Dual Ovarian Stimulation (DUOSTIM) for Poor Ovarian Responders

NCT03803228 | Completed Phase 3 DMC

• 1 other identifier: BISTIM
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

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®).

Conditions

Fertility Disorders

Outcome Measures

Primary Outcomes (1)

• cumulative number of oocytes on 2 punctures

  cumulative number of oocytes on 2 punctures

  up to 60 days

Secondary Outcomes (15)

• cumulative number of follicles> 14mm

  up to 60 days

• cumulative number of oocytes in metaphase II

  up to 60 days

• cumulative number of embryos obtained

  1 month

• number of embryos transferred

  up to 60 days

• number of frozen embryos

  1.5 month

Study Arms (2)

DUOSTIM

EXPERIMENTAL

(stim 1) flexible antagonist protocol with pre-treatment with estrogen (S1 between J1 and J8 under E2) and stimulation with Fertistartkit® 300 IU / d; triggering by rHCG (Ovitrelle®250μg) and puncture at 36h; oocyte freezing; (stim 2) resumption of stimulation only by Fertistratkit® 300 IU / day from the day after the puncture; introduction of Progestan® 7 days later to avoid menstruation during the second puncture; triggering with rHCG and second puncture at 36h associated with the devitrification of stim 1 oocytes, with sperm collection and embryonic vitrification. Transfer of frozen embryos to the subsequent cycle in the natural cycle (without HCG) and until the frozen embryos are exhausted.

Drug: DUOSTIM

Conventional stimuli

ACTIVE COMPARATOR

(stim 1) flexible antagonist protocol with pre-treatment with estrogen (S1 between J1 and J8 under E2) and stimulation with Fertistartkit® 300 IU / d; triggering by rHCG (Ovitrelle®250μg) and puncture at 36h; fresh embryonic transfer if satisfactory endometrial conditions with luteal phase support by vaginal micronized progesterone Progestan® 600 mg / d; otherwise embryonic freezing and transfer of frozen embryos to the subsequent cycle in the natural cycle until the frozen embryos are exhausted. (stim 2) ditto starting on the next cycle if possible or the next one. Hormonal Controls + Ultrasound During Stimulation: Blocking / S1 - S5 / S6 - S8 / S9 - SHCG / SHCG-1

Drug: Conventional stimuli

Interventions

DUOSTIM DRUG

2 consecutive stimulations by Fertistartkit® on the same cycle

Also known as: Same monthly cycle

DUOSTIM

Conventional stimuli DRUG

2 stimulations by Fertistartkit® performed on 2 different cycles

Also known as: Two different menstrual cycles

Conventional stimuli

Eligibility Criteria

• Age: 20 Years - 41 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women from 20 to 41 years old
• CFA \<5 and / or AMH \<1, 2 ng / ml
• ≤ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead
• Laboratoires Genévrier: collaborator
• IBSA Institut Biochimique SA: collaborator

Study Sites (4)

Polyclinique Jean Villar

Bruges, France

Location

CHI Creteil

Créteil, 94000, France

Location

Cabinet Médical Carré Saint Giniez

Marseille, France

Location

Polyclinique Saint Roch

Montpellier, France

Location

Related Publications (1)

• Massin N, Abdennebi I, Porcu-Buisson G, Chevalier N, Descat E, Pietin-Vialle C, Goro S, Brussieux M, Pinto M, Pasquier M, Bry-Gauillard H. The BISTIM study: a randomized controlled trial comparing dual ovarian stimulation (duostim) with two conventional ovarian stimulations in poor ovarian responders undergoing IVF. Hum Reprod. 2023 May 2;38(5):927-937. doi: 10.1093/humrep/dead038.

  PMID: 36864699 DERIVED

Study Officials

• Nathalie MASSIN, MD

  CHI Créteil

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: January 14, 2019
• Study Start: September 3, 2018
• Primary Completion: March 3, 2021
• Study Completion: November 24, 2021
• Last Updated: December 7, 2022

Record last verified: 2022-12

Locations

FR (4)