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

Poor Ovarian Response Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03447184
• Other study ID #: CS/BVMD/18/01
• Status: Completed
• Start date: March 26, 2018
• Est. completion date: March 1, 2019

Study information

• Verified date: July 2019
• Source: M? Ð?c Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 1, 2019
• Est. primary completion date: February 18, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 41 Years

Eligibility

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.

Related Conditions & MeSH terms

• Poor Ovarian Response

Intervention

Drug:
• Androgen priming
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), 3ß-hydroxy-steroid-dehydrogenase (3ßHSD), inhibin-Ba (INHB-A) receptor, androgen and FSH receptor

Locations

Country	Name	City	State
Vietnam	Lan N Vuong	Ho Chi Minh City

Sponsors (1)

Lead Sponsor	Collaborator
M? Ð?c Hospital

Country where clinical trial is conducted

Vietnam, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Follicular fluid concentration of estradiol	Aspiration of follicular fluid while doing ovum pick-up	Up to one hour after ovum pick-up
Other	Follicular fluid concentration of androstenedione	Aspiration of follicular fluid while doing ovum pick-up	Up to one hour after ovum pick-up
Other	Follicular fluid concentration of testosterone	Aspiration of follicular fluid while doing ovum pick-up	Up to one hour after ovum pick-up
Other	Follicular fluid concentration of progesterone	Aspiration of follicular fluid while doing ovum pick-up	Up to one hour after ovum pick-up
Other	Follicular fluid concentration of inhibin B	Aspiration of follicular fluid while doing ovum pick-up	Up to one hour after ovum pick-up
Other	Cumulus and mural Luteinising hormone receptor (LHR) gene expression	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.	Up to one hour after ovum pick-up
Other	Cumulus and mural 3ß-hydroxy-steroid-dehydrogenase (3ßHSD) gene expression	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.	Up to one hour after ovum pick-up
Other	Cumulus and mural inhibin-Ba (INHB-A) receptor gene expression	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.	Up to one hour after ovum pick-up
Other	Cumulus and mural androgen receptor gene expression	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.	Up to one hour after ovum pick-up
Other	Cumulus and mural FSH receptor gene expression	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.	Up to one hour after ovum pick-up
Primary	Serum concentrations of AMH	Blood sampling	8 weeks after starting androgen priming
Secondary	Number of antral follicles	Follicles 2-10mm on ultrasound	8 weeks after starting androgen priming
Secondary	Serum concentrations of testosterone	Blood sampling	Up to 2 weeks after starting FSH stimulation
Secondary	Serum concentrations of hCG	Blood sampling	Up to 2 weeks after starting FSH stimulation
Secondary	Serum concentrations of progesterone	Blood sampling	Up to 2 weeks after starting FSH stimulation
Secondary	Number of antral follicles	Follicles 2-10 mm on ultrasound	Up to 2 weeks after starting FSH stimulation
Secondary	Number of pre-ovulatory follicles	Follicles >/= 14 mm on ultrasound	Up to 2 weeks after starting FSH stimulation