Algorithm vs clinical experience: controlled ovarian stimulations with follitropin delta and individualised doses of follitropin alpha/beta

Abstract

In the registration trials, follitropin delta was compared with a fixed dose of 150 UI of follitropin alpha/beta, finding higher chances to reach a target response of 8–14 oocytes compared to controls. For this reason, follitropin delta is marketed as particularly useful in expected hyper-responder patients. The main outcome of this study is to report if comparable results are reached in a real-life scenario with follitropin alpha/beta doses chosen by the physician, based on patients’ characteristics. This is a retrospective study performed in two public fertility centres. All first cycles from January 2020 to June 2022 with either follitropin delta (cases) or alpha/beta (controls) in patients with anti-Müllerian hormone >2.5 ng/mL were compared by an inverse probability weighting approach based on propensity score. The follitropin total dose was higher in controls (1179.06 ± 344.93 vs 1668.67 ± 555.22 IU, P < 0.001). The target response of 8–14 oocytes was reached by 40.2% of cases and 40.7% of controls (odds ratio (OR): 0.99, 95% confidence interval (CI): 0.65–1.53, P = 0.98). Fewer than 8 oocytes were collected in 24.1% of cases and 22% of controls (OR: 1.10, 95% CI: 0.71–1.69, P = 0.67); more than 14 oocytes in 35.7% of cases and 37.3% of controls (OR: 0.83, 95% CI: 0.54–1.28, P = 0.40). Our experience did not find worse results in term of proportion of patients who reached the target response with an algorithm-chosen dose of follitropin delta compared to a personalised starting dose of follitropin alpha/beta, with follitropin delta having the advantage of objectivity. However, larger numbers are needed to confirm these results. Lay summary The starting dose of the drugs used to stimulate the ovaries in IVF (gonadotropins) is usually decided by the doctor, using their clinical experience and expertise and tailored to the individual patient. Recently one type of stimulating drug (follitropin delta) was marketed with an algorithm for deciding the starting dose based on the patient’s anti-Müllerian hormone (AMH) levels and weight. In the initial trials, it was compared with a fixed dose of standard follitropins (alpha/beta), and it was found to reduce the likelihood of an excessive response in patients at risk of ovarian hyperstimulation syndrome. We report on these results, in terms of number of eggs obtained, in patients with an expected high ovarian response, compared to doses of standard follitropins that were not fixed, but personalised, to see if this did not make a difference. We found similar results in the two groups, suggesting that using the algorithm to decide the dose of follitropin delta does not work less well than a personalised starting dose of follitropin alpha/beta, but has the advantage of being objective.