Ulipristal Acetate on Progesterone Levels and Glycodelin-A Endometrial Pattern

Study Overview
=================
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.

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

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Drug: ulipristal acetate
* Drug: placebo
* Drug: ulipristal acetate
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UPA, 300UI FSH<br>patients on COS with 300UI FSHu/GnRH Antagonist protocol and ulipristal acetate use | Drug: ulipristal acetate<br>* 30mg of ulipristal acetate orally the day of hCG injection in a unique dose<br>* Other names: UPA/FSH 300;|
| Placebo Comparator: No UPA, 300FSH<br>patients on COS with 300UI FSHu/GnRH Antagonist protocol and without ulipristal acetate use | Drug: placebo<br>* placebo orally in a unique dose the day of hCG injection<br>* Other names: No UPA/FSH 300;|
| Experimental: UPA, FSH 225<br>patients on COS with 225UI FSHu/GnRH Antagonist protocol and ulipristal acetate use | Drug: ulipristal acetate<br>* ulipristal acetate 30mg orally in a unique dose the day of hCG administration<br>* Other names: UPA/FSH225;|
| Placebo Comparator: no UPA, FSH225<br>patients on COS with 225UI FSHu/GnRH Antagonist protocol and without ulipristal acetate use | Drug: placebo<br>* placebo orally in a unique dose the day of hCG injection<br>* Other names: no UPA/FSH225;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
progesterone, glycodelin-A, ulipristal acetate