Association of the very early rise of human chorionic gonadotropin with adverse outcomes in singleton pregnancies after in vitro fertilization

Slower very early first-trimester human chorionic gonadotropin rise is associated with low birth weight but not gestational age at delivery among singleton in vitro fertilization conceptions.

Christopher B. Morse, M.D., Kurt T. Barnhart, M.D., M.S.C.E., Suneeta Senapati, M.D., M.S.C.E., Mary D. Sammel, Sc.D., Erica C. Prochaska, B.A., Anuja Dokras, M.D., Ph.D., Charalampos Chatzicharalampous, M.D., Christos Coutifaris, M.D., Ph.D.

Volume 105, Issue 5, Pages 1208-1214


To determine if very early serum hCG, a marker of trophoblast differentiation, is associated with adverse perinatal outcomes in singleton pregnancies.

Retrospective cohort study.

University fertility program.

A total of 360 singleton IVF live births.

Serial hCG measurements were used to determine the within-woman slope for hCG (hCG rise).

Main Outcomes Measure(s):
Primary outcomes included birth weight and gestational age at delivery. Statistical comparisons used t test, chi-square test, and linear and logistic regressions as appropriate.

hCG rise was positively associated with birth weight but not gestational age at delivery. Infant sex, gestational age, and type of embryo transfer (fresh vs. frozen/thawed) were significantly associated with birth weight and confounded the associations of interest. hCG rise was slower among subjects delivering an infant with low birth weight (slope 0.386 ± 0.05 vs. 0.407 ± 0.06) or small for gestational age (slope 0.371 ± 0.07 vs. 0.406 ± 0.06). Analysis of hCG rise by quartile showed that, compared with the first quartile (slowest), subjects with a rate of hCG rise in the fourth quartile (fastest) had a significantly decreased risk of delivering an infant of low birth weight. No relationship was noted between hCG rise and hypertensive disorders of pregnancy.

Slower very early first-trimester hCG rise is associated with low birth weight but not gestational age at delivery among singleton IVF conceptions. The rate of increase in serum hCG may reflect early trophoblast differentiation and placentation and, possibly, may predict subsequent development.

  • Kurt Barnhart

    Dear Dr Kaser
    Thank you for your kind comments. We did include all transfers (day 3 and day 5) in our analysis, and we did control for this difference. While the numbers are too small to say with confidence, there did not appear affect based on day 3 vs day 5.
    I hope others will replicate this novel finding!
    Kurt Barnhart

  • Daniel J. Kaser, MD

    Dear Dr. Morse and colleagues,

    Congratulations on this report demonstrating a significant positive association with slower hCG rise and low birth weight in an IVF population. For clarification, were all of the included cycles at the cleavage-stage or were blastocyst transfers included as well? If both, did you consider day of ET as a potential confounder?

    Thanks very much for your comments.

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