Follicular Activation in Poor Responders

Study Overview
=================
Brief Summary
-----------------
This study aims to assess whether activation of primordial follicles through ovarian cortex fragmentation may increase the number of antral follicles present in the ovary of patients with diminished ovarian reserve. Secondary outcomes include number of oocytes retrieved and pregnancy rates after IVF. Hypothesis; Evaluate whether the proposed intervention increases the pool of antral follicles (potentially stimulable ones).

Detailed Description
-----------------
Controlled, randomized, assessor-blind clinical trial. Thirty-six patients of La Fe University Hospital (Valencia), previously confirmed as poor responders according to the European Society of Human Reproduction and Embryology (ESHRE) criteria, will be randomized to two treatment arms: Arm 1 (control): no intervention. Arm 2 (intervention): ovarian cortex extraction by unilateral laparoscopic biopsy and ovarian tissue fragmentation in aliquots of 1 mm2. These fragments will be grafted under the ovarian cortex and meso-ovarium ipsilateraly. Subsequently the number of antral follicles in both intervention groups will be compared and also will be the number of antral follicles in the native ovary and the grafted one in each of the patients. Patients will receive a standard IVF treatment for poor responders according to the protocols of the assisted reproduction unit of La Fe University Hospital. The final aim is to assess the pregnancy rate in both groups, as well as parameters related to the reproduction technique when required.

Official Title
-----------------
Follicle Activation in Patients With Poor Ovarian Response Through Fragmentation of the Ovarian Tissue.

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

Intervention / Treatment
-----------------
* Procedure: In vitro fragmentation of the ovarian tissue


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria (must meet one): At least two episodes of poor ovarian response (≤ 3 oocytes retrieved with a standard protocol). A previous IVF cycle with ≤ 3 oocytes (following a standard stimulation protocol) and presence of an abnormal ovarian reserve test (antral follicle count of ≤ 5 or antimüllerian hormone ≤ 5pm). Exclusion Criteria (must not meet any): Patients under 18 or over 40 years. Clinical signs of endometriosis. Previous ovarian surgery. Genital tract malformations. Anovulatory patient (defined by the presence of irregular cycles and serum progesterone ≤ 10 ng / mL on cycle day 21). Partner with severe male factor: severe oligoasthenozoospermia, oligoasthenoteratozoospermia and azoospermia. All those patients who do not voluntarily give their express written consent.

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control arm<br>No intervention is performed. Assessment of antral follicle count. IVF treatment. | |
| Experimental: Experimental arm<br>Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. | Procedure: In vitro fragmentation of the ovarian tissue<br>* Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antral follicle count |  | Up to 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Poor ovarian response, Salvador/Warts/Hippo pathway, Follicular activation, Poor ovarian reserve