Intercycle variability of the ovarian response in patients undergoing repeated stimulation with corifollitropin alfa in a gonadotropin releasing hormone antagonist protocol

Capsule:
The considerable variability in individual ovarian responses observed between repeated IVF cycles conducted using the same protocol were not explained by baseline serum follicle-stimulating hormone concentrations or antral follicle count.

Authors:
Luk Rombauts, Ph.D., Cornelis B. Lambalk, M.D., Ph.D., Askan Schultze-Mosgau, Ph.D., Jacqueline van Kuijk, M.Sc., Pierre Verweij, Ph.D., Davis Gates, Ph.D., Keith Gordon, Ph.D., Georg Griesinger, Ph.D.

Volume 104, Issue 4, Pages 884-890

Abstract:

Objective:
To determine whether individual subject variation in ovarian response between repeated cycles with the same ovarian stimulation protocol can be predicted.

Design:
Retrospective data analysis.

Setting:
Not applicable

Patient(s):
Women aged 18–39 from a phase 3, open-label, uncontrolled trial with complete data across all cycles (n = 176).

Intervention(s):
Up to three cycles of a single injection of 150 μg corifollitropin alfa for 7 days, then daily recombinant FSH/hMG until three follicles reached ≥17 mm. Gonadotropin-releasing hormone antagonist from stimulation day 5 until day of hCG administration.

Main Outcome Measure(s):
Numbers of follicles ≥11 mm on day of hCG in cycles 1–3, transition in ovarian response type between cycles from low (0–<6), normal (6–<18), and high (≥18), and serum FSH concentrations and antral follicle count (AFC) at each cycle start. Result(s):
The mean (SD) numbers of follicles ≥11 mm on day of hCG were 13.4 (6.2), 13.3 (5.4), and 13.8 (6.4) in cycles 1, 2 and 3, respectively. Between cycles 1 and 2, 11.9% switched from normal to low or high response, and 12.5% switched from low or high to normal response; 75.6% remained in the same category. Between cycles 2 and 3, 15.9% switched from normal to low or high response, and 10.2% switched from low or high to normal response; 73.9% remained in the same category. These shifts are symmetrical in nature, in that the percentage of subjects who shift from normal to low or high response is comparable to the percentage of subjects who shift from low or high to normal response. Baseline FSH and AFC did not significantly predict transition in ovarian response.

Conclusion(s):
The variability in ovarian responses between repeated cycles using the same protocol was not explained by baseline FSH and AFC.

Clinical Trial Registration Number:
NCT00696878 Protocol P05714.

  • This study reveals that there is significant intercycle variability of the ovarian response across consecutive IVF cycles with the same protocol. This brings up the questions whether
    1) the practice of switching protocols after a previous low response is not helpful and another cycle with the same protocol should be attempted first
    2) counseling a patient about donor egg after one cycle with poor response may be premature.
    However this study was not done specifically in patients with poor ovarian reserve, in which the rate of switching from low to normal response may be less common.

    • Luk Rombauts

      Thanks Alex.
      Those are very valid points to make.

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