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Ulipristal Acetate on Progesterone Levels and Glycodelin-A Endometrial Pattern

Not Applicable
Conditions
Infertility
Interventions
Registration Number
NCT01391845
Lead Sponsor
Programa de Asistencia Reproductiva de Rosario
Brief 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.

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
16
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
No UPA, 300FSHplacebopatients on COS with 300UI FSHu/GnRH Antagonist protocol and without ulipristal acetate use
no UPA, FSH225placebopatients on COS with 225UI FSHu/GnRH Antagonist protocol and without ulipristal acetate use
UPA, 300UI FSHulipristal acetatepatients on COS with 300UI FSHu/GnRH Antagonist protocol and ulipristal acetate use
UPA, FSH 225ulipristal acetatepatients on COS with 225UI FSHu/GnRH Antagonist protocol and ulipristal acetate use
Primary Outcome Measures
NameTimeMethod
Changes in Glycodelin-A endometrial expression pattern and Progesterone serum levels in women expose to ulipristal acetate on stimulated ovarian cycles for FIVparticipants will be followed for the duration of one mesntrual cycle, from day 1 of the cycle until day 28-32

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.

Secondary Outcome Measures
NameTimeMethod
P levels during controlled ovarian stimulation since at least one follicle achieve ≥14mm of diameterparticipants will be followed for the duration of one mesntrual cycle,from day 1 until day 28-32
Serum P levels on two different doses of FSH in a GnRH Antagonist protocol for ovarian stimulationparticipants will be followed for the duration of one mesntrual cycle,from day 1 until day 28-32
Glycodelin-A endometrial expression pattern on two different doses of FSH in a GnRH Antagonist protocol for ovarian stimulationparticipants will be followed for the duration of one mesntrual cycle, from day 1 until day 28-32

Trial Locations

Locations (1)

PROAR (Programa de Asistencia Reproductiva de Rosario

🇦🇷

Rosario, Santa Fe, Argentina

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