Abnormal Development - Hydatidiform Mole

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Hydatidiform Mole

(hydatidiform mole, hydatid mole, molar pregnancy, gestational trophoblastic disease) A type of fertilisation abnormality, when only the conceptus trophoblast layers proliferates and not the embryoblast, no embryo develops, this is called a "hydatidiform mole". Due to the continuing presence of the trophoblastic layer, this abnormal conceptus can also implant in the uterus or ectopically. The trophoblast cells will secrete human chorionic gonadotropin (hCG), as in a normal pregnancy, and may appear maternally and by pregnancy test to be "normal". Prenatal diagnosis by ultrasound analysis demonstrates the absence of a embryo.

  • Complete Mole - Only paternal chromosomes.
  • Partial Mole - 3 sets of chromosomes ( (triploidy) instead of the usual 2.

There are several forms of hydatidiform mole: partial mole, complete mole and persistent gestational trophoblastic tumor. Many of these tumours arise from a haploid sperm fertilizing an egg without a female pronucleus (the alternative form, an embryo without sperm contribution, is called parthenogenesis). The tumour has a "grape-like" placental appearance without enclosed embryo formation. Following a first molar pregnancy, there is approximately a 1% risk of a second molar pregnancy.

  • The incidence of hydatidiform mole varies between ethnic groups, and typically occurs in 1 in every 1500 pregnancies.
  • All hydatidiform mole cases are sporadic, except for extremely rare familial cases.
  • A maternal gene has been identified for recurrent hydatidiform mole (chromosome 19q13.3-13.4 in a 15.2 cM interval flanked by D19S924 and D19S890).[1]

Links: hydatidiform mole | fertilization | meiosis | oocyte | Week 2 - Abnormalities | Placenta - Abnormalities | Abnormal Development
  Historic: 1920 Hydatiform Degeneration | 1921 Hydatiform Degeneration in Uterine Pregnancy | 1921 Hydatiform Degeneration in Tubal Pregnancy

Some Recent Findings

  • Identification of nonsynonymous TP53 mutations in hydatidiform moles[2] "Here we screened for specific missense mutations on several TP53 hotspots in 49 HMs using a highly sensitive pyrosequencing approach and revealed the significant existence of such mutations in HM tissues. A particularly high frequency (∼59% of the cases) of p53 inactivating mutation on exon 7 has been detected. Our identification of hitherto unreported TP53 mutations in HM suggests the presence of p53 mutants and reflects the advantages of using pyrosequencing for point mutation detection in clinical samples. Traditional sequencing method may have overlooked such mutations that only occur in a small population of trophoblasts."
  • Gestational Trophoblastic Disease: Clinical and Imaging Features[3] "Gestational trophoblastic disease (GTD) is a spectrum of both benign and malignant gestational tumors, including hydatidiform mole (complete and partial), invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. The latter four entities are referred to as gestational trophoblastic neoplasia (GTN). These conditions are aggressive with a propensity to widely metastasize. GTN can result in significant morbidity and mortality if left untreated. ...While GTN after a molar pregnancy is usually diagnosed with serial β-hCG titers, imaging plays an important role in evaluation of local extent of disease and systemic surveillance. Imaging also plays a crucial role in detection and management of complications, such as uterine and pulmonary arteriovenous fistulas."
  • Risk of recurrent molar pregnancies following complete and partial hydatidiform moles[4] "What is the risk of further molar pregnancies for women with one or more hydatidiform moles (HM) in relation to molar subtype. SUMMARY ANSWER: Women with a complete hydatidiform mole (CM) have a 1 in 100 and 1 in 4 risk of further CM after one or two consecutive CM, respectively, while women with a partial hydatidiform mole (PM) have only a small increase in risk for further molar pregnancies. WHAT IS KNOWN ALREADY: Women with a molar pregnancy have an increased risk of further HM. A small subgroup of women with recurrent HM has an autosomal recessive condition, familial recurrent hydatidiform moles (FRHM), that predisposes them to molar pregnancies."
  • NLRP7, Involved in Hydatidiform Molar Pregnancy (HYDM1), Interacts with the Transcriptional Repressor ZBTB16[5] "Mutations in the maternal effect gene NLRP7 cause biparental hydatidiform mole (HYDM1). HYDM1 is characterized by abnormal growth of placenta and lack of proper embryonic development. The molar tissues are characterized by abnormal methylation patterns at differentially methylated regions (DMRs) of imprinted genes. It is not known whether this occurs before or after fertilization, but the high specificity of this defect to the maternal allele indicates a possible maternal germ line-specific effect. ...Hence, the biological significance of the NLRP7-ZBTB16 interaction remains to be revealed. However, a clear effect of harvesting ZBTB16 to the cytoplasm when the NLRP7 protein is overexpressed may be linked to the pathology of the molar pregnancy disease." Molecular Development - Epigenetics
  • Minimally-aggressive gestational trophoblastic neoplasms[6] "We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome."
More recent papers  
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Search term: Hydatidiform Mole

Christophe Desterke, Rima Slim, Jean-Jacques Candelier A bioinformatics transcriptome meta-analysis highlights the importance of trophoblast differentiation in the pathology of hydatidiform moles. Placenta: 2018, 65;29-36 PubMed 29908639

B Kaur, N J Sebire ##Title## BJOG: 2018; PubMed 29904999

Pierre-Adrien Bolze, Mélodie Mathe, Touria Hajri, Benoit You, Yohann Dabi, Anne-Marie Schott, Sophie Patrier, Jérôme Massardier, François Golfier First-line hysterectomy for women with low-risk non-metastatic gestational trophoblastic neoplasia no longer wishing to conceive. Gynecol. Oncol.: 2018; PubMed 29887485

Houssine Boufettal, Naïma Samouh Invasive hydatidiform mole in the cervix. Pan Afr Med J: 2018, 29;27 PubMed 29875909

Yuto Maeda, Ruriko Oyama, Hirona Maeda, Yukihiro Imai, Shinya Yoshioka Choriocarcinoma with multiple lung metastases from complete hydatidiform mole with coexistent fetus during pregnancy. J. Obstet. Gynaecol. Res.: 2018; PubMed 29845692

International Classification of Diseases


Hydatidiform mole

Use additional code from category O08.-, if desired, to identify any associated complication.

Excl.: malignant hydatidiform mole (D39.2)

  • O01.0 - Classical hydatidiform mole
    • Complete hydatidiform mole
  • O01.1 - Incomplete and partial hydatidiform mole
  • O01.9 - Hydatidiform mole, unspecified
    • Trophoblastic disease NOS
    • Vesicular mole NOS
  • O08 - Complications following abortion and ectopic and molar pregnancy

Note: This code is provided primarily for morbidity coding. For use of this category reference should be made to the morbidity coding rules and guidelines in Volume 2.

  • D39.2 8 Placenta
    • Chorioadenoma destruens
    • Hydatidiform mole:
      • invasive
      • malignant

Excl.: hydatidiform mole NOS (O01.9)

Mole Types

Complete mole pathology and multiple fibroids within the uterus.[7]

Complete Mole

Only paternal chromosomes.

  • Chromosomal genetic material from the ovum (egg) is lost, by an unknown process.
  • Fertilization then occurs with one or two sperm and an androgenic (from the male only) conceptus (fertilized egg) is formed.
  • With this conceptus the embryo (fetus, baby) does not develop at all but the placenta does grow.
  • placenta it is abnormal and forms lots of cysts and has no blood vessels.
  • These cysts look like a cluster of grapes and that is why it is called a hydatidiform ("grape-like") mole.
  • A hydatidiform mole miscarries by about 16 to 18 weeks gestational age.
  • Since the diagnosis can be made by ultrasound before that time, it is better to have an evacuation of the uterus (D & C) so that there is no undue bleeding and no infection.
  • Human chorionic gonadotropin (hCG) levels will assist in making the diagnosis.

Partial Mole

Ultrasound of partial mole confirmed by triploidy[8]

Three sets of chromosomes instead of the usual two and this is called triploidy.

  • chromosomal (genetic) material from the ovum (egg) is retained and the egg is fertilized by one or two sperm.
  • with partial mole there are maternal chromosomes and there is a fetus.
  • the three sets of chromosomes means the fetus is always grossly abnormal and will not survive.

(Text modified from: International Society for the Study of Trophoblastic Diseases, see also JRM Gestational Trophoblastic Disease)


  • Ultrasound can indicate the absence of an embryonic heartbeat and a "bunch of grapes" appearance.
  • HCG level (>100000 mIU/ml)
  • Excessive uterine enlargement
  • Theca lutein cyst size ≥6 cm are considered a high risk for developing post molar tumors

A recent retrospective study of a large patient cohort[9] identified clinical characteristics (table below) between the complete and partial hydatidiform moles types. After mole evacuation most patients in both groups reach normal serum hCG concentrations within 14 weeks.

Mole Type Average serum hCG Post hCG normalization Gestational age
complete 4400 ng/mL 7 weeks 11.5 weeks
partial 875 ng/mL 6 weeks 13.0 weeks

Tumour Growth

Like any tumour, unless removed there is a risk of progression:

  1. Stage I: Tumor confined to uterus (non-metastatic)
  2. Stage II: Tumor involving pelvic organs and/or vagina
  3. Stage III: Tumor involving lungs, with or without involving pelvic structures and/or vagina
  4. Stage IV: Tumor involving distant organs
Uterine and ovarian metastasis[10] Pulmonary metastasis[10]
Hydatidiform mole metastasis Hydatidiform mole pulmonary metastasis


A highly malignant epithelial tumour often associated with hydatidiform mole.

Placental Mesenchymal Dysplasia

A rare disorder due to a similar "grape-like" placental appearance, this rare disorder has been mistaken both clinically and macroscopically for a partial hydatidiform molar pregnancy. Characterized by an increased size placenta with cystic villi and dilated vessels. This disorder also has a high incidence of intrauterine growth restriction (IUGR) and fetal death.

Twin Pregnancy Mole

Hydatidiform mole and co-existent healthy fetus is a very rare condition with only 30 cases documented in detail in the literature.[11]

Ectopic Molar Pregnancy

Ectopic molar pregnancy 01.jpg

Left-sided unruptured ampullary ectopic pregnancy at laparoscopy.[12]

Links: Ectopic Implantation


  1. Moglabey YB, Kircheisen R, Seoud M, El Mogharbel N, Van den Veyver I & Slim R. (1999). Genetic mapping of a maternal locus responsible for familial hydatidiform moles. Hum. Mol. Genet. , 8, 667-71. PMID: 10072436
  2. Chan KK, Wong ES, Wong OG, Ngan HY & Cheung AN. (2018). Identification of nonsynonymous TP53 mutations in hydatidiform moles. Mutat. Res. , 809, 20-23. PMID: 29655027 DOI.
  3. Shaaban AM, Rezvani M, Haroun RR, Kennedy AM, Elsayes KM, Olpin JD, Salama ME, Foster BR & Menias CO. (2017). Gestational Trophoblastic Disease: Clinical and Imaging Features. Radiographics , 37, 681-700. PMID: 28287945 DOI.
  4. Eagles N, Sebire NJ, Short D, Savage PM, Seckl MJ & Fisher RA. (2015). Risk of recurrent molar pregnancies following complete and partial hydatidiform moles. Hum. Reprod. , 30, 2055-63. PMID: 26202916 DOI.
  5. Singer H, Biswas A, Nuesgen N, Oldenburg J & El-Maarri O. (2015). NLRP7, Involved in Hydatidiform Molar Pregnancy (HYDM1), Interacts with the Transcriptional Repressor ZBTB16. PLoS ONE , 10, e0130416. PMID: 26121690 DOI.
  6. Cole LA. (2012). Minimally-aggressive gestational trophoblastic neoplasms. Gynecol. Oncol. , 125, 145-50. PMID: 22198244 DOI.
  7. Aguilera M, Rauk P, Ghebre R & Ramin K. (2012). Complete hydatidiform mole presenting as a placenta accreta in a twin pregnancy with a coexisting normal fetus: case report. Case Rep Obstet Gynecol , 2012, 405085. PMID: 22928132 DOI.
  8. Kinare A. (2008). Fetal environment. Indian J Radiol Imaging , 18, 326-44. PMID: 19774194 DOI.
  9. Eysbouts Y, Brouwer R, Ottevanger P, Massuger L, Sweep F, Thomas C & van Herwaarden A. (2017). Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational Trophoblastic Neoplasia. Int. J. Gynecol. Cancer , 27, 1035-1041. PMID: 28498241 DOI.
  10. 10.0 10.1 Aminimoghaddam S & Maghsoudnia A. (2017). Unusual Presentation of Invasive Mole: A Case Report. J Reprod Infertil , 18, 205-209. PMID: 28377901
  11. Piura B, Rabinovich A, Hershkovitz R, Maor E & Mazor M. (2008). Twin pregnancy with a complete hydatidiform mole and surviving co-existent fetus. Arch. Gynecol. Obstet. , 278, 377-82. PMID: 18273627 DOI.
  12. Bousfiha N, Erarhay S, Louba A, Saadi H, Bouchikhi C, Banani A, El Fatemi H, Sekkal M & Laamarti A. (2012). Ectopic molar pregnancy: a case report. Pan Afr Med J , 11, 63. PMID: 22655097


Kani KK, Lee JH, Dighe M, Moshiri M, Kolokythas O & Dubinsky T. (2012). Gestatational trophoblastic disease: multimodality imaging assessment with special emphasis on spectrum of abnormalities and value of imaging in staging and management of disease. Curr Probl Diagn Radiol , 41, 1-10. PMID: 22085657 DOI.

Ronnett BM, DeScipio C & Murphy KM. (2011). Hydatidiform moles: ancillary techniques to refine diagnosis. Int. J. Gynecol. Pathol. , 30, 101-16. PMID: 21293291 DOI.

Sharp AN, Heazell AE, Crocker IP & Mor G. (2010). Placental apoptosis in health and disease. Am. J. Reprod. Immunol. , 64, 159-69. PMID: 20367628 DOI.

Seckl MJ, Sebire NJ & Berkowitz RS. (2010). Gestational trophoblastic disease. Lancet , 376, 717-29. PMID: 20673583 DOI.


Hong T, Hills E & Aguinaga MDP. (2017). Radiographically occult pulmonary metastases from gestational trophoblastic neoplasia. Radiol Case Rep , 12, 292-294. PMID: 28491173 DOI.

Jauniaux E & Verheijen R. (2016). Diagnosis and management of hydatidiform mole and its complications: 2000 years of a medical challenge. BJOG , 123, 1183. PMID: 27206034 DOI.

Cavaliere A, Ermito S, Dinatale A & Pedata R. (2009). Management of molar pregnancy. J Prenat Med , 3, 15-7. PMID: 22439034


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Cite this page: Hill, M.A. (2018, June 22) Embryology Abnormal Development - Hydatidiform Mole. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Hydatidiform_Mole

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