Molar pregnancy (hydatiform mole)

Refers to an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus and converts a normal pregnancy into an abnormal one.

A gestational trophoblastic disease that grows into a mass in the uterus that has swollen chorionic villi.

Hydropic/swollen chorionic villi lead to small cystic spaces, creating a vascular pattern on ultrasound.

Occurs as a result of abnormal fertilization is characterized as complete or partial based on differences in morphology, karyotype, and malignant potential.

Most complete moles, 80%, occur as a result of the abnormal fertilization of the ovum lacking nuclear DNA, and have two identical paternal chromosome complement derived from duplication of the haploid genome of a single sperm.

The remaining 20% occur as a result of fertilization by 2 sperm.

Partial moles occur when a ovum retains its nucleus and abnormal fertilization occurs by-fertilization by single sperm with subsequent paternal chromosome duplication or by dispermy.

Partial hydatidiform moles (HM) contain fetal tissue, but complete moles do not.

Partial hydatidiform moles tend to grow more slowly and may present later in the first early second trimester, often with symptoms of incomplete or missed abortion and diagnosis made on histological examination of the curettage specimen.
Trophoblastic villi grow in clusters that resemble grapes.

Can develop when an egg that is missing its nucleus is fertilized.

It is characterized by the presence of a hydatidiform mole.

Hydatidiform moles are benign, pre-malignant disease.

Molar pregnancies are categorized into partial and complete moles.

Mole refers to mass of growing tissue.

Patients with MP commonly present with vaginal bleeding, typically around 6-16 weeks of gestation.
Most cases are detected before the onset of additional signs such as uterine enlargement beyond the expected for gestation date, preeclampsia, hyperemesis, anemia, and theca luteum  ovarian cysts, because of ultrasound screening and accurate hCG testing.

A complete hydatiform mole is caused by a single (90% of cases) or two (10% of cases) sperm combining with an egg which has lost its DNA.

A complete hydatiform mole has a genotype that is typically 46,XX (diploid) due to subsequent mitosis of the fertilizing sperm, but can also be 46,XY (diploid).

In complete moles, all the chorionic villi are vesicular, and there are no signs of embryonic or fetal development.

A partial hydatiform mole occurs when an egg is fertilized by one sperm or two sperm which reduplicates itself yielding the genotypes of 69,XXY (triploid) or 92,XXXY (tetraploid).

In partial moles some villi are vesicular, and others appear more normal, and embryonic/fetal development may be seen but the fetus is always malformed and is never viable.

Complete hydatidiform moles have a higher risk of developing into choriocarcinoma, a malignant tumor of trophoblast cells, than do partial moles.

A hydatidiform mole may be categorized as a missed miscarriage, because the pregnancy has become non-viable, and miscarried, but was not immediately expelled and noticed.

Malignant forms of gestational trophoblastic disease are collectively referred to as gestational trophoblastic neoplasia and include invasive mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor.

In a hydatidiform mole pregnancy the placenta contains grapelike vesicles that are usually visible with the naked eye.

The hydatiform mole vesicles arise by distention of the chorionic villi by fluid, with hyperplasia of the trophoblastic tissue.

If left untreated, a hydatidiform mole will almost always end as a spontaneous abortion.

Common complication of pregnancy, occurring once in every 1000 pregnancies in the US.

Molar pregnancies associated with much higher rates in Asia up to one in 100 pregnancies.

In rare cases can co-exist in the uterus with a normal, viable fetus.

The etiology is unknown, but risk factors may include defects in the egg, abnormalities within the uterus, or nutritional deficiencies with diets low in protein, folic acid, and carotene.

With the availability of both ultrasound and hCG measurements have led to earlier diagnosis of completed hydatidiform.

If a patient presents with irregular bleeding during pregnancy, ultrasound and hCG measurements, only obtained and me diagnose an abnormal pregnancy, leading to pregnancy termination.

Women under 20 or over 40 years of age have a higher risk.

The diploid set of sperm-only DNA leads to overgrowth of the syncytiotrophoblast whereas dual egg-patterned methylation leads to a devotion of resources to the embryo, with an underdeveloped syncytiotrophoblast.

In most complete moles, all nuclear genes are inherited from the father.

Such pregnancies usually present with painless vaginal bleeding in the fourth to fifth month of pregnancy, and the uterus may be larger than expected.

The ovaries may be enlarged.

May be associated with hyperemesis, hypertension and proteinuria.

Blood tests will show very high levels of human chorionic gonadotropin (hCG).

The diagnosis is suggested by ultrasound, resembling a bunch of grapes.

Definitive diagnosis requires histopathological examination.

Histologically there is increased trophoblast proliferation and enlarging of the chorionic villi.

Rarely associated with symptoms of hyperthyroidism due to the extremely high levels of hCG, which can mimic the normal thyroid-stimulating hormone.

Treated by evacuating the uterus by uterine suction or by surgical curettage as soon as possible.

Early recognition and treatment after diagnosis avoids the risks of choriocarcinoma.

Following uterine evacuation The serum human chorionic gonadotrophin has falls to undetectable level.

Invasive or metastatic moles require chemotherapy with methotrexate, with a nearly 100% response rate.

Patients are advised not to conceive for one year after a molar pregnancy, and the chances of having another molar pregnancy are approximately 1%.

Management is more complicated when the mole occurs together with one or more normal fetuses.

Carboprost (PGF2α) medication may be used to contract the uterus.

More than 80% of cases are benign.

In 10 to 15% of cases, hydatidiform moles may develop into invasive moles, named persistent trophoblastic disease (PTD),

In persistent trophoblastic disease moles may invade the uterine wall such that hemorrhage or other complications develop after evacuation.

In 2 to 3% of cases, hydatidiform moles may develop into choriocarcinoma.

Choriocarcinoma is a malignant, rapidly-growing, and metastatic form of cancer.

Over 90% of women with malignant, non-spreading moles are able to survive and retain their ability to conceive.

In patients with metastatic remission rate at 75 to 85%, although their childbearing ability is diminished.

The prognosis of hydatidiform moles can be estimated by the Modified WHO Prognostic Scoring System, wherein scores between 1 and 4 from various parameters are summed.

Modified WHO Prognostic Scoring System staged 0 1 2 4.

Criteria include: Age <40 ≥40,

Antecedent pregnancy status

Interval months from index pregnancy <4 4–6 7–12 >12

Pretreatment serum hCG (IU/L) <103 103–104 104–105 >105

Largest tumor size (including uterus) <3 3–4 cm ≥5 cm

Site of metastases lung spleen, kidney gastrointestinal liver, brain

Number of metastases – 1–4 5–8 >8

Previous failed chemotherapy – – single drug ≥2 drugs

Women with a score of 7 or greater are considered at high risk.

Follow up with hCG monitoring monitoring is essential after initial treatment of HM, to ensure that hCG levels return to normal.
Post molar gestational trophoblastic nrolasia develops in about 15% to 20% of complete moles, but in only 1-6 5% of partial moles.
The risk of recurrence is low, less than 2%, after a single molar pregnancy but increases significantly for women who experience one or more recurrences.
Following normalization of hCG a gestational trophoblastic neoplasia development is rare, and the recommended follow up, is  months monitoring.
Repeat dilatation and curettage or hysterectomy is considered for persistent post molar gestational trophoblastic neoplasia.

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