Uterine anteroposterior diameter predicts spontaneous pregnancy outcomes in women under 35 years with adenomyosis: a retrospective study

Background Women diagnosed with adenomyosis often suffer from infertility and frequently seek assisted reproductive techniques (ART). It remains unclear whether certain patients possess the potential to achieve spontaneous pregnancy. This study aimed to investigate the role of uterine parameters, which indicate the progression of adenomyosis, in predicting spontaneous pregnancy outcomes after controlling for other factors that affect natural infertility synergistically.

This retrospective study included 138 infertile women diagnosed with adenomyosis with uterine diameters < 70 mm, who pursued natural conception. Laparoscopy and hysteroscopy were conducted to exclude other factors impacting natural fertility such as hydrosalpinx, and to diagnose and treat endometriosis. The clinical pregnancy rate (CPR) and live birth rate (LBR) within 24 months were compared between patients with endometriosis (n = 98) and those without (n = 40). Logistic regression models were employed to identify predictors of the clinical pregnancy and live birth in both groups, the entire cohort, and subgroups stratified based on age or anti-Müllerian hormone (AMH). Their predictive performance was assessed utilizing receiver operating characteristic (ROC) curves.

Among the 138 patients, 81 (58.70%) achieved clinical pregnancies, comprising 75 live births (54.35%) and 6 early miscarriages (4.35%). No significant difference was found in CPR or LBR between patients with and without endometriosis. The uterine anteroposterior diameter (AD) predicted pregnancy outcomes in each group and overall. In patients under 35 years, uterine AD independently correlated with successful clinical pregnancy [odds ratio (OR) = 0.878, 95% confidence interval (CI) = 0.814–0.946] and live birth (OR = 0.884, 95% CI = 0.821–0.951). A uterine AD of < 41.5 mm predicts successful clinical pregnancy [sensitivity: 0.625, specificity: 0.652, area under the curve (AUC): 0.690] and live birth (sensitivity: 0.623, specificity: 0.656, AUC: 0.688).

Uterine AD predicted spontaneous pregnancy outcomes in patients under 35 years diagnosed with adenomyosis. Adenomyosis probably compromises fertility from the early stages of the condition. However, the Uterine anteroposterior diameter predicts spontaneous pregnancy outcomes in women under 35 years with adenomyosis: a retrospective study Jiaye Li1, Meiling Sun2, Pengrong Lu1 and Ting Zhao1* Page 2 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727

Adenomyosis is characterized as the invasion of endo - metrial glands and stroma into the uterine myometrium [1]. This condition is associated with an increased risk of pregnancy loss [ 2, 3], predominantly occurring at the early biochemical stage before fetal viability is achieved, thus contributing to infertility [ 4]. The presence of ade - nomyosis likely impairs implantation and reduces fertil - ity potential through perturbed uterine peristalsis and altered endometrial receptivity [ 5]. Patients diagnosed with adenomyosis frequently resort to assisted repro - ductive techniques (ART), and contemporary research on fertility issues associated with adenomyosis predomi - nantly centers on in vitro fertilization (IVF), with scant attention given to spontaneous pregnancies. However, during the process of superovulation in IVF, the fol - licles produce a substantial quantity of estrogen, which may exacerbate the progression of adenomyosis. Con - sequently, for patients with adenomyosis pursuing IVF, this situation presents a paradoxical challenge. Sponta - neous conception differs from IVF, wherein long-acting gonadotropin-releasing hormone agonists (GnRH-a) can be used prior to each embryo transfer to optimize the uterine environment. It remains unknown whether all patients with adenomyosis are unsuitable for attempting natural conception, or if certain individuals may still pos- sess the potential to achieve spontaneous pregnancy. Endometriosis (EM) is characterized by the growth of endometrial glands and stroma outside the uterus. EM and adenomyosis are closely related diseases and usu - ally coexist. It has been reported that 79% of EM patients exhibited adenomyosis under magnetic resonance imag - ing (MRI), and this ratio reached as high as 90% among EM patients with infertility [ 6]. EM can cause tubal fac - tor infertility through adhesions that block one or both fallopian tubes or impede tubal access to the Douglas pouch where follicular fluid containing an oocyte is often drained to [7]. EM may also adversely affect oocyte qual - ity by inducing inflammatory and oxidative damage to the oocytes [ 8]. A retrospective study revealed that in patients receiving surgical intervention for coexisting EM and adenomyosis, the endometriosis fertility index (EFI) and mean uterine diameter predicted live birth rate (LBR) after surgery, reflecting the adverse effects of EM and adenomyosis on pregnancy, respectively [ 9]. However, in that study merely a smaller cohort (26.23%, 48/183) opted for spontaneous conception, whereas a significant major- ity (73.77%, 135/183) underwent IVF. While the mean uterine diameter was identified as a predictive factor, the inclusion of patients with leiomyoma compromised the accuracy of uterine measurements. Furthermore, a subset of the cohort (76 patients) underwent excision of adenomyotic lesions, which may improve the pregnancy outcomes for these individuals. Consequently, the spe - cific initial uterine diameter at which adenomyosis signif- icantly impairs the likelihood of spontaneous pregnancy remains undetermined. Beyond EM, infertile women diagnosed with adeno - myosis may also have concurrent conditions such as hydrosalpinx due to pelvic inflammatory disease sequelae or uterine cavity abnormalities. These coexisting condi - tions could contribute to infertility in combination with adenomyosis. After excluding or addressing other factors that could affect natural conception, the isolated effect of adenomyosis on fertility can be observed. The primary

of this study is to assess, after excluding or addressing other factors that could influence spontane - ous conception and uterine measurements, the prognos - tic role of uterine parameters in predicting spontaneous pregnancy outcomes among patients with adenomyosis. This research contributes to our understanding of the specific stage at which adenomyosis begins to compro - mise fertility. Furthermore, it provides valuable insights that may assist in making therapeutic decisions.

Participants This retrospective study included patients diagnosed with female infertility, defined as at least 12 months of unpro - tected intercourse without achieving a pregnancy, who sought natural conception and presented to our clinical team between July 2019 and December 2022. Only those diagnosed with adenomyosis under transvaginal ultraso - nography (TVS, Voluson E8 General Electric, Milwaukee, Wisconsin) and with a maximum uterine diameter of < 70 mm were included, as those with a uterine diameter ≥ 70 mm in the retrospective dataset typically underwent sur - gical resection, a procedure reported to improve fertility in patients with severe adenomyosis [ 10]. The diagnostic criteria of adenomyosis adhered to the revised Morpho - logical Uterus Sonographic Assessment (MUSA) state - ment, which stipulates that the presence of at least one direct sign, such as myometrial cysts, hyperechogenic islands, or echogenic subendometrial lines and buds, is required [11]. The exclusion criteria were: (1) malignant tumors; (2) abnormal male semen examinations; (3) male/female chromosome abnormality; (4) serum anti-Müllerian retrospective design, the potential presence of confounding factors and limited sample size of this study indicate the necessity for large-scale prospective studies to validate these findings.

Adenomyosis, Endometriosis, Hysteroscopy, Laparoscopy, Pregnancy outcome Page 3 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 hormone (AMH) 45 years; (6) history of oophorectomy or oophorosalpingectomy; (7) his - tory of ectopic pregnancy; (8) use of hormone drugs or GnRH agonists or antagonists within the past 3 months; (9) hydrosalpinx or fallopian tubes obstruction under laparoscopy and/or hysteroscopy; (10) cesarean section incision diverticulum detected by ultrasound or hyster - oscopy; (11) intramural uterine fibroids; (12) intrauterine adhesions or uterine malformation detected by ultra - sound or hysteroscopy; (13) endometrial atypical hyper - plasia confirmed by pathology; (14) endocrine disease such as polycystic ovary syndrome and thyroid disease; (15) without intention of natural conception after surgery (Fig. 1). The study was approved by the ethics committee of the Obstetrics and Gynecology Hospital of Fudan Uni - versity, and verbal informed consent was obtained from all patients by telephone connection. Study design and data collection Uterine longitudinal diameter (LD) was defined as the distance from the cervical internal os to the fundus in the sagittal plane; transversal diameter (TD) was measured as the maximum diameter from the left side of the uter - ine corpus to the right side in the transverse plane; and anteroposterior diameter (AD) was measured from the anterior to the posterior serosa at the thickest point per - pendicular to the endometrial line in the sagittal plane. Uterine volume was calculated using the formula (3.14 * LD * TD * AD)/6 [ 12]. The visual analog scale (VAS) score for dysmenorrhea over the past three months was recorded through a face-to-face interview before surgery. All patients underwent simultaneous laparoscopy and hysteroscopy performed by the same two gynecologists from our clinical team within three days following men - struation. The diagnosis of EM was confirmed by lapa - roscopy and pathology. The revised American Society for Reproductive Medicine (rASRM) and EFI scores were evaluated according to the definitions [ 13, 14]. During the surgical procedure, peritoneal EM lesions underwent electrocoagulation. The cyst wall of endometrioma was stripped and the ovary was sutured. Efforts were made to avoid damage to the normal ovarian tissue as much as possible. Pelvic adhesions were separated through both blunt and sharp dissection. Intrauterine lesions or Fig. 1 The scheme of the study Page 4 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 adhesions were removed under hysteroscopy. Intubation was conducted in the interstitial segments of both fallo - pian tubes, followed by the injection of a diluted methy - lene blue solution to evaluate tubal patency. At the end of the operation, the pelvic cavity was washed repeatedly with a large amount of saline until a clear washing fluid was obtained. Patients received three doses of GnRH-a (3.75 mg Leu - prorelin Acetate Microspheres, Lizhu Pharmaceutical Company Limited, China) every 28 days, starting from the second day after surgery. The subsequent spontane - ous pregnancy outcomes within 24 months after the last dose of GnRH-a were followed up on through face-to- face consultations, telephone calls, or by consulting our hospital’s medical record system. Confirmed pregnancies were followed until termination. The conception interval was defined as the time from the last dose of GnRH-a to the calculated date of fertilization, assessed in months. Clinical pregnancy was defined as the observation of a gestational sac on early ultrasound including ectopic pregnancies. Live birth was defined as the spontane - ous delivery or cesarean section of a viable infant at ≥ 28 gestational weeks, with the newborns surviving at birth. Miscarriage was defined as pregnancy loss before 22 ges - tational weeks. These definitions are based on the Inter - national Glossary on Infertility and Fertility Care [ 15]. The primary and second endpoints were LBR and clinical pregnancy rate (CPR), respectively. Statistical analysis SPSS software (version 26.0, IBM Corp., Armonk, NY, USA) was used for statistical analysis. To determine the distribution of the variables, the Kolmogorov-Smirnov tests were used for parameters with sample sizes greater than 50, and the Shapiro-Wilk tests were used for param- eters with sample sizes smaller than 50. Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range). The t-tests and Mann-Whitney U tests were applied for normally and non-normally distributed data, respectively. Categorical variables were presented as numbers and percentages, with the Chi-square test used for comparisons. Kaplan- Meier curve was performed to compare the cumulative CPR. Variables were initially assessed using univariable logistic regression for their correlation with pregnancy outcomes. Those with p < 0.1 were then included in a multivariate conditional logistic regression model with a forward procedure. A p-value < 0.05 was considered sta - tistically significant.

Characteristics of the study population During the study period, a total of 285 women suspected of female infertility and diagnosed with adenomyosis with uterine diameters < 70 mm were presented to our clinical team for evaluation. According to the exclusion criteria, 156 patients were initially deemed eligible for the study. Of these, 12 patients ceased attempts at natural conception after trying for several months and resorted to IVF, and 6 patients were lost of follow-up. Ultimately, the spontaneous pregnancy outcomes of 138 patients were analyzed (Fig. 1). There were 98 (71.01%) patients with laparoscopically diagnosed and treated EM and 40 (28.99%) patients with- out EM. Among patients with EM, 29 (21.01%), 8 (5.80%), 30 (21.74%), and 31 (22.46%) were diagnosed with stages I, II, III and IV, respectively. Patients with EM presented lower body mass index (BMI), shorter menstrual cycles, and higher VAS scores for menstrual pain compared to those without EM (Table 1). Spontaneous pregnancy outcomes and the contributing factors in patients with or without EM and throughout the entire cohort Among 138 patients, there were 81 (58.70%) spontaneous clinical pregnancies, including 75 (54.35%) live births and 6 (4.35%) early miscarriages in total. No ectopic preg - nancy has been observed. In the subgroup with EM, the CPR and LBR were 59.18% (58/98) and 54.08% (53/98), respectively; the median time to conception was 8.37 [95% confidence interval (CI) = 4.64–12.10] months. In the subgroup without EM, the CPR and LBR were 57.50% (23/40) and 55.00% (22/40), respectively. The median time to conception was 7.83 months (95% CI = 4.96– 10.70). There was no difference in CPR and LBR between two subgroups (Table  1). Similarly, the Kaplan-Meier curve showed no difference in cumulative CPR between subgroups (Fig. 2). The correlation between age, preoperative AMH level, BMI, gravidity, parity, menstrual period and cycle, the VAS score for dysmenorrhea, uterine diameters, and uterine volume with clinical pregnancy or live birth was assessed using a logistic regression model. Additionally, for the subgroup with EM, the association between the rASRM and EFI scores with pregnancy outcomes was also analyzed. Uterine AD independently correlated with clinical pregnancy [OR (odds ratio) = 0.918, 95% CI = 0.856– 0.985, p = 0.017] and live birth (OR = 0.909, 95% CI = 0.845–0.978, p = 0.011) in the subgroup with EM. The rASRM score or EFI did not correlate with the preg - nancy outcomes. Uterine AD also independently cor - related with clinical pregnancy (OR = 0.838, 95% CI = 0.731–0.960, p = 0.011) and live birth (OR = 0.871, 95% CI = 0.770–0.986, p = 0.029) in the subgroup without EM. Since the pregnancy outcomes and their predictive fac - tors were comparable between the two subgroups, they were combined for analysis. Uterine AD was the only Page 5 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 Table 1 General characteristics and reproductive outcomes of adenomyosis subgroups with and without endometriosis Patient characteristic With endometriosis (n = 98) Without endometriosis (n = 40) p Age (years) 30.00 (28.00, 32.00) 30.00 (29.25, 33.00) 0.099 AMH (ng/mL) 3.07 (2.26, 4.14) 3.55 (1.92, 6.53) 0.337 BMI (kg/m2) 20.32 (19.11, 22.51) 21.94 (19.75, 25.03) 0.005 Gravidity 0.00 (0.00, 1.00) 0.00 (0.00, 1.00) 0.910 Parity 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.400 Menstruation period (days) 6.00 (5.00, 7.00) 7.00 (6.00, 7.00) 0.066 Menstrual cycle (days) 29.00 (28.00, 30.00) 30.00 (28.25, 33.00) 0.018 Menstrual phase during ultrasonography 0.179 Proliferative 54 (55.10) 17 (42.50) secretory 44 (44.90) 23 (57.50) Uterine longitudinal diameter (mm) 49.80 ± 5.67 50.30 ± 6.62 0.653 Uterine transverse diameter (mm) 49.08 ± 5.83 49.63 ± 6.96 0.640 Uterine anteroposterior diameter (mm) 41.00 (37.00, 46.00) 41.50 (37.00, 46.75) 0.860 Uterine volume (cm3) 52.97 (40.00, 64.29) 54.22 (39.45, 67.34) 0.864 VAS score for menstrual pain 4.00 (2.00, 5.00) 2.00 (0.00, 4.00) 0.016 Clinical pregnancy, n (%) 58 (59.18) 23 (57.50) 0.855 Live birth, n (%) 53 (54.08) 22 (55.00) 0.922 Miscarriage, n (%) 5 (83.3) 1 (16.67) 0.669 Data were presented as mean ± standard deviation, median (interquartile range) or frequencies (percentages) AMH anti-Müllerian hormone, BMI body mass index, VAS the visual analog scale Fig. 2 Cumulative spontaneous pregnancy rates of patients with and without endometriosis Page 6 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 independent factor correlated with successful clinical pregnancy (OR = 0.897, 95% CI = 0.842–0.956, p = 0.001) and live birth (OR = 0.898, 95% CI = 0.843–0.957, p = 0.001) in all patients (Table 2). Comparison of features between patients with and without live birth Patients with live births exhibited longer menstrual cycles, and smaller uterine diameters as well as volume compared to those without live births. Additionally, the parity and VAS scores for menstrual pain in patients with live births were marginally lower (Table 3). Pregnancy outcomes and the contributing factors in patients stratified by age and AMH level Patients were categorized into three age groups: < 30 years old (n = 56), 30–34 years old ( n = 61), and ≥ 35 years old ( n = 21). Additionally, patients were stratified into three groups according to their AMH levels: < 1.1 ng/ml (n = 6), 1.1–3.5 ng/ml ( n = 51), and ≥ 3.5 ng/ml ( n = 44). No significant differences were observed in CPR, LBR, or miscarriage rate among these groups (Table 4). In individuals under 30 years of age, uterine AD was the sole factor significantly associated with clinical preg - nancy (OR = 0.884, 95% CI = 0.790–0.988, p = 0.029) and live birth (OR = 0.869, 95% CI = 0.775–0.975, p = 0.017). Among patients aged 30–34 years, uterine AD was also the only variable linked to clinical pregnancy (OR = 0.874, 95% CI = 0.790–0.968, p = 0.009) and live birth (OR = 0.896, 95% CI = 0.814–0.986, p = 0.024). However, in patients aged 35 and above, no variables demonstrated an association with the pregnancy outcomes (Table  5). Overall, in patients under 35 years, uterine AD was con - sistently associated with clinical pregnancy (OR = 0.878, 95% CI = 0.814–0.946, p = 0.001) and live birth (OR = 0.884, 95% CI = 0.821–0.951, p = 0.001). In women with AMH levels of 1.1–3.5 ng/ml, uterine AD was significantly correlated with both clinical preg - nancy (OR = 0.847, 95% CI = 0.754–0.952, p = 0.005) and live birth (OR = 0.857, 95% CI = 0.765–0.960, p = 0.008). Similarly, among women with AMH levels ≥ 3.5 ng/ml, uterine AD showed significant association with clini - cal pregnancy (OR = 0.805, 95% CI = 0.693–0.935, p = 0.005) and live birth (OR = 0.864, 95% CI = 0.758–0.984, Table 2 Contributing factors for clinical pregnancy and live birth in patients with or without endometriosis and throughout the entire cohort using logistic regression model Factors With endometriosis (n=98) Without endometriosis (n=40) All (n=138) Univariate Multivariate Univariate Multivariate Univariate Multivariate p OR (95% CI) p p OR (95% CI) p p OR (95% CI) p Age pregnancy 0.751 0.486 0.578 live birth 0.942 0.815 0.571 AMH pregnancy 0.305 0.423 0.175 live birth 0.409 0.176 0.110 BMI  pregnancy 0.103 0.563 0.104 live birth 0.314 0.835 0.951 Gravidity pregnancy 0.898 0.247 0.404 live birth 0.279 0.332 0.149 Parity pregnancy 0.688 0.135 0.125 live birth 0.189 0.153 0.038 Menstruation period pregnancy 0.292 0.654 0.262 live birth 0.455 0.587 0.375 Menstrual cycle pregnancy 0.803 0.500 0.547 live birth 0.419 0.861 0.504 VAS score pregnancy 0.152 0.442 0.118 live birth 0.223 0.670 0.209 Uterine LD pregnancy 0.074 0.066 0.011 live birth 0.062 0.138 0.017 Uterine TD pregnancy 0.035 0.263 0.018 live birth 0.018 0.497 0.021 Uterine AD pregnancy 0.017 0.918 (0.856-0.985) 0.017 0.011 0.838 (0.731-0.960) 0.011 0.001 0.897 (0.842-0.956) 0.001 live birth 0.011 0.909 (0.845-0.978) 0.011 0.029 0.871 (0.770-0.986) 0.029 0.001 0.898 (0.843-0.957) 0.001 Uterine volume pregnancy 0.021 0.041 0.002 live birth 0.014 0.083 0.003 rASRM score pregnancy 0.081 live birth 0.260 EFI pregnancy 0.384 live birth 0.464 OR odds ratio, CI confidence interval, AMH anti-Müllerian hormone, BMI body mass index, VAS the visual analog scale, LD longitudinal diameter, TD transverse diameter, AD anteroposterior diameter, rASRM the revised American Society for Reproductive Medicine, EFI endometriosis fertility index Page 7 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 p = 0.014). In the 6 patients with AMH levels < 1.1 ng/ml, no variables exhibited an association with pregnancy out- comes (Table 6). The receiver operating characteristic (ROC) curves of uterine AD for predicting spontaneous pregnancy outcomes in patients with adenomyosis under 35 years The ROC curves of uterine AD for predicting clinical pregnancy and live birth in patients under 35 years are presented in Fig. 3. The optimal cutoff values were 41.5 mm for both clinical pregnancy (sensitivity: 0.625, speci - ficity: 0.652) and live birth (sensitivity: 0.623, specific - ity: 0.656). Among patients with uterine AD < 41.5 mm, 71.43% (45/63) reached a clinical pregnancy, and 66.67% (42/63) had a successful live birth.

It has been observed that in early stages, adenomyosis lesion shows preponderance in the sagittal midline of the mid-corporal and fundal part of the uterus under MRI and TVS. Pathologically, adenomyotic foci are generally localized in the posterior or anterior uterine walls, with infrequent occurrence in the lateral walls. In a previous study, we demonstrated that uterine AD, rather than other dimensions or volume, independently correlated with the diagnosis of adenomyosis under TVS [ 16]. A uterine AD of 38.5 mm (sensitivity: 0.723, specificity: 0.667) and 39.5 mm (sensitivity: 0.703, specificity: 0.723) predicted the diagnosis of adenomyosis in patients with and without EM, respectively. Similar results were also reported by other researchers [ 17]. These results sug - gest that increased uterine AD is a crucial feature of adenomyosis. Uterine AD also independently correlated with the VAS scores for menstrual pain regardless of the presence of EM. A uterine AD of 39.5 mm predicted dysmenor - rhea (VAS ≥ 4) in patients with (sensitivity: 0.806, speci - ficity: 0.656) and without (sensitivity: 0.721, specificity: 0.658) EM. In the present study, uterine AD was found to independently correlate with the spontaneous pregnancy Table 3 General characteristics of patients with and without live birth Patient characteristic With live birth (n = 75) Without live birth (n = 63) p Age (years) 30.00 (28.00, 32.00) 30.00 (28.00, 33.00) 0.624 AMH (ng/mL) (n = 101) 3.11 (1.99, 4.00) 3.20 (2.23, 5.91) 0.316 BMI (kg/m2) 20.83 (19.20, 22.72) 21.23 (19.29, 23.05) 0.622 Gravidity 0.00 (0.00, 1.00) 0.00 (0.00, 1.00) 0.232 Parity 0.00 (0.00, 0.00) 0.00 (0.00, 0.00) 0.057 Menstruation period (days) 6.00 (5.00, 7.00) 6.00 (6.00, 7.00) 0.414 Menstrual cycle (days) 30.00 (28.00, 30.00) 29.00 (28.00, 30.00) 0.031 Menstrual phase during ultrasonography 0.841 Proliferative 38 (50.67) 33 (52.38) secretory 37 (49.33) 30 (47.62) Uterine longitudinal diameter (mm) 48.81 ± 5.18 51.29 ± 6.53 0.014 Uterine transverse diameter (mm) 48.00 (44.00, 52.00) 50.00 (46.00, 54.00) 0.039 Uterine anteroposterior diameter (mm) 40.00 (36.00, 43.00) 43.00 (39.00, 48.00) 0.001 Uterine volume (cm3) 48.67 (38.59, 61.68) 60.41 (43.14, 73.43) 0.003 VAS score for menstrual pain 3.00 (2.00, 4.00) 4.00 (2.00, 6.00) 0.091 The presence of EM 53 (70.67) 45 (71.43) 0.922 rASRM score 26.00 (4.00, 40.00) 26.00 (3.50, 76.50) 0.635 EFI 8.00 (6.00, 8.50) 7.00 (6.00, 9.00) 0.619 Data were presented as mean ± standard deviation, median (interquartile range) or frequencies (percentages)  AMH anti-Müllerian hormone, BMI body mass index, VAS the visual analog scale, rASRM the revised American Society for Reproductive Medicine, EFI endometriosis fertility index Table 4 The pregnancy outcomes of patients classified according to age or anti-Müllerian hormone (AMH) Age (year) < 30 (n = 56) 30–34 (n = 61) ≥ 35 (n = 21) p Pregnancy 35 (62.50) 34 (55.74) 12 (57.14) 0.776 Live birth 32 (57.14) 32 (52.46) 11 (52.38) 0.870 Miscarriage 3 (5.36) 2 (3.28) 1 (4.76) 1.000 AMH (ng/ml) < 1.1 (n = 6) 1.1–3.5 (n = 51) ≥ 3.5 (n = 44) p Pregnancy 4 (66.67) 28 (54.90) 24 (54.54) 0.900 Live birth 3 (50.00) 27 (52.94) 22 (50.00) 0.948 Miscarriage 1 (16.67) 1 (1.96) 2 (4.55) 0.249 Data were presented as frequencies (percentages) Page 8 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 Table 5 Contributing factors for pregnancy outcomes in patients stratified by age using logistic regression model Factors < 30 (n = 56) 30–34 (n = 61) ≥ 35 (n = 21) Univariate Multivariate Univariate Multivariate Univariate p OR (95% CI) p p OR (95% CI) p  P Age pregnancy 0.917 0.755 0.745 live birth 0.838 0.696 0.606 miscarriage 0.655 0.105 0.808 AMH pregnancy 0.596 0.147 0.774 live birth 0.359 0.159 0.774 miscarriage 0.341 0.801 - BMI pregnancy 0.116 0.929 0.259 live birth 0.398 0.946 0.483 miscarriage 0.116 0.654 0.392 Gravidity pregnancy 0.281 0.502 0.565 live birth 0.153 0.494 0.834 miscarriage 0.267 0.853 0.998 Parity pregnancy 0.204 0.094 0.205 live birth 0.060 0.126 0.469 miscarriage 0.068 0.999 0.999 Menstruation period pregnancy 0.580 0.302 0.160 live birth 0.615 0.476 0.173 miscarriage 0.983 0.463 0.912 Menstrual cycle pregnancy 0.314 0.310 0.219 live birth 0.231 0.265 0.103 miscarriage 0.378 0.591 0.994 VAS score pregnancy 0.710 0.097 0.751 live birth 0.665 0.226 0.764 miscarriage 0.810 0.344 0.977 Uterine longitudinal diameter pregnancy 0.160 0.076 0.271 live birth 0.052 0.229 0.400 miscarriage 0.107 0.153 0.653 Uterine transverse diameter pregnancy 0.058 0.207 0.402 live birth 0.036 0.333 0.344 miscarriage 0.349 0.443 0.601 Uterine anteroposterior diameter pregnancy 0.029 0.884 (0.790–0.988) 0.029 0.009 0.874 (0.790–0.968) 0.009 0.437 live birth 0.017 0.869 (0.775–0.975) 0.017 0.024 0.896 (0.814–0.986) 0.024 0.351 miscarriage 0.056 0.386 0.494 Uterine volume pregnancy 0.056 0.028 0.256 live birth 0.019 0.070 0.268 miscarriage 0.100 0.249 0.791 OR odds ratio, CI confidence interval, AMH anti-Müllerian hormone, BMI body mass index, VAS the visual analog scale, rASRM the revised American Society for Reproductive Medicine, EFI endometriosis fertility index Page 9 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 outcomes in patients with adenomyosis under 35 years, regardless of whether EM was present. A uterine AD of < 41.5 mm forecasted a successful live birth (sensitivity: 0.623, specificity: 0.656). We used to believe that an obvi- ously enlarged uterus might compromise fertility; none - theless, our results suggest that the detrimental effects of adenomyosis on fertility may occur much earlier than previously assumed. Collectively, these findings under - score uterine AD as a critical marker of adenomyosis progression and its predictive potential for symptoms such as dysmenorrhea and fertility impairment. It was noteworthy that in patients aged 35 years and older with adenomyosis, uterine AD did not serve as a predictor in pregnancy outcomes, which may be attributed to confounding factors that potentially obscure its predictive capacity in this older cohort. These find - ings enhanced our understanding of the role of prognos - tic factors across different age groups. Regarding AMH, uterine AD correlated with pregnancy outcomes in patients with AMH levels ≥ 1.1 ng/ml or higher, whereas no correlation in patients with AMH levels below 1.1 ng/ ml. However, these results should be interpreted with caution due to the limited sample size of only six patients in the subgroup with AMH levels below 1.1 ng/ml. Although surgical eradication of EM probably did not confer benefits for IVF outcomes [ 18], it enhanced the spontaneous pregnancy rate compared to patients receiving only diagnostic-laparoscopy [ 19]. As a result, Table 6 Contributing factors for pregnancy outcomes in patients stratified by anti-Müllerian hormone (AMH) using logistic regression model Factors < 1.1 ng/ml (n=6) 1.1-3.5 ng/ml (n=51) ≥ 3.5 ng/ml (n=44) Univariate Univariate Multivariate Univariate Multivariate p p OR (95% CI) p p OR (95% CI) p Age pregnancy 0.998 0.626 0.151 live birth 0.305 0.781 0.220 miscarriage 0.617 0.557 0.770 BMI pregnancy 0.285 0.365 0.126 live birth 0.602 0.382 0.235 miscarriage - 0.991 0.495 Gravidity pregnancy 0.407 0.182 0.259 live birth 0.999 0.162 0.414 miscarriage - 0.639 0.999 Parity pregnancy 0.366 0.134 0.133 live birth 0.999 0.172 0.185 miscarriage - 0.999 1.000 Menstruation period pregnancy 0.403 0.338 0.806 live birth 0.390 0.661 0.505 miscarriage - 0.995 0.344 Menstrual cycle pregnancy 1.000 0.294 0.727 live birth 1.000 0.283 0.429 miscarriage - 0.796 0.252 VAS score pregnancy 1.000 0.136 0.034 live birth 1.000 0.255 0.106 miscarriage 1.000 0.996 0.230 Uterine longitudinal diameter pregnancy 0.490 0.013 0.025 live birth - 0.022 0.136 miscarriage - 0.534 0.138 Uterine transverse diameter pregnancy 0.997 0.040 0.028 live birth 0.998 0.070 0.070 miscarriage 0.999 0.411 0.478 Uterine anteroposterior diameter pregnancy 0.998 0.005 0.847 (0.754-0.952) 0.005 0.005 0.805 (0.693-0.935) 0.005 live birth 0.997 0.008 0.857 (0.765-0.960) 0.008 0.028 0.864 (0.758-0.984) 0.014 miscarriage 0.997 0.856 0.217 Uterine volume pregnancy 0.316 0.020 0.008 live birth - 0.030 0.037 miscarriage - 0.526 0.203 OR odds ratio, CI confidence interval, AMH anti-Müllerian hormone, BMI body mass index, VAS the visual analog scale, LD longitudinal diameter, TD transverse diameter, AD anteroposterior diameter, rASRM the revised American Society for Reproductive Medicine, EFI endometriosis fertility index Page 10 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 operative laparoscopy can be offered as a treatment option for EM-associated infertility [ 20]. EFI has been proven to predict the conception rates following laparo - scopic eradication of EM [ 9, 14]. Nonetheless, our study revealed that the EM group exhibited comparable spon - taneous pregnancy outcomes to those without EM, while EFI did not predict pregnancy outcomes in this cohort. The functional status of the tubes and fimbriae is one of the main focuses of the EFI scale [ 14]. EM can lead to the formation of adhesions and scarring, resulting in tubal obstruction [ 7], which may contribute to a low EFI score. These patients were excluded from the cohort due to ineligibility for natural conception ascribed to tubal factors. Consequently, the majority of the EM patients included in this study had an EFI score above 5 (80/98, 81.63%), which may account for the lack of predictive power of EFI for pregnancy outcomes in our analysis. By inducing a hypoestrogenic state, long-acting GnRH- a inhibits the proliferation of ectopic endometrial cells and attenuates inflammatory responses, thus prob - ably improving endometrial receptivity [ 21, 22]. In EM patients, post-surgical administration of GnRH-a, as compared to no medical therapy or placebo, may confer benefits in achieving pregnancy [ 23]. The scenario for patients with adenomyosis, however, is more complex. GnRH-a administration prior to frozen embryo trans - fer, rather than fresh embryo transfer, has been shown to enhance pregnancy rates [ 24]. In those receiving GnRH- a pretreatment before frozen embryo transfer, a uterine volume of < 98.81 cm³ was associated with improved pregnancy outcomes [ 25], suggesting that a specific subgroup of patients may derive greater benefit from GnRH-a therapy. While distinct from assisted reproduction, in which GnRH-a may be administered prior to each embryo transfer, GnRH-a can be utilized solely for a single course before attempting natural conception. Evidence sup - porting the role of GnRH-a in enhancing spontaneous pregnancy in patients with adenomyosis is limited. In a prospective study, Xie et al. administered Triptorelin 3.75 mg for 6 months to infertile patients diagnosed with ade - nomyosis. Of the 45 women, 12 (26.7%) became pregnant when menstruation was expected to resume. GnRH-a may enhance spontaneous pregnancy by improving uter - ine elasticity, despite the study’s lack of a control group [26]. However, the follow-up duration is not long enough to observe either the outcomes of the known pregnancy or the pregnancy after menstruation resumption. The hypoestrogenic efficacy of GnRH-a typically persists for a few months, as evidenced by the resumption of men - struation. However, several studies have observed that the relief of pain symptoms lasted up to one year after the final dose of the medication, suggesting a long-term benefit of this treatment modality [ 27]. In the current study, a subset of infertile women with adenomyosis, yet without other apparent contributing factors to infertility such as EM, successfully achieved live births. This find - ing seems to imply a possibility of potential long-term benefits of GnRH-a in improving spontaneous pregnancy outcomes. However, the lack of a control group necessi - tates a cautious interpretation of these results. Further - more, the absence of data regarding morphological or Fig. 3 Receiver operating characteristic (ROC) curves for clinical pregnancy ( A) and live birth ( B) estimated by uterine anteroposterior diameter (AD) in patients under 35 years with adenomyosis Page 11 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 elastic changes in the uterus following GnRH-a treat - ment renders it uncertain whether differential responses to GnRH-a influence pregnancy outcomes. Symptomatic adenomyosis, characterized by condi - tions such as dysmenorrhea, was reported to have a significant adverse effect on IVF outcomes [ 28]. In our study, although the VAS score for menstrual pain showed a marginal difference between patients with and without a live birth, it did not serve as a predictor for spontane - ous pregnancy outcomes according to the logistic regres - sion analysis. Similarly, another study also reported that neither the VAS score nor the duration of dysmenorrhea influenced the likelihood of achieving a live birth (includ- ing both IVF and spontaneous pregnancies) in patients with concurrent adenomyosis and EM [9]. The present study has several strengths. To our knowl - edge, this is the first study focusing on the predictor for spontaneous pregnancy outcomes in patients with ade - nomyosis. Through laparoscopy and hysteroscopy, we meticulously excluded or eliminated other conditions that could affect natural conception. Then, the isolated impact of adenomyosis on spontaneous pregnancy rates can be accurately assessed. We also excluded patients with factors that could affect uterine measurements, thereby allowing the determination of the accurate cutoff value of uterine AD in predicting pregnancy outcomes. Our results revealed that adenomyosis may exert a det - rimental effect on fertility at a very early stage. The selec - tion of optimal, evidence-based treatment strategies for adenomyosis in fertility clinics remains challenging due to the scant evidence linking fertility outcomes with the extent of adenomyosis [ 5]. Our findings may offer valu - able insights in guiding therapeutic choice. This study is subject to several limitations. Firstly, it is a retrospective analysis with a relatively small sample size, a constraint partially resulting from the rigorous exclusion criteria, and lacks an external control group of infertile women without gynecological disease. Secondly, there is a possibility of inter-operator variability in the ultrasound measurements. Thirdly, an internal control group of ade - nomyosis patients that did not utilize GnRH-a was absent due to patient interest considerations. Additionally, data on morphological or elastic changes in the uterus follow - ing GnRH-a treatment, which could indicate differential responses to the therapy, were absent. Consequently, definitive conclusions regarding the role of GnRH-a treatment in enhancing spontaneous conception among patients with adenomyosis cannot be drawn. Fourthly, the study was unable to reach a conclusion regarding the prognostic role of uterine AD in patients with preop - erative AMH levels below 1.1 ng/mL due to the limited sample size. Additionally, the study did not assess the association between postoperative AMH levels and preg - nancy outcomes because of incomplete data availability. These limitations underscore the need for further pro - spective studies with larger sample sizes. Lastly, the study did not evaluate the impact of adenomyosis location on pregnancy outcomes owing to the limitations of ultra - sound images inherent in the retrospective study design. Although the position of adenomyosis on the posterior or anterior uterine wall may not significantly affect LBR [29], adenomyosis affecting the inner myometrium has been observed more frequently in patients experiencing recurrent pregnancy loss [ 30]. The pathologic condition of the inner myometrium is characterized by increased thickness, a key indicator of adenomyosis on TVS and MRI, which probably contributes to increased uterine diameters. Further large-scale prospective studies are required to determine whether the inner myometrium thickness can predict spontaneous pregnancy outcomes.

This research identified that uterine AD, which indicates the progression of adenomyosis, is an independent pre - dictor for spontaneous pregnancy outcomes in affected patients under 35 years. A uterine AD of < 41.5 mm (sensitivity: 0.623, specificity: 0.656) predicts successful live births. These findings illuminate the early detrimen - tal effects of adenomyosis on fertility and offer critical insights that may assist in making therapeutic decisions. Abbreviations ART Assisted reproductive technique CPR Clinical pregnancy rate LBR Live birth rate AD Anteroposterior diameter IVF In vitro fertilization GnRH-a Gonadotropin-releasing hormone agonist EM Endometriosis MRI Magnetic resonance imaging EFI Endometriosis fertility index TVS Transvaginal ultrasonography AMH Anti-Müllerian hormone LD Longitudinal diameter TD Transversal diameter VAS Visual analog scale rASRM The revised American Society for Reproductive Medicine BMI Body mass index

Not applicable. Authors’ contributions J. L. contributed to data collection, data analysis, follow-up, and manuscript preparation; M. S. contributed to data collection and follow-up; P . L. participated in the supervision of the study and performed surgeries; T. Z. conceived and designed the study, performed surgeries, analyzed data, and prepared the manuscript. All authors reviewed and approved the final manuscript. Funding The research is supported by the National Natural Science Foundation of China (82301858) and the Shanghai Clinical Research Center for Gynecological Diseases (22MC1940200). Data availability All data supporting this study are included in this manuscript. Page 12 of 12 Li et al. BMC Pregnancy and Childbirth (2025) 25:727 Declarations Ethics approval and consent to participate This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki, and was approved by the ethics committee of the Obstetrics and Gynecology Hospital of Fudan University (Code: 2024 − 148). The verbal informed consent was obtained from all patients by telephone connection. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Author details 1Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, China 2Department of Gynecology, Affiliated Huaian Hospital of Xuzhou Medical University, 62 South Huaihai Road, Huaian, Jiangsu Province 223001, China Received: 9 December 2024 / Accepted: 10 June 2025

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