Pregnancy of unknown location

Abstract

Pregnancy of unknown location is a situation in which a positive pregnancy test occurs, but a transvaginal ultrasound does not show intrauterine or ectopic gestation. One great concern of pregnancy of unknown location is that they are cases of ectopic pregnancy whose diagnosis might be postponed. Transvaginal ultrasound is able to identify an ectopic pregnancy with a sensitivity ranging from 87% to 94% and a specificity ranging from 94% to 99%. A patient with pregnancy of unknown location should be followed up until an outcome is obtained. The only valid biomarkers with clinical application and validation are serum levels of the beta fraction of hCG and progesterone. A single serum dosage of hCG is used only to determine whether the value obtained is above or below the discriminatory zone, that means the value of serum hCG above which an intrauterine gestational sac should be visible on ultrasound. Serum progesterone levels are a satisfactory marker of pregnancy viability, but they are unable to predict the location of a pregnancy of unknown location: levels below 5 ng/mL are associated with nonviable gestations, whereas levels above 20 ng/mL are correlated with viable intrauterine pregnancies. Most cases are low risk and can be monitored by expectant management with transvaginal ultrasound and serial serum hCG levels, in addition to the serum progesterone levels. To minimize diagnostic error and intervene during progressive intrauterine gestation, protocol indicates active treatment only in situations when progressive intrauterine pregnancy is excluded and a high possibility of ectopic pregnancy exists.

Evaluating cut‐off levels for progesterone, β human chorionic gonadotropin and β human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study

“…In this large data set, PUL with a single βhCG as high as 105 006 IU/L, a single progesterone as low as 5 nmol/L, and a βhCG ratio as low as 1.02 have been associated with viable pregnancies at 11–14 weeks of gestation. Although cut‐off levels have been identified that are associated with non‐viability in our data set, again these only reflect our specific population and cannot be generalized 3–19 . Indeed, upon literature review, cases of VIUP have been reported with lower progesterone levels (3 nmol/L) and falling serial βhCG values (βhCG ratio <1) that begin as high as 167 343 IU/L, further supporting the argument that cut‐off levels in the differentiation of viability in PUL are subjective and unreliable 15,20,36,37 …”

“…Our findings categorically show that the use of single “discriminatory zone” measurements for serum βhCG have poor diagnostic performance and should not be used in clinical practice to exclude the presence of an intrauterine pregnancy. This is important as some guidelines still state that women classified with a PUL who are found to have a single βhCG measurement at presentation of more than 3000, 2000 or even 1000 IU/L are unlikely to have an intrauterine pregnancy and a presumption may be made that the pregnancy is in the fallopian tube 16–19 . Not surprisingly, this has led to the use of the discriminatory zone remaining part of local guidelines and is still being used by some clinicians 3,9,11 .…”

“…Literature and guidance in several countries including Brazil, the USA and France state that intrauterine pregnancy (IUP) should be reliably visualized on TVS when βhCG discriminatory levels are either more than 1500 to 2500 IU/L, more than 3500 IU/L, or more than 3510 IU/L. The presumption is that an EP is likely to be present if an IUP cannot be visualized 9,16–19 . Pregnancies with progesterone levels below 5–10 nmol/L are also classified as non‐viable according to some authors 17,19 …”

Ultrasound

“…PUL is defined as pregnancy in a woman showing positive results on serum ßhCG testing but without topical intrauterine pregnancy or EP on TVUS. PUL outcomes include the following: intrauterine pregnancy (viable, non-viable, or early pregnancy with uncertain evolution), EP, failed PUL (PULF), or persistent PUL (PULP) [20][21][22].…”

“…A spontaneous decline in serum ßhCG levels does not occur in PULP; usually a <15% increase is observed in the serum ßhCG level measured on three consecutive occasions at 48-hour intervals or this level tends to plateau. Additionally, an intrauterine or ectopic gestational sac is not visualized [22].…”