KEY POINTS:
- Have a high index of suspicion for ectopic pregnancy in any premenopausal woman with abnormal uterine bleeding and pain
- Pregnancy of unknown location requires follow up and a diagnosis
- If patient is clinically stable and pregnancy is desired
- Repeat transvaginal ultrasound and/or serial measurement of quantitative hCG (qHCG)
- If patient is clinically unstable, surgical management is warranted (uterine aspiration, laparoscopy, and /or laparotomy)
- The goal of diagnosing an ectopic pregnancy is to make the determination before rupture, allowing conservative, medical treatment
- Obtain blood type and Rh status on all women suspected of ectopic pregnancy and all Rh-negative women with bleeding should receive anti-D immune globulin (RhoGam), regardless of the final outcome of the pregnancy
- Choice of uterine aspiration for diagnosis should be based on shared decision making
BACKGROUND:
- Pregnancy of unknown location is defined as a pregnancy where intrauterine or ectopic location cannot be confirmed
- Over 90% of ectopic pregnancies are in the fallopian tube; the remainder can occur in the cervix, ovary, uterine cornua, or abdomen.
- Risk factors for ectopic pregnancy include (ACOG PB 193)
- Tubal surgery
- PID
- Previous ectopic pregnancy (10% with one previous ectopic rising to 25% with ≥2)
- Infertility
- Assisted reproductive technologies with multiple embryo transfer
- Previous pelvic/abdominal surgery
- Age >35 years
- Smoking
- Current IUD use
Note: IUDs are associated with fewer ectopics compared to women not using contraception because IUDs are such an effective method of birth control | However, if a woman does become pregnant with an IUD, the risk of an ectopic is approximately 50%
Diagnosis
- Diagnosis of ectopic pregnancy versus failed intrauterine pregnancy depends on the following factors
- qHCG (beta-hCG) ‘Discriminatory Level’ – the level at which an intrauterine gestation can be seen via transvaginal ultrasound with a skilled sonographer
- Levels are specific to sonographers and equipment but generally are set between qHCG of 1500-3500
qHCG Discriminatory Level
- Absence of gestational sac in the uterus above ‘discriminatory level’ has a PPV of 50 to 70% (based on a higher range qHCG level of 3500)
- Multiple gestation may have higher qHCG levels (>2,000 mIU/mL) before ultrasound evidence of pregnancy is visible
- Large fibroids can obscure an intrauterine gestation
- Even with a value of 4000 mIU/mL, 5.6% of women had an early IUP that wasn’t detected on ultrasound (Barnhart et al. Fertil Steril, 2015)
Trending qHCG Levels
- Gestational sac with yolk sac in the uterus is normally visible between 5 to 6 weeks
- Nondiagnostic transvaginal ultrasound: Fails to show a gestational sac with yolk sac in the uterus or the adnexa
- Measure qHCG and then repeat it in 48 hours
- Repeat again every 2 to 7 days based on level/pattern of qHCG results
- Higher the initial level, slower the expected rate of increase
- Expected qHCG rate increase (based on 99%ile rates, 99% of women with normal IUP will have a rise at this rate or faster [Barnhart et al. Obstet Gynecol, 2016])
- <1,500 mIU/mL: 49% increase rate
- 1,500 to 3,000 mIU/mL: 40% increase rate
- >3,000 mIU/mL: 33% increase rate
- An increase in qHCG <50% in 48 hours in an early pregnancy is very concerning but cannot determine location, i.e., ectopic vs intrauterine
- 1% of patients with early viable pregnancies may not meet minimal increase thresholds in 48 hours
Transvaginal Ultrasound (TVUS)
- With ectopic pregnancy, fluid in the uterus mimicking a gestational sac, called a “pseudosac”
- For diagnosis of intrauterine pregnancy need to see double decidual sign or yolk sac on ultrasound
- Mass or hypoechoic area separate from the ovary is ‘suspicious’ but not diagnostic
- PPV is only 80%
- May be confused with paratubal cyst, corpus luteum, hydrosalpinx, endometrioma or bowel
- Once IUP is confirmed on TVUS, trending qHCG is no longer useful or diagnostic for success or failure of IUP
- Some IUP milestones
- Yolk sac should be visualized by a gestational sac of 1.5cm
- Fetal pole should be visualized by gestational sac of 2 cm | However, cannot be sure it is a blighted ovum until approximately 4 cm empty sac.
- Cardiac activity when embryo 1 to 2mm in length
- Absence of FCA when embryo measures >7mm is diagnostic of pregnancy failure
- Absent embryo when mean sac diameter ≥25mm is diagnostic of pregnancy failure
Treatment
- If TVUS or qHCG is not available, or if clinical picture remains unclear
- Diagnostic endometrial aspiration to confirm chorionic villi may be necessary
- Patients should be counseled in advance that this will terminate the pregnancy if intrauterine
- >15% decrease in qHCG levels between 12- and 24-hours following aspiration suggests that villi have been removed
- Continue monitoring qHCG until negative and if a plateau or increase, consider non-visualized ectopic pregnancy, especially if villi do not appear in the specimen
Note: See Ectopic pregnancy management chapter (find link in ‘Related Topics’ below) for MTX and surgical management options
PRIMARY SOURCES:
Gracia and Barnhart. Obstet Gynecol, 2001
A decision analysis compared multiple algorithms to determine the best approach for diagnosing ectopic pregnancy
- Data derived from women presenting with abdominal pain or bleeding in their first trimester
- Results
- Ideal strategy for diagnosing ectopic pregnancy while minimizing interruption of early IUP was TVUS followed by serial qHCG in those cases where the ultrasound was non-diagnostic
- Only 1% of IUPs were interrupted and average time to diagnosis was 1.46 days.
- Progesterone did not prove to be a useful marker in this analysis as it was not specific for pregnancy location.
Seeber et al. Fertil Steril, 2006
- Publication that provides qHCG curves derived from a large cohort of patients to determine the validity of the curves and time to diagnosis
- Results
- By using the rate of change between 2 consecutive qHCG values vs a minimal rise of 35% (IUP curve) or minimal drop of 21 to 35% (SAB curve) the researchers were able to diagnose an ectopic pregnancy on average 2.5 days earlier than by standard clinical practice at the time
- 12% of ectopic cases were diagnosed later, as the initial rise mimicked a normal pregnancy
PROFESSIONAL RECOMMENDATIONS:
ACOG PB 193
- ACOG recommends that
A pregnancy of unknown location should not be considered a diagnosis, rather it should be treated as a transient state and efforts should be made to establish a definitive diagnosis when possible
A woman with a pregnancy of unknown location who is clinically stable and has a desire to continue the pregnancy, if intrauterine, should have a repeat transvaginal ultrasound examination, or serial measurement of hCG concentration, or both, to confirm the diagnosis and guide management
REFERENCES:
Diagnosing ectopic pregnancy and current concepts in the management of pregnancy of unknown location
ACOG Practice Bulletin 193: Tubal Ectopic Pregnancy
Nice guideline 126: Ectopic pregnancy and miscarriage: diagnosis and initial management
ASRM: Medical treatment of ectopic pregnancy: a committee opinion
Imaging of Acute Pelvic Pain: Pregnant (Ectopic and First-trimester Viability Updated)