Systematic Review: Risk Factors of Anxiety, Depressiveness, and (Lack of) Social Support in Women and Men Prior to Assisted Reproduction.

A comprehensive search was performed in the electronic databases PubMed, PubPsych, PsycINFO-Ebsco, and Web of Science for publications published in English and German before 2022. The articles were exported on 22 August 2022. The publications focused on the effect of infertility or the unfulfilled desire to have children on anxiety, depression, and social support. The search keywords were: infertil* AND anxiety AND depression AND social support. A total of 332 publications were found, plus relevant articles from the author search (n = 4). Fig. 1 illustrates the search process for identifying the relevant literature. Publications were added to the search results if they had been published in peer-reviewed journals; presented original results (i.e., no reviews); included infertile couples with an unfulfilled desire to have children, men and/or women; used validated measurement methods; included couples who had not yet begun the assisted reproduction treatment process. PRISMA flow chart (Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-analyses: The PRISMA Statement. PLoS Med 2009; 6(7): e1000097. doi: 10.1371/journal.pmed.1000097 ). Because the emotional stress of couples undergoing ART may vary, publications that focused on reproductive medicine treatment or on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were excluded 15 16 17 . Based on this, those studies were excluded in which it was clear that half or more of the participants were on or after ART. After excluding duplicates, 195 publications remained. Titles and abstracts were screened for inclusion criteria. Publications that did not address infertility (n = 41) or the psychological aspects prior to starting infertility treatment (n = 35) were excluded, as were publications that focused on cancer (n = 3), COVID (n = 5), effects of psychotherapeutic therapies (n = 28), questionnaire validation (n = 7), medical diagnoses such as endometriosis or polycystic ovary syndrome (PCOS) (n = 14), or outcome variables other than depression, anxiety, and lack of social support (n = 5). In addition, publications that were not written in English or German were excluded (n = 7), as well as reviews and meta-analyses (n = 19), and non-peer-reviewed publications (n = 2). A total of 166 publications were discarded, while 29 publications remained. Two reviewers (CLT and TW) independently conducted the review of the 29 studies using the full texts, and nine publications were subsequently excluded. The nine excluded studies were publications on the psychological aspects after or during ART. In 12 studies, it was unclear whether patients were undergoing intensive fertility treatment at the time of data collection. However, because their results did not differ significantly from the eight studies that clearly did not address ART, these 12 studies were included in the systematic review. Ultimately, 20 quantitative studies were included in the review. The quality of the studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Guideline 18 . This checklist includes a maximum score of 22 points covering the areas of title, abstract, introduction, methods, results, and discussion of a publication. One point corresponds to one item, provided that the criteria apply. 18 of the 22 items are applicable to all study designs and four items are specific to cross-sectional, case-control, and cohort studies. If the total study score was ≥ 17, the quality of the study was rated as high, with a score between 11 and 16 as moderate, and at ≤ 10 points as a low-quality study. No low-quality study could be found, while 17 of the 20 studies were rated as moderate-quality, and three studies were rated as high-quality ( Table 1 ).

All 20 selected studies were published in peer-reviewed journals. These included 15 cross-sectional studies, four case-control studies, and one cohort study. The studies include a heterogeneous patient population with 5226 participants from 15 different countries. These included six studies in Europe (Bulgaria, Germany, Greece, Italy, and the United Kingdom [UK]), nine studies in the Middle East (Iran, Pakistan, Saudi Arabia, Turkey), five in East Asia (China, India, Japan, Vietnam), one study in Africa (Ghana), and one study in North America (United States). Two publications focused on the comparison of infertile women between two countries (Bulgaria and Greece, UK and Pakistan). The publications all addressed the psychological aspects of depressiveness, anxiety, and (lack of) social support in the unfulfilled desire to have children. Among these, 18 studies addressed depressiveness, 15 studies addressed anxiety, and nine studies addressed social support. Fifteen publications elaborated on more than one of the psychological factors. Ten studies included both women and men, ten studies included only infertile women, and no study addressed infertile men alone. The results of the systematic review are listed in the following tables: The correlation between infertility and depressiveness ( Table 2 ), anxiety ( Table 3 ), and social support ( Table 4 ). Of the 18 publications that dealt with the risk factor of depressiveness, eight studies examined both men and women. These included six studies that explicitly included only infertile couples and two studies that had an unequal number of men and women and thus did not focus solely on the couple. Among these two publications was also a study comparing infertile patients with fertile patients. Ten studies included only women, and among these ten studies, three studies compared infertile women with fertile women. In addition, two publications dealt with the comparison of infertile women between two countries (Bulgaria and Greece, UK and Pakistan). The survey instruments were very heterogeneous. The following questionnaires were used to assess the participants’ level of depression: Beck Depression Inventory 20 21 25 28 34 , Beck Depression Inventory-II 36 , Center for Epidemiologic Studies Depression Scale 27 , Depression Anxiety Stress Scale 35 , General Health Questionnaire 28 23 22 , Hospital Anxiety and Depression Scale 19 31 32 ,Hamilton Depression Rating Scale 26 , Patient Health Questionnaire 9 37 , Symptom Check List 90-R 24 33 38 , and an “in-house” questionnaire 32 . In two Turkish publications that looked at both men and women, no clinically relevant depression was found in the couples 19 28 . In another Turkish study that compared infertile participants with fertile participants, 25% of participants were found to have mild levels of depressive symptoms and 40% had moderate levels 34 . Here, the infertile group had higher depression scores compared to the fertile participants. When depression scores were compared between the two sexes, four studies showed higher scores for women compared to men 28 22 34 36 . In contrast, again no differences between women and men were found in three studies 19 24 25 . When comparing women and men, respectively, with a representative sample, slightly higher scores for depression were found in women compared to the norm, whereas no differences were detected in men 38 . In the studies that included only women, different prevalences of depressiveness were noted. The study from Ghana was able to identify 62.0% of women with a mild to moderate form of depression 21 . According to the results of the Indian cross-sectional study, 58% of infertile women were identified with depression, including 35.6% with a moderate to severe form of depression 26 . The Iranian study identified 40.7% of participants with depression 36 . In contrast, in the Vietnamese study, the prevalence of depression was 12.2% 37 . The 2001 Japanese study comparing infertile women with pregnant women showed that 38.6% of infertile women were above the cut-off score of the HADS depression scale, compared with 16.0% of pregnant women 31 . The studies from Saudi Arabia and Iran also showed that infertile women have higher depression scores compared to fertile women 20 33 . The study, which examined cross-country differences between infertile Bulgarian and Greek women, did not find differences in depression scores between infertile women from Bulgaria and Greece 27 . Infertile Pakistani women were found to have higher scores on the depression subscale compared to infertile British women 23 . The importance of marital quality in relation to depressiveness among infertile women is demonstrated by two studies from Japan and Pakistan. The research results showed, on the one hand, that low marital quality is a significant predictor of depression and stress and, on the other hand, that depressiveness correlates with a lack of support from the husband and feelings of stress 32 35 . Among the 15 publications that addressed infertility and anxiety, eight studies addressed both women and men and seven studies addressed only infertile women. The survey instruments used were as follows: Beck Anxiety Inventory 34 , Depression Anxiety Stress Scale 35 , General Health Questionnaire 28 23 22 , Hospital Anxiety and Depression Scale 19 31 32 , Hamilton Anxiety Inventory, 26 , Symptom Check List 90 (revised) 24 33 38 , and State-Trait Anxiety Inventory 25 27 36 39 . In the British longitudinal study, a decrease in anxiety scores within 7–9 months was found in both men and women 25 . In three studies, women had higher scores for anxiety compared to men 19 22 34 , and trait anxiety in the Iranian study 36 . For trait anxiety, another study from Turkey demonstrated high scores in both genders 28 . It was highlighted in both Turkish studies that despite the gender difference, the overall and state anxiety scores were not in the pathological range 19 28 . This was also shown in the study from India, in which the group mean of infertile women was below the threshold for clinical relevance 26 . The German study found no difference in anxiety scores for infertile males compared to the norm, while females had slightly higher scores compared to the norm 38 . In the American study, which also examined men and women, no difference was found between the sexes 24 . This was also shown in the study by Shafierizi et al. (2022) for state anxiety. Here, however, 45.7% of participants showed increased anxiety. When infertile participants were compared with fertile participants, a Turkish study found higher anxiety scores in the infertile group 34 . The Iranian and Japanese study comparing infertile women with fertile women also demonstrated this difference 31 33 . According to the results of the study from Pakistan, marital quality was not a significant predictor of anxiety 35 , whereas results from the Japanese study showed that a lack of support from the husband correlated significantly with anxiety in the wife 32 . The comparative country studies did not find any relevant differences between infertile British and Pakistani women or between Bulgarian and Greek women 23 27 . The construct “social support” is generally defined as helpful interaction with others (e.g., partnership, family, friendships) in coping with a problem. Usually, a distinction is made between emotional support (e.g., comfort), instrumental support (e.g., practical help), and informational support (e.g., guidance). What is measured is mostly the subjectively perceived support (not the actual received support). Of the nine publications, three studies included only infertile women and six included both women and men in terms of social support. The nine studies used the Berlin Social Support Scale 23 , an in-house questionnaire 32 , Interpersonal Support Evaluation List 25 , Multidimensional Scale of Perceived Social Support 19 27 , Procidano and Heller’s Perceived Family Support and Perceived Peer Support 36 , Social Support Questionnaire 29 , and Social Support Rating 30 . Two studies found higher levels of social support from the family in women than in men 28 36 . This difference was also shown by the Italian study in the areas of emotional and practical support, social inclusion, and “Person of Trust” support 29 . However, results from the two Turkish and Iranian studies showed that the two genders did not differ in all areas of their perceived social support. For example, no differences between women and men were detectable in the total scales of social support 19 28 36 . It was also found that in women or couples, tangible social support from the environment was associated with low anxiety and depression scores 19 25 32 . The Chinese study showed the influence of social support in infertile women and men on their respective coping styles 30 . In the comparative country studies, Greek women were found to have lower perceived social support compared to infertile women from Bulgaria 27 . British women showed higher scores compared to Pakistani women on the “Actual Received Support” scale 23 .

A total of 20 studies were included in the systematic review, of which 18 focused on depressiveness and 15 on anxiety, while nine addressed the social support aspect. Both women and men were studied in half of the studies, while the other half included only women. Due to the large heterogeneity of the study results in the areas of depressiveness, anxiety, and social support, and considering the limitations, it is currently not possible to draw clearly provable conclusions about a difference between psychological risks of men versus women with an unfulfilled desire to have children. However, it could be shown that infertile couples or women compared to fertile participants experience an overall higher emotional stress in the form of depressiveness and anxiety, which can only be partially “buffered” by protective factors such as good social support. Accordingly, future interventions and research focusses should emphasize strengthening social relationships. It is important to promote the education of family and friends in order to strengthen the sympathy from this group and thus (somewhat) reduce the psychosocial stress of infertile women and men. This can be achieved, on the one hand, by education in the context of fertility treatment or in the media context, and, on the other hand, by involving both partners in the course of treatment. Further studies of depression, anxiety, and social support should be conducted to provide a more comprehensive picture of the impact of infertility on couples. In addition to cross-sectional studies, longitudinal studies should be performed at different times of ART. Here, it is necessary, among other things, to clearly identify the time of data collection during the course of assisted reproductive therapy (ART) to ensure comparability of study results. In addition, uniform measurement tools and larger samples should be used for better comparison.

The aim of this review, which comprised a total of 20 studies, was to provide an overview of the psychological aspects of women and men with an unfulfilled desire to have children prior to assisted reproduction in terms of depression, anxiety, and social support. For depressiveness, it was not found overall that women are more depressed compared to men. Since an equal number of studies each found a difference or no difference between the two genders, no clear conclusion can be drawn. It can be seen that the data are very heterogeneous. However, when comparing infertile couples and women, each with a representative sample, a difference in depression scores was shown in the corresponding studies. The very wide range of depressive prevalences is striking. While some studies found no pathological significance in couples (0%), prevalences of depression in other studies of infertile women ranged from 12 to 62%. As Kiani et al. (2021) describe in their work, the different prevalences of depression among infertile women worldwide can be explained by, among other things, different income levels between countries 40 . Here, while 44.3% of infertile women in low or middle-income countries were identified with depression, only 28% of infertile women from high-income countries showed depression. Using the Human Development Index (HDI) to measure human development, which comprises the three dimensions of “long and healthy life”, “knowledge”, and “adequate standard of living”, the different countries can be compared 41 . Thus, the HDI also reflects, in part, differences in the quality and availability of national health care systems (which, in the context of the question posed in this review, relates particularly to the financially as well as logistically low-threshold availability of professional infertility-specific diagnostics). By classifying the survey countries into the respective “human development” groups, orientation can be provided with regard to factors such as social development, health status of the population, and level of education. The survey countries in our studies that had high prevalences of depression were in the middle (Ghana and India) and high (Vietnam and Iran) “Human Development” group according to the 2022 index. The two Turkish studies, for which no clinical relevance was demonstrated, could be classified in the group with a very high HDI. The comparative country studies also support the assumption that the differences in psychological stress among infertile women and men can be explained by differences regarding cultural, social, and economic factors. It must additionally be taken into account when interpreting the prevalences that the different studies used different survey instruments. The results of Fisher and Hammarberg’s (2012) review found, in comparison, that both fertile and infertile men have as great a desire for parenthood as their female partners do 42 . This showed no clinically significant mental health problems in men compared with the general population. Anxiety related to involuntary childlessness also showed mixed results in terms of gender difference. While several studies showed a difference between anxiety scores in women and men, others showed no significant difference. In a majority of studies, higher anxiety scores were demonstrated in infertile couples or women compared to fertile participants. It can be assumed that women who have just received a diagnosis of infertility are anxious about the reproductive medical treatment that may follow. Infertile women face treatment-specific problems, feelings of failure, and also fear of operations compared to fertile women. It was found that women who felt better informed about infertility treatment had lower anxiety and depression scores 34 . Likewise, in the area of social support in infertility, an equal number of studies found a difference or no difference between men and women. A review by Cousineau and Domar (2007) concludes that men suffer silently to support their wives 43 . The importance of high social support among infertile women and men was demonstrated in several studies in our review by associated low levels of depression and anxiety. Infertile women, on the other hand, experience social isolation in very pronatalist cultures due to the stigma of childlessness and usually receive less support from their husbands or family and friends 3 . Regardless of the gender difference, good social support from the partner is negatively associated with the risk for depressiveness or anxiety in the sense of “buffering” 44 . In comparison to the results of this review, the systematic review by Luk and Loke (2015) shows that couples with infertility are impaired in the areas of life of psychological well-being, marital relations, sexual relations, and quality of life. It has been highlighted that involuntary childlessness has a negative impact on the psychological well-being of couples. That infertility is a more stressful experience for women than for men is inferred by Greil et al. (1997) with the help of their review. This is inconsistent with our results because no clear conclusion can be made about the gender difference with regard to psychological stress due to the heterogeneity of the study results. It can be surmised that over the past few decades, the defined roles of the genders have changed. This assumption is also held by Edelmann and Connolly, who argue that the claim that women react more negatively to infertility than their partners is shaped by outdated gender stereotypes 11 . On the other hand, the results can be explained by the fact that men now answer less in line with social desirability compared to the last decade.

With these findings, the results discussed here, which come from a total of 15 different countries, should be viewed with caution. As a further limitation of this review, it must be mentioned that due to the many different survey instruments used, a direct comparability of the study results is very limited. In addition, only publications in English or German could be included. The majority of the included studies were cross-sectional, so no conclusion can be drawn about the causality of psychological factors. Because cut-off scores of the questionnaires used were not presented in all included studies, the pathological relevance of the discussed results cannot be understood from each study. It must also be mentioned that, depending on the study, both pregnant women and postpartum women were used to compare the infertile participants with a fertile group. Due to various external influences (including hormonal), the groups may be subject to different emotional stresses that are not comparable. Furthermore, the number of publications found is comparatively low because [and] and not [or] was used in the search string. In this systematic review, no exclusion criterion was set in relation to the time of publication of the studies. However, the data collection of all studies took place after the introduction of IVF in 1978. In addition, it must be mentioned that in the included studies it is often assumed that only heterosexual couples are meant under the definition of couple. The significance of the psychosocial aspects of the unfulfilled desire to have children in same-sex couples or other sexual identities or in individuals is therefore only transferable to a limited extent.

Infertility is thought to affect between 48 million couples and 186 million individuals of reproductive age worldwide 1 2 . The stigma of infertility can cause great psychological pressure on patients and severely affect their quality of life 3 . Reviews have shown that the unfulfilled desire to have children can affect marital and sexual relationships in addition to psychological well-being and quality of life 4 5 6 . However, from a psychological perspective, other papers report an extensive depathologization of infertile couples 7 8 . On the one hand, research shows that women with an unfulfilled desire to have children are more likely than men to suffer from depression and infertility-related stress 9 10 . On the other hand, there is a view that the assumption that women suffer more from infertility than their partners is influenced by outdated gender stereotypes 11 . The role of the man, but also of the couple as a dyad, has become more of a focus of infertility research in recent years 12 . The coping strategies of both partners are interrelated in infertility-related problems, and unfavorable strategies of one partner may increase the other’s risk for depressiveness and anxiety 13 . In vitro fertilization was introduced in 1978 and represents a significant source of hope for patients with an unfulfilled desire to have children and thus a major factor influencing the psychological risk profile of patients 14 . According to the ESHRE guideline 13 , during an IVF/ICSI cycle, patients’ emotional stress levels fluctuate with peaks during oocyte collection, embryo transfer, and especially during the waiting period before the pregnancy test. In addition, one to two in ten women experience (transiently) clinically significant levels of depressive symptoms when treatment is unsuccessful. It is also emphasized that before the start of IVF treatment, patients are not more depressed than the general population 13 . Thus, it is necessary to differentiate between the influence of the sole diagnosis of infertility on the one hand and the influence of intensive fertility treatment in the form of assisted reproductive therapy (ART) on psychological stability on the other. Psychological findings on couples before ART tends to be underrepresented in the literature. Therefore, the AWMF guideline “Psychosomatic Diagnosis and Therapy in Fertility Disorders” comes to the following conclusion regarding psychological abnormalities (such as increased depressiveness and anxiety): “A generalization of these findings on couples not in treatment is only limited (see AWMF-LL 015–085)” 8 , p. 761). The aim of this systematic review is to provide an overview of the psychological characteristics of women and men with an unfulfilled desire to have children prior to ART, giving particular attention to the psychological risk factors of anxiety, depression, and lack of social support.