Dual Ovarian Stimulation (DUOSTIM) for Poor Ovarian Responders
Condition: Fertility Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      During ovarian stimulation, all the follicles grow under the action of FSH, only the selected
      follicles and with the faster growth are taken. However during this stimulation, other
      smaller follicles are also recruited and sensitized, which may increase the selection of
      follicles available on the follicular wave following. In patients with weak reserve this
      potentiation has a great interest, and the sequence of 2 stimulations on the same cycle could
      make it possible to obtain a larger number of oocytes and embryos, thus giving a better
      chance of delivery than on 2 distinct cycles of stimulation. However, this is preliminary
      data that needs to be confirmed with a randomized controlled trial. In this population of
      poor prognosis, the use of FSH-associated LH activity may optimize the ovarian response to
      stimulation, particularly the combination containing placental HCG (Fertistartkit®) that
      obtaining a slightly higher number of oocytes than highly purified HMG (Menopur®).
    

Detailed description: 
      Ovarian stimulation is an essential prerequisite for any in vitro fertilization attempt (IVF)
      to optimize the chances of delivery per cycle. These depend in the first place on the age of
      the patients and secondly on the number of oocytes collected. There is a strong correlation
      between these two factors, the ovarian reserve diminishing with age. In older patients or
      patients with decreased reserve, however, the number of oocytes collected remains a
      prognostic factor for the chances of delivery.

      At the present time, there is no validated intervention that would bring a significant
      interest on the number of oocytes obtained in the group of bad responder patients. However,
      it is a very heterogeneous population whose definition has been proposed only recently, the
      Bologna criteria and questioned by a new proposal from the Poseidon group. The latter is more
      focused on the prognosis of success, differentiating patients with a diminished reserve
      (count of antral follicles CFA <5 and / or AMH <1.2 ng / ml) from those with an "unexpected"
      bad response. As the profiles are better defined, it is easier to determine the impact of a
      strategy in a specific group.

      Recent clarifications on the ovarian cycle and folliculogenesis have shown that several waves
      of follicular development coexist on the same cycle and that it is perfectly possible to
      obtain a follicular development with a luteal phase equivalent oocyte quality, compared to
      conventional stimulations performed in the follicular phase. The main constraint of luteal
      phase stimulation is the lack of possibility of fresh transfer due to non-synchronization
      with the endometrium. This constraint is today secondary given the evolution of conservation
      techniques with the development of embryonic and oocyte vitrification.

      On the other hand, there is a differential dependence of FSH follicles, their sensitivity
      depending on the number of FSH receptors and their duration of exposure to FSH. During
      ovarian stimulation, all the follicles grow under the action of FSH, only the selected
      follicles and with the faster growth are taken. However during this stimulation, other
      smaller follicles are also recruited and sensitized, which may increase the selection of
      follicles available on the follicular wave following. In patients with weak reserve this
      potentiation has a great interest, and the sequence of 2 stimulations on the same cycle could
      make it possible to obtain a larger number of oocytes and embryos, thus giving a better
      chance of delivery than on 2 distinct cycles of stimulation. However, this is preliminary
      data that needs to be confirmed with a randomized controlled trial. In this population of
      poor prognosis, the use of FSH-associated LH activity may optimize the ovarian response to
      stimulation, particularly the combination containing placental HCG (Fertistartkit®) that
      obtaining a slightly higher number of oocytes than highly purified HMG (Menopur®).
    

Intervention name(s): DUOSTIM; Conventional stimuli
Intervention type(s): Drug; Drug
Intervention description(s): 2 consecutive stimulations by Fertistartkit® on the same cycle; 2 stimulations by Fertistartkit® performed on 2 different cycles
Other intervention name(s): Same monthly cycle; Two different menstrual cycles
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment