人绒毛膜促性腺激素水平恢复正常后磨牙妊娠恶性转化的风险很低,大约0.4%,但可能证明对某些患者调整监测策略是合理的。
本研究旨在确定磨牙妊娠妇女人绒毛膜促性腺激素正常化后妊娠滋养细胞瘤形成的风险,并确定这种恶性转化的危险因素,以优化人绒毛膜促性腺激素正常化后的随访方案。
这是一项基于法国国家滋养细胞疾病中心7761名患者的回顾性观察性国家队列研究,1999年至2020年期间治疗妊娠滋养细胞疾病,其人绒毛膜促性腺激素水平自发恢复正常。
在7761例人绒毛膜促性腺激素水平恢复正常的患者中,20(0.26%)发生了妊娠滋养细胞瘤。恶性转化的风险随痣的类型而变化,从组织学证实的部分葡萄胎的0%(2592例中的0例)到完全葡萄胎的0.36%(5045例中的18例)和双磨牙妊娠的2.1%(95例中的2例)。人绒毛膜促性腺激素正常化后诊断恶变的中位时间为11.4个月(范围,1-34个月)。诊断时,20例患者中有16例(80%)患有国际妇产科联合会I期肿瘤,根据国际妇产科联合会评分,20例患者中有10例(50%)的肿瘤被归类为低风险。20名患者中有9名(45%)最常见的一线治疗是联合化疗.这些肿瘤的四分之一(20个中的5个)是组织学证实的胎盘部位或上皮样滋养细胞肿瘤。在单变量分析中,与正常人绒毛膜促性腺激素监测期结束后发生妊娠滋养细胞瘤形成的高风险显著相关的因素是年龄≥45岁(比值比,8.3;95%置信区间,2.0-32.7;P=.004)和人绒毛膜促性腺激素正常化时间≥8周(比值比,7.7;95%置信区间,1.1-335;P=0.03)。人绒毛膜促性腺激素正常化时间≥17周的风险甚至更高(比值比,19.5;95%置信区间,3.3-206;P<.001)。
在这组妊娠滋养细胞疾病患者中,病理证实为部分痣的人都没有恶性转化,支持目前关于在连续3次试验阴性后停止人绒毛膜促性腺激素监测的建议。在完全葡萄胎或双葡萄胎妊娠的情况下,我们建议在具有已确定的晚期恶性转化危险因素的患者中,通过季度人类绒毛膜促性腺激素测量将监测期延长30个月(年龄,≥45岁;人类绒毛膜促性腺激素正常化的时间,≥8周)。
The risk of malignant transformation of molar pregnancies after human chorionic gonadotropin levels return to normal is low, roughly 0.4%, but may justify an adaptation of monitoring strategies for certain patients.
This study aimed to determine the risk of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in women with molar pregnancy and identify risk factors for this type of malignant transformation to optimize follow-up protocols after human chorionic gonadotropin normalization.
This was a retrospective observational national cohort study based at the French National Center for Trophoblastic Diseases of 7761 patients, treated between 1999 and 2020 for gestational trophoblastic disease, whose human chorionic gonadotropin levels returned spontaneously to normal.
Among 7761 patients whose human chorionic gonadotropin levels returned to normal, 20 (0.26%) developed gestational trophoblastic neoplasia. The risk of malignant transformation varied with the type of mole, from 0% (0 of 2592 cases) for histologically proven partial mole to 0.36% for complete mole (18 of 5045) and 2.1% (2 of 95) for twin molar pregnancy. The median time to diagnosis of malignant transformation after human chorionic gonadotropin normalization was 11.4 months (range, 1-34 months). At diagnosis, 16 of 20 patients (80%) had the International Federation of Gynecology and Obstetrics stage I tumor, and 10 of 20 patients (50%) had a tumor classified as low risk in terms of the International Federation of Gynecology and Obstetrics score. In 9 of 20 patients (45%), the most common first-line treatment was combination chemotherapy. A quarter of these tumors (5 of 20) were histologically proven placental site or epithelioid trophoblastic tumors. In univariate analysis, the factors significantly associated with a higher risk of developing gestational trophoblastic neoplasia after the end of the normal human chorionic gonadotropin monitoring period were age of ≥45 years (odds ratio, 8.3; 95% confidence interval, 2.0-32.7; P=.004) and time to human chorionic gonadotropin normalization of ≥8 weeks (odds ratio, 7.7; 95% confidence interval, 1.1-335; P=.03). The risk was even higher for human chorionic gonadotropin normalization times of ≥17 weeks (odds ratio, 19.5; 95% confidence interval, 3.3-206; P<.001).
In this group of patients with gestational trophoblastic disease, none of the those with pathologically verified partial mole had malignant transformation, supporting the current recommendation of stopping human chorionic gonadotropin monitoring after 3 successive negative tests. In cases of complete mole or twin molar pregnancy, we proposed to extend the monitoring period with quarterly human chorionic gonadotropin measurements for an additional 30 months in patients with the identified risk factors for late malignant transformation (age, ≥45 years; time to human chorionic gonadotropin normalization, ≥8 weeks).