Topic- impact of laparoscopic cystectomy and endometrioma size on IVF outcomes: insights from a retrospective cohort study

Background Endometrioma, a common manifestation of endometriosis, can impact fertility and are often encoun- tered in women undergoing assisted reproductive technologies (ART). Traditionally, surgical removal of endome- triomas has been considered standard practice before in vitro fertilization (IVF). However, recent research questions whether surgery is necessary, as its benefits in improving IVF outcomes remain debated. The findings of present study contribute to the ongoing debate by examining both surgical management and cyst size as factors influencing IVF outcomes. The present study also aimed to use the Ovarian Sensitivity Index (OSI) as a dynamic marker of ovarian responsiveness to compare operated and non-operated endometriomas, a factor that has not been investigated in previous studies.

This retrospective cohort study compared IVF outcomes between women with operated (n = 35) and non- operated (n = 48) endometriomas. We also evaluated the impact of endometrioma size ( 4 cm) on clinical outcomes. All participants were under 40 years of age and underwent their first cycle of IVF. The primary outcome was clinical pregnancy rate, while secondary outcomes included embryological parameters (total number of oocytes retrieved, mature oocytes, and good-quality embryos) and stimulation characteristics (total gonadotropin dose requirements and OSI). Statistical comparisons were made between the groups.

The total gonadotropin dose was significantly higher in the operated group (4050 IU vs. 3600 IU, p = 0.032). However, the number of oocytes, mature oocytes, and good-quality embryos were similar between oper- ated and non-operated groups. Regarding cyst size, no significant differences in IVF outcomes were found between women with smaller ( 4 cm) endometriomas.

This study suggests that IVF outcomes are not significantly affected by the removal of endometriomas. While laparoscopic cystectomy may slightly increase gonadotropin requirements and potentially compromise ovarian reserve, it does not negatively impact IVF success rates. In asymptomatic patients, IVF can be successfully performed without the need for endometrioma removal, as the presence of the endometrioma does not appear to hinder IVF outcomes. Additionally, endometrioma size did not significantly influence IVF outcomes in this study. For women with symptomatic endometriomas, surgical intervention may still be considered, as it does not seem to deteriorate IVF outcomes, provided that careful patient selection is made.

Endometrioma, IVF outcomes, Oocyte retrieval, Ovarian stimulation, Endometriotic cystectomy, Ovarian sensitivity index (OSI), Endometriosis *Correspondence: Prashanth K. Adiga [email protected] Full list of author information is available at the end of the article Page 2 of 10Firdaus et al. Middle East Fertility Society Journal (2025) 30:58

In the context of ART, endometriomas present a unique and substantial challenge. Its prevalence is estimated to be between 23% and 55% [1 ]. The treatment of endo - metriomas before IVF has long been a clinical dilemma, with opinions on whether surgery should be performed before IVF or whether the endometrioma should be left intact. Both strategies offer both benefits and draw - backs of their own [2 ]. Leaving the endometrioma intact during ovarian stimulation may lead to complications during ovum pickup, such as difficulty in accessing the ovaries, folli - cular fluid contamination, exposure to oxidative stress, and the potential formation of an abscess, all of which could negatively impact oocyte quality [2 – 4]. On the other hand, surgical removal of endometrio - mas requires a high level of surgical expertise and car - ries risks such as delayed ART, recurrence, increased cost, and the possibility of incomplete cyst removal, which may affect fertility outcomes [5 ]. Surgery for endometriomas can lower ovarian reserve, as measured by AMH, and reduce the response to stimulation [6 – 9]. Additionally, while endometriomas are thought to decrease ovarian responsiveness to stimulation [10], the exact mechanisms remain unclear. Some studies suggest that the size of the endometrioma may influ - ence ovarian response, with larger cysts potentially impairing stimulation results and pregnancy chances [11– 13]. However, there is still a debate regarding the size threshold beyond which fertility outcomes are compromised [11, 13, 14]. Currently, there is no clear consensus or standardized guidance in the literature concerning IVF treatment in endometriomas, specifi - cally with regards to decision making according to size of endometrioma. Given these gaps in knowledge, this study aims to address some of the unresolved issues in the lit - erature. The aim of this study is to compare IVF out - comes in patients with endometriomas by comparing: (1) patients who underwent IVF with and without cyst removal and (2) patients with endometriomas smaller and greater than 4 cm. This study will use the ovarian sensitivity index (OSI) as a dynamic measure for ovarian response to compare operated and non-operated endometriomas, a factor that has not been investigated in previous studies. This approach makes our study distinct by incorporating a dynamic marker OSI to assess ovarian responsiveness. The incorporation of OSI may yield significant insights into ovarian response and enhance the understanding of endometrioma effects on IVF results. Aim and objectives To Compare the IVF outcomes between operated and non-operated endometrioma. IVF Outcomes between endometrioma size 4cm.

This observational retrospective cohort study was con - ducted in the Department of Reproductive Medicine and Surgery, Kasturba Medical College and Hospital, Mani - pal, from May 2021 to April 2024, and included 83 sub - jects based on specific criteria. The study was approved by the Institutional Review Board of our medical center, ensuring compliance with ethical guidelines. Inclu - sion Criteria: Participants were included if they had a confirmed diagnosis of endometrioma on ultrasound and had undergone first cycle of IVF treatment. Endo - metriotic cysts appear as homogeneous low-echogenic fluid masses without papillary proliferation [15]. Some patients underwent laparoscopic endometriotic cystec - tomy prior to being recruited for IVF, while others were directly recruited for IVF without the removal of the cyst. In cases with bilateral and/or multiple cysts, the mean diameter of the endometriotic cyst was selected. Endo - metriotic cystectomy was performed by skilled special - ists with a strong emphasis on preserving the patient’s reproductive potential. Patients who underwent cystec - tomy were recruited for IVF within 1 year of laparoscopic endometriotic cystectomy. The decision to perform cys - tectomy was based on patient symptoms. Participants were excluded if they had other underlying medical conditions that could independently affect IVF outcomes, such as severe male factor infertility, autoim - mune disorders, presence of adenomyosis features, and uterine abnormalities (fibroids and uterine polyps). The data collected included personal history, fertility investi - gation results, age, body mass index (BMI), anti-Mülle - rian hormone concentration (AMH), antral follicle count (AFC), type (primary or secondary), duration of infertil - ity, and stimulation parameters. Stimulation protocol Women were monitored and managed according to the clinical protocol of our study center. Two ovarian stim - ulation protocols involving 150–600  IU/day of (FSH) follicle stimulating hormone were used: (i) a flexible antagonist protocol and (ii) an agonist flare protocol. Gonadotropin doses and stimulation protocol types were determined based on patient characteristics and clinician decisions. Final oocyte maturation was triggered when three or more ovarian follicles ≥ 18 mm in diameter were visible by ultrasound, using either 250 µg of recombinant Page 3 of 10 Firdaus et al. Middle East Fertility Society Journal (2025) 30:58 (HCG) human chorionic gonadotropin or 1  mg of sub - cutaneous leuprolide, if ovarian hyperstimulation syn - drome (OHSS) risk was identified. Oocyte retrieval was performed 35–36  h after transvaginal aspiration under ultrasound guidance, with 1.2 g of amoxicillin and clavu - lanic acid administered as antibiotic prophylaxis. Intra - cytoplasmic sperm injection (ICSI) was performed in all patients. Embryo grading was performed using the Istan - bul consensus, and cleavage-stage frozen embryos were transferred. Grade 1 and grade 2 embryos were taken as good quality embryos. Embryo transfer protocol Hormone replacement cycle (HRT) frozen embryo trans- fer was performed for all patients, (3.75  mg leuprolide) GnRH (gonadotrophin releasing hormone) agonist was given on day 21 of the previous cycle. Estradiol valerate 2  mg three times a day was given for the endometrial preparation. Luteal phase support included progesterone (gel) 90 mg twice daily, dydrogesterone 20 mg twice daily, continued for up to 10 weeks of pregnancy if beta HCG was positive 14 days after embryo transfer. Outcomes measured in terms of embryological (num - ber of oocytes retrieved, M2 oocytes, good-quality embryos grade1 & 2) and clinical outcomes (clinical pregnancy rate). Additional markers such as OSI (num - ber of oocytes retrieved/total gonadotrophin dose) was also calculated and compared between the groups. The Ovarian Sensitivity Index (OSI) was calculated using the formula: OSI = Total number of oocytes retrieved ÷ Total gonadotropin dose administered (in IU) × 1000. OSI serves as a standardized measure of ovarian responsiveness to exogenous gonadotropin stimulation, with higher values indicating better ovarian sensitivity [16]. This index has been validated as a reli - able marker for assessing ovarian responsiveness in ART cycles, allowing for comparison between different stimu - lation protocols and patient populations [17]. While the absolute number of oocytes retrieved remains an impor - tant measure of ovarian response, OSI provides a com - plementary marker that adjusts for gonadotropin dose, thereby minimizing inter-individual variability and offer - ing a more standardized assessment of ovarian sensitiv - ity [17]. Previous studies have demonstrated OSI to be a valid and reliable marker of ovarian sensitivity, offering a more accurate representation of the ovarian response to stimulation compared to oocyte yield or gonadotropin dose considered separately [16, 17]. Definition of outcomes Cumulative clinical pregnancy rate was taken as the primary outcome measure for comparison between groups. Secondary outcomes comprised embryological parameters including the total number of oocytes retrieved, number of mature oocytes, and number of good-quality embryos obtained. Additional secondary outcomes included stimulation parameters such as total gonadotropin dose requirements and ovarian sensitivity index (OSI). Statistical analyses were performed to com - pare these outcomes between the study groups. Clinical pregnancy rates Clinical pregnancy was determined by ultrasound documentation of at least one fetus with a heartbeat at 6–7  weeks of gestation [18]. The cumulative  clinical pregnancy rate(cCPR)  was defined as the proportion of women who had at least one clinical pregnancy whether from the first transfer attempt or subsequent transfers of frozen–thawed supernumerary embryos (per IVF/ICSI cycle). The mean number of embryo transfer cycles per patient has also been reported and compared. These outcome measures were compared between two groups: operated and non-operated endometriomas and between endometriomas 4 cm in size, all of whom underwent IVF. Statistical analysis Statistical analysis was performed with SPSS software. Continuous variables were presented as mean ± standard deviation (SD), median (interquartile range, IQR) and categorical variables as numbers (%), depending upon the normality of data. Data distribution was assessed through histograms and confirmed using HistoFit software. Primary analysis Continuous variables with non-normal distributions were compared using the Mann–Whitney U test, while normally distributed continuous variables were com - pared using the independent t-test. Categorical variables were analyzed using the chi-square test or Fisher’s exact test. Statistical significance was set at p < 0.05. Stratified analysis for confounder control To address potential confounding variables that might influence the association between endometrioma surgery and ART outcomes, we performed stratified analyses based on three key clinical factors: 1. Age stratification: Patients were divided into two groups: < 35 years and ≥ 35 years 2. AMH stratification: Based on pre-stimulation AMH levels (reflecting post-surgical status in the oper - ated group and baseline status in the non-operated group), patients were categorized as low AMH (< 1.5 ng/ml) or normal AMH (≥ 1.5 ng/ml) Page 4 of 10Firdaus et al. Middle East Fertility Society Journal (2025) 30:58 3. Endometrioma size stratification: Cysts were classi - fied as < 4 cm or ≥ 4 cm. Within each stratum, we compared IVF outcomes between operated and non-operated groups using the same statistical tests as the primary analysis. This approach allowed us to control for these important con - founders and assess whether treatment effects remained consistent across different patient subgroups.

Table  1 compares IVF outcomes between operated (n = 35) and non-operated endometrioma (n = 48). Age and BMI was comparable between the two groups. Anti- Müllerian hormone (AMH) levels and antral follicle count (AFC) were slightly higher in the non-operated group but comparable values. The mean size of the endo- metrioma was significantly smaller in the non-operated group (3.10  cm ± 1.75) than in the operated endometri - oma group (5.15 cm ± 2.1) (p = 0.012). The total gonado - trophin dose required was significantly higher in patients who underwent IVF after surgery for endometrioma than in the non-operated group (p = 0.032). OSI was lower in the operated endometrioma group than non the operated group (2.12 ± 1.40 vs 2.82 ± 2.95, p = 0.198), suggesting that ovarian responsiveness to stimulation was slightly reduced after surgery, but the difference was not statis - tically significant. Both groups had comparable num - bers of oocytes, mature (M2) oocytes, and good-quality embryos and clinical pregnancy with no significant dif - ferences in these outcomes (p = 0.395, 0.236, 0.740 and 1.00 respectively). Table 2 compares various parameters between patients with endometrioma of size less than 4  cm (n = 43) and those with endometrioma greater than 4  cm (n = 40). Baseline characteristics were found comparable between the two groups. The number of oocytes and mature (M2) oocytes, as well as the number of good quality embryos and clinical pregnancy showed no significant differences in two compared groups suggesting that size of endome - trioma is not significant determinant of stimulation out - comes. A significantly greater proportion of women with endometriomas ≥ 4  cm underwent surgery compared to those with cysts < 4 cm (62.5% vs. 23.3%, P = 0.009). Table 3 illustrates that stratified analysis by age groups revealed consistent patterns across both age strata. In younger women (< 35 years), surgical removal of endome- triomas did not significantly affect gonadotropin require- ments compared to conservative management (3653 vs 3287  IU, p = 0.121), while in older women (≥ 35  years), surgery was associated with significantly higher gonado - tropin needs (4444 vs 3892 IU, p = 0.045). Despite higher Table 1 Comparative analysis of IVF outcomes in operated and non-operated endometrioma AMH Anti−Mullerian Hormone, BMI Body mass index, AFC Antral follicle count, OSI Ovarian sensitivity index, IQR Inter quartile range a t−test b Mann−Whitney U test c Fisher’s exact test ** Significant at p<0.05 Parameters (N = 83) Operated (n = 35) Non-operated (n = 48) P value Baseline Variables Age (years) 32.36 ± 2.98 33.4 ± 2.63 0.098a BMI(kg/m 2) 22.8 ± 2.26 22.8 ± 3.23 0.87a AMH (ng/ml) 1.72 ± 0.90 2.09 ± 1.26 0.136a AFC(median, IQR) 9 (12–6) 11 (13–8) 0.052b Mean size of endometriotic cyst (cm) 5.15 ± 2.1 3.10 ± 1.75 0.012a** Stimulation protocol Flare agonist protocol 7 (20.0%) 8 (16.7%) 0.785c Antagonist protocol 28 (80.0%) 40 (83.3%) Total dose of gonadotrophins(IU) 3639.58 ± 712.97 3054.68 ± 888.14 0.032a** Embryo transfer cycles performed 1.5 ± 1.2 1.3 ± 1.2 0.607a OSI 2.12 ± 1.40 2.82 ± 2.95 0.198a Clinical Outcomes Number of oocytes 6 (8.25- 4.75) 6.5 (10–5) 0.395b M2 oocytes 5 (7–4) 6 (8–4) 0.236b Good quality embryos 4 (5–2.75) 4 (6–3) 0.740b Clinical pregnancy 13/35 (37.1%) 19/48 (39.6%) 1.000c Page 5 of 10 Firdaus et al. Middle East Fertility Society Journal (2025) 30:58 gonadotropin requirements in the older surgical group, oocyte retrieval numbers remained comparable between surgical and conservative approaches in both age groups (younger: 6 vs 7, p = 0.677; older: 6 vs 7, p = 0.883). Clini- cal pregnancy rates showed similar patterns across age groups, with no significant benefit of surgery observed in either younger (7/17 [41.1%] vs 11/23 [47.8%], p = 0.745) or older women (5/18 [27.7%] vs 9/25 [36.0%], p = 0.652). Table 4: On stratified analysis by AMH levels, the oper - ated group had significantly larger cyst size compared to the non-operated group in both strata (AMH < 1.5  ng/ ml: 5.4 ± 1.8 cm vs. 3.3 ± 1.6 cm, P = 0.001; AMH ≥ 1.5 ng/ Table 2 Endometrioma size based comparison of stimulation outcomes AMH Anti−Mullerian Hormone, BMI Body mass index, AFC Antral follicle count, IQR Inter quartile range, IU International units, OSI Ovarian sensitivity index a t-test b Mann-Whitney U test d chi-square test ** Significant at p < 0.05 Parameters Size 4 cm,(n = 40) P value Baseline Variables Age (years) 33.42 ± 2.84 32.65 ± 3.11 0.583a AMH (ng/ml) 1.93 ± 1.08 1.98 ± 1.23 0.746a AFC (median, IQR) 10 (13–8) 10 (12–6.25) 0.248b Total gonadotrophins dose (IU) 3505.55 ± 807.25 3534.86 ± 844.24 0.684a Duration of stimulation 9.19 ± 0.89 9.29 ± 0.95 0.456a Operated endometrioma 10/43 (23.25%) 25/40 (62.5%) 0.009d** OSI 2.38 ± 2.39 2.68 ± 2.51 0.579a Clinical Outcomes Number of oocytes 6 (9—4.5) 6.5 (9.75–5) 0.667b Number of M2 oocytes 5 (8–4) 5.5 (8–4) 0.362b Good quality embryos 4 (5–3) 4 (6–3) 0.664b Embryo transfer cycles performed 2.1 ± 0.9 1.5 ± 1.2 0.365a Clinical pregnancy 17/43 (39.53%) 15/40 (37.50%) 0.445d Table 3 Stratified analysis by age groups AMH Anti−Mullerian Hormone, AFC Antral follicle count, IQR Inter quartile range, IU International units a t-test b Mann-Whitney U test c Fisher’s exact test ** Significant at p < 0.05 Parameter Age < 35 Years Age ≥ 35 Years Operated (n = 17) Non-operated (n = 23) P-value Operated (n = 18) Non-operated (n = 25) P-value Baseline Characteristics Mean age (years) 31.4 ± 1.8 31.8 ± 1.9 0.456 36.2 ± 1.3 36.8 ± 1.2 0.167a AMH (ng/ml) 1.67 ± 0.71 1.92 ± 0.83 0.312 1.46 ± 0.68 1.71 ± 0.94 0.378a AFC (median, IQR) 10 (8–13) 11 (8–15) 0.423 8 (6–12) 10 (8–12) 0.189b Mean size of endometriotic cyst (cm) 5.2 ± 1.4 2.9 ± 1.1 < 0.001** 5.1 ± 2.7 3.2 ± 2.0 0.017a** Total gonadotropins dose(IU) 3653 ± 692 3287 ± 734 0.121 4444 ± 721 3892 ± 856 0.045a** IVF Outcomes Number of oocytes 6 (5–8) 7 (5–10) 0.677 6 (4–8) 7 (4–10) 0.883b M2 oocytes 5 (4–7) 6 (4–8) 0.798 4 (3–6) 6 (4–10) 0.678b Good quality embryos 4 (3–5) 4 (3–6) 0.634 3 (2–5) 3 (2–4) 0.721b Clinical pregnancy 7/17 (41.1%) 11/23 (47.8%) 0.745 5/18 (27.7%) 9/25 (36.0%) 0.652c Page 6 of 10Firdaus et al. Middle East Fertility Society Journal (2025) 30:58 ml: 4.9 ± 2.3 cm vs. 2.9 ± 1.9 cm, P = 0.003). However, IVF outcomes including number of oocytes (AMH < 1.5  ng/ ml: 5 vs. 5; AMH ≥ 1.5 ng/ml: 8 vs. 8), M2 oocytes, good quality embryos, and clinical pregnancy rates (26.6% vs. 35.0%; 40.0% vs. 46.4%) were comparable between oper - ated and non-operated women. Table  5: On stratified analysis by cyst size, oper - ated women had significantly larger cysts compared to non-operated in the ≥ 4  cm group (5.8 ± 1.2 vs. 4.7 ± 0.8  cm, P = 0.003), while cyst size was compa - rable in the < 4  cm group. However, gonadotropin requirement, oocyte yield, embryo quality, and clini - cal pregnancy rates were similar between operated and non-operated women across both strata, irrespective of surgery status. Table 4 Stratified analysis by AMH levels AMH Anti−Mullerian Hormone, AFC Antral follicle count, IQR Inter quartile range a t-test b Mann-Whitney U test c Fisher’s exact test ** Significant at p < 0.05 Parameter AMH (< 1.5 ng/ml) AMH (≥ 1.5 ng/ml) Operated (n = 15) Non-operated (n = 20) P-value Operated (n = 20) Non-operated (n = 28) P-value Baseline Characteristics Mean AMH (ng/ml) 1.03 ± 0.25 1.12 ± 0.28 0.336 2.11 ± 0.89 2.47 ± 1.12 0.245a Age (years) 34.7 ± 2.4 35.1 ± 2.8 0.678 33.0 ± 2.9 32.5 ± 3.2 0.567a AFC (median, IQR) 8 (6–10) 9 (7–11) 0.445 11 (9–14) 12 (10–16) 0.234b Mean size of endometriotic cyst (cm) 5.4 ± 1.8 3.3 ± 1.6 0.001** 4.9 ± 2.3 2.9 ± 1.9 0.003a** Total gonadotropins dose(IU) 4267 ± 643 4125 ± 789 0.567 3867 ± 734 3245 ± 712 0.006a** IVF Outcomes Number of oocytes 5 (4–5) 5 (4–6) 0.734 8 (6–12) 8 (5–11) 0.783b M2 oocytes 4 (3–4) 4 (3–5) 0.689 7 (6–8) 8 (5–10) 0.745b Good quality embryos 2 (2–3) 3 (2–4) 0.612 5 (4–6) 4 (3–6) 0.678b Clinical pregnancy 4/15 (26.6%) 7/20 (35.0%) 0.689 8/20 (40.0%) 13/28 (46.4%) 0.723c Table 5 Stratified analysis by endometrioma size AMH Anti−Mullerian Hormone, AFC Antral follicle count, IQR Inter quartile range a t-test b Mann-Whitney U test c Fisher’s exact test ** Significant at p < 0.05 Parameter Small Cysts (< 4 cm) Large Cysts (≥ 4 cm) Operated (n = 10) Non-operated (n = 33) P-value Operated (n = 25) Non-operated (n = 15) P-value Baseline Characteristics Mean 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** Age (years) 33.2 ± 2.8 33.5 ± 3.1 0.789 34.1 ± 2.9 34.8 ± 2.6 0.456a AMH (ng/ml) 1.78 ± 0.89 1.89 ± 1.02 0.734 1.45 ± 0.67 1.67 ± 0.78 0.378a AFC (median, IQR) 10 (8–13) 11 (9–14) 0.445 8 (6–11) 9 (7–12) 0.345b Total gonadotropins dose(IU) 3750 ± 645 3445 ± 678 0.234 4200 ± 723 3867 ± 834 0.212a IVF Outcomes Number of oocytes 8 (5–11) 8 (5–10) 0.732 7 (4–9) 7 (4–10) 0.678b M2 oocytes 7 (5–10) 7 (4–9) 0.789 6 (3–7) 6 (3–9) 0.645b Good quality embryos 5 (2–7) 5 (2–6) 0.823 4 (2–5) 4 (2–5) 0.712b Clinical pregnancy 3/10 (30.0%) 15/33 (45.45%) 0.352 9/25 (36.0%) 5/15 (33.3%) 0.772c Page 7 of 10 Firdaus et al. Middle East Fertility Society Journal (2025) 30:58

The present study was conducted with the aim of evalu - ating IVF outcomes in operated and non-operated endo - metrioma and to determine the impact of endometrioma size on clinical outcomes. One of the most significant findings of our study was the substantially higher gon - adotropin requirement in the operated group com - pared to the non-operated group (3639.58 ± 712.97 IU vs 3054.68 ± 888.14  IU, p = 0.032). This finding aligns with growing evidence that surgical excision of endometrio - mas may inadvertently damage healthy ovarian tissue and compromise ovarian reserve  [19, 20]. The ovarian sensitivity index (OSI), though not statistically signifi - cant, showed a trend toward reduced ovarian respon - siveness in the operated group (2.12 ± 1.40 vs 2.82 ± 2.95, p = 0.198), further supporting concerns about post-sur - gical ovarian function. However, despite the higher gon - adotropin requirement, IVF outcomes including oocyte yield and embryo quality, were comparable between the two groups. The cumulative clinical pregnancy rates were comparable between operated and non-operated groups (37.1% vs 39.6%, p = 1.000), suggesting that surgical removal of endometriomas may not confer reproductive advantages in the context of assisted reproductive tech - nology. This finding is important in-patient counseling, as it underscores the potential for increased treatment costs without a corresponding improvement in clinical outcomes. The size-based stratification revealed a clear selection bias in clinical practice, with 62.5% of large cysts (≥ 4 cm) underwent surgery compared to only 23.3% of small cysts (< 4  cm). The selection of endometriomas greater than 4  cm for surgical intervention may have introduced a potential selection bias, as these larger cysts were more often chosen for removal under the assumption that their excision could improve IVF outcomes. However, surgical intervention did not result in superior outcomes in either size category, with identical pregnancy rates observed in the large cyst group (36.0% vs 33.3%, p = 0.772). Our find- ings have clinical implications that are relevant to daily practice when deciding to proceed with stimulation in the presence of endometrioma. The absence of demon - strable surgical benefit, even for large cysts, indicates that cyst size should not be regarded as the sole determinant in surgical decision making. These findings underscore the need for a more individualized approach that inte - grates multiple patient specific factors to guide optimal management. In clinical practice, there has always been controversy regarding the best way to treat endometriomas during ART [ 21–23], particularly when there is a large endo - metrioma [1, 24–26]. The results of this study provide practitioners with new insights regarding treatment, as it was found that comparable outcomes can be obtained even with large endometriomas, thus suggesting that surgery for endometrioma  before ovarian stimulation is not mandatory. The present findings are consistent with the (ESHRE) European Society of Human Reproduction and Embryology recommendations [27], which state that in infertile women with endometriomas larger than 3 cm, there is no evidence that cystectomy prior to ART improves pregnancy outcomes. Similar results have been reported in the literature [28–30]. Although some studies have claimed that the presence of such a large endome - trioma warrants conservative procedures (transvaginal ultrasound-guided aspiration of ovarian endometrioma or ethanol sclerotherapy) before IVF [26]. Other studies have found that IVF outcomes are significantly impaired in women with endometriomas, with a higher risk of reduced ovarian response [31]. These discrepancies may be explained by the inclusion of heterogeneous patient populations, such as women with other forms of endo - metriosis, as well as variability in surgical techniques. In contrast, our study focused exclusively on women with endometriomas, with the operated group undergoing laparoscopic cystectomy, thereby reducing heterogeneity and providing a clearer assessment of surgical impact. In this study, the decision to perform surgery was based on patient symptoms, with a focus on preserving ovarian reserve. While surgery resulted in a slight decrease in ovarian reserve and an increased requirement for gonad - otropins, the number of oocytes and embryos retrieved remained comparable to those in patients without sur - gery. On the other hand, even in cases where the cyst was not removed, a comparable number of oocytes and embryos were obtained. This suggests that the presence of the endometrioma does not negatively affect oocyte retrieval, and IVF can be successfully performed without the need for endometrioma removal in asymptomatic patients. Additionally, symptomatic patients with good ovarian reserve can undergo IVF after endometrioma surgery without negatively impacting the outcomes. According to the current data, endometriotic cys - tectomy before IVF does not improve ovarian respon - siveness and IVF outcomes, irrespective of the endometrioma size [2, 32–34]. It has been reported that the presence of  endometrioma  can have a detrimental impact on ovarian responsiveness to ovarian stimula - tion [2, 12, 34–39], while earlier studies found that cyst size may be relevant and could negatively affect the suc - cess of IVF [11, 40], present study observed no notable difference in IVF outcomes based on different cyst size. Although the cyst size was significantly larger in the operated group compared to the non-operated group, this may have introduced a potential selection bias. However, the similar reproductive outcomes across size Page 8 of 10Firdaus et al. Middle East Fertility Society Journal (2025) 30:58 categories suggest that conservative management may be appropriate even for larger endometriomas, particularly when the primary goal is achieving pregnancy through assisted reproduction rather than symptom relief. Anti-Müllerian Hormone (AMH) was slightly lower in the surgery group (1.72 ± 0.90) compared to the non-sur - gery group (2.09 ± 1.26), although the difference was not statistically significant (p = 0.136). This observation aligns with previous evidence suggesting that surgical interven - tion may negatively impact ovarian reserve [41–44]. The AMH-based stratification provided particularly reveal - ing insights into the subtle effects of surgery on ovarian function. Even among women who maintained relatively preserved AMH levels post-surgery (≥ 1.5  ng/ml), the operated group required significantly higher gonadotro - pin doses (3867 vs 3245  IU, p = 0.006) to achieve com - parable oocyte yields and pregnancy rates. While AMH reflects the quantity of remaining follicles, it may not adequately reflect changes in ovarian sensitivity to gon - adotropins. The increased gonadotropin requirements in the normal AMH surgical group indicate that qualitative changes in ovarian responsiveness may occur after sur - gery even when quantitative markers appear preserved. The stratified analysis by age groups revealed particu - larly noteworthy findings regarding surgical interven - tion in older women. While younger women (< 35 years) showed no significant difference in gonadotropin require- ments between operated and non-operated groups (3653 vs 3287  IU, p = 0.121), older women (≥ 35  years) who underwent surgery required significantly higher gon - adotropin doses (4444 vs 3892  IU, p = 0.045). This find - ing has important clinical implications, as it suggests the increased gonadotropin requirements in older surgi - cal patients may reflect the combined negative effects of age-related ovarian decline and surgery-induced ovarian damage, creating a "double burden" on ovarian response. The lack of improvement in clinical pregnancy rates fol - lowing surgery in both age groups (younger: 41.1% vs 47.8%, p = 0.745; older: 27.7% vs 36.0%, p = 0.652) rein- forces the conclusion that surgical intervention does not provide reproductive benefits in the IVF setting, regard - less of maternal age. These findings are in line with those of Garcia-Velasco et al. [35], their study also suggested that the endometri - oma-removed group required a significantly higher dose of gonadotropins (3,880 ± 129  IU) than the endometri - oma-present group (3,404 ± 162 IU, P = 0.035), suggesting that prior surgical removal may impair ovarian respon - siveness but with comparable IVF outcomes in terms of mature oocyte recovery and pregnancy rates [35]. How - ever, our study adds valuable information by demonstrat- ing these findings across multiple stratification analyses, including age, AMH levels, and cyst size. These results demonstrate that the decision to per - form endometrioma surgery should be carefully assessed before IVF to prevent the possible harm to ovarian func - tion. With appropriate stimulation protocols, favorable IVF outcomes can still be achieved in women with endo - metriomas, regardless of their size and whether they have been surgically removed or remain in place. If laparoscopic surgery does not improve ovarian func - tion or enhance IVF outcomes, then one might question the rationale for performing the procedure. However, when endometrioma is not only associated with infer - tility but also with severe pain, surgery is the preferred option to address both issues simultaneously [27, 45]. Therefore, factors such as the patient’s age, certainty of diagnosis, and presence of symptoms are critical when counseling on whether to pursue conservative ovarian surgery or proceed directly to IVF [27, 45]. In conclusion, our study demonstrates that surgical removal of endometriomas does not improve IVF out - comes compared to conservative management, while potentially compromising ovarian function as evidenced by increased gonadotropin requirements. These find - ings were consistent across different patient age groups, AMH levels, and cyst sizes. Conservative management of endometriomas appears to be the preferred approach for women planning IVF treatment, with surgery reserved for cases where symptomatic relief is the primary indi - cation. This evidence supports a paradigm shift toward less invasive management strategies that may shorten the time to pregnancy, reduce patient costs, and prevent potential surgical complications while achieving compa - rable reproductive outcomes. Conversely, in symptomatic women, conservative ovarian surgery may still be consid - ered, as it did not negatively affect IVF success rates. Strengths Several methodological strengths enhance the validity and clinical relevance of our findings. First, our compre - hensive stratified analysis by age, AMH levels, and cyst size provides nuanced insights that can guide individu - alized patient counseling and treatment decisions. This multi-dimensional approach allows clinicians to apply our findings to specific patient populations rather than relying on broad generalizations. Our study also utilized the OSI as a dynamic marker of ovarian responsiveness to compare between operated and non-operated endome - triomas, a factor that has not been addressed in previous studies. OSI is a more reliable and objective method for assessing ovarian response in endometrioma, as it does not rely on antral follicle count and provides insights into the total gonadotropins used during stimulation. The inclusion of OSI and gonadotropin dose require - ments, provides valuable mechanistic insights beyond Page 9 of 10 Firdaus et al. Middle East Fertility Society Journal (2025) 30:58 simple pregnancy outcomes. This functional assessment offers a more complete picture of the impact of surgical intervention on ovarian physiology, which is crucial for understanding the biological basis of our observations. Previous studies in the literature exhibit heterogeneity in terms of surgical approaches, the strength of the pre - sent study lies in its focus on laparoscopic cystectomy and its impact on patients with endometriomas. Addi - tionally, this study uniquely considers both the size of the endometrioma and the surgery of endometrioma as factors influencing outcomes, an aspect not commonly addressed together in previous studies.

and suggestions for future research The relatively small sample size (n = 83) may have limited the statistical power to detect clinically meaningful differ- ences between groups, potentially leading to type II error where true differences might remain undetected. Future studies with larger cohorts and multicenter design would provide more robust evidence regarding the impact of endometrioma management on IVF outcomes. Since all surgeries were performed at our reproductive center, the

may not be generalizable. Unfortunately, there are no randomized controlled trials in the literature that have investigated the precise effects of endometriosis surgery before IVF. Because various endometriosis manifesta - tions, including ovarian endometrioma, deep endometri - osis (DE), and superficial endometriosis, are often treated concurrently during surgery, it is difficult to draw a clear correlation between endometrioma and its removal and IVF outcomes. Additional studies are needed to further elucidate these findings. Randomized controlled trials (RCTs) are needed to provide more robust evidence with clearly defined outcomes, particularly in relation to the size of the endometrioma. Abbreviations IVF In-Vitro Fertilization AMH Anti-Mullerian Hormone AFC Antral Follicular count GnRH Gonadotropin Releasing Hormone FSH Follicular Stimulating Hormone OSI Ovarian Sensitivity Index HCG Human Chorionic Gonadotropin cCPR Cumulative Clinical Pregnancy Rate IQR Inter-Quartile Range ICSI Intra Cytoplasmic Sperm Injection DIE Deep infiltrating endometriosis OHSS Ovarian hyperstimulation syndrome ART Assisted reproductive technology BMI Body mass index ESHRE European Society of Human Reproduction and Embryology

Not applicable. Authors’ contributions P .K.A and A.S contributed to the design and implementation of the research, A.F contributed to data collection, analysis of the results and writing of the manuscript. P .K.A and S.V to review, editing and revision of the manuscript. V.G.P , S.V and P .K.N helped in providing intellectual inputs and proofreading of manuscript and supervised the project. All authors read and approved the final manuscript. Funding This work did not receive any specific grant from any funding agency in the public, commercial, or non-profit sector. Data availability The datasets used and/ or analyzed during the current study are available from the corresponding author upon reasonable request. Declarations Ethics approval and consent to participate The present study was approved by Institutional Ethical Committee (Kasturba Medical College and Kasturba Hospital Institutional Ethical Committee, Regis- tration No. ECR/146/Inst/KA/2013/RR-19) on 23/10/ 2024 (IEC1: 396/2024). Consent for publication Not applicable. Competing interests The authors declare no competing interests. Author details 1 Department of Reproductive Medicine and Surgery, Kasturba Medical Col- lege Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India. 2 MMC IVF centre, Dubai, UAE. Received: 21 January 2025 Accepted: 19 October 2025

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