Ovarian stimulation with individualized follitropin delta dosing boosts IVF success

In women with elevated antimüllerian hormone (AMH) levels, tailoring follitropin delta doses based on AMH level and weight for ovarian stimulation helps improve live birth rates, according to the results of a meta-analysis.

Pooled data from three trials that involved 2,685 women undertaking 2,682 in-vitro fertilization cycles showed high-quality evidence that for those with elevated AMH levels (≥15 pmol/L), the use of individualized dosing of follitropin delta was associated with 64-percent greater odds of increased live birth rates as compared with conventional licensed dosing of follitropin alpha or beta (adjusted odds ratio [aOR], 1.64, 95 percent confidence interval [CI], 1.14–2.36; p=0.01). [Fertil Steril 2024;122: 445-454]

Safety outcomes also improved with individualized follitropin delta dosing. Specifically, the odds of early ovarian hyperstimulation syndrome (OHSS) and/or the need for preventative interventions decreased (aOR, 0.27, 95 percent CI, 0.15–0.49; p<0.001), as were the odds of early moderate or severe OHSS (aOR, 0.30, 95 percent CI, 0.16–0.58; p<0.001).

These outcomes, according to the investigators, were observed with a lower total dose of gonadotropin (−48.7 μg, 95 percent CI, −53.7 to −43.8), despite slightly more days of stimulation (adjusted mean difference, 1.02 days).

For women with AMH levels of <15 pmol/L, on the other hand, individualized dosing of follitropin delta showed no beneficial effect on live birth rates (aOR, 0.86, 95 percent CI, 0.63–1.17; p=0.33) and safety outcomes (early OHSS: aOR, 1.92, 95 percent CI, 0.76–4.87; p=0.17; early moderate or severe OHSS: aOR, 1.85, 95 percent CI, 0.63–5.38; p=0.26) relative to conventional licensed dosing of follitropin alpha or beta.

Neonatal outcomes did not significantly differ between treatment groups.

“The analysis indicates that these women, who are at a heightened risk of excessive ovarian response and OHSS, may benefit from the personalized dosing strategy of follitropin delta, which involves no dose adjustments and a lower cumulative dose of gonadotropin compared with conventional licensed dosing,” the investigators said.

“[Hence,] customizing treatment strategies on the basis of patients’ specific AMH levels may enhance assisted reproductive technology treatment outcomes, which supports further investigation into personalized medical approaches,” they added.

In the field of assisted reproduction, AMH levels have been used as a predictive biomarker for ovarian response, and the impact of adiposity and body weight on gonadotropin pharmacokinetics are well-established. [Hum Reprod Open 2020;2020:hoaa009; Hum Reprod Update 2014;20:124-140; Reprod Biomed Online 2011;23:150-159]

“Our study provides compelling evidence that supports the integration of patient-specific characteristics, specifically AMH levels and body weight, into the dosing algorithm for follitropin delta. This is of particular importance given the global diversity in body weights and the recognized ethnic variations in the ovarian reserve,” the investigators pointed out. [Reprod Biomed Online 2020;40:461-467; Reprod Biomed Online 2022;45:979-986]

“Women of Chinese and Southeast Asian heritage typically exhibit lower AMH concentrations compared with their European counterparts. Given the consistent pharmacokinetics of follitropin delta across Chinese, European, and Japanese women, it is plausible that considering these critical phenotypic factors in managing ovarian response could offer benefits for these populations,” they said. [Reprod Biomed Online 2020;40:461-467; Clin Drug Investig 2023;43:37-44]