Female infertility affects an estimated 9%–18% of women worldwide. Maintaining a stable uterine environment is essential for successful embryo implantation and development during pregnancy. Intrauterine adhesions (IUA) account for about 8% of infertility cases [1]. Asherman’s syndrome is defined as the presence of intrauterine adhesions accompanied by symptoms including a history of decreased fertility, recurrent miscarriages, dysmenorrhea, non-cyclic pelvic pain, abnormal placentation, or menstrual irregularities such as amenorrhea, hypomenorrhea, or oligomenorrhea [2, 3, 4]. Women affected by this disorder frequently experience challenges such as infertility, menstrual irregularities and recurrent pregnancy losses [5]. The presence of intrauterine scarring can significantly impact various aspects of the reproductive process, ultimately affecting the chances of successful fertilization and reproductive outcomes. IUAs may disrupt the transport of sperm through the cervix, uterus and fallopian tubes, leading to reduced fertility. Additionally, the presence of scarring can result in an avascular and unresponsive endometrium, which can reduce its receptivity and thickness, further impacting the likelihood of successful implantion and pregnancy [6]. A considerable proportion of women with IUA wish to conceive again following treatment [7]. Research indicates that hysteroscopy can effectively detect common uterine abnormalities, including endometrial polyps, submucosal myomas, uterine septum, and intrauterine adhesions, in approximately 10 to 15% of women who are seeking infertility treatment [8]. Hysteroscopy is considered the gold standard for the diagnosis and treatment of Asherman’s syndrome [9]. Transcervical resection of adhesion (TCRA) is performed using hysteroscopy to separate and eliminate scar tissue, thereby restoring the structure of the uterine cavity and preserving the remaining endometrium [10]. Currently, the primary approaches to preventing postoperative intrauterine re-adhesion involve intrauterine placement of physical barriers, such as the Cook balloon uterine stent, and postoperative drug therapy, including estrogen therapy [11]. The severity of IUA after TCRA has been suggested to be associated with clinical pregnancy rates in some studies [12, 13], while another study has found no such relationship [14]. The purpose of this retrospective study was to evaluate the relationship between reproductive outcomes and the characteristics of IUA following TCRA in a single center.

In total, 137 patients met the inclusion criteria and were enrolled in the study. Among them, the clinical pregnancy rate and the live birth rate were 60.6% and 51.1%, respectively. Seventeen women experienced preterm live birth, while the remaining 53 women had full-term delivery. Adherent placenta was identified as the most common delivery complication (Supplementary Table 1).

The baseline clinical characteristics for women with and without clinical pregnancy are presented in Table 1. It was found that patients with clinical pregnancy were significantly younger compared to those without clinical pregnancy (p = 0.013). However, there were no differences between women with or without clinical pregnancy in terms of menstrual pattern prior to hysteroscopy, history of recurrent spontaneous miscarriage, history of late miscarriage, total number of uterine curettage, and maximum endometrial thickness before TCRA. The clinical pregnancy rate for patients attempting conception through in vitro fertilization (IVF) (60.5%) did not significantly differ from that of the spontaneous conception group (60.7%, p = 0.988). Table 2 presents a comparison of hystoroscopic observations between women with clinical pregnancy and those without. Notably, the number of tubal ostia visuable showed a significant difference between the two groups (p = 0.022), with more tubal ostia visuable in women with clinical pregnancy compared to those without (91.6% vs. 77.8%). In the stratified analysis by ESGE classification, it was found that the clinical pregnancy rates significantly reduced in cases of severe IUA (p = 0.001). The relationship between the number of TCRA procedures and the clinical pregnancy rate was also examined. It was observed that TCRA $\le$2 significantly predicted higher clinical pregnancy rates (91.6% vs. 8.4%) in comparison to more than two operations (p = 0.026). However, there were no differences between the two groups in terms of the depth of the uterine cavity after TCRA and the type of adhesion.

Table 3 illustrates that women with live births were significantly younger than those without live births (p = 0.005). Women who had live births had a younger age (age 37) compared to their counterparts (94.3% vs. 79.1%, p = 0.011). No differences were observed in other baseline characteristics between the groups (Table 3). Analysis of hysteroscopy findings in women with and without live births revealed a significant correlation between the ESGE classification and live birth rates. However, there were no differences in the visualization of tubal ostia and the number of TCRA between women with and without live births (Table 4).

To further validate our findings, four significant variables were included in the multivariate logistic regression model (Supplementary Table 2). We identified a significant association between age and clinical pregnancy (Odds Ratio (OR) 3.928, p = 0.022). The results also indicated a significant association between ESGE classification and clinical pregnancy (OR 4.579, p = 0.002). In addition, binary logistic regression analysis was conducted to assess the association between age, ESGE classification, and live birth (Supplementary Table 3). Both age and ESGE classification showed significant associated with live birth (p 0.05).

Hysteroscopy is considered the gold-standard technique for the clinical diagnosis and treatment of IUA [5]. The majority of confirmed cases are treated using TCRA [16]. The main objective of surgery is to restore a normal uterine cavity and improve fertility. Studies have indicated that the recurrence rate following TCRA can be as high as 48.0–62.5%, while the reported pregnancy rate ranges from 22.5–33.3% [17]. In our investigation, the overall conception rate after TCRA was 60.6%, marking a significant improvement compared to the 40.4% reported in 2009 [18]. It is recommended to avoid using electrosurgery due to its potential adverse impact on pregnancy outcomes when compared with adhesiolysis without the application of energy [19]. Successful treatment of IUA depends not only on the complete separation of adhesive tissues but also on the prevention of adhesion band recurrence [20]. Previous studies have indicated a high recurrence rate of IUA (3.1% to 23.5%), particularly in cases of severe adhesions (20% to 41.9%) [21]. Hysteroscopic cold scissors have shown superior efficacy in preventing the recurrence of IUA, as well as promoting increased menstrual flow, reducing intraoperative blood loss, and shortening the overall operation time [22]. The heart-shaped balloon was employed to prevent the formation of adhesion bands following adhesiolysis and to support the newly separated uterine cavity by ensuring a physical separation of the opposing uterine walls [23]. After TCRA, all 137 patients exhibited normal intrauterine morphology, and post-operative estrogen supplementation facilitated endometrial growth.

Sun et al. [24] found that patients undergoing assisted reproductive technology (ART) had a higher live birth rate compared to those with spontaneous pregnancies. Conversely, our research did not reveal significant differences in clinical pregnancy and live birth rates between patients attempting conception through IVF and spontaneous conception, possibly due to the inclusion of patients with male infertility and tubal factor infertility, which could have adversely affected the reproductive outcomes of IVF patients. Consequently, it is imperative to conduct a randomized controlled trial to ascertain whether IVF or spontaneous pregnancy is the preferable choice for infertility patients with IUAs after TCRA treatment.

Proper disease classification is essential for assessing the extent of adhesions and predicting treatment outcomes. In this study, we classified the severity of IUA based on the ESGE classification (1995 version). Our findings indicate that reproductive outcomes were correlated with ESGE classification and age, consistent with Zhao et al. [25]. Furthermore, logistic regression analyses revealed that patients with “severe” IUA during their first-look hysteroscopy had significantly lower rates of clinical pregnancy and live birth compared to those with “moderate” IUA, suggesting that the severity of IUA is a crucial determinant of reproductive outcomes. A TCRA $\le$2 was significantly associated with higher clinical pregnancy rates compared to more than two operations. Patients with severe Asherman syndrome typically require multiple operations, indicating that the severity of IUA could predict the clinical outcomes. Female age is the most significant predictor for chromosomal abnormalities in embryos [26]. The rate of non-euploid embryos was at its lowest (2% to 6%) in women aged 26 to 37 [27], and this trend correlates with reproductive outcomes. Furthermore, there is a clear, positive relationship between age and female reproductive capacity [28]. Previous research has indicated that for women, age surpassing 30 is an important risk factor for infertility [25]. The fertility potential of women gradually diminishes starting around the age of 32, with a pronounced acceleration after the age of 37. The results of this study demonstrated that age ($\ge$37 years) constitutes a risk factor for infertility, as evidenced by a statistically significant p value 0.05 in both univariate and multivariate logistic regression models. Fouks et al. [29] demonstrated that women with moderate to severe Asherman’s Syndrome had a substantial reduction in the likelihood of live birth compared to women with mild disease. Their findings indicated that the age at which treatments were administered did not affect live births [29]. This observation could be attributed to the average age of patients in their study was over 37 years old, significantly older than the patients in our study.

In the univariate analyses, it was observed that there were noticeable differences in the visualization of tubal ostia and the number of TCRA between the clinical pregnancy group and no clinical pregnancy group. However, these differences were not found to be statistically significant in multivariate logistic regression analyses (p $>$ 0.05), which may be attributed to the limited sample size and the specific characteristics of the multivariate analysis model. Additionally, it may also reflect the multifactorial nature of fertility. Through controlling the influence of other factors, the multivariate model can independently demonstrate the impact of age and ESGE classification on clinical pregnancy.

The study has some limitations. The small sample size may diminish the statistical power of the test. Additionally, it was conducted as a retrospective analysis of 137 women, which carries inherent biases. Thus, the conclusions require validation through large-scale prospective randomized controlled studies.

To conclude, we found that the prognosis was mainly determined by two factors: age and severity of IUA. Furthermore, the chances of achieving clinical pregnancy and live birth were comparable between the IVF group and the spontaneous conception group, suggesting that IVF may not show superiority over spontaneous pregnancy. Therefore, a well-designed randomized controlled trial is needed to establish whether IVF or spontaneous pregnancy is the preferable option for infertility patients with IUAs following TCRA treatment in the future.

The original data presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

All authors have contributed to the study. The design of the study was conceived by CY and the manuscript was written by CY. Data analysis was performed SFH and YL. Data collection and manuscript editing were performed by WQX and XHH. All authors read and approved the final manuscript. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This retrospective cohort study was approved by the Medical Ethics Committee of the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (No. 0185). Written informed consent was obtained from all patients.

Not applicable.

This research received no external funding.

The authors declare no conflict of interest.