Evaluation of Priming Before in Vitro Maturation for Fertility Preservation in Breast Cancer Patients (PRIMIV)

May 16, 2019 updated by: Michael Grynberg, Hôpital Jean Verdier

Evaluation of Priming Before in Vitro Maturation for Fertility Preservation in Breast Cancer Patients: a Randomized Controlled Study

Oocyte vitrification after in vitro maturation (IVM) is one of the main techniques for preserving female fertility before chemotherapy for breast cancer. In this technique, originally developed for patients with ovarian pathology, polycystic ovarian syndrome, induction of an LH peak has been shown to improve outcomes. Young women with breast cancer, who are candidates for urgent fertility preservation, do not have ovarian pathology. The objective of the present study is to assess whether the absence of therapeutic intervention prior to oocyte retrieval for IVM in these patients is at least as effective as the injection of hCG or GnRH agonist used in routine practice.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In vitro maturation (IVM) is an assisted reproductive technology which consists in the retrieval of immature cumulus-oocyte complexes (COCs) from small antral follicles, followed by their in vitro maturation in specific culture conditions. Oocytes having reached metaphase II (MII) stage after 24 to 48 hours of IVM can then be fertilized. This procedure was first developed for patients presenting polycystic ovarian syndrome (PCOS), in order to avoid ovarian hyperstimulation syndrome (OHSS), an iatrogenic consequence of exogenous gonadotropins administration. However, the increasing use of GnRH antagonist protocols allowing ovulation trigger with GnRH agonist has dramatically reduced the indication of IVM in women at risk of OHSS. Yet, evidence indicate that IVM may be considered for patients presenting FSH resistance or contraindications to controlled ovarian stimulation. The recent development of female fertility preservation (FP) renewed interest to this technique. Indeed, it can be performed without any prior ovarian stimulation and whatever the phase of the menstrual cycle. Although it is still considered experimental, oocyte vitrification following IVM has been applied in different groups of patients, in particular those diagnosed with breast cancer, autoimmune or ovarian diseases. In physiologic conditions, final follicular maturation is induced by a double FSH and LH release which occurs when the dominant follicle reaches approximately 17 to 20 mm in diameter. This gonadotropin surge usually precedes the follicular rupture and mature oocyte release from 36 to 40 hours. In case of an assisted reproductive treatment, two strategies can be used to reproduce this hormonal signal: (i) either an injection of hCG, which binds to the LH receptor on granulosa cells, (ii) or a GnRH agonist (GnRHa) administration which induces an endogenous double peak of LH and FSH through a "flare up effect". Miming common practice for in vitro fertilization, priming with hCG or GnRHa injection 36 hours before the COCs retrieval has been suggested for patients undergoing IVM procedure in order to improve oocyte maturation rates and further IVM outcomes. Indeed, it is hypothesized that these iatrogenic hormonal activities might enhance the final oocyte maturation in vivo, therefore shortening the duration of the overall IVM process. Actually, in PCOS patients, several line of evidence indicate that IVM outcomes are improved after hCG priming. This positive effect might be explained by a premature expression of LH receptors on granulosa cells of small antral follicles <10 mm in diameter. Nevertheless, in normo-ovulatory non PCOS patients, LH receptor expression in these follicles remains very low, questioning the relevance of providing LH activity to improve oocyte maturation during IVM cycles performed for FP. The present investigation aimed to test whether the absence of therapeutic intervention prior to oocyte retrieval modifies IVM outcomes when compared with cycles primed either with recombinant hCG or GnRH agonist in breast cancer patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
204

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 38 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • age between 18 and 38 years;
  • diagnosis of breast cancer (BC)
  • indication for neoadjuvant chemotherapy;
  • body mass index (BMI) ≤27kg/m2; regular ovulatory cycles;
  • transvaginal ultrasound showing the presence of two ovaries with an antral follicle count (AFC) between 10 and 30 follicles;
  • affiliation to the national social security system.
  • Written informed consent was obtained from all participants

Exclusion Criteria:

  • - previous chemotherapy, ovarian surgery or endometrioma;

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: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Without injection group
no injection used as priming
Other: hCG
a subcutaneous injection of hCG (Choriogonadotropin alpha, Ovitrelle®, Merck Serono, 250 µg) is performed 36 hours before oocytes retrieval
Other: GnRH a
a subcutaneous injection of GnRH agonist (triptorelin, Decapeptyl, Ipsen, 0,2 mg) is performed 36 hours before oocytes retrieval
Active Comparator: hCG group
hCG used as priming
Other: GnRH a
a subcutaneous injection of GnRH agonist (triptorelin, Decapeptyl, Ipsen, 0,2 mg) is performed 36 hours before oocytes retrieval
Other: No hormone
No hormonal injection before oocytes retrieval
Active Comparator: GnRHa group
GnRH agonist used as priming
Other: hCG
a subcutaneous injection of hCG (Choriogonadotropin alpha, Ovitrelle®, Merck Serono, 250 µg) is performed 36 hours before oocytes retrieval
Other: No hormone
No hormonal injection before oocytes retrieval

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
total number of mature oocytes cryopreserved
Time Frame: 4 days
Total number of mature oocytes obtained and cryopreserved after IVM
4 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
number of COCS recovered
Time Frame: 36 hours
Total number of COCs recovered after COCs retrieval
36 hours
maturation rate
Time Frame: 4 days
ratio between the number of mature oocytes over the number of COCs recovered
4 days

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hôpital Jean Verdier

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 9, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 9, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 9, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 16, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 17, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-A00819-38

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

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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