Synchronization of Ovarian Stimulation with Follicle Wave Emergence in Patients undergoing in vitro fertilization with a Prior Suboptimal Response A Randomized Controlled Trial

Synchronizing ovarian stimulation with follicle wave emergence in patients with a prior suboptimal response resulted in an increase in the number of follicles that developed and serum E2 concentrations; however, corresponding improvements in oocyte, embryo, and pregnancy outcomes were not observed.

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Angela Baerwald, Ph.D., Paula Anderson, R.N., B.Sc.N., Albert Yuzpe, M.D., Allison Case, M.D., Margo Fluker, M.D.

Vol 98, Issue 4, Pages 881-887.e2



To test the hypothesis that synchronizing initiation of ovarian stimulation with follicle wave emergence would optimize IVF/intracytoplasmic sperm injection (ICSI) outcomes in patients with a prior suboptimal response.


Prospective, randomized, controlled trial.


Academic and private reproductive endocrinology and infertility centers.


Eighty women ≤43 years of age with a history of a suboptimal response.


Initiation of recombinant FSH/GnRH antagonist/recombinant LH/hCG on day 1 (n = 39) or day 4 (n = 41).

Main Outcome Measures:

Numbers of clinical and biochemical pregnancies, follicles >10 and >15 mm, oocytes collected, fertilized oocytes, cleavage-stage embryos, and blastocysts; serum estradiol concentrations. Outcomes were compared between treatment groups.


The numbers of follicles that developed to >10 and >15 mm and serum estradiol were greater when rFSH was initiated on day 1 (5.4, 4.3, 5827.2 pmol/L) versus day 4 (3.6, 2.5, 4230.1 pmol/L) (p<0.05). The numbers of collected, MII, and fertilized oocytes; cleavage-stage embryos; and blastocysts were not different between groups (p>0.05). When we evaluated only those cycles that proceeded to OPU, a lower implantation rate (16.1%, 56.0%; p=0.02), biochemical pregnancy rate (16.1%, 48.0%; p=0.01), and clinical pregnancy rate (12.9% versus 36.0%; p=0.03) were detected in the day 1 versus 4 group.


Synchronizing initiation of ovarian stimulation with follicle wave emergence in patients with a prior suboptimal response resulted in an increase in the number of dominant follicles and serum estradiol concentrations; however, improvements in oocyte, embryo or pregnancy outcomes did not occur.

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