Long-term Endogenous Androgen Priming in Bologna Criteria Poor Responder Patients - A Pilot Study

NCT03447184 | Completed

• 1 other identifier: CS/BVMD/18/01
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Until now no scientific clinical evidence exists regarding the possible impact of long term endogenous androgen priming in IVF patients aligned with the Bologna Criteria, in specific the impact of priming on serum parameters correlated with the ovarian reserve, antral follicle count, and the number of retrievable follicles. Thus, this pilot-study will explore a new suggested protocol for the Bologna criteria patient developed from basic physiology, and will if successful result in a subsequent randomized controlled trial in the same subset of patients, enabling a possible paradigm shift in the treatment of poor ovarian response (POR).

Conditions

Poor Ovarian Response

Outcome Measures

Primary Outcomes (1)

• Serum concentrations of AMH

  Blood sampling

  8 weeks after starting androgen priming

Secondary Outcomes (6)

• Number of antral follicles

  8 weeks after starting androgen priming

• Serum concentrations of testosterone

  Up to 2 weeks after starting FSH stimulation

• Serum concentrations of hCG

  Up to 2 weeks after starting FSH stimulation

• Serum concentrations of progesterone

  Up to 2 weeks after starting FSH stimulation

• Number of antral follicles

  Up to 2 weeks after starting FSH stimulation

Other Outcomes (10)

• Follicular fluid concentration of estradiol

  Up to one hour after ovum pick-up

• Follicular fluid concentration of androstenedione

  Up to one hour after ovum pick-up

• Follicular fluid concentration of testosterone

  Up to one hour after ovum pick-up

Study Arms (1)

Androgen priming

Eight weeks prior to stimulation for IVF - at the onset of menses, patients will start treatment with a low dose of rhCG (Ovitrelle). At the same time daily treatment with the aromatase inhibitor will commence, concomitantly with GnRHa down-regulation with a depot GnRHa (28days). After 8 weeks, a standard rFSH stimulation with either 300 IU rFSH or 300 IU rFSH+rLH will start. The androgen priming (hCG and aromatase inhibitor) will stop on the first day of stimulation.

Drug: Androgen priming

Interventions

Androgen priming DRUG

Androgen priming: with a low dose of recombinant hCG, aromatase inhibitor, and a depot GnRHa for 8 weeks Stimulation: a standard rFSH stimulation with either 300 IU rFSH or 300 IU (rFSH + rLH) Blood sampling: 6 blood samples to measure FSH, LH, E2, testosterone, and AMH Ultrasound examination: to count all antral follicles, 2-10 mm in each ovary Follicular fluid: to analyze E2, androstenedione, testosterone, progesterone, inhibin B. Granulosa cells: to analyze gene expression in cumulus and mural granulosa cells of Luteinising hormone receptor (LHR), 3β-hydroxy-steroid-dehydrogenase (3ßHSD), inhibin-Ba (INHB-A) receptor, androgen and FSH receptor

Also known as: low dose hCG and aromatase inhibitor priming

Androgen priming

Eligibility Criteria

• Age: 18 Years - 41 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Bologna poor responders: At least two of the following three features present: * Advanced maternal age (≥40 years) or any other risk factor for POR * A previous POR (≤3 oocytes with a conventional stimulation protocol) * An abnormal ovarian reserve test (i.e. antral follicle count \< 5-7 follicles or AMH\< 0.5 - 1.1 ng/mL) * Poor responder if - Two previous episodes of POR after maximal stimulation (300 IU)

You may qualify if:

• Age 18 - 41 years
• BMI \< 30 kg/m2
• Ovarian reserve, according to the ESHRE Bologna Criteria measured within two months prior to stimulation start
• Bologna criteria: At least two of the following three features present:
• Advanced maternal age (≥40 years) or any other risk factor for POR
• A previous POR (≤3 oocytes with a conventional stimulation protocol)
• An abnormal ovarian reserve test (i.e. antral follicle count \< 5-7 follicles or AMH\< 0.5 - 1.1 ng/mL)
• Poor responder if - Two previous episodes of POR after maximal stimulation (300 IU)
• Receiving GnRH-antagonist co-treatment during ovarian stimulation
• Agreement to participate in the study, and to disclose any medical events to the investigator. The subject must be willing and able to comply with the protocol requirements for the duration of the study.
• Have given written informed consent with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.

You may not qualify if:

• Chronical medical conditions like Diabetes, Crohns disease, Thyroid disease, Hepatitis B and Sexually Transmitted Diseases Simultaneous participation in an interventional clinical trial.

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (1)

Lan N Vuong

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• Vuong TNL, Ho MT, Ha TQ, Jensen MB, Andersen CY, Humaidan P. Effect of GnRHa ovulation trigger dose on follicular fluid characteristics and granulosa cell gene expression profiles. J Assist Reprod Genet. 2017 Apr;34(4):471-478. doi: 10.1007/s10815-017-0891-9. Epub 2017 Feb 14.

  PMID: 28197932 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples Follicular fluid Granulosa cells

Study Officials

• Tuong M Ho, MD

  Mỹ Đức Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: February 27, 2018
• Study Start: March 26, 2018
• Primary Completion: February 18, 2019
• Study Completion: March 1, 2019
• Last Updated: July 5, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)