Drospirenone-Primed Ovarian Stimulation Versus GnRH Antagonist Protocol in Poor Ovarian Responders Undergoing Freeze-All IVF/ICSI

Single-center, open-label, 1:1 parallel-group pilot RCT, stratified by POSEIDON group. Superiority framing is not used - this pilot is not powered for hypothesis testing on efficacy outcomes; those are reported descriptively with 95% confidence intervals.

Freeze-all is mandated in both arms by protocol (not patient choice). No patient is offered fresh transfer in either arm, so no patient is excluded for requesting one; this is stated explicitly in the consent process so expectations are set at enrollment.

Both arms use a unified flexible start, triggered by leading follicle diameter reaching 14mm - not a fixed calendar day. Rather than fixing both arms to the same stimulation day (which would not account for individual variability in follicular growth rate, a particular concern in POR), both the antagonist and the drospirenone are initiated on the same physiological trigger: once the leading follicle reaches 14mm, whichever arm the patient is randomized to. This achieves genuine unification across arms (identical starting criterion, applied identically) while remaining individualized to each patient's own stimulation pace. This design has direct precedent, as described in Section 2, and retrospective evidence in POR specifically favors flexible-start over fixed-day dosing on oocyte and fertilization outcomes without increased LH-surge risk.

Inclusion criteria

• Spontaneous menstrual cycles (21-35 days)
• Poor ovarian response per Bologna criteria (≥2 of 3): advanced age ≥40 or risk factor for POR; previous poor response (≤3 oocytes with conventional stimulation); abnormal ovarian reserve (AFC <7 or AMH <1.1 ng/mL)
• POSEIDON group recorded at enrollment (1-4) for stratified randomization and pre-specified subgroup description - corrects a known limitation of Bologna-only classification, which pools biologically distinct POR phenotypes
• Indication for IVF/ICSI
• Willing and able to undergo mandatory freeze-all/FET protocol
• Signed informed consent, including explicit acknowledgment that fresh transfer is not offered in either study arm

Exclusion criteria

• Contraindication to ovarian stimulation
• Known müllerian anomaly
• Uncontrolled systemic disease
• 5 prior failed IVF attempts
• Known contraindication to drospirenone (per product labeling, e.g., renal impairment, adrenal insufficiency, conditions predisposing to hyperkalemia)