Ovarian Stimulation Single Injection Elonva
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 3

Summary: 
      We would like to propose that it may be possible to use a solitary dose of Elonva
      (corifollitrophin alpha) as the sole gonadotrophin (FSH) stimulant for the vast majority of
      women undergoing IVF, assuming that it is possible that "coasting" (withholding short acting
      rFSH) from day 8 of the stimulation until trigger/ oocyte retrieval will still result in a
      significant number of mature oocytes being produced and an acceptable pregnancy rate.
    

Detailed description: 
      Elonva (corifollitrophin alfa) has been shown to be a very effective rFSH stimulant for
      Controlled Ovarian Hyperstimulation (COH) in the setting of IVF treatment. Its long duration
      of action (7 days) results in a significant reduction in the number of COH stimulation
      injections (average of 3 injections v 9 injections in the traditional "short acting" r FSH
      COH), with 30% of patients requiring only a single Elonva injection for their COH (Engage
      study, Devroey et al 2009). It is assumed that a reduction in the number of required COH
      injections will have the advantages of improved patient acceptability and better compliance
      due to a reduction in room for error. Despite these advantages the clinical uptake of Elonva
      has been slow due to 2 principal concerns among clinicians:

        1. A tendency for Elonva COH to result in a higher ovarian response with increased risk of
           Ovarian Hyper-Stimulation Syndrome (OHSS). While this risk of OHSS was not statistically
           significant in the pivotal Engage study, there was still a numerically greater chance of
           OHSS and a greater chance of the IVF cycle being cancelled due to OHSS risk in the
           Elonva arm compared to the traditional Puregon arm. Since women at high risk of OHSS
           were excluded from the Engage study, clinicians perceive that the risk of OHSS is likely
           to be significantly greater in the more heterogeneous general clinical population.
           Whether this is a correct assumption is still up for debate, but it is a perceived issue
           with the existing Elonva protocol that must be addressed if Elonva is to become used
           widely as a COH stimulant.

        2. According to the Engage and Ensure studies, the majority (70%) of women using Elonva
           require "top up"short acting Puregon rFSH, with an average of 2 doses being required
           before the patients reach the criteria for triggering and oocyte retrieval. As a result
           clinics are required to teach two different injection protocols, increasing the time
           required to educate the patient and possibly increasing the risk of confusion. The
           ability to deliver a solitary COH stimulant without the need for any "top up" Puregon
           would be a major advantage.

      Rationale We would like to propose that it may be possible to use a solitary dose of Elonva
      as the sole COS rFSH stimulant for the vast majority of women undergoing IVF, assuming that
      it is possible that "coasting" (withholding short acting rFSH) from day 8 of the stimulation
      until trigger/ oocyte retrieval will still result in a significant number of mature oocytes
      being produced.

      In the setting of OHSS it is common practice to withhold any further rFSH stimulant towards
      the end of the COS process. It is generally accepted that medium size follicles of 14 mm or
      greater will continue to develop to maturity in the absence of rFSH stimulation, while
      smaller follicles will regress. This has the therapeutic advantage of reducing estradiol
      levels and OHSS risk in women at high risk of OHSS. With this coasting physiology in mind, we
      propose that provided a single injection of Elonva can result in a significant number of
      follicles being 14 mm or greater by day 8 of stimulation, further rFSH will not be required.
      Results from the Engage study (Doody et al 2011) reveal that by day 8 of stimulation on
      average there were 5.1 follicles of 15 mm or greater. Therefore even if no further "top up"
      rFSH was given from day 8, one could expect to get at least 5 mature oocytes from an oocyte
      retrieval triggered by hCG in the next 2 days. While 5 mature oocytes is significantly less
      than what was produced by the traditional Elonva protocol using additional rFSH (average 10.8
      in the Engage study, 10.7 in the Ensure study), this could be perceived as a significant
      advantage since it will likely result in a significant reduction in OHSS risk, a perceived
      problem with the traditional Elonva protocol. If we assume a 70% fertilization rate and that
      approximately half of all embryos are of good quality by day 4/5 of culture, the production
      of > 3 mature oocytes should ensure the generation of at least one good quality embryo for
      transfer with a good chance of pregnancy. This type of low impact stimulation is likely to be
      very popular in Europe and Australia where clinicians already accept the benefits of mild
      COS.

      In summary, if we are able to provide evidence in this pilot study that a single injection of
      Elonva can result in the majority of women reaching oocyte retrieval with the production of
      at least 3 mature oocytes, while giving good fresh embryo transfer pregnancy rates and no
      OHSS, the coasting Elonva protocol may become a significant clinical protocol for low impact
      COS in the future.
    

Intervention name(s): corifollitrophin alfa
Intervention type(s): Drug
Intervention description(s): use of a single dose of corifollitrophin alfa to provide adequate controlled ovarian hyperstimulation during IVF treatment
Other intervention name(s): Elonva
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment