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Hydatidiform Mole

  • Author: Lisa E Moore, MD, FACOG; Chief Editor: Warner K Huh, MD  more...
 
Updated: Nov 30, 2015
 

Background

Gestational trophoblastic disease encompasses several disease processes that originate in the placenta. These include complete and partial moles, placental site trophoblastic tumors, choriocarcinomas, and invasive moles. A diet deficient in animal fat and carotene may be a risk factor.[1]  More recently, Japanese investigators have identified a novel homozygous nonsense mutation in the NLRP7 gene (c.584G>A; p.W195X) in a patient that appears to associated with recurrent hydatidiform mole.[2] They also noted that the mole was biparental, and there was a specific maternal loss of DNA methylation of differentially methylated regions (DMRs).[2]

Almost all women with malignant gestational trophoblastic disease can be cured with preservation of reproductive function. The following discussion is limited to hydatidiform moles (complete and partial).

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Pathophysiology

A complete mole contains no fetal tissue. Ninety percent are 46,XX, and 10% are 46,XY.[3, 4] Complete moles can be divided into two types, androgenetic complete mole and biparental complete mole.

Androgenetic complete mole

Homozygous

These account for 80% of complete moles, with two identical paternal chromosome complements, derived from duplication of the paternal haploid chromosomes. Affected individuals are always female; 46,YY has never been observed.

Heterozygous

These account for 20% of complete moles. Affected individuals may be male or female. All chromosomes are of paternal origin, most likely due to dispermy.

Biparental complete mole

The biparental complete mole is rare. Maternal and paternal genes are present but failure of maternal imprinting causes only the paternal genome to be expressed.[5]

A recurrent form of biparental mole, which is familial and appears to be inherited as an autosomal recessive trait, has been described. Al-Hussaini describes a series of 5 women with as many as 9 consecutive molar pregnancies.[6, 7]

Mutations in NLRP7 at 19q13.4 have been identified as causative in recurrent molar pregnancies.[8, 9, 10]

Partial mole

With a partial mole, fetal tissue is often present. Fetal erythrocytes and vessels in the villi are a common finding. The chromosomal complement is 69,XXX or 69,XXY.[11] This results from fertilization of a haploid ovum and duplication of the paternal haploid chromosomes or from dispermy. Tetraploidy may also be encountered. As in a complete mole, hyperplastic trophoblastic tissue and swelling of the chorionic villi occur.

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Epidemiology

United States statistics

By studying elective pregnancy terminations, hydatidiform moles were determined to occur in approximately 1 in 1200 pregnancies.[12]

International statistics

The reported frequency of hydatidiform mole varies greatly. Some of this variability can be explained by differences in methodology (eg, single hospital vs population studies, identification of cases). The reported frequencies range from 1 in 100 pregnancies in Indonesia to 1 in 200 pregnancies in Mexico to 1 in 5000 pregnancies in Paraguay.[13] The study of pathologic material from first- and second-trimester abortions established a frequency of complete and partial hydatidiform moles in Ireland of 1 per 1945 pregnancies and 1 per 695 pregnancies, respectively.[14]

Race-, sex-, and age-related demographics

Differences in the frequency of hydatidiform moles between ethnic groups have been reported internationally.[13, 15] In the United States, comparison of frequency of hydatidiform moles in African Americans and Caucasians have yielded conflicting results.[15] If differences exist, whether they are due to genetic differences or environmental factors is not clear.

Hydatidiform mole is a disease of pregnancy and therefore a disease of women.

Hydatidiform mole is more common at the extremes of reproductive age. Women in their early teenage or perimenopausal years are most at risk.[1, 13, 15, 16, 17] Women older than 35 years have a 2-fold increase in risk. Women older than 40 years experience a 5- to 10-fold increase in risk compared to younger women. Parity does not affect the risk.

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Prognosis

Because of early diagnosis and appropriate treatment, the current mortality rate from hydatidiform mole is essentially zero. Approximately 20% of women with a complete mole develop a trophoblastic malignancy. Gestational trophoblastic malignancies (ie, gestational trophoblastic neoplasia) are almost 100% curable.

Clinical factors that have been associated with risk of malignant disease are advanced maternal age, high levels of hCG (>100,000 mIU/mL), eclampsia, hyperthyroidism, and bilateral theca lutein cysts.[18]  Most of these factors appear to reflect the amount of trophoblastic proliferation. Predicting who will develop gestational trophoblastic disease remains difficult, and treatment decisions should not be based on the presence of any or all of these risk factors.

A study by Vargas et al indicated that in women who have had molar pregnancies, the outcomes of subsequent pregnancies are similar to pregnancy outcomes in the general population. The study looked at 1388 subsequent pregnancies in women with complete hydatidiform mole, as well as 357 pregnancies following partial hydatidiform mole and 667 pregnancies after gestational trophoblastic neoplasia. Although outcomes in these cases were similar to those of women who had never had a molar pregnancy, the investigators did find that about 1.7% of women with a molar pregnancy did have another molar pregnancy later. Moreover, in women with gestational trophoblastic neoplasia who underwent successful chemotherapy for the disease, the incidence of stillbirth in subsequent pregnancies rose slightly, to 1.3%.[19]

In contrast to the results of Vargas’ study, a report by Joneborg et al suggested that following a molar pregnancy, the risk of preterm birth is increased. The results also indicated that if at least one birth occurs between the molar pregnancy and the index birth, the likelihood of large-for-gestational-age birth and stillbirth is greater. However, the risk of adverse maternal outcomes was not found to be increased following molar pregnancy. The risk of having a repeat molar pregnancy in this study was found to be 0.4%.[20]

Mortality/morbidity

A hydatidiform mole is considered malignant if metastases or destructive invasion of the myometrium (ie, invasive mole) occurs, or when the serum hCG levels plateau or rise during the period of follow-up and an intervening pregnancy is excluded. Malignancy (see Medscape Reference's article Gestational Trophoblastic Neoplasia) is diagnosed in 15-20% of patients with a complete hydatidiform mole and 2-3% of partial moles.[21, 22]  Lung metastases are found in 4-5% of patients with a complete hydatidiform mole and rarely in cases of partial hydatidiform moles.[23, 24]

Complications

Perforation of the uterus during suction curettage sometimes occurs because the uterus is large and boggy. If perforation is noted, the procedure should be completed under laparoscopic guidance.

Hemorrhage is a frequent complication during the evacuation of a molar pregnancy. For this reason, intravenous oxytocin should be started at the initiation of the suctioning. Methergine and/or Hemabate should also be available. Blood for possible transfusion should be readily available.

Malignant trophoblastic disease develops in 20% of molar pregnancies. For this reason, quantitative hCG should be serially monitored as described above.

Factors released by the molar tissue could trigger the coagulation cascade. Patients should be monitored for disseminated intravascular coagulopathy (DIC).

Trophoblastic embolism could cause acute respiratory insufficiency.[25]  The greatest risk factor for this complication is a uterus larger than that expected for a gestational age of 16 weeks. The condition may be fatal.

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Patient Education

Because of the small but real potential for development of malignant disease and because these malignancies are absolutely curable, the importance of consistent follow-up care must be emphasized.

To avoid any confusion about the development of malignant disease, the patient must avoid pregnancy during the period of follow-up described above. Effective contraception should be used. If a pregnancy occurs, the elevation in beta-hCG levels cannot be differentiated from the disease process.

Future pregnancies should undergo early sonographic evaluation because of the increased risk of recurrence of a molar gestation.

The risk of recurrence is 1-2%. After 2 or more molar pregnancies, the risk of recurrence has been reported as 1 in 6.5 to 1 in 17.5.[26]

For patient education resources, see the Pregnancy Center as well as Birth Control Overview and Birth Control Methods.

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Contributor Information and Disclosures
Author

Lisa E Moore, MD, FACOG Professor, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Lisa E Moore, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Enrique Hernandez, MD, FACOG, FACS Chairman, Department of Obstetrics and Gynecology, Director of Gynecologic Oncology, Abraham Roth Professor of Obstetrics, Gynecology and Reproductive Science, Professor of Pathology, Temple University Hospital, Temple University School of Medicine

Enrique Hernandez, MD, FACOG, FACS is a member of the following medical societies: Alpha Omega Alpha, American Cancer Society, Association of Professors of Gynecology and Obstetrics, Pennsylvania Medical Society, Philadelphia County Medical Society, Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, Johns Hopkins Medical and Surgical Association, American Gynecological and Obstetrical Society, American College of Obstetricians and Gynecologists, American College of Surgeons, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

A David Barnes, MD, MPH, PhD, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, CA), Pioneer Valley Hospital (Salt Lake City, UT), Warren General Hospital (Warren, PA), and Mountain West Hospital (Tooele, UT)

A David Barnes, MD, MPH, PhD, FACOG is a member of the following medical societies: American College of Forensic Examiners Institute, American College of Obstetricians and Gynecologists, Association of Military Surgeons of the US, American Medical Association, Utah Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Warner K Huh, MD Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine

Warner K Huh, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, Massachusetts Medical Society, Society of Gynecologic Oncology, American Society of Clinical Oncology

Disclosure: I have received consulting fees for: Merck; THEVAX.

Additional Contributors

Jordan G Pritzker, MD, MBA, FACOG Adjunct Professor of Obstetrics/Gynecology, Hofstra North Shore-LIJ School of Medicine at Hofstra University; Attending Physician, Department of Obstetrics and Gynecology, Long Island Jewish Medical Center; Medical Director, Aetna, Inc; Private Practice in Gynecology

Disclosure: Nothing to disclose.

References
  1. Schorge JO, Goldstein DP, Bernstein MR, Berkowitz RS. Recent advances in gestational trophoblastic disease. J Reprod Med. 2000 Sep. 45(9):692-700. [Medline].

  2. Ito Y, Maehara K, Kaneki E, et al. Novel nonsense mutation in the NLRP7 gene associated with recurrent hydatidiform mole. Gynecol Obstet Invest. 2015 Nov 26. [Medline].

  3. Wolf NG, Lage JM. Genetic analysis of gestational trophoblastic disease: a review. Semin Oncol. 1995 Apr. 22(2):113-20. [Medline].

  4. Slim R, Mehio A. The genetics of hydatidiform moles: new lights on an ancient disease. Clin Genet. 2007 Jan. 71(1):25-34. [Medline].

  5. Fisher RA, Hodges MD. Genomic imprinting in gestational trophoblastic disease--a review. Placenta. 2003 Apr. 24 Suppl A:S111-8. [Medline].

  6. Al-Hussaini TK, Abd el-Aal DM, Van den Veyver IB. Recurrent pregnancy loss due to familial and non-familial habitual molar pregnancy. Int J Gynaecol Obstet. 2003 Nov. 83(2):179-86. [Medline].

  7. Fallahian M. Familial gestational trophoblastic disease. Placenta. 2003 Aug. 24(7):797-9. [Medline].

  8. Hodges MD, Rees HC, Seckl MJ, et al. Genetic refinement and physical mapping of a biparental complete hydatidiform mole locus on chromosome 19q13.4. J Med Genet. 2003 Aug. 40(8):e95. [Medline].

  9. Lawler SD, Fisher RA, Dent J. A prospective genetic study of complete and partial hydatidiform moles. Am J Obstet Gynecol. 1991 May. 164(5 Pt 1):1270-7. [Medline].

  10. Deveault C, Qian JH, Chebaro W, et al. NLRP7 mutations in women with diploid androgenetic and triploid moles: a proposed mechanism for mole formation. Hum Mol Genet. 2009 Mar 1. 18(5):888-97. [Medline].

  11. Watson EJ, Hernandez E, Miyazawa K. Partial hydatidiform moles: a review. Obstet Gynecol Surv. 1987 Sep. 42(9):540-4. [Medline].

  12. Atrash HK, Hogue CJ, Grimes DA. Epidemiology of hydatidiform mole during early gestation. Am J Obstet Gynecol. 1986 Apr. 154(4):906-9. [Medline].

  13. Grimes DA. Epidemiology of gestational trophoblastic disease. Am J Obstet Gynecol. 1984 Oct 1. 150(3):309-18. [Medline].

  14. Jeffers MD, O'Dwyer P, Curran B, Leader M, Gillan JE. Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis. Int J Gynecol Pathol. 1993 Oct. 12(4):315-23. [Medline].

  15. Palmer JR. Advances in the epidemiology of gestational trophoblastic disease. J Reprod Med. 1994 Mar. 39(3):155-62. [Medline].

  16. Bandy LC, Clarke-Pearson DL, Hammond CB. Malignant potential of gestational trophoblastic disease at the extreme ages of reproductive life. Obstet Gynecol. 1984 Sep. 64(3):395-9. [Medline].

  17. Bracken MB. Incidence and aetiology of hydatidiform mole: an epidemiological review. Br J Obstet Gynaecol. 1987 Dec. 94(12):1123-35. [Medline].

  18. Hurteau JA. Gestational trophoblastic disease: management of hydatidiform mole. Clin Obstet Gynecol. 2003 Sep. 46(3):557-69. [Medline].

  19. 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 May-Jun. 59(5-6):188-94. [Medline].

  20. Joneborg U, Eloranta S, Johansson AL, Marions L, Weibull CE, Lambe M. Hydatidiform mole and subsequent pregnancy outcome: a population-based cohort study. Am J Obstet Gynecol. 2014 Dec. 211(6):681.e1-7. [Medline].

  21. Lurain JR, Brewer JI, Torok EE, Halpern B. Natural history of hydatidiform mole after primary evacuation. Am J Obstet Gynecol. 1983 Mar 1. 145(5):591-5. [Medline].

  22. Goto S, Yamada A, Ishizuka T, Tomoda Y. Development of postmolar trophoblastic disease after partial molar pregnancy. Gynecol Oncol. 1993 Feb. 48(2):165-70. [Medline].

  23. Cheung AN, Khoo US, Lai CY, et al. Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole: genotyping and chromosome in situ hybridization analysis. Cancer. 2004 Apr 1. 100(7):1411-7. [Medline].

  24. Menczer J, Girtler O, Zajdel L, Glezerman M. Metastatic trophoblastic disease following partial hydatidiform mole: case report and literature review. Gynecol Oncol. 1999 Aug. 74(2):304-7. [Medline].

  25. Twiggs LB, Morrow CP, Schlaerth JB. Acute pulmonary complications of molar pregnancy. Am J Obstet Gynecol. 1979 Sep 15. 135(2):189-94. [Medline].

  26. 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 Jan. 110(1):22-6. [Medline].

  27. Mangili G, Garavaglia E, Cavoretto P, Gentile C, Scarfone G, Rabaiotti E. Clinical presentation of hydatidiform mole in northern Italy: has it changed in the last 20 years?. Am J Obstet Gynecol. 2008 Mar. 198(3):302.e1-4. [Medline].

  28. Soto-Wright V, Bernstein M, Goldstein DP, Berkowitz RS. The changing clinical presentation of complete molar pregnancy. Obstet Gynecol. 1995 Nov. 86(5):775-9. [Medline].

  29. Sun SY, Melamed A, Goldstein DP, et al. Changing presentation of complete hydatidiform mole at the New England Trophoblastic Disease Center over the past three decades: does early diagnosis alter risk for gestational trophoblastic neoplasia?. Gynecol Oncol. 2015 Jul. 138 (1):46-9. [Medline].

  30. Amir SM, Osathanondh R, Berkowitz RS, Goldstein DP. Human chorionic gonadotropin and thyroid function in patients with hydatidiform mole. Am J Obstet Gynecol. 1984 Nov 15. 150(6):723-8. [Medline].

  31. Sun SY, Melamed A, Joseph NT, et al. Clinical presentation of complete hydatidiform mole and partial hydatidiform mole at a regional trophoblastic disease center in the United States over the past 2 decades. Int J Gynecol Cancer. 2015 Nov 19. [Medline].

  32. Berkowitz RS, Goldstein DP, Bernstein MR. Natural history of partial molar pregnancy. Obstet Gynecol. 1985 Nov. 66(5):677-81. [Medline].

  33. Fishman DA, Padilla LA, Keh P, Cohen L, Frederiksen M, Lurain JR. Management of twin pregnancies consisting of a complete hydatidiform mole and normal fetus. Obstet Gynecol. 1998 Apr. 91(4):546-50. [Medline].

  34. Steller MA, Genest DR, Bernstein MR, Lage JM, Goldstein DP, Berkowitz RS. Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus. Obstet Gynecol. 1994 Jan. 83(1):35-42. [Medline].

  35. Florio P, Severi FM, Cobellis L, et al. Serum activin A and inhibin A. New clinical markers for hydatidiform mole. Cancer. 2002 May 15. 94(10):2618-22. [Medline].

  36. Fulop V, Mok SC, Berkowitz RS. Molecular biology of gestational trophoblastic neoplasia: a review. J Reprod Med. 2004 Jun. 49(6):415-22. [Medline].

  37. Fukunaga M. Immunohistochemical characterization of p57(KIP2) expression in early hydatidiform moles. Hum Pathol. 2002 Dec. 33(12):1188-92. [Medline].

  38. Genest DR, Dorfman DM, Castrillon DH. Ploidy and imprinting in hydatidiform moles. Complementary use of flow cytometry and immunohistochemistry of the imprinted gene product p57KIP2 to assist molar classification. J Reprod Med. 2002 May. 47(5):342-6. [Medline].

  39. Thaker HM, Berlin A, Tycko B, et al. Immunohistochemistry for the imprinted gene product IPL/PHLDA2 for facilitating the differential diagnosis of complete hydatidiform mole. J Reprod Med. 2004 Aug. 49(8):630-6. [Medline].

  40. Benachi A, Garritsen HS, Howard CM, Bennett P, Fisk NM. Absence of expression of RhD by human trophoblast cells. Am J Obstet Gynecol. 1998 Feb. 178 (2):294-9. [Medline].

  41. Eddy GL, Schlaerth JB, Nalick RH, Gaddis O Jr, Nakamura RM, Morrow CP. Postmolar trophoblastic disease in women using hormonal contraception with and without estrogen. Obstet Gynecol. 1983 Dec. 62(6):736-40. [Medline].

  42. 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 Jan 14. 379(9811):130-5. [Medline].

  43. 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 Jun. 114(6):760-2. [Medline].

  44. Batorfi J, Vegh G, Szepesi J, et al. How long should patients be followed after molar pregnancy? Analysis of serum hCG follow-up data. Eur J Obstet Gynecol Reprod Biol. 2004 Jan 15. 112(1):95-7. [Medline].

  45. Feltmate CM, Batorfi J, Fulop V, et al. Human chorionic gonadotropin follow-up in patients with molar pregnancy: a time for reevaluation. Obstet Gynecol. 2003 Apr. 101(4):732-6. [Medline].

  46. Garner EI, Lipson E, Bernstein MR, Goldstein DP, Berkowitz RS. Subsequent pregnancy experience in patients with molar pregnancy and gestational trophoblastic tumor. J Reprod Med. 2002 May. 47(5):380-6. [Medline].

  47. Amezcua CA, Bahador A, Naidu YM, Felix JC. Expression of human telomerase reverse transcriptase, the catalytic subunit of telomerase, is associated with the development of persistent disease in complete hydatidiform moles. Am J Obstet Gynecol. 2001 Jun. 184(7):1441-6. [Medline].

 
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Theca lutein cysts.
Complete mole.
Complete mole with an area of clot near cervix consistent with bleeding.
Twin gestation. Complete mole and normal twin.
 
 
 
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