Second Step Protocol in Poor Ovarian Responder (POR)

NCT ID: NCT03480412

Last Updated: 2018-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-09-01

Study Completion Date

2019-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Infertility, Female Premature Ovarian Failure Fertility Disorders

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Follicular Phase

Follicular Phase

Intervention Type PROCEDURE

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.

Luteal Phase

Luteal Phase

Intervention Type PROCEDURE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type PROCEDURE

Other Intervention Names

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First Step Second Step

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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

OTHER

Sponsor Role lead

Responsible Party

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Antonia Iacovelli

Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Ospedale G. Bernabeo

Ortona, Chieti, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Antonia Iacovelli, Doctor

Role: CONTACT

+393203595229

Gian Mario Tiboni, Professor

Role: CONTACT

+393478787545

Facility Contacts

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Antonia Iacovelli, Doctor

Role: primary

3203595229

Other Identifiers

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Second Step 1

Identifier Type: -

Identifier Source: org_study_id

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