Mechanical Stimulation of the Ovary for Infertility Treatment in Patients With Very Low Ovarian Reserve

Examine the possibility that mechanical stimulation and ovarian fragmentation in women with premature ovarian failure or low ovarian reserve intended for egg donation may cause early follicular recruitment and increase chances of achieving pregnancy through IVF.

Study Overview

• Status: Unknown
• Conditions: Ovarian Stimulation
• Intervention / Treatment: Procedure: Resection of ovarian tissue and mechanical stimulation

Detailed Description

The women will undergo a surgical laparoscopy during which one of the two technique will ensue.

1. One of the ovaries will be scratched ( 2 mm depth) with a knife. Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.
2. A piece of one ovary will be resected (up to one third of the ovary's volume, without harming the other ovary.

The resected ovarian tissue will be transferred immediately to the laboratory where the cortex will be divided from the medulla and sliced to small pieces of 1-2 square millimeters.

These pieces will be transferred back to the operation room in order for them to be transplanted under the serosa layer of the remaining ovary.

Any bleeding would be stopped using a stiches or hemostatic mesh (diathermy will not be used).

Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.

Post operational follow up ( up to two years) including: menstrual cycle surveillance, hormonal profile, AMH level, US of the pelvis and Antral Follicles Count (AFC).

A month after the surgery, an ovarian stimulation will commence following IVF while close monitoring the ovarian response and comparing the pre and post operation response.

Moreover, the treated ovary will be compared to the untreated one: using the US the ovarian volume and antral follicles size and count will be evaluated.

The preserved pieces of ovary will be histologically evaluated for ovarian reserve analysis.

Additionally, these pieces will be used for experiments for the evaluation of various methods for primordial follicles stimulation including mechanical stimulation like the laser or using substances like Akt Stimulators.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy women, aged 21-40. with premature ovarian failure.
• Healthy women, with poor ovarian reserve, aged 38-45, undergoing IVF Low ovarian response: recruitment of up to three eggs in previous treatments.
• After the failure of at least 4 cycles.
• Two functioning ovaries, follicular and hormonal response of both ovaries in prior therapies.
• Women candidates for egg donation, and seeking further treatment before switching to egg donation.

Exclusion Criteria:

• Women with kidney disease.
• Women with infertility factors other than ovarian failure, such as endometriosis, PCOS, male factor.
• Women with one non-functioning ovary, or that was removed.
• Women with an intrauterine or pelvic pathology.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Mechanical stimulation; Mechanical stimulation of ovarian tissue

Procedure: Resection of ovarian tissue and mechanical stimulation; he women will undergo a surgical laparoscopy during which one of the two technique will ensue.; One of the ovaries will be scratched ( 2 mm depth) with a knife. Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.; A piece of one ovary will be resected (up to one third of the ovary's volume, without harming the other ovary. The resected ovarian tissue will be transferred immediately to the laboratory where the cortex will be divided from the medulla and sliced to small pieces of 1-2 square millimeters. These pieces will be transferred back to the operation room in order for them to be transplanted under the serosa layer of the remaining ovary. Any bleeding would be stopped using a stiches or hemostatic mesh (diathermy will not be used). Simultaneously, a piece of the ovary will be preserved for further histologic analysis and research in the laboratory.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Menstrual cycle surveillance	Duration of the menstrual period (days)	2 years
AMH	Ovarian reserve measurements. AMH levels ng/ml	2 years
Estradiol	Estradiol levels at day of HCG in Pmol/L	2 years
Antral follicular count	measurement of. any antral follicles at day 3-5 with ultrasound	2 years
IVF outcomes	Number of oocytes at OPU	2 years
FSH levels	FSH levels at. day 2-3 of menstruation IU/L	2 years
IVF outcomes fertilization rates	fertilization rate. - number of fertilized oocytes relatively to total number of oocytes	2 years
IVF outcomes	pregnancy rates	2 years

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Alon Kedem, MD, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 20, 2017
• Primary Completion (ANTICIPATED): September 1, 2019
• Study Completion (ANTICIPATED): September 1, 2019

Study Registration Dates

• First Submitted: June 26, 2016
• First Submitted That Met QC Criteria: September 26, 2017
• First Posted (ACTUAL): October 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 10, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Mechanical Laboratory Ovarian Stimulation Poor responders
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: SHEBA-15-2289-AK-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No