Endometriosis and IVF: Clinical, Surgical, and Biological Factors Affecting Outcomes

Endometriosis and IVF: Clinical, Surgical, and Biological Factors Affecting Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Endometriosis and IVF: Clinical, Surgical, and Biological Factors Affecting Outcomes Arshiya Firdaus, Anjali S Mundkur, Vidyashree G Poojari, Pratap Kumar Narayan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6103638/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Endometriosis, particularly endometriotic cysts (endometriomas), is commonly related to infertility in women. In vitro fertilization (IVF) is a widely used treatment for these patients; however, its outcomes can be influenced by various factors. This retrospective study aimed to investigate the factors affecting IVF outcomes in women with endometriomas. Methods This retrospective study included 83 women who underwent IVF between May 2021 and April 2024. Various factors were assessed, including ovarian reserve (measured by anti-Müllerian hormone [AMH] levels), age, presence of bilateral endometriomas, surgical management of endometrioma, size of endometriomas, and ovarian stimulation protocols (antagonist & agonist flare). Multivariable linear and logistic regression analyses were performed to determine the relationships between these variables and IVF outcomes, including the number of oocytes retrieved and clinical pregnancy rates. Results Among the ovarian response parameters, the Ovarian Stimulation Index (OSI) showed the strongest correlation with both the number of oocytes (r = 0.886) and mature oocytes (r = 0.809), suggesting its reliability in assessing the ovarian response in women with endometriosis. AMH levels were a significant positive predictor of the number of oocytes retrieved (β = 3.210, 95% CI: 2.670, 3.752, p < 0.001). Conversely, age and the presence of bilateral endometriomas were negatively associated with oocyte retrieval (age: β = -0.1879, 95% CI: -0.397, 0.021, p = 0.07; bilateral endometriomas: β = -1.9670, 95% CI: -3.519, -0.415, p = 0.014). Surgical management and endometrioma size did not significantly affect the oocyte retrieval. Age was also a significant negative predictor of clinical pregnancy (β = -1.329, 95% CI: -1.955, -0.704, p < 0.001). Conclusion This study highlights the importance of ovarian reserve and age as significant factors influencing IVF outcomes in women with endometriotic cysts. The choice of ovarian stimulation protocol did not appear to significantly affect oocyte retrieval. Tailored IVF treatment strategies should focus on these factors to optimize results. Additionally, the ovarian sensitivity index (OSI) is a reliable tool for assessing ovarian response in these patients. Endometrioma IVF/ICSI outcomes Oocyte retrieval Ovarian stimulation endometriotic cystectomy FORT (follicular output rate) OSI (ovarian sensitivity index) FOI (follicle to oocyte index) Figures Figure 1 Figure 2 Introduction Endometriosis is a benign condition in which endometrial tissue and stroma are observed outside the uterine cavity [ 1 ]. The prevalence of endometriosis is increasing, mainly due to advancements in clinical diagnostic imaging techniques, such as ultrasound, magnetic resonance imaging (MRI), and laparoscopy. Nevertheless, the complete pathogenesis of infertility in patients with endometriosis remains unknown. Several hypotheses have been proposed to explain the association between endometriosis and infertility. They include anatomical deformation of the pelvis resulting from adhesions, impaired ovarian function due to chronic inflammation in the ovary, and inflammatory peritoneal fluid damage to the quality of oocytes [ 2 ]. Treatment with assisted reproductive technology (ART) is a validated therapeutic option for endometriosis-related infertility [ 3 , 4 , 5 , 6 ]. Nevertheless, it has been reported that the presence of endometrioma can have a detrimental impact on ovarian responsiveness to ovarian stimulation[ 7 , 8 ]. Despite the abundance of published studies on endometrioma-related infertility, the mechanisms by which it impairs ovarian stimulation remain unclear [ 9 ]. It can be postulated that the impact of stimulation on ovarian responsiveness is related to the size of the endometrioma [ 5 , 10 ]. The ovarian response to stimulation during IVF is typically evaluated using several established parameters, including Follicular Output Rate (FORT), follicle-to-oocyte index (FOI), and Ovarian Sensitivity Index (OSI) [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. FORT is calculated as the ratio of preovulatory follicles (16-22mm) on the day of trigger to the baseline antral follicle count (AFC) multiplied by 100. FOI is the number of oocytes retrieved divided by the number of baseline AFC multiplied by 100. OSI can be calculated by the number of oocytes retrieved divided by the total gonadotropins dose consumed multiplied by 1000. These indices have been widely utilized in general IVF populations to predict the ovarian response to controlled ovarian stimulation [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, despite their relevance in routine IVF practice, these parameters have not been extensively studied in endometriosis patients. The presence of endometriotic cysts can interfere with the accurate assessment of antral follicle count (AFC), which is a critical measure for estimating the ovarian reserve and response to stimulation. The resulting uncertainty in AFC measurement may confound the calculation of commonly used ovarian response indices, such as FORT and FOI, making their application in patients with endometriosis more complex and potentially unreliable. Given the challenges in evaluating the stimulation response in endometriosis patients, this study aimed to assess the applicability and reliability of these parameters in predicting ovarian response, specifically in this cohort. By determining which of these parameters can most accurately reflect the ovarian response in patients with endometriosis, this study sought to provide clinicians with better tools for individualizing treatment plans, optimizing IVF protocols, and improving patient counselling. The success of IVF in endometriosis patients can be influenced by a range of factors including patient age, baseline ovarian reserve, presence of endometriomas, previous surgical interventions, associated comorbidities, and the type of ovarian stimulation protocol employed. The impact of endometrioma during IVF/ICSI (intra cytoplasmic sperm injection) cycles has been widely investigated. Hence, this study was conducted to determine the factors that may influence treatment outcomes. These research findings can provide valuable insights into the clinical management of infertility cases associated with endometriosis, particularly when counselling and making treatment plans. Material and methods This retrospective cohort study was conducted in the Department of Reproductive Medicine and Surgery, Kasturba Medical College Manipal, a tertiary care center. The study was approved by the Institutional Review Board of our medical center, ensuring compliance with the ethical guidelines. Data of 83 patients from May 2021 to April 2024 were collected from medical records, including demographic information, clinical characteristics, IVF treatment protocols, and stimulation parameters and outcomes. Inclusion Criteria: Participants were included if they had a confirmed diagnosis of endometrioma on ultrasound or laparoscopy and had undergone at least one cycle of IVF treatment. In cases with bilateral and/or multiple cysts, the mean diameter of the largest endometrioma was selected. Participants were excluded if they had other underlying medical conditions that could independently affect IVF outcomes, such as severe male factor infertility, autoimmune disorders, presence of adenomyosis features, and uterine anomalies (fibroids and uterine polyps). A history of endometriotic cystectomy before IVF was also recorded. Cystectomy was performed by skilled specialists with a strong emphasis on preserving the patient's reproductive potential. Patients who underwent cystectomy were recruited for IVF within 3 months to 1 year of laparoscopic endometriotic cystectomy. The decision to perform cystectomy was based on patient symptoms, baseline ovarian reserve, and the clinician’s decision. Aim/Objective: This study aimed to explore and identify the factors that significantly influence IVF success in women diagnosed with endometrioma. Primary outcome: 1. Factors affecting oocyte retrieval rate in women having endometrioma 2. Factors affecting clinical pregnancy in patients having endometrioma Secondary outcome Which marker of response (FORT, FOI, or OSI) most reliably reflects stimulation response in IVF? Stimulation protocol Briefly, two ovarian stimulation protocols were used, with 150–600 IU/day of follicle stimulating hormone (FSH), and comprised (i) a gonadotropin-releasing hormone (GnRH) flexible antagonist protocol and (ii) gonadotropin-releasing hormone agonist (GnRH) flare protocol. Figure 1- Antagonist protocol used for ovarian stimulation Figure 1 shows the flexible antagonist protocol used for stimulation. Ovarian stimulation is initiated with gonadotropins (FSH/LH) on day 2 or 3 of the menstrual cycle to promote the development of multiple follicles. On day 5 or 6 of stimulation, a GnRH antagonist is started if the lead follicle measures 14 mm on ultrasound or if the serum estradiol value reaches 400 pg/ml. Follicle growth is closely monitored through ultrasound. When follicles reach an adequate size (18-20 mm), ovulation is triggered with an hCG injection or a GnRH agonist trigger, and egg retrieval is scheduled 35 hours later. Figure 2- Agonist flare protocol used for ovarian stimulation Figure 2 shows another protocol used for ovarian stimulation. A GnRH agonist, 80 μg of leuprolide acetate daily, was administered starting on day 2 or 3 of menses. Gonadotropins were started 2 days after the GnRH agonist and continued until the day of trigger. Follicle growth was closely monitored through ultrasound. When follicles reached an adequate size (18-20 mm), ovulation was triggered with an hCG injection, and egg retrieval was scheduled 35 hours later. The gonadotrophin doses and the ovarian stimulation protocol types were determined according to each patient's individual characteristics and clinician’s decision. The final oocyte maturation was triggered when three or more ovarian follicles that were ≥18 mm in diameter were visible by ultrasound using 250 µg of recombinant human chorionic gonadotrophin (rHCG) or 1 mg of leuprolide subcutaneously if ovarian hyperstimulation syndrome(OHSS) risk was found. Oocyte retrieval was performed after 35–36 hours by transvaginal aspiration under ultrasound guidance. Antibiotic prophylaxis was administered during the procedure (single of injection 1.2gm of amoxicillin and clavulanic acid combination). ICSI (intra cytoplasmic sperm injection) was performed in all patients. Embryo grading was performed using the Istanbul grading, and only patients with cleavage stage frozen embryos were included to create a homogenous study cohort, as most of the transfers in our center were cleavage stage embryos. Grades 1 and 2 was considered as good-quality embryos. Data were recorded using an Excel spreadsheet. Stimulation outcomes were measured in terms of embryological (number of oocytes retrieved, M2 oocytes, and good-quality embryos) and clinical outcomes (clinical pregnancy rate). Other markers of ovarian response were used to measure the outcomes, such as ovarian sensitivity index ( number of oocytes retrieved divided by total gonadotrophin dose consumed x1000), follicular output rate ( number of preovulatory follicles 16–22 mm on the day of trigger divided by number of baseline AFC x100), and follicle to oocyte index ( number of oocytes retrieved divided by number of baseline AFC x 100) to better reflect the dynamic response during stimulation. Embryo transfer protocol: Allpatients underwentdownregulated hormone replacement protocol (HRT) and (2 cleavage stage embryos transferred) frozen embryo transfer (FET) done. Estradiol valerate (2 mg three times a day) was administered for endometrial preparation. Luteal phase support was administered in the form of progesterone gel 90 mg twice a day vaginally and Dydrogesterone 20 mg twice a day orally. The luteal phase was continued for up to 10 weeks of pregnancy if beta HCG tested positive 14 days after embryo transfer. Definition of outcomes Clinical pregnancy was determined by the ultrasonographic documentation of at least one fetus with a heartbeat at 6–7 weeks of gestation. 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 transfer of frozen–thawed supernumerary embryos (per IVF/ICSI cycle). The mean number of transfers per woman has also been noted. Statistical Analysis All statistical analyses were performed using Python in Jupyter Notebook environment (version 3.12). Data are presented as means ± standard deviation (SD), medians with interquartile range (IQR), or frequencies with percentages (%) based on the distribution of the data. The normality of the data was assessed visually using histograms and the Histo Fit software. To evaluate the factors influencing the number of oocytes retrieved, a multiple linear regression model was used. The dependent variable in the model was the number of oocytes retrieved, while the independent variables included stimulation protocol (antagonist protocol and agonist flare protocol), AMH, BMI, endometrioma surgery (yes/no), cyst size (in cm), and laterality of the cyst. Surgical history, stimulation protocol, and cyst laterality were treated as categorical variables. The antagonist protocol, non-operated group, and unilateral cysts were used as reference categories for the categorical variables. All categorical variables were binary-coded (0 = reference group, 1 = comparison group) and included in the regression analysis. The comparison group among categorical variables consisted of the operated group, bilateral cysts, and the flare agonist protocol. The model’s goodness of fit was assessed using R², indicating the proportion of variance in the dependent variable explained by the independent variables. To assess the factors influencing clinical pregnancy, a logistic regression analysis was performed. The independent variables analyzed in the logistic regression model were age, BMI, endometrioma surgery (yes/no), and AMH levels. The model's goodness of fit was evaluated using pseudo-R² which provides an estimate of the variance explained by the model in the context of logistic regression. Pearson’s correlation coefficients were calculated to assess the strength and direction of the linear relationships between each of the response indicators ( FORT , FOI , and OSI ) and the outcomes (number of oocytes , M2 oocytes , and number of good quality embryos ). Correlation coefficients were interpreted as follows: values close to +1 or -1 indicate strong positive or negative correlations, respectively, while values closer to 0 indicate weak or no linear correlation. Results Table 1 Baseline characteristics of study population Patient Characteristics N = 83 Age (years) 33.65 ± 2.76 BMI( Body mass index) (kg/m 2) 22.75 ± 2.72 Duration of infertility (years ) 4.501 ± 1.95 AFC 10 (8–13) AMH ( ng/ml) 1.7 (1.1–2.3) Total gonadotropins dose (units) 3533.13 ± 823.17 PFC (preovulatory follicles 16-22mm) 7 (5–10) OSI (ovarian sensitivity index) 2.52 ± 2.42 Number of Oocytes 6 (5-9.5) Number of M2 Oocytes 5 (4–8) Good quality embryos (grade 1&2) 4 (3–6) Clinical pregnancy rate 32(38.55%) Number of days of Stimulation 9.19 ± 1.57 Secondary infertility 19 ( 22.8%) Primary infertility 64 (77.1%) Non operated endometrioma 48( 57.83%) Operated endometrioma 35( 42.1%) Mean size of endometrioma ( in cm ) 4.98 ± 2.85 Women with bilateral endometrioma 52 (62.65%) Antagonist protocol 68 ( 81.9%) Flare protocol 15 ( 18%) Table 1 shows that the average age of the study population was 33.65 ± 2.76, and the average BMI was 22.75 ± 2.72. Most patients required an average of 3533.13 units of gonadotropins. The stimulation lasted for 9.19 ± 1.57 days. Most of the patients (77.1%) had primary infertility. 48 patients were recruited for IVF without endometrioma removal, whereas 35 patients underwent IVF after endometrioma removal. A total of 62.65% of patients had bilateral endometrioma, and the antagonist protocol was used in 81.9% of cases, with the remaining 18% using the flare agonist protocol. The mean size of the endometrioma was 4.98 cm ± 2.85. Table 2 Pearsons correlation between response indicators and stimulation outcomes Response indicators Number of oocytes (r value) M2 oocytes (r value) Good quality embryos (r value) FORT 0.373 0.276 0.234 FOI 0.555 0.457 0.369 OSI 0.886 0.809 0.541 Table 2 shows the Pearson's correlation coefficients (r values) for the three known parameters used to measure the stimulation response: FORT, FOI, and OSI to the number of oocytes, M2 oocytes, and good-quality embryos. The correlations between FORT and the outcomes (number of oocytes, M2 oocytes, and good-quality embryos) were positive, but relatively weak. OSI showed the strongest correlations with oocytes and M2 oocytes (r values 0.886 and 0.809, respectively) retrieved but was moderately correlated with good quality embryos (r = 0.541), suggesting that it is a reliable indicator for predicting the success of these outcomes among all the three response indicators studied here. The FOI also showed moderate correlations, indicating a decent but weaker relationship with the outcomes. Table 3 Linear regression analysis of the relationship between the general characteristics and the number of oocytes retrieved Characteristics Regression coefficient Standard error 95% CI p value Age (years) -0.1879 0.105 –0.397, 0.021 0.071 BMI (kg/m 2 ) 0.0415 0.110 –0.178, 0.261 0.708 AMH (ng/ml) 3.210 0.272 2.670, 3.752 < 0.001 * Endometrioma surgery -0.7563 0.835 –2.421, 0.908 0.368 Bilateral endometrioma -1.9670 0.779 -3.519, -0.415 0.014 * Mean size of endometrioma (in cm) -0.1368 0.335 –0.804, 0.530 0.684 Agonist flare protocol -0.123 0.809 –1.736, 1.489 0.879 * Significant at p < 0.05, AMH = anti−Müllerian hormone; BMI = body mass index; CI = confidence interval . For the multiple linear regression model assessing factors influencing the number of oocytes retrieved, the model showed a significant fit with an R² value of 0.704, indicating that 70.4% of the variance in the number of oocytes retrieved was explained by the independent variables. AMH levels were significantly associated with the number of oocytes retrieved (Table 3 ). The regression coefficient for AMH was 3.20 (95% CI: 2.670–3.752), and the p-value was < 0.001, indicating a statistically significant positive relationship between AMH levels and oocyte retrieval. Age was negatively associated with the number of oocytes retrieved (β = -0.1879, 95% CI: -0.397, 0.021, p = 0.071), which was not found significant, but p value is close to the threshold of significance, might suggest a potential inverse relationship between age and oocyte retrieval that could be further explored in future studies with larger sample sizes. Bilateral endometriomas were significantly associated with a reduction in the number of oocytes retrieved during ovarian stimulation during IVF cycles (p = 0.014; 95% CI: -3.519, -0.415). Conversely, endometrioma size and surgical management did not have a significant impact on oocyte retrieval. Table 4 Factors affecting clinical pregnancy rates in endometriosis Predictors Regression coefficient Standard error 95% Confidence Interval (CI) p-value Age (years) -1.329 0.319 (-1.955, -0.704) < 0.001 * BMI -0.049 0.167 (-0.378, 0.279) 0.766 Surgery of endometrioma 0.152 0.955 (-1.719, 2.025) 0.873 AMH (ng/ml) 0.097 0.407 (-0.700, 0.895) 0.811 * Significant at p < 0.05, AMH = anti−Müllerian hormone; BMI = body mass index; CI = confidence interval . Table 4 reveals that age is a significant predictor of clinical pregnancy (95% CI: 0.-1.955, − 0.704, p < 0.001). Surgery for endometrioma did not significantly influence clinical pregnancy, with a 95% CI (-1.719,2.025) and a p-value of 0.873, indicating no significant effect. BMI also had a negative impact on clinical pregnancy, but this effect was not significant. The model fit for logistic regression was evaluated by calculating pseudo-R², which was found to be 0.59 reflecting the good fit of the model. Discussion This study aimed to identify the clinical, surgical, and biological factors that influence IVF outcomes in women with endometriosis. The findings of this study highlight that ovarian reserve, as measured by AMH, plays a crucial role in determining IVF success, positively correlating with the number of oocytes retrieved. Conversely, patient age emerged as a significant negative predictor, with advancing age being associated with decreased IVF success rates. Patient age emerged as a significant negative predictor, with advancing age associated with a decrease in clinical pregnancy rates. This finding is consistent with numerous other studies that have demonstrated that age is a critical factor influencing IVF outcomes [ 18 , 19 , 20 ]. As women age, there is a natural decline in ovarian reserve, oocyte quality, and embryo viability [ 21 , 22 , 23 , 24 , 25 ], all of which contribute to reduced success rates of assisted reproductive technologies [ 20 ]. Although age was found to have a negative association with the number of oocytes retrieved in this study (β = -0.1879, 95% CI: -0.397, 0.021, p = 0.071), this association was not found statistically significant. This result is consistent with the well-established understanding that age is associated with a decline in ovarian reserve and the number of oocytes retrieved. However, the p-value being close to the threshold for statistical significance suggests that a larger cohort might provide more robust evidence. Given the well-established impact of age on IVF outcomes, its contribution cannot be overlooked when analyzing factors that affect the likelihood of success. This study further reinforces the need for clinicians to consider age as a key determinant in the management and counselling of patients with endometriosis undergoing IVF. While age has long been considered a critical factor in determining IVF success, present study reaffirms that, despite evolving insights into the disease and treatment approaches, age continues to play a pivotal role in fertility outcomes. Interestingly, factors such as the type of ovarian stimulation protocol (antagonist and agonist flare protocols), surgical removal of endometriomas, and endometrioma size did not show a statistically significant impact on IVF success in the present study. These findings suggest that while these factors are often considered in clinical practice, they may not substantially influence the outcome of IVF in women with endometriosis in our study population. The results of our study demonstrated that bilateral endometriomas are significantly associated with a reduction in the number of oocytes retrieved during ovarian stimulation in IVF cycles. The negative impact of bilateral endometriomas on oocyte retrieval can be explained by several biological mechanisms. First, bilateral cysts may result in greater ovarian damage [ 26 ], potentially leading to reduced responsiveness to stimulation [ 27 ]. This is consistent with a previous study that showed that endometriomas, when present in both ovaries, can compromise ovarian responsiveness [ 27 ]. The bilateral nature of cysts might also lead to increased inflammation, which could further impair folliculogenesis and oocyte maturation. Another potential mechanism could be the increased likelihood of adhesions and scar tissue formation around the ovaries in cases of bilateral endometriomas, which could interfere with both ovarian function and the ability to effectively retrieve oocytes. Given that bilateral endometriomas are linked to a reduced number of oocytes retrieved, this raises concerns regarding the potential for additional damage to ovarian function through surgical intervention. This finding suggests that clinicians must weigh the benefits of surgical intervention against potential harm, particularly if bilateral cysts are present. However, one previous study found that the presence of bilateral cysts does not have any influence on fertility parameters and pregnancy rate [ 28 ]. The present study findings are also consistent with other studies that have demonstrated no significant differences in pregnancy rates per cycle and clinical pregnancy rates between women who underwent surgery for endometriomas and those who did not undergo surgery [ 29 ],[ 30 ],[ 31 ]. This suggests that IVF stimulation can be initiated without the need for surgical removal of endometriomas in many cases. This study also found that endometrioma size did not have a significant impact on oocyte retrieval. This aligns with a previous study by Bourdon et al. who also found no significant difference in the number of oocytes retrieved according to the endometrioma size [ 32 ]. None of the stimulation protocols currently applied in women with endometriosis have been shown to be superior, so early intervention with an Assisted Reproduction treatment, regardless of the chosen protocol, can provide these women with good chances of pregnancy[ 33 , 34 ]. The protocol choice often depends on patient-specific factors, and the findings of the present study indicate that the protocol may not be a major determinant of IVF success in women with endometriosis. This study employed two different ovarian stimulation protocols: antagonist protocol and short agonist flare protocol. While previous studies have suggested that a long agonist protocol may lead to a higher yield of oocytes [ 35 , 36 , 37 ], many studies have found that both antagonist and agonist protocols yield comparable results in women with endometriosis [ 38 , 39 ]. These findings highlight that despite the theoretical advantages of the long agonist protocol in increasing oocyte retrieval [ 35 , 36 , 37 ], the antagonist and short agonist flare protocols are equally effective in achieving similar IVF outcomes in this patient population. This suggests that protocol choice may not significantly alter IVF success rates in women with endometriosis, supporting growing evidence that both protocols can be considered viable options based on individual patient characteristics. While previous studies have demonstrated that parameters such as Follicle Output Rate (FORT), FOI (Follicle Oocyte Index), and OSI (Ovarian Sensitivity Index) can assess the response to ovarian stimulation[ 11 , 12 , 13 , 14 , 15 , 16 , 17 ], the present study found that among FORT and FOI, only the Ovarian Sensitivity Index (OSI) reliably reflects the response to stimulation in patients with endometriosis. There are two potential reasons for this. First, both FORT and FOI incorporate baseline AFC in their calculations, which may be less accurate in patients with endometriomas because the presence of cysts can obscure the precise measurement of AFC. In contrast, the OSI does not include AFC in its calculation, making it a more reliable indicator of ovarian response in this population. Second, subjective variability in estimating AFC, especially in the presence of endometriomas, could introduce measurement inconsistencies. The difficulty in accurately assessing AFC in such cases may explain why OSI, which bypasses this issue, offers a more consistent and reliable reflection of the ovarian response to stimulation in patients with endometriosis. The present study found that OSI was moderately related to good-quality embryos (r = 0.541). While OSI showed a strong positive correlation with the number of oocytes and M2 oocytes, suggesting that higher OSI values reliably predict an increased ovarian response and oocyte yield, the moderate correlation with good-quality embryos may be attributed to the fact that embryo formation is influenced by multiple factors beyond just the ovarian response. However, the present study exclusively included cleavage-stage embryo transfers, as patients with endometriosis may present with compromised ovarian reserve, making it more challenging to achieve blastocyst formation due to fewer available embryos. The decision to prioritize cleavage-stage transfers is grounded in our experience, clinical context of our patient population, and resources available in our IVF program. Despite this limitation, our findings highlight a positive aspect: the endometriosis cohort still achieved a clinical pregnancy rate of 38.55% with cleavage-stage embryos. This suggests that even in cases with limited embryo numbers, cleavage stage transfers can yield promising outcomes. Therefore, in situations where sufficient embryos are not available for blastocyst culture, attempting cleavage stage transfers could be a viable alternative for achieving clinical pregnancy in patients with endometriosis. Conclusion In conclusion, our study emphasizes the importance of ovarian reserve (AMH) as a predictor of IVF success in terms of oocyte retrieval in women with endometriosis. Age and bilaterality of cysts remained negative prognostic factors, while other factors such as surgical management and stimulation protocols did not significantly affect IVF outcomes in this cohort. Treatment protocols could be tailored to focus on ovarian reserve markers (such as AMH levels) and age, rather than performing unnecessary surgeries to remove endometriomas. This approach could reduce unnecessary surgical interventions and offer a less invasive path to IVF. OSI provides a valuable parameter for assessing ovarian response. Incorporating OSI into clinical practice can help compare stimulation outcomes between different protocols or patient groups, offering a more accurate reflection of response. Limitations and Suggestions for Future Research While this study provides valuable insights into the factors affecting oocyte retrieval and clinical pregnancy rates in patients with endometriosis undergoing IVF, several limitations must be considered. The severity of endometriosis according to the endometriosis stage was not mentioned. The exclusion of endometriosis severity, adenomyosis, and deep infiltrating endometriosis, as well as the focus on cleavage-stage embryo transfers, may restrict the generalizability of our findings. In addition, unaccounted factors such as aneuploidy and genetic influences could have confounded the results, highlighting the need for further exploration of these variables. Additionally, incorporating both cleavage stage and blastocyst transfers could provide a more holistic view of the factors influencing success rates. Prospective studies with larger, more diverse patient populations and improved methodologies are also necessary to confirm these findings and to further elucidate the mechanisms underlying IVF success in patients with endometriosis. 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 OHSS- Ovarian hyperstimulation syndrome ART- Assisted reproductive technology BMI- Body mass index FORT- Follicular output rate FOI- Follicular oocyte index Declarations Ethics approval and consent to participate: The study was approved by the Institutional Ethical Committee (Kasturba Medical College and Kasturba Hospital Institutional Ethical Committee, Registration No. ECR/146/Inst/KA/2013/RR-19) on 23/10/ 2024 (IEC1: 396/2024). Consent to participate: A permission letter was obtained from the Medical Superintendent of Kasturba Medical College and Hospital for collecting data for the study. Since the research was based on retrospective data gathered during routine patient care, individual informed consent was not obtained. The study involved anonymized data, with no patient identifiers used. Consent for publication: not applicable. Availability of data and materials : The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Competing interests: The author(s) declare(s) that they have no competing interests Funding: This work did not receive any specific grants from any funding agency in the public, commercial, or non-profit sectors. Author 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 reviewed and edited the manuscript; V.G.P. and P.K.N helped in providing intellectual input and proofreading of the manuscript and supervised the project. 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Ovarian sensitivity index (OSI): validating the use of a marker for ovarian responsiveness in IVF. J Reprod infertility. 2019;20(2):83. Revelli A, Gennarelli G, Biasoni V, Chiadò A, Carosso A, Evangelista F, Paschero C, Filippini C, Benedetto C. The ovarian sensitivity index (OSI) significantly correlates with ovarian reserve biomarkers, is more predictive of clinical pregnancy than the total number of oocytes, and is consistent in consecutive IVF cycles. J Clin Med. 2020;9(6):1914. Biasoni V, Patriarca A, Dalmasso P, Bertagna A, Manieri C, Benedetto C, Revelli A. Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF. Reproductive Biology Endocrinol. 2011;9:1–5. Van Loendersloot LL, Van Wely M, Limpens J, Bossuyt PM, Repping S, Van Der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010;16(6):577–89. Tomazevic T, Korosec S, Klun IV, Drobnic S, Verdenik I. Age, oestradiol and blastocysts can predict success in natural cycle IVF–embryo transfer. Reprod Biomed Online. 2007;15(2):220–6. Shingshetty L, Cameron NJ, Mclernon DJ, Bhattacharya S. Predictors of success following IVF. Fertil Steril. 2024 Mar 16. Moghadam AR, Moghadam MT, Hemadi M, Saki G. Oocyte quality and aging. JBRA Assist Reprod. 2022;26(1):105. Scheffer JB, Scheffer BB, De Carvalho RF, Rodrigues J, Grynberg M, Lozano DH. Age as a predictor of embryo quality regardless of the quantitative ovarian response. Int J fertility Steril. 2016;11(1):40. Ziebe S, Loft A, Petersen JH, Andersen AG, Lindenberg S, Petersen K, Andersen AN. Embryo quality and developmental potential is compromised by age. Acta Obstet Gynecol Scand. 2001;80(2):169. Cimadomo D, Fabozzi G, Vaiarelli A, Ubaldi N, Ubaldi FM, Rienzi L. Impact of maternal age on oocyte and embryo competence. Front Endocrinol. 2018;9:327. Wang L, Tang J, Wang L, Tan F, Song H, Zhou J, Li F. Oxidative stress in oocyte aging and female reproduction. J Cell Physiol. 2021;236(12):7966–83. Karadağ C, Yoldemir T, Demircan Karadağ S, Turgut A. The effects of endometrioma size and bilaterality on ovarian reserve. J Obstet Gynaecol. 2020;40(4):531–6. Benaglia L, Bermejo A, Somigliana E, Faulisi S, Ragni G, Fedele L, Garcia-Velasco JA. In vitro fertilization outcome in women with unoperated bilateral endometriomas. Fertil Steril. 2013;99(6):1714–9. Yilmaz N, Ceran MU, Ugurlu EN, Gulerman HC, Ustun YE. Impact of endometrioma and bilaterality on IVF/ICSI cycles in patients with endometriosis. J Gynecol Obstet Hum Reprod. 2021;50(3):101839. Nickkho-Amiry M, Savant R, Majumder K, Edi-O’sagie E, Akhtar M. The effect of surgical management of endometrioma on the IVF/ICSI outcomes when compared with no treatment? A systematic review and meta-analysis. Arch Gynecol Obstet. 2018;297:1043–57. Hamdan M, Dunselman G, Li TC, Cheong Y. The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis. Hum Reprod Update. 2015;21(6):809–25. Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril. 2009;92(1):75–87. Bourdon M, Dahan Y, Maignien C, Patrat C, Bordonne C, Marcellin L, Chapron C, Santulli P. Influence of endometrioma size on ART outcomes. Reprod Biomed Online. 2022;45(6):1237–46. Goyri E, Kohls G, Garcia-Velasco J. IVF stimulation protocols and outcomes in women with endometriosis. Best Pract Res Clin Obstet Gynecol. 2024;92:102429. Rodriguez-Purata J, Coroleu B, Tur R, Carrasco B, Rodriguez I, Barri PN. Endometriosis and IVF: are agonists really better? Analysis of 1180 cycles with the propensity score matching. Gynecol Endocrinol. 2013;29(9):859–62. Chen Q, Du S, Lin Y, Zheng B. Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH‐agonist or GnRH‐antagonist protocols: A retrospective study by propensity score matching. J Obstet Gynecol Res. 2023;49(5):1366–74. Wang X, Li W, Chen X, Zhang W, Chu M, Yin S, Chu Y, Liu X. Is the long-acting gonadotropin‐releasing hormone agonist long protocol better for patients with endometriosis undergoing IVF? Int J Gynecol Obstet. 2023;162(1):325–32. Kolanska K, Cohen J, Bendifallah S, Selleret L, Antoine JM, Chabbert-Buffet N, Darai E, d’Argent EM. Pregnancy outcomes after controlled ovarian hyperstimulation in women with endometriosis-associated infertility: GnRH-agonist versus GnRH-antagonist. J Gynecol Obstet Hum Reprod. 2017;46(9):681–6. Kuan KK, Omoseni S, Tello JA. Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: a systematic review. Therapeutic Adv Endocrinol Metabolism. 2023;14:20420188231173325. Pabuccu R, Onalan G, Kaya C. GnRH agonist and antagonist protocols for stage I–II endometriosis and endometrioma in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. 2007;88(4):832–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6103638","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":423272594,"identity":"fd1f1ccc-fdc5-4763-8a53-2c8aac28443a","order_by":0,"name":"Arshiya Firdaus","email":"","orcid":"","institution":"Manipal Academy of Higher Education","correspondingAuthor":false,"prefix":"","firstName":"Arshiya","middleName":"","lastName":"Firdaus","suffix":""},{"id":423272596,"identity":"421ba5ce-24db-46b5-a488-42312113a4da","order_by":1,"name":"Anjali S Mundkur","email":"","orcid":"","institution":"Manipal Academy of Higher Education","correspondingAuthor":false,"prefix":"","firstName":"Anjali","middleName":"S","lastName":"Mundkur","suffix":""},{"id":423272597,"identity":"ce2bd4e7-a1fb-461f-9f2d-f6f779ab7c7a","order_by":2,"name":"Vidyashree G Poojari","email":"","orcid":"","institution":"Manipal Academy of Higher Education","correspondingAuthor":false,"prefix":"","firstName":"Vidyashree","middleName":"G","lastName":"Poojari","suffix":""},{"id":423272599,"identity":"cdd98092-cb43-44e2-b401-69854fa6624a","order_by":3,"name":"Pratap Kumar Narayan","email":"","orcid":"","institution":"Manipal Academy of Higher Education","correspondingAuthor":false,"prefix":"","firstName":"Pratap","middleName":"Kumar","lastName":"Narayan","suffix":""},{"id":423272600,"identity":"a1bcece7-aa26-4b87-8de4-7667a3f4fc0b","order_by":4,"name":"Prashanth K. Adiga","email":"data:image/png;base64,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","orcid":"","institution":"Manipal Academy of Higher Education","correspondingAuthor":true,"prefix":"","firstName":"Prashanth","middleName":"K.","lastName":"Adiga","suffix":""}],"badges":[],"createdAt":"2025-02-25 09:23:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6103638/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6103638/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78249424,"identity":"27fba617-af1e-470d-a111-c5fed5d5b302","added_by":"auto","created_at":"2025-03-11 09:48:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":344048,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6103638/v1/d1968fc413dc0c8a27cb36a8.png"},{"id":78248963,"identity":"6147c8f4-d945-4e11-a78a-5dba86d108bd","added_by":"auto","created_at":"2025-03-11 09:40:59","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":290573,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6103638/v1/332bbdbe7d1e0a1f595c9515.png"},{"id":78251747,"identity":"d3238a4a-33a7-49ac-8530-a7dace16a7c0","added_by":"auto","created_at":"2025-03-11 10:05:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1404740,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6103638/v1/f661906c-2b65-4d9e-baf9-c4dec1f4d5fa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eEndometriosis and IVF: Clinical, Surgical, and Biological Factors Affecting Outcomes\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eEndometriosis is a benign condition in which endometrial tissue and stroma are observed outside the uterine cavity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence of endometriosis is increasing, mainly due to advancements in clinical diagnostic imaging techniques, such as ultrasound, magnetic resonance imaging (MRI), and laparoscopy. Nevertheless, the complete pathogenesis of infertility in patients with endometriosis remains unknown. Several hypotheses have been proposed to explain the association between endometriosis and infertility. They include anatomical deformation of the pelvis resulting from adhesions, impaired ovarian function due to chronic inflammation in the ovary, and inflammatory peritoneal fluid damage to the quality of oocytes [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTreatment with assisted reproductive technology (ART) is a validated therapeutic option for endometriosis-related infertility [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nevertheless, it has been reported that the presence of endometrioma can have a detrimental impact on ovarian responsiveness to ovarian stimulation[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Despite the abundance of published studies on endometrioma-related infertility, the mechanisms by which it impairs ovarian stimulation remain unclear [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It can be postulated that the impact of stimulation on ovarian responsiveness is related to the size of the endometrioma [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe ovarian response to stimulation during IVF is typically evaluated using several established parameters, including Follicular Output Rate (FORT), follicle-to-oocyte index (FOI), and Ovarian Sensitivity Index (OSI) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. FORT is calculated as the ratio of preovulatory follicles (16-22mm) on the day of trigger to the baseline antral follicle count (AFC) multiplied by 100. FOI is the number of oocytes retrieved divided by the number of baseline AFC multiplied by 100. OSI can be calculated by the number of oocytes retrieved divided by the total gonadotropins dose consumed multiplied by 1000. These indices have been widely utilized in general IVF populations to predict the ovarian response to controlled ovarian stimulation [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, despite their relevance in routine IVF practice, these parameters have not been extensively studied in endometriosis patients. The presence of endometriotic cysts can interfere with the accurate assessment of antral follicle count (AFC), which is a critical measure for estimating the ovarian reserve and response to stimulation. The resulting uncertainty in AFC measurement may confound the calculation of commonly used ovarian response indices, such as FORT and FOI, making their application in patients with endometriosis more complex and potentially unreliable.\u003c/p\u003e \u003cp\u003eGiven the challenges in evaluating the stimulation response in endometriosis patients, this study aimed to assess the applicability and reliability of these parameters in predicting ovarian response, specifically in this cohort. By determining which of these parameters can most accurately reflect the ovarian response in patients with endometriosis, this study sought to provide clinicians with better tools for individualizing treatment plans, optimizing IVF protocols, and improving patient counselling. The success of IVF in endometriosis patients can be influenced by a range of factors including patient age, baseline ovarian reserve, presence of endometriomas, previous surgical interventions, associated comorbidities, and the type of ovarian stimulation protocol employed. The impact of endometrioma during IVF/ICSI (intra cytoplasmic sperm injection) cycles has been widely investigated.\u003c/p\u003e \u003cp\u003eHence, this study was conducted to determine the factors that may influence treatment outcomes. These research findings can provide valuable insights into the clinical management of infertility cases associated with endometriosis, particularly when counselling and making treatment plans.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003eThis retrospective cohort study was conducted in the Department of Reproductive Medicine and Surgery, Kasturba Medical College Manipal, a tertiary care center. The study was approved by the Institutional Review Board of our medical center, ensuring compliance with the ethical guidelines. Data of 83 patients from May 2021 to April 2024 were collected from medical records, including demographic information, clinical characteristics, IVF treatment protocols, and stimulation parameters and outcomes. Inclusion Criteria: Participants were included if they had a confirmed diagnosis of endometrioma on ultrasound or laparoscopy and had undergone at least one cycle of IVF treatment.\u0026nbsp;In cases with bilateral and/or multiple cysts, the mean diameter of the largest endometrioma was selected.\u0026nbsp;Participants were excluded if they had other underlying medical conditions that could independently affect IVF outcomes, such as severe male factor infertility, autoimmune disorders, presence of adenomyosis features, and uterine anomalies (fibroids and uterine polyps). A history of endometriotic cystectomy before IVF was also recorded.\u0026nbsp;Cystectomy was performed by skilled specialists with a strong emphasis on preserving the patient\u0026apos;s reproductive potential. Patients who underwent cystectomy were recruited for IVF within 3 months to 1 year of laparoscopic endometriotic cystectomy. The decision to perform cystectomy was based on patient symptoms, baseline ovarian reserve, and the clinician\u0026rsquo;s decision.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAim/Objective:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study aimed to explore and identify the factors that significantly influence IVF success in women diagnosed with endometrioma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.\u0026nbsp;Factors affecting oocyte retrieval rate in women having endometrioma\u003c/p\u003e\n\u003cp\u003e2. Factors affecting clinical pregnancy in patients having endometrioma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhich marker of response (FORT, FOI, or OSI) most reliably reflects stimulation response in IVF?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStimulation protocol\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBriefly, two ovarian stimulation protocols were used, with 150\u0026ndash;600 IU/day of follicle stimulating hormone (FSH), and comprised (i) a gonadotropin-releasing hormone (GnRH) flexible antagonist protocol and (ii) gonadotropin-releasing hormone agonist (GnRH) flare protocol.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1- Antagonist protocol used for ovarian stimulation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1\u003c/strong\u003e shows the flexible antagonist protocol used for stimulation. Ovarian stimulation is initiated with gonadotropins (FSH/LH) on day 2 or 3 of the menstrual cycle to promote the development of multiple follicles. On day 5 or 6 of stimulation, a GnRH antagonist is started if the lead follicle measures 14 mm on ultrasound or if the serum estradiol value reaches 400 pg/ml. Follicle growth is closely monitored through ultrasound. When follicles reach an adequate size (18-20 mm), ovulation is triggered with an hCG injection or a GnRH agonist trigger, and egg retrieval is scheduled 35 hours later.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2- Agonist flare protocol used for ovarian stimulation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2\u003c/strong\u003e shows another protocol used for ovarian stimulation. A GnRH agonist, 80 \u0026mu;g of leuprolide acetate daily, was administered starting on day 2 or 3 of menses. Gonadotropins were started 2 days after the GnRH agonist and continued until the day of trigger. Follicle growth was closely monitored through ultrasound. When follicles reached an adequate size (18-20 mm), ovulation was triggered with an hCG injection, and egg retrieval was scheduled 35 hours later.\u003c/p\u003e\n\u003cp\u003eThe gonadotrophin doses and the ovarian stimulation protocol types were determined according to each patient\u0026apos;s individual characteristics and clinician\u0026rsquo;s decision. The final oocyte maturation was triggered when three or more ovarian follicles that were \u0026ge;18 mm in diameter were visible by ultrasound using 250 \u0026micro;g of recombinant human chorionic gonadotrophin (rHCG) or 1 mg of leuprolide subcutaneously if ovarian hyperstimulation syndrome(OHSS) risk was found. Oocyte retrieval was performed after 35\u0026ndash;36 hours by transvaginal aspiration under ultrasound guidance. \u0026nbsp;Antibiotic prophylaxis was administered during the procedure (single of injection 1.2gm of amoxicillin and clavulanic acid combination). \u0026nbsp;ICSI (intra cytoplasmic sperm injection) was performed in all patients. Embryo grading was performed using the Istanbul grading, and only patients with cleavage stage frozen embryos were included to create a homogenous study cohort, as most of the transfers in our center were cleavage stage embryos. Grades 1 and 2 was considered as good-quality embryos.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData were recorded using an Excel spreadsheet. Stimulation outcomes were measured in terms of embryological (number of oocytes retrieved, M2 oocytes, and good-quality embryos) and clinical outcomes (clinical pregnancy rate). Other markers of ovarian response were used to measure the outcomes, such as \u003cstrong\u003eovarian sensitivity index\u003c/strong\u003e ( number of oocytes retrieved divided by total gonadotrophin dose consumed x1000), \u0026nbsp;\u003cstrong\u003efollicular output rate\u003c/strong\u003e ( number of preovulatory follicles 16\u0026ndash;22 mm on the day of trigger divided by number of baseline AFC x100), and\u0026nbsp;\u003cstrong\u003efollicle to oocyte index\u003c/strong\u003e ( number of oocytes retrieved divided by number of baseline AFC x 100) to better reflect the dynamic response during stimulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEmbryo transfer protocol:\u0026nbsp;\u003c/strong\u003eAllpatients underwentdownregulated hormone replacement protocol (HRT) and (2 cleavage stage embryos transferred) frozen embryo transfer (FET) done. Estradiol valerate (2 mg three times a day) was administered for endometrial preparation. Luteal phase support was administered in the form of progesterone gel 90 mg twice a day vaginally and Dydrogesterone 20 mg twice a day orally. The luteal phase was continued for up to 10 weeks of pregnancy if beta HCG tested positive 14 days after embryo transfer.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDefinition of outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical pregnancy was determined by the ultrasonographic documentation of at least one fetus with a heartbeat at 6\u0026ndash;7 weeks of gestation. The cumulative clinical pregnancy rate(cCPR)\u0026nbsp;was defined as the proportion of women who had at least one clinical pregnancy, whether from the first transfer attempt or subsequent transfer of frozen\u0026ndash;thawed supernumerary embryos (per IVF/ICSI cycle). The mean number of transfers per woman has also been noted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using Python in \u003cstrong\u003eJupyter Notebook environment (version 3.12).\u003c/strong\u003e Data are presented as means \u0026plusmn; standard deviation (SD), medians with interquartile range (IQR), or frequencies with percentages (%) based on the distribution of the data. The normality of the data was assessed visually using histograms and the \u003cstrong\u003eHisto Fit software.\u003c/strong\u003e To evaluate the factors influencing the number of oocytes retrieved, a multiple linear regression model was used. The dependent variable in the model was the number of oocytes retrieved, while the independent variables included stimulation protocol (antagonist protocol and agonist flare protocol), AMH, BMI, endometrioma surgery (yes/no), cyst size (in cm), and laterality of the cyst. Surgical history, stimulation protocol, and cyst laterality were treated as categorical variables. The antagonist protocol, non-operated group, and unilateral cysts were used as reference categories for the categorical variables. All categorical variables were binary-coded (0 = reference group, 1 = comparison group) and included in the regression analysis. The comparison group among categorical variables consisted of the operated group, bilateral cysts, and the flare agonist protocol. The model\u0026rsquo;s goodness of fit was assessed using R\u0026sup2;, indicating the proportion of variance in the dependent variable explained by the independent variables.\u003c/p\u003e\n\u003cp\u003eTo assess the factors influencing clinical pregnancy, a logistic regression analysis was performed. The independent variables analyzed in the logistic regression model were age, BMI, endometrioma surgery (yes/no), and AMH levels. The model\u0026apos;s goodness of fit was evaluated using pseudo-R\u0026sup2; which provides an estimate of the variance explained by the model in the context of logistic regression. Pearson\u0026rsquo;s correlation coefficients were calculated to assess the strength and direction of the linear relationships between each of the response indicators (\u003cstrong\u003eFORT\u003c/strong\u003e, \u003cstrong\u003eFOI\u003c/strong\u003e, and \u003cstrong\u003eOSI\u003c/strong\u003e) and the outcomes (number of \u003cstrong\u003eoocytes\u003c/strong\u003e, \u003cstrong\u003eM2 oocytes\u003c/strong\u003e, and number of good quality \u003cstrong\u003eembryos\u003c/strong\u003e). Correlation coefficients were interpreted as follows: values close to +1 or -1 indicate strong positive or negative correlations, respectively, while values closer to 0 indicate weak or no linear correlation.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;83\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.65 \u0026plusmn; 2.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI( Body mass index) (kg/m\u003csup\u003e2)\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of infertility (years )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.501\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (8\u0026ndash;13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMH ( ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.7 (1.1\u0026ndash;2.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal gonadotropins dose (units)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3533.13\u0026thinsp;\u0026plusmn;\u0026thinsp;823.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePFC (preovulatory follicles 16-22mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (5\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOSI (ovarian sensitivity index)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.52\u0026thinsp;\u0026plusmn;\u0026thinsp;2.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of Oocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (5-9.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of M2 Oocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (4\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGood quality embryos (grade 1\u0026amp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical pregnancy rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(38.55%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of days of Stimulation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 ( 22.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary infertility\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (77.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon operated endometrioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48( 57.83%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperated endometrioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35( 42.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean size of endometrioma ( in cm )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.98\u0026thinsp;\u0026plusmn;\u0026thinsp;2.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWomen with bilateral endometrioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52 (62.65%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntagonist protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 ( 81.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFlare protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 ( 18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows that the average age of the study population was 33.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76, and the average BMI was 22.75\u0026thinsp;\u0026plusmn;\u0026thinsp;2.72. Most patients required an average of 3533.13 units of gonadotropins. The stimulation lasted for 9.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57 days. Most of the patients (77.1%) had primary infertility. 48 patients were recruited for IVF without endometrioma removal, whereas 35 patients underwent IVF after endometrioma removal. A total of 62.65% of patients had bilateral endometrioma, and the antagonist protocol was used in 81.9% of cases, with the remaining 18% using the flare agonist protocol. The mean size of the endometrioma was 4.98 cm\u0026thinsp;\u0026plusmn;\u0026thinsp;2.85.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePearsons correlation between response indicators and stimulation outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse indicators\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of oocytes\u003c/p\u003e \u003cp\u003e(r value)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM2 oocytes\u003c/p\u003e \u003cp\u003e(r value)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGood quality embryos\u003c/p\u003e \u003cp\u003e(r value)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFORT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFOI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.555\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOSI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.886\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.541\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the Pearson's correlation coefficients (r values) for the three known parameters used to measure the stimulation response: FORT, FOI, and OSI to the number of oocytes, M2 oocytes, and good-quality embryos. The correlations between FORT and the outcomes (number of oocytes, M2 oocytes, and good-quality embryos) were positive, but relatively weak. OSI showed the strongest correlations with oocytes and M2 oocytes (r values 0.886 and 0.809, respectively) retrieved but was moderately correlated with good quality embryos (r\u0026thinsp;=\u0026thinsp;0.541), suggesting that it is a reliable indicator for predicting the success of these outcomes among all the three response indicators studied here. The FOI also showed moderate correlations, indicating a decent but weaker relationship with the outcomes.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLinear regression analysis of the relationship between the general characteristics and the number of oocytes retrieved\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRegression coefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard error\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.1879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;0.397, 0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.0415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;0.178, 0.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.708\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMH (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.210\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.670, 3.752\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndometrioma surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.7563\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.835\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;2.421, 0.908\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.368\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral endometrioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.9670\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.519, -0.415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean size of endometrioma (in cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.1368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;0.804, 0.530\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.684\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAgonist flare protocol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.809\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;1.736, 1.489\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e* Significant at p \u0026lt; 0.05, AMH = anti\u0026minus;M\u0026uuml;llerian hormone; BMI = body mass index; CI = confidence interval\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor the multiple linear regression model assessing factors influencing the number of oocytes retrieved, the model showed a significant fit with an R\u0026sup2; value of 0.704, indicating that 70.4% of the variance in the number of oocytes retrieved was explained by the independent variables. AMH levels were significantly associated with the number of oocytes retrieved (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The regression coefficient for AMH was 3.20 (95% CI: 2.670\u0026ndash;3.752), and the p-value was \u0026lt;\u0026thinsp;0.001, indicating a statistically significant positive relationship between AMH levels and oocyte retrieval. Age was negatively associated with the number of oocytes retrieved (β = -0.1879, 95% CI: -0.397, 0.021, p\u0026thinsp;=\u0026thinsp;0.071), which was not found significant, but p value is close to the threshold of significance, might suggest a potential inverse relationship between age and oocyte retrieval that could be further explored in future studies with larger sample sizes.\u003c/p\u003e \u003cp\u003eBilateral endometriomas were significantly associated with a reduction in the number of oocytes retrieved during ovarian stimulation during IVF cycles (p\u0026thinsp;=\u0026thinsp;0.014; 95% CI: -3.519, -0.415). Conversely, endometrioma size and surgical management did not have a significant impact on oocyte retrieval.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFactors affecting clinical pregnancy rates in endometriosis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026minus;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRegression coefficient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard error\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% Confidence Interval (CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e(-1.955, -0.704)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.049\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e(-0.378, 0.279)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.766\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery of endometrioma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e(-1.719, 2.025)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.873\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAMH (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026minus;\" colname=\"c4\"\u003e \u003cp\u003e(-0.700, 0.895)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e* Significant at p \u0026lt; 0.05, AMH = anti\u0026minus;M\u0026uuml;llerian hormone; BMI = body mass index; CI = confidence interval\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e reveals that age is a significant predictor of clinical pregnancy (95% CI: 0.-1.955, \u0026minus;\u0026thinsp;0.704, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Surgery for endometrioma did not significantly influence clinical pregnancy, with a 95% CI (-1.719,2.025) and a p-value of 0.873, indicating no significant effect. BMI also had a negative impact on clinical pregnancy, but this effect was not significant. The model fit for logistic regression was evaluated by calculating pseudo-R\u0026sup2;, which was found to be 0.59 reflecting the good fit of the model.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study aimed to identify the clinical, surgical, and biological factors that influence IVF outcomes in women with endometriosis. The findings of this study highlight that ovarian reserve, as measured by AMH, plays a crucial role in determining IVF success, positively correlating with the number of oocytes retrieved. Conversely, patient age emerged as a significant negative predictor, with advancing age being associated with decreased IVF success rates.\u003c/p\u003e \u003cp\u003ePatient age emerged as a significant negative predictor, with advancing age associated with a decrease in clinical pregnancy rates. This finding is consistent with numerous other studies that have demonstrated that age is a critical factor influencing IVF outcomes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. As women age, there is a natural decline in ovarian reserve, oocyte quality, and embryo viability [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], all of which contribute to reduced success rates of assisted reproductive technologies [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Although age was found to have a negative association with the number of oocytes retrieved in this study (β = -0.1879, 95% CI: -0.397, 0.021, p\u0026thinsp;=\u0026thinsp;0.071), this association was not found statistically significant. This result is consistent with the well-established understanding that age is associated with a decline in ovarian reserve and the number of oocytes retrieved. However, the p-value being close to the threshold for statistical significance suggests that a larger cohort might provide more robust evidence. Given the well-established impact of age on IVF outcomes, its contribution cannot be overlooked when analyzing factors that affect the likelihood of success. This study further reinforces the need for clinicians to consider age as a key determinant in the management and counselling of patients with endometriosis undergoing IVF. While age has long been considered a critical factor in determining IVF success, present study reaffirms that, despite evolving insights into the disease and treatment approaches, age continues to play a pivotal role in fertility outcomes.\u003c/p\u003e \u003cp\u003eInterestingly, factors such as the type of ovarian stimulation protocol (antagonist and agonist flare protocols), surgical removal of endometriomas, and endometrioma size did not show a statistically significant impact on IVF success in the present study. These findings suggest that while these factors are often considered in clinical practice, they may not substantially influence the outcome of IVF in women with endometriosis in our study population.\u003c/p\u003e \u003cp\u003eThe results of our study demonstrated that bilateral endometriomas are significantly associated with a reduction in the number of oocytes retrieved during ovarian stimulation in IVF cycles. The negative impact of bilateral endometriomas on oocyte retrieval can be explained by several biological mechanisms. First, bilateral cysts may result in greater ovarian damage [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], potentially leading to reduced responsiveness to stimulation [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. This is consistent with a previous study that showed that endometriomas, when present in both ovaries, can compromise ovarian responsiveness [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The bilateral nature of cysts might also lead to increased inflammation, which could further impair folliculogenesis and oocyte maturation. Another potential mechanism could be the increased likelihood of adhesions and scar tissue formation around the ovaries in cases of bilateral endometriomas, which could interfere with both ovarian function and the ability to effectively retrieve oocytes. Given that bilateral endometriomas are linked to a reduced number of oocytes retrieved, this raises concerns regarding the potential for additional damage to ovarian function through surgical intervention. This finding suggests that clinicians must weigh the benefits of surgical intervention against potential harm, particularly if bilateral cysts are present. However, one previous study found that the presence of bilateral cysts does not have any influence on fertility parameters and pregnancy rate [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study findings are also consistent with other studies that have demonstrated no significant differences in pregnancy rates per cycle and clinical pregnancy rates between women who underwent surgery for endometriomas and those who did not undergo surgery [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e],[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e],[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. This suggests that IVF stimulation can be initiated without the need for surgical removal of endometriomas in many cases. This study also found that endometrioma size did not have a significant impact on oocyte retrieval. This aligns with a previous study by Bourdon \u003cem\u003eet al.\u003c/em\u003e who also found no significant difference in the number of oocytes retrieved according to the endometrioma size [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNone of the stimulation protocols currently applied in women with endometriosis have been shown to be superior, so early intervention with an Assisted Reproduction treatment, regardless of the chosen protocol, can provide these women with good chances of pregnancy[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The protocol choice often depends on patient-specific factors, and the findings of the present study indicate that the protocol may not be a major determinant of IVF success in women with endometriosis. This study employed two different ovarian stimulation protocols: antagonist protocol and short agonist flare protocol. While previous studies have suggested that a long agonist protocol may lead to a higher yield of oocytes [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], many studies have found that both antagonist and agonist protocols yield comparable results in women with endometriosis [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. These findings highlight that despite the theoretical advantages of the long agonist protocol in increasing oocyte retrieval [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], the antagonist and short agonist flare protocols are equally effective in achieving similar IVF outcomes in this patient population. This suggests that protocol choice may not significantly alter IVF success rates in women with endometriosis, supporting growing evidence that both protocols can be considered viable options based on individual patient characteristics.\u003c/p\u003e \u003cp\u003eWhile previous studies have demonstrated that parameters such as Follicle Output Rate (FORT), FOI (Follicle Oocyte Index), and OSI (Ovarian Sensitivity Index) can assess the response to ovarian stimulation[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], the present study found that among FORT and FOI, only the Ovarian Sensitivity Index (OSI) reliably reflects the response to stimulation in patients with endometriosis. There are two potential reasons for this. First, both FORT and FOI incorporate baseline AFC in their calculations, which may be less accurate in patients with endometriomas because the presence of cysts can obscure the precise measurement of AFC. In contrast, the OSI does not include AFC in its calculation, making it a more reliable indicator of ovarian response in this population. Second, subjective variability in estimating AFC, especially in the presence of endometriomas, could introduce measurement inconsistencies. The difficulty in accurately assessing AFC in such cases may explain why OSI, which bypasses this issue, offers a more consistent and reliable reflection of the ovarian response to stimulation in patients with endometriosis.\u003c/p\u003e \u003cp\u003eThe present study found that OSI was moderately related to good-quality embryos (r\u0026thinsp;=\u0026thinsp;0.541). While OSI showed a strong positive correlation with the number of oocytes and M2 oocytes, suggesting that higher OSI values reliably predict an increased ovarian response and oocyte yield, the moderate correlation with good-quality embryos may be attributed to the fact that embryo formation is influenced by multiple factors beyond just the ovarian response.\u003c/p\u003e \u003cp\u003eHowever, the present study exclusively included cleavage-stage embryo transfers, as patients with endometriosis may present with compromised ovarian reserve, making it more challenging to achieve blastocyst formation due to fewer available embryos. The decision to prioritize cleavage-stage transfers is grounded in our experience, clinical context of our patient population, and resources available in our IVF program. Despite this limitation, our findings highlight a positive aspect: the endometriosis cohort still achieved a clinical pregnancy rate of 38.55% with cleavage-stage embryos. This suggests that even in cases with limited embryo numbers, cleavage stage transfers can yield promising outcomes. Therefore, in situations where sufficient embryos are not available for blastocyst culture, attempting cleavage stage transfers could be a viable alternative for achieving clinical pregnancy in patients with endometriosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study emphasizes the importance of ovarian reserve (AMH) as a predictor of IVF success in terms of oocyte retrieval in women with endometriosis. Age and bilaterality of cysts remained negative prognostic factors, while other factors such as surgical management and stimulation protocols did not significantly affect IVF outcomes in this cohort. Treatment protocols could be tailored to focus on ovarian reserve markers (such as AMH levels) and age, rather than performing unnecessary surgeries to remove endometriomas. This approach could reduce unnecessary surgical interventions and offer a less invasive path to IVF.\u003c/p\u003e \u003cp\u003eOSI provides a valuable parameter for assessing ovarian response. Incorporating OSI into clinical practice can help compare stimulation outcomes between different protocols or patient groups, offering a more accurate reflection of response.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eLimitations and Suggestions for Future Research\u003c/h2\u003e \u003cp\u003eWhile this study provides valuable insights into the factors affecting oocyte retrieval and clinical pregnancy rates in patients with endometriosis undergoing IVF, several limitations must be considered. The severity of endometriosis according to the endometriosis stage was not mentioned. The exclusion of endometriosis severity, adenomyosis, and deep infiltrating endometriosis, as well as the focus on cleavage-stage embryo transfers, may restrict the generalizability of our findings. In addition, unaccounted factors such as aneuploidy and genetic influences could have confounded the results, highlighting the need for further exploration of these variables. Additionally, incorporating both cleavage stage and blastocyst transfers could provide a more holistic view of the factors influencing success rates. Prospective studies with larger, more diverse patient populations and improved methodologies are also necessary to confirm these findings and to further elucidate the mechanisms underlying IVF success in patients with endometriosis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eIVF \u0026ndash; In-Vitro Fertilization\u003c/p\u003e\n\u003cp\u003eAMH \u0026ndash; Anti-Mullerian Hormone\u003c/p\u003e\n\u003cp\u003eAFC \u0026ndash; Antral Follicular count\u003c/p\u003e\n\u003cp\u003eGnRH \u0026ndash; Gonadotropin Releasing Hormone\u003c/p\u003e\n\u003cp\u003eFSH \u0026ndash; Follicular Stimulating Hormone\u003c/p\u003e\n\u003cp\u003eOSI \u0026ndash; Ovarian Sensitivity Index\u003c/p\u003e\n\u003cp\u003eHCG \u0026ndash; Human Chorionic Gonadotropin\u003c/p\u003e\n\u003cp\u003ecCPR \u0026ndash; Cumulative Clinical Pregnancy Rate\u003c/p\u003e\n\u003cp\u003eIQR \u0026ndash; Inter-Quartile Range\u003c/p\u003e\n\u003cp\u003eICSI \u0026ndash; Intra Cytoplasmic Sperm Injection\u003c/p\u003e\n\u003cp\u003eOHSS- Ovarian hyperstimulation syndrome\u003c/p\u003e\n\u003cp\u003eART- Assisted reproductive technology\u003c/p\u003e\n\u003cp\u003eBMI- Body mass index\u003c/p\u003e\n\u003cp\u003eFORT- Follicular output rate\u003c/p\u003e\n\u003cp\u003eFOI- Follicular oocyte index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate: The study was approved by the Institutional Ethical Committee (Kasturba Medical College and Kasturba Hospital Institutional Ethical Committee, Registration No. ECR/146/Inst/KA/2013/RR-19) on 23/10/ 2024 (IEC1: 396/2024).\u003c/p\u003e\n\u003cp\u003eConsent to participate: A permission letter was obtained from the Medical Superintendent of Kasturba Medical College and Hospital for collecting data for the study. Since the research was based on retrospective data gathered during routine patient care, individual informed consent was not obtained. The study involved anonymized data, with no patient identifiers used.\u003c/p\u003e\n\u003cp\u003eConsent for publication: not applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests: \u003cstrong\u003eThe author(s) declare(s) that they have no competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunding: This work did not receive any specific grants from any funding agency in the public, commercial, or non-profit sectors.\u003c/p\u003e\n\u003cp\u003eAuthor 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 reviewed and edited the manuscript; V.G.P. and P.K.N helped in providing intellectual input and proofreading of the manuscript and supervised the project. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements: Figure 1 and 2 created by using Microsoft PowerPoint application.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Reviews Endocrinol. 2019;15(11):666\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlshehre SM, Narice BF, Fenwick MA, Metwally M. 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Int J Fertility Steril. 2014;8(1):29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSomigliana E, Palomino MC, Castiglioni M, Mensi L, Benaglia L, Vercellini P, Garcia-Velasco J. The impact of endometrioma size on ovarian responsiveness. Reprod Biomed Online. 2020;41(2):343\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang N, Hao CF, Zhuang LL, Liu XY, Gu HF, Liu S, Chen ZJ. Prediction of IVF/ICSI outcome based on the follicular output rate. Reprod Biomed Online. 2013;27(2):147\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma S, Garima DM, Sharma R, Verma A, Raksha H. FORT: Predicting IVF/ICSI Outcomes. Age.;31:3\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHassan A, Kotb M, AwadAllah A, Wahba A, Shehata N. Follicular output rate can predict clinical pregnancy in women with unexplained infertility undergoing IVF/ICSI: a prospective cohort study. 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J Clin Med. 2020;9(6):1914.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiasoni V, Patriarca A, Dalmasso P, Bertagna A, Manieri C, Benedetto C, Revelli A. Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF. Reproductive Biology Endocrinol. 2011;9:1\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Loendersloot LL, Van Wely M, Limpens J, Bossuyt PM, Repping S, Van Der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010;16(6):577\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTomazevic T, Korosec S, Klun IV, Drobnic S, Verdenik I. Age, oestradiol and blastocysts can predict success in natural cycle IVF\u0026ndash;embryo transfer. 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Gynecol Endocrinol. 2013;29(9):859\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen Q, Du S, Lin Y, Zheng B. Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH‐agonist or GnRH‐antagonist protocols: A retrospective study by propensity score matching. J Obstet Gynecol Res. 2023;49(5):1366\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Li W, Chen X, Zhang W, Chu M, Yin S, Chu Y, Liu X. Is the long-acting gonadotropin‐releasing hormone agonist long protocol better for patients with endometriosis undergoing IVF? Int J Gynecol Obstet. 2023;162(1):325\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKolanska K, Cohen J, Bendifallah S, Selleret L, Antoine JM, Chabbert-Buffet N, Darai E, d\u0026rsquo;Argent EM. Pregnancy outcomes after controlled ovarian hyperstimulation in women with endometriosis-associated infertility: GnRH-agonist versus GnRH-antagonist. J Gynecol Obstet Hum Reprod. 2017;46(9):681\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuan KK, Omoseni S, Tello JA. Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: a systematic review. Therapeutic Adv Endocrinol Metabolism. 2023;14:20420188231173325.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePabuccu R, Onalan G, Kaya C. GnRH agonist and antagonist protocols for stage I\u0026ndash;II endometriosis and endometrioma in in vitro fertilization/intracytoplasmic sperm injection cycles. Fertil Steril. 2007;88(4):832\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endometrioma, IVF/ICSI outcomes, Oocyte retrieval, Ovarian stimulation, endometriotic cystectomy, FORT (follicular output rate), OSI (ovarian sensitivity index), FOI (follicle to oocyte index)","lastPublishedDoi":"10.21203/rs.3.rs-6103638/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6103638/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEndometriosis, particularly endometriotic cysts (endometriomas), is commonly related to infertility in women. In vitro fertilization (IVF) is a widely used treatment for these patients; however, its outcomes can be influenced by various factors. This retrospective study aimed to investigate the factors affecting IVF outcomes in women with endometriomas.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 83 women who underwent IVF between May 2021 and April 2024. Various factors were assessed, including ovarian reserve (measured by anti-M\u0026uuml;llerian hormone [AMH] levels), age, presence of bilateral endometriomas, surgical management of endometrioma, size of endometriomas, and ovarian stimulation protocols (antagonist \u0026amp; agonist flare). Multivariable linear and logistic regression analyses were performed to determine the relationships between these variables and IVF outcomes, including the number of oocytes retrieved and clinical pregnancy rates.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the ovarian response parameters, the Ovarian Stimulation Index (OSI) showed the strongest correlation with both the number of oocytes (r\u0026thinsp;=\u0026thinsp;0.886) and mature oocytes (r\u0026thinsp;=\u0026thinsp;0.809), suggesting its reliability in assessing the ovarian response in women with endometriosis. AMH levels were a significant positive predictor of the number of oocytes retrieved (β\u0026thinsp;=\u0026thinsp;3.210, 95% CI: 2.670, 3.752, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conversely, age and the presence of bilateral endometriomas were negatively associated with oocyte retrieval (age: β = -0.1879, 95% CI: -0.397, 0.021, p\u0026thinsp;=\u0026thinsp;0.07; bilateral endometriomas: β = -1.9670, 95% CI: -3.519, -0.415, p\u0026thinsp;=\u0026thinsp;0.014). Surgical management and endometrioma size did not significantly affect the oocyte retrieval. Age was also a significant negative predictor of clinical pregnancy (β = -1.329, 95% CI: -1.955, -0.704, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study highlights the importance of ovarian reserve and age as significant factors influencing IVF outcomes in women with endometriotic cysts. The choice of ovarian stimulation protocol did not appear to significantly affect oocyte retrieval. Tailored IVF treatment strategies should focus on these factors to optimize results. Additionally, the ovarian sensitivity index (OSI) is a reliable tool for assessing ovarian response in these patients.\u003c/p\u003e","manuscriptTitle":"Endometriosis and IVF: Clinical, Surgical, and Biological Factors Affecting Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-11 09:40:53","doi":"10.21203/rs.3.rs-6103638/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e78048e-88e1-43e0-8928-4e03b2dff0c3","owner":[],"postedDate":"March 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-11T09:40:56+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-11 09:40:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6103638","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6103638","identity":"rs-6103638","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}