10.3 Gestational Trophoblastic Disease, Recurrent Loss, Stillbirth & Perinatal Bereavement
Key Takeaways
A complete mole is usually 46,XX (all paternal DNA) without fetal tissue, with markedly elevated hCG and a 'snowstorm' ultrasound pattern; a partial mole is triploid (69,XXY) with fetal parts.
Molar pregnancy is treated with suction curettage, followed by serial hCG until undetectable plus additional confirmatory values, with reliable contraception during surveillance.
A plateau or rise in hCG after molar evacuation signals gestational trophoblastic neoplasia, which is highly curable with chemotherapy such as methotrexate.
Stillbirth is fetal death at 20 weeks or later; the most useful evaluations are fetal autopsy, placental pathology, and genetic testing (chromosomal microarray), with Kleihauer-Betke and antiphospholipid testing.
Bereavement care includes offering to see and hold the baby, memory-making, lactation suppression guidance, screening for depression and complicated grief, and a plan for future pregnancy.
Gestational Trophoblastic Disease (GTD)
GTD is a spectrum of abnormal trophoblast proliferation, from benign hydatidiform mole to malignant gestational trophoblastic neoplasia (GTN). Risk is highest at the extremes of reproductive age and with a prior molar pregnancy.
| Feature | Complete Mole | Partial Mole |
|---|---|---|
| Karyotype | 46,XX (rarely 46,XY), all chromosomes paternal (an "empty" egg fertilized) | Triploid (69,XXY or 69,XXX): one maternal and two paternal sets |
| Fetal tissue | None | Present (often abnormal) |
| hCG | Often markedly elevated (frequently >100,000 mIU/mL) | Often normal or mildly elevated |
| Uterine size | Often large for dates | Often appropriate or small |
| Ultrasound | "Snowstorm" or cluster-of-grapes pattern; theca lutein cysts | Focal cystic placental changes with a fetus |
| Risk of GTN | About 15%–20% | About 0.5%–5% |
Presentation: Vaginal bleeding is most common. High hCG can cause hyperemesis, hyperthyroidism (hCG stimulates the TSH receptor), theca lutein cysts, and preeclampsia before 20 weeks, which should always raise suspicion of a mole.
Management
- Suction curettage is the treatment of choice, regardless of uterine size; obtain baseline hCG, CBC, type and screen, and a chest radiograph if GTN is suspected. Give Rh immune globulin to Rh(D)-negative patients (partial moles contain fetal red cells).
- hCG surveillance: Measure hCG every 1–2 weeks until undetectable. After a complete mole, obtain additional monthly values (commonly for about 3 months) to confirm it stays undetectable; after a partial mole, one confirmatory normal value a month later is usually enough.
- Contraception during surveillance prevents a new pregnancy from confusing the hCG trend. Hormonal methods are safe; an IUD is avoided until hCG is undetectable because of perforation risk with persistent disease.
Gestational Trophoblastic Neoplasia
Suspect GTN when post-evacuation hCG plateaus over about 3 weeks, rises over about 2 weeks, or stays detectable about 6 months, or when choriocarcinoma is found (it can follow any pregnancy and often metastasizes to the lungs). Low-risk GTN is treated with methotrexate (or actinomycin D) and is curable in nearly all patients; high-risk disease receives multi-agent chemotherapy.
Recurrent Pregnancy Loss
ASRM defines recurrent pregnancy loss as two or more clinical pregnancy losses. Evaluation includes:
- Parental karyotypes (balanced translocations).
- Uterine cavity assessment (septate uterus, submucosal fibroid, synechiae) with sonohysterography, 3D ultrasound, or hysteroscopy.
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-beta-2 glycoprotein I), repeated 12 weeks apart if positive.
- Endocrine factors: TSH, A1C or glucose, and prolactin when indicated.
About half of cases remain unexplained, yet the chance of a live birth in the next pregnancy is still good, which is an important message for patients. Antiphospholipid syndrome is treated with low-dose aspirin plus prophylactic heparin, and vaginal progesterone may help patients with prior losses who bleed in early pregnancy.
Stillbirth (Intrauterine Fetal Death)
In the United States, stillbirth is fetal death at 20 weeks or later, occurring in about 1 in 175 births. Risk factors include hypertension, diabetes, obesity, smoking, older age, multiple gestation, fetal growth restriction, infection, and placental abruption; Black patients face about twice the rate of White patients.
Diagnosis and Evaluation (ACOG/SMFM)
Confirm absent cardiac activity by ultrasound. The highest-yield tests are:
- Fetal autopsy (offer it respectfully; partial or noninvasive options exist).
- Placental, cord, and membrane pathology.
- Genetic testing, preferably chromosomal microarray on fetal or placental tissue.
- Maternal tests: Kleihauer-Betke or flow cytometry for fetomaternal hemorrhage, antiphospholipid antibodies, and others guided by history (syphilis, parvovirus, glucose testing, toxicology).
Delivery Options
- Induction of labor (misoprostol, oxytocin, or mechanical ripening) is the most common choice; dilation and evacuation is an option in the second trimester with experienced providers.
- Expectant management is reasonable for some patients because most labor within 2 weeks, but prolonged retention beyond about 4 weeks raises the risk of coagulopathy (monitor fibrinogen).
- Give Rh immune globulin to Rh(D)-negative patients.
Bereavement Care After Any Pregnancy Loss
- Use the baby's name if one is given, and offer, without pressure, the chance to see, hold, bathe, and photograph the baby and to keep mementos such as footprints and a lock of hair.
- Provide clear explanations, written information, chaplaincy or cultural support, and help with autopsy and burial decisions.
- Lactation may begin after a second- or third-trimester loss: advise a supportive bra, cold compresses, and NSAIDs; some patients choose to donate milk. Cabergoline is used off-label for suppression; bromocriptine is not recommended.
- Screen for depression, anxiety, PTSD, and complicated grief at follow-up; partners grieve too and may grieve differently.
- Plan the next pregnancy: Review the cause, optimize health, date the pregnancy early, and increase surveillance (serial growth scans and antenatal testing from about 32 weeks), recognizing the anxiety a new pregnancy brings.
A 41-year-old at 11 weeks of gestation presents with vaginal bleeding, severe nausea, and a uterus large for dates. Her serum hCG is 280,000 mIU/mL, and her blood pressure is 152/98 mmHg. Ultrasound shows a heterogeneous intrauterine mass with numerous small cystic spaces and no fetus. What is the most likely karyotype of this pregnancy?
69,XXY with one maternal and two paternal chromosome sets
45,X from loss of a paternal sex chromosome
46,XX with all chromosomes of paternal origin
47,XX,+21 from maternal meiotic nondisjunction
After suction evacuation of a complete mole, a patient's weekly hCG values are 1,200, 1,180, 1,210, and 1,190 mIU/mL over 3 weeks. What is the most appropriate interpretation and next step?
This is the expected slow decline after a mole; recheck the hCG level in 3 months.
The plateau suggests gestational trophoblastic neoplasia; she needs staging and oncology referral.
She has a new intrauterine pregnancy, so schedule a dating ultrasound and routine prenatal labs.
Repeat suction curettage is mandatory before any further evaluation or imaging is done.
A 33-year-old has a stillbirth at 34 weeks. She and her partner agree to a postmortem evaluation. Which combination of tests provides the highest diagnostic yield for the cause of death?
Fetal autopsy, placental pathology, and chromosomal microarray
TORCH titers on the mother and a maternal karyotype only
Maternal thrombophilia panel for factor V Leiden and protein C deficiency only
Repeat third-trimester ultrasound and maternal CA-125
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