RIOTC: Reducing the Impact of Ovarian Stimulation. Novel Approaches to Luteal Support in IVF-Study 2

NCT04524026 | Completed Phase 2 DMC

• 2 other identifiers: REG-210-20172017-004433-93
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of the randomised controlled study (RCT) is to identify novel strategies that can improve the luteal phase endocrinology after ovarian stimulation, with the aim of using less or no luteal support in IVF while making the endometrium thinner and more receptive to embryo implantation.

Conditions

IVF

Keywords

Letrozole, aromatase inhibitor, luteal phase, IVF

Outcome Measures

Primary Outcomes (1)

• Length of luteal phase (days from aspiration untill bleeding)

  Difference in lengths of days until bleeding (from aspiration until first day of bleeding) of the luteal phase between intervention group and control group.

  Up to three weeks

Secondary Outcomes (3)

• Phase of endometrial receptivity according to Endometrial Receptivity Array (ERA) test

  ERA-test is taken 5 days after aspiration of oocytes.

• Estradiol (E2),progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels.

  Blood samples are taken on 1 day of oocyte aspiration, 2 days after, 5 days after and 14 days after.

• Endometrium thickness.

  Endometrium thickness is measured on 1 day of oocyte aspiration, 2 days after and 5 days after.

Study Arms (2)

Intervention

EXPERIMENTAL

recFSH and co-treatment with letrozole 5 mg/day from stimulation day 1 on cycle day 2 or 3 until the day before gonadotrophin releasing hormone(GnRH) agonist administration to trigger final oocyte maturation. GnRH antagonist 0.25 mg/day from stimulation day 5 until day of GnRH agonist administration. No luteal phase support.

Drug: Letrozole 5 mg

Control group

NO INTERVENTION

recFSH from stimulation day 1 on cycle day 2 or 3 until the day before GnRH agonist administration to trigger final oocyte maturation. GnRH antagonist 0.25 mg/day from stimulation day 5 until day of GnRH agonist administration. No luteal phase support.

Interventions

Letrozole 5 mg DRUG

recFSH and co-treatment with letrozole 5 mg/day from stimulation day 1 on cycle day 2 or 3 until the day before GnRH agonist administration to trigger final oocyte maturation. GnRH antagonist 0.25 mg/day from stimulation day 5 until day of GnRH agonist administration. No luteal phase support.

Also known as: Aromatase inhibitor

Intervention

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Yes, but patients will have genitals examined.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Meet the clinical criteria for acceptance as oocyte donors (healthy women who volunteers to donate oocytes to other women).
• Regular ovulatory cycle of 26-32 days.
• Age: 18-35 years old.
• Written consent.

You may not qualify if:

• Contraindications for ovarian stimulation or aspiration of oocytes according to local guidelines
• Polycystic Ovary Syndrome (PCOS)
• Allergy towards study drug
• Women who have had a hormone or copper intra-uterine device (IUD) within 3 months
• Patient withdrawal of consent
• Lack of compliance with medication
• Medical complication arising from IVF treatment that requires the cycle to be terminated
• Serious adverse events (SAE) or serious adverse reactions (SAR) including severe allergy to study drug.
• Specific ARs to study drug: severe degree of hot flushed, severe degree of nausea/vomiting, severe diarrhea, severe degree of muscle and joint pain.

Sponsors & Collaborators

• Nicholas Macklon: lead
• Gedeon Richter Ltd.: collaborator
• Igenomix: collaborator

Study Sites (2)

Herlev Hospitals Fertilitetsklinik

Herlev, 2730, Denmark

Location

Sjællands Fertilitetsklinik

Køge, 4600, Denmark

Location

Related Publications (1)

• Dreyer Holt M, Skouby SO, Bulow NS, Englund ALM, Birch Petersen K, Macklon NS. The Impact of Suppressing Estradiol During Ovarian Stimulation on the Unsupported Luteal Phase: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3633-e3643. doi: 10.1210/clinem/dgac409.

  PMID: 35779242 DERIVED

MeSH Terms

Interventions

Letrozole; Aromatase Inhibitors

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

• Nicholas Stephen Macklon, Professor

  Professor

  PRINCIPAL INVESTIGATOR

• Marianne Dreyer Holt, MD

  PhD student

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: August 24, 2020
• Study Start: September 18, 2018
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: January 14, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)