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

Infertility Clinical Trial

— ConFIRM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03362489
• Other study ID #: 2017-A00862-51
• Status: Recruiting
• Phase: N/A
• Start date: January 10, 2018
• Est. completion date: January 2023

Study information

• Verified date: September 2022
• Source: University Hospital, Angers
• Contact: Pierre-Emmanuel BOUET, MD
• Phone: +33 (0)241354213
• Email: PierreEmmanuel.Bouet[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 462
• Est. completion date: January 2023
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

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

Related Conditions & MeSH terms

• Infertility

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Victor Pauchet Clinic	Amiens
France	UH Angers	Angers
France	UH Besançon	Besançon
France	Jean Verdier Hospital, APHP	Bondy
France	Polyclinique Jean Villar	Bruges
France	UH Caen	Caen
France	Clinique Léonard de Vinci	Chambray-lès-Tours
France	Cholet Hospital	Cholet
France	Antoine Béclère Hospital AP-HP	Clamart
France	Sud Francilien Hospital	Corbeil-Essonnes
France	IHC Créteil	Créteil
France	UH Grenoble	Grenoble
France	Tertre Rouge Clinic	Le Mans
France	UH Lille	Lille
France	Lorient Hospital	Lorient
France	UH La conception AP-HM	Marseille
France	Clinique Jules Verne	Nantes
France	UH Nantes	Nantes
France	Clinique Pierre Cherest	Neuilly-sur-Seine
France	UH Nîmes	Nîmes
France	Hospital of Orléans	Orléans
France	Cochin Hospital, APHP	Paris
France	Poissy Saint Germain en Laye Hospital	Poissy
France	UH Potiers	Potiers
France	Clinique Mutualiste de la Sagesse	Rennes
France	UH Rennes	Rennes
France	UH Rouen	Rouen
France	Polyclinique de L'Atlantique	Saint-Herblain
France	UH Strasbourg	Strasbourg
France	UH Toulouse	Toulouse
France	UHR Tours	Tours
Guadeloupe	UH Pointe-à-Pitre	Pointe-à-Pitre	Guadeloupe/France

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Countries where clinical trial is conducted

France,  Guadeloupe, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Clinical pregnancy rate	Defined as fetal cardiac activity at 6-7 weeks GA	6-7 Weeks
Secondary	Spontaneous pregnancy loss (PL) rate	Including early and late pregnancy losses	12 Weeks
Secondary	Multiple pregnancy rate	Defined as more than two embryos visualized on ultrasound at 7 weeks GA.	7-8 Weeks
Secondary	Term at delivery	Term at delivery in Gestational age (GA)	12 Months
Secondary	Neonatal complications	Neonatal complications	12 Months
Secondary	Neonatal survival	Neonatal survival	12 Months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cost-efficiency analysis at 12 months	Compare the cost-efficiency of both strategies at 12 months	12 Months