{"paper_id":"d704ab39-7e1b-4b47-83be-115620e22321","body_text":"RESEARCH Open Access\n© The Author(s) 2024. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, \nsharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and \nthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this \narticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included \nin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will \nneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The \nCreative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available \nin this article, unless otherwise stated in a credit line to the data.\nMori et al. BMC Women's Health          (2024) 24:251 \nhttps://doi.org/10.1186/s12905-024-03080-5\nBMC Women's Health\n*Correspondence:\nVictor Zaia\nvictor.zaia@fmabc.br\n1Programa de Pós-graduação em Ciências da Saúde, Centro Universitário \nFMABC, Av. Lauro Gomes, Santo André 2000, 09060-870, SP , Brazil\n2Instituto Ideia Fertil de Saúde Reprodutiva, , Santo Andre - SP , Brasil\nAbstract\nBackground A women’s chances of getting pregnant decreases in cases of infertility, which may have several \nclinical etiologies. The prevalence of infertility is estimated as 10–15% worldwide. One of the causes of infertility is \nendometriosis, defined as the presence of an endometrial gland and/or stroma outside the uterus, inducing a chronic \ninflammatory reaction. Thus, infertility and endometriosis are diagnoses that significantly affect women’s mental \nhealth. This study accessed and compared the levels of depression, anxiety, and quality of life in infertile women with \nand without endometriosis.\nMethods was an observational and cross-sectional study which included 201 infertile women, 81 of whom were \nalso diagnosed with endometriosis. The STROBE Guidelines was used. The data were collected using validated scales: \nHamilton D Questionnaire, Beck Depression Inventory, and Fertility Quality of Life Questionnaire; The data were \ncollected at the Ideia Fertil Institute (Santo Andre, Brazil), between February 28 and June 8, 2019.\nResults the infertile women with endometriosis reported higher presence of depressive symptoms and a lower \nquality of life compared to women with infertility only. Similar presence of anxiety symptoms was observed regardless \nof being diagnosed with endometriosis. Women with infertility and endometriosis presented lower levels in quality-\nof-life domains when compared to women with infertility only - Mind and Body (58.33 × 79.17, p < 0.001), Relational \n(75 × 81.25, p = 0.009), Social (66.67 × 77.08, p = 0.001), Emotional (50.62 × 67.43, p < 0.001).\nConclusion the findings indicate the need for increased psychosocial support care for women suffering from \ninfertility and endometriosis to assist them in maintaining and managing their own mental health and achieving their \nreproductive goals.\nKeywords Anxiety, Depression, Endometriosis, Infertility, Quality of life\nEndometriosis in infertile women: an \nobservational and comparative study \nof quality of life, anxiety, and depression\nLilian Pagano Mori1 , Victor Zaia1,2* , Erik Montagna1 , Fabia Lima Vilarino2  and Caio Parente Barbosa1,2\n\nPage 2 of 7\nMori et al. BMC Women's Health          (2024) 24:251 \nBackground\nEstimates show that healthy young women, under 25 \nyears old, have the best chances of becoming pregnant, \nwith a progressive decline in fertility ranging from 4.5% \n(25 years old) to 100% (50 years old) [ 1]. However, this \npercentage decreases greatly in cases of infertility, which \nmay have several clinical etiologies [ 2]. The prevalence of \ninfertility is estimated as 10–15% worldwide [ 3]. One of \nthe causes of infertility is endometriosis, defined as the \npresence of an endometrial gland and/or stroma outside \nthe uterus, inducing a chronic inflammatory reaction [ 4], \nwith a prevalence ranging from 5 to 10% among women \nof reproductive age [5]. .\nWomen with infertility lose control over reproduc -\ntive decisions and experience feelings of guilt, sadness, \nshame, and social isolation [ 6, 7]. These feelings reduce \nquality of life and negatively affect mental health [ 8, 9]. \nThe relationship between endometriosis and infertility is \nexpressive, about 40% of women with endometriosis are \ninfertile, and between 25% and 50% of infertile women \nhave endometriosis [ 10]. In addition, clinical symptoms \nof endometriosis such as menstrual irregularity, chronic \npelvic pain (CPP), dysmenorrhea, and dyspareunia can \nemotionally affect patients [11, 12].\nSome of the disorders associated with endometriosis \ninclude depression and anxiety [ 12, 13]. A meta-anal -\nysis indicated that the magnitude of the difference in \nthe occurrence of these two symptoms between healthy \nwomen and those with endometriosis is 0.71 for depres -\nsion and 0.60 for anxiety, with both showing greater \nprevalence in the group of women with endometriosis \n[14]. Another study conducted in the United Kingdom \nwith data from 202,276 women found that the group \nwith endometriosis had a higher prevalence of depres -\nsion (9.8%) and anxiety (3.6%) compared to the group \nof healthy women [ 15]. Additionally, endometriosis can \nimpair women’s functional capacity [ 16], particularly in \ncases with dyspareunia [17].\nConsequently, women diagnosed with endometriosis \nexperience a reduction in quality of life (QoL) [ 18– 20], \nwhich is defined as an individual’s perception of their \nown life, taking into account their cultural background, \nvalues, aspirations, and expectations [ 21– 23]. A study \n[24] comparing QoL levels between healthy women and \nthose with endometriosis revealed an average decrease of \n30 points in QoL among participants with endometriosis.\nPrevious studies [ 9, 11– 13, 25] demonstrated that \nendometriosis and infertility negatively affect QoL and \nfavor increased levels of anxiety and depression. To \nenable a more personalized and specific understanding of \nthis demographic, this study uniquely identified and com-\npared anxiety, depression, and QoL levels among infertile \nwomen both with and without endometriosis, while also \nexamining the correlations between these variables.\nMethods\nParticipants and setting\nThis was an observational and cross-sectional. Interna -\ntionally validated and self-applicable scales were used. \nThis study used the STROBE [ 26] for the reporting of \nobservational studies.\nSample size was calculated using the G*Power software, \na significance value of 5% and a minimum test power of \n95% were used. The analysis indicated a minimum of 71 \nparticipants per group. A larger number of participants \nwere invited to ensure the minimum number was met, \naccounting for possible participant loss. The participants \nwere subdivided into two groups: Comparator group (A): \n120 patients with infertility diagnosis only, and Endome -\ntriosis group (B): 81 patients with infertility and endome -\ntriosis diagnosed by video-laparoscopy and confirmed \nwith histopathology. Patients included were at the earlier \nstage of the treatment, after the first consultation or dur -\ning the clinical testing before the first ovulatory induction \ncycle and in their first assisted reproduction treatment.\nThis study was conducted at the Ideia Fertil Reproduc -\ntive Health Institute, located in São Paulo, Brazil. The \nsample was characterized as non-probabilistic type. The \ndata were collected between February 28 and June 8, \n2019. A total of 230 women were invited to participate. \nHowever, 29 of these women declined their participation, \nindicating no interest or no time. There were 201 infer -\ntile women who met the inclusion criteria: [ 1]age equal \nto or above 18 years and [ 2]diagnosis of infertility. The \nexclusion criteria were: [ 1]diagnosis of a psychiatric dis -\norder [2], psychotherapy in the last six months [ 3], psy -\nchotropic medication in the last six months [4], history of \nfibromyalgia [5], neuropathy [6], osteopathy, and [7]pres-\nence of malignant tumors. The participants were invited \nin person and individually exclusively by the author LPM \nto reduce possible biases while they waited for a medical \nconsultation at that Institute.\nMeasures\nSociodemographic Questionnaire - developed ad-hoc for \nthis study, included questions to characterize the partici -\npants, such as age, partner’s age, infertility time.\nFertility Quality of Life (FertiQol) [ 23] − 26 items in \nfour domains: Mind-Body, Relational, Social, and Emo -\ntional. The answers are on a five-point Likert scale. \nHigher scores mean higher QoL. The Brazilian version \nutilized in this study is official and accessible on the \nauthors’ website (Cardiff University), which was adapted \nfrom the Portuguese language validation process [ 27]. \nCronbach’s Alpha of the Fertiqol was 0.921.\nHospital Anxiety and Depression Scale (HADS), vali -\ndated in Brazilian Portuguese [ 28] − 14 items, seven of \nwhich cover anxiety symptoms and seven cover depres -\nsion. Each question is scored on a scale (0–3), composing \n\nPage 3 of 7\nMori et al. BMC Women's Health          (2024) 24:251 \na maximum score of 21 points for each scale. Higher \nscores indicate higher levels of anxiety and depression, \nand the scale has a cutoff: up to or equal to seven points \nindicates no anxiety/depression, and eight or higher \npoints indicates the presence of anxiety/depression. \nCronbach’s Alpha of the HADS (alpha = 0.809).\nBeck Depression Inventory II (BDI-II), validated in Bra-\nzilian Portuguese [ 29] - measures depressive symptoms \nand consists of 21 items, each corresponding to a specific \ncategory of symptoms and attitude, such as sadness, pes -\nsimism, loss of pleasure, guilty feelings, and other aspects \n[23]. Each question is scored on a scale (0–3), with a total \nscore ranging from 0 to 63. A score of 0–10 points indi -\ncates no depressive symptoms, 11–63 points indicates \nthe presence of depressive symptoms. Cronbach’s Alpha \nof the BDI (alpha = 0.877).\nStatistical analysis\nR 4.2.1 used for data transcription and analysis. Basic \nand Psych Packages were performed. The data were \nindependently typed by two researchers (LPM and VZ) \nand then combined to avoid transcription errors. Miss -\ning data were checked and not found. The distribution of \nnormality of continuous variables was verified using the \nKolmogorov-Smirnov test. For the aim of identifying and \ndescribing the sample, levels of anxiety, depression, and \nQoL, we conducted descriptive statistical analyses (e.g., \npercentile, mean/median) for each group (A and B).\nReliability measures of the psychometric scales were \nverified using the Cronbach’s Alpha with a rigorous value \n(cutoff ≥ 0.80) [30], which indicated the exclusion of the \ndepression dimension in HADS (alpha = 0.787).\nFor comparing variables between groups, we con -\nducted the chi-square test for categorical variables (e.g., \npresence of anxiety and group) and the Mann-Whitney \nU test for subgroups comparison (A and B). The Fer -\ntiQoL emotional domain was the only variable showing \na normal distribution, for which the t-test was applied \nto compare groups. Additionally, to explore correla -\ntions between study variables, we conducted Spearman \ncorrelation analysis (for continuous scoring of psycho -\nmetric variables – QoL, anxiety, and depression).\nA significance value of 5% was used. Correlation \nand Cohen coefficient values were considered as small \n(< 0.30), medium (0.30–0.49), or large ( ≥ 0.50) [31].\nResults\nThe population was subdivided into two groups: 120 \npatients (59.7%) were allocated to group A (with exclu -\nsive diagnosis of infertility) and 81 patients (40.3%) to \ngroup B (with diagnosis of infertility and endometriosis). \nThe groups were homogeneous for all sociodemographic \nvariables tested: age (34.61 ±4.78), infertility time (4.43 \n±3.11), partner’s age (36.71 ±6.31) and primary infertility \n(90.5%) (Table 1).\nA significant difference was observed between groups \nA and B for levels of depressive symptoms ( p = 0.002) and \nanxiety ( p = 0.026), being greater for group B, (infertility \nand endometriosis). Both groups showed statistically sig -\nnificant differences in relation to QoL, with group A hav-\ning better levels in all areas of QoL. Moreover, the effect \nsizes between the groups were significant, except for anx-\niety, indicating a medium effect for depression (higher \nlevels in Group B), QoL Relation and Social (both with \nhigher scores for Group A), and a large effect for QoL \nMind and Body, and Emotional (both with higher scores \nin Group A) – as shown in Table 2.\nCorrelations between the psychometric variables stud -\nied were verified, all of which were significant ( p ≤ 0.001), \nindicating inverse correlations of moderate level between \nthe relational domain in FertiQoL and anxiety (rho = \n-0.360) and depression (rho = -0.412), and between the \nsocial domain in FertiQoL and anxiety (rho = -0.420). \nThe other correlations between depression, anxiety, \nand the domains of QoL remained inverse and strong. \nDepression and anxiety were positively highly correlated \n(rho = 0.620).\nConsidering the division between Group A and B, a \nstronger inverse correlation between depressive symp -\ntoms and quality of life is observed in the group with \nendometriosis compared to the group with infertility \nonly (Table 3).\nDiscussion\nSummary of findings\nThis study measured QoL, and depressive and anxiety \nsymptoms in women with infertility, verifying the pos -\nsible impact between the psychological variables and the \ndouble diagnosis: infertility and endometriosis. The find -\nings indicate that women with an overlapping diagnosis \n(endometriosis-infertility) have higher levels of depres -\nsive symptoms and lower QoL than women with infer -\ntility only. In addition, lower QoL levels were related to \nhigher levels of anxiety and depressive symptoms.\nTable 1 Clinical and demographic characteristics of the \nparticipants (comparative)\nVariable Group A \n(n = 120)\nGroup B \n(n = 81)\nMann-\nWhitney \n(p)Mean(SD) Mean(SD)\nAge (years) 34.35(5.39) 34.99(3.69) 0.591\nInfertility (years) 4.54(3.53) 4.27(2.37) 0.477\nAge partner (years) 36.95(7.14) 35.35(4.83) 0.938\nn(%) n(%) Chi-\nsquare (p)\nPrimary Infertility 106 (88.3) 76 (93.8) 0.192\nSD = Standard Deviation; Group A: patients with infertility diagnosis only; Group \nB: patients with Endometriosis and infertility\n\nPage 4 of 7\nMori et al. BMC Women's Health          (2024) 24:251 \nData from the literature suggests that sociodemo -\ngraphic variables (e.g., age, infertility duration, partner’s \nage, and type of infertility) may influence QoL, anxiety, \nand depression [ 24, 32, 33], potentially introducing con -\nfounding factors in the psychometric measures used [ 34, \n35]. However, since our groups did not show differences \nin these variables, we suggest that they may not have \nbeen determining factors for the differences found in this \nstudy.\nThe levels of depressive symptoms found were higher \nthan those in the general population, estimated at 4.4% \naccording to a study by the World Health Organization \n[16], corresponding to less than a quarter of the pres -\nence of depressive symptoms in the population studied. \nFurthermore, higher levels of depressive symptoms were \nobserved in participants with both diagnoses: endo -\nmetriosis and infertility. A similar result was found in a \nstudy involving women with endometriosis, which dem -\nonstrated a correlation between depression and various \ncomorbidities, including infertility, indicating a stronger \nlink between depressive symptoms and the diagnosis of \ninfertility in women with endometriosis than with other \nmorbidities [36]. Additionally, such findings may be cor -\nroborated by the influence of clinical symptoms of endo -\nmetriosis, beyond infertility, on an individual’s mental \nhealth [19, 20, 23].\nQoL levels in both groups were lower than those of \nthe general population, consistent with previous stud -\nies examining the impact of infertility on QoL [ 37, 38]. \nSpecifically, lower QoL levels were observed in infer -\ntile participants with endometriosis compared to infer -\ntile women without endometriosis, aligning with prior \nresearch that identifies endometriosis as a factor exac -\nerbating the decline in quality of life and mental health \n[3, 8, 32, 39– 42]. This further supports a trend in the \ngroup with infertility alone towards higher quality of life \nand reduced levels of depressive and anxiety symptoms, \nas evidenced in this study through Cohen’s d, when con -\ntrasted with the group of women with endometriosis and \ninfertility.\nEndometriosis and infertility are associated with clini -\ncal conditions that cause emotional morbidity, affecting \nsocial, sexual, and professional lives [ 4, 43]. The unregu-\nlated immune and inflammatory reactions of endome -\ntriosis, which generate CPP , may explain a higher QoL \ndecrease, and more depressive symptoms compared to \nwomen with only infertility [ 12]. To partially restore this \nimpairment, clinical or surgical treatment has proven to \nbe effective in relieving pain [ 32], but emotional aspects \nmust also be respected and treated by specialists, such as \npsychologists [20].\nAnother potential explanation for the correlation \nbetween low QoL and mental health in the group with \nTable 2 Comparison between groups and depression, anxiety, and quality of life\nVariables Group A (n = 120) Group B (n = 81) p Cohen d p\nn (%) n (%) Chi-square\nAnxiety -0.2292\nAbsent 85 (70.8) 45 (55.6) 0.026 0.055\nPresent 35 (29.2) 36 (44.4)\nDepression -0.463 < 0.001\nAbsent 100 (75.6) 52 (64.2) 0.002\nPresent 20 (16.7) 29 (35.8)\nMedian (Interquartile range) Mann-Whitney U\nDomains Quality of Life\nMind and Body 79.17 (25.00) 58.33 (42.00) < 0.001 0.8482 < 0.001\nRelation 81.25 (24.00) 75.00 (23.00) 0.009 0.3465 0.009\nSocial 77.08 (29.00) 66.67 (31.00) 0.001 0.4623 0.001\nMean (Standard Deviation) T-Test\nEmotional 67.43 (22.49) 50.62 (22.77) < 0.001 0.7437 < 0.001\nGroup A: patients with infertility diagnosis only; Group B: patients with Endometriosis and infertility\nTable 3 Spearman correlation between BDI-II, HAD and quality of life domains\nGeral Group A Group B\nBDI-II HAD Anxiety BDI-II HAD Anxiety BDI-II HAD Anxiety\nHAD Anxiety 0.620*** - 0.605*** - 0.584*** -\nDomain FertiQoL Emotional − 0.628*** − 0.510*** − 0.543*** − 0.467*** − 0.637*** − 0.497***\nMind and Body − 0.599*** − 0.501*** − 0.515*** − 0.494*** − 0.589*** − 0.423***\nRelational − 0.412*** − 0.360*** − 0.352*** − 0.345*** − 0.450*** − 0.359***\nSocial − 0.558*** − 0.420*** − 0.483*** − 0.427*** − 0.560*** − 0.357***\n\nPage 5 of 7\nMori et al. BMC Women's Health          (2024) 24:251 \nendometriosis and infertility is the connection of endo -\nmetriosis with psychological factors [ 33, 36], such as per-\nceived pain and stress, sleep quality [ 33, 44], anxiety, and \ndepression [37, 45].\nModerate correlations were found between the emo -\ntional domain of QoL and depression, with a stronger \ncorrelation observed in the infertility with endometriosis \ngroup compared to the infertility group alone. This rein -\nforces the connection between impaired mental health \nand reduced quality of life in situations of heightened \nanxiety and depression, as seen in infertile women with \nendometriosis. The findings also indicate that higher lev -\nels of anxiety and depression are linked to lower QoL, \nconsistent with previous studies investigating these vari -\nables [12, 25, 45].\nThere are few studies [ 19, 25, 36] that address psy -\nchological aspects in women with both infertility and \nendometriosis diagnoses, and this study contributes to \nthat field. The data indicates that infertile women with \nendometriosis exhibit more severe depressive symptoms, \nanxiety, and decreased quality of life compared to women \nsolely diagnosed with infertility.\nClinical implications\nThese results emphasize the relevance of patient-cen -\ntered education and psychological support for women \nstruggling with endometriosis and infertility to help them \nmanage possible mental health problems and achieve \ntheir reproductive goals successfully [ 13, 45]. Thus, is it \npossible to question what changes in the reproductive \ntreatment routine which may provide support to patients \nwith infertility and endometriosis. Based on our findings, \none of the possibilities would be to include a psychologist \nin the reproductive team to support patients in maintain-\ning or re-establishing their mental health.\nStrengths and limitations\nSome limitations of the present study need to be dis -\ncussed. First, the study population comprised women \ndiagnosed with infertility and endometriosis at various \ntime intervals since diagnosis. This variation could poten-\ntially influence the overall levels of anxiety, quality of life, \nand depression examined [ 8, 37], thereby limiting the \ngeneralizability of findings to similar populations. Future \nstudies should differentiate the time of diagnosis of each \nparticipant. Second, the numerical difference between \nthe groups of infertile women with and without endo -\nmetriosis is a limiting factor, which hinders comparisons \nbetween the two sub-samples. However, the statistical \ntests used account for these differences in sample sizes, \nas well as satisfying the minimum sample size outlined by \nthe power calculation.\nThe use of validated instruments to measure QoL, anx -\niety and depression in patients is an important strength \nof the present study, allowing a robust and internation -\nally comparable measurement [ 11, 18, 46, 47], which is \nimportant particularly when considering populations \nwith higher vulnerability to psychiatric disorders such as \nindividuals with infertility [29, 30, 37, 48] and endometri-\nosis [23, 28, 39]. Another important aspect of this study \nwas differentiating the variables studied for the diagnos -\ntic overlap between endometriosis and infertility, which \nimproves the knowledge of the emotional aspects of \nthese populations, considering the high co-occurrence of \ninfertility and endometriosis [ 10]. Additionally, the find -\nings provide information that supports better emotional \nsupport and care in reproductive treatment.\nConclusion\nIn conclusion, QoL in infertile women is impaired by \nincreased depressive symptoms and anxiety. Compared \nto women exclusively diagnosed with infertility, infertile \nwomen with endometriosis are characterized by a sig -\nnificantly worse emotional state in terms of depressive \nsymptoms and QoL. This suggests the need for care and \nemotional support in infertility management, especially \nwhen associated with endometriosis.\nAbbreviations\nBDI  II-Beck Depression Inventory II\nCPP  chronic pelvic pain\nFertiQol  Fertility Quality of Life\nHADS  Hospital Anxiety and Depression Scale\nQoL  Quality of Life\nAcknowledgements\nWe would like to thank the participants who took part in the study and the \nresearch team.\nAuthor contributions\nVZ, LPM, FLV, CPB, conceived and designed the study. VZ and EM analyzed the \ndata and drafted the manuscript. VZ, EM and LPM interpreted the data and \ncriticized the manuscript for important intellectual content. All authors have \nread and approved the final version of the manuscript. This article is the work \nof the authors. All authors had full access to all the data (including statistical \nreports and tables) in the study and can take responsibility for the integrity of \nthe data and the accuracy of the data analysis.\nFunding\nThis work was supported by the FAPESP under Grant 2019/17853-2.\nData availability\nThe data of the present study can be requested from the correspondence \nauthor.\nDeclarations\nEthics approval and consent to participate\n.\nInformed consent\nwas obtained from all subjects, and all participated voluntarily. Anonymity was \nassured. This study was approved by the Research Ethics Committee of Centro \nUniversitario FAMBC (Number: 999.283/2015) and all assessments were in \naccordance with The Helsinki Declaration.\n\nPage 6 of 7\nMori et al. BMC Women's Health          (2024) 24:251 \nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAuthors’ information\nLPM is an obstetric gynecologist, specialized in Assisted Human Reproduction \n(AHR) and has a master’s in science in Health Science. VZ is a psychologist, a \nspecialist in psychometrics, data analysis and has a PhD in Health Psychology. \nEM is a pharmacist and biochemist, specialist in health data analysis, holds a \nPhD in Biological Science with an emphasis on education. FLV is an obstetric \ngynecologist, specialized in AHR and holds a PhD in Health Science. CPB is an \nobstetric gynecologist, specialized in AHR and holds a PhD in Medicine.\nReceived: 30 June 2023 / Accepted: 7 April 2024\nReferences\n1. Vander Borght M, Wyns C. Fertility and infertility: definition and epidemiol-\nogy. Clin Biochem. 2018;62:2–10.\n2. Tarin JJ, Garcia-Perez MA, Hamatani T, Cano A. 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