Phase IV Randomized Study of Follitropin Delta Added to hCG Versus Standard hCG for Ovulation Triggering in Low Ovarian Reserve Women Undergoing Fresh‑Embryo Transfer IVF

Primary objective: to evaluate whether adding follitropin δ to hCG ovulation triggering increases the number of mature (MII) oocytes in women with infertility and low ovarian reserve undergoing fresh embryo transfer IVF cycles. Secondary objectives: • compare the proportion of mature oocytes between study groups; • assess biochemical and ongoing pregnancy rates after fresh embryo transfer; • evaluate oocyte quality markers in granulosa cells.

The trial enrolled women with primary infertility and low ovarian reserve, aged 18 to 42 years, who met POSEIDON criteria for poor ovarian response. Participants were required to provide signed informed consent and were selected from a population of female patients undergoing fresh embryo transfer IVF cycles. The sponsor did not provide the total number of participants. No specific lifestyle restrictions such as diet or physical activity were stipulated in the available information.

The study is a Phase IV, single‑blind, randomized trial with three parallel arms comparing different ovulation‑triggering regimens in IVF cycles with fresh embryo transfer. Eligible participants are women aged 18–42 years with infertility and low ovarian reserve who meet POSEIDON criteria. After signed informed consent, a screening visit confirms eligibility; participants are then randomized to one of the three treatment arms. Each arm receives a standard protocol of gonadotropin stimulation followed by the assigned ovulation trigger (hCG alone, hCG + follitropin δ, or an alternative regimen). Oocyte retrieval is performed, and the primary endpoint, the number of metaphase II (MII) oocytes retrieved, is recorded. Follow‑up visits occur at oocyte pickup, embryo transfer, and at 2 weeks and 12 weeks post‑transfer to assess secondary outcomes including mature‑oocyte proportion, biochemical and ongoing pregnancy rates, and gene‑expression analyses. The end‑of‑study visit concludes participation after the final pregnancy assessment. Participant involvement spans approximately 8–10 weeks from screening to end‑of‑study. Early withdrawal may occur if a participant experiences a serious adverse event, deviates markedly from the protocol, becomes pregnant outside the study cycle, or withdraws consent. The overall study recruitment period is scheduled from 29 August 2026 to 31 January 2027.

Decapeptyl diario 0.1 mg powder for solution for injection contains the GnRH agonist triptorelin and is supplied as a solution for subcutaneous injection. Each administered dose provides 0.2 mg and is given once daily during the pituitary down‑regulation phase of the controlled ovarian stimulation protocol.

REKOVELLE 36 µg/1.08 mL pre‑filled pen delivers the recombinant follicle‑stimulating hormone analogue follitropin delta as a solution for subcutaneous injection. The prescribed dose is 15 µg per administration, administered once daily throughout the ovarian stimulation period.

REKOVELLE 72 µg/2.16 mL pre‑filled pen also contains follitropin delta and is provided as a solution for subcutaneous injection. The dosing schedule mirrors the 36 µg pen, with 15 µg administered once daily during the stimulation phase.

Ovitrelle 250 µg pre‑filled pen provides the recombinant hCG analogue choriogonadotropin alfa in a solution for subcutaneous injection. A single 250 µg dose is administered to trigger final oocyte maturation and ovulation after the completion of follicular development.

Orgalutran 0.25 mg/0.5 mL solution for injection contains the GnRH antagonist ganirelix acetate and is supplied as a solution for subcutaneous injection. The standard dose of 0.25 mg is given once daily from the onset of follicular stimulation until the day of ovulation trigger to prevent premature luteinising hormone surges.

Meriofert Kit 900 IU powder for solution for injection comprises recombinant human follicle‑stimulating hormone and luteinising hormone. The kit is reconstituted to provide a subcutaneous injection of 75 IU of each hormone per dose, administered according to the individualized ovarian stimulation regimen.

All study medications are administered under direct observation at the clinical site or by trained personnel following a documented injection log. Compliance is verified by reviewing the log entries, confirming vial counts, and cross‑checking with electronic medical records at each scheduled study visit.

Efficacy will be evaluated primarily by the number of metaphase II (MII) oocytes retrieved at oocyte pickup. The count will be obtained at the time of oocyte retrieval for each participant and recorded for comparative analysis between treatment arms.

Secondary efficacy assessments include the proportion of mature oocytes calculated as MII/total oocytes retrieved, the biochemical pregnancy rate and the ongoing pregnancy rate, and the analysis of gene expression of receptors and enzymes involved in folliculogenesis and ovarian steroidogenesis in mature oocytes. The proportion of mature oocytes will be derived from the retrieval data. Pregnancy outcomes will be determined through standard biochemical testing for hCG and subsequent clinical confirmation during follow‑up visits. Gene expression profiling will be performed on the harvested mature oocytes using appropriate molecular laboratory techniques.