Uterine artery embolization (UAE) represents a minimally invasive intervention frequently applied in the management of both acute and chronic genital hemorrhage stemming from a spectrum of obstetric and gynecological conditions (1). Optimal candidates for UAE encompass individuals afflicted with symptomatic fibroids, who express a desire for uterine preservation and/or seek alternatives to surgical procedures (2). Recent years have seen the extensive use of UAE in addressing conditions, such as uterine fibroids (UFs), postpartum hemorrhage (PPH), and cesarean scar pregnancy (CSP) (3–5). UAE has demonstrated efficacy in symptom improvement with a low incidence of major complications. However, certain studies have reported potential adverse effects, including postembolization syndrome and subclinical impairment of ovarian function (6, 7). Furthermore, radiation exposure during the procedure may pose a risk to the genital system, with particular concern for the ovaries and endometrium, potentially leading to future fertility issues (8).

The American College of Obstetricians and Gynecologists advises a cautious approach to the application of UAE for patients intending to conceive, due to the insufficiently explored effect of UAE on pregnancy (9). Conversely, guidelines from the Society of Interventional Radiology (SIR) advocate for the consideration of UAE as a viable option for those targeting subsequent fertility, contingent upon individual patient preferences and specific case nuances (10). Previous systematic reviews and meta-analyses have reported the fertility results and pregnancy outcomes after UAE. For example, a systematic review published by Li et al. revealed that the pregnancy rate after myomectomy (43%) was higher than 18% after high-intensity focused ultrasound (HIFU), and the latter was significantly higher than that after UAE (8%) (11). The study by Matsuzaki et al. demonstrated that women who had previously undergone UAE faced a heightened risk of PPH in subsequent pregnancies (12).

The assessment of the relative impacts of minimally invasive treatments for female patients is a critical field that informs clinical decisions, yet there is a noticeable scarcity of high-quality, long-term comparative studies. Understanding the potential risks associated with maternal and obstetric outcomes in pregnancies subsequent to UAE could prove instrumental in its antenatal diagnosis and treatment involving multidisciplinary care (13, 14). Therefore, we have implemented a current systematic review and meta-analysis on pregnancy rate and outcomes following UAE treatments for female patients and further performed subgroup analyses by patient populations (such as UFs, CSP, and PPH) or control treatments (myomectomy, HIFU, or other treatments) to find out whether a safe pregnancy is possible after UAE.

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in writing the current study (15). The protocol for this review has been prospectively registered in the PROSPERO database (CRD42023448257).

In recent years, the utilization of UAE has gained widespread recognition as an effective treatment for various benign gynecological and obstetric conditions, including PPH, placenta previa, UFs, and CSP (1, 41–43). However, concerns have been raised regarding the potential adverse effects of UAE on postoperative ovarian function and fertility, thereby limiting its applicability to patients desiring future fertility (2, 44). The preservation of fertility and pregnancy has emerged as a crucial consideration due to the compromised blood supply associated with the UAE. In this context, the compromise of both uterine and ovarian blood flow assumes significance, as achieving uterine arterial embolization, the primary objective of UAE, may threaten future pregnancy. Furthermore, the possibility of anastomoses between uterine and ovarian arteries raises concerns that the embolization agent could inadvertently enter the ovarian artery, leading to impaired ovarian function and subsequent infertility (45). Additionally, the radiation dose administered in UAE has the potential to detrimentally affect normal ovarian function and fertility (46). With significant improvements in the materials, size, and morphology of the embolic agents used in UAE, as well as the use of anti-Mullerian hormone (AMH), a new indicator for evaluating ovarian function, it has been found in recent studies that that UAE has no significant effect on ovarian reserve function (47, 48). To provide valuable insights into the standardized management of gynecological and obstetric conditions in women with fertility aspirations, this study aimed to explore the influence of UAE on pregnancy rate and outcomes in women of reproductive age.

Our analysis showed that in the total population, female patients had a significantly lower pregnancy rate after UAE treatment compared with the control group. However, the results of the subgroup analysis suggested that UAE did not play a role in reducing pregnancy rates in patients with PPH, CSP, UFs, or other conditions. Furthermore, UAE was not suggested to decrease postoperative pregnancy rate, either compared with myomectomy, HIFU, non-use of UAE, or other treatment modalities. The diminished pregnancy rate observed following UAE primarily stems from the impact on ovarian blood supply and endometrial function. Infertility can arise from various factors, including fallopian tube obstruction, compromised endometrial receptivity due to structural distortions, alterations in endometrial development, and hormonal imbalances (49). Furthermore, unshielded radiation during the procedure in UAE may jeopardize the uterus and ovaries, compromising fertility (50). Radiation exposure severely alters ovarian performance, manifesting as the shrinkage of follicles and a decrease in follicle reserves. This accelerates the innate depletion of follicle count, resulting in compromised ovarian hormone synthesis, uterine malfunction from insufficient estrogen, early-onset menopause, and infertility (51–53). Beyond impacting the ovaries, radiation exerts adverse effects on the uterus. This may manifest as placental anomalies (e.g., placenta accreta), fetal malposition, premature delivery, and even, albeit rarely, uterine rupture (46, 54). Nevertheless, we cannot generalize the overall analysis results to the whole population. The reasons need to be elucidated. The outcome of pregnancy rate revealed substantial heterogeneity between studies, impeding precise predictions regarding obstetric outcomes. Moreover, the overall analysis included studies with different patient origins and treatments of the control group, alongside discrepancies in study design, thereby contributing to significant heterogeneity between studies. Although subgroup analyses were conducted, further subgroup analyses based on the same patients and control group treatments were unfeasible due to the limited number of included studies. Mothers’ age and follow-up time may also be sources of heterogeneity in the overall analysis.

A previous review posited that the UAE serves as a safe alternative to surgery for women who do not desire to preserve fertility or for cases with elevated surgical risk (55). A subsequent review that did not include RCTs noted that UAE is an alternative treatment to myomectomy for women aspiring to conceive (56). Myomectomy, encompassing hysteroscopic, laparoscopic, abdominal, or transvaginal approaches, stands as a widely employed procedure for leiomyoma removal (57). For UF patients or compared with myomectomy, a significantly decreased risk of preterm delivery after UAE was observed in our subgroup analysis; no association was found between UAE and an increased risk of spontaneous abortion, live birth, ectopic pregnancy, cesarean section, PPH, and placenta previa. Mohan et al. conducted a comprehensive review of 21 studies and concluded that the impact of UAE on fertility remains uncertain, given the influential confounding factors of age and fibroid type in fertility evaluations (58). The Cochrane Review indicated limited evidence suggesting the potential benefits of myomectomy over UAE in improving fertility outcomes. However, this evidence was not substantial, necessitating further investigation (59). Consequently, in the absence of definitive data guiding patient advice, the SIR made the following recommendations (10): (i) For patients with a history of myomectomy, high-quality studies have not reported reproductive outcomes. Given the challenges associated with repeated surgery, embolization might be a preferable option. (ii) For patients deemed unsuitable for surgery due to factors such as complications, physical disposition, or the location or extent of leiomyomas, uterine embolization presents a viable option for those aspiring to conceive. CSP, a long-term complication of cesarean delivery, has exhibited a persistent upward trend (60). The gestational sac in CSP patients primarily resides within cicatrix tissue, characterized by a thin muscular layer. Consequently, arresting bleeding through the contraction of this delicate muscle layer poses a challenge. During the separation of the gestational sac or placental tissue, the previous incision site may rupture, leading to uncontrollable bleeding, thereby further compromising women’s wellbeing. UAE represents a treatment modality capable of promptly halting bleeding and averting massive hemorrhage (61, 62). Our subgroup analysis showed that UAE decreased the risk of cesarean section and was not associated with spontaneous abortion in patients with CSP. However, this subgroup analysis was limited by the fact that the results were pooled from only 2 studies (Chen et al. and Wang et al.) and that the patients in both studies were from China. It is not convincing to generalize the pooled results to the whole population. In addition, the control treatments in these two studies were HIFU. Thus, these findings offer certain reference values for UAE and HIFU treatment in CSP patients. More relevant research is needed to refine and validate the results. The pooled results of 2 studies indicated that UAE increased the risk of placenta previa and was not associated with cesarean section and preterm delivery in patients with PPH. Salomon et al. reported 4\u00B0cases of successful deliveries following previous UAE, yet all experienced recurrent PPH, necessitating hysterectomy in 2 patients. They postulated that uterine damage resulting from UAE, via an unknown mechanism, might contribute to abnormal placentation, thereby inducing PPH (63).

HIFU, a novel thermal ablation technique, exhibits lower toxicity when compared with alternative ablation methods (64). Compared with HIFU, UAE reduced the risk of cesarean section in the present analysis. The underlying mechanism of cesarean section following UAE remains unclear due to limited available data. Nevertheless, HIFU enables the precise focusing of waves to induce coagulation in targeted fibroids, thereby preserving the integrity of the myometrium and endometrium during ablation (65, 66). In this sense, HIFU ablation holds promise for achieving favorable pregnancy outcomes. In addition, UAE increased the risk of postoperative placenta previa compared with no use of UAE. Nonetheless, the relatively wide 95% CI suggested an instability of the result. Hence, additional studies are needed to further validate and supplement the above results.

Our overall analysis showed that compared with the control, UAE treatment increased the risk of postoperative PPH in the total population. Similar results were shown only in patients with PPH. There is only one RCS comparing UAE vs. control on postoperative PPH in PPH patients; we cannot generalize the results of only one study to the entire population. It is well established that women with a history of PPH are at elevated risk of recurrent PPH (67). Notably, the frequency of PPH demonstrates an increase after UAE therapy for uterine myoma, as compared with cases involving laparoscopic myomectomy, thereby implicating UAE as a potential risk factor for PPH (68). Moreover, independent investigators have also reported a heightened incidence of an abnormally invasive placenta in pregnancies following UAE (69, 70). A subsequent pregnancy following UAE treatment for severe PPH poses an amplified risk of recurrent severe PPH, likely attributed to the presence of an abnormally invasive placenta.

In the present study, several noteworthy points and limitations warrant consideration. First, a significant limitation of the meta-analysis was the presence of substantial heterogeneity. We recognized that numerous factors, including maternal age, fibroid location, and follow-up duration, may exert an effect on pregnancy rate and outcomes, it is regrettable that further sub-analysis based on these factors could not be pursued due to unavailable information in the relevant studies. Second, the cohort studies included did not specify whether the patients participating in the research suffered exclusively from a single disease. For instance, in Imafuku et al.’s study, the causes of PPH included conditions such as uterine atony, abnormally invasive placenta, placenta previa, and UFs. Third, it is ideal to ascertain the pregnancy rate specifically among women who actively desire to conceive. However, the lack of information on desired pregnancies in several studies necessitated an alternative approach. Consequently, the pregnancy rate was calculated by dividing the number of successful pregnancies by the total sample size, resulting in noticeable heterogeneity across studies. Fourth, there was an insufficient number of studies to continue sub-analysis by subgroup 1 and subgroup 2. Nevertheless, despite these limitations, the obtained findings hold direct relevance to daily clinical practice, providing valuable guidance for recommending appropriate treatment options to patients.

In conclusion, UAE treatment was associated with a lower postoperative pregnancy rate and increased risk of PPH. These findings cannot be explained by subgroup analysis at present. Additionally, when compared with myomectomy, HIFU, and non-use of UAE, UAE was shown to decrease the risk of preterm delivery and cesarean section and increase the risk of placenta previa, respectively. Similar results were found in patients with UFs, CSP, and PPH, respectively. More comparative studies and further subgroup analysis are needed to clarify the association between UAE and pregnancy rate and outcomes.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding authors.

XY: Formal Analysis, Software, Writing – original draft. LZ: Methodology, Writing – review & editing. GH: Methodology, Validation, Writing – review & editing. XL: Conceptualization, Data curation, Writing – original draft.