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Completed

NCT Number: NCT02939898

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

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.

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Key information

Conditions

Infertility Genital Diseases Urogenital Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Unit of Reproductive Medicine, Herlev Hospital

Herlev, Capital Region, 2730, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo

Drug

Adjuvant therapy to recFSH during ovarian stimulation

Other names: Lactose Monohydrate

letrozole

Drug

Adjuvant therapy to recFSH during ovarian stimulation

Other names: Aromatase Inhibitor

Primary outcomes

  1. Size of follicle cohort in relation to serum endocrine and paracrine markers

    Time frame: 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.

    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

Secondary outcomes

  1. Size of the cyclically recruited follicle cohort after ovarian stimulation with and without co-treatment with Aromatase Inhibitor.

    Time frame: The change in size of follicle cohort throughout the study completion, up to 3 years.

  2. Expression of cytokine and growth factors in endometrial secretions following co-treatment with Aromatase Inhibitor compared with placebo control.

    Time frame: Assessed in stimulated cycle at time of embryo transfer (throughout study completion, up to 3 years).

  3. Serum E2, P, Tst and Androstenedione levels

    Time frame: The change in levels throughout the study completion, up to 3 years.

  4. Area under the curve for P and 17-hydroxyprogesterone.

    Time frame: The change in levels throughout the study completion, up to 3 years.

  5. Total International Units of Follicle Stimulating Hormone used per treatment cycle.

    Time frame: Assessed throughout study completion, up to 3 years.

  6. Number of follicles > 12 mm

    Time frame: Assessed throughout the study completion, up to 3 years.

  7. Number of oocytes obtained

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  8. Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria.

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  9. Oocyte fertilization rate

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  10. Number and quality of embryos obtained.

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  11. Endometrial thickness

    Time frame: Assessed throughout the study completion, up to 3 years.

  12. Uterine contraction rate (contractions/minute)

    Time frame: Assessed throughout the study completion, up to 3 years.

  13. Implantation rate

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  14. Reported side effects

    Time frame: 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.

  15. Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis.

    Time frame: Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years)

  16. Clinical pregnancy rate

    Time frame: 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).

  17. Follicular fluid endocrine and paracrine markers following co-treatment with Aromatase Inhibitor compared with placebo control.

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  18. Biochemical pregnancy rate

    Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).

  19. Area under the curve for E2, P and LH

    Time frame: The change in levels throughout the study completion, up to 3 years.

Sponsors and collaborators

Lead sponsor

Sven O. Skouby

Other

Collaborators

  • Copenhagen University Hospital, Denmark
  • Region Capital Denmark
  • Rigshospitalet, Denmark

Registry information

Official study 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

Acronym: RIOT-B

Important dates

Study start
2016
Primary completion
2018
Study completion
2018
First posted
Oct 20, 2016
Registry last updated
Feb 5, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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