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InfertilityPhase 2/3RIOT-BNCT02939898

Mapping the Endocrine Determinants of Ovarian Stimulation to Optimize Outcomes in Fresh Embryo Transfer Cycles

A Phase 2/3 study testing Letrozole in people with Infertility, run by Sven O. Skouby at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this project is to identify autocrine, paracrine and endocrine factors which are associated with intercycle variation in cyclical follicle recruitment. Patients will be monitored in a natural cycle, a stimulated cycle and a follow up. Read more about this study

Who is it for?
Ages 18 to 40 years, women onlyHealthy volunteers can take part
Conditions the study is for
Infertility
What is being tested?
Letrozole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
33 participants
Where
1 siteDenmark
Study dates
Aug 2016to Jan 2018
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Indication for IVF/ICSI treatment
  • Eligible for IVF/ICSI treatment according to local criteria
  • Regular cycles 21-35 days (both included)
  • Age <40 years
  • AMH 8-32 (both included)
  • Written consent
  • Willing to undergo intensive monitoring in a natural cycle (the cycle prior to the monitored natural cycle must be hormone treatment free), stimulated cycle and follow up in the subsequent cycle

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Unit of Reproductive Medicine, Herlev Hospital

    Herlev, Capital Region, 2730

Other trials in Denmark

About this study

Official title: Reducing the Impact of Ovarian Stimulation - The RIOT Project Study RIOT-B: Mapping the Endocrine Determinants of Ovarian Stimulation to Optimize Outcomes in Fresh Embryo Transfer Cycles

The goal of this project is to identify autocrine, paracrine and endocrine factors which are associated with intercycle variation in cyclical follicle recruitment.

Patients will be monitored in a natural cycle, a stimulated cycle and a follow up. In the stimulated cycle patients will be randomized to co-treatment with aromatase inhibitor or placebo during ovarian stimulation.

Read the detailed description

The primary aim of this project is to explore the putative cyclic recruitment 'gatekeeping' functions of gonadotropins, sex steroids, anti-muellarian hormone and pregnancy associated plasma protein A in normal ovulatory cycles, and the impact of ovarian stimulation on cyclic follicle recruitment in the following cycle.

It is further proposed that supra-physiological levels of estradiol and progesterone which arise from ovarian stimulation may modulate the size of the secondarily recruited follicle cohort in the next cycle. In order to explore the relative contribution of sex steroids as determinants of the size of the next cycle 'wave' of recruitment further, a second aim of this study will be investigate whether limiting the rise in sex steroid levels during ovarian stimulation, by co-treatment with aromatase inhibitor impacts on cyclic recruitment.

Conditions
Infertility
Being tested
Placebo, Letrozole
Medical subject headings
Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Also called Lactose Monohydrate

    Adjuvant therapy to recFSH during ovarian stimulation

  • LetrozoleDrug

    Also called Aromatase Inhibitor

    Adjuvant therapy to recFSH during ovarian stimulation

Study groups in NCT02939898
Study groupRoleWhat they receive
Lactose MonohydratePlacebo comparator2 tablets of placebo are administered daily from stimulation start to day before hCG as adjunctive therapy to 150 International Units of recFSH
Receives: Drug: Placebo
LetrozoleActive comparator2 tablets of 2,5 mg Letrozole are administered daily from stimulation start to day before hCG as adjunctive therapy to 150 International Units of recFSH
Receives: Drug: Letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Size of follicle cohort in relation to serum endocrine and paracrine markers

    Markers for analysis include: anti-muellerian hormone, estradiol, follicle stimulating hormone, luteinizing hormone, testosterone, androstenedione, progesterone,17-hydroxyprogesterone, pregnancy associated plasma protein A and A2, Inhibin A and B, Bone morphogenic protein

    Measured: The change in size of follicle cohort in relation to change in endocrine and paracrine markers assessed throughout the study completion, up to 3 years.

Secondary outcomes (19)

  1. Size of the cyclically recruited follicle cohort after ovarian stimulation with and without co-treatment with Aromatase Inhibitor.

    Measured: The change in size of follicle cohort throughout the study completion, up to 3 years.

  2. Expression of cytokine and growth factors in endometrial secretions following co-treatment with Aromatase Inhibitor compared with placebo control.

    Measured: Assessed in stimulated cycle at time of embryo transfer (throughout study completion, up to 3 years).

  3. Serum E2, P, Tst and Androstenedione levels

    Measured: The change in levels throughout the study completion, up to 3 years.

  4. Area under the curve for P and 17-hydroxyprogesterone.

    Measured: The change in levels throughout the study completion, up to 3 years.

  5. Total International Units of Follicle Stimulating Hormone used per treatment cycle.

    Measured: Assessed throughout study completion, up to 3 years.

  6. Number of follicles > 12 mm

    Measured: Assessed throughout the study completion, up to 3 years.

  7. Number of oocytes obtained

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  8. Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria.

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  9. Oocyte fertilization rate

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  10. Number and quality of embryos obtained.

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  11. Endometrial thickness

    Measured: Assessed throughout the study completion, up to 3 years.

  12. Uterine contraction rate (contractions/minute)

    Measured: Assessed throughout the study completion, up to 3 years.

  13. Implantation rate

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  14. Reported side effects

    Measured: From start of stimulation and administration of study medication to pregnancy scan week gestational age 7-8. Assessed throughout the study completion, up to 3 years.

  15. Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis.

    Measured: Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years)

  16. Clinical pregnancy rate

    Measured: Pregnancy scan at gestational age week 7-8 (3-4 weeks after the positive hCG in serum) Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  17. Follicular fluid endocrine and paracrine markers following co-treatment with Aromatase Inhibitor compared with placebo control.

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  18. Biochemical pregnancy rate

    Measured: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  19. Area under the curve for E2, P and LH

    Measured: The change in levels throughout the study completion, up to 3 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionJan 2018
  4. Study completionJan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02939898
Sponsor's protocol ID
RIOTB2015
Other IDs
2015-005683-41, H-15021852, HGH-2016-033_I-Suite: 04482, 2015
Acronym
RIOT-B
Status last verified
Feb 2019
First submitted
15 Aug 2016
Last updated
5 Feb 2019
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: The study will share data with Study RIOT-A

Publications

  • Bulow NS, Warzecha AK, Nielsen MV, Andersen CY, Holt MD, Petersen MR, Sopa N, Zedeler A, Englund AL, Pinborg A, Grondahl ML, Skouby SO, Macklon NS. Impact of letrozole co-treatment during ovarian stimulation on oocyte yield, embryo development, and live birth rate in women with normal ovarian reserve: secondary outcomes from the RIOT trial. Hum Reprod. 2023 Nov 2;38(11):2154-2165. doi: 10.1093/humrep/dead182.

    PubMed 37699851

  • Poulsen LC, Warzecha AK, Bulow NS, Bungum L, Macklon NS, Yding Andersen C, Skouby SO. Effects of letrozole cotreatment on endocrinology and follicle development in women undergoing ovarian stimulation in an antagonist protocol. Hum Reprod. 2022 Jun 30;37(7):1557-1571. doi: 10.1093/humrep/deac119.

    PubMed 35652260

  • Dreyer Holt M, Warzecha AK, Bulow NS, Skouby SO, Englund ALM, Birch Petersen K, Macklon NS. Does adjuvant letrozole reduce uterine peristalsis prior to fresh embryo transfer? Hum Reprod Open. 2022 Mar 8;2022(2):hoac011. doi: 10.1093/hropen/hoac011. eCollection 2022.

    PubMed 35356508

  • Bulow NS, Skouby SO, Warzecha AK, Udengaard H, Andersen CY, Holt MD, Grondahl ML, Nyboe Andersen A, Sopa N, Mikkelsen ALE, Pinborg A, Macklon NS. Impact of letrozole co-treatment during ovarian stimulation with gonadotrophins for IVF: a multicentre, randomized, double-blinded placebo-controlled trial. Hum Reprod. 2022 Jan 28;37(2):309-321. doi: 10.1093/humrep/deab249.

    PubMed 34792133

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Letrozole in people with Infertility, run by Sven O. Skouby at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Size of follicle cohort in relation to serum endocrine and paracrine markers (time frame: The change in size of follicle cohort in relation to change in endocrine and paracrine markers assessed throughout the study completion, up to 3 years.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02939898, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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