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NCT Number: NCT03447184

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

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).

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Key information

Conditions

Poor Ovarian Response

Age range

18 year–41 year

Sex eligibility

Female

Study type

Observational

Primary location

Lan N Vuong

Ho Chi Minh City, Vietnam

About this study

A single center study pilot study in 30 IVF Bologna criteria POR patients. All patients fulfilling the ESHRE Bologna criteria will be eligible for inclusion.

Eight weeks prior to stimulation for IVF, patients will start treatment with a low dose of rhCG (Ovitrelle). At the same time daily treatment with the aromatase inhibitor daily will commence, concomitantly with GnRHa down-regulation with a depot GnRHa.

After 8 weeks, stimulation will be performed with a fixed dose of 300 IU rFSH (Gonal F, Merck) for the first 5 days in patients ≤ 34 years of age and 300 IU Pergoveris (Merck) in patients ≥ 35 years of age. The use of hCG and aromatase inhibitor will stop on the first day of stimulation.

Monitoring will be performed according to the standard procedure of the clinic. Patients will receive a bolus of 6.500 IU rhCG (Ovitrelle, Merck) for triggering of final oocyte maturation. Oocyte pick-up and embryo transfer will be performed according to the policy of the clinic. Oocyte pick-up (OPU) and embryo transfer will be performed according to standard procedures.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • 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.

Exclusion criteria

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

Treatment and study plan

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

Other names: low dose hCG and aromatase inhibitor priming

Primary outcomes

  1. Serum concentrations of AMH

    Time frame: 8 weeks after starting androgen priming

    Blood sampling

Secondary outcomes

  1. Number of antral follicles

    Time frame: 8 weeks after starting androgen priming

    Follicles 2-10mm on ultrasound

  2. Serum concentrations of testosterone

    Time frame: Up to 2 weeks after starting FSH stimulation

    Blood sampling

  3. Serum concentrations of hCG

    Time frame: Up to 2 weeks after starting FSH stimulation

    Blood sampling

  4. Serum concentrations of progesterone

    Time frame: Up to 2 weeks after starting FSH stimulation

    Blood sampling

  5. Number of antral follicles

    Time frame: Up to 2 weeks after starting FSH stimulation

    Follicles 2-10 mm on ultrasound

  6. Number of pre-ovulatory follicles

    Time frame: Up to 2 weeks after starting FSH stimulation

    Follicles >/= 14 mm on ultrasound

Other outcomes

  1. Follicular fluid concentration of estradiol

    Time frame: Up to one hour after ovum pick-up

    Aspiration of follicular fluid while doing ovum pick-up

  2. Follicular fluid concentration of androstenedione

    Time frame: Up to one hour after ovum pick-up

    Aspiration of follicular fluid while doing ovum pick-up

  3. Follicular fluid concentration of testosterone

    Time frame: Up to one hour after ovum pick-up

    Aspiration of follicular fluid while doing ovum pick-up

  4. Follicular fluid concentration of progesterone

    Time frame: Up to one hour after ovum pick-up

    Aspiration of follicular fluid while doing ovum pick-up

  5. Follicular fluid concentration of inhibin B

    Time frame: Up to one hour after ovum pick-up

    Aspiration of follicular fluid while doing ovum pick-up

  6. Cumulus and mural Luteinising hormone receptor (LHR) gene expression

    Time frame: Up to one hour after ovum pick-up

    Cumulus and mural granulosa cells from oocyte from the first follicle in each women were isolated immediately after ovum pick-up and snap frozen for analysis of LHR gene expression. qPCR was performed and calculation of the expression level of the gene of interest was carried out according to the comparative method, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for relative quantification of gene expression.

  7. Cumulus and mural 3β-hydroxy-steroid-dehydrogenase (3ßHSD) gene expression

    Time frame: Up to one hour after ovum pick-up

    Cumulus and mural granulosa cells from oocyte from the first follicle in each women were isolated immediately after ovum pick-up and snap frozen for analysis of 3ßHSD gene expression. qPCR was performed and calculation of the expression level of the gene of interest was carried out according to the comparative method, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for relative quantification of gene expression.

  8. Cumulus and mural inhibin-Ba (INHB-A) receptor gene expression

    Time frame: Up to one hour after ovum pick-up

    Cumulus and mural granulosa cells from oocyte from the first follicle in each women were isolated immediately after ovum pick-up and snap frozen for analysis of INHB-A gene expression. qPCR was performed and calculation of the expression level of the gene of interest was carried out according to the comparative method, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for relative quantification of gene expression.

  9. Cumulus and mural androgen receptor gene expression

    Time frame: Up to one hour after ovum pick-up

    Cumulus and mural granulosa cells from oocyte from the first follicle in each women were isolated immediately after ovum pick-up and snap frozen for analysis of androgen receptor gene expression. qPCR was performed and calculation of the expression level of the gene of interest was carried out according to the comparative method, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for relative quantification of gene expression.

  10. Cumulus and mural FSH receptor gene expression

    Time frame: Up to one hour after ovum pick-up

    Cumulus and mural granulosa cells from oocyte from the first follicle in each women were isolated immediately after ovum pick-up and snap frozen for analysis of FSH receptor gene expression. qPCR was performed and calculation of the expression level of the gene of interest was carried out according to the comparative method, normalised to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for relative quantification of gene expression.

Sponsors and collaborators

Lead sponsor

Mỹ Đức Hospital

Other

Registry information

Official study title

Will Long-term Endogenous Androgen Priming, Using a Combination of Low Dose HCG and Aromatase Inhibitor in Bologna Criteria Poor Responder Patients Increase Ovarian Reserve Parameters - A Pilot Study

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Feb 27, 2018
Registry last updated
Jul 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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