One jab of corifollitropin alfa equipotent to daily 300 IU of follitropin beta

In a combined analysis of three phase III randomized trials presented at ESHRE 2024, a single dose of 150 µg or 100 µg of corifollitropin alfa is found to provide an ovarian response equivalent to daily doses of 300 IU or 297 IU of follitropin beta, respectively, during a single in vitro fertilization (IVF) cycle.

The quantification aids in explaining the findings that a single dose of corifollitropin alfa provided a higher ovarian response than daily doses of 150 IU or 200 IU of follitropin beta in both predicted normal and predicted high responders. [ESHRE 2024, poster P-578]

The number of oocytes retrieved following either a 150-µg or a 100-µg dose of corifollitropin alfa was similar to that obtained with daily doses of 300 IU of follitropin beta, and this similarity remained across all predicted ovarian response groups.

Engage, Ensure, and Pursue

Corifollitropin alfa is a sustained follicle stimulant that has a pharmacodynamic profile similar to that of recombinant follicle-stimulating hormone (rFSH), but with a prolonged duration of action.

Structurally, corifollitropin alfa is composed of an unmodified FSH α subunit and an FSH β subunit fused with the carboxy-terminal peptide of the human chorionic gonadotropin β subunit. This modification extends the FSH analogue’s elimination half-life by approximately twofold, thus allowing for the replacement of 7 days of daily rFSH.

The three phase III trials included in the analysis — Engage, Ensure, and Pursue — have all demonstrated the noninferiority of corifollitropin alfa to daily follitropin beta for the first 7 days during a single IVF cycle, with respect to either pregnancy rate or the number of oocytes retrieved. [Hum Reprod 2009;24:3063-3072; Reprod Biomed Online 2010;21:66-76; Fertil Steril 2015;104:94-103.e1]

One advantage of corifollitropin alfa over follitropin beta, in addition to its convenience, is a higher number of oocytes retrieved with corifollitropin alfa, as demonstrated in the three trials. In Engage and Ensure, the replacement of follitropin beta with corifollitropin alfa for the first 7 days resulted in 1.2 and 2.5 additional oocytes retrieved, respectively (p=0.001 [Engage] and p<0.001 [Ensure]). In Pursue, the corifollitropin alfa arm had, on average, 0.5 additional oocytes retrieved, though it was not statistically significant.

Since the three trials did not use the same doses of corifollitropin alfa or follitropin beta, pooling the individual data allows for the determination of a precise equipotent dose between the two FSH agonists (n=3,292). A multivariate model was developed incorporating antral follicle count (AFC), age, body weight, and the AFC-age interaction as covariates.

An evident dose-response relationship for follitropin beta was observed in predicted normal responders (AFC 8–14) and predicted high responders (AFC ≥15). However, this relationship diminished in predicted low responders (AFC ≤7), as the number of oocytes retrieved in this group did not increase at the dose of 300 IU compared with the 150 IU or 200 IU doses.

In the case of corifollitropin alfa, both a single dose of 150 µg and 100 µg resulted in a comparable number of oocytes in predicted low responders, as well as in the other two responder groups.

“With corifollitropin alfa treatment, the potential of a single IVF cycle is maximized with an ovarian response comparable to daily 300 IU rFSH, which can be safely managed by gonadotropin-releasing hormone agonist triggering and a freeze-all strategy,” concluded leader author Professor Juan García-Velasco from IVI-RMA Madrid, Madrid, Spain.