Association Between Low Day 16 hCG and Miscarriage After Proven Cardiac Activity

Abstract & Commentary

By John C. Hobbins, MD, Professor and Chief of Obstetrics, University of Colorado Health Sciences Center, Denver, is Associate Editor for OB/GYN Clinical Alert.

Dr. Hobbins reports no financial relationship to this field of study.

A group from Australia recently published a study that provides some insight about miscarriage after 8 weeks of gestation. They analyzed data from 1050 patients having in vitro fertilization. Serum hCG levels were measured at 16 days post-conception (approximately for menstrual weeks). All patients had transvaginal ultrasound examinations at 6 to 7 menstrual weeks, but were followed at varying intervals thereafter. Most women in this study had nuchal translucency (NT) testing between 11 and 13 weeks.

The authors included only those embryos with documented fetal heart rate activity at the 6 to 7 week ultrasound examination because they were more interested in the ability of these hormonal levels to predict things to come, rather than events that have already happened. Spontaneous abortion was defined as an inability to document fetal life from 8 weeks until 19 menstrual weeks.

The overall miscarriage rate was 11% and the authors found that the average hCG level in those pregnancies ending in losses was 182 mIU/mL vs 233 mIU/mL in those who did not miscarry. If the hCG level was below the 25th percentile, the loss rate was 16.7%, compared with 8% if the hCG level was above the 75th percentile. The average age of those who miscarried vs those who did not was 38 and 36, respectively—and this was statistically significant.


This report strongly suggests that the writing is already on the wall for many seemingly normal pregnancies since their placentas produce lesser amounts of hCG at 4 weeks of gestation. Aneuploidy screening studies are further evidence to support the concept of showing that the beta subunit of hCG is lower in pregnancies destined for intrauterine demise.

The good news is that, even when the levels of hCG at 4 weeks are below the 25th percentile, more than 4 out of 5 pregnancies will continue at least past the 20th menstrual week.

Here are some milestones which may help the practitioner in following patients anxious about their chances of a successful pregnancy:

Seen on transvaginal ultrasound

Time of visualization

Appearance of gestational sac at 5 menstrual weeks

Appearance of a yolk sac at a mean sac diameter of 8 mm

Embryonic pole at 5 weeks or an hCG of 1000 mIU

Fetal heart activity when CRL is 5 mm

In addition, crown-rump length of the fetus should grow at a rate of 1 mm per day and, as indicated above, should increase by at least 66% in 48 hours.

Suggested Reading

  1. Tong S, et al. Association between low day 16 hCG and miscarriage after proven cardiac activity. Obstet Gynecol. 2006;107:300-304.
  2. Baird DD, et al. Rescue of the corpus luteum in human pregnancy. Biol Reprod. 2003;68:448-456.
  3. Dugoff L, et al. First-trimester maternal serum PAPP-A and free-beta subunit human chorionic gonadotropin concentrations and nuchal translucency are associated with obstetric complications: a population-based screening study (the FASTER Trial). Am J Obstet Gynecol. 2004;191:1446-1451.