Simplified Fertility Drug Dosing Matches Standard Approach in IVF Freeze-All Cycles

A large cohort study from Vietnam suggests that a simplified, fixed-dose regimen of follitropin delta, a next-generation follicle-stimulating hormone preparation, can deliver live birth rates comparable to the conventional follitropin alfa approach in women undergoing in vitro fertilisation with a freeze-all strategy. The research, published in the Journal of Ovarian Research, offers a pragmatic answer to a practical problem that has lingered since follitropin delta first entered the fertility clinic: its official dosing algorithm was designed for a specific hormonal protocol and fresh embryo transfer, leaving clinicians uncertain about how to use the drug in the increasingly popular progestin-based cycles where every embryo is frozen before transfer.

Follitropin delta is a recombinant follicle-stimulating hormone, or FSH, produced in a human cell line, which gives it higher biopotency than earlier recombinant products derived from hamster cells. Because of this increased potency, the drug is measured in micrograms rather than the international units used for other gonadotrophins. When regulators approved it, they endorsed an individualised dosing algorithm that takes a patient’s anti-Müllerian hormone level and body weight into account. That algorithm, however, was validated in gonadotrophin-releasing hormone antagonist protocols culminating in fresh embryo transfer. In freeze-all cycles, where ovarian stimulation is deliberately decoupled from embryo transfer to reduce the risk of ovarian hyperstimulation syndrome and to allow endometrial preparation on the patient’s own timetable, the algorithm’s assumptions no longer hold neatly, and many clinics have found it cumbersome to apply.

The progestin protocol has emerged as an increasingly adopted alternative for freeze-all IVF cycles. Instead of using a GnRH agonist or antagonist to prevent the premature surge of luteinising hormone that could trigger ovulation before egg retrieval, clinicians administer a progestin, a synthetic progesterone-like compound, which suppresses the surge effectively and inexpensively. Combined with the freeze-all strategy, in which all embryos are cryopreserved and transferred in a later, physiologically calmer cycle, the progestin protocol has expanded access to IVF in many settings. Yet no evidence existed on how follitropin delta’s simplified dosing regimens, which had shown promise in antagonist protocols, would perform in this context. The new study set out to fill that gap.

Researchers led by Tien Khac Le of IVFMD Phu Nhuan, My Duc Phu Nhuan Hospital, and colleagues across several Vietnamese institutions conducted a multicentre retrospective cohort study spanning May 2023 to September 2024 at three tertiary hospitals: My Duc Hospital and My Duc Phu Nhuan Hospital in Ho Chi Minh City, and the Family Hospital in Da Nang. They included women undergoing their first IVF or intracytoplasmic sperm injection cycle with a progestin protocol and a freeze-all indication. Patients received either follitropin delta at one of three fixed starting doses of 9, 12, or 18 micrograms per day, or follitropin alfa at 150, 225, or 300 international units per day, with the dose in both groups selected according to the woman’s anti-Müllerian hormone level. This stratified, fixed-dose approach deliberately bypasses the complex individualised algorithm, trading mathematical precision for bedside simplicity.

Because the study was observational rather than randomised, the investigators faced the familiar challenge of confounding: women prescribed one drug might differ systematically from those prescribed the other in age, weight, or ovarian reserve. To address this, they used propensity score matching, a statistical technique that pairs patients from the two treatment groups who share similar baseline characteristics. Matching was performed on age, body mass index, anti-Müllerian hormone, and antral follicle count, the ultrasound-based measure of resting follicles. After matching, 342 women per group were analysed for stimulation and laboratory outcomes, and 315 women in the follitropin alfa group and 314 in the follitropin delta group completed the analysis of their first frozen embryo transfer. The primary outcome was live birth following that first frozen transfer.

The headline result was reassuring equivalence. The live birth rate after the first frozen embryo transfer was 40.1 percent in the follitropin delta group compared with 41.6 percent in the follitropin alfa group, a difference captured by a relative risk of 0.97 with a 95 percent confidence interval of 0.8 to 1.2 and a p value of 0.8. In plain terms, the two regimens produced essentially indistinguishable chances of a baby from the first transfer, and the statistical interval comfortably spans the possibility of no difference at all. For a drug whose potency and dosing logic differ fundamentally from the long-standing standard, that finding carries considerable clinical weight.

Where the regimens diverged was in efficiency. Women receiving follitropin delta completed ovarian stimulation in a median of eight days, compared with nine days in the follitropin alfa group, a difference that was highly statistically significant. Crucially, the shorter stimulation did not come at the cost of follicular yield: the number of follicles measuring at least 14 millimetres and the number of oocytes retrieved were similar between the groups. The authors report that other embryological outcomes, pregnancy outcomes, and neonatal outcomes were also comparable, suggesting that the more potent hormone compressed the stimulation timeline without degrading the quality of the eggs, embryos, or eventual pregnancies that resulted.

Safety findings were equally notable. Not a single case of ovarian hyperstimulation syndrome occurred in either arm of the matched cohort, an outcome that reflects both the freeze-all strategy itself, which removes the pregnancy-driven amplification of the syndrome, and careful dose stratification by ovarian reserve. Ovarian hyperstimulation syndrome remains one of the most feared complications of IVF, and any regimen that maintains live birth rates while keeping that risk at zero in a large cohort will attract attention from clinicians seeking safer stimulation protocols, particularly in settings where high-responder populations are common.

The study’s design does impose limits on how far the conclusions can travel. As a retrospective propensity-matched cohort, it cannot eliminate residual confounding the way a randomised trial would, and the fixed-dose stratification was applied according to local clinical practice rather than a pre-specified protocol. The authors themselves are explicit on this point: while the findings suggest that the pragmatic follitropin delta regimen may offer clinical efficiency in progestin-protocol freeze-all cycles, well-designed prospective randomised controlled trials are required before it can be routinely recommended in clinical practice. The research received no external funding, and the authors declare no competing interests, with ethics approval granted by the Institutional Review Board of My Duc Hospital and patient consent waived given the anonymised, retrospective nature of the data.

Even with those caveats, the study marks a meaningful step in the evolution of personalised ovarian stimulation. Follitropin delta’s individualised algorithm, elegant on paper, has proven difficult to deploy in the protocols that now dominate modern IVF practice, especially freeze-all cycles built on progestin suppression. Demonstrating that a simple three-tier dosing scheme keyed to anti-Müllerian hormone can match the standard drug on live birth while shaving a day off stimulation offers clinics a practical, evidence-grounded option. If randomised trials confirm these results, the microgram-dosed hormone could move from a niche product constrained by its own dosing software to a mainstream tool for ovarian stimulation across the full spectrum of contemporary IVF protocols.

Subject of Research: Follitropin delta dosing for ovarian stimulation in IVF freeze-all cycles using a progestin protocol

Article Title: Novel follitropin delta dosing regimen during in vitro fertilisation using a progestin protocol and freeze-all strategy: a propensity score matching cohort study

Article References: Novel follitropin delta dosing regimen during in vitro fertilisation using a progestin protocol and freeze-all strategy: a propensity score matching cohort study. (n.d.). https://doi.org/10.1186/s13048-026-02292-7

Image Credits: AI Generated

DOI: 10.1186/s13048-026-02292-7

Keywords: follitropin delta, follitropin alfa, IVF, progestin protocol, freeze-all strategy, frozen embryo transfer, ovarian stimulation, anti-Müllerian hormone, live birth rate, ovarian hyperstimulation syndrome, propensity score matching, reproductive medicine