Author
Dr. Olusina D.O.
What You Will Learn
After reading this note, you should be able to...
- Define Gestational Trophoblastic Disease (GTD) and Molar Pregnancy.
- Identify the characteristic features of molar pregnancy, such as hydropic swelling and trophoblast hyperplasia.
- Recognize beta-hCG as a reliable tumor marker for molar pregnancy.
- Explain the variation in the incidence of molar pregnancy globally.
- Classify Molar Pregnancy into complete and partial types.
- Describe the macroscopic and microscopic differences between complete and partial moles.
- Distinguish complete and partial moles based on karyotype (diploid vs. triploid) and the presence or absence of fetal tissue.
- Identify the genetic origins of complete (androgenetic, biparental) and partial (triploid) moles.
- List key risk factors for molar pregnancy, including age, previous history, and diet.
- Recognize common clinical features and symptoms of molar pregnancy, such as abnormal uterine bleeding and hyperemesis.
- Identify diagnostic investigations used for molar pregnancy, including quantitative serum β-hCG and ultrasound.
- Explain the primary treatment method, which is suction evacuation.
- Discuss potential complications of treatment, such as hemorrhage and uterine perforation.
- Emphasize the critical importance of post-evacuation follow-up, particularly serial β-hCG monitoring.
- Identify criteria for the diagnosis of persistent GTD (GTN).
Note Summary
Molar pregnancy is a subtype of Gestational Trophoblastic Disease (GTD), originating from placental tissue and characterized by abnormal trophoblast proliferation and absent or abnormal fetal development. It is a significant form of GTD requiring prompt diagnosis, multidisciplinary management, and rigorous follow-up with β-hCG monitoring to ensure optimal outcomes. While having an excellent prognosis when treated early, there is a risk of progression to Gestational Trophoblastic Neoplasia (GTN), which is highly curable with chemotherapy.
- Definition and Nature of Molar Pregnancy:
- Molar pregnancy is a subtype of Gestational Trophoblastic Disease (GTD), which are tumors originating from the placenta.
- It arises from fetal tissue but involves an overproduction of chorionic tissue, which normally develops into the placenta.
- Key characteristics include hydropic swelling of the placental villi, hyperplasia of villous trophoblast, and absent or abnormal fetal development.
- These tumors originate from syncytiotrophoblastic and cytotrophoblastic cells.
- β-hCG is a reliable tumor marker for molar pregnancy.
- Molar pregnancy is the first and only disseminated solid tumor proven to be highly curable by chemotherapy, leading to the dictum: "God’s first cancer and man’s first cure."
- Epidemiology:
- Incidence varies globally, with a general rate of 1 per 1000 pregnancies worldwide.
- High-income countries see 1–3 per 1000 pregnancies.
- East Asia has a significantly higher incidence, 5- to 15-fold higher, approaching 1 in 120 pregnancies.
- West African countries show incidences ranging from 0.87–4.88 per 1000 deliveries (Nigeria) to 12.8 per 1000 deliveries (Tanzania).
- Classification of GTD and Molar Pregnancy:
- Molar pregnancy (Hydatidiform Mole) is the most common form of GTD and is benign in nature.
- Chromosomal abnormalities are integral to its development.
- Molar pregnancy is classified into:
- Complete Mole:
- Macroscopically resembles a bunch of grapes.
- Microscopically shows enlarged, edematous villi and abnormal trophoblastic proliferation throughout the placenta.
- No fetal tissue or amnion is produced.
- The mass of placental tissue completely fills the endometrial cavity.
- Arises from an empty ovum fertilized by sperm.
- Homozygous Form: Two identical paternal chromosome complements (46, XX) — 85–90% of complete moles.
- Heterozygous Form: Fertilized by two different sperms, resulting in 46, XX or 46, XY — 10–15%.
- Biparental Complete Hydatidiform Mole (CHM): Rare familial form due to failure of maternal imprinting.
- Partial Hydatidiform Mole (PHM):
- An ovum with an active nucleus fertilized by a duplicated sperm or two haploid sperms.
- Results in a triploid set of chromosomes: 69XXY (70%), 69XXX (27%), or 69XYY (3%).
- Contains fetal tissues and amnion along with placental tissue.
- Often associated with an irregularly shaped, nonviable fetus with multiple malformations and abnormal growth.
- Can occur in twin pregnancies with one normal fetus.
- Often undiagnosed until histologic review and typically ends in first trimester pregnancy loss.
- Histologically, villous edema and trophoblastic proliferation are less pronounced than in complete mole.
- Uterine enlargement beyond gestational age is uncommon.
- β-hCG levels and symptoms are less prominent compared to CHM.
- Complete Mole:
- Comparison of CHM & PHM involves differences in Karyotype, Embryo presence, Villi Edema, Trophoblasts, Implantation-Site Trophoblast, Fetal RBCs, β-hCG levels, and Risk of persistent GTT.
- Risk Factors:
- Extremes of reproductive age (< 20yrs and > 40yrs).
- Previous molar pregnancy.
- Nulliparous women.
- Low socio-economic status.
- Diets deficient in protein, folic acid, and carotene.
- Asian and black race.
- Blood group A women impregnated by blood group O men (10-fold risk increase).
- Blood group AB women have a relatively worse prognosis.
- Familial tendency.
- Clinical Features:
- Amenorrhea and abnormal uterine bleeding are the most common symptoms (>90% of cases).
- Hyperemesis occurs in 14–32% of cases.
- Uterine size greater than gestational age (GA) is common with complete mole.
- Bilateral theca lutein cysts in approximately 15–30% of cases.
- Preeclampsia in the 1st or early 2nd trimester is pathognomonic (seen in 10–12%).
- Hyperthyroidism in about 10% of cases.
- Management:
- Requires a multidisciplinary approach involving various specialists.
- Includes history, examination, investigations, treatments, and follow-up.
- Investigations:
- Quantitative serum β-hCG
- Ultrasound ("Snowstorm appearance" in CHM, focal changes and fetal tissue in PHM)
- Chest X-ray
- Histology
- Karyotyping
- Treatment:
- Resuscitation and treatment of medical complications before evacuation.
- Treatment should not be delayed.
- Suction evacuation is the preferred method — safe, rapid, and effective.
- Ultrasound-guided suction evacuation is preferred.
- Oxytocics should not be used prior to evacuation except in cases of significant hemorrhage.
- Complications: hemorrhage, uterine perforation, trophoblastic embolism.
- Hysterectomy: Rarely recommended; indicated for sterilization, women nearing menopause, or reducing risk of malignant sequelae.
- Follow-Up:
- The most essential aspect of management due to the risk of malignant transformation (~20–30%).
- Involves 1–2 weekly serial hCG determinations until normalization.
- Specific durations of follow-up depending on mole type and hCG normalization timeline.
- Avoid pregnancy during follow-up, ideally for 6 months after the first normal hCG result.
- Oral contraceptives are preferred for contraception during follow-up.
- Regular gynecological examinations to assess uterine size, cysts, and lesions.
- Post-Evacuation Treatment (for Persistent GTD/GTN):
- Indicated for persistent disease (plateau/increase in hCG, persistent hemorrhage, metastasis).
- Risk of requiring chemotherapy: 13–16% in CHM, 0.5–1.0% in PHM.
- Prophylactic chemotherapy may be considered for 'at risk' women but risks overtreatment.
- Psychological Effect:
- Molar pregnancy diagnosis can cause short-term psychological effects such as anxiety disorders, depressive disorders, and moderate to severe adaptational problems.
- Reproductive concerns are common.
- Differential Diagnosis/Other Phenomena:
- Includes hyperemesis gravidarum, incomplete abortion, ectopic pregnancy, hypertension, and hyperthyroidism.
- Hook Effect: Rare; gives false negative hCG results at very high levels. Overcome by serial dilution.
- Phantom hCG: False positive caused by heterophilic antibodies. Confirmed with combined serum and urine hCG testing.
- Twinning: Can occur with a complete mole and a normal fetus; increases risk of persistent disease; termination may be recommended.
- Familial Recurrent Hydatidiform Mole (FRHM): Extremely rare, autosomal recessive; associated with NLRP7 and KHDC3L gene mutations.
- Prognosis:
- Excellent prognosis if diagnosed and treated early.
- Potential for childbearing can be preserved.
- Current mortality rate is essentially zero.
- Even if GTN develops, it is almost 100% curable.
- Conclusion:
- Molar pregnancy is a significant form of GTD requiring a multidisciplinary approach, prompt diagnosis and management, and vigilant follow-up.
- Early detection and recognition are crucial for preventing complications and ensuring favorable outcomes.
Read a summary
- Gestational trophoblastic disease (GTD) refers to a spectrum of interrelated but histologically distinct tumors that originate from the placenta, with varied tendencies for invasion and spread.
- Molar pregnancy represents a subtype of GTD.
- Arises from fetal tissue within the maternal host, with overproduction of chorionic tissue, which is normally supposed to develop into the placenta.
- Characterized by:
- Hydropic swelling of the placental villi
- Hyperplasia of villous trophoblast
- Absent or abnormal fetal development
- Histologically, these tumors originate from syncytiotrophoblastic and cytotrophoblastic cells.
- Characterized by a reliable tumor marker: β-hCG.
- Known to be the first and only disseminated solid tumor proven to be highly curable by chemotherapy.
- Hence the dictum: “God’s first cancer and man’s first cure”.
- Incidence varies globally; generally 1 per 1000 pregnancies worldwide.
- In high-income countries: 1–3 per 1000 pregnancies.
- In East Asia: incidence is 5- to 15-fold higher, approaching 1 in 120 pregnancies.
- In West Africa, molar pregnancy incidence rates range between 0.87 and 4.88 per 1000 deliveries in Nigeria.
- Ghana: 0.80 per 1000 deliveries.
- Uganda: 3.42 per 1000 deliveries.
- Tanzania: 12.8 per 1000 deliveries.
- Nnewi, Nigeria: 4.7 per 1000 deliveries.
- Zaria, Nigeria: 7.2 per 1000 deliveries.
Molar Pregnancy (Hydatidiform Mole)
- The most common form of GTD.
- Benign in nature.
- Classically, the chorionic villi show varying degrees of trophoblast proliferation and edema of the stroma within villi.
- Chromosomal abnormalities play an integral role in the development of hydatidiform mole.
- Comprises complete and incomplete mole types.
Complete Mole
- Macroscopically, the chorionic villi are transformed into clusters of vesicles of varying dimensions, resembling a bunch of grapes — hence the name hydatidiform mole.
- Microscopically, complete moles display enlarged, edematous villi and abnormal trophoblastic proliferation, which diffusely involves the entire placenta.
- No fetal tissue or amnion is produced.
- As a result of these changes, the mass of placental tissue completely fills the endometrial cavity.
- Complete mole arises when an empty ovum (with absent or inactivated nucleus) is fertilized by sperm.
Homozygous Form
- Has two identical paternal chromosome complements, derived from duplication of the paternal haploid chromosomes.
- They are always 46, XX and account for 85–90% of complete hydatidiform moles (CHM).
- 46, YY has never been observed.
Heterozygous Form
- Arises when an empty ovum is fertilized by two different sperms (dispermic fertilization).
- The chromosome complement can be 46, XX or 46, XY.
- Accounts for 10–15% of complete moles.
- This diploid set is described as diandric.
Biparental Complete Hydatidiform Mole (CHM)
- Rare condition.
- Both maternal and paternal genes are present.
- Failure of maternal imprinting causes only the paternal genome to be expressed.
- A recurrent form of biparental mole has been described, which is familial and appears to be inherited as an autosomal recessive trait.
- A series of 5 women with as many as 9 consecutive molar pregnancies has also been described.
Partial Hydatidiform Mole (PHM)
- An ovum with an active nucleus is fertilized by a duplicated sperm or two haploid sperms.
- Results in a zygote with a triploid set of chromosomes: 69XXY (70%), 69XXX (27%), or 69XYY (3%).
- YYY karyotype has not been observed.
- In addition to placental tissue, partial moles contain fetal tissues and amnion.
- Often associated with the development of an irregularly shaped, nonviable fetus with multiple malformations and abnormal growth.
PHM in Twin and Singleton Pregnancies
- In less than 25% of cases, PHM occurs with the development of an euploid viable fetus.
- Most often presents as a twin pregnancy with one normal fetus and a complete molar pregnancy.
- May also be a twin pregnancy with one normal fetus and an incomplete mole.
- The rarest phenomenon is a singleton pregnancy with a chromosomally normal fetus and a partial molar placenta.
Clinical and Histological Features
- PHM often remains undiagnosed until histologic review of a curettage sample.
- Typically ends in first trimester pregnancy loss as an incomplete or missed abortion.
- Histologically, the degree and extent of villous edema and trophoblastic proliferation are less pronounced than in complete mole.
- Uterine enlargement in excess of gestational age is uncommon.
- β-hCG levels and associated symptoms are less prominent than in complete mole.
Comparison of CHM & PHM
| Characteristic | Complete Mole (CHM) | Partial Mole (PHM) |
|---|---|---|
| Karyotype | Diploid (46, XX, 46, XY) | Triploid (69, XXX, 69, XXY) |
| Embryo | Absent | Present |
| Villi Edema | Diffuse (Hydropic) | Focal (Few Hydropic) |
| Trophoblasts | Diffuse hyperplasia | Mild focal hyperplasia |
| Implantation-Site Trophoblast | Diffuse atypia | Focal atypia |
| Fetal RBCs | Absent | Present |
| β-hCG | High (>50,000) | Slight elevation (<50,000) |
Frequency of Classical Symptoms
|
Common
|
Rare
|
| p57Kip2 Immunostaining | Negative | Positive |
- Age: Extremes of reproductive age (< 20yrs and > 40yrs).
- Previous molar pregnancy.
- Nulliparous women.
- Low socio-economic status.
- Diets deficient in protein, folic acid, and carotene.
- Asian and black race.
- Blood group A women impregnated by blood group O men (10-fold risk increase).
- Blood group AB women have a relatively worse prognosis.
- Familial tendency.
- Amenorrhea.
- Abnormal uterine bleeding.
- Most common symptoms: > 90% of cases.
- Hyperemesis: Seen in 14–32% of cases.
- Uterine size > GA: Common with complete mole.
- Bilateral theca lutein cysts: Seen in ~15–30% of patients with molar pregnancy.
- Preeclampsia in 1st or early trimester: Pathognomonic for hydatidiform mole, seen in 10–12% of patients.
- Hyperthyroidism: Seen in 10% of patients.
- Multidisciplinary approach involving the Gynaecologist, Radiologist, Histopathologist, Chemical pathologist, Geneticist, Clinical psychologist, Oncologist, Endocrinologist, and nurses.
- History
- Examination
- Investigations
- Treatments
- Follow up
History
- Abnormal uterine bleeding
- Most common symptom – bright red or brownish
- Occurs in >90% of patients with molar pregnancy
- Passage of vesicles
- Nausea and vomiting
- Occurs in 14–32% of patients with hydatidiform mole
- May be confused with hyperemesis gravidarum
- Previous history of GTD
- Passage of grape-like tissue
- Lower abdominal pain – may be absent in early diagnosis
Examination
- General – may be anxious, pale, dehydrated +/- pedal edema
- Signs of thyrotoxicosis may be present
- CVS – tachycardia, BP normal or elevated, hyperactive precordium, signs of heart failure from hyperthyroidism
- Abdomen – doughy uterus; size may be:
- Large for date in 50% of cases
- Smaller in 30% of cases
- Pelvic examination
- Blood smeared vulva
- Adnexal mass (theca lutein cyst)
- +/- adnexal tenderness (cyst accident)
Investigations
- Serum pregnancy test (PT)
- Quantitative serum β-hCG
- FBC + differentials (urgent PCV)
- Coagulation studies
- Liver function test (LFT)
- Electrolytes, Urea, Creatinine (E/U/Cr)
- Urinalysis
- Blood group, Rhesus factor, Group and Crossmatch (GXM)
Imaging and Laboratory Evaluation
- Ultrasound
- Snowstorm appearance
- In partial mole: focal trophoblastic changes and fetal tissue may be noted
- Theca lutein cyst may be seen
- Chest X-ray – baseline film after diagnosis of molar pregnancy
- Histology
- Karyotyping – identifies triploidy
Treatment
Treatment of CHM
- Resuscitate the patient and treat medical complications before evacuation.
- Treatment should not be delayed—often initiated even before histological confirmation.
- Suction evacuation is the preferred method for hydatidiform mole.
- It is safe, rapid, and effective in nearly all cases.
Preparatory Steps
- Ensure the patient is properly evaluated and fit for surgery.
- Group and crossmatch (GXM) blood.
- Obtain informed consent.
- Prepare (ripen) the cervix using physical dilators or prostaglandins.
- Administer appropriate anaesthesia:
- General anaesthesia (GA) is preferred.
- Local anaesthesia (LA) may be used in stable patients with small uterine size.
Suction Evacuation Procedure
- Assemble instruments, scrub, and gown.
- Place the patient in lithotomy position, clean and drape appropriately.
- Empty the bladder.
- Assess uterine size and cervical dilation via bimanual exam.
- Insert Sim’s speculum to expose cervix.
- Grasp cervix with vulsellum and straighten the cervical canal.
- Insert a suction cannula (usually 12–14 mm, smaller than uterine size), should reach just beyond the internal os.
- Connect cannula to suction machine and switch on.
- Start oxytocin infusion toward the end or midway through the procedure.
- Completeness is indicated by a gritty sensation and presence of frothy blood.
- Disconnect suction machine.
- Perform gentle sharp curettage.
- Remove all instruments and ensure haemostasis.
- Clean the patient and reposition.
- Transfer to the recovery room and monitor post-op condition.
- Document findings thoroughly.
- Send tissue samples for histological examination.
- Administer anti-D prophylaxis to Rhesus-negative women after evacuation.
- Rhesus D antigen is expressed on the trophoblast.
- Cervical dilation should admit a 10–12 mm plastic curette.
- Ultrasound-guided suction evacuation is preferred to minimize uterine perforation and confirm completeness.
- Partial mole may require a combination of medical and surgical treatment.
- Oxytocics should not be used prior to evacuation:
- May be considered in cases of significant haemorrhage.
- Weigh the risk of oxytocin use against the possibility of tissue embolism.
- Do not commence oxytocin before evacuation begins.
Complications
- Hemorrhage
- In cases of large hydatidiform mole (HM) > 12 weeks, a laparotomy setup should be readily available.
- Hysterotomy or hysterectomy may be necessary in such cases.
- Uterine perforation
- May occur because the uterus is large and boggy.
- If perforation is noted, the procedure should be completed under laparoscopic guidance.
- Trophoblastic embolism
- May cause acute respiratory insufficiency.
- Avoid oxytocics before onset of uterine evacuation
Hysterectomy
- Rarely recommended, but indicated in:
- Patients desiring surgical sterilization
- Women approaching menopause
- Eliminates the risk of local myometrial invasion as a cause of persistent mole.
- Reduces risk of malignant postmolar sequelae to approximately 3–5% compared with 15–20% after suction evacuation.
- Does not eliminate the need for careful follow-up with β-hCG testing.
- Theca lutein cysts may be incidental findings during hysterectomy.
- Adnexa can be preserved bilaterally if cysts are present.
- Surgical treatment is indicated only in cases of:
- Rupture
- Torsion
- Infection
- Hemorrhage
Follow-Up
- The most essential aspect of patient management.
- Incidence of malignant transformation is approximately 20–30%.
- 1–2 weekly serial hCG determinations should begin within 48 hours after evacuation, and continue until three consecutive tests show normal hCG levels (<5 mIU/mL).
- This should be continued weekly until hCG declines to undetectable levels on three successive assays.
- For complete mole:
- If hCG reverts to normal (<5 IU/mL) within 56 days (8 weeks) of evacuation, follow-up continues for 6 months from the day of evacuation.
- If hCG does not revert to normal within 56 days, follow-up is for 6 months from the normalization of hCG levels.
- For partial mole, follow-up can be concluded once hCG returns to normal on two samples at least 4 weeks apart.
- Avoid pregnancy during follow-up, ideally until 6 months after the first normal hCG result.
- Oral contraceptives are preferred due to their ability to suppress endogenous luteinizing hormone (LH), which may interfere with hCG measurement.
- Gynaecological exams during follow-up should assess:
- Uterine size
- Presence of theca lutein cysts
- Presence of vulvar, vaginal, or cervical lesions
- Repeat examination at 4-week intervals throughout the observation period.
- Good prognostic signs include:
- Uterine involution
- Regression of theca-lutein cysts
- Cessation of vaginal bleeding
- Indicated when there is evidence of persistent GTD (referred to as GTN).
- Criteria include:
- Plateau of hCG over 4 measurements across ≥3 weeks
- hCG > 20,000 IU/L persisting 4+ weeks post-evacuation
- Persisting uterine haemorrhage
- Progressively increasing hCG at any point post-evacuation
- Elevated hCG still present 6 months post-evacuation, even if decreasing
- Histological diagnosis of choriocarcinoma
- Evidence of metastases, regardless of hCG level
- Risk of requiring chemotherapy:
- 13–16% in complete hydatidiform mole (CHM)
- 0.5–1.0% in partial molar pregnancy
Prophylactic Chemotherapy
- May be considered in ‘at risk’ women to prevent progression to GTN.
- ‘At risk’ factors include:
- Age > 35 years
- Initial serum hCG > 100,000 IU/mL
- Failure of hCG normalization by 7–9 weeks post-evacuation
- Histological diagnosis of infiltrative mole
- Post-evacuation haemorrhage
- Evidence of metastases irrespective of the level of hCG
- Previous molar pregnancy
- Patient unlikely to adhere to follow-up
- Disadvantage: Potential overtreatment-unnecessary exposure to chemotherapy, as 80–90% of women do not develop GTN.
Psychological Effect
- Molar pregnancy diagnosis can cause short-term psychological effects.
- Common presentations include:
- Anxiety disorders
- Depressive disorders
- Moderate to severe adaptational problems
- Reproductive concerns, especially regarding fertility
- Women who already have children often experience:
- Less concern about fertility
- Lower levels of psychological distress
- Hyperemesis Gravidarum
- Incomplete abortion
- Ectopic pregnancy
- Hypertension
- Hyperthyroidism and Thyrotoxicosis
Hook Effect
- A rare phenomenon
- Gives a false negative result at very high levels of β-hCG (usually >500,000 mIU/ml)
- There’s improper antigen-antibody ratio
- Normally, β-hCG binds to a capture molecule
- The “captured” molecule is then read by the assay against a standard concentration curve, to read as positive or negative
- In Hook effect, the amount of β-hCG is so high that it overwhelms the capture molecule
- Overcome by urine PT in serial dilution
Phantom hCG
- Gives a false positive result, due to heterophillic antibodies
- Persistently +ve hCG in a non-pregnant patient
- Often leads to a false diagnosis of malignancy and inappropriate treatment with chemotherapy or hysterectomy
- Heterophyllic antibodies are large and filtered by the glomerulus
- A quantitative serum hCG should be run in conjunction with a urine hCG (qualitative or quantitative)
- A +ve quantitative serum hCG coupled with a -ve urine hCG is supportive of the diagnosis of phantom hCG
- Urine hCG should be performed in all cases of persistent or irregular vaginal bleeding lasting more than 8 weeks after a pregnancy event
Twinning
- Twinning with a complete mole and a fetus with a normal placenta has been reported
- Cases of healthy infants in these circumstances have been reported
- Women with coexistent molar and normal gestations are at higher risk for developing persistent disease and metastasis
- Termination of pregnancy is a recommended option
- Continue pregnancy if maternal status is stable, without hemorrhage, thyrotoxicosis, or severe hypertension
- Patient should be informed of the risk of severe maternal morbidity from possible complications
- Prenatal genetic diagnosis by CVS or amniocentesis is recommended to evaluate
Familial Recurrent Hydatidiform Mole (FRHM)
- Extremely rare (reported in only 21 families in the medical literature)
- In these cases, the HM are diploid, but bi-parental, unlike the androgenetic origin of sporadic complete moles
- These patients have an autosomal recessive condition that results in recurrent molar pregnancies with little chance of a successful pregnancy
- Patients with a personal, but no family history of recurrent moles usually have androgenetic CHM
- Two gene mutations, NLRP7 and KHDC3L, account for ∼75% and 5% of the affected cases, respectively
- Normal pregnancy is achieved by IVF with pre-gestational diagnosis in the sporadic type, but with donor egg in FRHM
- Molar pregnancy has excellent prognosis, if diagnosed and treated early
- Potential for child bearing can be preserved
- With 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 (<5% in partial mole)
- Even when GTN develops, it is almost 100% curable
- Molar pregnancy is a significant form of GTD whose management requires a multidisciplinary approach with prompt diagnosis and management to prevent complications and ensure optimal outcomes.
- Hence, early detection and recognition through clinical signs, confirmatory investigations such as ultrasound scan and histology, as well as monitoring hCG levels post-evacuation to detect persistent disease, is very crucial.
- With appropriate treatment and follow-up, prognosis is generally favourable.
- However, continued research and awareness are essential to improving diagnosis techniques and patient care in cases of molar pregnancy.
Study Guide
Check how well you grasp the concepts by answering the following questions...
Quiz
- What is gestational trophoblastic disease (GTD), and how does molar pregnancy relate to it?
- Describe the characteristic overproduction of chorionic tissue seen in molar pregnancy.
- What are the key histological features used to characterize molar pregnancy?
- Explain why β-hCG is considered a reliable tumor marker for molar pregnancy.
- What are the chromosomal differences between a complete mole and a partial mole?
- Briefly describe the macroscopic appearance of a complete hydatidiform mole.
- How does the presence of fetal tissue or amnion differ between complete and partial moles?
- What are two of the risk factors associated with the development of molar pregnancy?
- What is the preferred method for evacuating a hydatidiform mole?
- Why is serial β-hCG testing essential after the evacuation of a molar pregnancy?
Answer Key
- GTD is a spectrum of tumors originating from the placenta with varying invasion and spread. Molar pregnancy is a specific subtype of GTD.
- In molar pregnancy, there is an abnormal and excessive growth of the chorionic villi, which are normally destined to become the placenta.
- Histologically, molar pregnancies are characterized by hydropic swelling of the villi and hyperplasia of villous trophoblast cells.
- β-hCG is produced by trophoblast cells, and in molar pregnancy, due to the overgrowth of these cells, β-hCG levels are significantly elevated, making it a useful marker for diagnosis and monitoring.
- A complete mole is typically diploid (46,XX or 46,XY) and paternal in origin, while a partial mole is triploid (69,XXX, 69,XXY, or 69,XYY) with both maternal and paternal chromosomal contributions.
- Macroscopically, a complete mole resembles a "bunch of grapes" due to the transformed chorionic villi becoming clusters of fluid-filled vesicles.
- Fetal tissue and amnion are absent in a complete mole but are typically present in a partial mole, although often abnormally developed.
- Risk factors include extremes of reproductive age (< 20 and > 40 years), previous molar pregnancy, low socio-economic status, and certain dietary deficiencies. (Any two acceptable.)
- Suction evacuation is the preferred method for removing a hydatidiform mole.
- Serial β-hCG testing is crucial for monitoring for persistent GTD (GTN) or malignant transformation after evacuation, as elevated or rising levels indicate continued trophoblastic activity.
SAQs
What is a molar pregnancy and how does it relate to Gestational Trophoblastic Disease (GTD)?
Molar pregnancy is a specific type of Gestational Trophoblastic Disease (GTD). GTD is a group of tumors that originate from the placenta, exhibiting varying tendencies for invasion and spread. In a molar pregnancy, there is an overproduction of chorionic tissue, which would normally develop into the placenta. This overproduction leads to characteristic features such as hydropic swelling of placental villi, hyperplasia of villous trophoblast, and absent or abnormal fetal development. These tumors arise from syncytiotrophoblastic and cytotrophoblastic cells and are reliably monitored using the tumor marker β-hCG.
What are the two main types of molar pregnancy and how do they differ?
The two main types are complete mole (CHM) and partial hydatidiform mole (PHM). Complete moles arise when an empty ovum is fertilized by one or two sperm, resulting in a diploid set of paternal chromosomes (usually 46,XX or 46,XY). Macroscopically, they resemble a "bunch of grapes", and microscopically show enlarged, edematous villi and abnormal trophoblastic proliferation with no fetal tissue or amnion. Partial moles occur when an ovum with an active nucleus is fertilized by a duplicated sperm or two haploid sperms, leading to a triploid set of chromosomes (most commonly 69,XXY). Partial moles contain both placental and fetal tissues, often with an irregularly shaped, nonviable fetus. Histologically, villous edema and trophoblastic proliferation are less pronounced than in complete moles, and β-hCG levels and associated symptoms are typically less prominent.
What are the risk factors associated with developing a molar pregnancy?
Several factors can increase the risk of a molar pregnancy. These include extremes of reproductive age (under 20 and over 40 years), a previous molar pregnancy, being nulliparous (never having given birth), low socio-economic status, and diets deficient in protein, folic acid, and carotene. Asian and black race, as well as specific blood group combinations (Blood group A women impregnated by blood group O men, and Blood group AB women), are also associated with increased risk. Finally, there can be a familial tendency for recurrent molar pregnancies.
What are the common clinical features that may indicate a molar pregnancy?
The most common symptom of a molar pregnancy is abnormal uterine bleeding, which occurs in over 90% of cases. Other clinical features can include hyperemesis (severe nausea and vomiting), a uterus size larger than expected for gestational age (especially with a complete mole), and bilateral theca lutein cysts. Preeclampsia in the first or early trimester is considered pathognomonic for hydatidiform mole. Hyperthyroidism can also be seen in some patients. Less common symptoms can include the passage of grape-like vesicles and lower abdominal pain.
How is a molar pregnancy typically diagnosed and managed?
Diagnosis of a molar pregnancy often involves a combination of clinical assessment, investigations, and imaging. A quantitative serum β-hCG test is crucial, as levels are often significantly elevated, particularly in complete moles. Ultrasound imaging is a key diagnostic tool, often revealing a characteristic "snowstorm appearance" in complete moles. Histological examination of tissue samples obtained through evacuation is essential for definitive diagnosis and classification (complete vs. partial). Management typically involves suction evacuation as the preferred method for removing the molar tissue. In rare cases, particularly for patients desiring sterilization or approaching menopause, a hysterectomy may be considered. A multidisciplinary approach involving various medical specialists is recommended for optimal care.
Why is follow-up after evacuation of a molar pregnancy so important?
Follow-up after evacuation is the most essential aspect of management due to the risk of persistent Gestational Trophoblastic Disease (GTD), which can become malignant (Gestational Trophoblastic Neoplasia, GTN). Serial β-hCG determinations are crucial for monitoring. For complete moles, β-hCG levels are monitored weekly until three consecutive normal results are achieved, and then follow-up continues for a specified period based on the time to normalization. For partial moles, follow-up can be shorter once hCG levels return to normal. Avoiding pregnancy during the follow-up period is strongly recommended.
What are some potential complications of molar pregnancy and its treatment?
Potential complications of molar pregnancy and its treatment include hemorrhage, which can be significant and may rarely necessitate a hysterotomy or hysterectomy in cases of large moles. Uterine perforation can occur during the evacuation procedure, especially if the uterus is large and boggy. Trophoblastic embolism, which can cause acute respiratory insufficiency, is a rare but serious complication that is more likely if oxytocics are used before uterine evacuation begins. The development of persistent GTD or choriocarcinoma after evacuation is also a significant concern, requiring careful monitoring and potentially chemotherapy.
What is the prognosis for a molar pregnancy?
The prognosis for molar pregnancy is generally excellent when diagnosed and treated early. With prompt diagnosis and appropriate management, the mortality rate is very low, approaching zero. While there is a risk of developing trophoblastic malignancy (around 20% after a complete mole and less than 5% after a partial mole), GTN is highly curable, with almost 100% cure rates. Early detection through clinical signs and investigations, along with meticulous post-evacuation follow-up by monitoring hCG levels, is critical for ensuring optimal outcomes and preserving potential for future childbearing.
Glossary of Key Terms
- Gestational trophoblastic disease (GTD): A group of disorders characterized by abnormal proliferation of trophoblastic tissue.
- Molar pregnancy (Hydatidiform mole): A subtype of GTD characterized by overproduction of chorionic tissue, hydropic swelling of villi, and absent or abnormal fetal development.
- Chorionic tissue: Tissue that normally develops into the placenta.
- Hydropic swelling: The accumulation of fluid within the placental villi, causing them to enlarge.
- Hyperplasia: An increase in the number of cells, in this context, of the villous trophoblast.
- Syncytiotrophoblastic cells: One of the two layers of the trophoblast, involved in hormone production and invasion.
- Cytotrophoblastic cells: The inner layer of the trophoblast, which gives rise to syncytiotrophoblast.
- β-hCG: Beta-human chorionic gonadotropin, a hormone produced by trophoblast cells and used as a tumor marker in molar pregnancy.
- Complete mole: A type of hydatidiform mole characterized by the absence of fetal tissue and diffuse hydropic swelling and trophoblastic hyperplasia.
- Partial mole: A type of hydatidiform mole that contains some fetal tissue (often abnormal) and exhibits focal hydropic swelling and trophoblastic hyperplasia.
- Hydatidiform mole: Another term for molar pregnancy, referring to the grape-like appearance of the affected villi.
- Diploid: Having two sets of chromosomes.
- Triploid: Having three sets of chromosomes.
- Diandric: Referring to a diploid set of chromosomes derived entirely from the father.
- Biparental complete hydatidiform mole: A rare form of complete mole where both maternal and paternal genes are present but maternal imprinting fails, leading to paternal genome expression.
- Theca lutein cysts: Ovarian cysts that can develop in response to high levels of hCG in molar pregnancy.
- Preeclampsia: A pregnancy complication characterized by high blood pressure and signs of damage to another organ system, often the liver and kidneys.
- Hyperemesis gravidarum: Severe nausea and vomiting during pregnancy.
- Suction evacuation: A surgical procedure using suction to remove the contents of the uterus.
- Curettage: A surgical procedure to scrape the lining of the uterus.
- Trophoblastic embolism: The migration of trophoblastic tissue into the bloodstream, potentially causing respiratory complications.
- Hysterectomy: Surgical removal of the uterus.
- Persistent GTD (GTN): The persistence or recurrence of trophoblastic tissue after treatment, which can be malignant.
- Hook effect: A phenomenon in some assays where very high concentrations of the substance being measured lead to a falsely low or negative result.
- Phantom hCG: A false positive hCG result caused by heterophilic antibodies in the patient's serum.
- Familial recurrent hydatidiform mole (FRHM): A rare, inherited condition causing recurrent molar pregnancies.
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