Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins

We report the 3-year developmental and neurodevelopmental data, growth, and medical history data from a group of children conceived in two large infertility trials (PPCOS II and AMIGOS) with gonadotropin, clomiphene, or letrozole.


Richard S. Legro, M.D., Michael P. Diamond, M.D., Christos Coutifaris, M.D., Ph.D., William D. Schlaff, M.D., Ruben Alvero, M.D., Peter Casson, M.D., Gregory M. Christman, M.D., R. Mitchell Rosen, M.D., Marcelle I. Cedars, M.D., Karl R. Hansen, M.D., Ph.D., Randal Robinson, M.D., Valerie Baker, M.D., Rebecca Usadi, M.D., William C. Dodson, M.D., Stephanie J. Estes, M.D., Allen Kunselman, M.A., Christina Stetter, B.S., Kurt T. Barnhart, M.D., M.S.C.E., R. Matthew Coward, M.D., J.C. Trussell, M.D., Stephen A. Krawetz, Ph.D., Nanette Santoro, M.D., Hao Huang, M.D., M.P.H., Heping Zhang, Ph.D., Esther Eisenberg, M.D., M.P.H., for the Reproductive Medicine Network



To study the development of children conceived from non-IVF infertility treatments consisting of gonadotropins, clomiphene, or letrozole.


Prospective cohort study.


U.S. academic health centers.


Children of women with polycystic ovary syndrome who conceived with letrozole (LTZ) or clomiphene (CC) in the PPCOS II study or women with unexplained infertility (AMIGOS study) who conceived with LTZ, CC, or gonadotropin (GN).


Longitudinal annual follow-up from birth to age 3.

Main Outcome Measure(s)

Scores from Ages and Stages Developmental Questionnaire (ASQ), MacArthur-Bates Communicative Development Inventory (MCDI), and annual growth.


One hundred eighty-five children from 160 families participated in at least one follow-up evaluation from the two infertility trials. Most multiple gestations in the follow-up study resulted from GN treatment (n = 14) followed by CC (n = 6) and LTZ (n = 3). There were no significant differences among the three groups at any time point with respect to abnormal scores on the ASQ. On the MCDI Words and Gestures, the LTZ group scored significantly higher than the GN group for most items (phrases, early gestures, later gestures, and total gestures). Children in the CC group scored significantly higher than the GN group for the later gestures and total gestures items.


Differences in growth and cognitive developmental rates among children conceived with first-line infertility therapies, including LTZ, are relatively minor and likely due to differences in multiple pregnancy rates.

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