Individual Participant Data Meta-Analysis

OBJECTIVE

To undertake a one-stage meta-analysis of IPD from randomised, controlled trials comparing individualised dosing of REKOVELLE^® (follitropin delta) vs other forms of follitropin (alfa and beta) for live-birth rates (LBR) and safety parameters in women undergoing ovarian stimulation for in vitro fertilisation (IVF) treatment.

DESIGN

A systematic review identified eligible phase 3 trials between January 2000 and February 2023. The IPD meta-analysis included women undergoing ovarian stimulation for IVF treatment. All IVF procedures were conducted according to routine clinical practice, including undertaking fresh embryo transfers.

The primary outcome was LBR per cycle started

Secondary outcomes included safety as indicated by early ovarian hyperstimulation syndrome (OHSS) and/or preventative interventions for early OHSS, early moderate and severe OHSS and/or preventative interventions for early OHSS, and that the delivered infant was alive at 4 weeks after birth

RESULTS

Overall, 2,685 women underwent 2,682 cycles across 3 different trials between October 2013 and May 2020, with live birth follow up until 1^st February 2023.

Table 1: Results Overview

*Primary endpoint; ^†Or the need for preventative measures.

Adapted from Nelson SM. et al. 2024

KEY PRIMARY OUTCOMES – LBR per cycle started

In women with high anti-Müllerian hormone (AMH) levels (≥15 pmol/L), individualised dosing with REKOVELLE^® significantly increased the chance of LB by 64% compared with follitropin alfa/beta (Figure 1)

Adjusted OR for patients with AMH <15 pmol/L: 0.86 (95% CI: 0.63–1.17), p=0.33

Adjusted OR for patients with AMH ≥15 pmol/L: 1.64 (95% CI: 1.14–2.36), p=0.01

Figure 1: Estimated probability of a LB (%) varying over AMH levels

Adapted from Nelson SM. et al. 2024

KEY SECONDARY OUTCOMES

In patients with AMH ≥15 pmol/L, REKOVELLE^® was shown to significantly reduce the risk of early OHSS (or the need for preventative measures) by 73% and early moderate/severe OHSS (or the need for preventative measures) by 70%, compared with follitropin alfa/beta (Figure 2A and 2B)
These results were achieved with a lower total dose of REKOVELLE^® vs follitropin alfa/beta (Figure 3)

Adjusted OR for patients with AMH <15 pmol/L: 1.92 (95% CI: 0.76–4.87), p=0.17

Adjusted OR for patients with AMH ≥15 pmol/L: 0.27 (95% CI:
0.15–0.49), p<0.001

Adjusted OR for patients with AMH <15 pmol/L: 1.85 (95% CI: 0.63–5.38), p=0.26

Adjusted OR for patients with AMH ≥15 pmol/L: 0.30 (95% CI: 0.16–0.58), p<0.001

Figure 2: (A) Risk of early OHSS or the need for preventative measures (%) in relation to AMH levels (B) Estimated probability of early moderate or severe OHSS or the need for preventative measures (%) varying over AMH levels

Figures adapted from Nelson SM. et al. 2024

Adjusted mean difference for patients with AMH <15 pmol/L: -11.10 (95% CI: -15.21– -7.00), p<0.001

Adjusted mean difference for patients with AMH ≥15 pmol/L: -48.76 (95% CI: -53.70– -43.81), p<0.001

Figure 3: Estimated total follicle-stimulating hormone (FSH) dose (μg) varying over AMH levels

Adapted from Nelson SM. et al. 2024

CONCLUSION

Individualised dosing of REKOVELLE^® (using AMH level and weight-based algorithm) for ovarian stimulation was associated with increased LBR and reduced risk of early OHSS (and/or the need for preventative interventions) and early moderate or severe OHSS (and/or the need for preventative interventions) in women with elevated AMH levels compared with conventional licensed dosing of follitropin alfa or beta (where the dosage is not adjusted to individual patient characteristics).

These findings demonstrate the importance of tailoring treatment strategies according to the individual patient and using biomarkers, such as AMH levels and body weight, to optimise outcomes in assisted reproductive technology

ACCESS THE FULL PAPER