Mild ovarian stimulation may be a viable alternative to intense ovarian stimulation in IVF.A subgroup analysis of the phase IV POSEIDON group 2 study presented at ESHRE 2026 shows the noninferiority of mild ovarian stimulation to an intense approach to yield good-quality blastocysts (GQBs) in in vitro fertilization (IVF).
The total gonadotropin dose was markedly lower among women who received mild ovarian stimulation as opposed to those who received an intense regimen (1,462.31 vs 2,964.42; estimated mean difference [EMD], –1,502.11). Yet, there were no differences between the two groups in terms of the number of oocytes retrieved (4.12 vs 5.16; EMD, –1.04), MII oocytes (3.37 vs 3.64; EMD, –0.27), total blastocysts (1.49 vs 1.72; EMD, –0.23), and cryopreserved embryos (0.88 vs 1.16; EMD, –0.2) in the per-protocol analysis.
There was also no statistically significant difference between the mild and the intense stimulation protocol in terms of the mean number of GQBs (0.60 vs 0.84; EMD, –0.23). [ESHRE 2026, abstract L26/P-753]
“With the noninferiority margin set at 1 GQB, the results demonstrate that mild stimulation is noninferior to intense stimulation in terms of GQBs obtained,” said the investigators from Dexeus University Hospital, Barcelona, Spain, at ESHRE 2026.
A key predictor of IVF success
Oocyte yield has been established as a key predictor of IVF success. [Hum Reprod 2011;26:1768-1774; Hum Reprod 2016;31:370-376; Fertil Steril 2018;110:661-670.e1; Best Pract Res Clin Obstet Gynaecol 2023;87:102307]
In women with good prognosis, strategies aimed at maximizing the number of oocytes retrieved can be easily implemented; however, a low ovarian response to stimulation remains a major clinical challenge, the researchers noted.
This single-centre study, conducted at a university-affiliated fertility unit, comprised 110 normal-weight women with antral follicle count (AFC) 5–10. The participants were randomized 1:1 to receive either mild stimulation with clomiphene citrate 50 mg daily (stimulation day 1–5) plus recombinant follitropin (rFSH) 150 IU daily (from stimulation day 1) or a more intense stimulation protocol with rFSH 300 IU daily throughout the stimulation phase.
Among women in the mild stimulation group, the mean age was 37.16 years, and the mean AFC was 6.93. In the intense stimulation group, the mean age was 36.88 years, and the mean AFC was 6.69.
In all participants, the luteinizing hormone surge was suppressed using a gonadotropin-releasing hormone antagonist at a daily dose of 0.25 mg from a leading follicle ≥14 mm until trigger. The final oocyte maturation was induced with recombinant human chorionic gonadotropin 250 µg.
The researchers acknowledged certain limitations, such as the single-centre and unblinded study design, which may have reduced external validity and potential performance and assessment bias. “Also, as the sample size was designed for GQBs, conclusions cannot be drawn regarding the secondary outcomes.”
“[Nonetheless, the study] addressed a clinically relevant and previously unexplored question in a well-defined POSEIDON group 2 subgroup, used a randomized controlled noninferiority design, and applied a fixed gonadotropin dosing without intracycle adjustments,” they said.
Moreover, the strict inclusion criteria and the protocolized endocrine monitoring enhance the interpretability of the findings, they added.
“In conclusion, in this population, mild stimulation seems a viable alternative [to intense ovarian stimulation] that reduces gonadotropin exposure, potentially lowering costs and treatment burden while maintaining embryo quality,” the researchers concluded.