Obstetrics and Gynecology/Ectopic Pregnancies, Spontaneous Abortion, and other First Trimester Complications

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Spontaneous Abortion[edit]

Solitary Spontaneous Abortion[edit]

Spontaneous abortion (SA) is defined as the expulsion or extraction of an embryo or fetus <500g in mass or before 20 weeks gestation. It may also be recognized by first trimester bleeding: recognize, however, that up to 30% of pregnancies encounter some form of first trimester bleeding but less than half of these will be complicated by SA.

Classification[edit]

  • Threatened abortion: presents with cramping and bleeding, with a closed cervical canal
  • Inevitable abortion: fully dilated cervical canal in the presence of cramping and escalating blood loss
  • Incomplete abortion: fully dilated cervical canal, cramping, bleeding, and some tissue passage, but with retention
  • Missed abortion: in utero fetal demise in the absence of tissue passage
  • Septic abortion: cramping, pain, discharge, bleeding, fever, and malaise.

Epidemiology[edit]

  • SA complicates >15% of recognized pregnancies.
  • 80% of SAs occur in the first trimester. Very few complicate the second and third trimesters.

Etiology[edit]

  • 60% of SA in the first trimester are due to abnormal karyotypes. By and large, up to 60% of SA are due to embryonic viability issues.
  • Few, up to 20% of SAs may be due to maternal factors such as maternal age, uterine abnormalities, infection, lifestyle factors (smoking, alcohol, and cocaine are major factors), and concurrent maternal disease.
  • The rest of SAs may have unknown etiologies.

Clinical Presentation[edit]

  • The major presenting factors are cramping, bleeding, and a history of amenorrhea.
  • The patient may have passed tissue
  • The cervical canal may be dilate
  • The uterus must be enlarged
  • Infection for septic abortions (rare in the developed world, especially in those countries with legalized abortion)

Management[edit]

See management for recurrent abortions, because management strategies are similar.

Recurrent Abortion[edit]

Definition and Clinical Presentation[edit]

  • Primary recurrent abortion: absence of any pregnancy greater than 20 weeks in duration.
  • Secondary recurrent abortion: three or more miscarriages in the context of a previous pregnancy lasting longer than 20 weeks.

Classification[edit]

Recurrent abortions can be classified into those occurring before 6 weeks, and between 6-10 weeks gestation.

Before 6 weeks:

  • Biochemical abortions occur before 4 weeks of gestation in the context of an Ultrasound negative and Beta-HCG positive pregnancy
  • Anembryonic abortions occur between the 4th and 5th weeks of gestation. It involves passage of a gestational sac with diameter greater than 8mm.
  • Yolk sac abortions occur between the 5th and 6th weeks and involve passage of a gestational sac with yolk sac. The total mass must be greater than 16mm.

Between 6-10 weeks:

  • Embryonic abortions occur between 6 and 10 weeks of gestation and involve passage of a circulatory arrested embryo with crown rump length greater than 5mm.
  • Fetal miscarriages occur between 10 and 20 weeks of gestation, but resemble embryonic abortions in other respects.

Epidemiology[edit]

  • 1-2% of couples experience recurrent abortions

Etiology[edit]

  • The risk of subsequent abortion increases exponentially with the number of prior abortions experienced by a couple.

Management[edit]

  • Grief counseling
  • Measure Rh status. If mother is Rh negative, administer Rho(D) Intravenous Immune Globulin.
  • Conservative approach: typically expulsion of fetal remains within 2 - 4 weeks.
  • Misoprostol (Prostaglandin E1 analogue): side effects include pain, diarrhea, fever, and bleeding.
  • Dilatation and curretage: indicated for hemodynamic instability, infection. Side effects include perforation, adhesions, trauma, and infection.

Ectopic pregnancies[edit]

Ectopic pregnancies are defined as the presence of gestational tissue outside of the uterine cavity. Ectopic pregnancies are life threatening emergencies.

Epidemiology[edit]

  • Ectopic pregnancies affect 2% of all pregnancies, and approximately 10% of individuals with first trimester bleeding.
  • Ectopic pregnancy is the leading cause of first trimester mortality.

Etiology[edit]

  • Half of all ectopic pregnancies occur in the context of absent risk factors.
  • A major risk factor for ectopic pregnancy is previous incidence of pelvic inflammatory disease.
  • Ectopic pregnancy recurs in 15% of women and this risk increases proportionally with the invasiveness of the initial treatment.
    • On the same note, tubal manipulation increases the risk for ectopic pregnancy.
  • Infertility (related to tubal manipulation)
  • Age under 18 (at sexual debut) or over 35.

Clinical Presentation[edit]

  • Abdominal pain
  • Bleeding
  • Amenorrhea
  • If ruptured, the ectopic pregnancy may cause intraperitoneal hemorrhage.

Diagnosis[edit]

  • Clinical diagnosis, however, lab tests and imaging may be used to confirm.
  • Beta-HCG will increase at a rate less than 50% per 48h.
  • 15% of ectopic pregnancies will have a normal doubling time, and 15% of normal pregnancies will be associated with doubling times <15%.
  • Progesterone measured in light of clinical findings may be helpful:
    • <15.9 pmol/L predicts EP or SA
    • >63.6 pmol/L predicts viable pregnancy located in the intrauterine cavity.
  • Ultrasound

Management[edit]

  • Conservative "watch and wait" approach: indicated by absent rupture, B-HCG <1500 U/L, declining change in B-HCG within 48h. B-HCG should be followed weekly until they extend below 5U/L. During this time, sexual intercourse is contraindicated.
  • Methotrexate: indicated for persistent ectopic pregnancy (BHCG >5000 and/or rising 2 days later), and works best for ectopic pregnancies <35mm in diameter.
    • Patient must be hemodynamically stable with no active bleeding
    • Patient must have stable hematological and hepatic function
    • Alcohol, folic acid, and intercourse are contraindicated during methotrexate therapy.
    • Hysterosalpingography should be conducted 3 months after methotrexate therapy and subsequent pregnancies should be delayed for an additional three months after methotrexate cessation.
  • Surgery: indicated for persistent ectopic pregnancy, in a hemodynamically unstable female
    • Patients with impending rupture of ectopic pregnancy are indicated for surgery
    • Patients who are not able to comply with treatment should be operated upon
    • Laparoscopy is indicated to provide definite diagnosis if required.
    • Surgery is indicated if medical therapy has failed.
    • Laparotomy should be favoured against laparoscopy if complex, hemodynamically unstable, complex reoperative. Salpingostomy if contralateral tube damaged/missing; salpingectomy if high-grade hemorrhage, overwhelming tubal damage, or recurrent ectopic pregnancies in one tube.

Molar Pregnancy[edit]

Epidemiology[edit]

  • Molar pregnancies occur in 1/1000 pregnancies
  • Molar pregnancies occur more often in asian women
  • Molar pregnancies occr at the extremes of age in pregnancy (under 20, over 40)

Choriocarcinoma[edit]

  • Choriocarcinomas arise in 1/40000 pregnancies
  • 50% of choriocarcinomas arise from normal pregnancies
  • 25% of choriocarcinomas arise from hydatidiform moles
  • 25% of choriocarcinomas arise from ectopic pregnancies/abortions

Placental Site Trophoblastic Tumor[edit]

  • Very rare

Etiology, Risk Factors, and Pathophysiology[edit]

Hydatidiform Mole[edit]

  • Complete moles arise when an empty ovum is fertilized by more than one sperm cell. This creates a situation in which the entire genome is paternal.
  • Incomplete (partial) moles arise when a normal ovum is fertilized by more than one sperm cell. This creates a polyploid zygote.

Invasive Mole[edit]

Risk factors for individuals with hydatidiform moles developing invasive moles include

  • Uterine size grossly disproportional to gestational age.
  • Bilateral thecal-lutein cysts.
  • Uterine bleeding following evacuation of hydatidiform mole by dilatation and curettage.
  • Age >40 years old.


  • Penetration of molar tissue into the uterine wall and specifically the venous drainage of the uterus/adenexae. This results in embolization of molar tissue.

Choriocarcinoma[edit]

  • From a complete hydatidiform mole, the risk of developing choriocarcinoma is 2-3%.
  • Biphasic proliferation of the cyto- and syncytiotrophoblasts in the absence of chorionic villi.
  • Invasion of the uterine vasculature and embolization to
    • Lungs
    • Brain
    • Liver
    • Lymph nodes
    • Skin
    • Kidney
    • GI tract
    • Vagina

Placental Site Trophoblastic Tumor[edit]

  • Placental site trophoblastic tumors (PSTTs) are composed mainly of intermediate trophoblast which produces human chorionic somatomammotropin and little hCG.

Clinical Presentation and Diagnostic Approach[edit]

Hydatidiform Mole[edit]

Complete moles typically present with

  • Abnormal bleeding between the 6th and 16th week of gestation.
  • Higher than expected HCG levels.
  • Larger than expected uterus.
  • Pre-eclampsia and hyperemesis gravidarum.
  • Bilateral thecal-lutein cysts.

Diagnosis of a complete hydatidiform mole may be done with ultrasound: absent embryo with "snowstorm" pattern.

Incomplete (partial) moles present with

  • Missed/incomplete abortion
  • Smaller HCG rise than in complete moles

Diagnosis of an incomplete (partial) mole is done through documentation of a missed abortion on ultrasound.

Invasive Mole[edit]

Invasive moles typically present with metastases to the

  • Lung
  • Broad ligament of the uterus
  • Vagina
  • Vulva
  • Cervix

Diagnosis of invasive mole is done via

  • Observation of persistent or rising HCG titres following removal of molar tissue.

Choriocarcinoma[edit]

  • Bleeding (from vagina or from metastases)

Diagnosis of choriocarcinoma is done by clinical evaluation and biopsy, although the latter is often not useful.

Placental Site Trophoblastic Tumour[edit]

  • Present as missed abortions

Pathology and Histology[edit]

Hydatidiform Moles[edit]

  • Complete moles are characterized by diffuse trophoblastic hyperplasia with villus thickening, and absent vasculature/embryoblast.
  • Partial moles are characterized by focal trophoblastic hyperplasia, villous swelling, scalloping of the villi, and an embryo and/or present.

Management[edit]

Hydatidiform Mole[edit]

  • Dilatation and curettage is the management of choice for complete and partial hydatidiform moles. With respect to the former, there is an 80% cure rate, with the other 20% developing invasive disease requiring chemotherapy. Fewer than 5% of partial moles develop invasive disease requiring chemotherapy.
    • Overall, 5-15% of patients will develop invasive molar disease and require chemotherapy.
  • Weekly monitoring of the HCG should be done until negative for three consecutive weeks. After this point, monthly monitoring of HCG should be conducted for 6 months.
  • Regular pelvic exams should be conducted and the patient should be advised to use contraception (oral contraceptive pill, if possible) for 6 months.

Invasive Mole[edit]

  • Prior to chemotherapy, the following lab tests should be recorded
    • CBC, Creatinine, Liver Enzymes and Liver Function Tests, CT scan of the head, thorax, and abdomen
  • Therapy delivered will be different based on patient risk profiling: either non-metastatic, low-risk metastatic, and high-risk metastatic (see table below).
    • Non-metastatic invasive moles receive methotrexate or actinomycin-D
    • Low risk patients receive methotrexate and/or actinomycin-D
    • High risk patients recieve surgery, chemotherapy, and radiotherapy
Low-Risk Metastatic High-Risk Metastatic
<4mo since last pregnanc >4mo since last pregnancy
Pretherapy hCG <40000 Pretherapy hCG >40000
No prior chemotherapy Prior chemotherapy
Brain and/or liver mets Brain and/or liver mets
No antecedent term pregnancy Antecedent term pregnancy

Choriocarcinoma[edit]

  • Same treatment as invasive mole

Placental Site Trophoblastic Tumours[edit]

  • Dilatation and curettage
  • Total abdominal hysterectomy