Sex-specific associations between psychological resilience and blastocyst quality

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This work was supported by Al Hadi Laboratory and Medical Center.

Baseline demographic, clinical, semen, and embryological characteristics are summarized in Table 1 . Women had a median age of 31 years (IQR: 7), and men had a median age of 35 years (IQR: 8). The median fertilization and blastulation rates were 75% (IQR: 42.8) and 50% (IQR: 47.5), respectively. Baseline characteristics of women and men, semen parameters and embryological outcomes. Values are reported as median (IQR) or as mean ± SD for continuous variables and as n (%) for categorical variables. BMI, body mass index (kg/m²); PCOS, polycystic ovary syndrome; ICSI, intracytoplasmic sperm injection; COC, cumulus–oocyte complexes. Good-quality blastocysts were defined as ≥3BB (Gardner & Schoolcraft classification). Resilience levels were significantly higher in men (median CD-RISC-10 score: 30 (IQR: 7)) than in women (median CD-RISC-10 score: 27 (IQR: 9)) (Wilcoxon signed-rank test: Z = −3.97, P < 0.001) ( Fig. 2A ). Resilience levels in men and women were positively correlated (Spearman’s rho ρ = 0.23, P = 0.008). Resilience scores were not associated with demographic or clinical characteristics in either sex (all P > 0.05) (Supplementary Table 2). Psychological resilience and gamete-related parameters. (A) Distribution of CD-RISC-10 total scores in women and men presented as box-and-whisker plots. The boxes represent the interquartile range (IQR), the horizontal line indicates the median, and the crosses indicate the mean. Whiskers extend to 1.5 × IQR, with values beyond this range shown as outliers. *** P < 0.001 for the comparison between women and men. (B) Representative bright-field microscopy images of spermatozoa stained with aniline blue. Spermatozoa with increased histone retention exhibit blue-stained nuclei (aniline blue-positive), whereas spermatozoa with normal protamination remain unstained (aniline blue-negative). (C) Correlation matrix showing Spearman correlation coefficients between male psychological resilience and sperm parameters, including total motility, normal morphology, total sperm count, and aniline blue positivity. * P < 0.05; ** P < 0.01; *** P < 0.001. (D) Forest plot of correlations between female psychological resilience and oocyte-related outcomes. The points represent Spearman correlation coefficients, and the horizontal lines indicate 95% confidence intervals for associations with the number of cumulus–oocyte complexes, number of metaphase II oocytes, and maturation rate. Male resilience was associated with sperm parameters, showing a positive correlation with normal morphology ( ρ = 0.28, P = 0.001) and a negative correlation with aniline blue positivity ( ρ = −0.26, P = 0.024). In addition, total motility and total sperm count were strongly interrelated ( ρ = 0.71, P < 0.001) and were each associated with morphology ( ρ = 0.42, P < 0.001, and ρ = 0.35, P < 0.001, respectively) and aniline blue positivity ( ρ = 0.32, P < 0.01, and ρ = −0.33, P < 0.01, respectively) ( Fig. 2B and C ). In contrast, female resilience was not associated with the number of collected COCs ( ρ = −0.09, P = 0.29), the number of MII oocytes ( ρ = −0.04, P = 0.61), or maturation rate ( ρ = 0.07, P = 0.39) ( Fig. 2D ). After adjustment for male age, female age, female BMI, number of MII oocytes, total sperm count, and total motility, male resilience remained positively associated with the adjusted good-quality blastocyst development rate ( B = 0.06, 95% CI: 0.01–0.11, P = 0.02), corresponding to an approximately 6% higher expected rate for each 1-point increase in male resilience score. The overall model was statistically significant (likelihood ratio chi-square = 17.6, df = 7, P = 0.01) ( Fig. 3A ; Supplementary Table 3A). Psychological resilience and good-quality blastocyst development. Forest plots of adjusted regression coefficients (B) and 95% confidence intervals for associations between resilience and good-quality blastocyst development rate from multivariable Gamma regression models with a log link. Panels (A) and (B) show the main models for male and female resilience, respectively, each adjusted for male age, female age, female body mass index, number of MII oocytes, total sperm count, and total motility. Panels (C) and (D) show sensitivity analyses of the male resilience model with additional adjustment for varicocelectomy and smoking status, and for aniline blue-positive percentage, respectively. The vertical line at B = 0 indicates the null value. In the adjusted model, female resilience was not associated with the adjusted good-quality blastocyst development rate ( B = −0.02, 95% CI: −0.06–0.02, P = 0.33). The overall model was not statistically significant (likelihood ratio chi-square = 13.18, df = 7, P = 0.06) ( Fig. 3B ; Supplementary Table 3B). In a sensitivity analysis including additional adjustment for smoking status and varicocelectomy, male resilience remained positively associated with the good-quality blastocyst development rate ( B = 0.06, 95% CI: 0.01–0.11, P = 0.01) ( Fig. 3C , Supplementary Table 4A). The overall model was statistically significant (likelihood ratio chi-square = 19.3, df = 8, P = 0.02). In the subset with available aniline blue measurements ( n = 74), male resilience remained positively associated with the good-quality blastocyst development rate ( B = 0.07, 95% CI: 0.006–0.146, P = 0.03), whereas aniline blue positivity was inversely associated with the outcome ( B = −0.05, 95% CI: −0.09 to −0.01, P = 0.009) ( Fig. 3D ; Supplementary Table 4B). In an additional sensitivity analysis using a binomial GLM with logit link, in which the number of good-quality blastocysts was modeled as the number of events and the number of 2PN embryos as the binomial denominator, male resilience remained significantly associated with good-quality blastocyst development ( B = 0.055, 95% CI: 0.014–0.095, P = 0.008). The overall model was statistically significant (likelihood ratio chi-square = 28.52, df = 7, P < 0.001; AIC = 284.58), supporting the robustness of the primary findings (Supplementary Table 4C). In adjusted binomial models, neither male nor female resilience was independently associated with the fertilization rate (Supplementary Table 5A and B). In adjusted binomial models for blastulation rate, neither male nor female resilience was independently associated with the probability of blastocyst formation (Supplementary Table 5C and D).

This was a prospective observational study of infertile couples undergoing ICSI ( n = 126). Psychological resilience was assessed separately in both men and women on the day of oocyte retrieval. The primary outcome was day 5 good-quality blastocyst development rate, while secondary outcomes included fertilization rate and blastulation rate ( Fig. 1 ). The study was conducted out at a single fertility center between May 2024 and November 2025. It was reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Supplementary Table 1; see the section on Supplementary materials given at the end of the article). Study design. Prospective observational study including 126 infertile couples undergoing intracytoplasmic sperm injection. Psychological resilience was assessed separately in men and women on the day of oocyte retrieval using in-person interviews. Semen analysis was performed according to World Health Organization (2021) guidelines, and oocyte-related parameters, including the numbers of cumulus–oocyte complexes and metaphase II (MII) oocytes, were recorded. Couples meeting the exclusion criteria were not included. Embryological outcomes were evaluated following intracytoplasmic sperm injection, with the day 5 good-quality blastocyst development rate as the primary outcome. Ethical approval was obtained from the Ethics Committee of Al-Hayat Hospital, Beirut, Lebanon (approval number: ETC-16-2024), and the study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from both partners before participation, and couples were informed that participation was voluntary and would not affect their clinical care. Couples were eligible if they were undergoing ICSI using fresh autologous gametes and if the female partner was aged 20–39 years. In-person interviews were conducted with each participant ( n = 126 couples) to collect medical history and assess psychological resilience. Couples were excluded if the female partner was aged > 39 years, had obesity (body mass index (BMI) ≥ 30 kg/m 2 ), or had fewer than three oocytes retrieved, to reduce the potential confounding effects of advanced maternal age, obesity, and poor ovarian response on embryo development ( Ribeiro et al. 2022 , Cimadomo et al. 2023 , Vitagliano et al. 2023 ). Additional exclusion criteria included severe male factor infertility (sperm concentration < 1 × 10 6 /mL); use of testicular, epididymal, or donor sperm; and incomplete questionnaire data, to ensure a relatively homogeneous study population and avoid procedural factors that could independently influence blastocyst quality ( Raad et al. 2018 , Colaco & Modi 2024 ). Psychological resilience was assessed using the 10-item Connor–Davidson Resilience Scale (CD-RISC-10), a validated self-report instrument widely used to measure individual resilience. Each item is rated on a 5-point Likert scale ranging from 0 (‘not true at all’) to 4 (‘true nearly all the time’), yielding a total score between 0 and 40, with higher scores indicating greater resilience ( Campbell-Sills & Stein 2007 ). The CD-RISC-10 instructions refer to experiences over the preceding 30 days, indicating that the score reflects a broader recent adaptive psychological profile rather than a purely acute psychological state. An Arabic version of the CD-RISC-10, previously validated in the general Arabic-speaking population, was used with authorization from the scale developers and the authors of the Arabic validation ( Fekih-Romdhane et al. 2024 ). The questionnaire was self-administered separately by both men and women on the day of oocyte retrieval, before ICSI. Scores were calculated by summing responses to all items. In accordance with the developers’ recommendations, CD-RISC-10 scores were analyzed as a continuous variable, as no established clinical cut-off exists for categorizing resilience levels. Clinical and demographic data were collected from both partners at the time of enrollment. For women, data included age, BMI, infertility etiology (polycystic ovary syndrome, tubal factor, endometriosis), history of uterine surgery (polypectomy, myomectomy), primary infertility, previous pregnancy losses, previous ICSI attempts, smoking status, and alcohol consumption. For men, data included age, BMI, history of orchidopexy, varicocelectomy, or inguinal hernia repair, primary infertility, previous pregnancy losses, previous ICSI attempts, smoking status, and alcohol consumption. Semen analysis was performed after 2–5 days of sexual abstinence in accordance with the World Health Organization laboratory guidelines ( WHO 2021 ). Semen analysis reporting adhered to the checklist proposed by Björndahl et al. to ensure the acceptability of human semen analysis studies ( Björndahl et al. 2016 ) (Supplementary material 1, checklist for authors 2023). Moreover, sperm histone retention was assessed using aniline blue staining. Embryological variables collected included the number of cumulus–oocyte complexes retrieved, proportion of mature oocytes, fertilization rate, blastulation rate, and good blastocyst development rate ( ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine 2017 , Coticchio et al. 2025 ). Two embryologists performing sperm and embryo assessments were blinded to psychological resilience scores. Controlled ovarian stimulation was performed using a gonadotropin-releasing hormone (GnRH) antagonist protocol. Ovarian stimulation was initiated on day 2 of the menstrual cycle with human menopausal gonadotropin (HMG; Merional, IBSA, Switzerland). From stimulation day 6 onwards, a GnRH antagonist (cetrorelix acetate; Cetrotide, Merck Serono, Germany) was administered daily. Final oocyte maturation was triggered with highly purified human chorionic gonadotropin (hCG; Choriomon, IBSA, Switzerland) when at least three follicles reached a mean diameter of ≥ 16 mm ( Motawi et al. 2017 ). Oocyte retrieval was performed 34–36 h after the trigger by transvaginal ultrasound-guided aspiration under conscious sedation ( D’Angelo et al. 2019 ). Following retrieval, cumulus–oocyte complexes (COCs) were cultured for 2 h in Global Total LP fertilization medium (LifeGlobal, CooperSurgical, Denmark) under an oil overlay at 37°C before enzymatic denudation using hyaluronidase (LifeGlobal, CooperSurgical, Denmark). The proportion of mature oocytes was calculated as the number of metaphase II (MII) oocytes divided by the total number of COCs retrieved ( ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine 2017 ). Semen samples were collected by masturbation on the day of oocyte retrieval in a dedicated private room within the laboratory. Following collection, samples were kept at 37°C until liquefaction was complete, in accordance with international guidelines ( Björndahl et al. 2016 , WHO 2021 ) (Supplementary material 1, checklist for authors 2023). Sperm concentration was quantified using an improved Neubauer hemocytometer. Motility was assessed by light microscopy at 37°C by evaluating a minimum of 200 spermatozoa and classifying them as progressive, non-progressive, or immotile. Sperm morphology was assessed on stained smears prepared using the Spermoscan kit (Ral Diagnostics, France) ( Yamdjeu et al. 2024 ), and defects were classified according to Kruger’s strict criteria. Sperm histone retention was assessed using the aniline blue staining method, which distinguishes lysine-rich histones from arginine- and cysteine-rich protamines. Semen samples ( n = 74) were smeared (10 μL) onto glass slides, air-dried, and fixed in 3% glutaraldehyde (Sigma-Aldrich Co., USA) in phosphate-buffered saline for 30 min. Slides were then stained with 5% aqueous aniline blue solution (pH 3.5) (Sigma-Aldrich Co., USA) for 5 min. Spermatozoa with increased histone retention exhibited blue-stained nuclei, whereas those with normal protamination remained unstained. The proportion of aniline blue-positive spermatozoa was determined by evaluating 200 cells per slide under bright-field microscopy ( Le Lannou & Blanchard 1988 ). After liquefaction, semen samples were prepared using a two-layer density gradient centrifugation technique (50 and 90%; ISolate Sperm Separation Medium, Irvine Scientific, USA). After centrifugation, the sperm pellet was washed in sperm washing medium (Irvine Scientific, USA) and resuspended for use in ICSI and subsequent sperm analyses. ICSI was performed according to standard laboratory procedures. Motile spermatozoa were mechanically immobilized in polyvinylpyrrolidone solution (10% PVP; Fujifilm, Irvine Scientific, USA) and injected individually into mature oocytes in HEPES-buffered medium (LifeGlobal, CooperSurgical, Denmark) under light mineral oil. Following ICSI, injected oocytes were placed in Oosafe culture dishes (SparMed, Denmark) using a mixed culture format with Global Total LP medium (LifeGlobal, CooperSurgical, Denmark) under light mineral oil (LifeGlobal, CooperSurgical, Denmark). Culture was performed in a G210 InviCell incubator (K-System, Germany) at 37°C in an atmosphere of 5% O 2 and 5% CO 2 , with uninterrupted incubation for 5 days ( Raad et al. 2025 ). Fertilization was assessed at approximately 16–18 h post-ICSI ( Coticchio et al. 2025 ). Embryo development was monitored until day 5, when blastulation and blastocyst morphology were evaluated (approximately 116 ± 2 h post-insemination) ( Coticchio et al. 2025 ). Blastocyst grading was performed according to the Gardner and Schoolcraft classification system ( Coticchio et al. 2025 ). Good-quality blastocysts were defined as those with an expansion stage ≥ 3 and inner cell mass and trophectoderm grades of A or B (≥3BB) ( ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine 2017 , Coticchio et al. 2025 ). The primary outcome was day 5 blastocyst quality, expressed as the good blastocyst development rate (≥3BB) ( ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine 2017 , Coticchio et al. 2025 ). Secondary outcomes included fertilization rate and blastulation rate. Fertilization rate was calculated as the number of normally fertilized oocytes (2 pronuclei and 2 polar bodies) divided by the number of injected MII oocytes. Blastulation rate was calculated as the number of blastocysts formed divided by the number of normally fertilized oocytes (2PN). Good blastocyst development rate was calculated as the number of good-quality blastocysts on day 5 (≥3BB) divided by the number of normally fertilized oocytes (2PN), with all values expressed as percentages ( ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine 2017 , Coticchio et al. 2025 ). An a priori sample size calculation was performed in G*Power 3.1 ( Faul et al. 2007 ), using a multiple regression framework with six predictors as a planning approximation for the primary generalized linear model. Assuming a small effect size ( f 2 = 0.10), α = 0.05 (two-sided), and 95% power, the minimum required sample size was n = 110. The final sample comprised 126 couples, exceeding this target. All analyses were performed using SPSS (IBM SPSS Statistics, version 26, IBM Corp., USA). Normality of continuous variables ( n = 126 couples) was assessed using the Shapiro–Wilk test. Continuous variables were found to be non-normally distributed and are therefore presented as median (interquartile range (IQR)), whereas categorical variables are presented as percentages. Resilience levels were compared between partners using the Wilcoxon signed-rank test. Associations between resilience scores and continuous clinical variables, including the correlation between male and female resilience scores, were assessed using Spearman’s rank correlation coefficient. Differences in resilience scores across categorical variables were evaluated using the Mann–Whitney U test or Kruskal–Wallis test, as appropriate. The primary outcome was analyzed using generalized linear models (GLMs) with a gamma distribution and log link because of the non-normal, right-skewed distribution of the outcome. The primary outcome was the good-quality blastocyst development rate (≥3BB), originally expressed as a percentage and converted to a continuous scale from 0 to 1. Because the outcome included zero values, a standard zero-adjustment transformation was applied to shift zeros to small positive values while preserving rank order ( y adj = ( y ( n − 1) + 0.5)/ n , where n is the sample size), thereby enabling gamma modeling. Multivariable models were adjusted for female age, male age, number of metaphase II oocytes, female BMI, total sperm count, and total motility. Covariates were selected a priori as plausible confounders of the resilience–blastocyst association. Additional confounding was minimized by design through eligibility criteria restricting maternal age, BMI, oocyte yield, and severe male factor infertility. Because resilience scores in men and women were correlated, male and female resilience were analyzed in separate models as the primary approach. As sensitivity analyses, the primary multivariable model for male resilience was additionally adjusted for smoking status and history of varicocelectomy and was repeated in the subset with available aniline blue measurements, including aniline blue positivity as a covariate. In addition, because the primary outcome represented a developmental rate derived from embryo counts, the model was repeated using a binomial generalized linear model with logit link, specifying the number of good-quality blastocysts graded ≥3BB as the number of events and the number of 2PN embryos as the binomial denominator. The same predictors as in the primary model were retained. Results are reported as regression coefficients with 95% confidence intervals and corresponding P values. Model fit was assessed using likelihood ratio chi-square statistics and Akaike’s information criterion. Male and female CD-RISC-10 scores were modestly correlated; therefore, they were evaluated primarily in separate multivariable models to preserve model stability and allow sex-specific interpretation. Given sperm selection during ICSI, baseline morphology was not included in the main multivariable model. Aniline blue positivity was evaluated only in sensitivity analyses because measurements were available in a smaller subset of patients ( n = 74). Therefore, total motility and total sperm count were used as semen-related covariates in the primary analysis. For the secondary outcomes, fertilization rate was analyzed using binomial generalized linear models with logit link, specifying the number of 2PN embryos as events and the number of MII oocytes as trials. Blastulation rate was analyzed using binomial generalized linear models with logit link, specifying the number of blastocysts as events and the number of 2PN embryos as trials. Adjusted models included female age, male age, female BMI, total sperm count, total motility, and either male or female resilience score. In the blastulation models, the number of MII oocytes was additionally included as a covariate. Cases with invalid events for the binomial models were excluded automatically by SPSS. All statistical tests were two-sided, and P < 0.05 was considered statistically significant.

In conclusion, this study identified a positive association between male psychological resilience and good-quality blastocyst development in ICSI cycles, whereas no such association was observed in women. These findings support the hypothesis that psychological factors may be reflected in biological processes relevant to reproduction and highlight the need for further interdisciplinary research integrating psychosomatic and reproductive biology approaches.

In this prospective observational study, higher psychological resilience in men, but not in women, was independently associated with a higher day 5 good-quality blastocyst development rate following intracytoplasmic sperm injection. This association remained significant after multivariable adjustment and in sensitivity analyses. Male psychological resilience was also associated with sperm characteristics, including morphology and chromatin maturity. From a psychosomatic perspective, these findings suggest that individual differences in psychological resilience may be reflected in biological parameters in patients undergoing infertility treatment. One possible explanation for this association relates to the expanding understanding of paternal contributions to early embryonic development. The traditional view of the spermatozoon as solely a vehicle for the paternal haploid genome has evolved, with increasing interest in broader paternal contributions to embryogenesis ( Tarozzi et al. 2021 ). Consistent with this, a growing body of evidence supports the hypothesis that sperm-related factors may influence embryo cleavage, blastocyst development, and subsequent reproductive outcomes ( Kaiyal et al. 2025 , Quintana-Vehí et al. 2026 ). In this context, the association observed in our study between male resilience and day 5 blastocyst quality may be related to its association with sperm characteristics. Of particular interest, male psychological resilience in the present study was associated with multiple markers of sperm quality. These findings are consistent with several studies reporting associations between psychological factors and sperm characteristics ( Clarke et al. 1999 , Bártolo et al. 2016 , Shao et al. 2025 ). One possible biological interpretation is that stress-related activation of the hypothalamic–pituitary–adrenal axis leads to increased glucocorticoid levels. These may impair testicular function by suppressing the hypothalamic–pituitary–gonadal axis and reducing gonadotropin secretion. In addition, glucocorticoids may directly affect Leydig and Sertoli cells through receptor-mediated mechanisms, including the induction of oxidative stress and apoptosis, thereby disrupting steroidogenesis, spermatogenesis, and sperm protamination ( Raad et al. 2021 a , Kaltsas et al. 2026 , Sengupta et al. 2026 ). In parallel, low resilience has been associated with increased oxidative stress and mitochondrial dysfunction. These alterations may contribute to a cascade of physiological disturbances, potentially reducing semen quality ( Russo et al. 2012 , Imai et al. 2019 , Trtica Majnarić et al. 2021 , Vahedi Raad et al. 2024 , Lahimer et al. 2025 ). These processes may not only influence conventional semen parameters but may also affect the molecular integrity of spermatozoa. Beyond genetic information, the mature spermatozoon is thought to contribute epigenetic elements of the sperm epigenome that are transmitted at fertilization, including DNA chemical modifications, retained histones with post-translational modifications, and non-coding RNAs ( Caroppo & Skinner 2024 ). Emerging data from both animal and human studies suggest that these epigenetic features may participate in the regulation of pre-implantation embryo development and the transmission of acquired psychological or metabolic conditions to offspring ( Guo et al. 2014 , Bohacek & Mansuy 2015 , Yeshurun & Hannan 2019 , Santiago et al. 2022 , Dodd & Luense 2024 , Hoffmann et al. 2024 , Isacson et al. 2025 ). In the present study, male psychological resilience was associated with sperm chromatin composition as assessed by aniline blue staining. The latter specifically detects retained histones, indicating incomplete protamine replacement during spermiogenesis. Beyond their structural role in DNA packaging and protection during transit through the female reproductive tract, retained histones are also components of the sperm epigenome and are involved in the regulation of early embryo development ( Kim et al. 2013 , Raad et al. 2019 , Cambiasso et al. 2024 , Gomes et al. 2025 ). Within this framework, experimental studies, largely derived from animal models, suggest that paternal exposure to psychological or metabolic stress may influence embryo development and offspring health through epigenetic modifications of spermatozoa ( Bohacek & Mansuy 2015 , Short et al. 2016 , Yeshurun & Hannan 2019 , Zheng et al. 2021 , Champroux et al. 2024 , Hoffmann et al. 2024 , Morgan et al. 2024 ). Stress-related neuroendocrine and metabolic alterations have been proposed to affect these epigenetic processes ( Dias & Ressler 2014 , Zheng et al. 2021 , Hoffmann et al. 2024 ). At the molecular level, stress-related signals, including glucocorticoids, inflammatory cytokines, and metabolic mediators, may interact with receptors expressed in male germ cells and testicular somatic cells ( Bohacek & Mansuy 2015 , Hoffmann et al. 2024 ). These signaling pathways can modulate the activity of key epigenetic enzymes, including DNA methyltransferases, ten-eleven translocation enzymes, and histone-modifying enzymes, thereby influencing the cellular epigenome ( Martins de Carvalho et al. 2021 , Persaud & Cates 2023 , Poggi et al. 2026 ). In humans, direct evidence associating paternal psychological characteristics with embryological outcomes remains limited. However, observational studies have reported associations between adverse paternal experiences, including psychological trauma, and altered sperm epigenetic profiles. Specifically, childhood abuse and early-life stress have been associated with differential sperm DNA methylation and altered non-coding RNA content in adult men ( Dickson et al. 2018 , Roberts et al. 2018 ). Together, these observations indicate that paternal psychological exposures may be reflected in measurable molecular changes in human sperm, although their implications for early embryonic development remain to be fully established. In parallel, no independent association was observed between female psychological resilience and blastocyst quality in this study. This finding contrasts with experimental animal models reporting adverse effects of maternal stress on early embryo development ( Liu et al. 2012 , Burkuš et al. 2015 , Dehdehi et al. 2020 , Zhao et al. 2021 ). Several biological and treatment-related factors may account for this discrepancy between experimental and clinical observations. In particular, mitochondrial adaptive capacity within oocytes may confer resilience to moderate stress-related perturbations by enabling dynamic bioenergetic and redox responses that help preserve developmental competence ( Picard & McEwen 2018 , Raad et al. 2021 b ). Moreover, in the context of MAR, the supraphysiological gonadotropin and steroid environment of controlled ovarian stimulation may act as potent survival and mitotic signals ( Abbara et al. 2019 , Casarini & Crépieux 2019 ), potentially attenuating stress-related effects on oocyte competence. Consistent with previous couple-based studies in infertility, men in the present cohort had higher psychological resilience scores than women, a pattern reported across several cultural settings and commonly attributed to differences in coping strategies, perceived responsibility for infertility, and the differential psychosocial and treatment-related demands experienced by women ( Zhang et al. 2021 , Liu et al. 2024 ). The present findings extend the existing literature by suggesting that psychological resilience may also be associated with biological parameters relevant to reproduction, particularly in men. Nevertheless, this study had several limitations. The observational and single-center design limits causal inference and generalizability. Moreover, the strict eligibility criteria may limit the generalizability of these findings to the broader IVF population, including women of advanced reproductive age, those with obesity or diminished ovarian reserve, and couples with severe male factor infertility. In addition, ovarian reserve markers and stimulation characteristics were not included as separate covariates. Their effects are likely to be partly captured by the number of MII oocytes retrieved, although residual confounding cannot be excluded ( Esteves et al. 2020 ). Physiological markers related to stress biology, such as inflammatory or oxidative stress biomarkers, were also not assessed. Therefore, the biological mechanisms underlying the observed associations remain speculative. Future investigations integrating psychological resilience assessments with molecular or biochemical markers are needed to clarify these pathways. Psychological resilience was assessed at a single time point on the day of oocyte retrieval. Although the CD-RISC-10 reflects resilience over the preceding 30 days rather than an acute psychological state, a single assessment may not fully capture psychological exposure throughout spermatogenesis and folliculogenesis. Resilience was assessed after completion of the routine infertility workup; therefore, participants’ prior knowledge of their fertility status, including semen quality, may have influenced their resilience scores. The cross-sectional design precludes determining the direction of this potential influence. Furthermore, resilience is a multidimensional construct, and the present analysis did not examine specific components, such as coping strategies, optimism, social support, or cognitive and emotional flexibility ( Southwick et al. 2023 ). Future studies should assess whether particular dimensions of resilience are differentially associated with reproductive outcomes in men and women. If confirmed, these findings may inform the design of gender-sensitive interventional studies, including randomized controlled trials, in MAR.

Infertility and medically assisted reproduction (MAR) are widely recognized as psychologically demanding experiences for affected patients ( Salari et al. 2024 , Gu et al. 2025 ). Systematic reviews and meta-analyses report a high prevalence of psychological distress, including stress-related symptoms, among patients undergoing MAR ( Salari et al. 2024 , Gu et al. 2025 ). Psychological stress can disrupt reproductive biology through sustained activation of stress–response pathways, leading to alterations in gonadotropin release, sex steroid production, and local gonadal function. Both the testes and ovaries are sensitive to stress-related neuroendocrine and inflammatory signals, which may impair gamete quality, follicular development, and endometrial receptivity, thereby influencing fertilization and implantation processes ( Raad et al. 2021 a ). Against this background, psychological resilience has been increasingly examined as a protective factor in infertility and MAR ( Khan et al. 2023 , Liu et al. 2024 ). Psychological resilience is a dynamic, multilevel adaptive process that enables individuals to maintain or regain adaptive functioning following exposure to significant stress or trauma ( Denckla et al. 2020 ). From a neurobiological perspective, resilience reflects the capacity of interacting brain and body systems to respond to stress in a temporally coordinated and adaptive manner. Immediately following stress exposure, activation of the sympathetic nervous system leads to rapid adrenaline and noradrenaline release, supporting arousal and vigilance. This response is short-lived and rapidly terminated ( Watanabe & Takeda 2022 ). This is followed by engagement of the hypothalamic–pituitary–adrenal axis, resulting in an increase in cortisol secretion that peaks within minutes and is efficiently downregulated thereafter. Concurrently, stress-responsive neural circuits involving the amygdala, hippocampus, and prefrontal cortex are dynamically engaged, with monoaminergic neurotransmission (e.g. dopamine, serotonin, and noradrenaline) supporting emotional regulation and cognitive flexibility. In resilient individuals, these responses are characterized by timely activation and effective resolution rather than sustained dysregulation ( Watanabe & Takeda 2022 ). In this context, systematic reviews, synthesizing mainly cross-sectional studies, consistently show that higher resilience is associated with lower infertility-related stress, anxiety, and depressive symptoms, as well as better fertility-related quality of life in both women and men undergoing MAR ( Khan et al. 2023 , Liu et al. 2024 ). Notably, existing research has focused almost exclusively on psychological outcomes, and no human studies have investigated whether psychological resilience is associated with embryological outcomes or underlying gamete-related parameters. Of particular interest, lower psychological resilience has been associated with increased inflammatory activity and oxidative stress ( Aschbacher et al. 2013 , Imai et al. 2019 , Trtica Majnarić et al. 2021 , Bennett et al. 2024 ). These pathways provide a plausible biological mechanism through which individual differences in resilience may extend beyond psychological adaptation to influence gamete competence and embryo development during MAR ( Martin et al. 2022 , Paira et al. 2022 , Câmara et al. 2025 , Tariq et al. 2025 ). Nevertheless, the impact of psychological resilience in both men and women undergoing MAR on embryological outcomes remains unclear. The primary objective of this study was to investigate whether psychological resilience in men and women undergoing intracytoplasmic sperm injection is associated with blastocyst quality. In addition, we explored associations between psychological resilience and gamete-related parameters, as well as fertilization and blastulation rates.

M Serdaroğulları is an Associate Editor of Reproduction & Fertility and was not involved in the peer review or editorial process for this paper, on which she is listed as an author. The authors declare no financial, commercial, or personal conflicts of interest that could be perceived to influence the work reported in this manuscript.

The data underlying this article cannot be shared publicly due to ethical and privacy considerations related to the study participants. De-identified data will be made available on reasonable request to the corresponding author.

GR and ChF conceived the study. GR, FI, and GEA acquired the data. GR, ZY, and MS performed formal analysis. GR designed the methodology. GR, GhGh, ZY, MS, YM, JELA, AN, and ChF wrote, reviewed, and edited the manuscript. AN, ChF, and YM supervised the study. All authors contributed to the interpretation of the data, critically revised the manuscript for important intellectual content, approved the final version for publication, and agree to be accountable for all aspects of the work.