Ectopic pregnancy: Zero in on these lab and imaging clues
Quantitative β-hCG measurements and transvaginal ultrasound findings interpreted in light of a β-hCG “cutoff” can reliably guide clinical decisions.
Serial ß-hCG levels. When the β-hCG level is below the discriminatory cutoff, serial β-hCG measurements every 2 to 3 days are needed to assess viability of the pregnancy. A “normal rise” of β-hCG indicates early viable pregnancy and “normal fall” indicates spontaneous abortion. An analysis of 287 women with abdominal pain or vaginal bleeding who ultimately had normal uterine pregnancies found that the median slope for rise of β-hCG was 1.5 times (50% increase) in 1 day, and 2.24 times (124% rise) in 2 days.21 A rapid fall in β-hCG is consistent with a miscarriage that may resolve spontaneously. However, if the β-hCG level does not decline by 21% to 35% in 2 days, suspect ectopic pregnancy.21
Arrange for transvaginal ultrasound
TVUS is the imaging modality of choice for diagnosis of ectopic pregnancy, with a sensitivity of 87.0% to 99.0% and specificity of 94.0% to 99.9%.22 Arrange for TVUS when a women has abdominal pain or vaginal bleeding and a positive urine pregnancy test, even if the β-hCG level is lower than the discriminatory cutoff of 1500 to 2500 mIU/mL.13,18-20 Ordering TVUS and β-hCG level at the same time yields the best outcome for diagnosis,19 while varying the discriminatory zone alone has not improved diagnosis.18,23
Other novel markers
The use of serum progesterone and other novel markers such as inhibin A, activin A, creatinine kinase, vascular endothelial growth factor, and cancer antigen 125 in the diagnosis of ectopic pregnancy has been studied extensively. To date, no single marker has demonstrated high sensitivity and specificity in differentiating ectopic pregnancy.24 However, when the initial progesterone level is ≤10 nmol/L (equivalent to 31.4 ng/mL) in a woman with a PUL, the probability that she will require any intervention is reported to be low (4 cases out of 227 PUL cases).25 Multiplex tools to combine multiple biomarkers may become available in the future.
Evacuation of uterine contents
When the β-hCG level is above the discriminatory cutoff but no evidence of an extrauterine or intrauterine pregnancy can be found by TVUS, the patient likely has a failing IUP or impending abortion. Some experts suggest considering evaluation of the uterine contents by dilation and curettage (D&C) or manual vacuum extraction at this time, to differentiate an abnormal intrauterine gestation from an ectopic pregnancy. Barnhart found that more than one-third of such cases were due to a failed uterine pregnancy, not ectopic pregnancy.26
If, after a D&C or manual extraction, chorionic villi are not confirmed by pathologic examination of the uterine contents, then treat as an ectopic pregnancy. Some clinicians alternatively recommend checking the β-hCG level again in 12 to 24 hours, expecting ≥15% decline with a spontaneous abortion.27 Alternatively, some recommend using methotrexate (MTX) without D&C to avoid unnecessary medical and surgical treatment.26
CASE 1 Helen’s serum β-hCG level is 4500 mIU/mL, and the TVUS image the next day shows an echogenic mass next to the right ovary—highly suspicious for ectopic pregnancy.
CASE 2 Mary’s TVUS does not show any evidence of IUP or any abnormality in either adnexa. Her serum β-hCG level is 650 mIU/mL. She has a PUL. Her FP informs her that she may have an early normal pregnancy, a failed IUP, or an ectopic pregnancy. She agrees to have her serum β-hCG measured every 2 days. Her β-hCG level increases to 1100, 2000, and 3500 mIU/mL, in 2, 4, and 6 days, respectively. TVUS on the sixth day is still nondiagnostic.
Treatment of ectopic pregnancy: Surgical vs medical
For hemodynamically unstable patients, laparotomy is still the mainstay of therapy. However, with early diagnosis and a stable patient, options are minimally invasive surgical intervention via laparostomy or medical management with MTX in a single or multidose regimen. Surgical and medical treatments have comparable outcomes, as documented by a Cochrane review.28
The risk of recurrent ectopic pregnancy after MTX treatment and salpingostomy is similar—about 10%.29 Ipsilateral tubal patency as documented by hysterosalpingography after MTX treatment or salpingostomy was reported to be equal.28 Reproductive outcomes after either treatment were similar, as well.30
We recommend urgent referral for OB/GYN consultation if the diagnosis of ectopic pregnancy is made by TVUS, since the recommended treatment is laparoscopic salpingostomy. In the case of a PUL, we recommend referral to an OB/GYN when the serum β-hCG level is above the discriminatory cutoff of 1500 to 2500 mIU/mL without signs of IUP as seen by a gestational sac via TVUS. When an urgent referral is not possible, initiate medical treatment. Regardless of the treatment method, give anti-D immunoglobulin to any woman whose blood is Rh negative (no D-antigen) and who has not been sensitized to D-antigen.
