22.3 Early Pregnancy Risks & Bleeding: Hyperemesis, Spontaneous Abortion, Recurrent Loss & Cervical Insufficiency, Ectopic Pregnancy, Hydatidiform Mole & Gestational Trophoblastic Neoplasia

Why this area matters

TOS area D asks you to:

• identify risk factors for abortion, molar pregnancy and gestational tumors, ectopic pregnancy and other causes of first-trimester bleeding;
• apply diagnostic tests;
• prescribe definitive and supportive treatment and anticipate its adverse effects;
• choose preventive measures.

Ruptured ectopic pregnancy and complications of abortion are preventable causes of maternal death in the Philippines. Induced abortion is a crime under the Revised Penal Code (Articles 256 to 259). The DOH policy on the Prevention and Management of Abortion Complications (AO 2016-0041) still requires every facility to give women with complications prompt, humane, compassionate and nonjudgmental care. That care includes post-abortion family planning counseling.

Approach to bleeding in early pregnancy

The main causes of first-trimester bleeding are:

• implantation bleeding;
• spontaneous abortion (the most common);
• ectopic pregnancy (the most dangerous);
• molar pregnancy;
• cervical lesions such as polyps, ectropion, infection or cancer.

Assessment proceeds in this order:

1. Hemodynamic status and signs of peritonitis.
2. Speculum examination: is the os open or closed, and is tissue present?
3. Quantitative beta-hCG, repeated after 48 hours if the location is unknown. A viable intrauterine pregnancy usually rises by at least about 35% to 50% in 48 hours.
4. Transvaginal ultrasound.
5. Blood type and Rh. Give Rh immune globulin to Rh-negative women who bleed, miscarry, have an ectopic or have a procedure.

Early Pregnancy Bleeding ($< 20\text{ Weeks}$ of Gestation)

Vaginal bleeding during the first 20 weeks of gestation mandates rapid clinical evaluation to differentiate between spontaneous abortion, ectopic pregnancy, and gestational trophoblastic disease.

Spontaneous Abortion (Miscarriage)

Spontaneous termination of pregnancy before 20 weeks of gestation or expulsion of an embryo/fetus weighing $< 500\text{ g}$. Chromosomal abnormalities (aneuploidy, predominantly autosomal trisomies such as trisomy 16) account for over 50% of first-trimester miscarriages.

• Management:
  • Threatened Abortion: Expectant management, pelvic rest, reassurance. Prophylactic Rh immune globulin (50 $\mu\text{g}$ or 300 $\mu\text{g}$) if the mother is Rh-negative.
  • Inevitable, Incomplete, or Missed Abortion: Options include expectant management, medical evacuation using oral or vaginal Misoprostol (prostaglandin $E_1$ analog), or surgical evacuation via suction curettage or manual vacuum aspiration (MVA). Surgical intervention is mandatory if hemodynamic instability, profuse hemorrhage, or infection is present.
  • Septic Abortion: Broad-spectrum IV antibiotics (Ampicillin + Gentamicin + Metronidazole) followed by prompt surgical evacuation of the infected uterine contents.

Ectopic Pregnancy

Implantation of the blastocyst outside the endometrial cavity. Over 90% occur within the fallopian tube, with the ampulla (about 70%) being the most common site, followed by the isthmus (about 12%), fimbria (about 11%), and interstitial segment (about 2%, which carries the highest risk of catastrophic hemorrhage because it lies within the vascular uterine wall). Ovarian, cervical, abdominal and cesarean-scar pregnancies are rare.

• Clinical Presentation: Classic triad of amenorrhea, unilateral lower abdominal pain, and vaginal bleeding. Rupture precipitates peritoneal irritation (rebound tenderness, guarding) and hemodynamic shock.
• Diagnostic Evaluation:
  • Quantitative Serum $\beta$-hCG and Transvaginal Ultrasound (TVUS): The discriminatory zone is the serum $\beta$-hCG level above which a normal intrauterine gestational sac must be visualized on TVUS (typically 1,500 to 2,000 mIU/mL, although a normal sac may not be seen until about 3,500 mIU/mL). An empty uterine cavity with $\beta$-hCG above the discriminatory zone strongly suggests an ectopic or failed pregnancy, and an adnexal mass separate from the ovary confirms the suspicion.
• Management:
  • Medical Management with Methotrexate (MTX): A folic acid antagonist that arrests rapidly dividing trophoblastic cells. Eligibility criteria:
    1. Hemodynamically stable with no active intra-abdominal hemorrhage.
    2. Unruptured ectopic mass $< 3.5\text{ cm}$ in greatest diameter.
    3. Absence of embryonic cardiac activity on ultrasound.
    4. Baseline serum $\beta\text{-hCG} < 5,000\text{ mIU/mL}$.
    5. Normal maternal renal and hepatic function.
    • Regimen: Single dose $50\text{ mg/m}^2$ IM. Serial serum $\beta$-hCG is monitored on Day 4 and Day 7; a drop of $\ge 15\text{\%}$ between Day 4 and Day 7 indicates successful treatment.
  • Surgical Management: Laparoscopic salpingectomy (removal of the tube) or salpingostomy (incision and evacuation preserving the tube). Mandatory for ruptured ectopic pregnancy, hemodynamic instability, or failed/contraindicated MTX.

Gestational Trophoblastic Disease (Hydatidiform Mole)

Aberrant fertilization characterized by abnormal trophoblastic proliferation and hydropic swelling of chorionic villi.

• Complete Hydatidiform Mole: Karyotype is 46,XX (90%) or 46,XY, entirely of paternal origin (androgenetic; an enucleated empty ovum fertilized by a single sperm that duplicates, or two sperm). Diffuse trophoblastic hyperplasia, generalized hydropic villi, and complete absence of fetal/embryonic tissue. Markedly elevated $\beta\text{-hCG} (> 100,000\text{ mIU/mL})$. Classic TVUS findings reveal a "snowstorm" or "bunch of grapes" pattern with multiple hypoechoic spaces. Features include hyperemesis gravidarum, early-onset preeclampsia ($< 20\text{ weeks}$), theca lutein ovarian cysts, and a 15% to 20% risk of progression to gestational trophoblastic neoplasia (choriocarcinoma).
• Partial Hydatidiform Mole: Karyotype is triploid: 69,XXX, 69,XXY, or 69,XYY, resulting from the fertilization of a normal haploid ovum by two sperm (dispermy). Focal trophoblastic hyperplasia, scalloped villi, and fetal/embryonic tissue is present. $\beta$-hCG levels are normal to slightly elevated, and malignant potential is low ($< 5\%$).
• Management: Suction curettage under ultrasound guidance. Serial quantitative serum $\beta$-hCG monitoring weekly until undetectable for 3 consecutive weeks, then monthly for a few months (FIGO 2018 shortened surveillance once hCG normalizes, especially after a partial mole). A plateau or rise in hCG signals gestational trophoblastic neoplasia. Reliable contraception (oral contraceptives) must be used during follow-up to prevent pregnancy from obscuring hCG monitoring.

More on miscarriage and its prevention

• Recurrent pregnancy loss (two or more losses) is investigated for:
  • antiphospholipid syndrome (lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein I antibodies), treated with low-dose aspirin plus heparin;
  • parental chromosomal translocations;
  • uterine anomalies such as a septate uterus;
  • poorly controlled diabetes and thyroid disease.
• Cervical insufficiency: painless cervical dilation leads to second-trimester loss. A history-indicated cerclage (McDonald or Shirodkar) is placed at 12 to 14 weeks.
• Manual vacuum aspiration (MVA) and misoprostol are the recommended methods for uterine evacuation in incomplete abortion up to about 12 to 14 weeks. They are safer than sharp curettage.
• After any evacuation:
  • offer family planning counseling and a method before discharge;
  • check for infection and give antibiotics if needed;
  • give anti-D to Rh-negative women.

Treating ectopic pregnancy: side effects and follow-up

• Methotrexate side effects: stomatitis, nausea, raised liver enzymes and transient abdominal pain ("separation pain") on days 3 to 7, which must be distinguished from rupture.
• During methotrexate treatment, patients should avoid:
  • folic acid-containing vitamins;
  • NSAIDs;
  • alcohol;
  • sexual intercourse;
  • pregnancy for at least 3 months.
• Salpingostomy preserves the tube but risks persistent trophoblast, so hCG must be followed to zero. Salpingectomy is preferred when the other tube is healthy.
• Prevention: most ectopics follow tubal damage. Prompt treatment of chlamydia and gonorrhea and prevention of PID reduce the risk.

Gestational trophoblastic neoplasia (GTN)

• GTN includes invasive mole, choriocarcinoma, placental-site trophoblastic tumor and epithelioid trophoblastic tumor.
• Diagnosis after a molar pregnancy is by hCG criteria: a plateau over 3 weeks, a rise over 2 weeks, or hCG persisting for 6 months or more.
• Choriocarcinoma can follow a mole, abortion, ectopic or term pregnancy. It spreads by blood, most often to the lungs, then the vagina, brain and liver. It contains sheets of cytotrophoblast and syncytiotrophoblast without villi.
• Treatment: the FIGO/WHO prognostic score separates low-risk disease (score 6 or less), treated with single-agent methotrexate or actinomycin D, from high-risk disease (7 or more), treated with multi-agent chemotherapy (EMA-CO). Cure rates are very high, even with metastases.
• Contraception (preferably hormonal) is used during hCG follow-up.

Hyperemesis gravidarum

• Definition: persistent vomiting in early pregnancy with weight loss of more than 5%, dehydration, ketonuria and electrolyte imbalance (hypokalemic, hypochloremic metabolic alkalosis). It is associated with high hCG, as in multiple and molar pregnancy.
• Management:
  • IV fluids, given with thiamine before dextrose to prevent Wernicke encephalopathy;
  • antiemetics: doxylamine-pyridoxine, metoclopramide or ondansetron;
  • small frequent meals;
  • exclusion of thyroid disease and molar pregnancy.
• Transient gestational thyrotoxicosis occurs because hCG stimulates the TSH receptor. It usually resolves by 18 to 20 weeks without antithyroid drugs.