Initial Psychological Evaluation in Couples with Unexplained Infertility: Focusing on Gender Differences

Abstract

This study explored psychological distress and gender differences among couples diagnosed with unexplained infertility (UI) and undergoing evaluation for assisted reproductive treatment at the AOUP Santa Chiara Hospital in Pisa, Italy. A total of 21 heterosexual couples (N = 42) completed the Perceived Stress Scale (PSS), Depression Anxiety Stress Scale (DASS-21), Defeat Scale (DS), and Core-Fertility Quality of Life questionnaire (Core-FertiQol). Women reported significantly higher levels of anxiety and stress compared to men, as confirmed both by DASS-21 and PSS scores. No significant gender differences emerged either in depressive symptoms or defeat. In the Core-FertiQol, women scored higher in the Mind–Body component. Within-couple comparisons mirrored between-gender findings, with women showing higher distress. Despite elevated distress levels, women also demonstrated relatively preserved quality of life, possibly reflecting more adaptive coping strategies. The study provides preliminary support for the development of mindfulness-based interventions tailored to couples coping with UI. Further research with larger samples is needed to clarify gender-specific mechanisms and inform integrated psychological care in fertility settings.

1. Introduction

The WHO (2024) defines infertility as a condition affecting the male or female reproductive system, diagnosable after 12–24 months of regular, unprotected intercourse without achieving pregnancy (WHO, 2024; Leslie et al., 2024). Infertility affects millions worldwide, with at least one in six people experiencing it during their lifetime (WHO, 2024). The recent WHO report “Infertility Prevalence Estimate 1990–2021” (2023), found a global infertility rate of 17.5%, with Europe among the regions with the highest rates (WHO, 2023). In Italy, 15% of couples are affected by infertility, and the average fertility rate is 1.3 children per woman—below population replacement levels (ISS, 2019; Luppi, 2011; Calamo & García Pereiro, 2014). The Italian National Institute of Statistics, ISTAT (2024), highlights a “demographic winter,” driven primarily by delayed parenthood due to late workforce entry and economic instability, factors that exacerbate fertility decline with age (WHO, 2023).

According to the Italian Ministry of Health, infertility is attributed to female factors in 35% of cases, male factors in 35%, couple-related factors in 15%, and unexplained causes in the remaining 15% (Ministero della Salute, 2012). Common causes include reproductive disorders, sexually transmitted infections, environmental exposures, and unhealthy lifestyles—such as poor diet, smoking, alcohol use, extreme weight, and physical inactivity (Adams et al., 2014; Carré et al., 2017; Damayanthi, 2018; Ding et al., 2018; Jurewicz et al., 2018; Ministero della Salute, 2021; Manouchehri et al., 2022). Age is also a major factor, as fertility declines significantly after age 35 in women and 40 in men (Sartorius & Nieschlag, 2010; ISS, 2019). Despite progress in infertility diagnosis and treatment, many couples still receive no clear explanation for their condition (Isaksson & Tiitinen, 2004). This condition, namely “unexplained infertility” (UI) or “idiopathic infertility,” affects approximately 30% of infertile couples in the US (ACOG, 2019). UI is diagnosed when infertility criteria are met, but standard evaluations—including ovulation, tubal patency, and sperm analysis—show entirely normal results, with no detectable organic, genetic, infectious, or hormonal causes (ACOG, 2019). It is estimated that around 40–65% of couples with idiopathic infertility will conceive naturally within three years, but after this period, the chances of conception progressively decrease; thus, among the positive prognostic factors are maternal age under 25 years, a duration of infertility less than three years, and a favorable obstetric history (Chiappetta, 2022). While infertility is commonly approached from a biomedical perspective, UI presents a distinct challenge that cannot be fully addressed through medical diagnostics alone. In the absence of identifiable physiological causes, couples are often left with unanswered questions, emotional strain, and a suspended sense of life progression, where future plans become uncertain and temporarily put on hold. This context justifies the adoption of a psychological perspective, particularly addressed by clinical health psychology and stress-coping models. More broadly, our approach aligns with the biopsychosocial model, which integrates biological, psychological, and relational dimensions of health and illness; this approach is especially appropriate in the context of UI, where the lack of medical explanation heightens the relevance of subjective experience and interpersonal dynamics.

In line with clinical models widely used in cognitive-behavioral therapy and clinical and health psychology—such as the stress–vulnerability framework and the case formulation approach (Kuyken et al., 2009)—psychological factors can be conceptualized as predisposing, precipitating, or maintaining influences.

In this perspective, several psychological variables have been proposed as possible predisposing, precipitating, or maintaining factors in UI: predisposing factors may include unresolved identity conflicts, ambivalence toward parenthood, and rigid gender or familial expectations, which can influence how individuals engage with the idea of reproduction (Scatoletti, 1996). Precipitating elements are often situational, such as the stress related to medical evaluations, feelings of urgency linked to age, or perceived social pressure to conceive (Greil et al., 2010); also, psychological distress may not only follow unsuccessful treatments but also emerge early in the diagnostic process. Maintaining factors may include persistent anxiety, depressive symptoms, and ineffective coping strategies, which can exacerbate distress and reduce quality of life throughout the infertility process (WHO & Key Centre for Women’s Health in Society, 2009). In parallel, some studies have also highlighted emerging biological hypotheses, such as the role of vaginal microbiota alterations in reducing fertility potential (Campisciano et al., 2017), further reinforcing the need for integrated models of understanding. Overall, the psychological impact of UI is shaped by a complex interplay of internal vulnerabilities, external stressors, and relational patterns that require holistic, person-centered approaches.

As understanding of UI grows, many couples continue to experience its effects. This condition can influence aspects of self-concept, parenthood ideals, and relationship functioning, which may result in anxiety, depression, and social isolation (Moro et al., 2009; Zurlo et al., 2018). The complex and often prolonged nature of ART further compounds this burden, introducing physical, psychological, and financial stressors (Schneider & Forthofer, 2005).

In recent years, greater attention has been paid to the psychological impact of infertility, but few studies have explored emotional distress in couples facing unexplained infertility from a dyadic perspective. Most research has focused on individual symptoms or on specific phases of ART, offering limited insight into how distress is experienced and shared within couples at earlier stages of the diagnostic process, especially when no medical cause is identified (Galhardo et al., 2016). In clinical settings, psychological support is usually sought by women, while men tend to be less involved—often due to cultural expectations, emotional restraint, or different coping strategies (Peterson et al., 2006). As a result, many interventions, including those based on mindfulness and stress reduction, are implicitly tailored to female participants—yet—infertility is a shared experience that affects the couple as a whole.

With this in mind, our study examines psychological differences between men and women experiencing unexplained infertility, intending to contribute to a more relational and balanced approach to psychological care. The present study aims to evaluate the psychological well-being of couples facing UI, with a specific focus on stress, anxiety, depression, and couple-level functioning. By comparing women and men both individually and within dyads, we aim to explore both gender-specific and shared emotional experiences, offering insights that may help guide early psychological screening and support strategies in fertility care. Furthermore, this research is part of a broader project aimed at establishing a psychological profile and baseline characteristics of this population, with the goal of tailoring mindfulness-based interventions to reduce emotional distress and enhance coping throughout the infertility treatments.

2. Materials and Methods

2.1. Participants

The study sample consisted of 21 couples (women and men) diagnosed with UI, recruited during an ART program at the Azienda Ospedaliera Universitaria Pisana (AOUP), Santa Chiara Hospital, Pisa, Italy. The median age was 35 years for women (IQR = 31–39) and 38 years for men (IQR = 34–40). Basic socio-demographic characteristics, including education level, are summarized in

Table 1. Descriptive statistics of demographic and psychometric variables for women and men. Values are reported as median and interquartile range (25th–75th percentile).

Variables		Women	Men
AGE (years)		35 (31–39)	38 (34–40)
EDUCATIONAL LEVEL (years)		18 (13–18)	13 (13–18)
DASS-21	Depression	6 (2–18)	4 (0–6)
	Anxiety	8 (4–12.5)	6 (1.5–6)
	Stress	14 (9.5–18.5)	10 (5.5–12)
PSS		19 (17–22)	17 (14–18)
DEFEAT SCALE		13 (8.5–20.25)	10 (5–15.25)
Core FertiQoL	Emotional	10 (2–11)	4 (1.75–6.25)
	Mind–Body	7 (4–11)	2 (0–6)
	Relational	5 (5–7.25)	6 (4.75–7)
	Social	8 (4.75–10.25)	6 (2.75–7.25)

and described in the Section 3. All participants were Italian-speaking and residing in Tuscany. Inclusion criteria required participants to be adults (age > 18), in a heterosexual couple undergoing diagnostic evaluation for unexplained infertility at the AOUP Santa Chiara Hospital in Pisa. Please note that, in accordance with Italian legislation (Law No. 40/2004), access to ART is limited to heterosexual couples. Exclusion criteria included the inability to complete the questionnaire and insufficient understanding or proficiency in the Italian language.

2.2. Recruitment Procedure

During their visit to the Santa Chiara Hospital (AOUP), couples were informed about the opportunity to participate in a research project. Participation was entirely voluntary, and those interested were invited to speak with trained psychologists in a separate room on the same floor, who supplied detailed explanations of the study’s objectives. Participants were provided with a tablet or computer to complete a structured questionnaire, which included the psychometric measures described in the Section 2.3 and a custom-designed questionnaire to collect demographic and clinical information. Participant recruitment took place between June and September 2023. The results of the study were based exclusively on the data from couples who provided explicit consent for data processing, representing 91% of the total participants. The study also included a second phase for participants who expressed interest, offering the opportunity to be recruited for a mindfulness-based intervention, which will be discussed in a separate article.

2.3. Measures

To assess psychological distress in unexplained infertility, we used several tools, as described below: the DASS-21 for affective symptoms (depression, anxiety, and stress), the Perceived Stress Scale (PSS) for subjective stress appraisal, the Defeat Scale for feelings of failure and social disconnection, and the Core-FertiQoL for fertility-related quality of life and functional well-being. Similar combinations of symptoms and quality-of-life scales have been used in prior infertility research (e.g., Rashidi et al., 2011; Musa et al., 2014). All tests were administered in their Italian versions, as all participants were native Italian speakers.

• Depression Anxiety Stress Scale—Short Version (DASS-21) (Henry & Crawford, 2005; Bottesi et al., 2015): a 21-item self-report questionnaire designed to assess three negative emotional constructs in adults: depression, anxiety, and stress. Each scale (Depression, Anxiety, Stress) contains seven specific items divided into subscales. Participants rate the presence of symptoms over the past seven days on a 4-point Likert scale, where 0 = “never” and 3 = “always”.
• Perceived Stress Scale (PSS) (Cohen et al., 1983): a tool that measures an individual’s perception of stress using simple, general questions about feelings and thoughts over the past month. This self-administered scale assesses the degree to which daily situations or events are perceived as unpredictable, uncontrollable, and stressful. Participants respond to 10 items on a 5-point Likert scale, where 0 = “never” and 4 = “very often”. The total score reflects the perceived stress level, classified as mild, moderate, or high.
• Defeat Scale (DS) (Gilbert & Allan, 1998): a 16-item self-report instrument assessing the sense of defeat, a negative emotional state characterized by feelings of hopelessness, helplessness, and loss of control. Each item evaluates these feelings over the past seven days on a 5-point Likert scale, from 1 = “never” to 5 = “always”.
• Core-Fertility Quality of Life (FertiQoL) (Boivin et al., 2011): This tool measures perceived quality of life during the experience of infertility across the following four domains.

  (4a)

  Emotional Scale (Em_QoL): Assesses the impact of negative emotions (e.g., jealousy, resentment, sadness, or depression) on quality of life.

  (4b)

  Mind–Body Scale (MndBdy_QoL): Evaluates the effect of infertility on physical health (e.g., fatigue, pain), cognition (e.g., concentration), and behavior (e.g., interruptions to daily activities or postponed life plans).

  (4c)

  Relational Scale (Rel_QoL): Examines how infertility affects marriage or partnership, exploring areas such as sexuality, communication, and mutual commitment.

  (4d)

  Social Scale (Soc_QoL): Measures the influence of infertility on social interactions, including social inclusion, expectations, stigma, and support.

The self-report instruments used in this study are validated tools with solid psychometric foundations both in their original and Italian versions. The Perceived Stress Scale—10 item version (PSS-10), originally by Cohen and Williamson (1988), showed good internal consistency (α = 0.84 in a U.S. general sample; α = 0.85 in students) and convergent validity with measures of depression and physical symptoms. The Italian version, validated by Mondo et al. (2019), reported a α value ranging between 0.74 and 0.85. The Depression Anxiety Stress Scales—21 item version (DASS-21), developed by Lovibond and Lovibond (1995), demonstrated high reliability (α = 0.91 Depression; 0.84 Anxiety; 0.90 Stress) and strong convergent validity with the Beck Depression and Anxiety Inventories. The Italian version validated by Bottesi et al. (2015), confirmed the three-factor structure and reported α values of 0.74, 0.82, and 0.85, respectively. The FertiQoL questionnaire, developed by Boivin et al. (2011), showed an internal consistency α = 0.92 for the Core module and 0.83 for the Treatment module. The Italian version (Donarelli et al., 2016), confirmed the questionnaire’s good reliability (α = 0.91 Core; 0.85 Treatment) and construct validity. The Defeat Scale, developed by Gilbert and Allan (1998), exhibited high internal consistency (α ≈ 0.94) and strong associations with depression and social rank constructs.

Additionally, data on participants’ age and education level were collected through a self-report ad hoc questionnaire administered before psychometric data collection. Participants self-identified as either women or men, in line with the binary gender categories used in this study.

2.4. Data Management and Analysis

In order to address both gender-level and dyadic-level psychological patterns, we performed two complementary sets of statistical analyses. First, we analyzed gender differences across the entire sample (women vs. men), treating female and male participants as independent groups. This approach allows general inferences about gender-related psychological differences. Second, to account for the relational structure of our data, we conducted paired comparisons within each couple (female partner vs. male partner), assessing the intra-dyadic contrast—relevant for capturing potential couple-level dynamics. Although some results are consistent across both approaches, we considered it important to present both analyses as they respond to distinct research questions and provide different yet complementary interpretative insights.

In the first phase of analysis, all variables (i.e., demographic and psychometric variables) were assessed for potential differences related to gender (women versus men), independently of the couple to which each participant belonged. The evaluation was performed using non-parametric statistical methods, as all variables, except for age, were discrete quantitative variables. Descriptive statistics are therefore presented as median and interquartile range (IQR), i.e., 25th–75th percentile. Gender differences (women vs. men) were analyzed using the Wilcoxon Rank Sum Test for independent samples (null hypothesis: no significant differences between women and men, irrespective of their respective partner).

Subsequently, gender differences were further investigated within the context of the couple by considering the “couple effect”. In this phase, intra-couple comparisons were performed using the Wilcoxon Signed Rank Test for paired samples (null hypothesis: no significant differences in the variable under evaluation between the female and male partner of each couple). Since the analyses were exploratory in nature, no corrections for multiple comparisons were applied. The threshold for statistical significance was set at p = 0.05. All analyses were conducted using customized code developed within the MATLAB environment (version 24.1, MathWorks, Natick, MA, USA), based on functions from the MATLAB Statistical Toolbox.

3. Results

3.1. Sample Description

The study sample included 21 couples, consisting of men and women diagnosed with UI. Participants ranged in age from 18 to 65 years. No statistically significant gender differences were observed in age or education level. Women had a median age of 35 years (IQR: 31–39) and men 38 years (IQR: 34–40), p = 0.11, z = –1.64 (Table 1). Regarding education, the median was 18 years for women (IQR: 13–18) and 13 years for men (IQR: 13–18), p = 0.25, z = 1.17 (Table 1). In matched comparisons (within couples), no significant difference was found in education (p = 0.40), and the age difference between male and female partners (p = 0.07, z = −1.85) did not reach statistical significance (

Table 2. Gender comparisons across psychological variables (Wilcoxon rank-sum test). For each test, the z-score and p-value are reported. Significant comparisons are highlighted in bold letters.

Variables		Test Statistics: Women vs. Men
		z-Score	p-Value
AGE		−1.64	<0.11
EDUCATIONAL LEVEL		1.17	<0.25
DASS-21	Depression	1.49	<0.14
	Anxiety	2.24	<0.03
	Stress	2.35	<0.02
PSS		2.70	<0.01
DEFEAT SCALE		1.48	<0.14
Core FertiQoL	Emotional	1.43	<0.16
	Mind–Body	2.20	<0.03
	Relational	0.06	<0.95
	Social	1.82	<0.07

).

3.2. Main Results

In the first set of analyses, we examined the existence of significant differences between women and men in the psychological variables under study, without considering the couple to which each subject belonged.

Regarding the DASS-21, stress and anxiety levels were found to be significantly higher in women as compared to men (p < 0.02, z = 2.35, and p < 0.03, z = 2.24, respectively), see Table 2). Conversely, no significant differences were observed between women and men in terms of depression levels (p < 0.14, z = 1.49).

The result concerning the level of stress is corroborated by the outcome of the PSS: indeed, perceived stress was significantly higher in women than in men (p < 0.01, z = 2.70). No significant between-gender difference was found in the scores of the Defeat Scale (p < 0.14, z = 1.48). The four subscales of the Core-FertiQol questionnaire were then analyzed: Emotional, Mind–Body, Relational, and Social. Women displayed significantly higher scores than men in the Mind–Body component (p < 0.03, z = 2.20). No significant differences emerged either for the Emotional (p < 0.16, z = 1.43), Relational (p < 0.95, z = 0.06), or Social (p < 0.07, z = 1.82) components.

In the second set of analyses, we examined the existence of significant differences between women and men for each variable, considering the couple to which each subject belonged (couple effect). In this case, pairwise comparisons between partners were made. Intra-couple comparisons were performed using the Wilcoxon Signed Rank Test for paired samples.

In the case of paired comparisons, the age of male partners was generally higher than that of female partners although the comparison did not reach the significance threshold (p < 0.07, z = −1.85); moreover, as in the previous analyses, no significant difference was found in the level of education (

Table 3. Paired comparisons between women and men (Wilcoxon signed-rank test). For each variable, z-scores and p-values are provided. Significant comparisons are highlighted in bold letters.

Variables		Intra-Pair Test Statistics
		z-Value	p-Value
AGE		−1.85	<0.07
EDUCATIONAL LEVEL		1.33	<0.19
DASS-21	Depression	1.80	<0.08
	Anxiety	2.09	<0.04
	Stress	2.18	<0.03
PSS		2.56	<0.01
DEFEAT SCALE		1.59	<0.12
Core FertiQoL	Emotional	2.07	<0.04
	Mind–Body	2.12	<0.04
	Relational	0.26	<0.80
	Social	1.60	<0.11

).

Also, when considering the paired comparisons for the DASS21, stress and anxiety levels were significantly higher in women as compared to men (p < 0.03, z = 2.18, and p < 0.04, z = 2.09, respectively). No significant difference was found in depression levels (p < 0.08, z = 1.80).

Similarly to the previous set of analysis, when considering within-couple comparisons, the perceived stress (PSS) was significantly higher in women than in men (p < 0.01, z = 2.56). No significant differences were found when considering the Defeat Scale’s scores (p < 0.12, z = 1.59).

The four subscales of the Core-FertiQoL questionnaire were finally considered: Emotional, Mind–Body, Relational, and Social. Women had significantly higher scores than men in both the Emotional (p < 0.04, z = 2.07) and Mind–Body (p < 0.04, z = 2.12) components. No significant differences were observed for the other two subscales, Relational (p < 0.80, z = 0.26) and Social (p < 0.11, z = 1.60).

To contextualize our findings, we compared participants’ scores with available Italian normative data. In a large non-clinical Italian sample, Mondo et al. (2019), reported a mean PSS-10 score of 18.98 (SD = 7.01), already higher than the international benchmark of 13.02 (SD = 6.35) reported by Cohen and Williamson (1988). In our sample, female participants had a median score of 19 (IQR = 17–22), and male participants had a median of 17 (IQR = 14–18). These values are consistent with the elevated stress levels already reported in the Italian general population and suggest that women may experience stress in the higher range of normative expectations. For the DASS-21, Bottesi et al. (2015), reported reference values from a non-clinical community sample, in which the mean scores were 5.18 (SD = 4.41) for Depression, 3.60 (SD = 3.44) for Anxiety, and 7.51 (SD = 4.86) for Stress. In our sample, female participants had median scores of 10 for Depression, 10 for Anxiety, and 20 for Stress—well above these normative values and within the mild-to-moderate clinical range according to Lovibond and Lovibond (1995). Male participants scored 6 for Depression, 6 for Anxiety, and 16 for Stress, also above community means but to a lesser extent. Unfortunately, normative data for the Defeat Scale are not available for the Italian population.

4. Discussion

Our findings reveal gender differences in psychological distress among individuals experiencing UI. Specifically, women reported significantly higher levels of anxiety and perceived stress than men, both in gender-level and within-couple comparisons. No significant gender differences were observed in depression scores or perceived quality of life. Both partners reported moderate levels of distress, with women consistently scoring higher across most measures. These patterns emerged in couples who had not yet undergone invasive ART procedures, highlighting that distress is already present in early stages of the process.

4.1. Key Findings: Gender Differences in Anxiety and Stress

In the initial phase of the analysis, we examined gender differences without considering couple pairing. Women reported significantly higher levels of anxiety and stress compared to men, as measured by the DASS-21 (p < 0.02, z = 2.35; p < 0.03, z = 2.24, respectively, see Table 2). No significant gender difference emerged in depression scores. This contrasts with studies showing higher depressive symptoms in women undergoing infertility treatment (Bogović et al., 2024; Musa et al., 2014). A plausible explanation is that our participants were still in the diagnostic phase and had not yet started invasive ART procedures, and as such depressive symptoms in the female group were still moderate. Depressive symptoms might intensify at later stages of the ART and even more after failed treatments, as suggested by longitudinal studies indicating peaks after 4–6 years of trying to conceive (Ramezanzadeh et al., 2004). Within-couple comparisons confirmed higher levels of anxiety and stress in women as compared to their partners (p < 0.03, z = 2.18; p < 0.04, z = 2.09, respectively) (Table 3). These results are consistent with the literature showing that women tend to report greater emotional distress in the context of UI (Martinelli & La Sala, 2009; Musa et al., 2014; Ho et al., 2020). Self-reported stress, as measured by the PSS, also showed a significant gender gap, with women reporting higher perceived stress in both group- and couple-level analyses (Table 2 and Table 3), in line with previous studies (Zaidouni et al., 2018; Keshavarz et al., 2018). When compared with Italian normative data (Bottesi et al., 2015), anxiety, depression, and stress scores were elevated—particularly among women—while men’s scores remained within mild ranges.

4.2. Coping Strategies and Emotional Resilience

The lack of significant gender differences in depression together with a higher quality of life score in the female group (Mind–Body dimension), despite clear differences in anxiety and stress, may reflect different coping styles between men and women. Although women in our sample reported higher distress overall, they may also be more likely to engage in adaptive coping strategies that mitigate the psychological burden of infertility. The literature suggests that women typically adopt emotion-focused and problem-focused coping strategies—such as seeking information, social support, and reframing—more frequently than men, who tend to rely on avoidance, denial, or passive behaviors, especially when male factor infertility is involved (Peterson et al., 2006; De Camillis, 2010). These gender-specific coping patterns might help explain why women, despite experiencing higher stress and anxiety, did not report either worse depression or lower quality of life. Emotion-focused coping strategies, such as distancing, acceptance, positive reappraisal, and support seeking, may facilitate a reinterpretation of the infertility experience as part of a broader personal growth process (Draye et al., 1988; De Camillis, 2010). Seeking social support has been shown to improve perceived quality of life among women with infertility (Yazdani et al., 2016; Zurlo et al., 2018). In line with these findings, psychological interventions that strengthen coping strategies—such as mindfulness-based programs—have demonstrated positive effects on emotional adjustment and well-being in infertile populations (Domar et al., 2015).

4.3. Shared Experience of Defeat

Regarding the Defeat Scale, no significant gender differences were found—either in between-gender comparisons (p < 0.14, z = 1.48), or in within-couple analyses (p < 0.12, z = 1.59) (Table 2 and Table 3). This suggests that infertility may represent a deeply disempowering experience for both partners, regardless of gender. Feelings of helplessness, social disconnection, and failure seem thus to be shared. Although research on gendered experiences of defeat in infertility is still limited, Galhardo et al. (2016), found that a stronger sense of defeat was associated with higher depressive symptoms, especially in individuals with a strong investment in parenthood. Similarly, Li et al. (2024) reported a link between feelings of defeat and lower marital satisfaction, reinforcing the importance of assessing this construct in couples undergoing fertility evaluation.

4.4. Depression and Quality of Life: Unexpected Trends

An unexpected finding of our study was the absence of significant gender differences in depression and perceived quality of life. However, several factors may explain these results. First, depression symptoms may develop more prominently in later stages of the infertility journey—especially after failed ART attempts—whereas our sample consisted of couples still at the diagnostic stage (Ramezanzadeh et al., 2004). Second, as noted earlier, women’s more frequent use of adaptive coping strategies might help mitigate the emotional impact of infertility and partially preserve quality of life (Peterson et al., 2006; Draye et al., 1988; De Camillis, 2010). In contrast, men may underreport depressive symptoms due to emotional inhibition or social desirability. Despite clear instructions and anonymous participation, it is possible that both partners, especially at this early and uncertain stage, minimized their distress to avoid being perceived as psychologically vulnerable. This may be relevant in the context of infertility, where participants could be concerned that revealing psychological difficulties might influence medical decisions or eligibility during the diagnostic process.

4.5. Clinical Implications and Mindfulness-Based Interventions

Although this is a small pilot study, one key strength lies in the dual-level analysis (between-gender and intra-couple), which allowed us to explore psychological functioning not only at the gender-level but also in the relational dynamics of couples facing unexplained infertility. While the limited sample size precludes broad generalizations, our findings suggest that women are more vulnerable to psychological distress but may also be more likely to adopt effective coping strategies that help preserve aspects of quality of life. These preliminary insights have potential clinical relevance as they suggest that psychological support in infertility care should be both gender-sensitive and couple-oriented. Interventions should thus consider not only individual distress but also how partners cope together with the shared experience of infertility. In this regard, mindfulness-based interventions (MBIs), may be particularly beneficial. Indeed, accumulating evidence shows that MBIs can promote emotional regulation, improve communication, and strengthen relational well-being—factors that may contribute to better psychological outcomes and indirectly support treatment adherence and success (Galhardo et al., 2013; Patel et al., 2020; Massaro, 2021; Kundarti et al., 2023; Wang et al., 2023).

5. Strengths, Limitations, and Future Directions

These findings, although preliminary, provide valuable insight into the psychological experience of unexplained infertility in couples. One strength of the study lies in the dual-level analysis (between-group and dyadic), which allowed us to explore both personal and relational aspects of distress.

This study also presents several limitations. First, the sample consisted of only 21 couples, which limits the generalizability of the findings herein described. Such a small sample size may not adequately reflect the demographic and psychological diversity of the broader population undergoing ART. Second, the use of self-report measures to assess psychological variables may introduce response biases. Third, information regarding previous offspring was not collected in the present study. As this variable may represent a relevant background factor, its potential impact should be explored in future research. Another important limitation is the absence of a control group composed of couples not undergoing ART. Although couple-level effects were considered in the second part of the analysis, individual data may still be influenced by interpersonal dynamics and patterns of mutual support, which can vary considerably between couples. In addition, the study did not control other potentially influential factors, such as external social support, previous infertility experiences, or the number of prior ART cycles—all of which may substantially impact psychological well-being. The couples who chose to participate in the study may also differ in important psychological or socioeconomic characteristics from those who declined to participate, introducing a potential selection bias that could limit the external validity of the results. Finally, participants in our study self-identified as either women or men, in line with the binary categories adopted. We acknowledge that this approach does not capture the full spectrum of gender identities, and future research should consider more inclusive frameworks to reflect the diversity of individuals and couples affected by infertility.

Future studies should aim to replicate these findings in larger and more diverse samples, examine the evolution of psychological distress throughout the different stages of the ART process, and evaluate the effectiveness of tailored psychological interventions—particularly those based on mindfulness and dyadic support. We also recognize that cultural, historical, and contextual factors—such as regional differences in gender roles and expectations around parenthood—may shape the psychological experience of infertility. These aspects should be further explored to understand how socio-demographic and cultural variables interact with gendered responses in this context.

6. Conclusions

This study confirms that UI is associated with significant psychological distress, especially among women, who reported higher levels of stress, anxiety, and perceived stress. Nonetheless, women also showed relatively higher quality of life in some domains (lower presence of negative emotions as well as of physical and other behavioral symptoms), possibly due to more adaptive coping strategies. These findings highlight the importance of integrated psychological support in infertility care, aimed at enhancing emotional regulation and relational well-being.