Triggering with 1,500 IU of hCG plus FSH compared to a standard human chorionic gonadotropin trigger dose for oocyte competence in in vitro fertilization cycles: a randomized, double-blinded, controlled noninferiority trial

Compared to the standard human chorionic gonadotropin dose, triggering with 1,500 IU human chorionic gonadotropin plus 450 IU follicle-stimulating hormone produced noninferior oocyte competence in in vitro fertilization.

VOLUME 118, ISSUE 2, P266-278


Yanett Anaya, M.D., Hakan Cakmak, M.D., Douglas A. Mata, M.D., Joseph Letourneau, M.D., Li Zhang, Ph.D., Nikolaus Lenhart, B.S., Flor Juarez-Hernandez, B.A., Liza Jalalian, M.S., Marcelle I. Cedars, M.D., Mitchell Rosen, M.D.



To assess if triggering with 1,500 IU of human chorionic gonadotropin (hCG) with 450 IU of follicle-stimulating hormone (FSH) induces noninferior oocyte competence to a standard dose of hCG trigger used in in vitro fertilization (IVF). The alternative trigger will be considered noninferior if it is at least 80% effective in promoting oocyte competence.


Randomized, double-blinded, controlled noninferiority trial.


Academic infertility practice.


Women aged 18–41 undergoing IVF with antral follicle count ≥8, body mass index ≤30 kg/m2, and no history of ≥2 IVF cycles canceled for poor response were enrolled. Participants with a serum estradiol >5,000 pg/mL on the day of trigger were excluded because of high risk of ovarian hyperstimulation syndrome.


Participants were randomized to receive an alternative trigger of 1,500 IU of hCG plus 450 IU of FSH or a standard trigger dose of hCG (5,000 or 10,000 IU) for final oocyte maturation.

Main outcome measures

The primary outcome was total competent proportion, defined as the probability of 2 pronuclei from an oocyte retrieved. The alternative trigger will be considered noninferior to the standard trigger if a 1-sided 95% confidence interval (CI) of the relative risk (RR) is not <0.8. Secondary outcomes included oocyte recovery and maturity, intracytoplasmic sperm injection fertilization, embryo quality, pregnancy rates, as well as serum and follicular hormones. Secondary outcomes were compared using a 2-sided superiority test. Outcomes were analyzed by intention-to-treat and per-protocol.


A total of 105 women undergoing IVF were randomized from May 2015 to June 2018. The probability of the primary outcome was 0.59 with the alternative trigger and 0.65 with the standard trigger, with a RR of 0.91 and a 1-sided 95% CI of 0.83. Noninferiority of the alternative trigger was demonstrated. Live birthrate from all fresh transfers in the alternative trigger group vs. standard trigger was 46.9 vs. 46.4% (RR, 1.01; 95% CI, 0.62–1.62), respectively. Live birthrate per randomized participant was 48.1% in the alternative trigger group vs. 62.7% with the standard trigger (RR, 0.73; 95% CI, 0.48–1.11). No participants had a failed retrieval.


Triggering with 1,500 IU of hCG plus 450 IU of FSH promoted noninferior oocyte competence compared to a standard hCG trigger dose.

Trial registration


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