{"paper_id":"815b216c-c84a-4895-a299-a10e6f20c657","body_text":"RESEARCH Open Access\n© The Author(s) 2023. 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.\nYan et al. BMC Women's Health          (2023) 23:244 \nhttps://doi.org/10.1186/s12905-023-02406-z\nBMC Women's Health\n*Correspondence:\nYuan Yuan\nyuanyuan3@mail.sysu.edu.cn\nFull list of author information is available at the end of the article\nAbstract\nBackground Endometriosis affects many reproductive aged patients with fertility decline and poor outcomes of \nassisted reproductive treatments, mainly by decreased ovarian reserve and lower fertilization and implantation rates. \nIn recent decade, altered oocyte microenvironments and abnormal spindle organization have been reported to \nbe critical to oocyte chromosomal segregation, organization and aneuploid formation. However, clinical evidences \nare still limited on whether endometriosis influences oocyte and embryo development. We aimed to figure out the \nimpact of endometrioma on embryo aneuploid formation.\nMethod This retrospective cohort study included 1,021 patients (7,092 biopsied embryos) from January 2012 to \nDecember 2020. Fertile patients without a history of miscarriage who underwent PGT-M treatment with aneuploid \nscreening were included. Patients with ovarian endometrioma were defined as the study group, while patients \nwithout endometriosis were defined as the control group. All demographic, controlled ovarian stimulation treatment \nand aneuploid screening data were recorded and compared.\nResults The incidence of endometrioma in our study population was 6.5%. There were 7,092 embryos biopsied in \ntotal, with 308 embryos in the study group and 6,784 embryos in the control groups. The demographic characteristics \nwere comparable between the two groups except the basal FSH level (6.02 IU/L vs. 5.52 IU/L, p = 0.012). The euploid \nrate of the study group was significantly lower than that of the control group (52.6% vs. 61.8%, p = 0.012), while the \noocyte maturation, fertilization, usable embryo and blastocyst formation rates were comparable. Adjusted for basal \nFSH level, starting stimulating gonadotropin dosage, total gonadotropin dosage and FSH level on hCG day, euploid \nrate was still negatively related to endometrioma status.\nConclusions Endometrioma status disturbs oocyte and embryo development. For infertile patients with \nendometrioma who require assisted reproductive treatment, pre-treatment is necessary to improve treatment \noutcomes.\nTrial registration Not applicable.\nOvarian endometrioma increases the embryo \naneuploid rate: an analysis of 7092 biopsied \nblastocysts from fertile monogenetic disease \ncarriers\nNiwei Yan1, Xi Yuan2, Sunxing Huang1, Huiying Jie1, Jing Wang1 and Yuan Yuan1*\n\nPage 2 of 6\nYan et al. BMC Women's Health          (2023) 23:244 \nBackground\nEndometriosis is a common chronic inflammatory dis -\nease for women of reproductive age, with a prevalence \nof 6–10% in the general female population [ 1]. With the \nprogressive disruption of the pelvic and ovarian envi -\nronment, fertility decline is the main complaint of many \npatients [ 2]. However, infertile patients with endome -\ntriosis seeking assisted reproductive treatments are also \nassociated with poor clinical outcomes [ 3– 5]. Decreased \novarian reserve and lower fertilization and implantation \nrates are the main contributors to unpleasant treatment \noutcomes [ 6]. In recent years, an increasing number of \nstudies have reported an altered oocyte microenviron -\nment [ 7] and abnormal spindle organization [ 8], which \nare critical to oocyte chromosomal segregation, organi -\nzation and aneuploid formation. However, real-world \nclinical data are still limited.\nIn 2017, Juneau et al. reported that patients with endo -\nmetriosis undergoing IVF had aneuploidy rates equiva -\nlent to their age-matched peers in an IVF population \nwho did not have endometriosis from a sample of 4,103 \npatients [ 9]. There were several weaknesses that lim -\nited the interpretation of this result. Firstly, the diagno -\nsis of endometriosis was not stratified. Secondly, all the \npatients enrolled were receiving PGS treatment. There \nmight be other vital confounders of aneuploid involve -\nment that were not properly adjusted during the analysis. \nThirdly, all the patients were infertile, which limits the \ninvestigation of the pathology of endometriosis itself.\nTherefore, we recruited a group of patients with mono-\ngenetic disease seeking PGT-M treatment without diag -\nnosis of infertility. The aneuploid rate was calculated \naccording to the endometriosis status. To avoid the het -\nerogeneity of endometriosis, only patients with ovarian \nendometrioma were enrolled in the study group. With \nall the above strict settings, we anticipate revealing the \nbona fide impact of endometrioma on embryo aneuploid \nformation.\nMethods\nThis retrospective cohort study was performed from \nJanuary 2012 to December 2020 in the Reproductive \nMedicine Center and was approved by the Ethics Com -\nmittee of The First Affiliated Hospital, Sun Yat-Sen Uni -\nversity. Written informed consent was obtained from all \nthe patients for anonymous use of their personal data. \nAll procedures performed in this study involving human \nparticipants were in accordance with the Declaration of \nHelsinki.\nStudy population\nAll patients who underwent PGT-M treatment with \naneuploid screening were included. All the clinical files \nof the patients were scrutinized to verify the diagnosis \nof endometriosis. Previous history, medical records (sur -\ngery) and results of transvaginal ultrasound examination \nplus histological evidence were the main considerations \nof endometriosis diagnosis. With the confirmed endome-\ntriosis diagnosis, only the aneuploid rate of patients with \npresent ovarian endometrioma was calculated, defined \nas the study group. Patients without any sign of endo -\nmetriosis were defined as the control group. Patients \nwith infertility and spontaneous abortion history were \nexcluded from both groups. If the patients had several \ncontrolled ovarian stimulation cycles, only the first cycle \nwas analysed. All demographic information, baseline \nendocrinologic data and controlled ovarian stimulation \nparameters were recorded.\nControlled ovarian stimulation and PGT-M\nRoutine controlled ovarian stimulation protocols were \nimplemented, including an agonist long protocol, an \nantagonist protocol and mild ovarian stimulation cycles. \nBoth recombined and highly purified urinary gonado -\ntropins were utilized. Final oocyte maturation was typi -\ncally induced with 6,000 to 10,000 IU of human chorionic \ngonadotropin when at least three follicles had reached \n18  mm in maximal diameter. Transvaginal oocyte \nretrieval was performed 36  h after human chorionic \ngonadotropin administration.\nIntracytoplasmic sperm injection, embryo culture, \nblastocyst culture and trophectoderm biopsy were rou -\ntine procedures. Usable blastocysts were biopsied on \nDays 5 and 6. Monogenetic disease was diagnosed with \nspecific probes. Aneuploid screening was performed \nthrough next-generation sequencing (NGS) or a single-\nnucleotide polymorphism (SNP) microarray platform. All \nusable euploid blastocysts were cryopreserved for future \nuse.\nStatistical analysis\nStatistical analysis was performed using SPSS version 26 \n(IBM). The euploid rate was defined as the number of \nblastocysts biopsied divided by the number of euploids. \nContinuous data are presented as the mean ± standard \ndeviation, and Student’s t-test was performed for inter -\ngroup comparisons. Categorical data are presented as \npercentages, and the Chi-square test was used for inter -\ngroup comparisons. Associations between endometriosis \nstatus and euploid rate were assessed using multivari -\nable linear regression. The analysis was adjusted for basal \nKeywords Endometriosis, Endometrioma, Oocyte, Embryo development, Aneuploid, PGT-M\n\nPage 3 of 6\nYan et al. BMC Women's Health          (2023) 23:244 \nFSH level, starting stimulation gonadotropin dosage, \ntotal gonadotropin usage, and FSH level on hCG day. A \np value < 0.05 was considered significant. The Post-hoc \npower analyses were conducted using G*Power (Version \n3.1.9.2.).\nResults\nIn total, 1,021 fertile patients who underwent PGT-M \ntreatment and aneuploid analysis were enrolled in this \nstudy. There were 67 patients with confirmed endometri-\nosis diagnosis. The incidence of endometrioma was 6.5%. \nFourteen patients were excluded from the final analysis \nsince there was no evidence of ovarian endometrioma \naccording to ultrasonographic examination. Thus, there \nwere 53 patients in the study group and 954 patients in \nthe control group. The rate of bilateral endometriomas \nin the study group is 60.4% (32/53). The aetiologies of \nPGT-M treatment were thalassemia, haemophilia, Duch -\nenne’s muscular dystrophy, neurofibroma, spinal muscu-\nlar atrophy, mucopolysaccharidosis, etc. With a one-sided \nsignificance level of 0.05 and our current sample size, the \npower was 0.815 to detect the difference of euploid rate \nbetween the two groups.\nThe demographic characteristics are summarized in \nTable  1. Age, BMI, anti-Mullerian hormone level and \nbasal gynaecological endocrinology status were compa -\nrable in the two groups except the basal FSH level, which \nwas significantly higher in the study group than in the \ncontrol group.\nRoutine controlled ovarian stimulation protocols were \napplied in our study, such as agonist, antagonist and \nmild ovarian stimulation protocols. The different proto -\ncol proportions in the two groups were equivalent. The \nstarting stimulation dosage in the study group was sig -\nnificantly higher than that in the control group. With \na similar stimulation duration, the total gonadotropin \nusage in the study group was significantly higher than \nthat in the control group. The FSH level on the day of \nhCG administration was significantly higher than that \nof the control group. However, the E2 level on the day of \nhCG administration and the number of oocytes retrieved \nwere comparable between the two groups. Although two \ndifferent aneuploid screening platforms were used, the \nproportions in the two groups were comparable. The \ndetails are provided in Table 2.\nThe mature oocyte, fertilization, multipronuclear, \ncleavage and blastocyst formation rates were similar \nin the two groups. The usable embryo rate of the study \ngroup was lower than that of the control group; however, \nthe difference between the two groups was not statisti -\ncally significant. There were 7,092 embryos biopsied in \ntotal, with 308 embryos in the study group and 6,784 \nembryos in the control group. The euploid rate was cal -\nculated per person but not for the whole group. The \neuploid rate of the study group was significantly lower \nthan that of the control group. And the mosaicism rate \nin the study group is 16.32% and 15.41% in the control \ngroup. All the details are provided in Table 3.\nWe used multivariable linear regression to analyse the \nassociation between endometrioma status and embry -\nonic treatment outcomes and further adjusted for basal \nFSH level, starting stimulating gonadotropin dosage, total \ngonadotropin dosage and FSH level on hCG day. Unlike \nthe rest of the factors, the euploid rate was negatively \nrelated to endometriosis status. The details are shown in \nTable 4.\nTable 1 Baseline characteristics of the study population\nParameter Study group Control group P value\nAge 31.46 ± 4.14 31.69 ± 4.34 0.699\nBMI 21.11 ± 3.18 21.37 ± 2.67 0.493\nAMH 3.65 ± 2.74 4.28 ± 3.49 0.280\nFSH 6.02 ± 2.05 5.52 ± 1.37 0.012\nLH 3.35 ± 1.75 3.57 ± 2.19 0.467\nE2 34.38 ± 16.44 33.72 ± 18.37 0.801\nPRL 18.10 ± 14.49 16.90 ± 14.39 0.558\nT 0.28 ± 0.10 0.42 ± 0.20 0.670\nTable 2 Treatment parameters of the study population\nParameter Study group Control group P value\nProtocol 0.923\n Agonist 66.04% (35) 66.87% (638)\n Antagonist 32.08% (17) 31.87% (304)\n Mild stimulation 1.88% (1) 1.26% (12)\nStarting dosage 244.58 ± 60.02 218.25 ± 59.30 0.002\nTotal GN 2625.80 ± 916.88 2319.86 ± 843.94 0.011\nCOS duration 10.45 ± 1.75 10.37 ± 1.81 0.736\nFSH on HCG day 16.24 ± 5.78 13.42 ± 5.09 0.000\nLH on HCG day 1.15 ± 1.03 1.23 ± 1.35 0.667\nE2 on HCG day 2696.93 ± 1334.92 2841.02 ± 1155.18 0.430\nP on HCG day 1.03 ± 0.48 0.90 ± 0.77 0.218\nNO. of oocytes 16.68 ± 8.29 18.33 ± 8.49 0.167\nPGT-A Platform 0.535\n NGS 75.5% (40) 70.5% (673)\n SNP 24.5% (13) 29.5% (281)\nTable 3 Embryonic parameters of the study population\nParameter Study group Control group P value\nMature oocyte 0.828 ± 0.136 0.832 ± 0.133 0.807\nFertilization rate 0.647 ± 0.179 0.670 ± 0.156 0.296\nMPN rate 0.022 ± 0.057 0.021 ± 0.055 0.937\nCleavage rate 0.986 ± 0.034 0.989 ± 0.037 0.619\nEmbryo rate 0.371 ± 0.163 0.414 ± 0.174 0.078\nBlastocyst rate 0.685 ± 0.192 0.700 ± 0.192 0.566\nGood Blastocyst rate 0.726 ± 0.144 0.704 ± 0.232 0.369\nEuploid rate 0.526 ± 0.294 0.618 ± 0.256 0.012\n\nPage 4 of 6\nYan et al. BMC Women's Health          (2023) 23:244 \nDiscussion\nIn recent years, with the rapid development of reproduc -\ntive technology, accumulating evidence has emerged to \nuncover the relationship between infertility and endome-\ntriosis. Although the poor ART treatment outcomes are \nuniversally understood [ 3– 5], the specific pathophysiol -\nogy of endometriosis is still obscure.\nEndometriosis is a heterogeneous disease with three \nwell-recognized phenotypes: superficial peritoneal \nlesions, ovarian endometriomas and deep infiltrating \nendometriosis [ 10]. Endometriosis is stratified by the \nAmerican Society for Reproductive Medicine (ASRM) \nclassification into four stages (I, II, III and IV) according \nto surgical evaluation of the size, location and severity of \nendometriotic lesions and the occurrence of extensions \nof adhesions [11]. However, during everyday practice, not \nall patients undergo surgery to diagnose endometriosis, \nwhich makes it difficult to unify the study population. In \nour study, based on the history, medical records, ultra -\nsound examination and histological results, we obtained \na raw incidence of 6.5%, which was consistent with pre -\nvious reports [ 1]. Since our study population was fertile, \nit makes sense that our incidence of endometriosis was \nnear the lower portion of the previous report.\nIn 2019, Horton et al. reported the reproductive out -\ncomes of women with endometriosis through a system -\natic review and meta-analysis. They found that milder \nforms of endometriosis were most likely to affect the fer -\ntilization rate and earlier implantation processes, while \nthe more severe forms of the disease (ASRM III and IV) \ninfluenced all stages of reproduction. Ovarian endome -\ntriosis negatively affects the oocyte yield and number of \nmature oocytes [ 6]. Based on this result, to detect the \nlatent effect of endometriosis on aneuploid formation, \nwhich might be minor but does exist, we ruled out the \nsuperficial peritoneal lesion phenotype. Ovarian endo -\nmetrioma confirmed by transvaginal ultrasound exami -\nnation and histological results was the only criterion of \nthe study group, which means that we covered all the \nphenotypes that might influence embryo formation and \ndevelopment, even though not all the patients underwent \nsurgery for diagnosis and stratification. Under this strict \nsetting, the mature oocyte, fertilization, cleavage, mul -\ntiple pronuclear, blastocyst formation rates and usable \nembryo rate of the endometriosis group were all compa -\nrable to those of the control group. The euploid rate of \nthe endometriosis group was significantly lower than the \ncontrol group. The endometriosis patients in our study \ngroup were all fertile, which means that their lesions \nmight be limited to the ovaries without other pelvic tis -\nsue infiltration and adhesion. Ovarian space-occupying \nlesions decreased ovarian reserve [ 12], however, the dif -\nference of serum anti-Mullerian hormone level between \nthe two groups didn’t reach statistically significant level \nin our study. The oocyte maturation and embryo forma -\ntion processes were not affected by these ovarian lesions. \nThe mature oocyte, fertilization, cleavage, multiple pro -\nnuclear and blastocyst formation rates of the endometri -\nosis group were all comparable with those of the control \ngroup. However, the euploid rate in the endometriosis \ngroup was significantly lower than that in the control \ngroup, which means that the quality of the embryos was \nalso reduced.\nOur study results were not consistent with Juneau’s \nstudy [9]. A previous study obtained a large sample size \nof 4,103 patients who underwent PGS treatment. How -\never, their study population was not stratified. For dif -\nferent stages or phenotypes, the pathophysiology of \nendometriosis is not the same [ 13– 15]. The aneuploid \nrate might only contribute slightly to the poor treatment \noutcome. Considering all the phenotypes as a whole \nfor analysis, the chance of detecting minor differences \nmight be missed. In their study, the study population was \npatients who underwent PGS treatment. Moreover, they \ndid not state the indications of PGS treatment. PGS is \nutilized in patients of advanced reproductive age, recur -\nrent spontaneous miscarriage or pregnancy loss [ 16]. The \naverage age of their study population was approximately \n36, which was not well accepted as over 38. This means \nthat the majority of their study population was patients \nwith an unpleasant pregnancy history. Age is the most \npowerful contributor to aneuploidy [ 17– 19]. For age-\nindependent aneuploids, the inherent miosis process \nwas the major influencing factor [ 20]. If the major study \npopulation was patients suffering from recurrent spon -\ntaneous miscarriage, it is unsurprising that other minor \naetiological factors of aneuploid formation could not be \ndetected. Finally, the study population consisted of infer -\ntile patients, meaning that other factors influenced the \nembryo formation or implantation processes. Similar to \ntheir own thoughts, if alterations in the spindle appara -\ntus resulted in developmental arrest before the blasto -\ncyst stage, those embryos would not have been included \nin their analysis. They did not provide much data about \nembryo development, which makes it hard to interpret \nTable 4 Association between endometrioma status and \ntreatment outcomes\nTreatment outcome Multivariable linear regression\nB p 95%CI\nMature oocyte -0.008 0.704 -0.048—0.032\nFertilization rate -0.020 0.565 -0.061—0.033\nMPN rate 0.005 0.891 -0.016—0.018\nCleavage rate -0.036 0.302 -0.017—0.005\nEmbryo rate -0.045 0.186 -0.087—0.017\nBlastocyst rate -0.008 0.816 -0.065—0.051\nEuploid rate -0.071 0.037 -0.160— -0.005\nNote: B for coefficient of independent variable, p for significance\n\nPage 5 of 6\nYan et al. BMC Women's Health          (2023) 23:244 \ntheir final results. The overall euploid rate in their study \nwas higher than ours, which might be due to the different \naneuploid screening platforms [ 21] since the majority of \nour study utilized NGS while PCR in their study.\nThere have been many studies evaluating the impact \nof the microenvironment of endometriosis patients on \noocyte development. In 2009, Barcelos et al. reported no \nsignificant differences in the frequency of meiotic anom -\nalies between metaphase II oocytes matured in vitro \nfrom MI or GV of infertile patients with endometriosis \nor not in a preliminary study [ 22], but with a tendency \nof more telophase I oocytes in the endometriosis group. \nIn 2013, Dib et al., other researchers from the previous \nresearch group, reported that in vivo matured oocytes \nof infertile patients with endometriosis did not demon -\nstrate significant differences in terms of the nuclear mat -\nuration stage, the percentage of oocytes in metaphase II \nwith visible spindles, or spindle localization when com -\npared to the control group under polarization micros -\ncopy [ 23]. However, in 2014, using an animal model, \nother researchers from the same previous research group \nreported that bovine oocytes matured in vitro in follicle \nfluid collected from mild endometriosis patients and had \na higher immature rate and percentage of meiotic abnor -\nmalities, such as misaligned chromosomes or abnormal \nspindles [ 7]. Conflicting data were presented from the \nsame research group as the studies went further, from in \nvitro to in vivo, from human oocytes to an animal model. \nAlthough no conclusion could be drawn about aneuploid \nformation from their study, they do suggest that the fol -\nlicular fluid of endometriosis patients may undergo some \npathological changes. Therefore, the oocytes that went \nthrough in vitro maturation out of this toxic environ -\nment might be saved from the error development pro -\ncess, while those still caught in this environment were \ndoomed.\nThere are many strengths of our study to investigate the \nimpact of endometrioma on aneuploid formation. Firstly, \nthe study population was homogeneous. Although we \ncould not stratify fertile patients with ovarian endome -\ntrioma according to the ARSM classification, the number \nof fertile patients with ovarian endometrioma was equal \nto that of mild endometriosis patients without extensive \npelvic adhesions. Secondly, all the patients were fer -\ntile monogenetic disease carriers without an unpleasant \npregnancy history. Their inherent oocyte and embryo \ndevelopment processes were relatively normal compared \nwith infertile or recurrent miscarriage patients. Under \nthis setting, the confounding factor of aneuploid forma -\ntion could be reduced to a minimum. Thirdly, with 7,092 \nbiopsied embryos and 1,021 patients, our study popula -\ntion was large enough to obtain a proper power to detect \nthe difference of euploid rate between the two groups \nwhich was tested by the Post-hoc power analyses.\nThere are still some weaknesses in our study. Firstly, it \nwas a single centre-based retrospective study. Secondly, \nthe study population was monogenetic disease carriers. \nEvidence concerning embryo development and monoge -\nnetic disease is rare. The majority of our study population \nwas patients suffering from thalassemia. Our previous \nstudy reported that maternal thalassemia carrier status \ndid not impair ovarian response or embryo development \n[24]. There are still many other rare monogenetic diseases \nlacking information or evidence on embryo development.\nConclusions\nOur study found that the aneuploid rate of fertile patients \nwith ovarian endometrioma was increased, although \noocyte maturation, fertilization and early development \nprocesses were not interfered with. To illustrate the \nunderlying pathological mechanism, in vitro experiments \nor animal models are needed in the near future.\nList of Abbreviations\nASRM  American Society for Reproductive Medicine (ASRM)\nAMH  Anti-Mullerian hormone\nART  Assisted reproductive technology\nBMI  Body mass index\nCOS  Controlled ovarian stimulation\nE2  Estradiol\nFSH  Follicle-stimulating hormone\nGV  Germinal vesicle\nGH  Growth hormone\nhCG  Human chorionic gonadotropin\nICSI  Intracytoplasmic sperm injection\nIVF  In vitro fertilization\nLH  Luteinizing hormone\nMI  Metaphase I\nMPN  Multiple pronuclear\nNGS  Next-generation sequencing\nPCR  Polymerase chain reaction\nPGS  Preimplantation Genetic Screening\nPGT-A  Preimplantation genetic testing for aneuploidies\nPGT-M  Pre-implantation genetic testing for monogenic/ single gene \ndefects\nPRL  Prolactin\nSNP  Single-nucleotide polymorphism\nT  Testosterone\nAcknowledgements\nNot applicable.\nAuthors’ contributions\nFormal analysis, Jing Wang; Investigation, Huiying Jie; Methodology, Niwei \nYan and Sunxing Huang; Supervision, Writing – original draft, Niwei Yan and \nYuan Yuan; Writing – review and editing, Xi Yuan. All authors contributed to \nmanuscript revision, read, and approved the final manuscript.\nFunding\nThis study was supported by the Guangdong Provincial Key Laboratory of \nReproductive Medicine(2020B1212090029).\nData Availability\nThe analyzed data sets generated during the present study are available from \nthe corresponding authors on reasonable request.\n\nPage 6 of 6\nYan et al. BMC Women's Health          (2023) 23:244 \nDeclarations\nEthics approval and consent to participate\nThe present study was approved by the Ethics Committee of The First \nAffiliated Hospital, Sun Yat-Sen University. Written informed consent was \nobtained from all the patients for anonymous use of their personal data. All \nprocedures performed in this study involving human participants were in \naccordance with the Declaration of Helsinki.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthor details\n1Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-Sen \nUniversity, 1, Zhongshan Road II, Guangzhou 510080, China\n2Department of Obstetrics and Gynecology, National University Hospital, \n5 Lower Kent Ridge Road, Singapore 119228, Singapore\nReceived: 23 November 2022 / Accepted: 3 May 2023\nReferences\n1. Giudice LC, Kao LC. Endometr Lancet. 2004;364(9447):1789–99.\n2. Vercellini P , Viganò P , Somigliana E, Fedele L. Endometriosis: pathogenesis and \ntreatment. Nat Rev Endocrinol. 2014;10(5):261–75.\n3. Li A, Zhang J, Kuang Y, Yu C. Analysis of IVF/ICSI-FET outcomes in women \nwith Advanced Endometriosis: influence on ovarian response and oocyte \ncompetence. Front Endocrinol (Lausanne). 2020;11(17):427.\n4. Sanchez AM, Pagliardini L, Cermisoni GC, Privitera L, Makieva S, Alteri A, \nCorti L, Rabellotti E, Candiani M, Viganò P . Does Endometriosis Influence the \nembryo quality and/or development? Insights from a large Retrospective \nMatched Cohort Study. Diagnostics (Basel). 2020;10(2):83.\n5. Senapati S, Sammel MD, Morse C, Barnhart KT. Impact of endometriosis on in \nvitro fertilization outcomes: an evaluation of the society for assisted Repro-\nductive Technologies Database. Fertil Steril. 2016;106(1):164–71.\n6. Horton J, Sterrenburg M, Lane S, Maheshwari A, Li TC, Cheong Y. Reproduc-\ntive, obstetric, and perinatal outcomes of women with adenomyosis and \nendometriosis: a systematic review and meta-analysis. Hum Reprod Update. \n2019;25(5):592–632.\n7. Da Broi MG, Malvezzi H, Paz CC, Ferriani RA, Navarro PA. Follicular fluid from \ninfertile women with mild endometriosis may compromise the meiotic \nspindles of bovine metaphase II oocytes. Hum Reprod. 2014;29(2):315–23.\n8. Mansour G, Sharma RK, Agarwal A, Falcone T. Endometriosis-induced altera-\ntions in mouse metaphase II oocyte microtubules and chromosomal align-\nment: a possible cause of infertility. Fertil Steril. 2010;94(5):1894–9.\n9. Juneau C, Kraus E, Werner M, Franasiak J, Morin S, Patounakis G, Molinaro T, \nde Ziegler D, Scott RT. Patients with endometriosis have aneuploidy rates \nequivalent to their age-matched peers in the in vitro fertilization population. \nFertil Steril. 2017;108(2):284–8.\n10. Chapron C, Marcellin L, Borghese B, Santulli P . Rethinking mechanisms, \ndiagnosis and management of endometriosis. Nat Rev Endocrinol. \n2019;15(11):666–82.\n11. Revised American Society for Reproductive Medicine classification of endo-\nmetriosis. : 1996. Fertil Steril. 1997;67(5):817 – 21.\n12. Boucret L, Bouet PE, Riou J, Legendre G, Delbos L, Hachem HE, Descamps \nP , Reynier P , May-Panloup P . Endometriosis lowers the cumulative live birth \nrates in IVF by decreasing the number of embryos but not their quality. J Clin \nMed. 2020;9(8):2478.\n13. Ferreira EM, Giorgi VSI, Rodrigues JK, de Andrade AZ, Junior AAJ, Navarro \nPA. Systemic oxidative stress as a possible mechanism underlying the \npathogenesis of mild endometriosis-related infertility. Reprod Biomed Online. \n2019;39(5):785–94.\n14. Inagaki J, Hao L, Nakatsuka M, Yasuda T, Hiramatsu Y, Shoenfeld Y, Matsuura E. \nA possible mechanism of autoimmune-mediated infertility in women with \nendometriosis. Am J Reprod Immunol. 2011;66(2):90–9.\n15. Roux P , Perrin J, Mancini J, Agostini A, Boubli L, Courbiere B. Factors associated \nwith a poor prognosis for the IVF-ICSI live birth rate in women with rAFS \nstage III and IV endometriosis. J Assist Reprod Genet. 2017;34(7):921–28.\n16. Bhatt SJ, Marchetto NM, Roy J, Morelli SS, McGovern PG. Pregnancy outcomes \nfollowing in vitro fertilization frozen embryo transfer (IVF-FET) with or \nwithout preimplantation genetic testing for aneuploidy (PGT-A) in women \nwith recurrent pregnancy loss (RPL): a SART-CORS study. Hum Reprod. \n2021;36(8):2339–44.\n17. Franasiak JM, Forman EJ, Hong KH, Werner MD, Upham KM, Treff NR, Scott \nRT Jr. The nature of aneuploidy with increasing age of the female partner: \na review of 15,169 consecutive trophectoderm biopsies evaluated with \ncomprehensive chromosomal screening. Fertil Steril. 2014;101(3):656–63.\n18. Ntostis P , Iles D, Kokkali G, Vaxevanoglou T, Kanavakis E, Pantou A, Huntriss \nJ, Pantos K, Picton HM. The impact of maternal age on gene expression \nduring the GV to MII transition in euploid human oocytes. Hum Reprod. \n2021;37(1):80–92.\n19. La Marca A, Capuzzo M, Longo M, Imbrogno MG, Spedicato GA, Fiorentino \nF, Spinella F, Greco P , Minasi MG, Greco E. The number and rate of euploid \nblastocysts in women undergoing IVF/ICSI cycles are strongly dependent on \novarian reserve and female age. Hum Reprod. 2022;37(10):2392–401.\n20. Webster A, Schuh M. Mechanisms of Aneuploidy in Human Eggs. Trends Cell \nBiol. 2017;27(1):55–68.\n21. Popovic M, Dhaenens L, Boel A, Menten B, Heindryckx B. Chromosomal \nmosaicism in human blastocysts: the ultimate diagnostic dilemma. Hum \nReprod Update. 2020;26(3):313–34.\n22. Barcelos ID, Vieira RC, Ferreira EM, Martins WP , Ferriani RA, Navarro PA. \nComparative analysis of the spindle and chromosome configurations of in \nvitro-matured oocytes from patients with endometriosis and from control \nsubjects: a pilot study. Fertil Steril. 2009;92(5):1749–52.\n23. Dib LA, Araújo MC, Giorgenon RC, Romão GS, Ferriani RA, Navarro PA. \nNoninvasive imaging of the meiotic spindle of in vivo matured oocytes from \ninfertile women with endometriosis. Reprod Sci. 2013;20(4):456–62.\n24. Yuan Y, Yuan X, Zhou C. Does thalassemia influence ovarian response? An \nanalysis of 127 cycles involving pre-implantation genetic diagnosis of thalas-\nsemia in southern China. J Obstet Gynaecol. 2016;36(6):778–82.\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in \npublished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}