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

NCT ID: NCT04524026

Last Updated: 2021-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-18
• Study Completion Date: 2020-11-30

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.

Detailed Description

The high estradiol levels generated in IVF by multiple dominant follicles at the follicular-luteal phase transition generate powerful negative feedback at the pituitary gland, effectively switching off gonadotropin production. Without stimulation by endogenous luteinizing hormone (LH), the corpora lutea undergo involution and menstruation follows, preventing the establishment of pregnancy.

To address these detrimental effects of ovarian stimulation, the investigators will do a RCT with the use of aromatase inhibitors, which suppress the conversion of androgens to estrogens to ameliorate the unwanted effects of high estrogens.

This study is designed to test the hypothesis that preventing supra-physiological estrogen levels during ovarian stimulation restricts pituitary suppression sufficiently to allow LH levels to rise and support the corpora lutea, leading to a normal post-ovulatory luteal phase, evidenced by a normal duration and luteal phase endocrine profile. To test this, consenting oocyte donors will be randomized to receive co-treatment with aromatase inhibitors or no co-treatment during ovarian stimulation. Following oocyte retrieval, no luteal support will be provided to donors in both Groups.

Conditions

IVF

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention

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.

Group Type: EXPERIMENTAL

Letrozole 5 mg

Intervention Type: 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.

Control group

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Letrozole 5 mg

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.

Intervention Type: DRUG

Other Intervention Names

Aromatase inhibitor

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

Exclusion of patients after earlier inclusion in the study in case of

• 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.

In case of exclusion of a patient after earlier inclusion in the study, a new patient will be included.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Gedeon Richter Ltd.

INDUSTRY

Sponsor Role: collaborator

Igenomix

INDUSTRY

Sponsor Role: collaborator

Nicholas Macklon

OTHER

Sponsor Role: lead

Responsible Party

Nicholas Macklon

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nicholas Stephen Macklon, Professor

Role: PRINCIPAL_INVESTIGATOR

Professor

Marianne Dreyer Holt, MD

Role: STUDY_DIRECTOR

PhD student

Locations

Herlev Hospitals Fertilitetsklinik

Herlev, , Denmark

Sjællands Fertilitetsklinik

Køge, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 35779242 (View on PubMed)

Other Identifiers

2017-004433-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

REG-210-2017

Identifier Type: -

Identifier Source: org_study_id