Effect of Addition of Aromatase Inhibitor to Ovarian Stimulation Therapy in IVF Treatment

NCT02946684 | Completed Phase 2 DMC

• 4 other identifiers: RIOTA20152015-005682-24H-15021850HGH-2016-045_04513
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 4

Brief Summary

This project seeks to determine whether estradiol suppression achieved with adjuvant treatment with an aromatase inhibitor improves end-follicular and midluteal phase parameters during IVF. 128 patients will be randomized to either placebo or active treatment.

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

• Serum progesterone level

  Assessed during stimulation treatment on day before hCG injection (throughout the study completion, up to 3 years)

Secondary Outcomes (15)

• Serum estradiol, testosterone and androstenedione levels

  Assessed on stimulation day 5, day of hCG administration (or the day before), day 7 and 10 after hCG administration. Assessed throughout study completion, up to 3 years.

• P and 17-hydroxyprogesterone (17-HP) Area Under the Curve.

  Assessed during stimulation treatment throughout the study completion, up to 3 years.

• Follicular fluid concentration of estradiol, testosterone, inhibin B and AMH levels

  Assessed during stimulation treatment (throughout the study completion, up to 3 years

• Total IU of Follicle Stimulating Hormone used per cycle.

  Assessed throughout study completion, up to 3 years

• Number of follicles > 12 mm

  Assessed in stimulated cycle on day of hCG administration or the day before (throughout the study completion), up to 3 years. Cycle length is between 21 and 35 days

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 IU of recFSH

Drug: Placebo

Letrozole 5mg

ACTIVE COMPARATOR

2 tablets of 2,5mg Letrozole are administered daily from stimulation start to day before hCG as adjunctive therapy to 150 IU of recFSH

Drug: Letrozole

Interventions

Letrozole DRUG

Adjuvant therapy to recFSH during ovarian stimulation

Also known as: Aromatase Inhibitor

Letrozole 5mg

Placebo DRUG

Adjuvant therapy to recFSH during ovarian stimulation

Also known as: Lactose Monohydrate

Lactose Monohydrate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (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
• AMH 8- 32 (both included)
• Written consent

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

Sponsors & Collaborators

• Sven O. Skouby: lead
• Rigshospitalet, Denmark: collaborator
• Hvidovre University Hospital: collaborator
• Holbaek Sygehus: collaborator
• Region Capital Denmark: collaborator
• Copenhagen University Hospital, Denmark: collaborator
• Zealand University Hospital: collaborator

Study Sites (4)

Unit of Reproductive Medicine, Herlev Hospital

Herlev, Capital Region, 2730, Denmark

Location

Department of Fertility, Juliane Marie Centeret

Copenhagen, Capitol Region, 2100, Denmark

Location

Clinic of Fertility, Hvidovre Hospital

Hvidovre, Capitol Region, 2650, Denmark

Location

Clinic of Fertility, Holbæk Hospital

Holbæk, Region of Zealand, 4300, Denmark

Location

Related Publications (2)

• 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: 37699851 DERIVED

• 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: 34792133 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Letrozole; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological 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: July 11, 2016
• First Posted: October 27, 2016
• Study Start: February 1, 2017
• Primary Completion: October 30, 2018
• Study Completion: October 30, 2018
• Last Updated: July 8, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (4)