Detecting defects: low initial serum human chorionic gonadotropin (hCG) level may predict future fetal anomalies following frozen embryo transfer (FET)

Abstract

Purpose: To investigate the relationship between early serum hCG levels after frozen embryo transfer and fetal anomalies.

Methods: This was a case-control study at a single academic fertility center between 1/2010 and 12/2021, including all patients who underwent euploid frozen embryo transfers resulting in any fetal anomaly confirmed at the time of induced abortion > 10 weeks or any anomaly reported at delivery. Controls included patients with healthy live births matched for age and day/grade of embryo after euploid FET. The primary outcome was fetal anomaly, with comparisons made using serum hCG levels from cycle day 28 to cycle day 35 and percent change between days 28 and 35.

Results: Both cycle day 28 serum hCG levels and day 35 serum hCG levels were significantly lower in the anomalous group (day 28: 152 vs 177.5 mIU/mL, p < 0.04; day 35: 3033 vs 3744 mIU/mL, p < 0.05). Patients with anomalous outcomes had a significantly lower hCG to start with 5/78 (6.4%) < 50 mIU/mL, 16/78 (20.5%) 51-100 mIU/mL, and 57/78 (73.1%) > 101 mIU/mL, compared to controls 3/78 (3.8%) < 50 mIU/mL, 8/77 (10.3%) 51-100 mIU/mL, and 66/77 (85.7%) > 101 mIU/mL (p < 0.02). However, the rate of rise between day 28 and day 35 was not statistically different (1758.0% vs 2097.0%, p = 0.23).

Conclusion: Patients with anomalous fetal outcomes following frozen embryo transfer had lower early serum hCG levels than controls with healthy live births, highlighting the potential utility of this serum marker to identify high-risk pregnancies in the first trimester and expedite treatment as appropriate for this rare but devastating outcome.

Keywords: Fetal anomaly; Frozen embryo transfer; Human chorionic gonadotropin predictions.