Mapping the Endocrine Determinants of Ovarian Stimulation to Optimize Outcomes in Fresh Embryo Transfer Cycles

Infertility Clinical Trial

— RIOT-B  

Official title:

Reducing the Impact of Ovarian Stimulation - The RIOT Project Study RIOT-B: Mapping the Endocrine Determinants of Ovarian Stimulation to Optimize Outcomes in Fresh Embryo Transfer Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02939898
• Other study ID #: RIOTB2015
• Secondary ID: 2015-005683-41H-
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 2016
• Est. completion date: January 2018

Study information

• Verified date: February 2019
• Source: Herlev Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The primary aim of this project is to explore the putative cyclic recruitment 'gatekeeping' functions of gonadotropins, sex steroids, anti-muellarian hormone and pregnancy associated plasma protein A in normal ovulatory cycles, and the impact of ovarian stimulation on cyclic follicle recruitment in the following cycle.

It is further proposed that supra-physiological levels of estradiol and progesterone which arise from ovarian stimulation may modulate the size of the secondarily recruited follicle cohort in the next cycle. In order to explore the relative contribution of sex steroids as determinants of the size of the next cycle 'wave' of recruitment further, a second aim of this study will be investigate whether limiting the rise in sex steroid levels during ovarian stimulation, by co-treatment with aromatase inhibitor impacts on cyclic recruitment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: January 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Placebo
Adjuvant therapy to recFSH during ovarian stimulation
• Letrozole
Adjuvant therapy to recFSH during ovarian stimulation

Locations

Country	Name	City	State
Denmark	Unit of Reproductive Medicine, Herlev Hospital	Herlev	Capital Region

Sponsors (4)

Lead Sponsor	Collaborator
Sven O. Skouby	Copenhagen University Hospital, Denmark, Region Capital Denmark, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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).
Secondary	Serum E2, P, Tst and Androstenedione levels		The change in levels throughout the study completion, up to 3 years.
Secondary	Area under the curve for P and 17-hydroxyprogesterone.		The change in levels throughout the study completion, up to 3 years.
Secondary	Total International Units of Follicle Stimulating Hormone used per treatment cycle.		Assessed throughout study completion, up to 3 years.
Secondary	Number of follicles > 12 mm		Assessed throughout the study completion, up to 3 years.
Secondary	Number of oocytes obtained		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria.		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Oocyte fertilization rate		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Number and quality of embryos obtained.		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Endometrial thickness		Assessed throughout the study completion, up to 3 years.
Secondary	Uterine contraction rate (contractions/minute)		Assessed throughout the study completion, up to 3 years.
Secondary	Implantation rate		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Reported side effects		From start of stimulation and administration of study medication to pregnancy scan week gestational age 7-8. Assessed throughout the study completion, up to 3 years.
Secondary	Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis.		Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years)
Secondary	Clinical pregnancy rate		Pregnancy scan at gestational age week 7-8 (3-4 weeks after the positive hCG in serum) Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Follicular fluid endocrine and paracrine markers following co-treatment with Aromatase Inhibitor compared with placebo control.		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Biochemical pregnancy rate		Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Secondary	Area under the curve for E2, P and LH		The change in levels throughout the study completion, up to 3 years.