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Dual Ovarian Stimulation (DUOSTIM) for Poor Ovarian Responders

Comparison of the Cumulative Number of Oocytes Obtained With 2 Controlled Ovarian Hyperstimulations (COH) Within the Same Cycle With FertistartKit® (DUOSTIM) Versus 2 Conventional COH in Poor Ovarian Responders Undergoing IVF. Bistim Study

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03803228
Enrollment
88
Registered
2019-01-14
Start date
2018-09-03
Completion date
2021-11-24
Last updated
2022-12-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fertility Disorders

Brief 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®).

Interventions

DRUGDUOSTIM

2 consecutive stimulations by Fertistartkit® on the same cycle

DRUGConventional stimuli

2 stimulations by Fertistartkit® performed on 2 different cycles

Sponsors

Laboratoires Genévrier
CollaboratorINDUSTRY
IBSA Institut Biochimique SA
CollaboratorINDUSTRY
Centre Hospitalier Intercommunal Creteil
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
20 Years to 41 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
cumulative number of oocytes on 2 puncturesup to 60 dayscumulative number of oocytes on 2 punctures

Secondary

MeasureTime frameDescription
progesterone levelup to 20 daysprogesterone level
cumulative number of follicles> 14mmup to 60 dayscumulative number of follicles\> 14mm
cumulative number of oocytes in metaphase IIup to 60 dayscumulative number of oocytes in metaphase II
cumulative number of embryos obtained1 monthcumulative number of embryos obtained
number of embryos transferredup to 60 daysnumber of embryos transferred
number of frozen embryos1.5 monthnumber of frozen embryos
dose of FSHup to 60 dayscumulative total dose of FSH
LH levelup to 20 daysLH level
estradiol levelup to 20 daysestradiol level
transfer rate3 monthscancellation or no transfer rate
rates of early pregnancyup to 9 monthscumulative rates of early pregnancy (HCG\> 100) and ultrasound (6-7SA)
number of beginner pregnancyup to 9 monthsnumber of beginner pregnancy in each groups
cumulative costup to 9 monthscumulative cost of 2 attempts including frozen embryo transfers (treatments, consultations, MPA laboratory and monitoring exams)
Side effectsup to 9 monthsreported side effects
the number of stimulation daysup to 20 daysthe number of stimulation days

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 9, 2026