Postpartum hemorrhage (PPH), which is defined as blood loss $\ge$1000 mL in the first 24 hours after delivery or cesarean section, remains a leading cause of maternal mortality worldwide. The rapid onset and potential severity of PPH necessitate urgent identification of modifiable risk factors [1]. Uterine fibroids are non-cancerous tumors caused by excessive growth of uterine smooth muscle cells and a common gynecological condition affecting women of reproductive age [2]. Accumulating evidence has demonstrated a strong association between uterine fibroids and adverse pregnancy outcomes. These outcomes include maternal complications, such as PPH and others that involve the fetus, such as preterm birth and even extreme prematurity (28 gestational weeks). Notably, the global prevalence of uterine fibroids has been increasing [3, 4, 5]. Routine performance of myomectomy during cesarean section is controversial. However, in specific cases, myomectomy is safe and feasible and is associated with favorable outcomes [6]. The advantages of addressing uterine fibroids at the time of cesarean section include reducing fibroid-related postpartum complications and obviating the requirement for later uterine fibroid resection. Liu et al. [7] showed that after cesarean section, 48 patients (aged 26–41 years) had a dominant leiomyoma $>$50 mm. During the follow-up period, for an average of 38.5 months, 11 patients underwent surgery for symptomatic fibroids. Therefore, simultaneous removal of uterine fibroids during cesarean section, also known as cesarean myomectomy, has been advocated [8, 9, 10, 11].

Nonetheless, PPH remains a serious complication because cesarean myomectomy may increase the risk of PPH [12, 13]. A recent Cochrane review of cesarean myomectomy concluded that the available evidence for all critical outcomes is of very low certainty [14]. Therefore, drawing definitive conclusions regarding the effects of cesarean myomectomy on the risk of requiring blood transfusion, risk of hemorrhage, length of hospitalization, duration of surgery, and risk of major surgery at the time of the procedure is not possible.

This study aimed to identify the risk factors for PPH following cesarean myomectomy and to evaluate their predictive value. Hopefully, our findings will assist in reducing the incidence of PPH and developing targeted interventions for high-risk pregnancies.

The limited research on the association between cesarean myomectomy and PPH has added an extra burden to obstetricians in clinical management. This study showed that the diameter of individual uterine fibroids was a risk factor for PPH, particularly those with a diameter $>$7.5 cm. A previous study supports this finding. Large fibroids are frequently associated with aberrant vascular proliferation. The resection of these fibroids necessitates a larger myometrial incision, which disrupts uterine wall integrity and expands the exposed vascular surface area, thereby increasing the likelihood of PPH. Some studies have suggested that the removal of fibroids $>$5 cm during cesarean section is associated with increased intraoperative blood loss and should be approached with caution [18]. By contrast, other studies used 7 cm as the threshold [19]. The variation in the cutoff diameter for predicting PPH may be closely related to our hospital’s proactive management of cesarean myomectomy and the skilled techniques of the surgeons, which play a major role in reducing the risk of PPH.

Multiple uterine fibroids were an independent risk factor for PPH in this study. Multifocal fibroids destroy the gap junctions between uterine smooth muscle cells, weakening their ability to contract synchronously. Specifically, in our study, a sum of the maximum diameters of the fibroids exceeding 14.5 cm had good predictive value for PPH, which is slightly different from a finding by Li et al. [18]. They found that the number of fibroids has no effect on the risk of PPH. Lee et al. [20] found that larger ($>$10 cm) and heavier ($>$500 g) fibroids were associated with complications after cesarean myomectomy, whereas the number or type of fibroids was not. They also noted that while multiple fibroids were independently associated with bleeding at delivery, they were not associated with PPH ($\ge$1000 mL), and there was no significant correlation between the maximum diameter of multiple uterine fibroids and PPH. This difference between studies may be due to differences in patients’ characteristics between the studies. Our study included women with at least one fibroid with a diameter $\ge$4 cm, and this was measured during surgery. By contrast, the minimum diameter in a study by Andreani et al. [21] was 5 cm, which was determined on preoperative ultrasonography. Therefore, they may have missed fibroids that grew rapidly late in pregnancy. Consequently, further research examining the association between the sum of the maximum diameters of multiple uterine fibroids and PPH is warranted.

We also found that particular fibroid locations were an independent risk factor for PPH, possibly because of differences in uterine contraction and vascularity. The lower uterine segment is predominantly composed of longitudinal muscle fibers and it shows weaker contractility than the circular myometrial layers of the fundal region. This architectural disparity predisposes this area to localized uterine atony after fibroid resection. Furthermore, the dual blood supply of the uterine segment from the cervical-vaginal arteries creates rich anastomotic vasculature, posing challenges in achieving complete hemostasis during surgery, which is in contrast to the fundal region’s singular uterine arterial supply. This partially aligns with the findings of Kwon et al. [13], who studied cesarean myomectomy for intramural fibroids. They reported that lower segment fibroids and those with a diameter $\ge$8 cm are independent risk factors for operative bleeding. They also suggested that myomectomy may be considered at the time of cesarean section if fibroids are located in the fundus or body of the uterus and have a diameter 8 cm. Therefore, removal of fibroids at particular sites, such as those located at sites predisposed to developing PPH, should be avoided at the time of cesarean section.

Akbaba and Kilicci [22] demonstrated that bilateral uterine artery ligation reduced intraoperative blood loss in patients who underwent laparoscopic and open myomectomy. Furthermore, Hiratsuka et al. [23] reported that temporary uterine artery occlusion decreased hemorrhage during laparoscopic myomectomy. Although these studies confirmed the value of uterine artery ligation in reducing hemorrhage from non-pregnant uteri, the underlying mechanism (reducing uterine artery perfusion pressure) may also apply to cesarean myomectomy. The propensity score-matched analysis in our study indicated that bilateral uterine artery ligation before myomectomy protected against PPH in cesarean myomectomy. Several studies have shown that using potent uterotonic agents during abdominal myomectomy can reduce intraoperative blood loss [24, 25]. However, research on whether the use of these agents before cesarean myomectomy truly protects against PPH is relatively limited. Our study suggested that using uterotonic agents before cesarean myomectomy protected against PPH. In patients undergoing cesarean myomectomy who have a high risk of PPH, bilateral uterine artery ligation or the administration of potent uterotonic agents before myomectomy can considerably reduce intraoperative blood loss, lower the incidence of PPH, and decrease the occurrence of severe complications.

Our findings provide critical guidance for the prevention and management of PPH during cesarean myomectomy. When investigating PPH in this context, preventative strategies are important, particularly for patients with multiple fibroids or fibroids in certain locations, and for those whose operation time is expected to be prolonged. Meticulous surgical management is crucial in these cases, and procedures should ideally be performed by experienced obstetricians to ensure rapid suturing and to minimize the length of the operation.

To further mitigate the risk of PPH, bilateral uterine artery ligation should be strongly considered, especially for patients at high risk. This intervention reduces blood flow to the uterus, thereby decreasing the likelihood of excessive intraoperative bleeding. Additionally, the use of potent uterotonic drugs is highly recommended to enhance uterine contractions and promote hemostasis after delivery. These preventive measures should be considered critical components of the surgical plan because they greatly contribute to reducing the incidence of PPH and improving patients’ outcomes.

This study has several limitations. As a retrospective, single-center, non-randomized analysis, it was susceptible to selection and information biases. Although we attempted to control for confounders using PSM and other statistical methods, confounding may still have been present. Therefore, large-scale, multicenter, prospective studies with diverse patient populations are required. A multi-indicator predictive model should be a key focus of future prospective studies to further refine risk stratification.

Independent risk factors for PPH following cesarean myomectomy include multiple fibroids, fibroids in certain locations, and a prolonged duration of surgery. A fibroid diameter $>$7.5 cm in patients with a single fibroid and a sum of diameters $>$14.5 cm in those with multiple fibroids are also independent risk factors. Bilateral uterine artery ligation and the administration of potent uterotonics during this procedure considerably reduce the risk of PPH.

The datasets used and analyzed during this study are available from the corresponding author on reasonable request.

XW: methodology, validation, formal analysis, investigation, data curation, writing-original draft; DZ: conceptualization, resources, writing-original draft, project administration, writing-review & editing, supervision; QS: validation, resources, formal analysis, investigation, data curation; XY: writing-review & editing,reviewing it critically for important intellectual content, supervision; HC: Conceptualization (retrospective study design), methodology (outcome definition and interpretation), writing – review & editing, supervision (data validation and methodological oversight). All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Shenyang Women’s and Children’s Hospital (Approval Number: 202358). All data were fully anonymized. The requirement for informed consent was waived owing to the study’s retrospective design.

The authors would like to thank all the journal’s anonymous reviewers for their opinions and suggestions, and Liwen Bianji (Edanz) (https://www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

This work was supported by Shenyang Young and middle-aged science and technology innovation talents support program project Fund, Shenyang Science and Technology Bureau (grant number RC210043).

The authors declare no conflict of interest.