Poor Ovarian Reserve, Infertility (IVF Patients)
Conditions
Keywords
poor ovarian response, diminished ovarian reserve, Drospirenone, progestin primed ovarian stimulation, GnRH antagonist, Freeze all
Brief summary
Participants will: * Take either drospirenone (a daily pill) or the standard daily injection during their ovarian stimulation cycle, alongside their regular fertility hormone injections * Undergo egg retrieval, with all resulting embryos frozen (no fresh embryo transfer in this study) * Have a frozen embryo transferred in a later cycle * Complete two short questionnaires about their treatment experience - once before starting the injections/pills, and once after the stimulation phase ends * Be followed to determine if the embryo transfer results in a pregnancy
Detailed description
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.
Interventions
A drug drospirenone in the form of 1 tablet / d from 14 mm follicle till hCG trigger day
Cetrorelix a drug injection daily sc. from 14 mm follicle till hCG trigger day
Sponsors
Ahmed Saad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
stastician
Intervention model description
100 cases in this novel trial. 50 in each group will be randomized after taking 5 days of ovarian stimulation to either drospirenone tablet/d or cetrorelix injection/d till the day of hCG.
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 42 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metaphase II (Mii) oocytes | Day 0 | Number of mature (MII) oocytes retrieved between drospirenone-PPOS and GnRH antagonist protocols, both using a unified flexible start (leading follicle 14mm), in POR patients undergoing a mandatory freeze-all strategy, |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of oocytes retrieved | Day 0 | Total numbers |
| Fertilization rate 2 pronuclei (2PN) | on day 1 | Fertilization rate (2PN) check |
| Quality of day-3 embryos | on day 3 | Quality of day-3 embryos (gradeing) |
| LH measure | on trigger day ( 2 days before day 0) | LH measure to follow premature LH surge (LH \>15 mIU/mL on trigger day) and premature LH rise (LH \>10 mIU/mL) |
| Patient burden score | Day 0 | Patient-reported treatment burden and satisfaction, measured using the validated Controlled Ovarian Stimulation Impact Measure (COSI; four domains - Interference in Daily Life, Injection Burden, Psychological Health, Compliance Worry), administered at day 0. each patient will give a score from 0-4 |
| CPR ( clinical pregnancy rate) | At 6 wks of pregnancy | Clinical pregnancy rate per embryo transfer |
| Cost per cycle | at day 0 | Cost per stimulation cycle (drug cost only) in EGP |
| Number of Day 3 embryos | Day 3 | Measure the numbers of day 3 embryos |
Countries
Egypt
Contacts
CONTACTAhmed S Saad, phD
CONTACTWalid A Abdel Halim, phD
STUDY_DIRECTORAhmed s Saad, phD
Professor of OB & GYN
Outcome results
None listed