The Impact of Laparoscopic Versus Open Conservative Surgery for Adenomyosis on Subsequent In Vitro Fertilization Outcomes: A Retrospective Cohort Study

Background: With the widespread adoption of fertility-preserving conservative surgery for adenomyosis in clinical practice, the impact of different surgical approaches on subsequent reproductive outcomes has become a key clinical concern. This study aimed to investigate the impact of laparoscopic versus open conservative surgery for adenomyosis on subsequent in vitro fertilization (IVF) outcomes. Ade- nomyosis is a recognized cause of female infertility; yet, the optimal surgical approach for patients seeking to preserve fertility remains debated, and comparative data on their effect on subsequent IVF outcomes are limited. Methods: This single-center retrospective cohort study included 162 infertile women with adenomyosis who underwent primary conservative surgery (98 laparoscopic, 64 open) between January 2018 and December 2023. Diagnosis was confirmed by imaging and histopathology. Strict exclusion criteria were applied to minimize confounding. The primary outcome was live birth rate following postoperative IVF. Multivariate logistic regression was used to evaluate the independent effects of surgical approach and intraoperative factors on live birth. Results: Baseline characteristics were comparable between groups, except for a higher proportion of diffuse adenomyosis in the open surgery group (65.6% vs. 28.6%, p < 0.001). As expected, open surgery was associated with longer intraoperative blood loss (103 [55–140] vs. 61 [30–80] mL, p < 0.001), and larger resected lesion volume (40 [22–58] vs. 23 [12–32] cm 3, p < 0.001). However, postoperative IVF parameters and pregnancy outcomes showed no significant differences. Clinical pregnancy rates (laparoscopic vs. open: 48.0% vs. 50.0%, p = 0.795) and live birth rates (36.7% vs. 37.5%, p = 0.917) were similar. Multivariate analysis confirmed that surgical approach was not an independent predictor of live birth (adjusted odds ratio [OR] = 1.05, 95% confidence interval [CI]: 0.54–2.04, p = 0.882). Intraoperative blood loss and resection volume were likewise not significantly associated with live birth. Conclusions: Within the limitations of this retrospective design, the choice between laparoscopic and open conservative surgery in infertile patients with adenomyosis was not found to signif- icantly affect subsequent IVF live birth outcomes. Surgical decisions may therefore be guided by individual lesion characteristics and surgeon expertise, as the approach alone does not appear to compromise fertility potential based on the available evidence.

adenomyosis; infertility; conservative surgical treatment; pregnancy outcome 1. Introduction Adenomyosis is a common benign gynecological con- dition affecting approximately 20% of women of reproduc- tive age. Its main clinical manifestations include abnor- mal uterine bleeding, pelvic pain, and infertility [ 1,2]. The pathological hallmark of adenomyosis is the invasion of en- dometrial glands and stroma into the myometrium, lead- ing to uterine enlargement, disruption of myometrial ar- chitecture, and functional impairment of the endometrio- myometrial junctional zone, which may subsequently inter- fere with embryo implantation and early pregnancy main- tenance [ 3,4]. In recent years, advances in imaging tech- niques and growing emphasis on fertility preservation have led to the widespread adoption of conservative surgical treatment for adenomyosis in clinical practice [ 5,6]. The primary surgical approaches include laparoscopic surgery and open abdominal surgery. The choice between these procedures typically depends on the extent and loca- tion of the lesions, symptom severity, and the patient’s fer- tility goals [ 7,8]. For diffuse adenomyosis or extensive le- sions involving the posterior uterine wall, open abdominal surgery is often preferred to achieve more complete lesion resection. In contrast, laparoscopic surgery is generally fa- vored for focal adenomyosis or cases with mild pelvic ad- hesions, due to its minimally invasive nature and faster re- covery [ 9,10]. Nevertheless, the two surgical approaches may differ in terms of intraoperative blood loss, extent of lesion resection, and postoperative uterine healing, all of which could potentially impact outcomes following assisted reproductive technology (ART) [11,12]. Current studies have investigated natural conception and in vitro fertilization (IVF) outcomes in infertile patients with adenomyosis following conservative surgery, suggest- ing that postoperative reductions in uterine volume and symptom improvement may be associated with higher fer- tility success rates [ 13,14]. However, comparative studies specifically examining the impact of different surgical ap- proaches, laparoscopic versus open surgery, on subsequent IVF outcomes remain relatively limited [ 15,16]. Further- more, the existing literature lacks a systematic evaluation of the relationship between intraoperative variables, such as blood loss and resection volume, and live birth outcomes following IVF. Therefore, this study retrospectively analyzed clinical data from infertile patients with adenomyosis who under- went conservative surgical treatment at our center. The ob- jectives were to compare intraoperative indicators and post- operative IVF outcomes between laparoscopic and open ab- dominal surgery, to explore whether the surgical approach and associated intraoperative factors influence live birth rate, and to provide evidence to inform clinical decision- making regarding the choice of surgical technique. 2. Methods 2.1 Study Design and Participant Selection This was a single-center retrospective cohort study. Patients with infertility and adenomyosis who attended the reproductive center of Sir Run Run Shaw Hospital be- tween January 2018 and December 2023 were systemati- cally screened for eligibility. All participants underwent primary conservative surgical treatment (laparoscopic or open surgery). The diagnosis of adenomyosis was con- firmed by preoperative transvaginal ultrasonography and/or pelvic magnetic resonance imaging and subsequently ver- ified by postoperative histopathological examination. In- fertility was defined according to international standards as the failure to achieve a clinical pregnancy after at least 12 months of regular unprotected intercourse. 2.2 Inclusion and Exclusion Criteria The inclusion criteria were as follows: (1) age be- tween 20 and 45 years; (2) meeting the diagnostic cri- teria for both adenomyosis and infertility as previously described; (3) undergoing first-time conservative surgical treatment for adenomyosis; and (4) receiving postoperative IVF treatment at our center. To minimize the interference of confounding factors on the outcomes, strict exclusion criteria were applied: (1) male factor as the primary cause of infertility; (2) pres- ence of other gynecological conditions significantly affect- ing fertility, such as uncontrolled ovulatory disorders, poly- cystic ovary syndrome (PCOS), or other uterine anomalies (e.g., uncorrected uterine septum); (3) comorbid major sys- temic diseases (e.g., malignant neoplasm, autoimmune dis- eases); (4) history of prior uterine surgery (e.g., myomec- tomy, prior adenomyosis resection); and (5) incomplete sur- gical records or postoperative follow-up data. Of 215 pa- tients initially screened, 162 were included after applying the exclusion criteria. Patient allocation at each stage is de- tailed in Fig. 1. 2.3 Clinical Definitions and Outcome Measures Based on histopathological findings, adenomyosis was classified as diffuse or focal. The diffuse type was de- fined as widespread infiltration of endometrial glands and stroma throughout the myometrium, whereas the focal type (adenomyoma) presented as relatively well-circumscribed nodular lesions within the myometrium. Primary infertility was defined as never having achieved a clinical pregnancy, and secondary infertility referred to the inability to conceive following at least one previous clinical pregnancy. The primary outcome measure of this study was the live birth rate following postoperative IVF cycles. Sec- ondary outcome measures included clinical pregnancy rate (confirmed by the presence of an intrauterine gestational sac and fetal cardiac activity on ultrasound), biochemical preg- nancy rate (elevated serum human chorionic gonadotropin (hCG) not meeting clinical pregnancy criteria), miscarriage rate, and incidence of postoperative complications. All pregnancy outcomes were calculated per patient who under- went at least one embryo transfer cycle after surgery. Ac- cordingly, the denominators for live birth rate and clinical pregnancy rate were based on the number of patients who received at least one embryo transfer following postopera- tive IVF. In this cohort, all 162 included patients underwent at least one embryo transfer cycle after surgery. 2.4 Surgical Intervention and Data Collection Surgical indication was determined based on a com- prehensive assessment encompassing: (1) clinical symp- toms (e.g., severe dysmenorrhea or heavy menstrual bleed- ing poorly controlled by medication); (2) imaging findings suggestive of significant uterine enlargement (uterine vol- ume equivalent to ≥8 weeks of gestation) or lesions poten- tially compromising the uterine cavity environment; and (3) coexisting symptomatic pelvic endometriosis. The surgical approach was determined by senior at- tending physicians based on lesion characteristics, in accor- dance with routine clinical practice rather than a random- ized allocation. Open abdominal surgery was preferred for patients with diffuse lesions, lesions predominantly involv- ing the posterior uterine wall, or those for whom preopera- tive assessment indicated severe pelvic adhesions, with the aim of achieving more complete lesion resection and reli- able uterine closure. Laparoscopic surgery was prioritized for patients with focal disease or mild adhesions. This non- randomized selection process introduced potential selection bias, which is addressed in the statistical analysis and dis- cussion. 2 Fig. 1. Flowchart of patient selection . All surgeries were performed or supervised by experi- enced senior surgeons. Standardized techniques were used for both approaches: following lesion excision, the uterine wall was reconstructed in multiple layers using delayed ab- sorbable sutures (e.g., Vicryl) to ensure adequate myome- trial closure. For focal adenomyosis, complete excision of the adenomyoma with preservation of surrounding healthy myometrium was attempted. For diffuse adenomyosis, a cytoreductive approach was used to reduce adenomyotic volume while maintaining uterine integrity. With the ex- ception of the access method and suturing instrumentation, the surgical technique did not differ substantially between the laparoscopic and open approaches. Intraoperative data, including operative time and es- timated blood loss, were recorded. The volume of re- sected lesions was calculated using the prolate ellipsoid for- mula (volume = 0.52 × length × width × height), based on measurements obtained from preoperative imaging or postoperative specimens. When endometriosis was iden- tified intraoperatively, it was staged according to the re- vised American Fertility Society (rAFS) classification and treated accordingly. Concurrent tubal pathologies (e.g., hy- drosalpinx) and intrauterine pathologies (e.g., polyps de- tected during hysteroscopy) were also addressed at the time of surgery. Postoperatively, patients were advised to defer pregnancy for 3 to 12 months based on the depth of myome- trial involvement and extent of resection. The timing of the first postoperative IVF cycle was recorded. Postoperative IVF protocol: Following the recom- mended waiting period, patients underwent controlled ovar- ian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist or agonist protocol, selected accord- ing to individual ovarian reserve and prior response at the discretion of the treating reproductive endocrinologist. Embryo transfer was performed as either fresh or frozen- thawed, with frozen-thawed embryo transfer being pre- ferred when endometrial preparation was required or to re- duce the risk of ovarian hyperstimulation syndrome. The number of embryos transferred followed national guide- lines based on patient age and embryo quality. Live birth was defined as delivery of a live infant beyond 24 weeks of gestation. Data on IVF cycles, including the number of cycles per patient, were collected. For patients who under- went multiple cycles, only the first postoperative cycle was included to avoid within-patient clustering effects. 2.5 Statistical Analysis Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp, Armonk, NY , USA). Normality of continuous variables was assessed using the 3 Shapiro-Wilk test. Normally distributed variables are pre- sented as mean ± standard deviation (SD) and were com- pared using the independent samples t-test. Non-normally distributed variables are presented as median (interquartile range, IQR) and were compared using the Mann-Whitney U test. In the current manuscript, some continuous variables that deviated from normality are presented as median (IQR) in the tables, and the text descriptions have been aligned ac- cordingly. Categorical variables are described by frequency (percentage) and were compared using the chi-square test or Fisher’s exact test. To assess the independent effect of the surgical ap- proach on live birth outcomes, multivariate logistic regres- sion analysis was performed. V ariables with a p-value <0.2 in univariate analysis, including age, surgical approach, intraoperative blood loss, resected lesion volume, adeno- myosis type, coexisting endometriosis, duration of infer- tility, and prior ART attempts, were considered for inclu- sion. The final multivariable model included the follow- ing variables based on observed data: age, preoperative anti-Müllerian hormone (AMH), adenomyosis type (diffuse vs. focal), duration of infertility, and prior ART attempts. Surgical approach (open vs. laparoscopic), intraoperative blood loss, and resected lesion volume were also retained in the model to test their independent effects. A stepwise forward selection method (likelihood ratio) was used for variable selection. Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. All tests were two-sided, and a p-value < 0.05 was considered statis- tically significant. Given the non-randomized assignment and baseline imbalance in adenomyosis type, we adjusted for these factors in the regression model. However, resid- ual confounding due to unmeasured variables (e.g., lesion severity, surgical difficulty) cannot be entirely excluded and is acknowledged as a limitation. 3. Results The patient selection process is detailed in Fig. 1, which shows that 215 patients were initially screened, 53 were excluded, and 162 met the eligibility criteria. After applying strict inclusion and exclusion criteria, a total of 162 patients were ultimately included in the analysis, com- prising 98 in the laparoscopic surgery group and 64 in the open abdominal surgery group. Comparison of baseline characteristics between the two groups (Table 1) showed no statistically significant differences in age, body mass index (BMI), distribution of infertility type, basal FSH level, or preoperative AMH level (p > 0.05), indicating comparability between the two groups in terms of basic fertility characteristics. Addi- tional baseline variables, including duration of infertility and number of prior ART attempts, were also compara- ble between groups. However, the proportion of diffuse adenomyosis was significantly higher in the open abdomi- nal surgery group compared with the laparoscopic surgery group (65.6% vs. 28.6%, p < 0.001), indicating greater dis- ease severity in the open surgery group. Analysis of surgical outcomes (Table 2) showed that the open abdominal surgery group presented significantly greater operative time, intraoperative blood loss, and re- sected lesion volume compared with the laparoscopic surgery group ( p < 0.001). Specifically, the median (IQR) operative time was 146 (115–178) minutes for the open ab- dominal surgery group, compared with 125 (100–150) min- utes in the laparoscopic surgery group. Median (IQR) blood loss was 103 (55–140) mL in the open abdominal surgery group versus 61 (30–80) mL in the laparoscopic surgery group. The median (IQR) resected lesion volume was 40 (22–58) cm 3 in the open abdominal surgery group and 23 (12–32) cm3 in the laparoscopic surgery group. Comparison of postoperative IVF treatment parame- ters (Table 3) revealed no significant differences between the two groups in the duration of gonadotropin (Gn) use, total Gn dosage, number of oocytes retrieved, fertilization rate, or high-quality embryo rate ( p > 0.05). Endometrial thickness at the time of embryo transfer was also compara- ble (median (IQR): 10.1 (8.5–11.7) mm vs. 9.9 (8.0–11.8) mm, p = 0.593). The median interval from surgery to the first postoperative IVF cycle was 6.0 months (IQR: 4.0–8.0 months) in the laparoscopic group and 6.0 months (IQR: 4.0–9.0 months) in the open abdominal surgery group ( p = 0.612). Postoperative cancer antigen 125 (CA-125) lev- els at 6 months were compared using the Mann-Whitney U test. The median (IQR) values were 58 (32–80) U/mL in the laparoscopic surgery group and 96 (60–130) U/mL in the open abdominal surgery group, with a p-value of 0.105. Although the numerical values differed, the difference did not reach statistical significance, likely due to high inter- patient variability and limited sample size. Analysis of pregnancy outcomes (Table 4) showed no significant differences between the two groups regarding clinical pregnancy rate, miscarriage rate, or live birth rate. The clinical pregnancy rate was 48.0% (47/98) in the la- paroscopic surgery group and 50.0% (32/64) in the open abdominal surgery group ( p = 0.795). Regarding live birth rate, it was 36.7% (36/98) in the laparoscopic surgery group and 37.5% (24/64) in the open abdominal surgery group (p = 0.917). The denominator for these rates was the to- tal number of patients in each group. All pregnancy out- comes were calculated per patient who underwent at least one embryo transfer cycle after surgery. In this cohort, all 162 included patients underwent at least one embryo trans- fer; therefore, the denominator for each group is the full group size. Biochemical pregnancy rates and ectopic preg- nancy rates were also similar between the groups. Multivariate logistic regression analysis, adjusted for potential confounding factors, showed that the surgical ap- proach was not an independent factor affecting live birth rate (OR = 1.05, 95% CI: 0.54–2.04, p = 0.882) (Table 5). Age was a significant factor influencing live birth rate (OR = 0.91, 95% CI: 0.84–0.99, p = 0.032), whereas preopera- 4 Table 1. Baseline characteristics of study patients . Parameter Laparoscopic surgery (n = 98) Open abdominal surgery (n = 64) p-value Age (years), median (IQR) 34 (31–37) 35 (32–38) 0.423 BMI (kg/m2), median (IQR) 22.0 (20.0–24.5) 22.0 (19.5–24.5) 0.521 Duration of infertility (months), median (IQR) 24 (12–36) 24 (12–36) 0.682 Prior ART attempts, median (IQR) 1 (0–2) 1 (0–2) 0.754 Infertility type 0.690 Primary infertility, n (%) 52 (53.1) 36 (56.3) Secondary infertility, n (%) 46 (46.9) 28 (43.8) Basal FSH (IU/L), median (IQR) 7.6 (6.1–9.5) 8.0 (6.3–9.8) 0.445 Preoperative AMH (ng/mL), median (IQR) 2.6 (1.2–4.1) 2.5 (1.1–4.3) 0.872 Adenomyosis type, n (%) <0.001 Diffuse 28 (28.6) 42 (65.6) Focal 70 (71.4) 22 (34.4) Coexisting endometriosis, n (%) 53 (54.1) 38 (59.4) 0.507 Note: Continuous variables were tested for normality; non-normally distributed variables are presented as median (IQR). The p-values for infertility type and coexisting endometriosis were calculated using the chi-square test. BMI, body mass index; IQR, interquartile range; FSH, follicle-stimulating hormone; AMH, anti-Müllerian hormone; ART, assisted reproductive tech- nology. Table 2. Comparison of intraoperative parameters between surgical groups . Surgical parameter Laparoscopic surgery (n = 98) Open abdominal surgery (n = 64) p-value Operative time (min), median (IQR) 125 (100–150) 146 (115–178) <0.001 Blood loss (mL), median (IQR) 61 (30–80) 103 (55–140) <0.001 Resected lesion volume (cm 3), median (IQR) 23 (12–32) 40 (22–58) <0.001 Postoperative hospital stay (days), median (IQR) 3 (2–4) 5 (4–6) <0.001 Note: All continuous variables were non-normally distributed and are therefore presented as median (IQR). Group comparisons were performed using the Mann-Whitney U test. Table 3. Postoperative IVF treatment parameters . IVF parameter Laparoscopic surgery (n = 98) Open abdominal surgery (n = 64) p-value Gn duration (days), median (IQR) 10 (9–12) 10 (9–12) 0.387 Total Gn dose (IU), median (IQR) 2250 (1600–2900) 2380 (1700–3100) 0.356 Oocytes retrieved (n), median (IQR) 8 (4–12) 8 (3–12) 0.645 Fertilization rate (%), median (IQR) 75 (62–88) 74 (60–88) 0.598 High-quality embryo rate (%), median (IQR) 53 (35–70) 51 (33–68) 0.658 Endometrial thickness on transfer day (mm), median (IQR) 10.1 (8.5–11.7) 9.9 (8.0–11.8) 0.593 Postoperative CA-125 (U/mL), median (IQR) 58 (32–80) 96 (60–130) 0.105 Surgery-to-IVF interval (months), median (IQR) 6.0 (4.0–8.0) 6.0 (4.0–9.0) 0.612 Note: p-values were calculated using the Mann-Whitney U test for continuous variables. IVF, in vitro fertilization; Gn, gonadotropin. Table 4. Comparison of pregnancy outcomes . Pregnancy outcome Laparoscopic surgery (n = 98) Open abdominal surgery (n = 64) p-value Clinical pregnancy, n (%) 47 (48.0) 32 (50.0) 0.795 Biochemical pregnancy, n (%) 9 (9.2) 6 (9.4) 0.964 Miscarriage, n (%) 11 (11.2) 8 (12.5) 0.799 Ectopic pregnancy, n (%) 2 (2.0) 1 (1.6) 1.000 Live birth, n (%) 36 (36.7) 24 (37.5) 0.917 Note: Denominator is the number of patients who underwent at least one embryo transfer cycle after surgery (laparoscopic surgery group, n = 98; open abdominal surgery group, n = 64). All outcomes are reported per patient. 5 Table 5. Multivariate logistic regression analysis of factors affecting live birth rate . V ariable Adjusted OR 95% CI p-value Surgical approach (open vs. laparoscopic) 1.05 0.54–2.04 0.882 Age (years) 0.91 0.84–0.99 0.032 Preoperative AMH (ng/mL) 1.14 0.99–1.32 0.072 Intraoperative blood loss (mL) 1.00 0.99–1.01 0.665 Resected lesion volume (cm 3) 1.01 0.99–1.02 0.423 Adenomyosis type (diffuse vs. focal) 0.87 0.45–1.68 0.674 Duration of infertility (months) 1.01 0.98–1.04 0.520 Prior ART attempts (n) 0.92 0.70–1.21 0.550 Note: V ariables were selected using forward stepwise (likelihood ratio) method. The model was adjusted for age, AMH, adenomyosis type, duration of infertil- ity, and prior ART attempts. OR, odds ratio; CI, confidence interval; AMH, anti- Müllerian hormone; ART, assisted reproductive technology. Table 6. Comparison of postoperative and pregnancy complications . Complication Laparoscopic surgery (n = 98) Open abdominal surgery (n = 64) p-value Postoperative complications Postoperative fever, n (%) 2 (2.0) 6 (9.4) 0.038 Wound infection, n (%) 1 (1.0) 2 (3.1) 0.560 Pregnancy complications Hypertensive disorders, n (%) 4 (4.1) 3 (4.7) 1.000 Gestational diabetes mellitus, n (%) 8 (8.2) 7 (10.9) 0.581 Placenta previa, n (%) 3 (3.1) 2 (3.1) 1.000 Preterm birth, n (%) 5 (5.1) 4 (6.3) 1.000 Uterine rupture, n (%) 0 (0) 0 (0) - Note: Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. The denom- inator for all pregnancy-related complications was the total number of patients in each surgical group (laparoscopic surgery group, n = 98; open abdominal surgery group, n = 64). tive AMH levels showed marginal significance (OR = 1.14, 95% CI: 0.99–1.32, p = 0.072). Intraoperative blood loss (OR = 1.00, 95% CI: 0.99–1.01, p = 0.665) and resected lesion volume (OR = 1.01, 95% CI: 0.99–1.02, p = 0.423) were not significantly correlated with live birth rate. The regression model also included duration of infertility and prior ART attempts, neither of which reached statistical sig- nificance. Regarding postoperative complications, the incidence of postoperative fever was significantly higher in the open abdominal surgery group compared with the laparoscopic surgery group (9.4% vs. 2.0%, p = 0.038) (Table 6). For pregnancy complications, there were no significant differ- ences in the rates of hypertensive disorders of pregnancy, gestational diabetes mellitus, placenta previa, or preterm birth between the two groups. Furthermore, no uterine rup- ture occurred in any of the live birth cases in this study. We further performed a subgroup analysis based on adenomyosis type. Among patients with diffuse adeno- myosis, there was no statistically significant difference in live birth rate between the laparoscopic and open abdom- inal surgery groups (35.7% vs. 38.1%, p = 0.832). Simi- larly, among patients with focal adenomyosis, the live birth rates were comparable between the two groups (37.1% vs. 36.4%, p = 0.954). 4. Discussion This retrospective study analyzed the clinical data from 162 patients with infertility and adenomyosis who un- derwent conservative surgery, either laparoscopic or open abdominal surgery. Although the open abdominal surgery group presented with a higher proportion of diffuse lesions, resulting in greater intraoperative blood loss, larger resected lesion volume, and longer operative time (all p < 0.001), re- flecting the greater surgical complexity in this group, mul- tivariate analysis showed that the surgical approach itself was not an independent predictor of live birth rate follow- ing postoperative IVF. Furthermore, intraoperative blood loss and the extent of resection were not significantly corre- lated with live birth outcomes. Within the limitations of the retrospective design and the substantial baseline imbalance in disease severity between groups (diffuse adenomyosis: 65.6% in the open group vs. 28.6% in the laparoscopic group), these findings suggest that the choice of surgical 6 approach may not be a key determinant of subsequent IVF success in this cohort. These results provide preliminary ev- idence supporting individualized surgical planning in clin- ical practice; however, causal inference remains limited by the non-randomized design. Previous studies on the impact of adenomyosis surgery on fertility have largely focused on comparisons between surgical versus non-surgical treatment, or on the general evaluation of surgical efficacy [ 17,18]. However, for infertile patients and clinicians, clear evidence regarding which of the two most common approaches, laparoscopic or open abdominal surgery, better optimizes IVF outcomes has been lacking [11]. This study directly compared the two surgical approaches and systematically evaluated surgery- related variables, such as blood loss and lesion resection volume, finding that none of these factors independently af- fected live birth rate. This aligns with earlier studies [ 6,19], which reported that various surgical techniques could im- prove fertility outcomes; however, our study further clar- ifies, through multivariate analysis, that the surgical ap- proach itself is not the key determinant of outcome. These findings should not be interpreted as evidence of equivalence between laparoscopic and open abdominal surgery. Rather, they indicate that, in this cohort and af- ter adjustment for measured confounders, no statistically significant difference in live birth rates was observed. The absence of a significant difference may reflect the limited sample size, the marked imbalance in disease severity be- tween groups, and potential residual confounding. There- fore, caution is warranted when generalizing these results to all patients with adenomyosis, and the choice of surgical ap- proach should continue to be guided by lesion characteris- tics and surgical expertise rather than assumed equivalence. Our findings may address concerns raised in the litera- ture regarding the potential impact of laparoscopic suturing quality on uterine healing and subsequent pregnancy out- comes [ 19]. Although open surgery may theoretically of- fer more robust suturing conditions, the laparoscopic group in this study demonstrated comparable live birth rates and pregnancy safety, with no cases of uterine rupture [ 20]. This suggests that, in the hands of experienced surgeons, la- paroscopic multilayer closure using delayed absorbable su- tures can achieve adequate uterine wall reconstruction, and postoperative healing appears sufficient to withstand the physiological demands of pregnancy [ 21]. Therefore, for patients with focal lesions or with diffuse lesions suitable for laparoscopic surgery, opting for the minimally invasive approach does not compromise fertility outcomes based on the current data. Postoperative CA-125 levels at 6 months, analyzed by the Mann-Whitney U test, showed no statistically signifi- cant difference between groups (median [IQR]: 58 [32–80] vs. 96 [60–130] U/mL, p = 0.105). The higher CA-125 lev- els in the open group may reflect more extensive or diffuse disease, consistent with the baseline characteristics; how- ever, the lack of statistical significance, likely due to high inter-individual variability and limited sample size, under- scores the difficulty in isolating the effect of surgical ap- proach from underlying disease severity. The principal clinical implication of this study is that, for infertile patients with adenomyosis requiring surgery, the choice of surgical approach should be guided primar- ily by lesion-specific characteristics, such as extent, loca- tion, relationship to surrounding tissues [ 22], surgeon pro- ficiency with each technique [ 17], and individual patient circumstances [23], rather than by potential concerns about adverse effects of a particular approach on IVF outcomes. When the surgeon possesses the requisite technical exper- tise, the balance of clinical decision-making scale may fa- vor laparoscopic surgery given its minimally invasive na- ture and associated faster recovery [ 24].

This study has several limitations. First, the retrospec- tive, non-randomized design carries an inherent risk of se- lection bias. The choice of surgical approach was deter- mined by lesion characteristics and physician judgement rather than random assignment, resulting in a significantly higher proportion of diffuse adenomyosis in the open ab- dominal surgery group (65.6% vs. 28.6%). Although con- founding was addressed through strict inclusion and exclu- sion criteria and multivariate analysis, residual confounding by unmeasured factors cannot be entirely excluded. This limits any causal interpretation of the observed absence of significant differences in IVF outcomes between the two groups. Second, the statistical reporting of continuous vari- ables in the original manuscript did not consistently reflect the normality assumptions. Some variables that deviated from normality were initially reported as mean ± SD rather than median (IQR). After re-analysis using appropriate non- parametric methods (e.g., Mann-Whitney U test for CA- 125), the conclusions remained unchanged; nonetheless, this inconsistency is acknowledged as a limitation. Specif- ically, postoperative CA-125 levels had median (IQR) val- ues of 58 (32–80) U/mL in the laparoscopic group and 96 (60–130) U/mL in the open abdominal surgery group, and the Mann-Whitney U test yielded a p-value of 0.105. Although the median was higher in the open abdominal surgery group, the difference did not reach statistical sig- nificance, likely attributable to large inter-individual vari- ability, as reflected by the wide IQRs, and limited sample size. The possibility of a type II error cannot be ruled out. Third, although the sample size exceeds that of some pre- vious studies, it remains insufficient for detecting rare out- comes such as uterine rupture or for performing more re- fined subgroup analyses, for example, stratified by lesion location or extent of resection. Fourth, surgical decision- making and operative techniques reflect the experience of a single center, and these conclusions should therefore be generalized with caution. The strengths of this study in- clude a relatively large sample size, systematic data col- 7 lection, and multivariable adjustment for multiple potential confounding factors. 5. Conclusions In summary, within the limitations of this retrospec- tive cohort study and the substantial baseline imbalance in disease severity between the two surgical groups, no sta- tistically significant difference in subsequent IVF live birth outcomes was observed between laparoscopic and open ab- dominal surgery in infertile patients with adenomyosis. In- traoperative blood loss and extent of lesion resection were likewise not significantly associated with the live birth rate. Based on these findings, and acknowledging that residual confounding by indication cannot be excluded despite mul- tivariable adjustment, the surgical approach in clinical prac- tice may be selected according to lesion characteristics and surgeon expertise, as the available evidence does not sup- port an independent effect of the specific approach on IVF live birth outcomes. However, the present findings should not be interpreted as evidence of equivalence between the two surgical approaches. Larger prospective studies with improved control for disease severity and case selection are needed to confirm these observations and to establish more definitive comparative conclusions. Availability of Data and Materials All data reported in this paper will also be shared by the corresponding author upon request. Author Contributions XLi, JC, LX and DH designed the research study. XLi, JC, LX, YH, JY and YC performed the experiments and acquired the data. XLi and DH analyzed and interpreted the data. WY , XLiu and AZ contributed to data curation and validation, and provided critical input for the interpreta- tion of results. All authors contributed to editorial changes in the manuscript. All authors read and approved the fi- nal manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work. Ethics Approval and Consent to Participate This study was approved by Sir Run Run Shaw Hos- pital IRB on February 21, 2025. (Approval number: 2025 No.1055). Informed consent was obtained from all partic- ipants. The study was conducted in accordance with the principles of the Declaration of Helsinki. Acknowledgment We appreciate the whole staff at Sir Run Run Shaw Hospital for their clinical work and data recording for the patients we reported in this article. Funding This study was funded by the “Pioneer” and “Lead- ing Goose” R&D Program of Zhejiang (2024C03200) and the Major Social Public Plan of Zhejiang Province (2023C03167). Conflicts of Interest The authors declare no conflicts of interest. Supplementary Material Supplementary material associated with this article can be found, in the online version, at https://doi.org/10. 31083/CEOG51376.

[1] V ercellini P , Bandini V , Viganò P , Ambruoso D, Cetera GE, Somigliana E. Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adeno- myosis. Part II: medical interventions. Human Reproduction (Oxford, England). 2024; 39: 18–34. https://doi.org/10.1093/hu mrep/dead206 [2] Park JH, Chae KH, Kim S, Park JY , Song JY , Chung YJ, et al. Prevalence, incidence, and treatment trends of adenomyosis in South Korean women for 15 years: A national population-based study. International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2024; 167: 197–205. https://doi.org/10.1002/ij go.15550 [3] Alson S, Jokubkiene L, Henic E, Sladkevicius P . Prevalence of adenomyosis features in women scheduled for assisted repro- ductive treatment, using the Morphological Uterus Sonographic Assessment group definitions. Acta Obstetricia et Gynecologica Scandinavica. 2024; 103: 1142–1152. https://doi.org/10.1111/ aogs.14812 [4] Zhang L, Zhu L, Che P , Sun X, Guo Y , Gao M, et al. Cyto- toxic T Lymphocytes, Tc17 Cells, Th1 Cells, and ThGM Cells are Increased in the Blood and Ectopic Endometrium of Pa- tients With Adenomyosis. American Journal of Reproductive Immunology (New Y ork, N.Y .: 1989). 2024; 92: e13901. https: //doi.org/10.1111/aji.13901 [5] Lu K, Zhong G, Lian B, Zhong X, Xie M, Wu Y . Recurrence rates and associated risk factors after conservative surgery for adenomyosis: a retrospective study. BMC Women’s Health. 2024; 24: 619. https://doi.org/10.1186/s12905-024-03457-6 [6] Ioannidou A, Louis K, Sioutis D, Panagopoulos P , Theofanakis C, Machairiotis N. Conservative Surgical Management of Ade- nomyosis: Implications for Infertility and Pregnancy Outcomes- A Perspective Review. Journal of Clinical Medicine. 2025; 14: 6956. https://doi.org/10.3390/jcm14196956 [7] V an den Bosch T, Dueholm M, Leone FPG, V alentin L, Ras- mussen CK, V otino A, et al. Terms, definitions and measure- ments to describe sonographic features of myometrium and uter- ine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group. Ultrasound in Obstet- rics & Gynecology: the Official Journal of the International So- ciety of Ultrasound in Obstetrics and Gynecology. 2015; 46: 284–298. https://doi.org/10.1002/uog.14806 [8] Shunshi Y , Li J, Li J, Huang L, Chen Y , Zhao X, et al. Transvaginal ultrasound- and laparoscopy-guided percutaneous microwave ablation for adenomyosis has short- and long-term benefits: a single-center study. International Journal of Hyper- thermia: the Official Journal of European Society for Hyperther- 8 mic Oncology, North American Hyperthermia Group. 2023; 40: 2233713. https://doi.org/10.1080/02656736.2023.2233713 [9] Cao Y , Tian J, Liu X, Nie J. Uterus-preserving surgery for dif- fuse adenomyosis via transumbilical single-port laparoscopy: combining dual-flap reconstruction and temporary uterine artery occlusion. Fertility and Sterility. 2026; 125: 536–539. https: //doi.org/10.1016/j.fertnstert.2025.12.014 [10] Xie L, Y ang M, Chen X, Y ao L, Xu W, Shi Q, et al. The present adenomyosis treatment status in Luzhou, China: a small scope observational cross-sectional survey. BMC Women’s Health. 2025; 25: 92. https://doi.org/10.1186/s12905-025-03619-0 [11] Tan J, Moriarty S, Taskin O, Allaire C, Williams C, Y ong P , et al. Reproductive Outcomes after Fertility-Sparing Surgery for Focal and Diffuse Adenomyosis: A Systematic Review. Journal of Minimally Invasive Gynecology. 2018; 25: 608–621. https: //doi.org/10.1016/j.jmig.2017.12.020 [12] Barat M, Dohan A, Kohi M, Marcelin C, Pelage JP , Denys A, et al. Treatment of adenomyosis, abdominal wall endometriosis and uterine leiomyoma with interventional radiology: A review of current evidences. Diagnostic and Interventional Imaging. 2024; 105: 87–96. https://doi.org/10.1016/j.diii.2023.11.005 [13] Wang XL, Xu ZW, Huang YY , Lin S, Lyu GR. Different sub- types of ultrasound-diagnosed adenomyosis and in vitro fertil- ization outcomes: A systematic review and meta-analysis. Acta Obstetricia et Gynecologica Scandinavica. 2023; 102: 657–668. https://doi.org/10.1111/aogs.14580 [14] Zhang J, Lian N, Guo S, Xie X. Analysis of factors affect- ing pregnancy rate after laparoscopic surgery for infertility as- sociated with endometriosis. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2024; 297: 214–220. https://doi.org/10.1016/j.ejogrb.2024.04.034 [15] Kwack JY , Im KS, Kwon YS. Conservative surgery of uter- ine adenomyosis via laparoscopic versus laparotomic approach in a single institution. The Journal of Obstetrics and Gynaecol- ogy Research. 2018; 44: 1268–1273. https://doi.org/10.1111/jo g.13658 [16] Mikos T, Lioupis M, Anthoulakis C, Grimbizis GF. The Out- come of Fertility-Sparing and Nonfertility-Sparing Surgery for the Treatment of Adenomyosis. A Systematic Review and Meta- analysis. Journal of Minimally Invasive Gynecology. 2020; 27: 309–331.e3. https://doi.org/10.1016/j.jmig.2019.08.004 [17] Jiang L, Han Y , Song Z, Li Y . Pregnancy Outcomes after Uterus- sparing Operative Treatment for Adenomyosis: A Systematic Review and Meta-analysis. Journal of Minimally Invasive Gy- necology. 2023; 30: 543–554. https://doi.org/10.1016/j.jmig .2023.03.015 [18] Li S, Li Z, Lin M, Li X, Gao L, Qiu J, et al. Efficacy of Transab- dominal Ultrasound-guided Percutaneous Microwave Ablation in the Treatment of Symptomatic Adenomyosis: A Retrospec- tive Cohort Study. Journal of Minimally Invasive Gynecology. 2023; 30: 137–146. https://doi.org/10.1016/j.jmig.2022.11.004 [19] Osada H. Uterine adenomyosis and adenomyoma: the surgical approach. Fertility and Sterility. 2018; 109: 406–417. https://do i.org/10.1016/j.fertnstert.2018.01.032 [20] Alexander KG, Lee SC, Haddad CN, Tanos V . Minimally inva- sive techniques in myomectomy and fertility outcomes: a nar- rative review of the current evidence. Clinical and Experimen- tal Obstetrics &Gynecology. 2024; 51: 151. https://doi.org/10. 31083/j.ceog5107151 [21] Soriano D, Adler I, Bouaziz J, Zolti M, Eisenberg VH, Gold- enberg M, et al. Fertility outcome of laparoscopic treatment in patients with severe endometriosis and repeated in vitro fertil- ization failures. Fertility and Sterility. 2016; 106: 1264–1269. https://doi.org/10.1016/j.fertnstert.2016.06.003 [22] Xu P , He X, Zhang Y , Wang Y , Zou G, Wang J, et al. Perina- tal Outcomes were Associated with the Positional Relationship between Placenta and Adenomyotic Lesion in Pregnant Patients with Adenomyosis. Clinical and Experimental Obstetrics &Gy- necology. 2024; 51: 14. https://doi.org/10.31083/j.ceog5101014 [23] Miao J, Lu J, Tang J, Lu P . Long-term treatment of dienogest with symptomatic adenomyosis: retrospective analysis of effi- cacy and safety in clinical practice. Gynecological Endocrinol- ogy: the Official Journal of the International Society of Gyne- cological Endocrinology. 2022; 38: 656–660. https://doi.org/10. 1080/09513590.2022.2098948 [24] Pickett CM, Seeratan DD, Mol BWJ, Nieboer TE, Johnson N, Bonestroo T, et al. Surgical approach to hysterectomy for be- nign gynaecological disease. The Cochrane Database of Sys- tematic Reviews. 2023; 8: CD003677. https://doi.org/10.1002/ 14651858.CD003677.pub6 9