Hydatidiform mole: Management
- Ross S Berkowitz, MD
Ross S Berkowitz, MD
- William H. Baker Professor of Gynecology
- Harvard Medical School
- Director of Gynecologic Oncology and Gynecology
- Brigham and Women's Hospital and Dana Farber Cancer Institute
- New England Trophoblastic Disease Center
- Donald Peter Goldstein, MD
Donald Peter Goldstein, MD
- Professor of Obstetrics, Gynecology, and Reproductive Biology
- Harvard Medical School
- Founder and Co-Director
- New England Trophoblastic Disease Center
- Neil S Horowitz, MD
Neil S Horowitz, MD
- Assistant Professor of Obstetrics, Gynecology, and Reproductive Biology
- Harvard Medical School
- Director of Clinical Research, Gynecologic Oncology
- Brigham and Women’s Hospital
- Section Editors
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Deputy Editors
- Sandy J Falk, MD, FACOG
Sandy J Falk, MD, FACOG
- Director, Editorial Relations — UpToDate
- Deputy Editor — Obstetrics, Gynecology and Women's Health
- Instructor of Obstetrics, Gynecology and Reproductive Biology, Part-time
- Harvard Medical School
- Sadhna R Vora, MD
Sadhna R Vora, MD
- Deputy Editor — Oncology
- Instructor in Medicine
- Harvard Medical School
Hydatidiform mole (HM) is part of a group of diseases classified as gestational trophoblastic disease (GTD), which originate in the placenta and have the potential to locally invade the uterus and metastasize. The pathogenesis of GTD is unique because the maternal tumor arises from gestational rather than maternal tissue .
HM is made up of two distinct entities, complete hydatidiform mole and partial hydatidiform mole. These differ on the basis of chromosomal pattern, gross and microscopic histopathology, and clinical presentation and outcome [2-4]. Molar pregnancies, although benign, are considered to be premalignant because they have the capability of developing into a malignancy. Malignant disease is referred to as gestational trophoblastic neoplasia (GTN); the histologic entities included in this group are:
●Placental site trophoblastic tumor
- Berkowitz RS, Goldstein DP. Current advances in the management of gestational trophoblastic disease. Gynecol Oncol 2013; 128:3.
- Vassilakos P, Riotton G, Kajii T. Hydatidiform mole: two entities. A morphologic and cytogenetic study with some clinical consideration. Am J Obstet Gynecol 1977; 127:167.
- Szulman AE, Surti U. The clinicopathologic profile of the partial hydatidiform mole. Obstet Gynecol 1982; 59:597.
- Szulman AE, Surti U. The syndromes of hydatidiform mole. I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol 1978; 131:665.
- Berkowitz RS, Goldstein DP. Clinical practice. Molar pregnancy. N Engl J Med 2009; 360:1639.
- Tidy JA, Gillespie AM, Bright N, et al. Gestational trophoblastic disease: a study of mode of evacuation and subsequent need for treatment with chemotherapy. Gynecol Oncol 2000; 78:309.
- Elias KM, Shoni M, Bernstein M, et al. Complete hydatidiform mole in women aged 40 to 49 years. J Reprod Med 2012; 57:254.
- Elias KM, Goldstein DP, Berkowitz RS. Complete hydatidiform mole in women older than age 50. J Reprod Med 2010; 55:208.
- Lurain JR, Brewer JI, Torok EE, Halpern B. Natural history of hydatidiform mole after primary evacuation. Am J Obstet Gynecol 1983; 145:591.
- Tse KY, Chan KK, Tam KF, Ngan HY. 20-year experience of managing profuse bleeding in gestational trophoblastic disease. J Reprod Med 2007; 52:397.
- Kashimura Y, Kashimura M, Sugimori H, et al. Prophylactic chemotherapy for hydatidiform mole. Five to 15 years follow-up. Cancer 1986; 58:624.
- Berkowitz RS, Goldstein DP, DuBeshter B, Bernstein MR. Management of complete molar pregnancy. J Reprod Med 1987; 32:634.
- Fu J, Fang F, Xie L, et al. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia. Cochrane Database Syst Rev 2012; 10:CD007289.
- Kim DS, Moon H, Kim KT, et al. Effects of prophylactic chemotherapy for persistent trophoblastic disease in patients with complete hydatidiform mole. Obstet Gynecol 1986; 67:690.
- Uberti EM, Fajardo Mdo C, da Cunha AG, et al. Prevention of postmolar gestational trophoblastic neoplasia using prophylactic single bolus dose of actinomycin D in high-risk hydatidiform mole: a simple, effective, secure and low-cost approach without adverse effects on compliance to general follow-up or subsequent treatment. Gynecol Oncol 2009; 114:299.
- Goldstein DP, Berkowitz RS. Prophylactic chemotherapy of complete molar pregnancy. Semin Oncol 1995; 22:157.
- Limpongsanurak S. Prophylactic actinomycin D for high-risk complete hydatidiform mole. J Reprod Med 2001; 46:110.
- Nagataki S, Mizuno M, Sakamoto S, et al. Thyroid function in molar pregnancy. J Clin Endocrinol Metab 1977; 44:254.
- Berkowitz RS, Goldstein DP, Bernstein MR. Laparoscopy in the management of gestational trophoblastic neoplasms. J Reprod Med 1980; 24:261.
- Soto-Wright V, Bernstein M, Goldstein DP, Berkowitz RS. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol 1995; 86:775.
- Braga A, Moraes V, Maestá I, et al. Changing Trends in the Clinical Presentation and Management of Complete Hydatidiform Mole Among Brazilian Women. Int J Gynecol Cancer 2016; 26:984.
- Twiggs LB, Morrow CP, Schlaerth JB. Acute pulmonary complications of molar pregnancy. Am J Obstet Gynecol 1979; 135:189.
- Massad LS, Abu-Rustum NR, Lee SS, Renta V. Poor compliance with postmolar surveillance and treatment protocols by indigent women. Obstet Gynecol 2000; 96:940.
- Committee on Practice Bulletins-Gynecology, American College of Obstetricians and Gynecologists. ACOG Practice Bulletin #53. Diagnosis and treatment of gestational trophoblastic disease. Obstet Gynecol 2004; 103:1365.
- Tuncer ZS, Bernstein MR, Goldstein DP, et al. Outcome of pregnancies occurring within 1 year of hydatidiform mole. Obstet Gynecol 1999; 94:588.
- Wolfberg AJ, Feltmate C, Goldstein DP, et al. Low risk of relapse after achieving undetectable HCG levels in women with complete molar pregnancy. Obstet Gynecol 2004; 104:551.
- Wolfberg AJ, Berkowitz RS, Goldstein DP, et al. Postevacuation hCG levels and risk of gestational trophoblastic neoplasia in women with complete molar pregnancy. Obstet Gynecol 2005; 106:548.
- Wolfberg AJ, Growdon WB, Feltmate CM, et al. Low risk of relapse after achieving undetectable HCG levels in women with partial molar pregnancy. Obstet Gynecol 2006; 108:393.
- Kerkmeijer LG, Wielsma S, Massuger LF, et al. Recurrent gestational trophoblastic disease after hCG normalization following hydatidiform mole in The Netherlands. Gynecol Oncol 2007; 106:142.
- Lavie I, Rao GG, Castrillon DH, et al. Duration of human chorionic gonadotropin surveillance for partial hydatidiform moles. Am J Obstet Gynecol 2005; 192:1362.
- Sebire NJ, Foskett M, Short D, et al. Shortened duration of human chorionic gonadotrophin surveillance following complete or partial hydatidiform mole: evidence for revised protocol of a UK regional trophoblastic disease unit. BJOG 2007; 114:760.
- Schmitt C, Doret M, Massardier J, et al. Risk of gestational trophoblastic neoplasia after hCG normalisation according to hydatidiform mole type. Gynecol Oncol 2013; 130:86.
- Braga A, Maestá I, Matos M, et al. Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation. Gynecol Oncol 2015; 139:283.
- Coyle C, Short D, Dayal L, et al. Time to hCG normalization in patients with hydatidiform molar pregnancy and risk of persistent gestational trophoblastic disease. XVII World Congress on Gestational Trophoblastic Disease, 2013, p.60 (abstract).
- Lybol C, Sweep FC, Ottevanger PB, et al. Linear regression of postevacuation serum human chorionic gonadotropin concentrations predicts postmolar gestational trophoblastic neoplasia. Int J Gynecol Cancer 2013; 23:1150.
- van Cromvoirt SM, Thomas CM, Quinn MA, et al. Identification of patients with persistent trophoblastic disease after complete hydatidiform mole by using a normal 24-hour urine hCG regression curve. Gynecol Oncol 2014; 133:542.
- Kim BW, Cho H, Kim H, et al. Human chorionic gonadotrophin regression rate as a predictive factor of postmolar gestational trophoblastic neoplasm in high-risk hydatidiform mole: a case-control study. Eur J Obstet Gynecol Reprod Biol 2012; 160:100.
- Growdon WB, Wolfberg AJ, Feltmate CM, et al. Postevacuation hCG levels and risk of gestational trophoblastic neoplasia among women with partial molar pregnancies. J Reprod Med 2006; 51:871.
- Kohorn EI. The new FIGO 2000 staging and risk factor scoring system for gestational trophoblastic disease: description and critical assessment. Int J Gynecol Cancer 2001; 11:73.
- FIGO Committee on Gynecologic Oncology. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009; 105:3.
- Ngan HY, Bender H, Benedet JL, et al. Gestational trophoblastic neoplasia, FIGO 2000 staging and classification. Int J Gynaecol Obstet 2003; 83 Suppl 1:175.
- Agarwal R, Teoh S, Short D, et al. Chemotherapy and human chorionic gonadotropin concentrations 6 months after uterine evacuation of molar pregnancy: a retrospective cohort study. Lancet 2012; 379:130.
- Braga A, Torres B, Burlá M, et al. Is chemotherapy necessary for patients with molar pregnancy and human chorionic gonadotropin serum levels raised but falling at 6months after uterine evacuation? Gynecol Oncol 2016; 143:558.
- Cole LA. Hyperglycosylated hCG, a review. Placenta 2010; 31:653.
- Kohorn EI. What we know about low-level hCG: definition, classification and management. J Reprod Med 2004; 49:433.
- Ngu SF, Chan KK. Management of Chemoresistant and Quiescent Gestational Trophoblastic Disease. Curr Obstet Gynecol Rep 2014; 3:84.
- Cole LA, Khanlian SA. Inappropriate management of women with persistent low hCG results. J Reprod Med 2004; 49:423.
- Cole LA, Muller CY. Hyperglycosylated hCG in the management of quiescent and chemorefractory gestational trophoblastic diseases. Gynecol Oncol 2010; 116:3.
- Hancock BW. hCG measurement in gestational trophoblastic neoplasia: a critical appraisal. J Reprod Med 2006; 51:859.
- Hwang D, Hancock BW. Management of persistent, unexplained, low-level human chorionic gonadotropin elevation: a report of 5 cases. J Reprod Med 2004; 49:559.
- Khanlian SA, Cole LA. Management of gestational trophoblastic disease and other cases with low serum levels of human chorionic gonadotropin. J Reprod Med 2006; 51:812.
- Stone M, Bagshawe KD. An analysis of the influences of maternal age, gestational age, contraceptive method, and the mode of primary treatment of patients with hydatidiform moles on the incidence of subsequent chemotherapy. Br J Obstet Gynaecol 1979; 86:782.
- Ho Yuen B, Burch P. Relationship of oral contraceptives and the intrauterine contraceptive devices to the regression of concentrations of the beta subunit of human chorionic gonadotropin and invasive complications after molar pregnancy. Am J Obstet Gynecol 1983; 145:214.
- Berkowitz RS, Goldstein DP, Marean AR, Bernstein M. Oral contraceptives and postmolar trophoblastic disease. Obstet Gynecol 1981; 58:474.
- Curry SL, Schlaerth JB, Kohorn EI, et al. Hormonal contraception and trophoblastic sequelae after hydatidiform mole (a Gynecologic Oncology Group Study). Am J Obstet Gynecol 1989; 160:805.
- Adewole IF, Oladokun A, Fawole AO, et al. Fertility regulatory methods and development of complications after evacuation of complete hydatidiform mole. J Obstet Gynaecol 2000; 20:68.
- Costa HL, Doyle P. Influence of oral contraceptives in the development of post-molar trophoblastic neoplasia--a systematic review. Gynecol Oncol 2006; 100:579.
- Goldstein DP, Berkowitz RS. The diagnosis and management of molar pregnancy. In: Gestational Trophoblastic Neoplasms: Clinical Principles of Diagnosis and Management, Saunders, Philadelphia 1982. p.143.
- Curry SL, Hammond CB, Tyrey L, et al. Hydatidiform mole: diagnosis, management, and long-term followup of 347 patients. Obstet Gynecol 1975; 45:1.
- Gestational Trophoblastic Disease, 3rd edition, Hancock BW, Seckl MJ, Berkowitz RS, Cole LA (Eds), International Society for the Study of Trophoblastic Disease, www.isstd.org 2009. p.1-502.
- Bagshawe KD. Trophoblastic neoplasia. In: Cancer Medicine, 3, Holland JF, Frei F III, Bast R Jr., et al. (Eds), Williams & Wilkins, Baltimore 1993. p.1691.
- Tow WS. The influence of the primary treatment of hydatidiform mole on its subsequent course. J Obstet Gynaecol Br Commonw 1966; 73:544.
- Xia ZF, Song HZ, Tang MY. Risk of malignancy and prognosis using a provisional scoring system in hydatidiform mole. Chin Med J (Engl) 1980; 93:605.
- Tsukamoto N, Iwasaka T, Kashimura Y, et al. Gestational trophoblastic disease in women aged 50 or more. Gynecol Oncol 1985; 20:53.
- Tsuji K, Yagi S, Nakano R. Increased risk of malignant transformation of hydatidiform moles in older gravidas: a cytogenetic study. Obstet Gynecol 1981; 58:351.
- Martin DA, Sutton GP, Ulbright TM, et al. DNA content as a prognostic index in gestational trophoblastic neoplasia. Gynecol Oncol 1989; 34:383.
- Braga A, Growdon WB, Bernstein M, et al. Molar pregnancy in adolescents. J Reprod Med 2012; 57:225.
- Feltmate CM, Growdon WB, Wolfberg AJ, et al. Clinical characteristics of persistent gestational trophoblastic neoplasia after partial hydatidiform molar pregnancy. J Reprod Med 2006; 51:902.
- Czernobilsky B, Barash A, Lancet M. Partial moles: a clinicopathologic study of 25 cases. Obstet Gynecol 1982; 59:75.
- Wielsma S, Kerkmeijer L, Bekkers R, et al. Persistent trophoblast disease following partial molar pregnancy. Aust N Z J Obstet Gynaecol 2006; 46:119.
- Wong LC, Ma HK. The syndrome of partial mole. Arch Gynecol 1984; 234:161.
- Ohama K, Ueda K, Okamoto E, et al. Cytogenetic and clinicopathologic studies of partial moles. Obstet Gynecol 1986; 68:259.
- Bolis G, Belloni C, Bonazzi C, et al. Analysis of 309 cases after hydatidiform mole: different follow-up program according to biologic behavior. Tumori 1988; 74:93.
- Seckl MJ, Fisher RA, Salerno G, et al. Choriocarcinoma and partial hydatidiform moles. Lancet 2000; 356:36.
- Goto S, Yamada A, Ishizuka T, Tomoda Y. Development of postmolar trophoblastic disease after partial molar pregnancy. Gynecol Oncol 1993; 48:165.
- Hancock BW, Nazir K, Everard JE. Persistent gestational trophoblastic neoplasia after partial hydatidiform mole incidence and outcome. J Reprod Med 2006; 51:764.
- Parazzini F, Mangili G, Belloni C, et al. The problem of identification of prognostic factors for persistent trophoblastic disease. Gynecol Oncol 1988; 30:57.
- Vargas R, Barroilhet LM, Esselen K, et al. Subsequent pregnancy outcomes after complete and partial molar pregnancy, recurrent molar pregnancy, and gestational trophoblastic neoplasia: an update from the New England Trophoblastic Disease Center. J Reprod Med 2014; 59:188.
- Bagshawe KD, Dent J, Webb J. Hydatidiform mole in England and Wales 1973-83. Lancet 1986; 2:673.
- Sebire NJ, Fisher RA, Foskett M, et al. Risk of recurrent hydatidiform mole and subsequent pregnancy outcome following complete or partial hydatidiform molar pregnancy. BJOG 2003; 110:22.
- BRANDES J, PERETZ A. RECURRENT HYDATIDIFORM MOLE; REPORT OF A CASE. Obstet Gynecol 1965; 25:398.
- Rice LW, Lage JM, Berkowitz RS, et al. Repetitive complete and partial hydatidiform mole. Obstet Gynecol 1989; 74:217.
- Uterine evacuation
- Patients at high risk for GTN
- - Hysterectomy
- - Prophylactic chemotherapy
- Rh(D) immune globulin
- MANAGEMENT OF COMPLICATIONS
- Ovarian theca lutein cysts
- Cardiopulmonary symptoms
- Serial hCG
- - Surveillance protocol
- Shorter duration of monitoring
- - Diagnosis of GTN
- - Persistent low hCG (quiescent GTN)
- Gestational trophoblastic neoplasia
- Subsequent pregnancy
- - Repeat molar pregnancy
- - Obstetric management
- SUMMARY AND RECOMMENDATIONS