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

IVF Clinical Trial

— RIOTC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04524026
• Other study ID #: REG-210-2017
• Secondary ID: 2017-004433-93
• Status: Completed
• Phase: Phase 2
• Start date: September 18, 2018
• Est. completion date: November 30, 2020

Study information

• Verified date: January 2021
• Source: Zealand University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: November 30, 2020
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• IVF

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Denmark	Herlev Hospitals Fertilitetsklinik	Herlev
Denmark	Sjællands Fertilitetsklinik	Køge

Sponsors (3)

Lead Sponsor	Collaborator
Nicholas Macklon	Gedeon Richter Ltd., Igenomix

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Phase of endometrial receptivity according to Endometrial Receptivity Array (ERA) test	Difference in established endometrial tissue and secretion markers of endometrial receptivity between intervention group and controls (genomic profile assessed by ERA test).	ERA-test is taken 5 days after aspiration of oocytes.
Secondary	Estradiol (E2),progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels.	Differences in the area under the curve for plasma E2, P, LH and FSH levels from day of OPU until day 14 post OPU between intervention group and control group.	Blood samples are taken on 1 day of oocyte aspiration, 2 days after, 5 days after and 14 days after.
Secondary	Endometrium thickness.	Difference in endometrium thickness 5 days post oocyte pick-up (OPU) between intervention group and controls.	Endometrium thickness is measured on 1 day of oocyte aspiration, 2 days after and 5 days after.