Ovarian response to recombinant human follicle stimulating hormone A randomized antiMüllerian hormone stratified dose response trial in women undergoing in vitro fertilization intracytoplasmic sperm injection

Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner.

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Joan-Carles Arce, M.D., Ph.D., Anders Nyboe Andersen, M.D., Ph.D., Manuel Fernández-Sánchez, M.D., Ph.D., Hana Visnova, M.D., Ph.D., Ernesto Bosch, M.D., Ph.D., Juan Antonio García-Velasco, M.D., Ph.D., Pedro Barri, M.D., Ph.D., Petra de Sutter, M.D., Ph.D., Bjarke M. Klein, Ph.D., Bart C.J.M. Fauser, M.D., Ph.D.

Volume 102, Issue 6, Pages 1633-1640



To evaluate the dose–response relationship of a novel recombinant human FSH (rhFSH; FE 999049) with respect to ovarian response in patients undergoing IVF/intracytoplasmic sperm injection treatment; and prospectively study the influence of initial anti-Müllerian hormone (AMH) concentrations.


Randomized, controlled, assessor-blinded, AMH-stratified (low: 5.0–14.9 pmol/L [0.7–


Seven infertility centers in four countries.


Two hundred sixty-five women aged ≤37 years.


Controlled ovarian stimulation with either 5.2, 6.9, 8.6, 10.3, or 12.1 μg of rhFSH, or 11 μg (150 IU) of follitropin alfa in a GnRH antagonist cycle.

Main Outcome Measure(s):

Number of oocytes retrieved.


The number of oocytes retrieved increased in an rhFSH dose–dependent manner, from 5.2 ± 3.3 oocytes with 5.2 μg/d to 12.2 ± 5.9 with 12.1 μg/d. The slopes of the rhFSH dose–response curves differed significantly between the two AMH strata, demonstrating that a 10% increase in dose resulted in 0.5 (95% confidence interval 0.2–0.7) and 1.0 (95% confidence interval 0.7–1.3) more oocytes in the low and high AMH stratum, respectively. Fertilization rate and blastocyst/oocyte ratio decreased significantly with increasing rhFSH doses in both AMH strata. No linear relationship was observed between rhFSH dose and number of blastocysts overall or by AMH strata. Five cases of ovarian hyperstimulation syndrome were reported for the three highest rhFSH doses and in the high AMH stratum.


Increasing rhFSH doses results in a linear increase in number of oocytes retrieved in an AMH-dependent manner. The availability of blastocysts is less influenced by the rhFSH dose and AMH level.

Clinical Trial Registration Number


Read the full text at: http://www.fertstert.org/article/S0015-0282(14)02072-X/fulltext

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.