Ectopic pregnancy is defined as an abnormal pregnancy in which the fertilized ovum implants outside the uterine cavity. Among all ectopic pregnancies, tubal pregnancy (TP) is the most common, accounting for over 90%. When tubal pregnancy is complicated by rupture and hemorrhage, it can lead to hemorrhagic shock and potentially fatal outcomes, making prompt intervention critical. Medical therapy is a conservative treatment option for tubal pregnancy, offering advantages of being non-invasiveness, reduced pelvic adhesions, and preservation of the affected fallopian tube [1, 2]. The expanding role of medical treatment is partly due to improvements in early recognition and diagnosis of ectopic pregnancy. Diagnostic curettage (D&C) is frequently employed as a supplemental diagnostic tool for early ectopic pregnancy. Although ultrasound can diagnose the majority of ectopic pregnancies, D&C remains particularly valuable when imaging results are inconclusive. By examining uterine contents obtained via D&C, clinicians can distinguish ectopic pregnancy from intrauterine pregnancy, thus avoiding misdiagnosis and inappropriate use of medications such as methotrexate [3]. However, despite its diagnostic utility, the invasive nature of D&C raises concerns about its potential interference with efficacy of medical treatment. Early medical treatment for tubal pregnancy offers several advantages, including preservation of the affected fallopian tube, reduction of pelvic adhesions, avoidance of surgical trauma, and decreased treatment costs. This approach also optimizes the pelvic environment and helps maintain future fertility for patients who wish to conceive again [1, 2]. Although integrated traditional Chinese and Western medicine has proven effective in appropriately selected patients [4, 5], some tubal pregnancy patients still fail to respond to medical therapy and require surgical intervention. Therefore, early assessment of the condition and avoidance of high-risk factors are critically important in the medical management of tubal pregnancy. Diagnostic curettage is widely used as an adjunct tool to distinguish early pregnancies of unknown location. By analyzing pathological findings from endometrial tissue and post-procedure changes in specific serum beta human chorionic gonadotropin ($\beta$-hCG) levels, clinicians can rule out normal intrauterine pregnancy and effectively manage conditions such as early miscarriage or hydatidiform mole. Nevertheless, as an invasive procedure, diagnostic curettage carries certain risks of infection and bleeding and is not recommended as a routine diagnostic method. The decision of whether to perform curettage in patients with suspected ectopic pregnancy is a key clinical issue addressed in this study. Existing literature focuses predominantly on diagnostic accuracy, while the impact of D&C on pharmacological outcomes—especially in patients eligible for conservative therapy—remains underexplored. This gap is clinically significant, as unnecessary D&C may delay treatment, compromise fertility preservation, or exacerbate treatment failure rates.

In this study, we focused on patients with tubal pregnancy who met the pharmacological treatment criteria described in the Guidelines for Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Tubal Pregnancy [6], using treatment outcomes as the primary measure. The objective was to elucidate the impact of D&C on the medical management of tubal pregnancy and provide clinical guidance for optimizing therapeutic strategies.

This study evaluated the impact of diagnostic curettage on the outcomes of medical treatment for tubal pregnancy in a cohort of 369 patients. We found that patients who underwent diagnostic curettage had a significantly higher rate of treatment failure compared to those who did not. After adjusting for relevant confounding factors, diagnostic curettage was associated with a more than twofold increase in the odds of treatment failure. Notably, in the subgroup of patients with $\beta$-hCG levels $\le$2000 IU/L, the risk was nearly threefold higher, whereas no significant difference was observed in patients with $\beta$-hCG $>$2000 IU/L. These findings suggest that diagnostic curettage may adversely affect medical treatment efficacy, particularly in patients with lower $\beta$-hCG levels. Compared with the control group, the curettage group had significantly higher median values of endometrial thickness (11.0 mm), blood $\beta$-hCG value (1545.5 IU/L), “hCG value/days of amenorrhea” ratio (14.55 IU/L/d), and progesterone value (19.19 nmol/L), indicating that patients with thicker endometrium, higher blood $\beta$-hCG value, and higher progesterone value are more likely to undergo diagnostic curettage to exclude intrauterine pregnancy in clinical practice. Due to the limited development of trophoblast cells in tubal pregnancy, insufficient secretion of $\beta$-hCG, reduced progesterone secretion by the corpus luteum, delayed endometrial decidualization, endometrial thickness, blood $\beta$-hCG value, and progesterone value have certain reference values for differentiating between intrauterine and ectopic pregnancies [15, 16, 17, 18, 19]. Thus, endometrial thickness, blood $\beta$-hCG level, and progesterone level are important indicators that guide clinicians when deciding whether to perform diagnostic curettage. However, no clear consensus exists regarding threshold values for these parameters in the early diagnosis of ectopic pregnancy. Several studies report that mean endometrial thickness is 6–8 mm in ectopic pregnancy at 5–8 weeks of gestation, whereas it is 11–12 mm in normal intrauterine pregnancy [15, 16, 17, 18]. Taking 11–12 mm as a reference, patients with an endometrial thickness in this range often undergo diagnostic curettage if intrauterine pregnancy cannot be definitively ruled out. In addition, assessing blood $\beta$-hCG and progesterone levels is crucial for early diagnosis of ectopic pregnancy. In clinical practice, serum $\beta$-hCG levels and their dynamic changes play a critical role in evaluating pregnancies of unknown location. A study [15] suggests that when $\beta$-hCG levels are below 2000 IU/L and no intrauterine gestational sac is visualized on ultrasound, the diagnostic rate for ectopic pregnancy is limited (generally $\le$50%). Performing diagnostic curettage at this stage may risk disrupting a potential viable intrauterine pregnancy that is too early to confirm sonographically. Conversely, if $\beta$-hCG exceeds 5000 IU/L without evidence of an intrauterine gestational sac, the likelihood of ectopic pregnancy becomes significantly high (exceeding 90%), rendering diagnostic curettage unnecessary for differential diagnosis. Additionally, serial $\beta$-hCG monitoring over 48 hours is recommended to assess the rate of increase; a suboptimal rise (50%) may further support suspicion of ectopic pregnancy or nonviable gestation, guiding clinical decision-making while minimizing invasive interventions. Some scholars believe that the blood $\beta$-hCG value should be measured by the percentage increase in 48 hours. If the increase in blood $\beta$-HCG value in 48 hours is less than 52.6%, normal intrauterine pregnancy can be basically excluded. In practice, for suspected tubal pregnancy patients with endometrial thickness $\ge$10–11 mm, blood $\beta$-hCG value $>$2000 IU/L and $\le$5000 IU/L, and progesterone value $>$5.6 ng/mL but 25 ng/mL, clinicians might perform diagnostic curettage if ectopic pregnancy cannot be confirmed or excluded by ultrasound alone. However, since diagnostic curettage is an invasive uterine cavity operation, it may cause endometrial growth restriction or intrauterine adhesions, and even lead to a decrease in clinical pregnancy rate and infertility [20, 21]. Therefore, the patient’s fertility goals and personal preferences must be thoroughly considered before recommending diagnostic curettage.

Previous studies have not definitively clarified whether diagnostic curettage influences the outcomes of medical therapy in tubal pregnancy. However, this 5-year retrospective cohort study indicates that, even after controlling for factors such as blood $\beta$-hCG levels, progesterone, endometrial thickness, and treatment plan, diagnostic curettage may be an independent risk factor for the failure of drug therapy in tubal pregnancy.

Recognizing the significant role of blood $\beta$-hCG levels in treatment outcomes, we conducted a subgroup analysis using 2000 IU/L as a cutoff. In patients with blood $\beta$-hCG $\le$2000 IU/L, the odds of treatment failure among those who underwent curettage were approximately 2–3 times greater than in those who did not, independent of other factors such as endometrial thickness, progesterone level, or treatment plan.

Consequently, clinicians should avoid diagnostic curettage whenever possible in patients with $\beta$-hCG $\le$2000 IU/L who qualify for medical therapy to reduce the likelihood of treatment failure.

The diagnostic curettage operation process includes intravenous anesthesia, curettage operation, and postoperative anti-infection treatment. The use of anesthetic and broad-spectrum antibiotics may inhibit the intestinal flora and affect liver and kidney function to some extent, thereby affecting the absorption and metabolism of drugs and weakening the therapeutic effect of drugs on early tubal pregnancy.

In addition, the curettage operation removes the thick functional layer of the endometrium, which is rich in estrogen and progesterone receptors. This may reduce the local estrogen and progesterone receptors in the endometrium, thereby affecting the regulatory mechanism of estrogen and progesterone and further affecting the progress of early tubal pregnancy.

From the perspective of traditional Chinese medicine, uterine cavity operation damages the blood vessels of the uterus to some extent, causing some blood to overflow outside the vessels. The blood that leaves the meridians is transformed into blood stasis, blocking the uterine vessels and causing qi stagnation in the uterus and Chong and Ren meridians. In addition, there is a deficiency of essence and blood. The kidney governs the uterus and stores essence, and the kidney essence and qi are indirectly damaged, resulting in failure to store essence and the fetus is not restrained, leading to disease progression.

Although the mechanisms remain speculative, the findings of this study warrant clinical attention. Because this was a single-center, retrospective study with a relatively modest sample size, further research in multi-center settings with larger sample sizes is recommended. A future prospective, randomized controlled trial could provide more definitive evidence on whether diagnostic curettage affects the outcomes of drug therapy for tubal pregnancy. Considering comprehensively the auxiliary diagnostic value of diagnostic curettage for tubal pregnancy and its impact on drug treatment, for suspected tubal pregnancy patients with a blood $\beta$-hCG value $>$2000 IU/L and $\le$5000 IU/L, endometrial thickness $\ge$11 mm, and progesterone value $>$5.6 ng/mL and 25 ng/mL, diagnostic curettage can be used for auxiliary diagnosis in combination with the patient’s fertility requirements and personal wishes. However, for tubal pregnancy patients with a blood $\beta$-hCG value $\le$2000 IU/L who meet the drug treatment indications, curettage should be avoided as much as possible. Therefore, for those patients, a wait-and-see approach can be a potential option. This approach can reduce the possibility of trauma and infection, avoid the loss of a viable embryo, and reduce the failure rate of drug treatment management. Clinicians should improve other diagnostic methods, such as In hemodynamically stable patients, combining posterior culdocentesis with simultaneous measurement of $\beta$-hCG concentrations in serum and peritoneal fluid can improve both the diagnostic accuracy of ectopic pregnancy and the procedural reliability of culdocentesis [22, 23]. In addition, it is expected that the sample size can be further increased in the future and multi-hospital and multi-center cooperation can be carried out. If necessary, a prospective randomized controlled trial can be conducted to observe the impact of diagnostic curettage on the outcome of drug treatment for tubal pregnancy to obtain more accurate results. Given the retrospective nature of the data and the limited sample size, we did not perform subgroup analyses to compare the efficacy of each individual treatment modality. Furthermore, treatment decisions were based on clinicians’ judgment and patient conditions, making it difficult to ensure balanced group sizes or eliminate potential confounding factors. Nevertheless, we acknowledge that understanding the individual contribution of each treatment would be valuable, especially mifepristone treatment [24], and future prospective studies should address this question in a more controlled setting. Meanwhile, we have considered the role of TCM in the management of tubal pregnancies. Although the current body of high-quality randomized controlled trials remains limited, emerging evidence from clinical studies [4, 7] and an evidence-based guideline [6] suggests that certain herbal formulations used in TCM may offer adjunctive benefits. These include promoting the resorption of ectopic gestational tissue, reducing local inflammation, and facilitating the recovery of tubal function following conservative treatment [25, 26]. Such effects are thought to be mediated by the pharmacological properties of specific herbs traditionally used to regulate blood flow and resolve stasis [27].

In conclusion, our findings indicated that diagnostic curettage may increase the likelihood of medical treatment failure in tubal pregnancy, particularly when blood $\beta$-hCG levels were $\le$2000 IU/L. While curettage remains a valuable diagnostic tool, clinicians should use it sparingly—especially in patients with a strong desire to preserve fertility—to minimize invasive procedures and potential complications.

The authors serve as custodians of the anonymized data, which may be made available from the corresponding author upon reasonable request.

LY and XW performed the research. JQ and CZ provided help and advice on acquisition of data, LY and XW analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors agreed to be accountable for all aspects of the work.

This study was carried out in accordance with the guidelines of the Declaration of Helsinki. The protocol was approved by the Ethics Committee of Guangzhou University of Chinese Medicine (ethical approval number: JY [2021] 099). Written informed consent was obtained from all participants or their legal guardians prior to their inclusion in the study.

This research received no external funding.

The authors declare no conflict of interest.