Early Follicular Phase vs Lutheal Phase Ovarian Stimulation in Bologna Criteria IVF/ICSI Cycles (LUTEAL Trial)

Study Overview
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Brief Summary
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Exploratory, prospective, randomized, comparative, open trial with control group treated to assess the efficacy of follicular phase ovarian stimulation compared to lutheal phase ovarian stimulation in women with Bologna criteria for poor ovarian response.

Detailed Description
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Two arms is established, the study group that will start ovarian stimulation in the luteal phase and the control group that will start ovarian stimulation in the follicular phase. The randomization will be made in the 2-3 day of the menstrual cycle, according to a list of random allocation of treatments. After check that there is no contraindication to start the stimulation, the patients will be assigned to the treatment group. The patients in the control group (follicular phase group) will start stimulation with two vials of 150 IU recombinant FSH + 75 IU recombinant LH (Pergoveris® 150/75). The patients in the study group (luteal phase group) will perform daily urine LH test from day 7th of the cycle and will start the administration of 150 IU recombinant FSH + 75 IU recombinant LH (Pergoveris® 150/75) at two vials daily from the 4th day of the LH positive test. Antagonist cetrorelix acetate (Cetrotide® ) administration will start when the largest follicle shall be equal or greater than 14 mm. From this moment controls every 24-72 hours with foliculometría by ultrasound and blood hormone analysis with determination of estradiol and progesterone. For the final oocyte maturation 2 vials daily of 0.2 mg triptorelin acetate (Decapeptyl®) is administered. Oocyte collection will be made by transvaginal ultrasound-guided puncture according to IB protocol The dosages and protocols used will be the usual for patients with diagnostic of poor ovarian response.

Official Title
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Early Follicular Phase vs Lutheal Phase Ovarian Stimulation in Bologna Criteria IVF/ICSI Cycles: A Randomized Comparative Single Center Trial. LUTEAL Trial

Conditions
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Reproductive Techniques, Assisted

Intervention / Treatment
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* Procedure: Follicular phase
* Procedure: Luteal phase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient Bologna meets the criteria to be diagnosed as low responder Age under 41 years Regular menstrual cycles between 21 and 35 days Indication of in vitro fertilization Indication of start stimulation with 300 IU of FSH Presence of both ovaries Ability to participate and comply with the study protocol Having signed the written consent form Exclusion Criteria: Presence of follicles larger than 10 mm in the randomization visit Endometriosis III / IV Concomitant uterine pathology: adenomyosis, submucosal myomas, Asherman's syndrome... Concurrent participation in another study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Active Comparator: Follicular phase<br>Controlled ovarian stimulation starts during follicular phase on day 2-3 of the menstrual cycle | Procedure: Follicular phase<br>* Controlled ovarian stimulation starts on day 2-3 of the menstrual cycle with recombinant recombinant FSH + LH, adding cetrorelix when the follicles reach 14 mm size and ovarian maturation with triptorelin acetate<br>* Other names: Ovarian stimulation starts during the follicular phase;|
| Experimental: Luteal phase<br>Controlled ovarian stimulation starts during luteal phase on day 3 to 5 after first LH positive urine test | Procedure: Luteal phase<br>* Controlled ovarian stimulation is started between 3rd and 5th day after the first LH positive urine test, adding cetrorelix when follicles reached 14 mm size and ovarian maturation with triptorelin acetate<br>* Other names: Ovarian stimulation starts during the luteal phase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of oocytes in metaphase II obtained | number of oocytes in metaphase II obtained by follicular puncture | Through study completion, average 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of oocytes cumulus complexes | number of oocytes cumulus complexes obtained by follicular puncture | Through study completion, average 2 weeks | 
| duration of stimulation (days) | number of days from the start of ovarian stimulation until the day of follicular puncture | Through study completion, average 2 weeks | 
| cycle cancellation rate | ratio of canceled cycles regarding the number of ovarian stimulation cycles initiated | Through study completion, average 2 weeks | 
| Luteinizing hormone levels following administration of agonist for final oocyte maturation | Luteinizing hormone blood levels the day after administration of agonist for final oocyte maturation | Through study completion, average 2 weeks | 
| occurrence of side effects | occurrence of side effects at the end of study | Through study completion, average 2 weeks | 
| fertilization rate | Number of correct fertilization oocytes 18 hours post-insemination | Through study completion, average 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Controlled Ovarian stimulation, Follicular phase, Luteal phase, Reproductive Techniques, Assisted