{"paper_id":"94a27c74-7678-45a0-9cf6-9fb877aefc42","body_text":"Firdaus et al. \nMiddle East Fertility Society Journal           (2025) 30:58  \nhttps://doi.org/10.1186/s43043-025-00265-2\nRESEARCH Open Access\n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http://creativecommons.org/licenses/by/4.0/.\nMiddle East Fertility\nSociety Journal\nTopic- impact of laparoscopic cystectomy \nand endometrioma size on IVF outcomes: \ninsights from a retrospective cohort study\nArshiya Firdaus1, Anjali S Mundkur1, Vidyashree G Poojari1, Pratap Kumar Narayan1, Srisailesh Vitthala2 and \nPrashanth K. Adiga1* \nAbstract \nBackground Endometrioma, a common manifestation of endometriosis, can impact fertility and are often encoun-\ntered in women undergoing assisted reproductive technologies (ART). Traditionally, surgical removal of endome-\ntriomas has been considered standard practice before in vitro fertilization (IVF). However, recent research questions \nwhether surgery is necessary, as its benefits in improving IVF outcomes remain debated. The findings of present study \ncontribute to the ongoing debate by examining both surgical management and cyst size as factors influencing IVF \noutcomes. The present study also aimed to use the Ovarian Sensitivity Index (OSI) as a dynamic marker of ovarian \nresponsiveness to compare operated and non-operated endometriomas, a factor that has not been investigated \nin previous studies.\nMethods This retrospective cohort study compared IVF outcomes between women with operated (n = 35) and non-\noperated (n = 48) endometriomas. We also evaluated the impact of endometrioma size (< 4 cm vs > 4 cm) on clinical \noutcomes. All participants were under 40 years of age and underwent their first cycle of IVF. The primary outcome \nwas clinical pregnancy rate, while secondary outcomes included embryological parameters (total number of oocytes \nretrieved, mature oocytes, and good-quality embryos) and stimulation characteristics (total gonadotropin dose \nrequirements and OSI). Statistical comparisons were made between the groups.\nResults The total gonadotropin dose was significantly higher in the operated group (4050 IU vs. 3600 IU, p = 0.032). \nHowever, the number of oocytes, mature oocytes, and good-quality embryos were similar between oper-\nated and non-operated groups. Regarding cyst size, no significant differences in IVF outcomes were found \nbetween women with smaller (< 4 cm) and larger (> 4 cm) endometriomas.\nConclusion This study suggests that IVF outcomes are not significantly affected by the removal of endometriomas. \nWhile laparoscopic cystectomy may slightly increase gonadotropin requirements and potentially compromise ovarian \nreserve, it does not negatively impact IVF success rates. In asymptomatic patients, IVF can be successfully performed \nwithout the need for endometrioma removal, as the presence of the endometrioma does not appear to hinder IVF \noutcomes. Additionally, endometrioma size did not significantly influence IVF outcomes in this study. For women \nwith symptomatic endometriomas, surgical intervention may still be considered, as it does not seem to deteriorate \nIVF outcomes, provided that careful patient selection is made.\nKeywords Endometrioma, IVF outcomes, Oocyte retrieval, Ovarian stimulation, Endometriotic cystectomy, Ovarian \nsensitivity index (OSI), Endometriosis\n*Correspondence:\nPrashanth K. Adiga\nprashanth.adiga@manipal.edu\nFull list of author information is available at the end of the article\n\nPage 2 of 10Firdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \nIntroduction\nIn the context of ART, endometriomas present a unique \nand substantial challenge. Its prevalence is estimated to \nbe between 23% and 55% [1 ]. The treatment of endo -\nmetriomas before IVF has long been a clinical dilemma, \nwith opinions on whether surgery should be performed \nbefore IVF or whether the endometrioma should be left \nintact. Both strategies offer both benefits and draw -\nbacks of their own [2 ].\nLeaving the endometrioma intact during ovarian \nstimulation may lead to complications during ovum \npickup, such as difficulty in accessing the ovaries, folli -\ncular fluid contamination, exposure to oxidative stress, \nand the potential formation of an abscess, all of which \ncould negatively impact oocyte quality [2 – 4].\nOn the other hand, surgical removal of endometrio -\nmas requires a high level of surgical expertise and car -\nries risks such as delayed ART, recurrence, increased \ncost, and the possibility of incomplete cyst removal, \nwhich may affect fertility outcomes [5 ]. Surgery for \nendometriomas can lower ovarian reserve, as measured \nby AMH, and reduce the response to stimulation [6 – 9].\nAdditionally, while endometriomas are thought to \ndecrease ovarian responsiveness to stimulation [10], \nthe exact mechanisms remain unclear. Some studies \nsuggest that the size of the endometrioma may influ -\nence ovarian response, with larger cysts potentially \nimpairing stimulation results and pregnancy chances \n[11– 13]. However, there is still a debate regarding the \nsize threshold beyond which fertility outcomes are \ncompromised [11, 13, 14]. Currently, there is no clear \nconsensus or standardized guidance in the literature \nconcerning IVF treatment in endometriomas, specifi -\ncally with regards to decision making according to size \nof endometrioma.\nGiven these gaps in knowledge, this study aims \nto address some of the unresolved issues in the lit -\nerature. The aim of this study is to compare IVF out -\ncomes in patients with endometriomas by comparing: \n(1) patients who underwent IVF with and without cyst \nremoval and (2) patients with endometriomas smaller \nand greater than 4 cm.\nThis study will use the ovarian sensitivity index (OSI) \nas a dynamic measure for ovarian response to compare \noperated and non-operated endometriomas, a factor \nthat has not been investigated in previous studies. This \napproach makes our study distinct by incorporating a \ndynamic marker OSI to assess ovarian responsiveness. \nThe incorporation of OSI may yield significant insights \ninto ovarian response and enhance the understanding \nof endometrioma effects on IVF results.\nAim and objectives\nTo Compare the IVF outcomes between operated and \nnon-operated endometrioma.\nIVF Outcomes between endometrioma size < 4cm \nand > 4cm.\nMaterial and methods\nThis observational retrospective cohort study was con -\nducted in the Department of Reproductive Medicine and \nSurgery, Kasturba Medical College and Hospital, Mani -\npal, from May 2021 to April 2024, and included 83 sub -\njects based on specific criteria. The study was approved \nby the Institutional Review Board of our medical center, \nensuring compliance with ethical guidelines. Inclu -\nsion Criteria: Participants were included if they had a \nconfirmed diagnosis of endometrioma on ultrasound \nand had undergone first cycle of IVF treatment. Endo -\nmetriotic cysts appear as homogeneous low-echogenic \nfluid masses without papillary proliferation [15]. Some \npatients underwent laparoscopic endometriotic cystec -\ntomy prior to being recruited for IVF, while others were \ndirectly recruited for IVF without the removal of the cyst. \nIn cases with bilateral and/or multiple cysts, the mean \ndiameter of the endometriotic cyst was selected. Endo -\nmetriotic cystectomy was performed by skilled special -\nists with a strong emphasis on preserving the patient’s \nreproductive potential. Patients who underwent cystec -\ntomy were recruited for IVF within 1 year of laparoscopic \nendometriotic cystectomy. The decision to perform cys -\ntectomy was based on patient symptoms.\nParticipants were excluded if they had other underlying \nmedical conditions that could independently affect IVF \noutcomes, such as severe male factor infertility, autoim -\nmune disorders, presence of adenomyosis features, and \nuterine abnormalities (fibroids and uterine polyps). The \ndata collected included personal history, fertility investi -\ngation results, age, body mass index (BMI), anti-Mülle -\nrian hormone concentration (AMH), antral follicle count \n(AFC), type (primary or secondary), duration of infertil -\nity, and stimulation parameters.\nStimulation protocol\nWomen were monitored and managed according to the \nclinical protocol of our study center. Two ovarian stim -\nulation protocols involving 150–600  IU/day of (FSH)\nfollicle stimulating hormone were used: (i) a flexible \nantagonist protocol and (ii) an agonist flare protocol. \nGonadotropin doses and stimulation protocol types were \ndetermined based on patient characteristics and clinician \ndecisions. Final oocyte maturation was triggered when \nthree or more ovarian follicles ≥ 18 mm in diameter were \nvisible by ultrasound, using either 250 µg of recombinant \n\nPage 3 of 10\nFirdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \n \n(HCG) human chorionic gonadotropin or 1  mg of sub -\ncutaneous leuprolide, if ovarian hyperstimulation syn -\ndrome (OHSS) risk was identified. Oocyte retrieval was \nperformed 35–36  h after transvaginal aspiration under \nultrasound guidance, with 1.2 g of amoxicillin and clavu -\nlanic acid administered as antibiotic prophylaxis. Intra -\ncytoplasmic sperm injection (ICSI) was performed in all \npatients. Embryo grading was performed using the Istan -\nbul consensus, and cleavage-stage frozen embryos were \ntransferred. Grade 1 and grade 2 embryos were taken as \ngood quality embryos.\nEmbryo transfer protocol\nHormone replacement cycle (HRT) frozen embryo trans-\nfer was performed for all patients, (3.75  mg leuprolide) \nGnRH (gonadotrophin releasing hormone) agonist was \ngiven on day 21 of the previous cycle. Estradiol valerate \n2  mg three times a day was given for the endometrial \npreparation. Luteal phase support included progesterone \n(gel) 90 mg twice daily, dydrogesterone 20 mg twice daily, \ncontinued for up to 10 weeks of pregnancy if beta HCG \nwas positive 14 days after embryo transfer.\nOutcomes measured in terms of embryological (num -\nber of oocytes retrieved, M2 oocytes, good-quality \nembryos grade1 & 2) and clinical outcomes (clinical \npregnancy rate). Additional markers such as OSI (num -\nber of oocytes retrieved/total gonadotrophin dose) was \nalso calculated and compared between the groups.\nThe Ovarian Sensitivity Index (OSI) was calculated \nusing the formula: OSI = Total number of oocytes \nretrieved ÷ Total gonadotropin dose administered (in \nIU) × 1000. OSI serves as a standardized measure of \novarian responsiveness to exogenous gonadotropin \nstimulation, with higher values indicating better ovarian \nsensitivity [16]. This index has been validated as a reli -\nable marker for assessing ovarian responsiveness in ART \ncycles, allowing for comparison between different stimu -\nlation protocols and patient populations [17]. While the \nabsolute number of oocytes retrieved remains an impor -\ntant measure of ovarian response, OSI provides a com -\nplementary marker that adjusts for gonadotropin dose, \nthereby minimizing inter-individual variability and offer -\ning a more standardized assessment of ovarian sensitiv -\nity [17]. Previous studies have demonstrated OSI to be a \nvalid and reliable marker of ovarian sensitivity, offering a \nmore accurate representation of the ovarian response to \nstimulation compared to oocyte yield or gonadotropin \ndose considered separately [16, 17].\nDefinition of outcomes\nCumulative clinical pregnancy rate was taken as the \nprimary outcome measure for comparison between \ngroups. Secondary outcomes comprised embryological \nparameters including the total number of oocytes \nretrieved, number of mature oocytes, and number of \ngood-quality embryos obtained. Additional secondary \noutcomes included stimulation parameters such as total \ngonadotropin dose requirements and ovarian sensitivity \nindex (OSI). Statistical analyses were performed to com -\npare these outcomes between the study groups.\nClinical pregnancy rates\nClinical pregnancy was determined by ultrasound \ndocumentation of at least one fetus with a heartbeat at \n6–7  weeks of gestation [18]. The cumulative  clinical \npregnancy rate(cCPR)  was defined as the proportion of \nwomen who had at least one clinical pregnancy whether \nfrom the first transfer attempt or subsequent transfers of \nfrozen–thawed supernumerary embryos (per IVF/ICSI \ncycle). The mean number of embryo transfer cycles per \npatient has also been reported and compared.\nThese outcome measures were compared between two \ngroups: operated and non-operated endometriomas and \nbetween endometriomas < 4 cm and > 4 cm in size, all of \nwhom underwent IVF.\nStatistical analysis\nStatistical analysis was performed with SPSS software. \nContinuous variables were presented as mean ± standard \ndeviation (SD), median (interquartile range, IQR) and \ncategorical variables as numbers (%), depending upon the \nnormality of data. Data distribution was assessed through \nhistograms and confirmed using HistoFit software.\nPrimary analysis\nContinuous variables with non-normal distributions \nwere compared using the Mann–Whitney U test, while \nnormally distributed continuous variables were com -\npared using the independent t-test. Categorical variables \nwere analyzed using the chi-square test or Fisher’s exact \ntest. Statistical significance was set at p < 0.05.\nStratified analysis for confounder control\nTo address potential confounding variables that might \ninfluence the association between endometrioma surgery \nand ART outcomes, we performed stratified analyses \nbased on three key clinical factors:\n1. Age stratification: Patients were divided into two \ngroups: < 35 years and ≥ 35 years\n2. AMH stratification: Based on pre-stimulation AMH \nlevels (reflecting post-surgical status in the oper -\nated group and baseline status in the non-operated \ngroup), patients were categorized as low AMH \n(< 1.5 ng/ml) or normal AMH (≥ 1.5 ng/ml)\n\nPage 4 of 10Firdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \n3. Endometrioma size stratification: Cysts were classi -\nfied as < 4 cm or ≥ 4 cm.\nWithin each stratum, we compared IVF outcomes \nbetween operated and non-operated groups using \nthe same statistical tests as the primary analysis. This \napproach allowed us to control for these important con -\nfounders and assess whether treatment effects remained \nconsistent across different patient subgroups.\nResults\nTable  1 compares IVF outcomes between operated \n(n = 35) and non-operated endometrioma (n = 48). Age \nand BMI was comparable between the two groups. Anti-\nMüllerian hormone (AMH) levels and antral follicle \ncount (AFC) were slightly higher in the non-operated \ngroup but comparable values. The mean size of the endo-\nmetrioma was significantly smaller in the non-operated \ngroup (3.10  cm ± 1.75) than in the operated endometri -\noma group (5.15 cm ± 2.1) (p = 0.012). The total gonado -\ntrophin dose required was significantly higher in patients \nwho underwent IVF after surgery for endometrioma than \nin the non-operated group (p = 0.032). OSI was lower in \nthe operated endometrioma group than non the operated \ngroup (2.12 ± 1.40 vs 2.82 ± 2.95, p = 0.198), suggesting \nthat ovarian responsiveness to stimulation was slightly \nreduced after surgery, but the difference was not statis -\ntically significant. Both groups had comparable num -\nbers of oocytes, mature (M2) oocytes, and good-quality \nembryos and clinical pregnancy with no significant dif -\nferences in these outcomes (p = 0.395, 0.236, 0.740 and \n1.00 respectively).\nTable 2 compares various parameters between patients \nwith endometrioma of size less than 4  cm (n = 43) and \nthose with endometrioma greater than 4  cm (n = 40). \nBaseline characteristics were found comparable between \nthe two groups. The number of oocytes and mature (M2) \noocytes, as well as the number of good quality embryos \nand clinical pregnancy showed no significant differences \nin two compared groups suggesting that size of endome -\ntrioma is not significant determinant of stimulation out -\ncomes. A significantly greater proportion of women with \nendometriomas ≥ 4  cm underwent surgery compared to \nthose with cysts < 4 cm (62.5% vs. 23.3%, P = 0.009).\nTable 3 illustrates that stratified analysis by age groups \nrevealed consistent patterns across both age strata. In \nyounger women (< 35 years), surgical removal of endome-\ntriomas did not significantly affect gonadotropin require-\nments compared to conservative management (3653 vs \n3287  IU, p = 0.121), while in older women (≥ 35  years), \nsurgery was associated with significantly higher gonado -\ntropin needs (4444 vs 3892 IU, p = 0.045). Despite higher \nTable 1 Comparative analysis of IVF outcomes in operated and non-operated endometrioma\nAMH Anti−Mullerian Hormone, BMI Body mass index, AFC Antral follicle count, OSI Ovarian sensitivity index, IQR Inter quartile range\na t−test\nb Mann−Whitney U test\nc Fisher’s exact test\n** Significant at p<0.05\nParameters (N = 83) Operated (n = 35) Non-operated (n = 48) P value\nBaseline Variables\n Age (years) 32.36 ± 2.98 33.4 ± 2.63 0.098a\n BMI(kg/m 2) 22.8 ± 2.26 22.8 ± 3.23 0.87a\n AMH (ng/ml) 1.72 ± 0.90 2.09 ± 1.26 0.136a\n AFC(median, IQR) 9 (12–6) 11 (13–8) 0.052b\n Mean size of endometriotic cyst (cm) 5.15 ± 2.1 3.10 ± 1.75 0.012a**\nStimulation protocol\n Flare agonist protocol 7 (20.0%) 8 (16.7%) 0.785c\n Antagonist protocol 28 (80.0%) 40 (83.3%)\n Total dose of gonadotrophins(IU) 3639.58 ± 712.97 3054.68 ± 888.14 0.032a**\n Embryo transfer cycles performed 1.5 ± 1.2 1.3 ± 1.2 0.607a\n OSI 2.12 ± 1.40 2.82 ± 2.95 0.198a\nClinical Outcomes\n Number of oocytes 6 (8.25- 4.75) 6.5 (10–5) 0.395b\n M2 oocytes 5 (7–4) 6 (8–4) 0.236b\n Good quality embryos 4 (5–2.75) 4 (6–3) 0.740b\n Clinical pregnancy 13/35 (37.1%) 19/48 (39.6%) 1.000c\n\nPage 5 of 10\nFirdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \n \ngonadotropin requirements in the older surgical group, \noocyte retrieval numbers remained comparable between \nsurgical and conservative approaches in both age groups \n(younger: 6 vs 7, p = 0.677; older: 6 vs 7, p = 0.883). Clini-\ncal pregnancy rates showed similar patterns across age \ngroups, with no significant benefit of surgery observed in \neither younger (7/17 [41.1%] vs 11/23 [47.8%], p = 0.745) \nor older women (5/18 [27.7%] vs 9/25 [36.0%], p = 0.652).\nTable 4: On stratified analysis by AMH levels, the oper -\nated group had significantly larger cyst size compared to \nthe non-operated group in both strata (AMH < 1.5  ng/\nml: 5.4 ± 1.8 cm vs. 3.3 ± 1.6 cm, P = 0.001; AMH ≥ 1.5 ng/\nTable 2 Endometrioma size based comparison of stimulation outcomes\nAMH Anti−Mullerian Hormone, BMI Body mass index, AFC Antral follicle count, IQR Inter quartile range, IU International units, OSI Ovarian sensitivity index\na t-test\nb Mann-Whitney U test\nd chi-square test\n** Significant at p < 0.05\nParameters Size < 4 cm,(n = 43) Size > 4 cm,(n = 40) P value\nBaseline Variables\n Age (years) 33.42 ± 2.84 32.65 ± 3.11 0.583a\n AMH (ng/ml) 1.93 ± 1.08 1.98 ± 1.23 0.746a\n AFC (median, IQR) 10 (13–8) 10 (12–6.25) 0.248b\n Total gonadotrophins dose (IU) 3505.55 ± 807.25 3534.86 ± 844.24 0.684a\n Duration of stimulation 9.19 ± 0.89 9.29 ± 0.95 0.456a\n Operated endometrioma 10/43 (23.25%) 25/40 (62.5%) 0.009d**\n OSI 2.38 ± 2.39 2.68 ± 2.51 0.579a\nClinical Outcomes\n Number of oocytes 6 (9—4.5) 6.5 (9.75–5) 0.667b\n Number of M2 oocytes 5 (8–4) 5.5 (8–4) 0.362b\n Good quality embryos 4 (5–3) 4 (6–3) 0.664b\n Embryo transfer cycles performed 2.1 ± 0.9 1.5 ± 1.2 0.365a\n Clinical pregnancy 17/43 (39.53%) 15/40 (37.50%) 0.445d\nTable 3 Stratified analysis by age groups\nAMH Anti−Mullerian Hormone, AFC Antral follicle count, IQR Inter quartile range, IU International units\na t-test\nb Mann-Whitney U test\nc Fisher’s exact test\n** Significant at p < 0.05\nParameter Age < 35 Years Age ≥ 35 Years\nOperated (n = 17) Non-operated (n = 23) P-value Operated (n = 18) Non-operated (n = 25) P-value\nBaseline Characteristics\n Mean age (years) 31.4 ± 1.8 31.8 ± 1.9 0.456 36.2 ± 1.3 36.8 ± 1.2 0.167a\n AMH (ng/ml) 1.67 ± 0.71 1.92 ± 0.83 0.312 1.46 ± 0.68 1.71 ± 0.94 0.378a\n AFC (median, IQR) 10 (8–13) 11 (8–15) 0.423 8 (6–12) 10 (8–12) 0.189b\n Mean size of endometriotic cyst \n(cm)\n5.2 ± 1.4 2.9 ± 1.1  < 0.001** 5.1 ± 2.7 3.2 ± 2.0 0.017a**\n Total gonadotropins dose(IU) 3653 ± 692 3287 ± 734 0.121 4444 ± 721 3892 ± 856 0.045a**\nIVF Outcomes\n Number of oocytes 6 (5–8) 7 (5–10) 0.677 6 (4–8) 7 (4–10) 0.883b\n M2 oocytes 5 (4–7) 6 (4–8) 0.798 4 (3–6) 6 (4–10) 0.678b\n Good quality embryos 4 (3–5) 4 (3–6) 0.634 3 (2–5) 3 (2–4) 0.721b\n Clinical pregnancy 7/17 (41.1%) 11/23 (47.8%) 0.745 5/18 (27.7%) 9/25 (36.0%) 0.652c\n\nPage 6 of 10Firdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \nml: 4.9 ± 2.3 cm vs. 2.9 ± 1.9 cm, P = 0.003). However, IVF \noutcomes including number of oocytes (AMH < 1.5  ng/\nml: 5 vs. 5; AMH ≥ 1.5 ng/ml: 8 vs. 8), M2 oocytes, good \nquality embryos, and clinical pregnancy rates (26.6% vs. \n35.0%; 40.0% vs. 46.4%) were comparable between oper -\nated and non-operated women.\nTable  5: On stratified analysis by cyst size, oper -\nated women had significantly larger cysts compared \nto non-operated in the ≥ 4  cm group (5.8 ± 1.2 vs. \n4.7 ± 0.8  cm, P = 0.003), while cyst size was compa -\nrable in the < 4  cm group. However, gonadotropin \nrequirement, oocyte yield, embryo quality, and clini -\ncal pregnancy rates were similar between operated and \nnon-operated women across both strata, irrespective of \nsurgery status.\nTable 4 Stratified analysis by AMH levels\nAMH Anti−Mullerian Hormone, AFC Antral follicle count, IQR Inter quartile range\na t-test\nb Mann-Whitney U test\nc Fisher’s exact test\n** Significant at p < 0.05\nParameter AMH (< 1.5 ng/ml) AMH (≥ 1.5 ng/ml)\nOperated (n = 15) Non-operated (n = 20) P-value Operated (n = 20) Non-operated (n = 28) P-value\nBaseline Characteristics\n Mean AMH (ng/ml) 1.03 ± 0.25 1.12 ± 0.28 0.336 2.11 ± 0.89 2.47 ± 1.12 0.245a\n Age (years) 34.7 ± 2.4 35.1 ± 2.8 0.678 33.0 ± 2.9 32.5 ± 3.2 0.567a\n AFC (median, IQR) 8 (6–10) 9 (7–11) 0.445 11 (9–14) 12 (10–16) 0.234b\n Mean size of endometriotic cyst \n(cm)\n5.4 ± 1.8 3.3 ± 1.6 0.001** 4.9 ± 2.3 2.9 ± 1.9 0.003a**\n Total gonadotropins dose(IU) 4267 ± 643 4125 ± 789 0.567 3867 ± 734 3245 ± 712 0.006a**\nIVF Outcomes\n Number of oocytes 5 (4–5) 5 (4–6) 0.734 8 (6–12) 8 (5–11) 0.783b\n M2 oocytes 4 (3–4) 4 (3–5) 0.689 7 (6–8) 8 (5–10) 0.745b\n Good quality embryos 2 (2–3) 3 (2–4) 0.612 5 (4–6) 4 (3–6) 0.678b\n Clinical pregnancy 4/15 (26.6%) 7/20 (35.0%) 0.689 8/20 (40.0%) 13/28 (46.4%) 0.723c\nTable 5 Stratified analysis by endometrioma size\nAMH Anti−Mullerian Hormone, AFC Antral follicle count, IQR Inter quartile range\na t-test\nb Mann-Whitney U test\nc Fisher’s exact test\n** Significant at p < 0.05\nParameter Small Cysts (< 4 cm) Large Cysts (≥ 4 cm)\nOperated (n = 10) Non-operated (n = 33) P-value Operated (n = 25) Non-operated (n = 15) P-value\nBaseline Characteristics\nMean size of endometriotic cyst (cm) 3.0 ± 0.7 2.8 ± 0.9 0.567 5.8 ± 1.2 4.7 ± 0.8 0.003a**\nAge (years) 33.2 ± 2.8 33.5 ± 3.1 0.789 34.1 ± 2.9 34.8 ± 2.6 0.456a\nAMH (ng/ml) 1.78 ± 0.89 1.89 ± 1.02 0.734 1.45 ± 0.67 1.67 ± 0.78 0.378a\nAFC (median, IQR) 10 (8–13) 11 (9–14) 0.445 8 (6–11) 9 (7–12) 0.345b\nTotal gonadotropins dose(IU) 3750 ± 645 3445 ± 678 0.234 4200 ± 723 3867 ± 834 0.212a\nIVF Outcomes\nNumber of oocytes 8 (5–11) 8 (5–10) 0.732 7 (4–9) 7 (4–10) 0.678b\nM2 oocytes 7 (5–10) 7 (4–9) 0.789 6 (3–7) 6 (3–9) 0.645b\nGood quality embryos 5 (2–7) 5 (2–6) 0.823 4 (2–5) 4 (2–5) 0.712b\nClinical pregnancy 3/10 (30.0%) 15/33 (45.45%) 0.352 9/25 (36.0%) 5/15 (33.3%) 0.772c\n\nPage 7 of 10\nFirdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \n \nDiscussion\nThe present study was conducted with the aim of evalu -\nating IVF outcomes in operated and non-operated endo -\nmetrioma and to determine the impact of endometrioma \nsize on clinical outcomes. One of the most significant \nfindings of our study was the substantially higher gon -\nadotropin requirement in the operated group com -\npared to the non-operated group (3639.58 ± 712.97 IU vs \n3054.68 ± 888.14  IU, p = 0.032). This finding aligns with \ngrowing evidence that surgical excision of endometrio -\nmas may inadvertently damage healthy ovarian tissue \nand compromise ovarian reserve  [19, 20]. The ovarian \nsensitivity index (OSI), though not statistically signifi -\ncant, showed a trend toward reduced ovarian respon -\nsiveness in the operated group (2.12 ± 1.40 vs 2.82 ± 2.95, \np = 0.198), further supporting concerns about post-sur -\ngical ovarian function. However, despite the higher gon -\nadotropin requirement, IVF outcomes including oocyte \nyield and embryo quality, were comparable between the \ntwo groups. The cumulative clinical pregnancy rates were \ncomparable between operated and non-operated groups \n(37.1% vs 39.6%, p = 1.000), suggesting that surgical \nremoval of endometriomas may not confer reproductive \nadvantages in the context of assisted reproductive tech -\nnology. This finding is important in-patient counseling, \nas it underscores the potential for increased treatment \ncosts without a corresponding improvement in clinical \noutcomes.\nThe size-based stratification revealed a clear selection \nbias in clinical practice, with 62.5% of large cysts (≥ 4 cm) \nunderwent surgery compared to only 23.3% of small cysts \n(< 4  cm). The selection of endometriomas greater than \n4  cm for surgical intervention may have introduced a \npotential selection bias, as these larger cysts were more \noften chosen for removal under the assumption that their \nexcision could improve IVF outcomes. However, surgical \nintervention did not result in superior outcomes in either \nsize category, with identical pregnancy rates observed in \nthe large cyst group (36.0% vs 33.3%, p = 0.772). Our find-\nings have clinical implications that are relevant to daily \npractice when deciding to proceed with stimulation in \nthe presence of endometrioma. The absence of demon -\nstrable surgical benefit, even for large cysts, indicates that \ncyst size should not be regarded as the sole determinant \nin surgical decision making. These findings underscore \nthe need for a more individualized approach that inte -\ngrates multiple patient specific factors to guide optimal \nmanagement.\nIn clinical practice, there has always been controversy \nregarding the best way to treat endometriomas during \nART [ 21–23], particularly when there is a large endo -\nmetrioma [1, 24–26]. The results of this study provide \npractitioners with new insights regarding treatment, as \nit was found that comparable outcomes can be obtained \neven with large endometriomas, thus suggesting that \nsurgery for endometrioma  before ovarian stimulation is \nnot mandatory. The present findings are consistent with \nthe (ESHRE) European Society of Human Reproduction \nand Embryology recommendations [27], which state \nthat in infertile women with endometriomas larger than \n3 cm, there is no evidence that cystectomy prior to ART \nimproves pregnancy outcomes. Similar results have been \nreported in the literature [28–30]. Although some studies \nhave claimed that the presence of such a large endome -\ntrioma warrants conservative procedures (transvaginal \nultrasound-guided aspiration of ovarian endometrioma \nor ethanol sclerotherapy) before IVF [26]. Other studies \nhave found that IVF outcomes are significantly impaired \nin women with endometriomas, with a higher risk of \nreduced ovarian response [31]. These discrepancies may \nbe explained by the inclusion of heterogeneous patient \npopulations, such as women with other forms of endo -\nmetriosis, as well as variability in surgical techniques. In \ncontrast, our study focused exclusively on women with \nendometriomas, with the operated group undergoing \nlaparoscopic cystectomy, thereby reducing heterogeneity \nand providing a clearer assessment of surgical impact.\nIn this study, the decision to perform surgery was based \non patient symptoms, with a focus on preserving ovarian \nreserve. While surgery resulted in a slight decrease in \novarian reserve and an increased requirement for gonad -\notropins, the number of oocytes and embryos retrieved \nremained comparable to those in patients without sur -\ngery. On the other hand, even in cases where the cyst \nwas not removed, a comparable number of oocytes and \nembryos were obtained. This suggests that the presence \nof the endometrioma does not negatively affect oocyte \nretrieval, and IVF can be successfully performed without \nthe need for endometrioma removal in asymptomatic \npatients. Additionally, symptomatic patients with good \novarian reserve can undergo IVF after endometrioma \nsurgery without negatively impacting the outcomes.\nAccording to the current data, endometriotic cys -\ntectomy before IVF does not improve ovarian respon -\nsiveness and IVF outcomes, irrespective of the \nendometrioma size [2, 32–34]. It has been reported that \nthe presence of  endometrioma  can have a detrimental \nimpact on ovarian responsiveness to ovarian stimula -\ntion [2, 12, 34–39], while earlier studies found that cyst \nsize may be relevant and could negatively affect the suc -\ncess of IVF [11, 40], present study observed no notable \ndifference in IVF outcomes based on different cyst size. \nAlthough the cyst size was significantly larger in the \noperated group compared to the non-operated group, \nthis may have introduced a potential selection bias. \nHowever, the similar reproductive outcomes across size \n\nPage 8 of 10Firdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \ncategories suggest that conservative management may be \nappropriate even for larger endometriomas, particularly \nwhen the primary goal is achieving pregnancy through \nassisted reproduction rather than symptom relief.\nAnti-Müllerian Hormone (AMH) was slightly lower in \nthe surgery group (1.72 ± 0.90) compared to the non-sur -\ngery group (2.09 ± 1.26), although the difference was not \nstatistically significant (p = 0.136). This observation aligns \nwith previous evidence suggesting that surgical interven -\ntion may negatively impact ovarian reserve [41–44]. The \nAMH-based stratification provided particularly reveal -\ning insights into the subtle effects of surgery on ovarian \nfunction. Even among women who maintained relatively \npreserved AMH levels post-surgery (≥ 1.5  ng/ml), the \noperated group required significantly higher gonadotro -\npin doses (3867 vs 3245  IU, p = 0.006) to achieve com -\nparable oocyte yields and pregnancy rates. While AMH \nreflects the quantity of remaining follicles, it may not \nadequately reflect changes in ovarian sensitivity to gon -\nadotropins. The increased gonadotropin requirements in \nthe normal AMH surgical group indicate that qualitative \nchanges in ovarian responsiveness may occur after sur -\ngery even when quantitative markers appear preserved.\nThe stratified analysis by age groups revealed particu -\nlarly noteworthy findings regarding surgical interven -\ntion in older women. While younger women (< 35 years) \nshowed no significant difference in gonadotropin require-\nments between operated and non-operated groups (3653 \nvs 3287  IU, p = 0.121), older women (≥ 35  years) who \nunderwent surgery required significantly higher gon -\nadotropin doses (4444 vs 3892  IU, p = 0.045). This find -\ning has important clinical implications, as it suggests \nthe increased gonadotropin requirements in older surgi -\ncal patients may reflect the combined negative effects of \nage-related ovarian decline and surgery-induced ovarian \ndamage, creating a \"double burden\" on ovarian response. \nThe lack of improvement in clinical pregnancy rates fol -\nlowing surgery in both age groups (younger: 41.1% vs \n47.8%, p = 0.745; older: 27.7% vs 36.0%, p = 0.652) rein-\nforces the conclusion that surgical intervention does not \nprovide reproductive benefits in the IVF setting, regard -\nless of maternal age.\nThese findings are in line with those of Garcia-Velasco \net al. [35], their study also suggested that the endometri -\noma-removed group required a significantly higher dose \nof gonadotropins (3,880 ± 129  IU) than the endometri -\noma-present group (3,404 ± 162 IU, P = 0.035), suggesting \nthat prior surgical removal may impair ovarian respon -\nsiveness but with comparable IVF outcomes in terms of \nmature oocyte recovery and pregnancy rates [35]. How -\never, our study adds valuable information by demonstrat-\ning these findings across multiple stratification analyses, \nincluding age, AMH levels, and cyst size.\nThese results demonstrate that the decision to per -\nform endometrioma surgery should be carefully assessed \nbefore IVF to prevent the possible harm to ovarian func -\ntion. With appropriate stimulation protocols, favorable \nIVF outcomes can still be achieved in women with endo -\nmetriomas, regardless of their size and whether they have \nbeen surgically removed or remain in place.\nIf laparoscopic surgery does not improve ovarian func -\ntion or enhance IVF outcomes, then one might question \nthe rationale for performing the procedure. However, \nwhen endometrioma is not only associated with infer -\ntility but also with severe pain, surgery is the preferred \noption to address both issues simultaneously [27, 45]. \nTherefore, factors such as the patient’s age, certainty of \ndiagnosis, and presence of symptoms are critical when \ncounseling on whether to pursue conservative ovarian \nsurgery or proceed directly to IVF [27, 45].\nIn conclusion, our study demonstrates that surgical \nremoval of endometriomas does not improve IVF out -\ncomes compared to conservative management, while \npotentially compromising ovarian function as evidenced \nby increased gonadotropin requirements. These find -\nings were consistent across different patient age groups, \nAMH levels, and cyst sizes. Conservative management of \nendometriomas appears to be the preferred approach for \nwomen planning IVF treatment, with surgery reserved \nfor cases where symptomatic relief is the primary indi -\ncation. This evidence supports a paradigm shift toward \nless invasive management strategies that may shorten \nthe time to pregnancy, reduce patient costs, and prevent \npotential surgical complications while achieving compa -\nrable reproductive outcomes. Conversely, in symptomatic \nwomen, conservative ovarian surgery may still be consid -\nered, as it did not negatively affect IVF success rates.\nStrengths\nSeveral methodological strengths enhance the validity \nand clinical relevance of our findings. First, our compre -\nhensive stratified analysis by age, AMH levels, and cyst \nsize provides nuanced insights that can guide individu -\nalized patient counseling and treatment decisions. This \nmulti-dimensional approach allows clinicians to apply \nour findings to specific patient populations rather than \nrelying on broad generalizations. Our study also utilized \nthe OSI as a dynamic marker of ovarian responsiveness to \ncompare between operated and non-operated endome -\ntriomas, a factor that has not been addressed in previous \nstudies. OSI is a more reliable and objective method for \nassessing ovarian response in endometrioma, as it does \nnot rely on antral follicle count and provides insights \ninto the total gonadotropins used during stimulation. \nThe inclusion of OSI and gonadotropin dose require -\nments, provides valuable mechanistic insights beyond \n\nPage 9 of 10\nFirdaus et al. Middle East Fertility Society Journal           (2025) 30:58 \n \nsimple pregnancy outcomes. This functional assessment \noffers a more complete picture of the impact of surgical \nintervention on ovarian physiology, which is crucial for \nunderstanding the biological basis of our observations. \nPrevious studies in the literature exhibit heterogeneity \nin terms of surgical approaches, the strength of the pre -\nsent study lies in its focus on laparoscopic cystectomy \nand its impact on patients with endometriomas. Addi -\ntionally, this study uniquely considers both the size of \nthe endometrioma and the surgery of endometrioma as \nfactors influencing outcomes, an aspect not commonly \naddressed together in previous studies.\nLimitations and suggestions for future research\nThe relatively small sample size (n = 83) may have limited \nthe statistical power to detect clinically meaningful differ-\nences between groups, potentially leading to type II error \nwhere true differences might remain undetected. Future \nstudies with larger cohorts and multicenter design would \nprovide more robust evidence regarding the impact of \nendometrioma management on IVF outcomes. Since all \nsurgeries were performed at our reproductive center, the \nresults may not be generalizable. Unfortunately, there are \nno randomized controlled trials in the literature that have \ninvestigated the precise effects of endometriosis surgery \nbefore IVF. Because various endometriosis manifesta -\ntions, including ovarian endometrioma, deep endometri -\nosis (DE), and superficial endometriosis, are often treated \nconcurrently during surgery, it is difficult to draw a clear \ncorrelation between endometrioma and its removal and \nIVF outcomes. Additional studies are needed to further \nelucidate these findings. Randomized controlled trials \n(RCTs) are needed to provide more robust evidence with \nclearly defined outcomes, particularly in relation to the \nsize of the endometrioma.\nAbbreviations\nIVF  In-Vitro Fertilization\nAMH  Anti-Mullerian Hormone\nAFC  Antral Follicular count\nGnRH  Gonadotropin Releasing Hormone\nFSH  Follicular Stimulating Hormone\nOSI  Ovarian Sensitivity Index\nHCG  Human Chorionic Gonadotropin\ncCPR  Cumulative Clinical Pregnancy Rate\nIQR  Inter-Quartile Range\nICSI  Intra Cytoplasmic Sperm Injection\nDIE  Deep infiltrating endometriosis\nOHSS  Ovarian hyperstimulation syndrome\nART   Assisted reproductive technology\nBMI  Body mass index\nESHRE  European Society of Human Reproduction and Embryology\nAcknowledgements\nNot applicable.\nAuthors’ contributions\nP .K.A and A.S contributed to the design and implementation of the research, \nA.F contributed to data collection, analysis of the results and writing of the \nmanuscript. P .K.A and S.V to review, editing and revision of the manuscript. \nV.G.P , S.V and P .K.N helped in providing intellectual inputs and proofreading \nof manuscript and supervised the project. All authors read and approved the \nfinal manuscript.\nFunding\nThis work did not receive any specific grant from any funding agency in the \npublic, commercial, or non-profit sector.\nData availability\nThe datasets used and/ or analyzed during the current study are available \nfrom the corresponding author upon reasonable request.\nDeclarations\nEthics approval and consent to participate\nThe present study was approved by Institutional Ethical Committee (Kasturba \nMedical College and Kasturba Hospital Institutional Ethical Committee, Regis-\ntration No. ECR/146/Inst/KA/2013/RR-19) on 23/10/ 2024 (IEC1: 396/2024).\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAuthor details\n1 Department of Reproductive Medicine and Surgery, Kasturba Medical Col-\nlege Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, \nIndia. 2 MMC IVF centre, Dubai, UAE. \nReceived: 21 January 2025   Accepted: 19 October 2025\nReferences\n 1. 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