{"paper_id":"117392dd-870d-427c-b391-8cf4b35c90a9","body_text":" Corresponding author: Roshika Nirmani \nCopyright © 2024 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. \nThe effect of endometriosis on the fertility of women \nRoshika Fernando * \nDiagnostic Radiology Department, Daugavpils Regional Hospital, Latvia. \nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \nPublication history: Received on 11 June 2024; revised on 20 July 2024; accepted on 22 July 2024 \nArticle DOI: https://doi.org/10.30574/wjbphs.2024.19.1.0441  \nAbstract \nEndometriosis is defined by the presence of ectopic endometrial tissue outside the uterus, frequently located on pelvic \norgans such as the fallopian tubes and ovaries, and occasionally beyond the pelvic region. This condition manifests as \ndysmenorrhea, chronic pelvic pain, dyspareunia, and subfertility. Despite extensive research, the etiology and \npathogenesis of endometriosis remain unclear, with laparoscopy being the definitive diagnostic method. \nThe association between endometriosis and infertility has been extensively debated. Endometriosis can impair fertility \nby disrupting embryo implantation, altering hormone levels, and compromising oocyte quality. This literature review \naims to examine the effects of endometriosis on female fertility. \nThe review encompasses documents from clinical trials with control groups involving 196 to 22,416 reproductive-age \nparticipants (25-42 years), and case studies published over the past thirty-seven years from various regions (USA, \nAustralia, Turkey, Africa, and Europe. Reputable databases such as BMJ, NEJM, Elsevier, AJR, Medline, and PubMed were \nutilized, with references compiled in the bibliography. \nA risk-benefit analysis indicates that up to 50% of women with endometriosis experience infertility. Consensus on \ntreatment options remains elusive. The relationship between endometriosis and infertility is supported by studies of \nboth fertile and infertile women, animal studies, donor sperm studies, and in vitro fertilization outcomes. Diagnostic \nmethodologies based on endometrial changes are providing insights into potential mechanisms of infertility, especially \nin women with milder disease. However, clinical management of endometriosis-related infertility has not shown \nconclusive success beyond in vitro fertilization.  \nKeywords: Endometriosis; Female fertility; Infertility; Diagnostic methodologies \n1. Introduction\nEndometriosis is a prevalent condition characterized by the abnormal growth of endometrial cells outside the uterus. \nThese aberrant growths are most commonly found in pelvic organs such as the ovaries, peritoneum, uterosacral \nligaments, pouch of Douglas, and rectovaginal septum. Although rare, extra pelvic endometrial abnormalities can occur \nin locations such as the umbilicus and stomach. The presence of endometrial tissue in these areas can cause irritation, \npain, and adhesions on the affected structures [23, 5]. \n\n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n321 \n \nFigure 1 Endometriosis locations [10] \n1.1. Aetiology and Pathogenesis \nThe etiology and pathogenesis of endometriosis remain largely unclear, although there is increasing evidence that it is \na complex multifactorial disease with both genetic and environmental components contributing to its development [17]. \n Heritability: Individuals with a family history of endometriosis, particularly among first -degree relatives, are at \na higher risk of developing t he condition [17, 9]. \n Retrograde menstruation flow: The most widely accepted theory for the pathophysiology of endometriosis \nsuggests that endometrial cells are transported intra-abdominally from the uterine cavity through the fallopian \ntubes during menstr uation [6, 9].  Various risk factors may enable endometrial cells to survive in ectopic \nlocations [6]. \n Adhesions: Surgical scar implantations may attach to endometrial cells, leading to the development of \nendometriosis [6]. \n Mu  llerian metaplasia: This theory posits that coelomic epithelium transforms into endometrium -like cells [6, \n9].   \n Lymph vascular emboli of endometrial cells: Endometrial cells may be transported to distant sites, such as the \npleural cavity, through the lymphatic or circulatory systems [6]. \n Increased incidence of luteinized unruptured ovarian follicle syndrome (Trapped Oocyte): Patients with severe \nendometriosis and distorted pelvic anatomy exhibit a high rate of infertility, potentially due to abnormalities in \noocyte development and tubal transport [6]. \n Early menarche or Late menopause: These complications may arise in response to hormonal changes during \nthe menstrual cycle [1]. \n1.2. Symptoms of Endometriosis \nCommon signs and symptoms of endometriosis include [12, 5, 20] \n Painful periods (Dysme norrhea): Pelvic pain and cramping may begin before and extend for several days into \nthe menstrual period, often accompanied by lower back and abdominal pain.  \n Dyspareunia: Pain during or after sexual intercourse, which is a frequent symptom.  \n Pain with bowel movements or urination: These symptoms are most pronounced during menstruation.  \n Excessive bleeding: Patients may experience heavy menstrual periods or intermenstrual bleeding.  \n Infertility: Defined as the inability to conceive after one year (or more) of unprotected sexual intercourse. \n1.3. Use of the Endometriosis Fertility Index \nThe Endometriosis Fertility Index (EFI) is a tool designed to predict the likelihood of achieving pregnancy following \nsurgery. Its utility is assessed for forecasting the capacity to conceive without assisted reproductive technology (ART) \nafter laparoscopic surgery. A study conducted in France from 2013 to 2016 involved 196 infertile patients to evaluate \nthe effectiveness of the EFI [3]. \n\n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n322 \n \nFigure 2 Endometriosis Fertility Index [11] \nThe study population met the following criteria: \n1.4. Criteria for Study Inclusion \nParticipants in the study met the following criteria: \n Infertility persisting for over 12 months  \n Presence of asymptomatic pelvic pain, dysmenorrhea, and/or deep dyspareunia  \n Normal or abnormal hysterosalpingogram results  \n Normo-ovulation or failure to conceive after three cycles of superovulation, with or without intrauterine \ninsemination (IUI), used as first -line therapy for unexplained infertility  \n Laparoscopic diagnosis of endometriosis  \n Partner’s semen classified as normal according to World Health Organisation (WHO) criteria [3]  \n2. Results \nAmong the 196 infertile women who underwent laparoscopic surgery for endometriosis -related infertility, the study \nyielded the following outcomes: \n 9 women (4.6%) were lost to follow -up. \n 26 women (13.2%) with an EFI score of 4 were referred directly to ART . \n 56 women (28.9%) with EFI scores of 5–6 received non-ART management for 3–6 months. \n 114 women (58.2%) with EFI scores of 7 or higher received non-ART management for up to 12 months.  \n 73 women (37.2%) achieved pregnancy through non -ART management: \n 18 women (32.1%) had EFI scores of 5–6. \n 55 women (48.2%) had EFI scores of 7.  \nThe mean time to conceive for women with EFI scores of 5 –6 and 7 was 5.2 m onths (SD 2.8) and 3.9 months (SD 2.9), \nrespectively [3]. \n\n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n323 \nIn routine clinical practice, 149 women (76%) achieved pregnancy, with 37.2% after non-ART management and 38.8% \nafter ART management. The 'baby take-home rate' was 57.1% [3]. \nThe Endometriosis Ferti lity Index proved to be a valuable tool for predicting fertility outcomes in infertile patients \nundergoing surgery for endometriosis. Patients with a low EFI score should be promptly referred to ART to increase \noverall pregnancy rates [3]. \n2.1. Effect of Endometriosis on Infertility \n2.1.1. Endometriosis-Associated Infertility \nThe prevalence of endometriosis is notably higher among women of Filipino, Indian, Japanese, and Korean descent [21].  \nClinical manifestations of endometriosis vary based on the location of the ec topic endometrial tissue and can include \ndysmenorrhea, dyspareunia, chronic pelvic pain, and infertility, though some individuals may be asymptomatic. A \nsignificant challenge in the timely diagnosis and management of endometriosis is the lack of a clear correlation between \nsymptoms and disease severity [21, 2]. \nEndometriosis is a leading cause of infertility through various mechanisms, although not all women with endometriosis \nexperience difficulty conceiving [21, 2].   \nThe primary mechanism involves altered anatomical structures. Pelvic adhesions impair oocyte release and ostial \npickup, alter sperm motility, and affect myometrial contractions, leading to modified embryo transport and fertilization. \nEndometriosis can impact any stage of the reproductiv e process. Inflammatory cells in the peritoneal fluid and \nendometriomas have detrimental effects on oocytes, embryos, and sperm, impairing tubal function and reducing tubal \nmobility. This results in a lower fertilization rate in both natural and in vitro c ycles [8, 14]. \nEndometriosis negatively affects the physiology of granulosa cells, leading to increased apoptosis and altered \nsteroidogenesis by decreasing aromatase expression. This causes an imbalance in estrogen production, resulting in \nlower estradiol concentrations during the preovulatory phase and at the LH surge. The follicular phase is prolonged in \nthese patients, as the LH surge is delayed or biphasic, leading to altered postovulatory progesterone release, which may \naffect oocyte maturation [8, 21]. \nThe impact of endometriosis on the endometrium is also significant. A 2012 study demonstrated that cells could migrate \nfrom ectopic endometrial implants back to the uterine endometrium. These migrating cells exhibit upregulation of the \nWnt7A gene, which affects endometrial receptivity during the implantation window. The Wnt7A gene is associated with \nestrogen-mediated uterine development and implantation [14, 19]. Another important gene is Hoxa10, which is \ninvolved in endometrial regeneration. Women with e ndometriosis have lower levels of Hoxa10, potentially explaining \nthe reduced implantation rates. Additionally, higher levels of matrix metalloproteinases, which cause persistent \nendometrial breakdown, and lower levels of αβ -integrin, which impair embryo attachment, further contribute to lower \nimplantation rates [14]. \n2.1.2. The Impact of Endometriosis on Early Embryo Morpho kinetics \nA study conducted in Turkey evaluated 82 In Vitro Fertilisation (IVF) cycles, including 53 cycles with endometriosis and \n29 cycles with tubal factor infertility. A total of 439 embryos were assessed for embryo morpho kinetics [4].  \nThe presence of endometriosis was confirmed through laparotomy or laparoscopy in 27 patients and via transvaginal \nultrasonography (TVUSG) in 26 patients, given the high diagnostic accuracy of TVUSG (Savelli 2009). Post-laparoscopic \nsurgery, the diagnosis of endometriosis was verified by expert pathologists. The study included patients with grade 3 –\n4 endometriosis. The control group consisted of 30 women with l aparoscopically confirmed tubal factor infertility \nundergoing their first IVF attempt, with no evidence of endometriosis or hydrosalpinx at the time of laparoscopy. \nClinical pregnancy was confirmed by the visualization of a gestational sac and foetal heart beat using TVUSG two weeks \nafter serum Human Chorionic Gonadotropin (βhCG) measurement [4].  \nIn all cycles, ejaculated spermatozoa were used. Exclusion criteria included women over 40 years of age, those with \npartners suffering from male factor infertility, individuals requiring preimplantation genetic diagnosis due to structural \nor numerical chromosomal errors, and patients with uterine anomalies or polycystic ovary syndrome [4].  \nThe study's findings indicate that endometriosis significantly influences early morpho kinetic events and cell cycles [4]. \n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n324 \nTable 1 Embryo morpho kinetics data of the study and control groups, respectively [4]  \n Study Group Control Group p-value \nNo, of embryos  264 175  \ntPB2 6.51 ± 9.07 3.71 ± 1.98 p < 0.01 \ntPNa 12.50 ± 7.87 11.13 ± 174 p < 0.01 \ntPNf 25.90 ± 6.31 25.30 ± 7.87 NS \nt2 28.64 ± 5.24 28.25 ± 5.40 NS \nt3 38.02 ± 6.87 37.67 ± 6.33 NS \nt4 41.44 ± 7.35 40.19 ± 6.29 NS \nt5 50.51 ± 9.86 49.76 ± 10.41 NS \nt6 55.28 ± 10.14 53.77 ± 9.91 NS \nt7 58.11 ± 10.14 58.33 ± 10.28 NS \nt8 62.67 ± 11.80 61.45 ± 11.09 NS \nt9 71.57 ± 13.37 69.62 ± 1158 NS \nVP (tPNf-tPNa) 13.25 ± 6.23 14.87 ± 7.79 NS \nECC1 (tPb2-12) 22.19 ± 8.23 24.56 ± 5.66 p < 0.01 \ncc2a (t3-t2) 9.37 ± 5.08 9.42 ± 4.89 NS \nECC2 12.87 ± 5.47 12.02 ± 4.73 NS \nFCC3 22.56 ± 9.4.6 22.03 ± 9.30 NS \n52(t4-t3) 3.40 ± 5.31 2,53 ± 4,24 p z 0.01 \nS3(t8t5)  12.40 ± 9.20 12.59 ± 10.01 NS \nGQE (%) 78 ± 41,2 93 ± 25,3 p < 0.01 \nValues are shown as mean±SD. Differences between means were tested by t-test for equality of means. NS = not significant GQE = Good Quality \nEmbryos \nTable 2 Differences in morpho kinetic data in contro l and study groups with respect to good and poor embryo quality \n[4]  \n  GOOD   POOR  \nStudy group Control \ngroup \np-value Study group Control \ngroup \np-\nvalue \nNo. of \nembryos \n207 163  57 12  \ntPB2 7.12 ± 9.91 3.69 ± 1.98 p < 0.01 4.27 ± 4.24 3.89 ± 1.96 NS \ntPNa 12.88 ±- 8.56 11.15 ±- 3.76 p < 0.05 11.10 ± 4.35 10.79 ± 3.48 NS \ntPNf 25.51 ± 6.46 25.99 ± 8.11 NS 27.29 ± 5.53 26.05 ± 3.36 N5 \nt2 27.85 ± 3.76 28.22 ± 5.49 N5 31.47 ± 8.12 28.60 ± 4.07 NS \nt3 37.10 ± 6.19 37.63 ± 6.20 NS 41.31 ± 8.15 38.07 ± 8.20 N5 \nt4 40.40 ± 6.60 40.03 ± 5.90 NS 45.18 ± 8.66 42.35 ± 10.36 NS \nt5 50.43 ± 10.04 49.23 ± 9.24 N5 50.75 ± 9.25 56.74 ± 19.83 NS \nt6 55.04 ± 10.17 53.54 ± 8.82 NS 56.46 ± 10.02 56.82 ± 19.82 NS \n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n325 \nt7 58.11 ± 10.12 58,32 ± 10.28 NS 58.25 ± 11.36 ND  \nt8 62.66 ± 11.83 61.45 ± 11.09 N5 ND ND  \nt9 71.56 ± 13.37 69.62 ± 11.57 NS ND ND  \nVP (tPNf -\ntPNa) \n12.61 ± 6.41 14.83 ± 7.96 p < 0.05 15.69 ± 4.82 15.26 ± 5.15 NS \nECC1 (tPb2-\nt2) \n21.18 ± 8.10 24.51 ± 5.75 p < 0.01 26.10 ± 7.60 25.15 ± 4.20 NS \ncc2a (t342) 9.24 ± 5.04 9.41 ± 4.77 NS 9.84 ± 5.23 9.47 ± 6.59 NS \nECC2 12.54 ± 5.32 11.81 ± 4.45 NS 14.55 ± 6.01 15.40 ± 7.48 N5 \nECC3 22.25 ± 9.46 22.02 ± 9.29 NS ND ND  \n52(t4-t3) 3.28 ± 5.18 2.40 ± 4.05 NS 3.87 ± 5.78 4.28 ± 6.20 NS \n53(t8-15) 12.47 ± 9.17 12.58 ± 10.09 NS ND ND  \ntPB2 7.12 ± 9.91 3.69 ± 1.98 p < 0.01 4.27 ± 4.24 3.89 ± 1.96 NS \ntPNa 12.88 ±- 8.56 11.15 ±- 3.76 p < 0.05 11.10 ± 4.35 10.79 ± 3.48 NS \ntPNf 25.51 ± 6.46 25.99 ± 8.11 NS 27.29 ± 5.53 26.05 ± 3.36 N5 \nt2 27.85 ± 3.76 28.22 ± 5.49 N5 31.47 ± 8.12 28.60 ± 4.07 NS \nt3 37.10 ± 6.19 37.63 ± 6.20 NS 41.31 ± 8.15 38.07 ± 8.20 N5 \nt4 40.40 ± 6.60 40.03 ± 5.90 NS 45.18 ± 8.66 42.35 ± 10.36 NS \nt5 50.43 ± 10.04 49.23 ± 9.24 N5 50.75 ± 9.25 56.74 ± 19.83 NS \nt6 55.04 ± 10.17 53.54 ± 8.82 NS 56.46 ± 10.02 56.82 ± 19.82 NS \nt7 58.11 ± 10.12 58,32 ± 10.28 NS 58.25 ± 11.36 ND  \nt8 62.66 ± 11.83 61.45 ± 11.09 N5 ND ND  \nt9 71.56 ± 13.37 69.62 ± 11.57 NS ND ND  \nVP (tPNf -\ntPNa) \n12.61 ± 6.41 14.83 ± 7.96 p < 0.05 15.69 ± 4.82 15.26 ± 5.15 NS \nECC1 (tPb2-\nt2) \n21.18 ± 8.10 24.51 ± 5.75 p < 0.01 26.10 ± 7.60 25.15 ± 4.20 NS \ncc2a (t342) 9.24 ± 5.04 9.41 ± 4.77 NS 9.84 ± 5.23 9.47 ± 6.59 NS \nECC2 12.54 ± 5.32 11.81 ± 4.45 NS 14.55 ± 6.01 15.40 ± 7.48 N5 \nECC3 22.25 ± 9.46 22.02 ± 9.29 NS ND ND  \n52(t4-t3) 3.28 ± 5.18 2.40 ± 4.05 NS 3.87 ± 5.78 4.28 ± 6.20 NS \n53(t8-15) 12.47 ± 9.17 12.58 ± 10.09 NS ND ND  \nWith these discoveries, it is clear that endometriosis dominatingly influences the term of the early morpho kinetic \noccasions and cell cycles.  \n2.1.3. Oocyte Quality in Women with Endometriosis-Associated Infertility  \nEndometriosis significantly impacts clinical markers of oocyte quality, which is a critical factor in reproduction. This \nstudy aims to evaluate the quality of oocytes in women with inferti lity related to endometriosis. The investigation \ninvolved infertile women of reproductive age, ranging from 29 to 40 years, who underwent IVF and Intra -Cytoplasmic \nSperm Injection (ICSI) procedures. Participants were divided into three groups:  \n Group I: 50 patients with recurrent unilateral endometriomas  \n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n326 \n Group II: 50 patients with unilateral endometriomas after surgical treatment  \n Control Group: 30 patients with tubal factor infertility  \nClinical and morphological assessments of oocyte quality were performed i n all IVF/ICSI cycles [16, 18, 20,22, 24]. \nTable 3 Baseline Characteristics of Women with Infertility [16] \nCharacteristics Group I in = \n501 \nGroup II \n(n=50) \nControl group (n = \n30) \nAge, years 3336 ± 45 32.64±4,2 31.73 ± 421 \nInfertility duration 4.6 ± 2_4 4.2 ± 2.1 33±2.6 \nAMH 2.2 ± 13 2.1 ± 1,8 3.0±1.8 \nThe number of antral follicles in the affected ovary 4.1 ± 15 5.4± 13 125±2.9 (at both \nsides) \nThe number of antral follicles in the intact ovary 72±2.6 7.8 ± 23  \nTotal number of nocytes recovered 8.8 ± 3.9 9.2±3.2 10.1 ±6.8 \nThe number of high -quality oocytes obtained (oocyte in \nmetaphase II) \n4.1 ± 2_0 5.2 ± 2.6 9.6 ±3..5 \n \nTable 4 Characteristic of patients with endometriomas [16] \nSize of endometriomas Group I (n = SO) Group II (n = 50) \n>10mm 18 (36%) 24 (48%) \n10-20 mm 20 (40%) 18 (36%) \n20-30 mm 8 (16%) 6 (12%) \n30-40 mm 4 (8%) 1 (2%) \n \nThe findings of the investigation indicate a statistically significant increase in the number of immature oocytes at \nmetaphase I (MI) and the germinal vesicle (GV) stage in patients with endometriosis-associated infertility compared to \nthe control group (p < 0.005). Additionally, there was notable degeneration of oocytes in patients with endometriomas \nexceeding 3 cm in diameter. These results suggest that endometriomas negatively impact oocyte quality, and that even \nafter cystectomy, endometriomas continue to have a detrimental effect on the ovaries [16, 18, 20, 22, 24].  \nTherefore, it can be concluded that endometriomas, both before and after surgical intervention, adversely affect ovarian \nquality [16, 18, 20, 22, 24]. \n2.2. Chronic Niche Inflammation in Endometriosis Development \nChronic inflammation within the tissue niche, particularly in the peritoneal cavity, ovaries, and uterus, plays a crucial \nrole in the development of endometriosis [13].   \n2.3. Peritoneal Cavity \nThe presence of peritoneal fluid in the peritoneal cavity results from the exudation of developing follicles and the corpus \nluteum. This fluid contains electrolytes, urea, steroidal hormones such as estrogen and progesterone, and other \ncomponents like endometrial cells, macrophages, lymphocytes, and eryth rocytes. Some of these components have \nsecretory functions; for instance, endometrial cells secrete glycodelin, and macrophages secrete cytokines and \nangiogenic factors [13].   \nInfertility in most cases of endometriosis is primarily due to chronic inflamma tion induced by the abnormal \nenvironment, such as the increased volume of peritoneal fluid. Significant changes in the immune system include the \n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n327 \ninhibition of T-cell-mediated cytotoxicity, decreased natural killer cell activity, and a rapid increase in pro-inflammatory \ncytokines and activated macrophages. These sudden changes create an oxidative and immunotolerant \nmicroenvironment conducive to endometriotic implantations [13].   \nEndometriotic implants secrete various substances, including estradiol, progest erone, monocyte chemoattractant \nprotein (MCP)-1, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF). Additionally, pro-\ninflammatory cytokines such as interleukins (IL) -1, IL -6, and IL -8, and tumour necrosis factor alpha (TNF -α) are \nsecreted. This mixture of secretions in the peritoneal fluid stimulates proliferative and angiogenic processes, \ncontributing to the development and rapid progression of endometriosis [13].   \nThe formation of endometriomas in the ovaries disrupts org an functionality and induces localized effects. The cystic \nfluid within endometriomas contains pro -inflammatory cytokines (IL-6 and IL-8), reactive oxygen species (ROS), TGF -\nβ, and matrix metalloproteinases (MMPs). These components of cystic fluid alter th e surrounding tissue of nearby \nendometriomas, leading to decreased follicular density, increased fibrosis, and loss of cortical stroma. Caspase -3 \nimmunostaining has revealed signs of atresia in early follicles in tissue biopsies from ovaries containing endometriomas \n[13].   \nTGF-β1 and ROS contribute to fibrosis and adhesion formation through the differentiation of myofibroblasts and the \nexpression of profibrotic genes mediated by plasminogen activator inhibitor -1. The loss of ovarian stroma has a \ndetrimental effect on follicle formation. Pathogenesis is marked by a reduced blood supply and depletion of specific \ngrowth factors that would normally be secreted by healthy stromal cells [13].   \n2.4. Deep Infiltrating Endometriosis   \nA retrospective cohort study was conducted to investigate the impact of previous surgery for endometriosis on assisted \nreproductive technology (ART) cumulative live -birth rates in patients with deep infiltrating endometriosis (DE). The \nstudy included 222 DE patients who underwent ART [7]. \nThe diagnosis of DE was established based on strict imaging criteria and histological confirmation of the disease. Women \nwith a prior history of surgery for endometriosis were included, and their ART outcomes were compared with those of \npatients without a history of such surgery [7]. \nThe cohort selection process is detailed in Figure 3. From January 2008 to December 2016, a total of 222 DE patients \nunderwent 440 ART cycles [7]. \nThe patient characteristics are summarized in Table 4. It is noteworthy that in 1 49 cases (67.1%), DE was associated \nwith ovarian endometrioma (OMA) lesions [7]. \n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n328 \n \nFigure 3 The process of the cohort selection [7]  \nTable 4 provides detailed information on the patient characteristics and their ART outcomes. Figure 3 illustrates the \ncohort selection process, ensuring a comprehensive understanding of the study design and its findings [7].  \n\n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n329 \nTable 5 Patients’ characteristics in the general population (n = 222) [7]  \n \nDE, deep infiltrating endometriosis; OSIS, endometriosis; OMA, endometrioma; FSH, follicle -stimulating hormone; AFC, antral follicle count; AMH, \nanti- Mu  llerian hormone a Continuous data are presented as mean ± standard deviation; categorical data are presented as number (percentages).  \nAbbreviation \nART  - Assisted Reproductive Technology \nDE  - Deep infiltrating Endometriosis  \nEFI  - Endometriosis Fertility Index \nGV  - Germinal Vesicle  \nICSI  - Intra-Cytoplasmic Sperm Injection  \nIL  - Iinterleukins  \nIUI  - Intra-Uterine Insemination \nIVF  - In Vitro Fertilisation \nLH  - Luteinizing Hormone \nMCP  - Monocyte Chemoattractant Protein  \nMMPs  - Matrix MetalloProteinases  \nOMA  - Ovarian Endometrioma  \nROS  - Reactive Oxygen Species  \nTGF  - Transforming Growth Factor  \nTNF-α  - Tumor Necrosis Factor alpha \nTVUSG - Trans-Vaginal UltraSonography \nVEGF  - Vascular Endothelial Growth Factor  \nWHO  - World Health Organisation \n\n\nWorld Journal of Biology Pharmacy and Health Sciences, 2024, 19(01), 320–331 \n330 \nβhCG  - Human Chorionic Gonadotropin \n3. Conclusion \n Heterogeneity of Endometriosis:  Endometriosis is a complex and heterogeneous disorder that affects various \naspects of the reproductive cycle, including mechanical, molecular , and genetic factors. \n Pathophysiological Factors Affecting Infertility:  Several key pathophysiological factors contribute to infertility \nassociated with endometrioma. Inflammatory changes in the peritoneal cavity can alter sperm -oocyte \ninteraction. Distorted pelvic anatomy may impair oocyte release and utero -tubal transport. Additionally, \novarian endometriomas can adversely affect ovarian reserve and oocyte quality. \n Impact of Pro -inflammatory Microenvironment:  The pro -inflammatory microenvironment in the ectopic \nendometrium can alter endometrial resp onsiveness, further contributing to infertility. \n Predictors of Reproductive Outcomes:  While endometrioma is significantly associated with infertility, ovarian \nreserve status and response to ovarian stimulation are more critical predictors of reproductive o utcomes than \nthe mere presence of endometrioma.  \n Individualized Treatment Approaches:  In vitro fertilization (IVF) is the most effective treatment for infertility \nin endometriosis patients. However, treatment decisions should be individualized, considering the patient’s age, \novarian reserve, other causes of infertility, duration of infertility, and male factors. \n Multidisciplinary Management:  The management of patients with endometriosis -related infertility should \ninvolve a multidisciplinary team to address the complex and multifaceted nature of the disorder   \nCompliance with ethical standards \nStatement of informed consent \nInformed consent was obtained from all individual participants included in the study.  \nReferences \n[1] Ashrafi M, Sadatmahalleh SJ, Akhoond  MR, Talebi M. Evaluation of Risk Factors Associated with Endometriosis \nin Infertile Women. Int J Fertil Steril. 2016 Apr-Jun;10(1):11-21. doi: 10.22074/ijfs.2016.4763. Epub 2016 Apr 5. \nPMID: 27123195; PMCID: PMC4845520.          \n[2] Bodean O, Voicu D, Muntean u O, Bra ̆ tila ̆  E, Boha ̂ lţea R, Daviţoiu D, Cîrstoiu M. Chronic Pelvic Pain And \nEndometriosis. 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Epub 2012 Sep 11. \nPMID: 22968642; PMCID: PMC3473215.  \n[20] Senapati S, Sammel MD, Morse C, Barnhart KT. Impact of endometriosis on in  vitro fertilization outcomes: an \nevaluation of the Society for Assisted Reproductive Tec hnologies Database. Fertil Steril. 2016 Jul;106(1):164 -\n171.e1. doi: 10.1016/j.fertnstert.2016.03.037. Epub 2016 Apr 7. PMID: 27060727; PMCID: PMC5173290.  \n[21] Vassilopoulou L, Matalliotakis M, Zervou MI, Matalliotaki C, Spandidos DA, Matalliotakis I, Goulielim os GN. \nEndometriosis and in vitro fertilisation Exp. Ther. Med. 2018 Aug; 16 (2): 1043 - 1051.              \n[22] Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. \n2014 May;10(5):261-75. doi: 10.1038/nrendo.2013.255. Epub 2013 Dec 24. PMID: 24366116.  \n[23] Vercellini, P., Vigano ̀ , P., Somigliana, E. et al. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10, \n261–275 (2014). https://doi.org/10.1038/nrendo.2013.255   \n[24] . Xu B, Guo N, Zhang XM, Shi W, Tong XH, Iqbal F, Liu YS. Oocyte quality is decreased in women with minimal or \nmild endometriosis. Sci Rep. 2015 May 29;5:10779. doi: 10.1038/srep10779. PMID: 26022105; PMCID: \nPMC4448226  \nAuthors short Biography \n \nRoshika Nirmani Habarawa Batuwattage Fernando  graduated from Riga Stradins \nUniversity with a Doctor of Medicine (MD) degree in 2020. Currently working in the Diagnostics \nRadiology Department at Daugavpils Regional Hospital in Latvia.","source_license":"CC0","license_restricted":false}