Follicular Activation in Poor Responders

Not Applicable

Completed

Conditions: Infertility

Interventions: Procedure: In vitro fragmentation of the ovarian tissue

Registration Number: NCT02354963

Lead Sponsor: César Díaz García

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental arm	In vitro fragmentation of the ovarian tissue	Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment.

Primary Outcome Measures

Name	Time	Method
Number of Metaphase II (MII)	36 hours after triggering	Number of mature MII oocytes retrieved in the IVF cycles after triggering.

Secondary Outcome Measures

Name	Time	Method
Total Antral Follicle Count (AFC) - Initial Measure	Baseline, day 2-5 of the menstrual cycle prior to treatment	AFC assessment was done on day 2-5 of the menstrual cycle. Ultrasound scan was performed using a GE iVoluson (General Electric, Spain) equipped with a 3D vaginal probe (6.5-9MHz). A bilateral two-dimensional scan was performed and the mean of the two largest diameters of each intra-ovarian avascular anechoic image was recorded. Antral follicles with a mean diameter from 2 to 10 mm were counted to establish AFC. Initial data refers to the measure taken before treatment.
Final AMH Levels	Day 2-5 of the menstrual cycle 6 months after the treatment	AMH levels were determined using a microparticle immunoassay kit integrated in the ABBOTT AxSYM® Plus system and software 5.20 (Abbott Laboratories, Abbot Park, IL, USA) 6 months after recruitment or basaline assessment.
Fertilization Rate	18 hours after insemination	All the mature oocytes retrieved were inseminated by intracytoplasmic sperm injection (ICSI). Percentage of successfully fertilized oocytes were registered 18 hours after oocyte insemination.
Number of Cycles With Embryo Transfer (ET)	On day 3 after egg collection	One or 2 embryos were transferred on day 3 after egg collection. This outcome represents the number of cycles that culminate with embryo transfer.
Total Antral Follicle Count (AFC) - Final	Day 2-5 of the menstrual cycle 6 months after treatment	AFC assessment was done on day 2-5 of the menstrual cycle and was followed for 6-month. To determine AFC, ultrasound scan was performed using a GE iVoluson (General Electric, Spain) equipped with a 3D vaginal probe (6.5-9MHz). A bilateral two-dimensional scan was performed and the mean of the two largest diameters of each intra-ovarian avascular anechoic image was recorded. Antral follicles with a mean diameter from 2 to 10 mm were counted to establish AFC. Final measure refers to the AFC count after ovarian fragmentation treatment.
Initial Antimüllerian Hormone (AMH) Levels	Baseline, day 2-5 of the menstrual cycle prior to treatment	AMH levels were determined on day 2-5 of the menstrual cycle to establish the initial baseline levels for each patient. A microparticle immunoassay kit integrated in the ABBOTT AxSYM® Plus system and software 5.20 (Abbott Laboratories, Abbot Park, IL, USA) was used to determine AMH levels prior treatment.
Number of Cancelled IVF Cycles	End of stimulation cycle (less than or equal to 30 days)	Number of cancelled IVF cycles for low or no response to controlled ovarian stimulation. Cycles were cancelled because of a lack of an adequate follicular formation (one follicle of at least 17 mm) the day of triggering.
Number and Percentage of Cycles With Clinical Pregnancy	6 weeks after embryo transfer	Clinical pregnancy was defined as the presence of a gestational sac and heart beat under ultrasonography
Live Birth Rate	9 months or birth of one or more live babies	Live birth rate was calculated by dividing the number of patients who achieved live birth in each cycle by the number of patients who initiated that cycle