Ulipristal Acetate on Progesterone Levels and Glycodelin-A Endometrial Pattern

Infertility Clinical Trial

Official title:

Effect of Ulipristal Acetate Administration on Serum Progesterone Levels and Glycodelin-A Endometrial Pattern in Women Undergoing Controlled Ovulation Stimulation.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01391845
• Other study ID #: ist1979
• Status: Not yet recruiting
• Phase: N/A
• First received: June 28, 2011
• Last updated: July 19, 2011
• Start date: July 2011
• Est. completion date: June 2012

Study information

• Verified date: May 2011
• Source: Programa de Asistencia Reproductiva de Rosario
• Contact: Idelma Serpa, MD
• Phone: +54 0341 155668963
• Email: idelmaserpa[@]yahoo.com.ar
• Is FDA regulated: No
• Health authority: Argentina: Human Research Bioethics Committee
• Study type: Interventional

Clinical Trial Summary

Controlled ovarian stimulation (COS) for FIV increases progesterone (P) and estradiol (E2) serum levels in supraphysiologic concentrations at the end of follicular phase. Elevated serum P levels leads to an accelerated endometrial maturation which interferes with the dialogue between embryo and endometrium. It has been reported that serum progesterone levels ≥ 1.5 ng/ml on the last day of COS are related to a significant decrease in the ongoing pregnancy rate following IVF cycles. Also, it has been reported a significant alteration in the endometrial gene expression profile related to P elevated levels.

Glycodelin-A is an immunomodulatory glycoprotein synthesized by luteal-phase endometrial epithelium and its expression seems to be related to the action of P. Because glycodelin-A has immunosuppressive activity, it may facilitate the process of implantation and the maintenance of pregnancy.

It is already know that ulipristal acetate (UPA) decrease serum P levels. The hypothesis of this study is that UPA is been able to modify P serum levels and glycodelin-A endometrial expression pattern on FSH/GnRH Antagonist cycles for FIV.

Description:

Controlled ovarian stimulation (COS) for FIV increases progesterone (P) and estradiol (E2) serum levels in supraphysiologic concentrations at the end of follicular phase. Elevated serum P levels leads to an accelerated endometrial maturation which interferes with the dialogue between embryo and endometrium. It has been reported that serum progesterone levels ≥ 1.5 ng/ml on the last day of COS are related to a significant decrease in the ongoing pregnancy rate following IVF cycles. Also, it has been reported a significant alteration in the endometrial gene expression profile related to P elevated levels.

Glycodelin-A is an immunomodulatory glycoprotein synthesized by luteal-phase endometrial epithelium and its expression seems to be related to the action of P. Because glycodelin-A has immunosuppressive activity, it may facilitate the process of implantation and the maintenance of pregnancy.

Objective: to evaluate the endometrial effect of Progesterone through Glycodelin-A expression pattern on women exposed or not to ulipristal acetate in GnRH Antagonist cycles using two different doses of FSH for ovarian controlled stimulation.

Methods: prospective controlled randomized study. It will be enrolling 16 oocytes donors from Oocyte Donation Program of PROAR (a Reproductive Center of Rosario, Argentina). On day 3 of menstrual cycle FSH serum levels and antral follicular count (AFC) will be measure. If those results fulfill with inclusions criteria, patients will be randomize for FSH 225UI or 300UI GnRH-Antagonist/ urinary FSH protocol. P serum levels will be measure every 48 hours since at least 1 follicle ≥14 mm will be achieve until at least 1 follicle reach 19mm of diameter. The next day of hCG administration a new P circulating will be measure and then the patient will be randomize trough opaque envelopes for receive 30mg of ulipristal acetate or placebo. An endometrial biopsy with Cornier´s Pipelle will be performing 3 and 5 days after hCG injection (hCG+3 and hCG+5 days) to evaluate endometrial dating and Glycodelin-A expression pattern.

Statistical analysis: nominal variables will be analyzing using t-Student test and the effect of ulipristal with ANOVA.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: June 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 21 Years to 35 Years

Eligibility

Inclusion Criteria:

• Age <35 years old

• FSH on day 3: <12 UI/ml

• Antral follicular count = 6 on day 3 of the cycle

• BMI: <30 Kg/m2

Exclusion Criteria:

• Hypothyroidism

• Hyperprolactinemia

• Kidney or liver disease

• Smoking

• Alcoholism

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• ulipristal acetate
30mg of ulipristal acetate orally the day of hCG injection in a unique dose
• placebo
placebo orally in a unique dose the day of hCG injection
• ulipristal acetate
ulipristal acetate 30mg orally in a unique dose the day of hCG administration
• placebo
placebo orally in a unique dose the day of hCG injection

Locations

Country	Name	City	State
Argentina	PROAR (Programa de Asistencia Reproductiva de Rosario	Rosario	Santa Fe

Sponsors (1)

Lead Sponsor	Collaborator
Programa de Asistencia Reproductiva de Rosario

Country where clinical trial is conducted

Argentina, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Glycodelin-A endometrial expression pattern and Progesterone serum levels in women expose to ulipristal acetate on stimulated ovarian cycles for FIV	to evaluate Glycodelin-A expression pattern by immunohistochemistry and Progesterone serum levels on women exposed or not to ulipristal acetate in FSH/GnRH Antagonist protocol.	participants will be followed for the duration of one mesntrual cycle, from day 1 of the cycle until day 28-32	No
Secondary	P levels during controlled ovarian stimulation since at least one follicle achieve =14mm of diameter		participants will be followed for the duration of one mesntrual cycle,from day 1 until day 28-32	No
Secondary	Serum P levels on two different doses of FSH in a GnRH Antagonist protocol for ovarian stimulation		participants will be followed for the duration of one mesntrual cycle,from day 1 until day 28-32	No
Secondary	Glycodelin-A endometrial expression pattern on two different doses of FSH in a GnRH Antagonist protocol for ovarian stimulation		participants will be followed for the duration of one mesntrual cycle, from day 1 until day 28-32	No