Trial Outcomes & Findings for Follicular Activation in Poor Responders (NCT NCT02354963)

NCT ID: NCT02354963

Last Updated: 2024-01-08

Results Overview

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

Recruitment status

COMPLETED

Study phase

Target enrollment

34 participants

Primary outcome timeframe

36 hours after triggering

Results posted on

2024-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Control Arm No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Overall Study STARTED	18	16
Overall Study COMPLETED	16	15
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Follicular Activation in Poor Responders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Control Arm n=18 Participants No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=16 Participants Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.	Total n=34 Participants Total of all reporting groups
Age, Continuous	37 years n=5 Participants	37.5 years n=7 Participants	37.3 years n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index (BMI)	21 kg/m^2 n=5 Participants	22.4 kg/m^2 n=7 Participants	21.7 kg/m^2 n=5 Participants
Previous gestations	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Previous deliveries	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Previous miscarriages	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Infertility etiology Only POR	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Infertility etiology Tubal factor	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Infertility etiology Male factor	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Infertile duration	36 months n=5 Participants	48 months n=7 Participants	42 months n=5 Participants
Baseline Antral Follicle Count (AFC)	5 number of follicles n=5 Participants	4 number of follicles n=7 Participants	4.5 number of follicles n=5 Participants
Baseline AMH	0.36 ng/mL n=5 Participants	0.44 ng/mL n=7 Participants	0.4 ng/mL n=5 Participants
Number of previous IVF cycles	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 36 hours after triggering

Population: Of the 18 patients in the initial control group, 2 dropped out of the study (one because she did not want to follow up and the other because she divorced). Of the 16 patients in the experimental group, one patient left the study before treatment because she moved to another city.

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

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Number of Metaphase II (MII)	4 Oocytes Interval 1.0 to 8.0	2 Oocytes Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: Baseline, day 2-5 of the menstrual cycle prior to treatment

Population: Of the 18 patients in the initial control group, 2 dropped out of the study (one because she did not want to follow up and the other because she divorced her husband). Of the 16 patients in the experimental group, one patient left the study before treatment because she moved to another city.

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.

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Total Antral Follicle Count (AFC) - Initial Measure	5 Follicles Interval 2.0 to 5.0	4 Follicles Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Total Antral Follicle Count (AFC) - Final	5 Follicles Interval 3.0 to 6.0	5 Follicles Interval 3.0 to 7.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Initial Antimüllerian Hormone (AMH) Levels	0.36 ng/mL Interval 0.08 to 0.56	0.44 ng/mL Interval 0.18 to 0.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Final AMH Levels	0.35 ng/mL Interval 0.11 to 0.66	0.29 ng/mL Interval 0.2 to 0.69

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Number of Cancelled IVF Cycles	3 Number of cycles	2 Number of cycles

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control Arm n=33 Number of mature oocytes No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=23 Number of mature oocytes Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Fertilization Rate	100 Percentage of fertilized oocytes	33.3 Percentage of fertilized oocytes

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Number of Cycles With Embryo Transfer (ET)	8 Number of IVF cycles	4 Number of IVF cycles

SECONDARY outcome

Timeframe: 6 weeks after embryo transfer

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

Outcome measures

Outcome measures
Measure	Control Arm n=16 Number of IVF cycles No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Number of IVF cycles Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Number and Percentage of Cycles With Clinical Pregnancy	3 Number of IVF cycles	2 Number of IVF cycles

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Control Arm n=16 Participants No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 Participants Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
Live Birth Rate	3 Participants	1 Participants

Adverse Events

Control Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Experimental Arm

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Control Arm n=16 participants at risk No intervention is performed. Assessment of antral follicle count. IVF treatment.	Experimental Arm n=15 participants at risk Perform intervention described: Laparoscopy. In vitro fragmentation of the ovarian tissue. Assessment of antral follicle count. IVF treatment. In vitro fragmentation of the ovarian tissue: Unilateral ovarian cortex extraction, in vitro fragmentation and reimplantation.
General disorders Minor postsurgical complication	0.00% 0/16 • Day 1 (recruitment) up to final follow-up (6 months after recruitment) No serious adverse events were registered. Just a postsurgical complication consisting of a 2-day fever episode was registered in 1 patient.	6.7% 1/15 • Number of events 1 • Day 1 (recruitment) up to final follow-up (6 months after recruitment) No serious adverse events were registered. Just a postsurgical complication consisting of a 2-day fever episode was registered in 1 patient.

Additional Information

Dr Cesar Diaz-Garcia

IIS La Fe

Phone: 961 24 67 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place