# 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