Follicular Activation in Poor Responders

Infertility Clinical Trial

— FAPPOR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02354963
• Other study ID #: FAPPOR (2014/0004)
• Status: Completed
• Phase: N/A
• Start date: November 2014
• Est. completion date: December 2019

Study information

• Verified date: March 2023
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility

Intervention

Procedure:
• In vitro fragmentation of the ovarian tissue
Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.

Locations

Country	Name	City	State
Spain	La Fe University Hospital	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
César Díaz García

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Metaphase II (MII)	Number of mature MII oocytes retrieved in the IVF cycles after triggering.	36 hours after triggering
Secondary	Total Antral Follicle Count (AFC) - Initial Measure	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.	Baseline, day 2-5 of the menstrual cycle prior to treatment
Secondary	Total Antral Follicle Count (AFC) - Final	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.	Day 2-5 of the menstrual cycle 6 months after treatment
Secondary	Initial Antimüllerian Hormone (AMH) Levels	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.	Baseline, day 2-5 of the menstrual cycle prior to treatment
Secondary	Final AMH Levels	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.	Day 2-5 of the menstrual cycle 6 months after the treatment
Secondary	Number of Cancelled IVF Cycles	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.	End of stimulation cycle (less than or equal to 30 days)
Secondary	Fertilization Rate	All the mature oocytes retrieved were inseminated by intracytoplasmic sperm injection (ICSI). Percentage of successfully fertilized oocytes were registered 18 hours after oocyte insemination.	18 hours after insemination
Secondary	Number of Cycles With Embryo Transfer (ET)	One or 2 embryos were transferred on day 3 after egg collection. This outcome represents the number of cycles that culminate with embryo transfer.	On day 3 after egg collection
Secondary	Number and Percentage of Cycles With Clinical Pregnancy	Clinical pregnancy was defined as the presence of a gestational sac and heart beat under ultrasonography	6 weeks after embryo transfer
Secondary	Live Birth Rate	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	9 months or birth of one or more live babies