Double Stimulation in Women With Low Prognosis in ART

Study Overview
=================
Brief Summary
-----------------
The main objective of this study is to compare the cumulative ongoing pregnancy rates of two different IVF protocols in women candidate for ART characterized by low prognosis.

Detailed Description
-----------------
The patients will be allocated into two groups: control and study group _ In study group, patients will be treated by DuoStim protocol: The first phase of ovarian stimulation is started on the second day or third day of period. GnRH agonist will be used to trigger when at least two follicles ≥ 17 mm. Approximately 36 hours later, oocytes will be retrieved vaginally under ultrasound monitoring and ICSI will be performed. Five days later after oocyte retrieval, the second stimulation will be started. All embryos will be cryopreserved. _ In control group, patients will be treated with antagonist protocol: The cycle of ovarian stimulation is started on the second day or third day of period. hCG will be used to trigger when at least two follicles ≥ 17 mm. Approximately 36 hours later, oocytes will be retrieved vaginally under ultrasound monitoring and ICSI will be performed. If serum progesterone on the day of trigger ≥ 1.5 ng/ml, all embryos will be cryostored; otherwise, fresh embryos will be transferred.

Official Title
-----------------
Impact of Double Stimulation (DuoStim) in Women Affected by Low Prognosis to Assisted Reproductive Technologies

Conditions
-----------------
Assisted Reproductive Techniques

Intervention / Treatment
-----------------
* Procedure: double stimulation
* Procedure: conventional ovarian stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≤ 40. AMH ≥ 0.3 ng/ml and ≤ 1.2 ng/ml. OR 3 ≤ AFC ≤7. Normal shape of uterus (based on ultrasound). Body mass index within 28 - 37 kg/m2 Exclusion Criteria: Asherman's syndrome. Endometriosis. Leiomyomas distorting the endometrium Sperm extracted from surgical procedures (i.e. PESA, TESE). Patients refuse to continue participating in the study. Patients injected with wrong dose of gonadotropins during the treatment. Serious complications or accidents arise forcing the patients to discontinue the treatments. Ovarian surgery Previous chemotherapy or pelvic irradiation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study<br>the patients in this group will be treated with double stimulation | Procedure: double stimulation<br>* the patients will be treated with two consecutive ovarian stimulations in one cycle<br>* Other names: DuoStim;|
| Active Comparator: Control<br>the patients in this group will be treated with conventional ovarian stimulation | Procedure: conventional ovarian stimulation<br>* the patients will be treated with one conventional ovarian stimulation in one cycle<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Ongoing pregnancy rate | calculated by the number of ongoing pregnancy patients divided by the total number of patients in appropriate group | week 11 - 14 of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy rate | beta-hCG test is positive | 2 weeks after embryo transfer | 
| Ongoing pregnancy rate | defined as the pregnancy completed 11 - 14 weeks of gestation and having vital fetus | week 11 - 14 of pregnancy | 
| Number of oocytes retrieved | Number of oocytes retrieved identified by the embryologists | 4 hours after occyte pick-up | 
| Number of mature oocytes | Number of mature oocytes identified by the embryologists | 4 hours after oocyte pick-up | 
| Number of competent embryos | Number of embryos that can be transferred | 3 days to 5 days after oocyte pick-up | 
| Fertilization rate | number of fertilized oocyted divided by number of mature oocytes | 1 to 3 days after oocyte pick-up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
double ovarian stimulation, low prognosis women, ongoing pregnancy