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Completed

NCT Number: NCT02354963

Follicular Activation in Poor Responders

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).

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Key information

Conditions

Infertility Genital Diseases Urogenital Diseases

Age range

18 year–40 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

La Fe University Hospital

Valencia, Spain

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

In vitro fragmentation of the ovarian tissue

Procedure

Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.

Primary outcomes

  1. Number of Metaphase II (MII)

    Time frame: 36 hours after triggering

    Number of mature MII oocytes retrieved in the IVF cycles after triggering.

Secondary outcomes

  1. Total Antral Follicle Count (AFC) - Initial Measure

    Time frame: 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.

  2. Total Antral Follicle Count (AFC) - Final

    Time frame: 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.

  3. Initial Antimüllerian Hormone (AMH) Levels

    Time frame: 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.

  4. Final AMH Levels

    Time frame: 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.

  5. Number of Cancelled IVF Cycles

    Time frame: 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.

  6. Fertilization Rate

    Time frame: 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.

  7. Number of Cycles With Embryo Transfer (ET)

    Time frame: 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.

  8. Number and Percentage of Cycles With Clinical Pregnancy

    Time frame: 6 weeks after embryo transfer

    Clinical pregnancy was defined as the presence of a gestational sac and heart beat under ultrasonography

  9. Live Birth Rate

    Time frame: 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

Sponsors and collaborators

Lead sponsor

César Díaz García

Other

Registry information

Official study title

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

Acronym: FAPPOR

Important dates

Study start
2014
Primary completion
2019
Study completion
2019
First posted
Feb 3, 2015
Registry last updated
Jan 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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