Clinical trial NCT01391845: Ulipristal Acetate on Progesterone Levels and Glycodelin-A Endometrial Pattern
Official title: Effect of Ulipristal Acetate Administration on Serum Progesterone Levels and Glycodelin-A Endometrial Pattern in Women Undergoing Controlled Ovulation Stimulation.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Infertility
Keywords: progesterone
glycodelin-A
ulipristal acetate
Lead sponsor: Programa de Asistencia Reproductiva de Rosario
Sponsor class: OTHER
First posted: 2011-07-12
Enrollment: 16
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

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

Primary outcomes:
measure: Changes in Glycodelin-A endometrial expression pattern and Progesterone serum levels in women expose to ulipristal acetate on stimulated ovarian cycles for FIV
timeFrame: participants will be followed for the duration of one mesntrual cycle, from day 1 of the cycle until day 28-32
Secondary outcomes:
measure: P levels during controlled ovarian stimulation since at least one follicle achieve ≥14mm of diameter
timeFrame: participants will be followed for the duration of one mesntrual cycle,from day 1 until day 28-32
measure: Serum P levels on two different doses of FSH in a GnRH Antagonist protocol for ovarian stimulation
timeFrame: participants will be followed for the duration of one mesntrual cycle,from day 1 until day 28-32
measure: Glycodelin-A endometrial expression pattern on two different doses of FSH in a GnRH Antagonist protocol for ovarian stimulation
timeFrame: participants will be followed for the duration of one mesntrual cycle, from day 1 until day 28-32
Other outcomes:
Locations:
city: Rosario
country: Argentina
facility: PROAR (Programa de Asistencia Reproductiva de Rosario
state: Santa Fe
Study officials:
affiliation: PROAR-IUNIR
name: Idelma Serpa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Programa de Asistencia Reproductiva de Rosario
name: Carlos Morente, MD
role: STUDY_CHAIR
References: