When a pregnancy fails early
None of the authors has a conflict of interest to report with respect to the content of this article.
From the start, pregnancy poses significant risk to a woman’s health, and differentiating normal from abnormal gestation may be challenging for a clinician. The time from a positive urine pregnancy test (UPT) to a confirmed viable pregnancy can be a few weeks, during which there can be cramping, spotting, and lack of early pregnancy signs, all of which may lead to anxiety for a patient.
The major goal for the clinician is to confirm the location and viability of the pregnancy. Diagnosing a normal intrauterine, an abnormal intrauterine, or abnormally located pregnancy may be complicated and is integral for management of pregnancy. Certain conditions (eg, ectopic pregnancy, molar pregnancy) can not only fail to result in a live birth but also impose significant maternal morbidity and mortality unless treated promptly. The term early pregnancy loss or failure (EPF) refers to a non-viable, intrauterine pregnancy with either an empty gestational sac or a gestational sac containing an embryo or fetus without heart activity within the first 12 6/7 weeks of gestation.1 At the same time premature assumption of the non-viability of a pregnancy can result in over-diagnosis of EPF and irreversible treatment measures in cases of very early but potentially viable pregnancies. That can be detrimental when the pregnancy is desired. Since falsely diagnosing a pregnancy as failed carries potentially more harmful consequences than delay in diagnosing a failed pregnancy, the specificity goal for the criteria for the diagnosis of non-viability is 100%.2 The formulation of this goal in the context of several large multicenter studies necessitated challenging the prior diagnostic cutoffs and timelines. The consequence was a recent change in guidelines for diagnosis of EPF, which on one hand made the criteria more strictly outlined and, on the other hand, allowed for longer waiting time prior to making the final determination of non-viability.3,4 Here we review the current guidelines and available literature on early pregnancy diagnosis (up to 12 6/7 weeks’ gestation), localization and identification of viability as well as management options and counseling.
In most cases, the diagnosis of pregnancy is made with a positive pregnancy test (using urine or blood) in a reproductive-age women. This may be done when a woman is anticipating a pregnancy or she develops normal pregnancy-related symptoms (such as amenorrhea, nausea and vomiting, and breast tenderness) or abnormal pregnancy-related symptoms (unusual vaginal bleeding, back or lower abdominal pain) or even signs of clinical instability (life-threatening vaginal bleeding, syncopal episode, etc.).
Human chorionic gonadotropin
The pregnancy test in current use is based on detection of human chorionic gonadotropin (hCG) in a woman’s urine or blood. hCG is a 237 aminoacid glycoprotein hormone produced largely by syncytiotrophoblast cells and composed of alpha and beta subunits. Its main function is to stimulate progesterone production by the corpus luteum until approximately 14 weeks’ gestation. In normal singleton pregnancy hCG starts to rise as early as 6–12 days after ovulation and reaches its peak of 100,000 at ~10 weeks’ gestation, after which it slowly decreases to a plateau of 20,000 mIU/mL in the mid-second trimester, where it stays until delivery.5,6
Although beta hCG is the predominant form of hCG in the urine of pregnant women, home pregnancy tests are designed to detect both hCG and beta hCG. The sensitivity of over-the-counter tests varies greatly among brands and ranges from 0.4 to 6.3 IU/L (despite manufacturer-claimed sensitivity of 25 IU/L).8
Most serum assays are now designed to measure hCG and hCG-beta equally. The sensitivities of current quantitative pregnancy tests are ~25 IU/L and 1 IU/L for enzyme-linked assays and fluoroimmunoassays, respectively. The upper limit of the reference range is ~3 IU/L in non-pregnant women <50 years old and ~5.4 IU/L in women >50 years old.9