed to variations in the PCOS population, including factors such as BMI and hyperandrogenism.
Our results align with a recent Dutch study that evaluated generic quality of life between infertile and obese women with and without PCOS, revealing no significant differences between the two groups (Wang et al., 2021). Additionally, our study is in accordance with earlier research that identified associations between higher BMI and depression and negative body image (Alleva et al., 2016; Blasco et al., 2020). Furthermore, our results match a recent meta-analysis showing increased body image concerns in women with PCOS, regardless of the assessment method (Davitadze et al., 2023). Nevertheless, these results are mainly based on the comparison to healthy controls.
Prior research demonstrated that specific PCOS symptoms, such as hirsutism, acne, and higher BMI, can negatively affect body image in various patient populations (Himelein and Thatcher, 2006; de Niet et al., 2010). In our study, we observed that women with PCOS reported lower body appreciation than women without PCOS, irrespective of their BMI. It is possible that the clinical manifestations of hyperandrogenism may have contributed to the slightly lower body appreciation score observed in the PCOS group. It may be relevant to investigate the associations between specific patient characteristics and mental health issues within a PCOS population while accounting for fertility treatment.
Although rates were similar based on the HADS, women with PCOS reported slightly higher rates of a medical history for diagnosed anxiety (16.5% in PCOS and 13.6% without PCOS) and similar rates for a history of depression (18% in both groups). It is worth noting that only half of the women with a medical history of anxiety reported clinically relevant anxiety symptoms, and just 25% of those with a history of depression exhibited clinically relevant depression symptoms. Yet, symptom fluctuations and prior treatments for anxiety or depression (e.g. therapy and/or psychopharmacological treatments) may contribute to such differences. Nevertheless, we found that anxiety and depression could be more prevalent in fertility clinics than expected based on medical history alone, emphasizing the need for healthcare professionals to be aware of this issue.
The main strength of our study is the focus on women with infertility. Furthermore, the large sample size from different clinics across the country suggests this population is representative for the general Dutch population of women undergoing fertility treatment. Additionally, the used HADS cut-off scores of 8 and 11, along with the mean scores, are commonly utilized in international studies, ensuring that our findings can be effectively compared to other research. The current study also has certain limitations. The most notable limitation is that PCOS diagnosis was based on participant self-report without medical record verification, due to the nature of this study. On the other hand, 91% of participants met the Rotterdam Criteria, strengthening the likelihood of the diagnosis. Another limitation is that participants were self-selected, leading to potential selection bias. The decision to participate may have been influenced by pre-existing levels of anxiety, depression, or body image concerns. Moreover, these psychological factors could impact a woman’s decision to join patient organizations, which served as a significant recruitment source. This experimental design limitation precludes us from determining how many women encountered the advertisements but chose not to participate, and whether they differed from those who did participate.
Our study highlights the substantial impact of infertility on mental well-being in any women, given the absence of notable differences in anxiety and depression levels between infertile women with and without PCOS. This finding emphasizes the need for targeted emotional support, not only for women with PCOS but for all women experiencing infertility. Although recommended in women with PCOS, mental health screening is not routine practice in Dutch fertility clinics yet. Given the rather moderate to high levels of anxious and depressive symptoms, routine screening could lead to an immense additional healthcare load, while resources are limited and could potentially lead to stigma and overdiagnosis.
However, we would support training of health professionals in recognizing mental health problems and we underscore the need for recruiting and training more mental health professionals. Additionally, we highlight the importance for developing or expanding programs to address the mental health needs of fertility patients, particularly through support groups. These groups might efficiently address concerns like stigma and isolation, extending their impact with fewer providers.
In conclusion, we found that having PCOS in infertile women is not associated with a higher likelihood of anxiety and depressive symptoms when compared to women with other infertility diagnoses. However, PCOS may result in slightly less body appreciation. Recognizing mental health challenges in any woman experiencing infertility can contribute to improved self-worth and increased quality of life. Consequently, we advise fertility clinics to be aware of the potentially severe impact of infertility on mental well-being and to offer these women support as a part of routine treatment, if possible.
Supplementary Material
Acknowledgements
We thank all participants who helped us in the study, as well as Freya, Stichting PCOS and the fertility clinics and their staff.
Contributor Information
T Jannink, Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Reproduction and Development Institute, Amsterdam UMC, Amsterdam, The Netherlands.
E M Bordewijk, Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Reproduction and Development Institute, Amsterdam UMC, Amsterdam, The Netherlands.
J Aalberts, Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
J Hendriks, Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
V Lehmann, Amsterdam Reproduction and Development Institute, Amsterdam UMC, Amsterdam, The Netherlands; Department of Medical Psychology Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
A Hoek, Department of Obstetrics and Gynaecology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
M Goddijn, Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Reproduction and Development Institute, Amsterdam UMC, Amsterdam, The Netherlands.
M van Wely, Department of Obstetrics and Gynaecology, Centre for Reproductive Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Reproduction and Development Institute, Amsterdam UMC, Amsterdam, The Netherlands.
ANDES study group:
J P de Bruin, C A H Jansen, C Koks, G de Krom, A F Lambeek, M J Lambers, M L Maarsen, J M Munster, S J Tanahatoe, M Verberg, and M Vermeulen
Data availability
The data underlying this article will be shared upon reasonable request to the corresponding author.
Authors’ roles
E.M.B. and M.v.W. initiated and established the study. V.L. contributed to selecting assessment tools and creating the online questionnaire. T.J. was in charge of executing the study and collecting the data. T.J. took the lead in writing the article. T.J. and M.v.W. performed the analyses. E.M.B., J.A., J.H., V.L., A.H., M.G., and M.v.W. advised in the interpretation of the outcomes. All authors read, edited, and approved the final article.
Funding
This study did not receive any particular funding.
Conflict of interest
All authors report no conflict of interest related to the current research.
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Associated Data
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Supplementary Materials
Data Availability Statement
The data underlying this article will be shared upon reasonable request to the corresponding author.