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

Spontaneous Abortion

Solitary Spontaneous Abortion

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

• 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

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

Etiology

• 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

• 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

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

Recurrent Abortion

Definition and Clinical Presentation

• 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

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

• 1-2% of couples experience recurrent abortions

Etiology

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

Management

• 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

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

Epidemiology

• 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

• 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

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

Diagnosis

• 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

• 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

Epidemiology

• 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

• 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

• Very rare

Etiology, Risk Factors, and Pathophysiology

Hydatidiform Mole

• 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

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

• 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

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

Clinical Presentation and Diagnostic Approach

Hydatidiform Mole

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

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

• 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

• Present as missed abortions

Pathology and Histology

Hydatidiform Moles

• 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

Hydatidiform Mole

• 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

• 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 receive 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

• Same treatment as invasive mole

Placental Site Trophoblastic Tumours

• Dilatation and curettage
• Total abdominal hysterectomy