NCT02939898

Brief 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. In the stimulated cycle patients will be randomized to co-treatment with aromatase inhibitor or placebo during ovarian stimulation.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
33

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Aug 2016

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2016

Completed
14 days until next milestone

First Submitted

Initial submission to the registry

August 15, 2016

Completed
2 months until next milestone

First Posted

Study publicly available on registry

October 20, 2016

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2018

Completed
Last Updated

February 5, 2019

Status Verified

February 1, 2019

Enrollment Period

1.4 years

First QC Date

August 15, 2016

Last Update Submit

February 4, 2019

Conditions

Infertility

Outcome Measures

Primary Outcomes (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

    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)

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

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

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

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

  • Serum E2, P, Tst and Androstenedione levels

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

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

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

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

    Assessed throughout study completion, up to 3 years.

  • +14 more secondary outcomes

Study Arms (2)

Lactose Monohydrate

PLACEBO COMPARATOR

2 tablets of placebo are administered daily from stimulation start to day before hCG as adjunctive therapy to 150 International Units of recFSH

Drug: Placebo

Letrozole

ACTIVE COMPARATOR

2 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

Drug: Letrozole

Interventions

PlaceboDRUG

Adjuvant therapy to recFSH during ovarian stimulation

Also known as: Lactose Monohydrate
Lactose Monohydrate
LetrozoleDRUG

Adjuvant therapy to recFSH during ovarian stimulation

Also known as: Aromatase Inhibitor
Letrozole

Eligibility Criteria

Age18 Years - 40 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Unit of Reproductive Medicine, Herlev Hospital

Herlev, Capital Region, 2730, Denmark

Location

Related Publications (4)

  • 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.

    PMID: 37699851DERIVED

  • 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.

    PMID: 35652260DERIVED

  • 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.

    PMID: 35356508DERIVED

  • 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.

    PMID: 34792133DERIVED

MeSH Terms

Conditions

Infertility

Interventions

LetrozoleAromatase Inhibitors

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Intervention Hierarchy (Ancestors)

NitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsSteroid Synthesis InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesEstrogen AntagonistsHormone AntagonistsHormones, Hormone Substitutes, and Hormone AntagonistsPhysiological Effects of Drugs

Study Officials

  • Sven O. Skouby, Professor

    Unit of Reproductive Medicine, Herlev/Gentofte Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

August 15, 2016

First Posted

October 20, 2016

Study Start

August 1, 2016

Primary Completion

January 1, 2018

Study Completion

January 1, 2018

Last Updated

February 5, 2019

Record last verified: 2019-02

Data Sharing

IPD Sharing
Will share

The study will share data with Study RIOT-A

Locations

DK(1)