Clinical trial NCT03362489: Conversion of in Vitro Fertilization Cycles to Intrauterine Inseminations in Patients With a Poor Ovarian Response to Stimulation
Official title: Conversion of in Vitro Fertilization Cycles to Intrauterine Inseminations in Patients With a Poor Ovarian Response to Stimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: In Vitro Fertilization
Intra-Uterine Insemination
Poor responders
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2017-12-05
Enrollment: 462
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: The main criterion is the live birth rate
timeFrame: 12 months
Secondary outcomes:
measure: Biochemical pregnancy rate
timeFrame: 5 Weeks
measure: Clinical pregnancy rate
timeFrame: 6-7 Weeks
measure: Spontaneous pregnancy loss (PL) rate
timeFrame: 12 Weeks
measure: Multiple pregnancy rate
timeFrame: 7-8 Weeks
measure: Term at delivery
timeFrame: 12 Months
measure: Neonatal complications
timeFrame: 12 Months
measure: Neonatal survival
timeFrame: 12 Months
measure: 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)
timeFrame: 12 Months
measure: All outcome measures will be further analyzed in the subgroup of women considered poor responders according to the Bologna criteria
timeFrame: 12 Months
measure: The rate of IVF cycles with empty follicle syndrome and no embryo transfers.
timeFrame: 1 Week
measure: Cumulative clinical pregnancy and live birth rates in the IVF group, thus taking into account fresh and frozen embryos transferred in subsequent cycles
timeFrame: 12 Months
measure: Cost-efficiency analysis at 12 months
timeFrame: 12 Months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Victor Pauchet Clinic
city: Angers
country: France
facility: UH Angers
city: Besançon
country: France
facility: UH Besançon
city: Bondy
country: France
facility: Jean Verdier Hospital, APHP
city: Bruges
country: France
facility: Polyclinique Jean Villar
city: Caen
country: France
facility: UH Caen
city: Chambray-lès-Tours
country: France
facility: Clinique Léonard de Vinci
city: Cholet
country: France
facility: Cholet Hospital
city: Clamart
country: France
facility: Antoine Béclère Hospital AP-HP
city: Corbeil-Essonnes
country: France
facility: Sud Francilien Hospital
city: Créteil
country: France
facility: IHC Créteil
city: Grenoble
country: France
facility: UH Grenoble
city: Le Mans
country: France
facility: Tertre Rouge Clinic
city: Lille
country: France
facility: UH Lille
city: Lorient
country: France
facility: Lorient Hospital
city: Marseille
country: France
facility: UH La conception AP-HM
city: Nantes
country: France
facility: Clinique Jules Verne
city: Nantes
country: France
facility: UH Nantes
city: Neuilly-sur-Seine
country: France
facility: Clinique Pierre Cherest
city: Nîmes
country: France
facility: UH Nîmes
city: Orléans
country: France
facility: Hospital of Orléans
city: Paris
country: France
facility: Cochin Hospital, APHP
city: Poissy
country: France
facility: Poissy Saint Germain en Laye Hospital
city: Potiers
country: France
facility: UH Potiers
city: Rennes
country: France
facility: Clinique Mutualiste de la Sagesse
city: Rennes
country: France
facility: UH Rennes
city: Rouen
country: France
facility: UH Rouen
city: Saint-Herblain
country: France
facility: Polyclinique de L'Atlantique
city: Strasbourg
country: France
facility: UH Strasbourg
city: Toulouse
country: France
facility: UH Toulouse
city: Tours
country: France
facility: UHR Tours
city: Pointe-à-Pitre
country: Guadeloupe
facility: UH Pointe-à-Pitre
state: Guadeloupe/France
Study officials:
affiliation: University Hospital of Angers
name: Pierre-Emmanuel BOUET, MD
role: STUDY_DIRECTOR
References:
citation: 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.