Second Step Protocol in Poor Ovarian Responder (POR) (POR)

March 30, 2018 updated by: Antonia Iacovelli, Università degli Studi 'G. d'Annunzio' Chieti e Pescara

Repeated Luteal Phase Ovarian Stimulation (Second Step Protocol) in Poor Responder Patients

Reduced ovarian reserve and the consequent poor ovarian response are very recurent in infertile patients, indeed a percentage of 10%-24% of couples addressed to infertility program may be classified as Poor Ovarian Responder (POR).

Objective: To evaluate whether the repeated luteal phase stimulation (Second Step) permits a significantly higher number of oocytes retrieved in POR when compared to conventional follicular stimulation.

Interventions: The follicular phase stimulation is conduced according to a standardized Antagonist protocol or Short protocol (with GnRH agonist) using recombinant or urinary gonadotropins (starting dose 300 or 450 UI) or a long lasting recombinant gonadotropin (Corifollitropin alfa 150 mcg).

Two - six days after the first oocyte retrieval a second gonadotropin stimulation will be started with a GnRH antagonist protocol (the stimulation will be started with 250 UI of human menopausal gonadotropin (hMG) and a GnRH antagonist (GnRH-an) 0,25 mg\die will be administered when the leading follicle is ≥ 14 mm until hCG (human chorionic gonadotropin) criteria are met. When at least two follicles had reached 17-18 mm in diameter, ovulation will be triggered with a single subcutaneous bolus of urinary human chorionic gonadotropin (10.000 UI ) and oocyte retrieval will be performed after 35 hours.

Two or Three months after the second oocyte retrieval the Embryo transfer (ET) will be performed after endometrial preparation with Estradiol Valerate and intramuscular Progesterone.

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

Reduced ovarian reserve and the consequent poor ovarian response are very recurent in infertile patients, indeed a percentage of 10%-24% of couples addressed to infertility program may be classified as Poor Ovarian Responder (POR).

Poor ovarian response and reduced ovarian reserve can be caused by different factors such as advanced female age, smoking, autoimmune diseases, aneuploidies and genetic diseases or can be idiopathic.

An Eshre ( European Society of Human Reproduction and Embryology) consensus in 2011 established the "Bologna Criteria" that consented a standardize definition of poor ovarian response (POR).

According with the Bologna Criteria we can diagnose a Poor Ovarian Response or an expected Poor Ovarian Response when at least two of the following three features are present:

  • Advanced maternal age (≥40 years) or any other risk factor for POR;
  • A previous POR (≤3 oocytes with a conventional stimulation protocol);
  • An abnormal ovarian reserve test (i.e. AFC -Antral Follicular Count- 5-7 follicles or AMH ,0.5-1.1 ng/ml). The diagnosis and the prediction of poor ovarian response consent the selection of the best treatment with the aim of the retrieval of an high number of oocytes.

A lot of treatment have been proposed to optimize in vitro fertilization outcomes in POR (high dosage of Gonadotropins; short protocol, administration of androgens or Aromatase Inhibitors, administration of Growth Hormone and the repeated luteal phase stimulation).

The Luteal Phase Stimulation was initially proposed for fertility preservation procedures, but in last years is used in POR patients too. The recently diffused "wave theory" support this technique. According to the wave theory two or three cohorts of antral follicles are recruited during the follicular and luteal phase of each ovarian cycle and in one of this follicular wave will be selected the dominant follicle.

A trial performed in 2014 (Kuang et al, 2014) pubblished results of repeated luteal phase stimulation (Shanghai Protocol) showing that double ovarian stimulations in the same menstrual cycle provide more opportunities for retrieving oocytes in poor responders. More recently another trial (Ubaldi et al 2016) did not observe significant differences in term of number of oocytes retrieved and euploid blastocyst rate from follicular versus luteal phase stimulation.

Objective: To evaluate whether the repeated luteal phase stimulation (Second Step) permits a significantly higher number of oocytes retrieved in POR when compared to conventional follicular stimulation.

Interventions: The follicular phase stimulation is conduced according to a standardized Antagonist protocol or Short protocol (with GnRH agonist) using recombinant or urinary gonadotropins (starting dose 300 or 450 UI) or a long lasting recombinant gonadotropin (Corifollitropin alfa 150 mcg) from the second day of the menstrual cycle. When at least two follicles had reached 17-18 mm in diameter, ovulation will be triggered with a single subcutaneous bolus of urinary human chorionic gonadotropin (10.000 UI ) and oocyte retrieval will be performed after 35 hours.

Two - six days after the first oocyte retrieval a second gonadotropin stimulation will be started with a GnRH antagonist protocol (the stimulation will be started with 250 UI of human menopausal gonadotropin (hMG) and a GnRH antagonist (GnRH-an) 0,25 mg\die will be administered when the leading follicle is ≥ 14 mm until hCG criteria are met). When at least two follicles had reached 17-18 mm in diameter, ovulation will be triggered with a single subcutaneous bolus of urinary human chorionic gonadotropin (10.000 UI ) and oocyte retrieval will be performed after 35 hours.

Two or Three months after the second oocyte retrieval the Embryo transfer (ET) will be performed after endometrial preparation with Estradiol Valerate and intramuscular Progesterone.

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.
Observational

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.
50

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

  • Name: Gian Mario Tiboni, Professor
  • Phone Number: +393478787545
  • Email: tiboni@unich.it

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Infertil Women classified as Poor Ovarian Responder according with Bologna Criteria (2011) for which an IVF is indicated and in which the number of oocyte retrieved with First oocyte retrieval ≤ 2

Description

Inclusion Criteria:

  • Antral Follicular Count ≤7 follicles
  • Number of oocyte retrieved with First oocyte retrieval ≤ 2

Exclusion Criteria:

  • Antral follicular Count < 7
  • Anti-Müllerian hormone (AMH) >1.1 ng \mL
  • Number of oocyte retrieved with First oocyte retrieval > 2
  • Absence of antral follicles after First oocyte retrieval

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

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.
Follicular Phase
Procedure: Follicular Phase
The follicular phase stimulation is conduced according to a standardized Antagonist protocol or Short protocol (with GnRH agonist) using recombinant or urinary gonadotropins (starting dose 300 or 450 UI) or a long lasting recombinant gonadotropin (Corifollitropin alfa 150 mcg) from the second day of the menstrual cycle. When at least two follicles had reached 17-18 mm in diameter, ovulation will be triggered with a single subcutaneous bolus of urinary human chorionic gonadotropin (10.000 UI ) and oocyte retrieval will be performed after 35 hours.
Other Names:
  • First Step
Luteal Phase
Procedure: Luteal Phase
Two - six days after the first oocyte retrieval a second gonadotropin stimulation will be started with a GnRH antagonist protocol (the stimulation will be started with 250 UI of human menopausal gonadotropin (hMG) and a GnRH antagonist (GnRH-an) 0,25 mg\die will be administered when the leading follicle is ≥ 14 mm until hCG criteria are met). When at least two follicles had reached 17-18 mm in diameter, ovulation will be triggered with a single subcutaneous bolus of urinary human chorionic gonadotropin (10.000 UI ) and oocyte retrieval will be performed after 35 hours.
Other Names:
  • Second Step

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
Number of oocyte Retrieved
Time Frame: 15 days after the Second oocyte retrieval
Number of oocyte Retrieved after the first oocyte retrieval vs Number of oocyte Retrieved after the second oocyte retrieval
15 days after the Second oocyte retrieval

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 Embryos Obtained
Time Frame: 15 days after the Second oocyte retrieval
Number of Embryos Obtained after the Follicular Phase Stimulation and intracytoplasmic sperm injection vs Number of Embryos obtained after Luteal Phase Stimulation and intracytoplasmic sperm injection
15 days after the Second oocyte retrieval

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.
Università degli Studi 'G. d'Annunzio' Chieti e Pescara

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 1, 2017

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.
March 30, 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.
September 1, 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).
March 21, 2018

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.
March 21, 2018

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.
March 29, 2018

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.
April 2, 2018

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.
March 30, 2018

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.
March 1, 2018

More Information

Terms related to this study

Keywords

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.
  • Second Step 1

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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