Hydatidiform Mole (Molar Pregnancy)

Notes

Early Pregnancy | Obstetric Conditions | Obstetrics and Gynecology

Overview

Hydatidiform moles are part of a group of diseases falling under gestational trophoblastic disease. A hydatidiform mole refers to the abnormal growth of trophoblastic cells in the placenta, resulting in edematous placental villi that form hydatidiform structures. It is classified as either partial or complete, causing either abnormal foetal development (resulting in foetal demise) or the prevention of foetal development completely, respectively. It is often identified within the first trimester of pregnancy, usually ending in miscarriage. Key features of hydatidiform moles may include first-trimester PV bleeding and severe nausea and vomiting.

Molar pregnancies are rare, affecting 1 in 1000 pregnancies in Australia, with the major risk factor being older maternal age. Molar pregnancies commonly end in miscarriage due to incompatibility with life. Early detection of a molar pregnancy reduces morbidity from uterine evacuation. Further, surveillance of B-hCG is crucial for the detection of complications such as cancer.^1,2

Definition

Hydatidiform mole – An abnormal pregnancy with trophoblastic proliferation and hydropic swelling of chorionic villi, resulting in a non-viable conception.
Gestational trophoblastic disease – A spectrum of pregnancy-related disorders arising from trophoblasts, including hydatidiform mole, invasive mole, choriocarcinoma, and PSTT.
Trophoblast – Placental cells (cytotrophoblasts and syncytiotrophoblasts) that normally form the chorionic villi and produce hCG.
Chorionic villi – Finger-like projections of the placenta that become swollen, oedematous, and avascular in hydatidiform mole.

Anatomy/ Physiology

In normal pregnancy, fertilisation refers to the fusion of one haploid maternal gamete (oocyte) and one haploid paternal gamete (sperm), resulting in a diploid zygote containing one set of chromosomes from each parent. After fertilisation, the zygote continues to proliferate to form a solid ball of cells. This then hollows out to form a blastocyst, ready to implant into the uterus. A blastocyst is one cell thick (made of trophoblasts), except on one side of the blastocyst, which has the inner cell mass (about 3-4 cells thick). The inner cell mass develops into the embryo, and the outer trophoblasts form the placenta (see image below).

The placenta produces several hormones to support the pregnancy. Notably, human chorionic gonadotropin (hCG) is produced to prevent further ovulation and to increase the production of estrogen and progesterone.³

Risk Factors

Established risk factors for abnormal fertilisation include a previous history of molar pregnancy and advancing age. There is a 2.5- and 5-fold increased risk of molar pregnancy in mothers over the age of 35 and 40, respectively.¹

Pathophysiology

Hydatidiform moles arise from abnormal genetic material fusion during fertilisation.
Complete mole:
- Occurs when an empty ovum is fertilised by 1 or 2 sperms.
- Results in diploidy with purely paternal genetic material.
Partial mole:
- Occurs when a viable ovum is fertilised by 2 or more sperms.
- Results in triploidy, with excess paternal genetic contribution.
After implantation, the abnormal genetic fusion causes:
- Excessive proliferation of trophoblasts
- Hydropic (oedematous) swelling of chorionic villi
Morphological differences:
- Complete mole → diffuse hydrops, no fetal tissue
- Partial mole → focal hydrops, some fetal development
Clinical consequence:
- Excessive trophoblastic proliferation leads to markedly elevated serum hCG
- Produces exaggerated pregnancy symptoms (e.g., hyperemesis, early pre-eclampsia, ovarian cysts)

Classification

Belongs to the spectrum of gestational trophoblastic disease. There are three broad groups.

Non-neoplastic trophoblastic lesions

Exaggerated placental site reaction (EPS)
Placental site nodule (PSN) / atypical PSN

Pre-malignant GTD (Hydatidiform mole)
- Complete hydatidiform mole (CHM)
- Partial hydatidiform mole (PHM)
Malignant GTD = Gestational Trophoblastic Neoplasia (GTN)
- Invasive mole
- Choriocarcinoma
- Placental-site trophoblastic tumour (PSTT)
- Epithelioid trophoblastic tumour (ETT)

Hydatidiform mole (molar pregnancy) there are two types:

Complete Hydatidiform mole
Partial Hydatidiform mole

Feature	Complete Mole	Partial Mole
Genetic origin	Empty ovum + 1/2 sperm → 46,XX/XY paternal only	Normal ovum + 2 sperm → 69,XXX/XXY
Fetal tissue	Absent	Present/abnormal
Villous oedema	Diffuse	Focal
Trophoblastic proliferation	Diffuse, circumferential	Focal, mild
hCG levels	Very high	Mildly elevated
Risk of malignancy	15–20% (higher)	1–5% (lower)

Histopathology

Complete	Partial
Poorly vascularised chorionic villiHydropic swellingOedematous stromaCistern with stromal fluid	Less trophoblastic proliferationFocal distribution of proliferative areasSparse regions of oedematous villi

Remember

Complete mole = completely paternal → empty ovum, no fetus, diffuse trophoblastic proliferation, very high hCG.

Remember

Partial mole = partly maternal → abnormal fetus present, triploidy, focal villous changes, lower hCG than complete mole.

Clinical manifestations

Severe nausea and vomiting/hyperemesis gravidarum
Pelvic pressure/pain
High blood pressure, may result in pre-eclampsia if pregnancy continues longer
Clinical features of miscarriage: PV bleeding (usually dark red), abdominal pain
Uterine size:
- Complete mole: larger than expected for gestational age
- Partial mole: small than expected for gestational age
Later sign: clinical features of anaemia: fatigue, SOB, dizziness, pallor
Later sign: clinical features of thyrotoxicosis: tachycardia, tremors, diarrhoea, insomnia, anxiety

Think

Picture molar pregnancies as an exaggerated pregnancy: e.g., larger uterus, severe nausea and vomiting, anaemia and thyroid issues .

Think

Very high β-hCG → may cause exaggerated pregnancy symptoms (hyperemesis gravidarum, hyperthyroidism, theca lutein cysts).

Remember

Pre-eclampsia before 20 weeks → pathognomonic for molar pregnancy until proven otherwise.

Diagnosis

First line investigation: ultrasonography

Complete mole:
- anechoic cystic spaces resembling “grape clusters”
- echogenic mass
- “snowstorm” appearance’
Partial moles
- May contain fetal parts on USS

Other investigations

Baseline Serum bHcg: frequently >100,000 mIU/mL
TSH: may be elevated

Definitive (gold standard)^:Dilation and curretage with histopathology

Complete moles:
- edematous hydropic villi
- circumferential and hyperplastic trophoblastic cells
partial moles:
- large hydropic villi
- small fibrotic villi.

Remember

“Snowstorm” or “cluster of grapes” ultrasound → hallmark of complete mole, no fetus seen.

Differential Diagnosis

Abnormal villous morphology
Hyperemesis gravidarum
Gestational trophoblastic neoplasia
Hyperthyroidism or other causes of thyrotoxicosis
Trophoblastic hyperplasia resulting in abortion
Hypertension in pregnancy

Treatment

General measures

Evacuation of uterus via suction curettage
Anti-D immunoglobulin for Rh-negative women
Weekly serum B-Hcg until 3 consecutive weeks are in normal range (surveillance for gestational trophoblastic neoplasia), then monthly
- Partial: after 3 consecutive normals, do not need anymore
- Complete: continue surveillance for 6 months, monthly

Chemotherapy (methotrexate or actinomycin-D):

Indicated if hCG plateaus/rises → persistent GTD (typically complete molar)

Complications and Prognosis

Complications

The most alarming complication of Gestational Trophoblastic Disease is Gestational Trophoblastic Neoplasia (GTN), a pregnancy-related cancerous tumour. B-Hcg surveillance as outlined above is the gold standard investigation for monitoring of GTN.

GTN occurs in 15-20% of complete moles
GTN occurs in 0.5-5% of partial moles
2–3% of complete moles progress to choriocarcinoma

Prognosis

Excellent with treatment
- Cure rates approach 100% with uterine evacuation and appropriate follow-up.
- Chemotherapy (methotrexate, actinomycin-D) is highly effective for persistent GTD or choriocarcinoma.
Choriocarcinoma: >90% survival if treated early, worse with brain/liver metastases.
Most women retain fertility after treatment.

Remember

β-hCG surveillance is vital for preventing GTN. It must be measured at baseline, then weekly, until it returns to normal for 3 consecutive weeks. Then, if a complete molar pregnancy, continue monitoring monthly for 6 months.

References

Cue L, Farci F, Ghassemzadeh S, et al. Hydatidiform Mole. Treasure Island (FL): StatPearls Publishing; 2024.https://www.ncbi.nlm.nih.gov/books/NBK459155/
The Women’s. Hydatidiform mole. The Royal Women’s Hospital. Accessed July 10, 2025. https://www.thewomens.org.au/health-information/pregnancy-and-birth/pregnancy-problems/early-pregnancy-problems/hydatidiform-mole
Munoz JL. Stages of fetal development. MSD Manual; 2024 [Update 2024 Nov; cited 2025 Jul 13]. Available from: https://www.msdmanuals.com/home/women-s-health-issues/normal-pregnancy/stages-of-fetal-development
Lepore A, Conran RM. Educational Case: Hydatidiform Molar Pregnancy. Acad Pathol. 2021;8:2374289520987256. doi: 10.1177/2374289520987256.
Yu Y. Molar Pregnancy. Radiopedia. May 18 2024. Accessed July 10, 2025. https://radiopaedia.org/articles/molar-pregnancy-2
Duggan P, Leung Y, Neesham D, McNally O, Garrett A, Brand A, Vaughn M, Skyes P. Management of gestational trophoblastic disease. RANZCOG. 2020;31.