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

Study Overview
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Brief Summary
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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
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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: Oocyte retrieval is performed and the IVF cycle continued, despite the low number of mature follicles. 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. 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.

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

Conditions
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Infertility

Intervention / Treatment
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* Procedure: IVF / IVF-ICSI
* Procedure: IUI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: IVF / IVF-ICSI<br>In Vitro Fertilization / In Vitro Fertilization - Intracytoplasmic Sperm Injection (ICSI) | Procedure: IVF / IVF-ICSI<br>* 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.<br>|
| Other: IUI<br>Intrauterine insemination | Procedure: IUI<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In Vitro Fertilization, Intra-Uterine Insemination, Poor responders