RIOT STUDY B: MAPPING OF SPECIFIC FACTORS THAT DETERMINE STIMULATION OF THE OVARIES UNDER FERTILITY TREATMENT IN ORDER TO IMPROVE PREGNANCY CHANCE

REDUCING THE IMPACT OF OVARIAN STIMULATION - THE RIOT PROJECT RIOT STUDY B: MAPPING THE ENDOCRINE DETERMINANTS OF OVARIAN STIMULATION TO OPTIMIZE OUTCOMES IN FRESH EMBRYO TRANSFER CYCLES

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-005683-41-DK

Enrollment

Registered

2016-01-07

Start date

2016-03-16

Completion date

Unknown

Last updated

2018-08-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infertility MedDRA version: 20.0 Level: LLT Classification code 10016401 Term: Female infertility of other specified origin System Organ Class: 100000004872 MedDRA version: 20.0 Level: LLT Classification code 10025511 Term: Male infertility, unspecified System Organ Class: 100000004872 MedDRA version: 20.0 Level: LLT Classification code 10016403 Term: Female infertility of tubal origin System Organ Class: 100000004872

Interventions

Trade Name: Letrozole "Accord" Product Name: Letrozole Pharmaceutical Form: Capsule INN or Proposed INN: LETROZOLE CAS Number: 112809-51-5 Concentration unit: mg milligram(s) Concentration type: equal

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: INCLUSION CRITERIA Indication for IVF/ICSI treatment Eligible for IVF/ICSI treatment according to local criteria IVF/ICSI treatment with single embryo transfer Regular cycles 21-35 days (both included) Age =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: EXCLUSION CRITERIA Any contraindication for IVF/ICSI treatment according to local criteria Previous stimulation for IVF/ICSI with < 4 oocytes obtained PCOS Undergoing IVF/ICSI for the purpose of fertility preservation Allergy towards study drug

Design outcomes

Primary

Measure	Time frame
Primary end point(s): KEY ENDPOINTS 1. Size of follicle cohort in relation to serum endocrine and paracrine markers including AMH, E2, FSH, LH, Tst, Androstenedione, P, 17-HP PAPP-A and A2 Inhibin A and B BMPs 2. Size of the cyclically recruited follicle cohort (AFC) after ovarian stimulation with and without co-treatment with AI. 3. Expression of cytokine and growth factors in endometrial secretions, uterine contractility and follicular fluid endocrine and paracrine markers following co-treatment with AI compared with placebo control. ;Timepoint(s) of evaluation of this end point: DURATION Patient recruitment: March 2016 – March 2018 Data analysis: March 2018 – September 2018 Publication of results: September 2018 – March 2019 The duration for each patient will not exceed 3 months from inclusion to last visit. ;Main Objective: 1. Do specific autocrine, paracrine and endocrine factors act as gate keepers to cyclic follicle recruitment? 2. Does ovarian stimulation disrupt cyclic follicle recruitment by altering these factors and can this effect be modulated by suppressing the associated supra-physiological rise in sex steroids using co-treatment with aromatase inhibitors? 3. Does suppression of supra-physiological estradiol with AI alter the intrafollicular endocrine milieu, reduce uterine contractility and the disruption of cytokine markers of endometrial receptivity caused by ovarian stimulation with exogenous gonadotropin? ;Secondary Objective: Oocyte fertilization, embryo quality, implantation, pregnancy rate	—

Measure

Time frame

Primary end point(s): KEY ENDPOINTS 1. Size of follicle cohort in relation to serum endocrine and paracrine markers including AMH, E2, FSH, LH, Tst, Androstenedione, P, 17-HP PAPP-A and A2 Inhibin A and B BMPs 2. Size of the cyclically recruited follicle cohort (AFC) after ovarian stimulation with and without co-treatment with AI. 3. Expression of cytokine and growth factors in endometrial secretions, uterine contractility and follicular fluid endocrine and paracrine markers following co-treatment with AI compared with placebo control. ;Timepoint(s) of evaluation of this end point: DURATION Patient recruitment: March 2016 – March 2018 Data analysis: March 2018 – September 2018 Publication of results: September 2018 – March 2019 The duration for each patient will not exceed 3 months from inclusion to last visit. ;Main Objective: 1. Do specific autocrine, paracrine and endocrine factors act as gate keepers to cyclic follicle recruitment? 2. Does ovarian stimulation disrupt cyclic follicle recruitment by altering these factors and can this effect be modulated by suppressing the associated supra-physiological rise in sex steroids using co-treatment with aromatase inhibitors? 3. Does suppression of supra-physiological estradiol with AI alter the intrafollicular endocrine milieu, reduce uterine contractility and the disruption of cytokine markers of endometrial receptivity caused by ovarian stimulation with exogenous gonadotropin? ;Secondary Objective: Oocyte fertilization, embryo quality, implantation, pregnancy rate

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Secondary

Measure	Time frame
Secondary end point(s): 1.Area under the curve from day 4 to day 10 post hCG administration for, P and 17-hydroxyprogesterone (17-HP). 2.Serum E2, P T and androstenedione levels on Stimulation day 5, day of hCG administration (or the day before), day of oocyte pick up, day 7 and 10 after hCG administration. 3. Total IU of FSH used per cycle. 4. Number of follicles > 12 mm on day of hCG (or the day before) and oocytes obtained. 5. Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria. 6. Oocyte fertilization rate 7. Number and quality of embryos obtained. 8. Endometrial thickness on day of hCG (or the day before) and day of embryo transfer. 9. Uterine contraction rate (contractions/minute) day 3 or 4 or 5 after ovulation (determined by urine LH test) in natural cycle and just prior to embryo transfer in stimulated cycle 10. Implantation rate, biochemical and ongoing pregnancy rate (viable intra-uterine pregnancy recorded at week 7-8 ultrasound). 11. Reported side effects 12. Morphometric/kinetic markers of embryo quality ;Timepoint(s) of evaluation of this end point: DURATION Patient recruitment: August 2016 – March 2018 Data analysis: March 2018 – September 2018 Publication of results: September 2018 – March 2019 The duration for each patient will not exceed 3 months from inclusion to last visit.	—

Measure

Time frame

Secondary end point(s): 1.Area under the curve from day 4 to day 10 post hCG administration for, P and 17-hydroxyprogesterone (17-HP). 2.Serum E2, P T and androstenedione levels on Stimulation day 5, day of hCG administration (or the day before), day of oocyte pick up, day 7 and 10 after hCG administration. 3. Total IU of FSH used per cycle. 4. Number of follicles > 12 mm on day of hCG (or the day before) and oocytes obtained. 5. Proportion of oocytes resulting in top quality day 2 (or day 3) embryos according to validated morphological criteria. 6. Oocyte fertilization rate 7. Number and quality of embryos obtained. 8. Endometrial thickness on day of hCG (or the day before) and day of embryo transfer. 9. Uterine contraction rate (contractions/minute) day 3 or 4 or 5 after ovulation (determined by urine LH test) in natural cycle and just prior to embryo transfer in stimulated cycle 10. Implantation rate, biochemical and ongoing pregnancy rate (viable intra-uterine pregnancy recorded at week 7-8 ultrasound). 11. Reported side effects 12. Morphometric/kinetic markers of embryo quality ;Timepoint(s) of evaluation of this end point: DURATION Patient recruitment: August 2016 – March 2018 Data analysis: March 2018 – September 2018 Publication of results: September 2018 – March 2019 The duration for each patient will not exceed 3 months from inclusion to last visit.

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Countries

Denmark

Contacts

Public ContactUnit of Reproductive Medicine

Sven O. Skouby, Professor, MD, DMSc. Unit of reproductive Medicine, Herlev Hospital

sven.olaf.skouby@regionh.dk+4538683796

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026