Dual Ovarian Stimulation (DUOSTIM) for Poor Ovarian Responders

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®).

Inclusion criteria

• Women from 20 to 41 years old
• CFA <5 and / or AMH <1, 2 ng / ml
• 19 ≤ BMI ≤ 32
• Supports IVF or ICSI
• If antecedent IVF / ICSI, number of oocytes collected <4
• Attack rank (puncture with transfer) <3
• Affiliation to the general social security scheme and benefiting from 100% infertility

Exclusion criteria

• Confirmed ovarian insufficiency (amenorrhea)
• FSH> 20 IU / l or CFA <1
• Puncture rank> 3
• Azoospermia or cryptozoospermia
• Against indication to ovarian stimulation
• Presence of a cyst of indeterminate etiology, ovarian, uterine or mammary carcinoma, hypothalamic or pituitary tumors
• Hypersensitivity to any of the medicines in the protocol
• Moderate or severe pathology of renal or hepatic function
• Evolutionary thromboembolic accidents