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

OBJECTIVE: To investigate an association between low human chorionic gonadotrophin (hCG) levels at the end of the first week of implantation and later clinical miscarriage occurring after ultrasound confirmation of a live pregnancy. METHODS: This was an observational retrospective study of 1,054 women who underwent in vitro fertilization and achieved an ultrasound-confirmed live singleton pregnancy with cardiac activity. The incidence of miscarriage diagnosed at 8–19 weeks +6 days of gestation was estimated in these 3 subgroups according to their hCG concentrations at day 16 after conception: less than the 25th, 25th–75th, and more than the 75th percentiles. RESULTS: The overall incidence of miscarriage was 11.1% (117/1,054), and the median gestational age at diagnosis was 10 weeks and 4 days. The median (95% confidence interval) day 16 hCG level in the miscarriage group was 182 mIU/mL (157–211), significantly lower than the median level in those who had an ongoing pregnancy (223 mIU/mL [213–233], P < .003). There was an increasing risk of miscarriage associated with decreased hCG levels (8.0% at > 75th percentile; 9.9% at 25th–75th percentiles; 16.7% at < 25th percentile; P = .003). CONCLUSION: Low hCG levels in very early pregnancy are associated with an increased risk of miscarriage occurring after the clinical recognition of pregnancy. The mechanisms underlying late first-trimester and second-trimester miscarriages may have begun as early as the first week of implantation. LEVEL OF EVIDENCE: III