A retrospective descriptive study was conducted at the Department of Gynecology and Oncology of the University Hospital Center of Analankininina Toamasina (CHUAT), a tertiary referral hospital in eastern Madagascar.

January 2019 to December 2024.

All patients diagnosed with GTD and managed at CHUAT during the study period were included.

Patients were included if they met at least one of the following criteria:

Histopathological confirmation of hydatidiform mole or GTN. Availability of complete medical records: A “complete medical record” was defined as a file containing at least: demographic data, clinical presentation, serum hCG measurements, treatment information, and documented outcomes.

In cases without histopathological confirmation, hydatidiform mole was diagnosed based on typical clinical presentation (vaginal bleeding after amenorrhea), markedly elevated serum hCG levels, and characteristic ultrasound findings such as a “snowstorm” appearance.

The diagnosis of GTN was based on FIGO criteria, including one or more of the following:

Plateau of serum hCG levels over at least three consecutive weeks.Rise in serum hCG levels over two consecutive weeks.Persistence of detectable hCG beyond 6 months after molar evacuation.Histological diagnosis of choriocarcinoma.

Data were extracted from medical records and included sociodemographic characteristics, obstetric history, clinical presentation, serum hCG levels, histopathological findings, FIGO score, treatment modalities, and outcomes.

Low-risk GTN patients (FIGO score ≤ 6) were treated with single-agent chemotherapy, primarily methotrexate-based regimens.

High-risk patients (FIGO score > 6) received combination chemotherapy, most commonly EMA-CO protocol when feasible.

Criteria for switching from single-agent to combination therapy included:

Plateau or rise in hCG levels.Clinical or radiological evidence of disease progression.

After uterine evacuation, patients were monitored with weekly serum hCG measurements until normalization, followed by monthly monitoring for at least 6 months.

Complete remission was defined as normalization of serum hCG levels maintained for at least three consecutive weeks. Recurrence was defined as a subsequent rise in hCG after normalization. Subsequent pregnancies were identified through follow-up records and patient reports.

Data were analyzed using descriptive statistics. Quantitative variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages.

Confidentiality was maintained, and institutional authorization was obtained.

The mean age and predominance of women aged 20 - 29 years are consistent with findings from other low- and middle-income countries, reflecting peak reproductive age [1][2]. Although extreme maternal ages (<20 and ≥40 years) are recognized risk factors, their lower representation in this cohort may reflect demographic patterns and fertility distribution in the study population [3][4].

The predominance of patients with low socioeconomic status, particularly farmers and housewives, reflects structural inequalities in access to healthcare. Similar observations have been reported in sub-Saharan Africa, where delayed diagnosis is often linked to limited access to reproductive health services and reduced health literacy [5][6]. These determinants may contribute to late presentation and more advanced disease at diagnosis.

The majority of patients were paucigravida (66.0%) and pauciparous (45.3%). While some studies report increased GTD risk in multiparous women, the relationship between parity and GTD remains inconsistent across populations [6]. A history of abortion was reported in 37.7% of cases, comparable to findings from other African series, although causal links between prior pregnancy loss and GTD are not firmly established [7][8]. Notably, the index pregnancy was overwhelmingly a molar pregnancy (94.3%), consistent with the known epidemiology of GTD, where hydatidiform mole constitutes the most frequent entity [1].

Contraceptive use was suboptimal, with 39.6% of patients reporting no method, while injectable contraception was the most frequently used (37.7%). This pattern mirrors national trends in Madagascar and other sub-Saharan African countries, where access to modern contraceptive methods remains limited [9]. Although contraceptive methods are not directly associated with GTD risk, limited access to family planning and reproductive health services may contribute to delayed diagnosis and suboptimal monitoring of early pregnancies.

Clinically, vaginal bleeding following amenorrhea was the most common presenting symptom, consistent with classical descriptions of GTD [1][2]. Persistent vaginal bleeding after molar evacuation was reported in 15.1% of cases, highlighting the need for close post-evacuation surveillance. Less frequent symptoms included vomiting (11.3%), vaginal expulsion of molar vesicles (5.7%), and persistent or rising serum hCG levels (5.7%). Rare presentations, such as hemoptysis and hematuria (each 1.9%), may indicate metastatic disease and underscore the potential severity of GTN in advanced stages [1][10].

However, the high proportion of patients with serum hCG levels ≥ 100,000 IU/L suggests a substantial tumor burden at diagnosis, likely reflecting delayed presentation [4][6]. Serum hCG measurement remains the cornerstone for both diagnosis and follow-up, particularly in settings where histopathological confirmation is limited [1][11].

A major limitation of this study is the absence of histopathological confirmation in 77.4% of cases. This finding highlights significant constraints in pathology infrastructure in low-resource settings. Although diagnosis based on clinical presentation and hCG dynamics is acceptable in certain contexts, the lack of histopathology may lead to misclassification, inadequate risk stratification, and potential deviations from optimal management [1][4][12]. Similar challenges have been reported in other developing countries, emphasizing the urgent need to strengthen pathology services and standardize diagnostic pathways [5][6].

Regarding therapeutic management, uterine curettage was the mainstay of treatment and remains the standard initial intervention for molar pregnancy worldwide [1]. This procedure allows rapid evacuation of trophoblastic tissue and facilitates subsequent monitoring. However, it carries risks such as hemorrhage, uterine perforation, and infection, particularly in settings lacking ultrasound guidance [12]. Despite these risks, curettage remains widely used in low-resource settings due to its accessibility, cost-effectiveness, and feasibility compared with more advanced techniques, such as minimally invasive suction evacuation or hysteroscopic techniques, which may not be available [4][6].

Chemotherapy was administered in all patients with gestational trophoblastic neoplasia (GTN), in accordance with FIGO risk-adapted protocols [1]. The high remission rate observed in this study is consistent with the well-established chemosensitivity of GTN, even in metastatic stages [1]. These findings demonstrate that adherence to standardized treatment protocols can yield favorable outcomes, even in resource-constrained environments.

However, loss to follow-up remains a significant concern, affecting 17.0% of patients. This issue is commonly reported in low-resource settings and may compromise long-term outcomes, including detection of relapse and monitoring of subsequent pregnancies [6]. Strengthening follow-up systems and patient education is therefore essential.

Recent evidence has also highlighted the importance of long-term surveillance, as patients with a history of GTD may have an increased risk of subsequent malignancies, although this risk remains low [13]. Additionally, advances in imaging and diagnostic strategies have improved disease characterization and management in high-resource settings, but these innovations remain largely inaccessible in many low-income countries [11][12].

Overall, this study underscores the dual reality of GTD management in low-resource settings: while effective treatments exist and outcomes can be favorable, major challenges persist in early diagnosis, access to histopathology, and continuity of care. Addressing these gaps is essential to further improve patient outcomes in Madagascar and similar contexts.

This study provides valuable data from an underrepresented region and contributes to the limited literature on GTD in Madagascar. However, this study has several limitations. Its retrospective design and single-center setting may introduce selection bias, particularly as a tertiary referral center likely receives more severe cases. Additionally, exclusion of incomplete records may have introduced selection bias. The high proportion of missing histopathological data limits diagnostic accuracy. Finally, loss to follow-up may affect the reliability of outcome assessment.

The study underscores the importance of early diagnosis through improved reproductive health education and access to ultrasound and hCG monitoring. Strengthening regional reference centers and implementing standardized follow-up protocols could further improve outcomes. Additionally, enhancing access to family planning services may reduce the frequency of unmonitored pregnancies and facilitate early detection of abnormal gestations.