Evaluation of endometrioma size effect on IVF outcomes in young infertile women candidates for IVF cycle

Background Endometriomas are ovarian cysts associated with endometriosis, potentially impacting ovarian reserve and in vitro fertilization (IVF) outcomes. The effect of endometrioma size on IVF success remains controversial. This study aimed to evaluate the influence of endometrioma size on ovarian reserve parameters, oocyte and embryo qual- ity, and pregnancy outcomes in infertile women undergoing IVF.

This cross-sectional study included 57 infertile women with unilateral endometriomas undergoing IVF at Akbarabadi Hospital, Iran. Participants were divided into two groups based on endometrioma size: < 3 cm (n = 26) and ≥ 3 cm (n = 31). Ovarian reserve markers (AMH, AFC, FSH), oocyte and embryo quality, clinical pregnancy rate, and live birth rate were compared between groups. Statistical analyses were performed using SPSS 27.

There were no significant differences between the two groups in age, BMI, duration of infertility, AMH, AFC, or FSH levels. Oocyte quality, embryo quality, and clinical pregnancy rates were also comparable (P > 0.05). However, a significantly lower live birth rate was observed in the ≥ 3 cm endometrioma group compared to the < 3 cm group (28.6% vs. 70.0%, P = 0.004).

Endometrioma size does not significantly affect ovarian reserve, oocyte retrieval, or early embryo development. However, larger endometriomas (≥ 3 cm) may be associated with a lower live birth rate, possibly due to inflammatory or mechanical effects. Further multicenter studies with larger sample sizes are needed to confirm these findings and optimize IVF strategies for women with endometriomas.

Endometrioma, IVF, Oocytes, Ovarian stimulation

The general prevalence of endometriosis is about 10 to 20%, with stage-specific prevalence ranging from 2% for stage 4 to 20% for stage 1 [1, 2]. The prevalence rate of endometriosis among women experiencing infertility is about 30 to 50% [2–4]. Depending on the endometriosis site, it can be categorized into various subtypes, includ - ing endometrioma, deep infiltrating endometriosis (DIE), and superficial endometriosis [5–7]. Around 17 to 44% of women with a diagnosis of endometriosis will develop an endometrioma, lesions that contain thick, dark brown fluid and are called chocolate cysts [4, 8]. Recent meta-analyses have indicated that both serum anti-Müllerian hormone (AMH) levels and antral fol - licle count (AFC) are significantly lower in patients with endometriomas when compared to other benign ovarian cysts or non-cystic ovaries [9, 10]. The ovulation rate in ovaries impacted by an endometrioma is lower than in the opposite unaffected ovary. The average ovulation rate in affected ovaries is 34.4 ± 6.6%, less than the anticipated *Correspondence: Saeedeh Shirdel [email protected] 1 Shahid Akbar Abadi Clinical Research Development Unit, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 2 Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran Page 2 of 7Javedani Masroor et al. Middle East Fertility Society Journal (2025) 30:19 rate of 50% in unaffected ovaries [11]. Assessing the reproductive outcomes of women with endometriomas who have not previously had adnexal surgery revealed a decreased response to ovarian stimulation, indicated by an increased cycle cancellation rate, a reduced number of retrieved m2 oocytes, but high-quality embryos, clini - cal pregnancy rate, implantation rate (IR) and live birth rate(LBR) were similar in women with and without endo- metrioma. The number of embryos varied in different studies [12–14]. The surgical procedure for an endome - trioma is still controversial. Although specific research indicates that surgically excising large endometriomas might enhance oocyte quality by lowering inflammation and clearing the ovarian environment, the surgery can also diminish ovarian reserve; clinicians should consider its risk-benefit balance [14–16]. Although numerous studies examined the effect of endometriomas and their surgical treatment on repro - ductive characteristics and in vitro fertilization (IVF) out- comes, there is a scarcity of research with mixed results regarding the impact of endometrioma size on these fac - tors. According to some studies, larger endometriomas (≥ 3–5 cm) at the time of IVF significantly decrease the number of oocytes retrieved and ovarian reserve com - pared with the contralateral healthy ovaries [17–19]. However, in other studies, the larger size did not increase adverse IVF outcomes, including embryo quality [20]. Considering the conflicting and lack of evidence on the impact of endometrioma size on IVF outcomes, our study aims to investigate further the effect of endometrioma size on IVF outcomes, which can assist in optimizing future treatment strategies and improving reproductive outcomes in patients.

Study setting and design This cross-sectional study was conducted at the infertil - ity clinic of Akbarabadi Hospital, Tehran, from March 2022 to March 2024. The study aimed to evaluate endo - metrioma size on various IVF outcomes among infertile women. Eligibility criteria The inclusion criteria were women aged between 20 and 37 years undergoing IVF for infertility, the presence of unilateral endometrioma diagnosed via transvaginal ultrasonography (TVUS), no history of IVF failure, and no previous ovarian or pelvic surgery. The exclusion cri - teria were severe male factor infertility, hydrosalpinx, primary ovarian insufficiency (POI), hyperprolactinemia, uterine abnormality, history of recurrent miscarriage, polycystic ovarian syndrome, and history of autoimmune disease or malignancy. Participants were aged 20–37 years to minimize age-related confounding on ovarian reserve and IVF outcomes, as reproductive potential declines significantly beyond this threshold [21]. Ethical consideration The study was approved by the Iran University of Medical Science ethics committee (approval number:IR.IUMS. FMD.REC.1401.124). Written informed consent was obtained from all participants, ensuring confidentiality. Sample size and calculation The sample size was calculated using the information obtained from the Ferrero 2017 study and the G POWER software [19]. Considering the first type error of 0.05 and the second type error of 0.2, as well as the average of 3.5 (± 1.7) MΙ eggs for the small endometrioma group and 2 for the large endometrioma group, we determined that at least 21 participants were needed for each group. Data collection This cross-sectional study with longitudinal follow- up prospectively collected IVF outcome data (March 2022–2024) while utilizing medical records for baseline characteristics. Gynecologists actively recorded IVF out - comes during patient follow-up visits, ensuring real-time data collection for critical endpoints like oocyte quality, embryo transfer results, and live birth rates. Baseline data (endometrioma size, AMH levels, AFC) were extracted from medical records but verified by clinicians. Participants were divided into two groups according to their endometrioma size (diameter) measurement by TVUS (centimeter). One group had endometriomas smaller than 3 cm in diameter, and the other had 3 cm or greater endometriomas. The 3  cm cutoff was chosen to balance clinical significance and alignment with existing literature [17, 22]. Endometrioma size was determined by averaging the transverse and longitudinal diameters measured via TVUS. This approach accounts for poten - tial irregular cyst morphology and reduces measurement bias compared to single-diameter reporting. Data were collected through patients’ medical records. Variable gathered included: Demographic data: age (years), body mass index (BMI), (kg/m2), and the duration of infertility (years). The reproductive parameters before IVF: anti-Mülle - rian hormone (AMH) level (ng/ml), antral follicle count (AFC), and follicle-stimulating hormone (FSH) level (IU/L). IVF-related outcomes: quality of retrieved oocytes, number and quality of transferred embryos, clinical preg- nancy rate, and live birth rate (LBR). Page 3 of 7 Javedani Masroor et al. Middle East Fertility Society Journal (2025) 30:19 Patients were included in the gonadotropin-releasing hormone (GnRH) antagonist protocol for IVF. The gon - adotropin dose was modified based on the assessment of follicular growth observed through TVUS. When at least two follicles reached a mean diameter of 18 mm, oocyte maturation was induced with 4,000 to 10,000  IU dose of human chorionic gonadotropin (HCG), and oocyte retrieval, assisted by TVUS, was conducted about 36 h following the hCG injection. Then, the number and qual- ity of oocytes were checked according to the degree of nucleus maturity (MΙ/MΙΙ/GV). It should be noted that the injected sperm of all patients have normal parameters according to WHO criteria. The quality of the resulting embryos by the embryologist of the center on the third day of fertilization was evaluated and divided into four groups: grading A (equal blasto - meres without fragments or less than 10%), B (equal blas- tomeres with fragments between 10 and 30%), C (equal or unequal blastomeres with fragments 30–50%), and D (uneven blastomeres with fragment with more than 50% fragments). Then, fresh embryos were transferred after 6  weeks The second transfer was done among patients with failure in first time. The third transfer was done in cases of second transfer failure. An ultrasound examina - tion was performed to determine clinical pregnancy. The live birth rate was also evaluated. Statistical analysis The information was inputted into the SPSS software version 27. The mean and standard deviation (SD) were employed to describe continuous variables, while cate - gorical data were presented as frequency and percentage. Rank variables were analyzed using the k2 test or Fisher’s exact test, whereas quantitative variables were assessed with the t-test or Mann–Whitney test. The Kolmogorov– Smirnov test was utilized to evaluate the distribution of the data. Quantitative parametric data were evaluated using an independent t-test, while non-parametric data were assessed with the Mann–Whitney test. Qualitative data were examined through the χ2 (chi-square) test. A P-value of less than 0.05 was determined to be statisti - cally significant. Multivariate regression analysis was conducted to adjust potential confounding variables like maternal age.

In this study, 57 infertile women with unilateral endo - metrioma who underwent IVF were evaluated. Partici - pants were allocated into two groups: 26(45.6%) patients in the group with endometriomas smaller than 3  cm and 31(54.4%) patients with endometriomas equal to or greater than 3 cm in diameter. When comparing the maternal demographic variables, including age, BMI, and the duration of infertility, there were no significant differences between the two groups (P > 0.05). FSH levels were consistent between the two groups: 8.99 ± 0.45 IU in the group with endometrioma < 3 cm and 8.0187 ± 0.50 in the other group (P = 0.53). There was no significant difference concerning AMH lev- els between the smaller endometrioma group, 1.38 ± 0.83 ng/dl, and the larger endometrioma group, 1.44 ± 0.85 ng/dl (P = 0.79). Also, the mean number of antral folli - cles on the right and left sides in the two endometrioma size groups had no statistically significant difference (P = 0.477). All the above-mentioned data are summarized in Table 1. Regarding oocyte quality, there were no significant dif - ferences between the two groups. The number of patients with high-quality oocytes (MΙΙ) was 112(58.6%) in the endometrioma group < 3 cm and 97 (51.9%) in the endo - metrioma group ≥ 3 cm, which is not statistically signifi - cant (P = 0.63) (Table 2). There was no significant difference in the number and quality of embryos between the two groups, with Table 1 Comparison of the characteristics of patients before starting IVF cycle in two group P < 0.05 is considered statistically significant n sample size Data are presented as mean±standard deviation (SD) Variable Endometrioma < 3 cm (n = 26) Endometrioma ≥ 3 cm (n = 31) Total (n = 5 7) P-value Age (years) 29.38 ± 3.93 29.03 ± 4.17 29/19 ± 4/03 0.74 BMI (kg/m2) 21.96 ± 1.90 22.67 ± 1.81 22/350/41/87 0.15 Infertility duration (years) 2.65 ± 0.65 2.64 ± 0.75 2/65 ± 0/72 0.96 FSH (IU/L) 8.09 ± 0.45 8.01 ± 0.50 8/05 ± 0/48 0.53 AMH (ng/ml) 1.38 ± 0.83 1.44 ± 0.85 1/4 ± 0/84 0.79 AFC (number) 4.23 ± 2.64 3.74 ± 2.50 3.96 ± 2.56 0.47 Page 4 of 7Javedani Masroor et al. Middle East Fertility Society Journal (2025) 30:19 82 (76.6%) A, 17 (15.9%) B, and 8 (7.5%) C in the endo - metrioma group < 3 cm and 75(69.5%) A, 24 (22.2%) B, 9(8.3%) C in the endometrioma group ≥ 3 cm. Grade D (uneven blastomeres with more than 50% fragment) was not observed in the examined cases (P = 0.67) (Table 3). The mean number of transferred embryos was investi - gated in the first, second, and third transfer times. For the first time in the < 3 cm endometrioma group, 1.92 ± 0.74 embryos were transferred, compared to 1.81 ± 0.60 in the other group (P = 0.47). For the second time in the group of endometrioma < 3 cm, 1.92 ± 0.48 embryos vs. 1.93 ± 0.68 in the endometrioma group ≥ 3 cm were trans - ferred (P = 0.93). For the third time in the endometrioma group < 3 cm, 1.73 ± 0.78 embryos compared to 1.81 ± 0.75 embryos in the endometrioma ≥ 3 cm were trans - ferred (P = 0.71). This indicates no significant differences in the number of transferred embryos between the two groups (Table 4). Two groups’ cumulative clinical pregnancy rate was evaluated, and no statistically significant differences existed. In the first embryo transfer, 30.8% of the endo - metrioma group < 3 cm had a positive clinical pregnancy. This rate was 25.8% in the endometrioma group ≥ 3 cm (P = 0.678). In the second transfer, 11.5% of the endome - trioma group < 3 cm had a positive clinical pregnancy. This rate was 3.2% in the endometrioma group ≥ 3 cm (P = 0.387). In the third transfer, 34.6% of the endometri - oma group under 3 cm had a positive clinical pregnancy, and this rate was 16.1% in the endometrioma group above 3 cm (P = 0.137) (Table 5). In terms of pregnancy outcome, 14(70.0%) patients in the endometrioma group < 3 and 4 (28.6%) patients in the endometrioma group ≥ 3 cm had a live birth, which is statistically significant (P = 0.004) (Table 6).

Our study aimed to evaluate the effect of endometrioma size on IVF outcomes of infertile women. We divided patients into two groups: those with endometriomas less than 3  cm in diameter and those with 3  cm and larger endometriomas. Our findings indicate that the endo - metrioma size does not significantly impact most of our measured variables, such as AMH level, FSH level, AFC, and retrieved oocyte and embryo quality, suggesting that endometrioma size may not affect the oocyte and early stage of embryo development or transfer. However, although there are no statistical differences in the clinical pregnancy rate, a trend of higher pregnancy rate, particu- larly on the third transfer, is observed among the smaller endometrioma group. This trend, while not statistically significant, may suggest that larger endometriomas could affect the implantation rate of uterine receptivity, poten - tially due to mechanical or inflammatory factors associ - ated with larger cysts. There is a significant difference in live birth rates, with a higher rate in the smaller endome - trioma group than in the larger one (76.9% vs. 48.4%, P = 0.028). This finding indicates that larger endometrioma could negatively affect the pregnancy rate with mecha - nisms such as inflammatory response in the later stage of pregnancy. Similar to our observations, in a 2020 descriptive study, Akgul et  al. found no association between AMH level and endometrioma size (greater than 40 mm and less than 40 mm) [23]. However, In contrast to our finding, a case-control study by Marcellin et al. in 2019 showed that serum AMH levels increased with endometrioma size. Chen et al. in 2014 discovered that the damage of ovarian reserve in endometrioma correlated with the presence Table 2 Comparison of oocyte quality and number P < 0.05 is considered statistically significant n sample size Data presented as number of patients (n) and percentages (%) Variable Endometrioma < 3 cm Endometrioma ≥ 3 cm P-value M1 21 28 0.63 M2 112 97 GV 58 62 total 191 187 Table 3 Comparison of the number and quality of embryos P < 0.05 is considered statistically significant n Sample size Data presented as number of patients (n) and percentages (%) Variable Endometrioma < 3 cm (n = 26) Endometrioma ≥ 3 cm (n = 31) P-value A 82 75 0.67 B 17 24 C 8 9 total 107 108 Table 4 Comparison of the number of embryos at three different transfer cycles P < 0.05 is considered statistically significant n sample size Data are presented as mean±standard deviation (SD) Variable Endometrioma < 3 cm Endometrioma ≥ 3 cm P-value First transfer 1.92 ± 0.74 1.80 ± 0.60 0.51 Second transfer 1.92 ± 0.48 1.93 ± 0.68 0.93 Third transfer 1.73 ± 0.77 1.80 ± 0.74 0.71 Page 5 of 7 Javedani Masroor et al. Middle East Fertility Society Journal (2025) 30:19 of bilateral cysts and larger size (notably for cysts larger than 7 cm), and larger endometrioma is associated with lower serum levels of AMH [24]. Regarding the size of the endometrioma and its effect on IVF outcomes, in line with our results, Almog et  al. (2011) compared the impact of endometrioma larger than 25 mm with smaller endometriomas on the num - ber of oocytes retrieved And determined no relation - ship between the size of the endometrioma and the total number of oocytes retrieved [25]. In agreement with our findings, in a cross-sectional study by Zareii et al. in 2023, patients with unilateral and bilateral endometrioma were divided into three groups based on the size of the endometrioma (1–3 cm, 3–6 cm, 6–10 cm). Although the AMH level declined as the size of the endometrioma increased, this difference was not statistically significant (P = 0.07). Additionally, there was no significant differ - ence in embryo quality between the groups based on the endometrioma size. However, this study did not evaluate the effect of endometrioma size on pregnancy complica - tions and LBR [20]. Unlike the outcomes observed in our study, in 2020, Somigliana et  al. concluded that endometrio - mas greater than 4  cm could reduce ovarian respon - siveness during IVF cycles [26]. Furthermore, Orazov et al. (2019) found a deterioration in oocyte quality in patients with endometriomas larger than 3  cm, and endometriomas adversely impact oocyte quality [27]. A 2017 study by Ferrero et al. reported that the quality and number of oocytes retrieved were lower in ovaries with large endometriomas (≥ 5 cm) compared to con - tralateral healthy ovaries. However, it did not compare this endometrioma size with a smaller group [19]. There are many reasons for our study’s findings to vary from those of others. This study specifically examines the impact of endometrioma size on IVF outcomes. In contrast, many others evaluate broader comparisons such as endometrioma vs. no endome - triomas or unilateral vs. bilateral. For instance, Ferrero et al. and Somigliana et al. focused on larger endome - trioma (≥ 5 cm or ≥ 4 cm), while our cutoff was 3 cm. In addition, our sample size and selection criteria can limit the patient pool and explain the lack of significant differences compared to studies such as Somigliana et al., which include a more heterogeneous population [19, 26]. An increasing number of studies have examined the impact of endometrioma itself and endometrioma sur - gery on ovarian reserve and IVF outcomes [4 , 12, 14, 15, 28]. Still, there is a lack of sufficient data regarding the influence of endometrioma size on ovarian reserve and fertility outcomes, including the number and qual - ity of retrieved oocytes and embryos, fertilization rate, and pregnancy outcomes and complications. Since dif - ferent results have been obtained regarding the effect of endometrioma surgery on reproductive function and IVF outcomes, examining the impact of the size of endometrioma size can prevent unnecessary, inef - fective, and optimizing future treatment strategies [15, 29– 32]. Some limitations of the present study should be con - sidered. Our sample size is relatively small, especially after dividing participants into two groups, which lim - its the statistical power to detect subtle differences. Moreover, it is a single-center study, and the findings may not be generalizable to other populations or set - tings. This study also does not evaluate bilateral endo - metrioma, the severity of endometriosis (beyond Table 5 Comparison of the cumulative clinical pregnancy rate after 3 times of embryo transfer P < 0.05 is considered statistically significant n sample size Data presented as number of patients (n) and percentages (%) Variable Endometrioma < 3 cm Endometrioma ≥ 3 cm P-value First transfer Positive 8(30.8%) 8(25.8) 0.67 Negative 18(69.2%) 23(74.15%) Second transfer Positive 3(11.5%) 1(3.2%) 0.38 Negative 15(57.7%) 22(71%) Third transfer Positive 9(34.6%) 5(16.1%) 0.13 Negative 6(23.1%) 14(45.2%) Table 6 Comparison of pregnancy outcomes among participants with positive clinical pregnancy P < 0.05 is considered statistically significant n sample size Data presented as number of patients (n) and percentages (%) Variable Endometrioma < 3 cm (n = 20) Endometrioma ≥ 3 cm (n = 14) Total P-value Live birth rate 14(70.0%) 4(28.6%) 28 0.004 Page 6 of 7Javedani Masroor et al. Middle East Fertility Society Journal (2025) 30:19 endometrioma size), fertilization rate, chemical preg - nancy, and inflammatory markers. However, this study has several notable strengths compared to previous studies. First, it is among the few to specifically inves - tigate the impact of endometrioma size (stratified by a clinically relevant 3 cm cutoff) on live birth rates (LBR), a critical IVF outcome often overlooked in prior stud - ies focusing solely on ovarian reserve or embryo qual - ity. Second, our hybrid design—combining prospective outcome tracking with rigorous baseline data verifica - tion—enhances the reliability of findings while mini - mizing recall bias. Third, we isolated the effect of cyst size by excluding confounders (e.g., bilateral cysts, prior ovarian surgery) and controlling for age (20–37 years). Finally, using standardized IVF protocols and centralized embryology assessments ensures consist - ency in outcome measurements. Future research should involve larger groups from mul- tiple centers to improve the generalizability and statistical power. A prospective design could provide more reliable evidence and reduce biases. Furthermore, categorizing participants into more specific size groups (e.g., 5 cm) could yield more accurate insights into the effects of size. Also, Investigating inflammatory or oxidative stress markers associated with endometriomas and their potential difference in variable cyst size could clarify the mechanisms that affect infertility.

Our study evaluates the effect of endometrioma size on ovarian reserve and IVF outcomes in infertile women. The findings indicate that the endometrioma size does not significantly affect ovarian reserve parameters, including AMH, AFC, or FSH levels. It also does not affect the quality of retrieved oocytes, the number and quality of embryos, or the clinical pregnancy rate. How - ever, a larger size could negatively impact the live birth rate compared to a smaller size. Future multicenter pro - spective studies with a larger sample size and broader comparison are necessary to confirm these findings. Abbreviations DIE Deep infiltrating endometriosis AFC Antral follicle count IR Implantation rate LBR Live birth rate IVF In vitro fertilization TVUS Trans vaginal ultrasonography BMI Body mass index FSH Follicular stimulating hormone HCG Human chorionic gonadotropin WHO World Health Organization

Acknowledgements: We acknowledge using ChatGPT-4 (OpenAI) for language editing and improving paragraph structure in this manuscript. We confirm that the authors solely developed all research content, data analysis, interpretations, and conclusions. The AI tool was used strictly for linguistic refinement and did not contribute to the scientific content or conclusions of the study. Conflicts of interest The authors declare that they have no conflicts of interest. Authors’ contributions M.J.M. Conception, supervision, data revising; S.G. original draft preparation. Collecting data; Z.Z. Statistical analysis; E.GH: collecting data; S.SH: Writing – original draft. Review article. Funding No financial support/funding was received for this study. Data availability The corresponding author can provide the datasets used in the current study upon a reasonable request. Declarations Ethics approval and consent to participate The ethics committee of Iran University of Medical Science approved the study (approval number: IR.IUMS.FMD.REC.1401.124). Consent for publication Not applicable. Conflict The authors declare no competing interests. Received: 16 February 2025 Accepted: 31 May 2025

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