Infertility now is a public health concern and is associated with increased psychological distress.
We enrolled 1247 infertile couples and assessed their anxiety and depression status before and during assisted reproductive technology (ART) treatment using the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). The Chi-square or fisher’s exact test was used to analyze the prevalence of anxiety and depression in infertile couples. Multivariate logistical regression was performed to analyze the risk factors for anxiety and depression.
The prevalence of anxiety was 13.5% and 8.7% (p < 0.05), and that of depression was 9.4% and 7.9% (p = 0.2) in female and male partners, respectively. Female SAS and SDS scores were positively associated with male SAS and SDS scores, respectively (r = 0.52 and r = 0.50, respectively, both p < 0.0001), and were positively associated with their own SDS and SAS scores, respectively (r = 0.63 and r = 0.62, respectively, both p < 0.0001). Their own depression or partners’ anxiety was associated with the anxiety, and their own anxiety or partners’ depression was associated with the depression in infertile couples. No children, unemployment, and low education level were also associated with female anxiety. SAS and SDS scores were significantly decreased during ART treatment.
Females were more vulnerable to having anxiety than males in infertile couples. Anxiety and depression in infertile couples could interact, therefore, anxiety and depression would be simultaneously counseled, and their partners also should be given supportive psychotherapy.
It was an observational study and had no health care interventions on participants. So it was not registrated.
The inability to conceive after at least 12 months of regular, unprotected sexual intercourse was defined as infertility . The number of infertility was rising globally over the last several decades, with an annual percentage increase of 0.370% in women and 0.291% in men from 1990 to 2017 , and reached 8–12% in reproductive couples . Infertility is one of the most stressful events that the pressure from traditional ideals, families, and society can make adverse psychological and mental impacts including loss of self-esteem, lack of self-confidence, and even psychiatric disorders for infertile couples . It was estimated that the prevalence of anxiety and depression in infertile women reached 23.2% and 17% in China, respectively . Therefore, infertility is not only a medical problem but also a public health issue.
Assisted reproductive technology (ART) treatment was an effective solution to infertility that was widely accepted by infertile couples. However, ART is costly and needs a series of complex processes such as ovarian stimulation, retrieving oocytes, and transferring embryos into the woman’s uterus , which can increase the psychological burden on infertile couples, especially on the female partner . The success rate of in vitro fertilization (IVF) is about 30% per cycle , so most infertile couples would face failure. Some women dropped out of treatment  or even never started the treatments  due to these reasons. More importantly, the psychological state of infertile couples could affect the outcome of treatment. Women with higher stress and anxiety scores on the day prior to oocyte retrieval had a lower probability of pregnancy . There were significant associations between depression and anxiety scores before ART treatment and reduced pregnancy chances with ART [12, 13]. Therefore, it needs a health mental state to face ART treatment, and psychosocial intervention is of crucial importance for infertile couples.
To offer effective counseling and psychological support, it is necessary to fully understand the risk factors for adverse psychology especially anxiety and depression in infertile couples. A previous study showed that anxiety and depression scores were inversely correlated with their ages in women and were significantly correlated with the duration of infertility in men . In infertile couples, the incidence of anxiety in women was related to age, education level, and family income, and the incidence of depression was related to the age and duration of infertility . However, most previous studies mainly enrolled infertile women while men were underrepresented [16, 17]. In addition, less attention has been paid to the interaction between psychological disorders, and between female and male partners. Here, we enrolled 1247 infertile couples undergoing ART and conducted a longitudinal observational study with the purpose of evaluating the prevalence of depression and anxiety, and comprehensively analyzing the risk factors, especially the association between anxiety and depression in infertile couples.
Subjects and ethics statement
Infertile couples who planned to undergo ART at the Centre of Reproductive Medicine of Shanghai Jiao Tong University Affiliated Sixth People's Hospital between January 2016 and December 2018 were consecutively recruited in our study. The inclusion criteria were as follows: infertile couples could complete the ART treatment and the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) survey before and during ART treatment. The exclusion criteria included subjects who had a history of mental illness or psychiatric disorders; the presence of complications during the ART cycle (such as ovarian hyperstimulation syndrome, oocyte retrieval bleeding, pelvic infection, etc.). All subjects did not undergo psychological counseling before enrollment. The study was approved by the Institutional Review Board of Shanghai Jiao Tong University Affiliated Sixth People's Hospital. All methods were carried out in accordance with relevant guidelines and regulations. Written informed consent was provided by all subjects.
Questionnaires and data collection
All subjects completed two questionnaires: SDS, designed by Zung in 1965 , and SAS, designed by Zung in 1971  at the following stages: (i) on the first day of ovarian stimulation (Visit 1), (ii) on the day of oocyte retrieval (Visit 2), and (iii) on the day of embryo transfer (Visit 3). SAS and SDS questionnaires have been validated and are widely used for assessing an individual’s mental state [15,16,17]. Both SAS and SDS questionnaires cover 20 questions. Each question is scored on a 4-point scale ranging from 1 (none, or a little of the time) to 4 (most, or all of the time). The raw total scores are obtained by summarizing the scores of the 20 questions and are converted to percentile standard scores. The subjects with SAS scores ≥ 50 are diagnosed with anxiety, while scores ranging from 50 to 59 are classified as “mild”, from 60 to 69 are “moderate”, and more than 69 are “severe” . The subjects with SDS scores ≥ 53 are identified as depression, while scores ranging from 53 to 62 are “mild”, from 63 to 72 are “moderate”, and more than 72 are “severe” .
A researcher formally interviewed face to face all enrolled subjects. Sociodemographic data (such as age, education, and profession), and clinical data including reproductive history, previous treatments, and the causes of infertility were collected from ART medical records.
We analyzed all data using SPSS software, version 24.0 (SPSS Inc., Chicago, IL, USA). For categorical variables, we calculated proportions. For continuous variables, we calculated the mean and standard deviation. We compared categorical variables, such as the prevalence of anxiety and depression in infertile couples, using the Chi-square test or Fisher’s exact test. We used the repeated measures ANOVA test (including Tukey post hoc correction) to compare the SAS and SDS scores of infertility couples on Visit 1, Visit 2, and Visit 3. Factors between anxiety and no anxiety (or between depression and no depression) were firstly analyzed by univariate analysis, when factors with a p < 0.1 were included in the multivariate logistical regression. We considered p < 0.05 at two-sided to be statistically significant.
Clinical characteristics of the enrolled infertile couples
As shown in Fig. 1, there were 1290 infertile couples undergoing ART in our center between January 2016 and December 2018. Four couples were excluded because they had a history of mental illness or psychiatric disorders. In addition, 11 couples who failed to complete ART treatment, 5 couples who were present with complications during the ART treatment, and 23 couples who could not complete the survey, were excluded. Therefore, a total of 1247 infertile couples were enrolled in this study. The clinical characteristics of the 1247 infertile couples were shown in Table 1. The age was 31.64 ± 5.11 years for female partners and 33.33 ± 5.88 years for male partners. The college degree was dominant in infertile couples and accounted for 54.5%(679/1247) and 55.6% (693/1247) in males and females, respectively. The majority of male partners were employed (96.8%,1207/1247), but 249 (20%) of female partners were unemployed. The duration of infertility was 3.55 ± 2.59 years. The causes of infertility were 40.3%(503/1247) for female factors, 20.3%(253/1247) for male factors, 36.3% (453/1247) for both female and male factors, and 3.0%(38/1247) for unknown factors.
Female was more likely to have anxiety than male in infertile couples
To analyze the psychological state of infertile couples, the anxiety and depression of 1247 infertile couples planning ART were assessed using SAS and SDS. As shown in Table 2, the prevalence of anxiety in female partners was 13.5% (168/1247) and was higher than that in male partners [8.7% (108/1247)] (p < 0.05). Of them,148 females (88.1%,148/168) were mild anxiety, and 20 females (11.9%, 20/168) were moderate anxiety (p < 0.05). Mild, moderate, and severe anxiety accounted for 76.9% (83/108), 21.3% (23/108), and1.9% (2/108) among 108 male partners with anxiety, respectively. The number of mild anxiety was significantly more than those of moderate, and severe anxiety (both p < 0.05). The prevalence of depression was 9.4%(117/1247) and 7.9%(99/1247) in female and male partners, respectively (p = 0.2). Similar to anxiety, most of them were mild depression, which was 75.2% (88/117) and 78.8% (78/99) in female and male partners, respectively, and were higher than moderate, and severe depression (all p < 0.05).
Among 1247 infertile couples, 233 females (18.7%, 233/1247) had anxiety and/or depression, of whom 52 females (22.3%,52/233) were comorbidity of anxiety and depression (Fig. 2A). A total of 171 males (13.7%, 171/1247) had anxiety and/or depression, of whom 36 males (21.1%, 36/171) were comorbidity of anxiety and depression (Fig. 2B). The prevalence of anxiety and/or depression in females was higher than that in males (18.7% vs 13.7%, p = 0.0009). 238 infertile couples with one or both partners (19.1%,238/1247) had anxiety. Of them, 38 infertile couples (16.0%,38/238) had anxiety in both partners (Fig. 2C). 176 infertile couples with one or both partners (14.1%,176/1247) had depression. Of them, 40 infertile couples (22.7%,40/176) had depression in both partners (Fig. 2D). The prevalence of anxiety was higher than depression in infertile couples (19.1% vs 14.1%, p = 0.0008). A total of 323 infertile couples (25.9%,323/1247) with at least one partner had anxiety, depression, or both (Fig. 2E).
The levels of anxiety and depression were positively associated between female and male partners in infertile couples
To investigate the interaction of different psychological disorders in infertile couples, we analyzed the association of SAS and SDS scores between female and male partners. As shown in Fig. 3A&B, female SAS and SDS scores were both positively associated with male SAS and SDS scores (r = 0.52 and r = 0.50, both p < 0.0001, respectively). In addition, female SAS scores were correlated with their own SDS scores (r = 0.63, p < 0.0001) (Fig. 3C). Male SAS scores were correlated with their own SDS scores (r = 0.62, p < 0.0001) (Fig. 3D).
Their own or partners’ anxiety or depression were risk factors for anxiety and depression in infertile couples
To further discover the risk factors for anxiety and depression in infertile couples, we analyzed the association between the education levels, age, the causes of infertility, no children, their partners’ anxiety/depression, their own anxiety/depression, duration of disease, the state of employment, and the anxiety/depression using multivariate logistic regression. As shown in Table 3, no children (odds ratio (OR) 2.12, p = 0.04), their own depression (OR 6.03, p < 0.0001), their partners’ anxiety (OR 3.45, p < 0.0001), unemployment (OR 1.69, p = 0.02) were associated with female anxiety. In addition, compared to the above college degree, a high school degree (OR 5.49, p = 0.04), and a college degree (OR 4.84, p = 0.04) were also risk factors for female anxiety. Their own depression (OR 3.42, p < 0.0001) and their partners’ anxiety (OR 6.94, p < 0.0001) were positively associated with male anxiety. Their own anxiety (OR 5.88, p < 0.0001) and their partners’ depression (OR 6.67, p < 0.0001) were positively associated with female depression. Similarly, their own anxiety (OR 7.14, p < 0.0001) and their partners’ depression (OR 6.67, p < 0.0001), were positively associated with male depression.
The SAS and SDS scores of infertility couples during ART significantly declined
To investigate the dynamic change of psychological states undergoing ART, we compared the SAS and SDS scores of 1247 infertility couples on the initiation day (Visit 1), oocyte retrieval day (Visit 2), and embryo transplantation day (Visit 3). As shown in Fig. 4A, female SAS scores were 39.81 ± 8.62,38.22 ± 8.46, and 37.79 ± 8.83 on Visit 1, Visit 2, and Visit 3, respectively, which significantly decreased compared to Visit 1(both p < 0.0001). Female SDS scores were 38.67 ± 10.04, 37.78 ± 10.28, and 37.78 ± 10.83 on Visit 1, Visit 2 and Visit 3, respectively. The scores on Visit 2 and Visit 3 were lower than that on Visit 1(both p < 0.0001) (Fig. 4B). Similar to females, male SAS and SDS scores on Visit 2 and Visit 3 were all lower than those on Visit 1(all p < 0.0001) (Fig. 4C&D).
Infertility now is a public health concern affecting millions of couples . It has an immense impact on the psychosocial well-being of affected couples [11, 12]. In this study, we found that 25.9% of infertile couples with at least one partner had anxiety, depression, or both. Of them, 18.7% of females and 13.7% of males were anxiety and/or depression disorders. A previous study showed that 40.2% had a psychiatric disorder among 112 women visiting the assisted reproduction clinic, including 23.2% with anxiety disorder, and 17.0% with depressive disorder . Liu et al.’s study also found that the incidences of anxiety and depression on the first day of entering the IVF-ET cycle were 29.96% and 15.79% in women, and 20.65% and 13.77% in men among 247 infertile couples, respectively . These studies demonstrated that anxiety and depression disorders were common in infertile couples. Consistent with Liu et al.’s study , most of them were mainly mild anxiety and depression in our study. It is generally considered that women are primarily blamed in cases of infertility, so women are more vulnerable to being affected by infertility than men [21, 22]. The prevalence of anxiety for females (13.5%) was significantly higher than that for males (8.7%) in this study. Liu et al.’s study also showed that the incidence of anxiety in women was higher compared to men . Consequently, more attention should be paid to female partners.
Our study demonstrated that 52 females (22.3%) were comorbidity of anxiety and depression among 233 females who had anxiety and/or depression. Among 171 males who had anxiety and/or depression, 36 males (21.1%) were comorbidity of anxiety and depression. Anxiety and depression often co-existed in many people suffering from mental health conditions [23, 24]. The association of high levels of anxiety with COVID-19 complications and comorbid depression had been found amongst hospitalized COVID-19 patients . 14% of patients with Parkinson had a comorbid depressive disorder with anxiety . More importantly, we found that SAS and SDS scores were positively associated with their own SDS and SAS scores. Their own anxiety and depression were independent risk factors for depression and anxiety, respectively. Similar to our findings, anxiety was an independent risk factor for depression, and depression was a risk factor for anxiety in COVID-19 patients . Collectively, these studies indicated that it could present interactions between anxiety and depression in infertile couples. Compared with either disorder alone, comorbid depression and anxiety could increase impairment [26, 27]. Therefore, to more effectively psychosocial intervention and support, anxiety, and depression should be intervened simultaneously under the condition of the comorbidity of anxiety and depression in infertile couples.
Another finding in our study was that female SAS and SDS scores were positively associated with male SAS and SDS scores. Partners’ anxiety or depression were risk factors for anxiety/depression in infertile couples. A previous study showed that men with anxious partners were vulnerable to having depressive and anxious symptoms . There was a strong correlation between psychological stress and psychopathology not only within the subject but also between the male and female partners within the couple . Based on these studies, infertile couples may benefit from the treatment of both partners. Besides the above risk factors, low education levels, no children, and female unemployment were also risk factors for female anxiety. Liu et al.’s study also showed that the incidence of anxiety in women was related to education level, and annual family income . The prevalence of depression was higher among women with a family income ≤ 3000 CNY/month . Oman‑Samani et al. showed that a higher education level was less likely to develop anxiety symptoms .
The SAS and SDS scores of infertility couples significantly declined during ART. Massarotti C et al.’s study also indicated that the levels of anxiety and general distress were significantly decreased and the quality of life was improved during IVF . Since the first baby was born using IVF in 1978 , ART has great progress and is now widely accepted by the public. As of 2019, the total number of births achieved through ART likely exceeded 8 million globally . ART can resolve their infertility and give hope to infertile couples. In addition, knowing other infertile couples in the waiting room helped them to feel less alone in their problems. Therefore, anxiety and depression could be relieved during the process of ART.
Female partners were more vulnerable to having anxiety. Low education levels, no children, and female unemployment were risk factors for female anxiety. More importantly, there was the comorbidity of anxiety and depression in infertile couples, and the levels of anxiety were positively associated with the levels of depression. The anxiety/depression of their own or their partner were independent risk factors for the anxiety/depression of infertile couples. Therefore, to cope with these risk factors, anxiety and depression should be simultaneously counseled, and their partners also should be given supportive psychotherapy.
Limitations and strengths
In our study, we enrolled 1247 infertile couples which was a larger sample size compared to the previous studies. To avoid selection bias, we consecutively recruited patients into the study. Data was collected from female and male partners and from three-time points including before and during ART. The levels of anxiety and depression and risk factors for anxiety and depression in infertile couples were comprehensively assessed. However, there were two limitations to our study. On the one hand, we recruited patients from a single center of reproductive medicine treatment in China. Due to cultural and economic differences, the prevalence of anxiety and depression in infertile couples could be inconsistent with the other regions of China and other countries. On the other hand, because we only screened the mental state of infertile couples but not the fertile couples in our center during the same period, the prevalence of anxiety and depression between infertile couples and fertile couples can’t be compared.
Availability of data and materials
The data used during the current study are available from the corresponding author on reasonable request.
Assisted reproductive technology (ART)
Self-Rating Anxiety Scale
Self-Rating Depression Scale
Analysis of Variance
Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, et al. The International glossary on infertility and fertility care, 2017. Fertil Steril. 2017;108(3):393–406.
Sun H, Gong TT, Jiang YT, Zhang S, Zhao YH, Wu QJ. Global, regional, and national prevalence and disability-adjusted life-years for infertility in 195 countries and territories, 1990–2017: results from a global burden of disease study, 2017. Aging (Albany NY). 2019;11(23):10952–91.
Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiology. Clin Biochem. 2018;62:2–10.
Keramat A, Masoomi SZ, Mousavi SA, Poorolajal J, Shobeiri F, Hazavhei SM. Quality of life and its related factors in infertile couples. J Res Health Sci. 2014;14(1):57–63.
Chen TH, Chang SP, Tsai CF, Juang KD. Prevalence of depressive and anxiety disorders in an assisted reproductive technique clinic. Hum Reprod. 2004;19(10):2313–8.
Raef B, Ferdousi R. A review of machine learning approaches in assisted reproductive technologies. Acta Inform Med. 2019;27(3):205–11.
Karimzadeh M, Salsabili N, Akbari Asbagh F, Teymouri R, Pourmand G, Soleimanieh NT. Psychological disorders among Iranian infertile couples undergoing assisted reproductive technology (ART). Iran J Public Health. 2017;46(3):333–41.
Toftager M, Bogstad J, Løssl K, Prætorius L, Zedeler A, Bryndorf T, et al. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017;32(3):556–67.
Gameiro S, Boivin J, Peronace L, Verhaak CM. Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment. Hum Reprod Update. 2012;18(6):652–69.
Crawford NM, Hoff HS, Mersereau JE. Infertile women who screen positive for depression are less likely to initiate fertility treatments. Hum Reprod. 2017;32(3):582–7.
Turner K, Reynolds-May MF, Zitek EM, Tisdale RL, Carlisle AB, Westphal LM. Stress and anxiety scores in first and repeat IVF cycles: a pilot study. PLoS ONE. 2013;8(5):e63743.
Matthiesen SM, Frederiksen Y, Ingerslev HJ, Zachariae R. Stress, distress and outcome of assisted reproductive technology (ART): a meta-analysis. Hum Reprod. 2011;26(10):2763–76.
Purewal S, Chapman SCE, van den Akker OBA. A systematic review and meta-analysis of psychological predictors of successful assisted reproductive technologies. BMC Res Notes. 2017;10(1):711.
Abdishahshahani M, Torabi M, Kazemi A. Investigating related factors to psychological symptoms of infertile couples undergoing assisted reproductive treatment. J Educ Health Promot. 2020;9:21.
Liu YF, Zheng FU, Chen SW, He XP, Fan LY. The Analysis of Anxiety and Depression in Different Stages of in vitro Fertilization-Embryo Transfer in Couples in China. Neuropsychiatric Disease and Treatment. 2021;17:649–57.
Wu G, Yin T, Yang J, Xu W, Zou Y, Wang Y, et al. Depression and coping strategies of Chinese women undergoing in-vitro fertilization. Eur J Obstet Gynecol Reprod Biol. 2014;183:155–8.
Ogawa M, Takamatsu K, Horiguchi F. Evaluation of factors associated with the anxiety and depression of female infertility patients. Biopsychosoc Med. 2011;5(1):15.
Zung WW. A self-rating depression scale. Arch Gen Psychiatry. 1965;12:63–70.
Zung WW. A rating instrument for anxiety disorders. Psychosomatics. 1971;12(6):371–9.
Wasilewski T, Łukaszewicz-Zając M, Wasilewska J, Mroczko B. Biochemistry of infertility. Clin Chim Acta. 2020;508:185–90.
Maroufizadeh S, Hosseini M, Rahimi Foroushani A, Omani-Samani R, Amini P. Application of the dyadic data analysis in behavioral medicine research: marital satisfaction and anxiety in infertile couples. BMC Med Res Methodol. 2018;18(1):117.
Maroufizadeh S, Hosseini M, Rahimi Foroushani A, Omani-Samani R, Amini P. The effect of depression on quality of life in infertile couples: an actor-partner interdependence model approach. Health Qual Life Outcomes. 2018;16(1):73.
Mazza MG, De Lorenzo R, Conte C, Poletti S, Vai B, Bollettini I, et al. Anxiety and depression in COVID-19. One-year mental health outcomes in a cohort of COVID-19 survivors. J Psychiatr Res. 2021;145:118–24.
Wee N, Kandiah N, Acharyya S, Chander RJ, Ng A, Au WL, et al. Depression and anxiety are co-morbid but dissociable in mild Parkinson’s disease: a prospective longitudinal study of patterns and predictors. Parkinsonism Relat Disord. 2016;23:50–6.
Ngasa SN, Tchouda LAS, Abanda C, Ngasa NC, Sanji EW, Dingana TN, et al. Prevalence and factors associated with anxiety and depression amongst hospitalized COVID-19 patients in Laquintinie Hospital Douala, Cameroon. PLoS ONE. 2021;16(12): e0260819.
Kuzel RJ. Treating comorbid depression and anxiety. J Fam Pract. 1996;43(6 Suppl):S45–53.
Brown C, Schulberg HC, Madonia MJ, Shear MK, Houck PR. Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Am J Psychiatry. 1996;153(10):1293–2130.
Haimovici F, Anderson JL, Bates GW, Racowsky C, Ginsburg ES, Simovici D, et al. Stress, anxiety, and depression of both partners in infertile couples are associated with cytokine levels and adverse IVF outcome. Am J Reprod Immunol. 2018;79:e12832.
Omani-Samani R, Ghaheri A, Navid B, Sepidarkish M, Maroufizadeh S. Prevalence of generalized anxiety disorder and its related factors among infertile patients in Iran: A cross-sectional study. Health Qual Life Outcomes. 2018;16(1):129.
Massarotti C, Gentile G, Ferreccio C, Scaruffi P, Remorgida V, Anserini P. Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization. Gynecol Endocrinol. 2019;35(6):485–9.
Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet. 1978;2(8085):366.
Hanson BM, Kaser DJ, Franasiak JM. Male Infertility and the Future of In Vitro Fertilization. Urol Clin North Am. 2020;47(2):257–70.
Ethics approval and consent to participate
The study was approved by the Institutional Review Board of Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Written informed consent was provided by all subjects.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Zhang, L., Shao, H., Huo, M. et al. Prevalence and associated risk factors for anxiety and depression in infertile couples of ART treatment: a cross-sectional study. BMC Psychiatry 22, 616 (2022). https://doi.org/10.1186/s12888-022-04256-9
- Depression; infertile couple
- Risk factors