Hydatidiform moles (HM), also known as molar pregnancy, encompass both complete and partial forms and represent a benign subset of gestational trophoblastic diseases (GTDs) that arise from abnormal fertilization and aberrant proliferation of placental tissue, predominantly of androgenetic origin. These conditions are characterized by villous hydrops and trophoblastic hyperplasia, with or without embryonic development [1, 2]. HM can be divided into two morphologically and genetically distinct groups: complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM). The risk of progression to gestational trophoblastic neoplasia (GTN) after HM depends on the histological type, with rates of approximately 15–20% in CHM and only 1–5% in PHM [3].

The global incidence of HM shows marked geographic variation, with rates generally higher in Asia than in Europe or North America. The lowest incidence is reported in Europe, North America, Australia, and New Zealand, with rates ranging from 0.57 to 1.1 per 1000 pregnancies. In contrast, studies from Asian countries demonstrate greater variability, with reported incidences of 1.5–3 per 1000 in Japan, 1.6–4.4 in South Korea, 0.81 in China, 2.8 in Malaysia, 1.2 in Singapore, 2.4 in the Philippines, and 1.7 in Thailand [3, 4]. In Vietnam, available data indicate a notably higher incidence, reaching up to 11 per 1000 births, suggesting potential regional or methodological differences [5].

Suction evacuation under ultrasound guidance remains the standard treatment for molar pregnancy, whereas hysteroscopic removal of residual tissue serves as an adjunct option. Hysterectomy with ovarian preservation may be considered for women who have completed childbearing, whereas medical induction and hysterotomy are discouraged due to increased morbidity and risk of GTN. Prophylactic chemotherapy can reduce the incidence of GTN but should be limited to high-risk cases [4].

Beta-human chorionic gonadotropin ($\beta$-hCG) remains the most reliable biomarker for disease monitoring, treatment response, and postevacuation surveillance. Its use in postmolar follow-up is essential for early detection of postmolar GTN. Current consensus recommendations advise weekly quantification of serum $\beta$-hCG until negative, followed by monthly measurements for at least 6 months [3]. Several studies have demonstrated the predictive value of $\beta$-hCG kinetics after molar evacuation, as a slow or abnormal decline is associated with an increased risk of postmolar GTN [6, 7]. In China, a centralized surveillance system based on serial serum $\beta$-hCG monitoring has effectively reduced the incidence of postmolar GTN and the need for prophylactic chemotherapy [8].

Hormonal contraception is considered safe during follow-up, and a structured program incorporating nursing care, psychosocial support, and telemedicine-based monitoring can improve patients’ compliance, thereby optimizing patient care and preventing dropouts and delays in the diagnosis and treatment of complications [9].

This study aimed to describe the incidence and clinical features of HM and to analyze factors associated with mole subtype, treatment, and follow-up compliance at a tertiary obstetrics and gynecology hospital in Hanoi, northern Vietnam. The findings of this study provide updated epidemiological and clinical data from a tertiary referral center in Northern Vietnam and offer region-specific insights into the diagnosis, management, and long-term follow-up of patients with HM.

During the study period, 223 cases with an initial diagnosis of HM were identified among 57,203 deliveries at the institution. After exclusion of cases not confirmed and not treated as HM, 205 cases met the inclusion criteria and were used to calculate the incidence rate, corresponding to 3.6 per 1000 deliveries over the two-year study period. Among these, 50 cases lacked histopathological subclassification and were therefore excluded from subgroup analyses. The remaining 155 women were eligible for classification-based correlation analysis (Fig. 1). Of these, 17 patients had missing anemia data at T0 and 12 patients had missing first $\beta$-hCG posttreatment; these cases were excluded from the corresponding analyses (Tables 1,2,3).

Fig. 1.

Flowchart of patient selection and inclusion in the study. CHM, complete hydatidiform mole; PHM, partial hydatidiform mole.

3.3 Follow-Up Completion and Associated Factors

During the follow-up period, 54% of patients achieved complete monitoring, defined as at least three consecutive negative $\beta$-hCG results (Fig. 2).

Fig. 2.

Posttreatment $\beta$-hCG follow-up compliance. (A) Overall posttreatment $\beta$-hCG follow-up completion. (B) Distribution within the incomplete follow-up group, which includes patients who had not yet achieved three consecutive negative $\beta$-hCG results (62%), those with persistently detectable $\beta$-hCG (23%), and those lost to follow-up (15%).

Univariate analysis showed that age $\ge$40 years, CHM, hysterectomy, and chemotherapy were significantly associated with completion of follow-up. Specifically, age $\ge$40 years (OR = 2.5, 95% CI: 1.2–5.0), CHM (OR = 2.4, 95% CI: 1.2–5.0), hysterectomy (OR = 2.4, 95% CI: 1.1–5.0), and chemotherapy (OR = 6.4, 95% CI: 2.9–14.2) were more likely to complete surveillance. However, in the multivariate analysis, only chemotherapy remained an independent predictor (OR = 5.7, 95% CI: 2.3–14.0). These findings highlight that, although several clinical factors influence follow-up completion in univariate analysis, chemotherapy is the sole independent determinant, emphasizing its pivotal role in ensuring adherence to postmolar monitoring (Table 4).

Table 4. Univariate and multivariate logistic regression analysis results for the follow-up outcomes (n = 155).

Variables		Univariate analysis		Multivariate analysis
		OR (95% CI)	p-value	OR (95% CI)	p-value
Age (years)			0.010		0.462
	40	1		1
	$\ge$40	2.5 (1.2–5.0)		1.6 (0.5–5.2)
Type of HM			0.016		0.357
	PHM	1		1
	CHM	2.4 (1.2–5.0)		1.5 (0.7–3.2)
Invasive HM			0.056		/
	No	1		/
	Yes	2.5 (0.98–6.4)		/
Hysterectomy			0.020		0.543
	No	1		1
	Yes	2.4 (1.1–5.0)		0.7 (0.2–2.5)
Chemotherapy			0.001		0.001
	No	1		1
	Yes	6.4 (2.9–14.2)		5.7 (2.3–14.0)

This study provides an updated overview of the epidemiology, clinical features, treatment patterns, and follow-up outcomes of HM at a tertiary obstetrics and gynecology hospital in northern Vietnam. The findings contribute new evidence on the contemporary management of HM in a middle-income country setting, highlighting key determinants of treatment choice and adherence to postmolar surveillance.

In this study, the incidence of HM at Hanoi Obstetrics and Gynecology Hospital was 3.6 per 1000 deliveries, which is lower than earlier reports from Vietnam but consistent with findings from other Asian countries. The incidence of HM varies globally, with rates of 0.66 to 1.21 per 1000 pregnancies in Europe and North America and 1.5–4.4 per 1000 in East and Southeast Asia [3, 4]. Differences across studies likely reflect variations in genetic background, nutritional status, and diagnostic methods. Previous Vietnamese data from a national referral hospital in southern Vietnam reported a higher incidence, up to 11 per 1000 births [5], compared with the rate observed in the present study. However, the lower rate observed here may be partly explained by differences in delivery volume, disease patterns, and regional context, as this institution, one of the largest obstetric and gynecologic centers in northern Vietnam, records more than 40,000 births annually in the pre-Coronavirus Disease 2019 (COVID-19) period. Our study also showed that CHM accounted for 72% of all HM cases, similar to domestic studies [5], but higher than rates reported in Europe, North America, and other developed Asian regions, where CHMs occur in approximately 1 to 3 per 1000 pregnancies and PHMs in about 3 per 1000 [11]. Across developed countries, variations in CHM and PHM proportions have been reported. In Japan, CHM accounted for 46.5% of cases between 1992 and 2018, rising to 58.8% in recent years [12]. In the United States, CHM and PHM were nearly equal (53% vs. 47%) [13]. In Sweden, improved diagnostic techniques have increased PHM detection [14]. Taken together, these findings suggest that although the overall incidence of HM in Vietnam remains higher than in developed countries, the apparent predominance of CHM may reflect underdiagnosis of PHM, as many partial moles are misclassified as spontaneous or missed abortions without histopathologic confirmation.

The widespread use of ultrasonography has facilitated earlier detection of molar pregnancy, often before overt clinical manifestations appear. Consequently, the frequency of clinical symptoms such as vaginal bleeding or abdominal pain was lower in this study than in earlier reports. CHM occurred more frequently in older women, whereas PHM predominated in younger patients, a distribution pattern also observed in Japan, Korea, and Thailand [3, 4]. The strong association between maternal age and CHM may be related to age-dependent oocyte abnormalities and defects in genomic imprinting, which can lead to androgenetic conceptions [7]. In our cohort, patients with CHM were generally older, presented more frequently with vaginal bleeding, exhibited higher pre-evacuation $\beta$-hCG levels, and showed a greater risk of invasive HM. In contrast, PHM was more common in younger women and was often associated with a delayed menstrual period, which reflects milder trophoblastic proliferation and slower $\beta$-hCG elevation [6]. Savage et al. [15] showed that the risk of CHM increases sharply with maternal age, from 1 in 1000 for women aged 18 to 40 to 1 in 156 at age 45, and 1 in 8 for those aged 50 years and older. Other studies have confirmed that the risk of PHM varies little with age, with CHM accounting for most of the age-related increase in molar pregnancy risk [16].

Most molar pregnancies regress after uterine evacuation, yet a small proportion invade the myometrium, which may lead to uterine perforation or extension to adjacent structures. An invasive mole is typically defined histologically as trophoblastic invasion of the myometrium and uterine vessels, most often confirmed after hysterectomy [17, 18, 19]. In recent years, the preference for uterine preservation has increased, which has led to a lower reported incidence of invasive mole relative to overall molar pregnancies. In our study, invasive mole was identified in 25 cases (0.45 per 1000 deliveries per year). Of these, 23 were confirmed histopathologically following hysterectomy, and two were diagnosed based on postevacuation histology combined with ultrasonographic evidence of myometrial invasion. The relatively higher incidence observed in our cohort likely reflects a higher hysterectomy rate, which allows more histopathologic confirmation, as well as improved detection practices. By contrast, a large population-based study from Sweden (1994–2013) reported an incidence of only 0.01 case per 1000 deliveries [20], which reflects the rarity of invasive mole in settings with comprehensive follow-up and widespread uterine preservation. Notably, nearly all invasive moles in our cohort arose from CHM, consistent with previous studies [21, 22].

Vacuum aspiration remains the first-line treatment for HM, whereas hysterectomy is reserved for women aged $\ge$40 years, those who have completed childbearing, or patients at high-risk of developing postmolar GTN. However, the use of hysterectomy has become increasingly limited, as modern management prioritizes uterine evacuation followed by strict $\beta$-hCG surveillance to preserve fertility and prevent overtreatment [23]. In our study, 71% of patients underwent uterine evacuation and 29% underwent hysterectomy, primarily among older women or those without a desire for future fertility. The proportion of hysterectomies in our cohort is comparable to that reported in other Vietnamese studies, yet remains notably higher than in international reports. As reported by Giorgione et al. (2017) [24], hysterectomy was performed in only 4 of 442 women (5%) aged $\ge$40 years with molar pregnancy. Similarly, in a recent multicenter cohort study of women aged $\ge$40 years with CHM, Desmarais et al. (2025) [25] found that hysterectomy was used as the initial treatment in only 11% of cases, with the majority managed with uterine evacuation. This discrepancy may be attributed to the lack of a nationwide trophoblastic disease registry in Vietnam and limited compliance with postevacuation $\beta$-hCG surveillance. Furthermore, a meta-analysis by Zhao et al. (2019) [26] demonstrated that total hysterectomy significantly reduces the risk of postmolar GTN among women aged $\ge$40 years and/or with CHM, which may further justify the higher hysterectomy rate observed in this population.

Regarding prophylactic chemotherapy, 34.2% of patients received methotrexate (MTX) monotherapy. Independent risk factors associated with chemotherapy administration included maternal age $\ge$40 years, CHM, and invasive mole. Chemotherapy administration was independent of pre-evacuation $\beta$-hCG levels $>$100,000 IU/L or even $>$200,000 IU/L, as reported in several previous studies. This proportion was notably lower than that reported in previous domestic and regional studies. At Tu Du Hospital in South Vietnam, 80.8% of patients received prophylactic chemotherapy for pre-evacuation $\beta$-hCG $\ge$100,000 IU/L. Similarly, Cagayan (2014) [27] in the Philippines reported a rate of 70%. In contrast, our chemotherapy rate remained higher than that reported in China, where only 51 out of 680 patients (7.5%) received prophylactic chemotherapy in a large multicenter study [8]. Such variations likely reflect differences in clinical practice patterns, the degree of individualized management for high-risk patients, and the availability of postevacuation $\beta$-hCG surveillance across countries. Although prophylactic chemotherapy administered at or immediately after molar evacuation can reduce the risk of postmolar GTN [28], current evidence does not support its routine use due to the potential for drug resistance, delayed GTN diagnosis, and unnecessary toxicity [28]. Consistently, both the centralized molar pregnancy surveillance program and recent national guidelines in China discourage the use of prophylactic chemotherapy for women with high-risk CHM when reliable $\beta$-hCG monitoring is available, reserving it only for cases with exceptionally high risk or when follow-up is not feasible [4, 8].

Follow-up compliance remains a key determinant of patient outcomes in HM. In this cohort, only 54% of patients completed posttreatment monitoring with three consecutive undetectable $\beta$-hCG results. This rate is considerably lower than that reported in countries with centralized GTD registries, such as China or Canada, where compliance exceeds 96% [8, 29]. In this study, chemotherapy was the only independent predictor of complete follow-up, which indicates that patients who received chemotherapy benefited from more intensive monitoring and counseling. In contrast, those managed with evacuation alone may have faced barriers such as distance to the hospital, lack of awareness, or financial limitations, issues also reported in other Southeast Asian populations [18, 19]. Improving follow-up compliance is therefore crucial to optimizing outcomes. Lessons from China demonstrate that a centralized registry and telemedicine-based $\beta$-hCG monitoring system can markedly improve patient adherence and reduce postmolar GTN incidence [29]. Implementing similar approaches in Vietnam, including telehealth integration, local healthcare coordination, and patient education, may strengthen posttreatment surveillance and facilitate earlier detection of GTN.

The present study provides updated evidence on the clinical management and follow-up of patients with HM at a tertiary referral center in Northern Vietnam. Several important findings merit emphasis. First, the incidence of HM in our cohort (3.6 per 1000 deliveries) was substantially lower than that reported in earlier Vietnamese and regional studies. Second, posttreatment follow-up compliance was suboptimal, which likely reflects the absence of a centralized and structured follow-up management system. Third, this limitation in follow-up care may have influenced clinical decision-making, particularly in women aged 40 years and older, and may have contributed to the relatively high reliance on definitive surgical treatment, such as hysterectomy, in this age group.

In this single-center study, the incidence of HM was lower than that reported in previous Vietnamese studies. Age $\ge$40 years, CHM, and elevated pre-evacuation $\beta$-hCG levels were the main factors associated with surgical management, whereas age $\ge$40 years, CHM, and invasive mole predicted the need for chemotherapy. Chemotherapy was also the only factor associated with completion of follow-up. Follow-up compliance after treatment remained suboptimal. Strengthening centralized surveillance and standardized follow-up programs is essential to improve early detection and management of GTN in Vietnam.

The raw data of this study are deposited to REDCap (https://redcap.benhvienphusanhanoi.vn/) and will be publicly available as of the date of publication. All data reported in this paper will also be shared by the lead contact upon request.

MTH and TTVT designed the research study. MTH performed the research. LTKL collected the data. NMT, NDP, NCC, NKT, VTTH, NCD, NDL, and VTV contributed to study design, clinical data interpretation, and critical revision of the manuscript. MTH analyzed the data. MTH and TTVT developed the manuscript. All authors contributed to editorial revisions of the manuscripts. 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.

The study was carried out in accordance with the guidelines of the Declaration of Helsinki. Ethical approval was obtained from the Ethics Committee of Hanoi Obstetrics and Gynecology Hospital (IRB code: IRB-VN02.030; approval No. CS/PSHN/DC/23/21). As this study was a retrospective review of anonymized medical records, the Ethics Committee waived the requirement for written informed consent.

We gratefully acknowledge Ms. Ha Nguyen Thi and Mr. Anh Nguyen Xuan for their support in data collection at Hanoi Obstetrics and Gynecology Hospital.

This research received no external funding.

The authors declare no conflict of interest.

During the preparation of this work, the authors used ChatGPT-5.1 to support English language editing. After using this tool, the authors reviewed and edited the content as needed and took full responsibility for the final version of the manuscript.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/CEOG48315.