O-012 Three Injections Protocol for IVF; a proof of concept study into elaborating the outmost patient friendly protocol in IVF
Authors: Papanikolaou E , Chouliara F , Peitsidis N , Gkekas A , Bouchlariotou S , Chartomatsidou T , Kostoglou K , Kakani O , Timotheou E , Najdecki R 
Published: July 2024

Abstract

Study question
To examine if 3 injections in follicular phase, with long-acting FSH, long-acting antagonist and HCG/Agonist triggering can result in efficient egg retrieval and blastocyst formation.

Summary answer
In this proof-of-concept study, all patients retrieved mature oocytes and ended having adequate blastocysts by receiving only 3 injections in the follicular phase.

What is known already
The old-fashioned way with multiple injections (majority minimum 15 injections) is still the golden IVF standard. Twenty years ago, a long-acting FSH gonadotropin brought into market (corifollitropin alpha) which represented a huge step in simplifying the follicular phase Recently, a new long-acting GnRH-antagonist emerged (degarelix) which can downregulate the hypophysis for 30 days. We have published that titrating this long-acting antagonist to 0,1mg single dose we can downregulate hypophysis without LH surge.

Study design, size, duration
A prospective proof of concept study included in total 15 patients 30-39 years old who followed IVF treatment with homologous oocytes during 2020-2022 in Assisting Nature IVF Clinic, Thessaloniki, Greece. In this study, we test if by delaying one day the long-FSH and also delaying the long-antagonist, still patients can produce mature eggs without needed extra FSH doses. Institutional review board approved the protocol.

Participants/materials, setting, methods
Patients were enrolled if AMH was 1,5-3,0 ng/ml and antagonist protocol applied. 150IU fixed corifollitropin-a (Elonva) for ovarian stimulation administered either on evening cycle Day-3 or morning day-4. Fixed 0,1 mg of long-acting GnRH-antagonist (Degarelix) administered on cycle Day 8. Fixed 250mcg recombinant-hCG (Ovitrelle) or 0,3 mg of Triptorelin (Arvekap) for ovulation triggering administered as soon as 3 follicles of 18mm were present. Produced blastocysts were all cryopreserved and transferred in subsequent thawed cycles.

Main results and the role of chance
All 15 patients reached ovum pick-up with mature eggs retrieved (mean 13,5 oocytes). None experienced any LH surge, however, 3/15 (20%) required an extra dose of 300IU FSH (Puregon) to enhance follicular development. The majority 12/15 reached OPU without any FSH adjuvant. All 15 patients had blastocysts formed (mean 3,3) and in their subsequent thawed cycles the cumulative live birth rate was 53,3% (8/15). Patient satisfaction was excellent though closer monitoring was applied due to novelty of the protocol.

Limitations, reasons for caution
Limited number of patients as it is a complete novel protocol with unknown outcome. Protocol was focused in normo-ovarian-reservers to secure follicular production. Some patients might need an extra dose of gonadotropin. Long-acting antagonist still not registered for IVF use.

Wider implications of the findings
Current study promising results indicate that a 3-injection follicular stimulation can efficiently produce mature eggs, viable blastocysts and pregnancies. Although, few patients required an extra fourth injection of FSH, if such approach will be tested in larger studies will re-establish our way for stimulation at least for normo-reservers.

Trial registration number
NCT03877185