Ovarian Needle Puncture for Follicle Activation in IVF Patients With Diminished Ovarian Reserve

September 18, 2022 updated by: Sezcan Mumusoglu, Hacettepe University

Premature ovarian insufficiency (POI), is cessation of ovarian function characterized by hypergonadotropic amenorrhea and hypoestrogenic syndrome before 40 years of age. About 1% of women younger than 40 years old and 0.1% before 30 are affected. POI imposes a great challenge on women's reproductive and long-term health, such as infertility, amenorrhea, osteoporosis, and cardiovascular disease. Most patients already had impaired or complete loss of fecundity when diagnosed. Currently, no optimal regimen exists to ameliorate ovarian function. Typically, they end up with egg donation or adoption as an alternative way. Less severe form of POI is diminished ovarian reserve (DOR). Although lack of consensus according to Bologna criteria cut off for DOR was defined as (antral follicle count (AFC) <5-7 follicles or anti-Mullerian hormone (AMH) <0.5-1.1 ng/ml).

Previously it has been showed that 24% of women with POI had resumption of ovarian function and 4% resulted in baby births. These data indicates residual follicles are available in atrophic ovaries and have potential for development and even fertilization. In routine IVF practice 15% percent of patients have poor ovarian response to ovarian stimulation. Patients with DOR with a previous poor ovarian response (cycles cancelled or yielding ≤3 oocytes with a conventional protocol) might have benefit from the strategies increasing follicle activation and number of growing follicles and oocyte retrieved. Therefore, strategies enabling ovarian resumption predictable and follicle activation feasible are promising for POI/DOR treatment. Recently, In vitro Activation (IVA) approach has been proposed and live births have been achieved in patients with POI. Phosphatase and tensin homolog (PTEN) enzyme inhibitors and phosphatidylinositol-3 kinase activators could activate AKT pathway and activate the dormant follicles. Ovarian fragmentation could lead to ovarian primary follicle growth by interfering with Hippo signaling pathway. Residual follicles in patients with POI could be activated to develop for egg retrieval by combination of mechanical and chemical stimulation.

In 2019, Zhang et al retrospectively analyzed the follicle development and pregnancy outcome in 80 POI patients after laparoscopic ovarian biopsy/scratch without using chemical agents as was the case in IVA. 11 (13.75%) patients presented with ovarian function resumption, three metaphases II oocytes were retrieved in 10 patients and two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. They concluded that the technique of ovarian biopsy/scratch without chemical activation could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI.

In patient with POI/DOR, activation of residual follicles is a promising option and further studies are warranted. Previous studies included laparoscopic surgery which may lead to possible surgical complications. Without using chemical agents and laparoscopic surgery, main object of this study is mechanical follicle activation with trans-vaginal ovarian needle puncture with 17 gauge oocyte pickup needle in IVF patients with DOR.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

34

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey
      • Ankara, Turkey, 06100
        • Recruiting
        • Hacettepe UniversityHacettepe University School of Medicine, Department of Ob/Gyn
        • Sub-Investigator:
          • Esra Uyanık, MD
        • Sub-Investigator:
          • Haldun Murat Erden, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 40 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patients with diminished ovarian reserve
  • <3 oocytes collected in previous cycle (with anti-mullerian hormone <0.5 ng/mL and/or antral follicle count <5)
  • Cycles stimulated with flexible antagonist protocol
  • Cycles triggered with recombinant hCG
  • Fresh transfer cycles
  • Patients with <40 years of age
  • BMI <30 kg/m2

Exclusion Criteria:

  • Preimplantation genetic testing
  • Azospermia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Control ovary
EXPERIMENTAL: Punctured ovary
Procedure: Ovarian puncture
One side ovary of each patient included in the study, will be punctured 10 times under trans-vaginal ultrasound guidance with 17 gauge ovarian pick up needle, 1 month before the scheduled IVF cycle. Control group will be the other side ovary for each patient. Number of ≥ 14 mm follicle and collected oocytes will be compared.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of ≥14 mm follicle
Time Frame: 4 month after intervention as a response to ovarian stimulation
Number of ≥14 mm follicle on the trigger day
4 month after intervention as a response to ovarian stimulation
Antral follicle count
Time Frame: 4 month after intervention on the second/third day of menstrual cycle
Antral follicle count
4 month after intervention on the second/third day of menstrual cycle

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of collected oocytes
Time Frame: 4 month after intervention as a response to ovarian stimulation
Number of collected oocytes on the oocyte pick-up day
4 month after intervention as a response to ovarian stimulation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hacettepe University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 1, 2020

Primary Completion (ANTICIPATED)

July 1, 2023

Study Completion (ANTICIPATED)

September 1, 2023

Study Registration Dates

First Submitted

October 25, 2020

First Submitted That Met QC Criteria

October 25, 2020

First Posted (ACTUAL)

October 29, 2020

Study Record Updates

Last Update Posted (ACTUAL)

September 21, 2022

Last Update Submitted That Met QC Criteria

September 18, 2022

Last Verified

September 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • HU02

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Activation of Primordial Follicles

Clinical Trials on Ovarian puncture

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe