Clinical Outcomes in WHO Type I Anovulatory Women Using r-hFSH+r-hLH in a 2:1 Ratio or hMG-HP

June 17, 2012 updated by: Domenico Carone, Centro Riproduzione e Andrologia

Prospective Randomized Open Label Study to Compare the Efficacy and Safety of Ovarian Stimulation With Pergoveris® and Menopur® in Women With Severe Luteinizing Hormone (LH) and Follicular Stimulating Hormone (FSH) Deficiency.

The aim of the study is to compare the efficacy and safety of r-hFSH+r-hLH in a 2:1 ratio with human Menopausal Gonadotropin Highly Purified (hMG-HP), in WHO type I anovulation, HH women.

This open-label monocentric, randomized comparative trial, to receive the two different standard clinical practice treatments:

  • 1 vial of Pergoveris: (vial/powder 150 International unit (IU) r-hFSH+ 75IU r-hLH)
  • 2 vials of Menopur: (vials/powder hMG 75IU).

Follicular development were monitored until the protocol hCG requirement is met and a single injection of hCG was administered.

Main Outcome Measures were follicular development i.e. follicle ≥ 17 millimeters (mm), pre-ovulatory E2 ≥ 400 picomole/Liter (pmol/L) and mid-luteal phase Progesterone (P4) ≥ 25 nanomole/Liter (nmol/L).

Study Overview

Detailed Description

World Health Organization (WHO) type I hypogonadotropic anovulation (hypogonadotropic hypogonadism, HH) is a rare alteration of the reproductive system with absent or decreased function of the gonads, caused by congenital, including genetic, or acquired reduced hypothalamic or pituitary activity. This results in abnormally low serum levels of Follicular Stimulation Hormone (FSH) and Luteinizing Hormone (LH) and negligible oestrogen (E2) activity.

The most convenient treatment is daily injections of exogenous gonadotropins that has been proven to be effective.

Patients lacking an effective hypothalamic-pituitary activity (WHO type I anovulation) do not produce sufficient threshold levels of endogenous LH, which is required to obtain optimal follicular development and steroidogenesis when treated with FSH alone. Therefore a combination therapy with adequate doses of both FSH and LH in an optimal ratio is required in order to restore fertility.

The LH activity could be produced by LH itself or by human Chorionic Gonadotropin (hCG) and the two gonadotropins are available to be used in the WHO type I patients in two different formulations both in indication for this type of patients. It would be worth of interest to assess if these two different formulations could elicit the same clinical outcomes in standard clinical practice or not.

The aim of the study is to compare the efficacy and safety of recombinant human FSH and recombinant human LH (r-hFSH+r-hLH) in a 2:1 ratio with human Menopausal Gonadotropin Highly Purified (hMG-HP), containing LH-like activity, in women with severe LH and FSH deficiency (WHO type I anovulation, HH).

All patients were diagnosed with HH according to a negative progesterone (P4) challenge test, serum LH<1.2 IU/L and FSH <5 IU/L, a transvaginal ultrasound showing a uterus with a midline echo, no ovarian tumor or cyst and ≤ 13 small follicles (mean diameter ≤ 10millimeters (mm)) on the largest section through each ovary, a Body Mass Index (BMI) between 18 and 32 Kilograms for square meters(Kg/m2), and no systemic diseases.

In this open-label monocentric, randomized comparative trial, patients was randomized in two arms in 1:1 ratio, to receive the two different standard clinical practice treatments:

  • 1 vial of Pergoveris: (vial/powder 150 International Units (IU) r-hFSH+ 75IU r-hLH)stimulation day 1 until required hCG level is met. The dose can be adjusted at stimulation Day 6 according to subject ovarian response and standard clinical practice
  • 2 vials of Menopur: (vial/powder hMG containing 75IU FSH + 75IU LH-like activity). stimulation day 1 until required hCG level is met. The dose can be adjusted at stimulation Day 6 according to subject ovarian response and standard clinical practice Follicular development were monitored according clinical practice by ultrasound (US) and/or estradiol (E2) levels, until the protocol hCG requirement is met (i.e., at least one follicle greater than or equal to 17 mm). After this, a single injection of hCG was administered in order to induce final oocyte maturation.

Main Outcome Measures were ovulation induction as measured by follicular development i.e. follicle ≥ 17 mm, pre-ovulatory E2 ≥ 400 picomole/Liter (pmol/L) and mid-luteal phase Progesterone ≥ 25 nanomole/Liter (nmol/L). Secondary efficacy endpoints included estradiol levels/follicle at mid-cycle, number of follicles at mid-cycle and pregnancy rate (PR).

Drug safety was assessed by monitoring adverse events and the incidence of local reactions after drug injection at local site. Ovarian hyperstimulation syndrome (OHSS) was assessed and recorded according to Golan classification According to this protocol, patients were initially treated for one cycle. If consenting, patients who did not become pregnant during the first cycle were treated for a further optional one or two series of cycles with the same criteria of randomization, i.e. maintaining the same treatment as the previous cycle.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • 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 Locations

      • Taranto, Italy, 74100
        • Centro Riproduzione e Andrologia

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

23 years to 34 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • WHO Type I HH Women
  • Serum LH <1.2 IU/L
  • Serum FSH <5 IU/L
  • Age 25-36 years
  • No ovarian tumor
  • No cyst
  • ≤ 13 small follicles (mean diameter ≤ 10mm)
  • BMI between 18 - 32 Kg/m2
  • no systemic diseases

Exclusion Criteria:

-

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pergoveris: 150IU r-hFSH+ 75IU r-hLH
This is a prospective randomized study using two in-label treatments for the patient disease: Pergoveris and Menopur. Pergoveris arms can be considered as experimental for the aim of the study, anyway it is standard routine practice for HH women.
Fixed formulation of two recombinant gonadotropins
Other Names:
  • Pergoveris
Experimental: Menopur: hMG-HP (150IU)
This is a prospective randomized study using two in-label treatments for the patient disease: Pergoveris and Menopur. Menopur can be considered as experimental for the aim of the study, anyway it is standard routine practice for HH women
Human Menopausal Gonadotropin is an urinary estract from menopausal women containing 150IU of FSH and 150 IU of LH-like activity (HCG)
Other Names:
  • Menopur

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
E2 in pmol/L
Time Frame: Day after the protocol hCG requirement is met (at least one follicle of 17mm is monitored by ultrasound)
Evaluate the patients steroidogenesis
Day after the protocol hCG requirement is met (at least one follicle of 17mm is monitored by ultrasound)
Number of Follicles > 17mm
Time Frame: last US day before hCG administration
To evaluate the efficacy of the stimulation and maturity of follicles
last US day before hCG administration
P4 in nmol/L
Time Frame: Day after the protocol hCG requirement is met (at least one follicle of 17mm by US)
Progesteron level to evaluate the endometrial receptivity
Day after the protocol hCG requirement is met (at least one follicle of 17mm by US)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endometrial thickness
Time Frame: Day 5 and Day 10 of stimulation treatment
Evaluation of endometrial development and receptivity
Day 5 and Day 10 of stimulation treatment
Total number of Follicles
Time Frame: Last US day before hCG administration
To evaluate the overall efficacy of stimulation treatment, also including follicles < 17mm
Last US day before hCG administration
Clinical Pregnancy rate
Time Frame: days 35-42 post hCG
Evaluate the ratio between primary end points and final stimulation outcome
days 35-42 post hCG
Occurence of any adverse events (early or late ovarian hyperstimulation syndrome)
Time Frame: Days 15-20 post hCG
Days 15-20 post hCG

Collaborators and Investigators

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

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.

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

March 1, 2011

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

June 17, 2012

First Submitted That Met QC Criteria

June 17, 2012

First Posted (Estimate)

June 20, 2012

Study Record Updates

Last Update Posted (Estimate)

June 20, 2012

Last Update Submitted That Met QC Criteria

June 17, 2012

Last Verified

June 1, 2012

More Information

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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