Is There A Role For Mechanical Stimulation In Ovarian Follicular Activation?

July 30, 2023 updated by: Laura Melado, ART Fertility Clinics LLC

Is There A Role For Mechanical Stimulation In Ovarian Follicular Activation? A Randomized Control Trial.

Premature ovarian failure (POI) is a loss of normal function before age 40, leading to infertility and hypoestrogenism. About 1% of women younger than 40 years old and 0.1% before 30 are affected. Most patients already had impaired or complete loss of fecundity when diagnosed. Hence, the treatment of POI is particularly tough. Currently, no optimal regimen exists to ameliorate ovarian function.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

In women, the non-growing population of follicles that comprise the ovarian reserve is determined at birth and serves as the reservoir for future fertility. This reserve of dormant, primordial follicles and the mechanisms controlling their selective activation which constitute the committing step into folliculogenesis are essential for determining fertility outcomes in women.

While POI is sometimes called premature menopause, it is not identical with menopause. Women with POI may still have occasional irregular periods and may even occasionally achieve a pregnancy. Symptoms of POI include irregular menses or amenorrhea, infertility, hypoestrogenic symptoms and decreased libido. POI may be caused by chromosomal defects such as mosaic Turner's syndrome, exposure to toxins (chemotherapy or radiation), autoimmunity, genetic factors (FMR1) and other unknown factors.

Recently, new promising approaches have emerged for infertility treatment in patients with POI, which are based on arousing the still available primordial follicle pool. It is supposed that these techniques activate dormant primordial follicles using a combination of mechanical signaling and biochemical factors. The hypothesis that mild local ovarian injury, such as ovarian puncture, which is a usual procedure in an IVF center with minimal side effects, might exert a similar favorable effect in women with POI arouses our curiosity.

Different groups have published case series of ovarian procedures, injecting substances in the ovaries (A-PRP) or ovarian biopsies / scratch in infertile patients with low ovarian reserve (LOR) or/and patients with POF. However, those studies were underpowered, including not enough number of cases, with variable inclusion criteria and reporting results with very low scientific evidence. Furthermore, the mechanical effect of injecting the ovary should be taken into consideration during the evaluation of these patients, yet it might improve the ovarian function as well.

There are no previous randomized controlled trials considering a procedure as ovarian puncture, which is easier and accessible at any fertility center.

Study Type

Observational

Enrollment (Estimated)

70

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

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

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Adult women with primary or secondary infertility with a diagnosis of POI, willing to perform an IVF treatment

Description

Inclusion Criteria:

  • Signed and dated informed consent
  • Women 40 years of age and younger with documented primary ovarian insufficiency (12).
  • Normal Karyotype
  • BMI </= 35 kg/m2
  • Oligo/amenorrhea for at least 4 months
  • FSH > 25 IU/mL
  • AMH </= 0,1 ng/ml
  • No evidence of follicles > 4mm
  • Must have two ovaries of approximately equal volume.
  • Willingness to undergo further fertility treatment, including IVF if there is evidence of response
  • A transvaginal scan including Doppler for arteria ovarica will be performed previously to the surgical procedure.

Exclusion Criteria:

  • Premature ovarian failure due to a genetic origin, such as Turner's Syndrome or chromosomal abnormality.
  • Oncological diseases (specially, skeletal system and blood).
  • Autoimmune diseases, for example, lupus erythematosus, etc.
  • Previous treatments including radiotherapy or chemotherapy.
  • Other conditions not suitable for surgical procedures and/or anesthesia.
  • Anticoagulant or antiaggregant treatment.
  • Acute and chronic infectious diseases.
  • Active substance abuse or dependence.
  • Major Mental health disorder.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Intervention
The cortex of selected ovary will be punctured up to ten times. In the surgical report, the surgeon will state how many punctures have been done.
Procedure: Ovarian puncture
Egg collection
Other: Hormonal blood Test
AMH (ng/ml), FSH (IU/mL), E2(pg/mL), P4(ng/mL), LH (IU/mL)
Diagnostic test: Transvaginal ultrasound
Doppler of arteria ovarica. Resistance index
Control
No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Follicle growth above 4 mm
Time Frame: 1 day
One or more follicles evaluated by transvaginal ultrasound. Defined by number of follicles growing, quantitative variable.
1 day
Anti-Müllerian hormone evaluation after intervention.
Time Frame: 1 day
Anti-Müllerian hormone evaluation after intervention.
1 day
Follicle-stimulating hormone evaluation after intervention.
Time Frame: 1 day
Follicle-stimulating hormone evaluation after intervention.
1 day
Luteinizing hormone evaluation after intervention.
Time Frame: 1 day
Luteinizing hormone evaluation after intervention.
1 day
Estradiol hormone evaluation after intervention.
Time Frame: 1 day
Estradiol hormone evaluation after intervention.
1 day
Progesterone hormone evaluation after intervention.
Time Frame: 1 day
Progesterone hormone evaluation after intervention.
1 day
Spontaneous menstruation.
Time Frame: 1 day
Spontaneous menstruation.
1 day
Arteria ovarica doppler results.
Time Frame: 1 day
Arteria ovarica doppler results. Resistance index.
1 day

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of follicles
Time Frame: 1 day
Number of follicles
1 day
Number of oocytes retrieved
Time Frame: 1 day
Number of oocytes retrieved
1 day
Fertilization rate
Time Frame: 1 day
percentage of 2PN embryos per oocyte injected
1 day
Blastulation rate
Time Frame: 1 day
percentage of blastocysts per 2PN embryos
1 day
Aneuploidy rate
Time Frame: 1 day
percentage of aneuploid blastocysts per total blastocyst biopsied
1 day

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy by blood test
Time Frame: 12 weeks
pregnancy (yes or no) defined by a βhCG test of > 15IU
12 weeks
Implantation rate (%)
Time Frame: 4 weeks
defined by the number of gestational sacs/number of embryos transferred
4 weeks
Clinical pregnancy by ultrasound
Time Frame: 12 weeks
defined by the ultrasonographic visualization of one or more gestational sacs, including ectopic pregnancies
12 weeks

Collaborators and Investigators

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

Sponsor

ART Fertility Clinics LLC

Investigators

  • Principal Investigator: Laura Melado, PhD, ART Fertility Clinics LLC

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

Helpful Links

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 (Estimated)

October 1, 2023

Primary Completion (Estimated)

June 30, 2024

Study Completion (Estimated)

July 31, 2024

Study Registration Dates

First Submitted

May 11, 2020

First Submitted That Met QC Criteria

May 14, 2020

First Posted (Actual)

May 15, 2020

Study Record Updates

Last Update Posted (Actual)

August 1, 2023

Last Update Submitted That Met QC Criteria

July 30, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2004-ABU-005-LM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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.

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