Clinical trial NCT02354963: Follicular Activation in Poor Responders
Official title: Follicle Activation in Patients With Poor Ovarian Response Through Fragmentation of the Ovarian Tissue.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: Poor ovarian response
Salvador/Warts/Hippo pathway
Follicular activation
Poor ovarian reserve
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
First posted: 2015-02-03
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Metaphase II (MII)
timeFrame: 36 hours after triggering
Secondary outcomes:
measure: Total Antral Follicle Count (AFC) - Initial Measure
timeFrame: Baseline, day 2-5 of the menstrual cycle prior to treatment
measure: Total Antral Follicle Count (AFC) - Final
timeFrame: Day 2-5 of the menstrual cycle 6 months after treatment
measure: Initial Antimüllerian Hormone (AMH) Levels
timeFrame: Baseline, day 2-5 of the menstrual cycle prior to treatment
measure: Final AMH Levels
timeFrame: Day 2-5 of the menstrual cycle 6 months after the treatment
measure: Number of Cancelled IVF Cycles
timeFrame: End of stimulation cycle (less than or equal to 30 days)
measure: Fertilization Rate
timeFrame: 18 hours after insemination
measure: Number of Cycles With Embryo Transfer (ET)
timeFrame: On day 3 after egg collection
measure: Number and Percentage of Cycles With Clinical Pregnancy
timeFrame: 6 weeks after embryo transfer
measure: Live Birth Rate
timeFrame: 9 months or birth of one or more live babies
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: La Fe University Hospital
Study officials:
affiliation: La Fe University Hospital. University of Valencia
name: Cesar Diaz-Garcia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diaz-Garcia C, Herraiz S, Pamplona L, Subira J, Soriano MJ, Simon C, Seli E, Pellicer A. Follicular activation in women previously diagnosed with poor ovarian response: a randomized, controlled trial. Fertil Steril. 2022 Apr;117(4):747-755. doi: 10.1016/j.fertnstert.2021.12.034.