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

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ClinicalTrials.gov Identifier: NCT04608695
Recruitment Status : Recruiting
First Posted : October 29, 2020
Last Update Posted : November 2, 2020
Sponsor:
Information provided by (Responsible Party):
Sezcan Mumusoglu, Hacettepe University

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Activation of Primordial Follicles Procedure: Ovarian puncture Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ovarian Needle Puncture for Follicle Activation in IVF Patients With Diminished Ovarian Reserve
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : September 1, 2021
Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. Antral follicle count [ Time Frame: 4 month after intervention on the second/third day of menstrual cycle ]
    Antral follicle count


Secondary Outcome Measures :
  1. 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


Eligibility Criteria
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Ages Eligible for Study:   up to 40 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04608695


Contacts
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Contact: Sezcan Mumusoglu, Assoc. Prof. +905326404673 sezcanmumusoglu@gmail.com

Locations
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Turkey
Hacettepe UniversityHacettepe University School of Medicine, Department of Ob/Gyn Recruiting
Ankara, Turkey, 06100
Contact: Sezcan Mumusoglu, Assoc. Prof.    +905326404673    sezcanmumusoglu@gmail.com   
Principal Investigator: Gurkan Bozdag, Prof.         
Principal Investigator: Sezcan Mumusoglu, Assoc. Prof.         
Sub-Investigator: Esra Uyanık, MD         
Sub-Investigator: Haldun Murat Erden, MD         
Sponsors and Collaborators
Hacettepe University
Investigators
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Principal Investigator: Sezcan Mumusoğlu, Assoc. Prof. Hacettepe University
More Information
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Publications:

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Responsible Party: Sezcan Mumusoglu, Associate Professor, Hacettepe University
ClinicalTrials.gov Identifier: NCT04608695    
Other Study ID Numbers: HU02
First Posted: October 29, 2020    Key Record Dates
Last Update Posted: November 2, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sezcan Mumusoglu, Hacettepe University:
Follicle Activation
Premature Ovarian Insufficiency
Diminished Ovarian Reserve
Ovarian Puncture