Conversion of in Vitro Fertilization Cycles to Intrauterine Inseminations in Patients With a Poor Ovarian Response to Stimulation (ConFIRM)

The purpose of this study is to compare the efficiency of conversion to IUI and IVF in patients with a poor ovarian response to stimulation

Study Overview

• Status: Recruiting
• Conditions: Infertility
• Intervention / Treatment: Procedure: IVF / IVF-ICSI; Procedure: IUI

Detailed Description

In 5 to 10% of in vitro fertilization (IVF) cycles, a poor response to ovarian stimulation (defined as less than 4 mature follicles) is noted, even though high doses of exogenous gonadotropins are used. To date, there is no consensus on the ideal management strategy in poor responders. There are three therapeutic options available nowadays:

1. Oocyte retrieval is performed and the IVF cycle continued, despite the low number of mature follicles.
2. Conversion of the IVF cycle to an intrauterine insemination (IUI), on the condition of having at least one patent fallopian tube and good semen parameters.
3. Cancelation of the IVF cycle. In everyday practice, it is difficult for the physician to cancel the IVF cycle in the presence of 2, 3 or 4 mature follicles, especially following a lengthy stimulation.

If live birth rates were comparable between IUI and IVF, conversion to IUI would be the better option for poor responders, since it would avoid an invasive procedure (oocyte retrieval) and the associated risk of complications, and is associated with at a lower cost.

To our knowledge, no prospective randomized controlled trial comparing IVF to conversion to IUI in poor responders has been published to date. The studies published so far have been retrospective and observational, and had several methodological flaws.

Therefore, we aimed to analyze whether conversion of IVF cycles to IUI in poor responders would result in the same live birth rates as oocyte retrievals followed by embryo transfers.

• Study Type: Interventional
• Enrollment (Anticipated): 462
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pierre-Emmanuel Bouet, MD; Phone Number: +33 (0)241354213; Email: PierreEmmanuel.Bouet@chu-angers.fr

Study Locations

• France
  • Amiens, France
    • Recruiting
    • Victor Pauchet Clinic
    • Contact: Clémence VIFQUAIN-HEBERT
  • Angers, France, 49000
    • Recruiting
    • UH Angers
    • Contact: Pierre-Emmanuel Bouet, MD; Phone Number: +33 (0)241354213; Email: PierreEmmanuel.Bouet@chu-angers.fr
  • Besançon, France
    • Recruiting
    • UH Besançon
    • Contact: Aurélie BERDIN
  • Bondy, France
    • Recruiting
    • Jean Verdier Hospital, APHP
    • Contact: Michaël GRYNBERG
  • Bruges, France, 33520
    • Recruiting
    • Polyclinique Jean Villar
    • Contact: Xenia Lechat, MD
  • Caen, France, 14000
    • Recruiting
    • UH Caen
    • Contact: Claire De Vienne, MD
  • Chambray-lès-Tours, France, 37170
    • Recruiting
    • Clinique Léonard de Vinci
    • Contact: Claudine Vasseur, MD
  • Cholet, France
    • Recruiting
    • Cholet Hospital
    • Contact: Mariette BRUAND
  • Clamart, France, 92140
    • Recruiting
    • Antoine Béclère Hospital AP-HP
    • Contact: Michaël Grynberg, MD PhD
  • Corbeil-Essonnes, France
    • Recruiting
    • Sud Francilien Hospital
    • Contact: Antoine TORRE
  • Créteil, France, 94000
    • Recruiting
    • IHC Créteil
    • Contact: Nathalie Massin, MD
  • Grenoble, France, 38000
    • Recruiting
    • UH Grenoble
    • Contact: Aurore Gueniffey, MD
  • Le Mans, France
    • Recruiting
    • Tertre Rouge Clinic
    • Contact: Pierre-Humbert HAYOT
  • Lille, France
    • Recruiting
    • UH Lille
    • Contact: Geoffroy ROBIN
  • Lorient, France, 561000
    • Recruiting
    • Lorient Hospital
    • Contact: Sophie Fressard, MD
  • Marseille, France, 13005
    • Recruiting
    • UH La conception AP-HM
    • Contact: Blandine Courbière, MD PhD
  • Nantes, France, 44000
    • Recruiting
    • Clinique Jules Verne
    • Contact: Marie-Laure Langlois, MD
  • Nantes, France, 44000
    • Recruiting
    • UH Nantes
    • Contact: Florence Leperlier, MD
  • Neuilly-sur-Seine, France, 92200
    • Recruiting
    • Clinique Pierre Cherest
    • Contact: Frédéric Lamazou, MD
  • Nîmes, France
    • Recruiting
    • UH Nîmes
    • Contact: Stéphanie HUBERLANT
  • Orléans, France
    • Recruiting
    • Hospital of Orleans
    • Contact: Emiline TEILLET
  • Paris, France
    • Recruiting
    • Cochin Hospital, APHP
    • Contact: Pietro SANTULLI
  • Poissy, France
    • Recruiting
    • Poissy Saint Germain en Laye Hospital
    • Contact: Nelly SWIERKOWSKI-BLANCHARD
  • Potiers, France
    • Recruiting
    • UH Potiers
    • Contact: Stéphanie ROBERT BITAUDEAU
  • Rennes, France, 35000
    • Recruiting
    • Clinique Mutualiste de La Sagesse
    • Contact: Anne Guivarc'h-Levêque, MD
  • Rennes, France, 35000
    • Recruiting
    • UH Rennes
    • Contact: Mathilde Domin, MD
  • Rouen, France
    • Recruiting
    • UH Rouen
    • Contact: Maria LETAILLEUR
  • Saint-Herblain, France, 44800
    • Recruiting
    • Polyclinique de l'Atlantique
    • Contact: Anne-Cécile Vasseur, MD
  • Strasbourg, France, 67000
    • Recruiting
    • UH Strasbourg
    • Contact: olivier Pirrello, MD
  • Toulouse, France
    • Recruiting
    • Uh Toulouse
    • Contact: Jean PARINAUD
  • Tours, France, 37000
    • Recruiting
    • UHR Tours
    • Contact: Marion Cornuau, MD
• Guadeloupe
  • Guadeloupe/France
    • Pointe-à-Pitre, Guadeloupe/France, Guadeloupe, 97110
      • Not yet recruiting
      • UH Pointe-à-Pitre
      • Contact: Catherine Morinière, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients who accepted being included and signed the consent forms.
• Age ≥18 years et <43 years.

• IVF cycle with and without Intra Cytoplasmic Sperm Injection (ICSI):

  • "Conventional" Agonist (long and short) or antagonist protocol, using urinary or recombinant gonadotropins.
  • Having only 2, 3 or 4 mature follicles (≥14 mm) on ovulation trigger day.

Exclusion Criteria:

• Confirmed bilateral tubal occlusion
• Non-French speaking patients
• Partners with severe oligoasthenoteratospermia (OATS) (<5 millions motile spermatozoa in the ejaculate)

• Suboptimal stimulation protocols:

  • Protocols ≤ 150 IU of daily gonadotropins
  • Mild stimulation protocols
  • Natural and modified natural cycle protocols
• Women under legal guardianship
• Women with no health or social security coverage
• Women participating in other interventional trials

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: IVF / IVF-ICSI; In Vitro Fertilization / In Vitro Fertilization - Intracytoplasmic Sperm Injection (ICSI)	Procedure: IVF / IVF-ICSI; In the "IVF" arm, oocyte retrieval is performed 36 hours after the HCG injection, in the operating room, under transvaginal ultrasound guidance, under local or general anesthesia. The procedure lasts about 20 minutes and the patients are discharged on the same day. The oocytes retrieved from the follicles are transported immediately to the lab for fertilization with the partner's sperm. Fertilization is done either via conventional IVF, or via ICSI, depending on the indication. Embryos are later transferred into the uterus on day 3 or day 5, under ultrasound guidance, in the outpatient department.
OTHER: IUI; Intrauterine insemination	Procedure: IUI; In the "conversion to IUI" arm, IUI is performed 24 to 36 hours after ovulation trigger. The partner provides the sperm on site on the morning of the insemination, which is performed in the outpatient department.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The main criterion is the live birth rate	Defined as the birth of a living infant after 22 weeks gestational age (GA), or weighing ≥ 500 g.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical pregnancy rate	Defined as serum HCG levels >10 IU/L, 14 days after the IUI or the embryo transfer, followed by a rapid decrease until being undetectable.	5 Weeks
Clinical pregnancy rate	Defined as fetal cardiac activity at 6-7 weeks GA	6-7 Weeks
Spontaneous pregnancy loss (PL) rate	Including early and late pregnancy losses	12 Weeks
Multiple pregnancy rate	Defined as more than two embryos visualized on ultrasound at 7 weeks GA.	7-8 Weeks
Term at delivery	Term at delivery in Gestational age (GA)	12 Months
Neonatal complications	Neonatal complications	12 Months
Neonatal survival	Neonatal survival	12 Months
All outcome measure will be further analyzed according to the number of follicles on trigger day (2, 3 or 4) and patients' age (<40 years vs. ≥40 years)	Assess the impact of conversion to IUI, compared to IVF, on overall outcomes in in women with a poor ovarian response to stimulation, according to the number of follicles on trigger day (2, 3 or 4) and patients' age (<40 years vs. ≥40 years)	12 Months
All outcome measures will be further analyzed in the subgroup of women considered poor responders according to the Bologna criteria	Assess the clinical efficiency of conversion to IUI, compared to IVF, in women considered "poor ovarian responders" according to the Bologna criteria	12 Months
The rate of IVF cycles with empty follicle syndrome and no embryo transfers.	Analyze the rate of IVF cycles with empty follicle syndrome and no embryo transfers	1 Week
Cumulative clinical pregnancy and live birth rates in the IVF group, thus taking into account fresh and frozen embryos transferred in subsequent cycles	Assess the impact of conversion to IUI, compared to IVF, on the cumulative clinical pregnancy and live birth rates - taking into account frozen embryo transfers in IVF - in women with a poor ovarian response to stimulation	12 Months
Cost-efficiency analysis at 12 months	Compare the cost-efficiency of both strategies at 12 months	12 Months

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Study Director: Pierre-Emmanuel BOUET, MD, University Hospital of Angers

Publications and helpful links

General Publications

• Delbos L, Parot-Schinkel E, El Hachem H, Legendre G, Descamps P, Boucret L, Ferre-L'Hotellier V, Jeanneteau P, Dreux C, Moriniere C, May-Panloup P, Bouet PE. ConFIRM trial - conversion of in vitro fertilization cycles to intrauterine inseminations in patients with a poor ovarian response to stimulation: a protocol for a multicentric, prospective randomized trial. Trials. 2018 Oct 17;19(1):565. doi: 10.1186/s13063-018-2936-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2018
• Primary Completion (ANTICIPATED): January 1, 2023
• Study Completion (ANTICIPATED): January 1, 2023

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (ACTUAL): December 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 26, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: In Vitro Fertilization; Poor responders; Intra-Uterine Insemination
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 2017-A00862-51

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No