Biochemical Pregnancies and Their Management

Abstract

There is little information in the literature about biochemical pregnancies (BP). However, BP (a pregnancy that regresses before imaging with ultrasound) is a significant problem in IVF and recurrent miscarriage clinics. The incidence of between 13-22% of pregnancies may be confounded as today’s sensitive pregnancy tests may detect endometrial, pituitary, or phantom hCG. A false positive result may also follow extraneous hCG administered in an ART cycle. Hence, the author has suggested a rising hCG level at two consecutive tests as a definition and that one raised hCG level should be known as a raised isolated hCG level. The etiology remains unclear. Embryonic aneuploidy, thinned endometrium, sperm defects, and defective angiogenesis have been suggested. Additionally, several biochemical pregnancies are early ectopic pregnancies that fail to develop further. 
We see a subsequent live birth rate of 53% in untreated patients with two or more biochemical pregnancies. However, our team treats recurrent BP’s as recurrent pregnancy loss (RPL) as suggested by ESHRE. However, treatment to prevent further BPs is empiric, with no evidence in the literature. The author uses hCG supplementation to enhance implantation. 61 of 87 patients (70%) with >2 biochemical pregnancies and 12 out of 14 patients (86%) with >4 biochemical pregnancies delivered with hCG supplementation. These figures compare favorably to the 53% live birth rate with no treatment, but power analysis shows that 228 patients would be required to show statistical significance. The author has used IVIg on 20 patients with >5 biochemical pregnancies, with 50% terminated as live births. However, the results may be confounded as the previous biochemical pregnancies may have been early ectopic pregnancies, and the subsequent pregnancy intra-uterine. 
If a biochemical pregnancy becomes persistent and hCG levels fail to fall, methotrexate may be required, as in early ectopic pregnancies.