Effect of Ovarian Stimulation With r-hLH/r-hFSH,r-hFSH and hMG in Reducing Apoptosis Rate in Cumulus Cells of Patients Undergoing ICSI

June 5, 2013 updated by: Centro di Biologia della Riproduzione, Palermo, Italy

A Pilot Study on the Effect of Ovarian Stimulation With r-hLH/r-hFSH, r-hFSH and hMG in Reducing Apoptosis Rate in Cumulus Cells of Patients Undergoing ICSI

HP-hMG, recombinant FSH (r-hFSH) and a combination of r-hFSH/r-hLH, are commonly used for ovarian stimulation in infertile women undergoing IVF/ICSI treatments. Several publications have compared the effectiveness of these compounds, in terms of clinical outcomes.

The aim of our study is to investigate the effects of three different ovarian stimulation protocols (HP-hMG, r-hFSH and r-hFSH/r-hLH), in a pilot prospective observational study, evaluating the effects of recombinant LH and extractive hCG (with LH like activity) on the biological outcome as well as on the clinical outcome. We will use the apoptosis rate of the cumulus cell, usually discarded after oocyte collection, as molecular biomarker to assess the oocyte quality, as biological outcome. The clinical outcome was estimated measuring implantation and ongoing pregnancy rates within and between the three different ovarian stimulation protocols

Study Overview

Status

Completed

Conditions

Detailed Description

HP-hMG, recombinant FSH (r-hFSH) and a combination of r-hFSH/r-hLH, are commonly used for ovarian stimulation in infertile women undergoing IVF/ICSI treatments. Several publications have compared the effectiveness of these compounds, in terms of clinical outcomes . Most of the studies have been performed in women undergoing pituitary down-regulation with a GnRH agonist long protocol, focusing on the outcome after r-hFSH and HP-hMG ovarian stimulation . Two meta-analyses showed a better outcome in terms of live birth rate for HP-hMG ovarian stimulation compared to r-hFSH in the GnRH agonist long protocol. These studies mainly compare different dose regimen of the two drugs used in the same clinical population, r-hFSH and HP-hMG. Recently other two clinical randomized studies compared, in a non-inferiority design, the same dose regimen of the two drugs. The results confirmed non inferiority of the HP-hMG formulation in terms of pregnancy rate compared to the r-hFSH formulations, but significantly higher drug consumption and lower yield in oocyte recovery.

In clinical practice HP-hMG is a clinical favored treatment when LH activity is requested for the ovarian stimulation success, due to LH activity guaranteed by extractive hCG added to this formulation.

Several studies have addressed the issue of the need or convenience of adding LH activity to FSH in ovarian stimulation in IVF/ICSI-ET in order to increase clinical outcomes in IVF/ICSI cycles , but they have not been able to address the role that LH administration plays during the follicular phase of a stimulated cycle for IVF-ET under pituitary suppression. In the case of r-hFSH administration, in normo-gonadotrophic patients, low levels of endogenous LH can persist despite pituitary down-regulation with GnRH analogues. It is known that only 1% of LH receptors need to be occupied to drive adequate ovarian steroidogenesis for reproduction. But the potential benefit of additional exogenous LH supplementation in ART is still controversial .

Different meta-analyses did not demonstrate any benefit of the r-hLH supplementation in increasing clinical outcome . However, in patients of advanced age undergoing ART, likely to include a larger proportion of poor responders, the addition of r-hLH seems to be beneficial .

In a previous study, the investigators demonstrated that r-hLH supplementation during ovarian stimulation, significantly reduces apoptosis in the cumulus cells, improving oocyte competence that is necessary for adequate fertilization and the consecutive embryogenesis that ends with implantation.

Given this background, it seems appropriate to investigate the effects of three different ovarian stimulation protocols (HP-hMG, r-hFSH and r-hFSH/r-hLH), used as routine in the ovarian stimulation therapy, in a pilot prospective observational study, evaluating the effects of recombinant LH and extractive hCG (with LH like activity) on the biological outcome as well as on the clinical outcome. The apoptosis rate of the cumulus cell, usually discarded after oocyte collection, was used as molecular biomarker to assess the oocyte quality, as biological outcome. The clinical outcome was estimated measuring implantation and ongoing pregnancy rates within and between the three different ovarian stimulation protocols

Study Type

Observational

Enrollment (Actual)

61

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

  • Italy
      • Palermo, Italy, 90141
        • Centro di Biologia della Riproduzione

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

28 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Infertile women after 2 years of failed spontaneous conception

Description

Inclusion Criteria:

  • normal basal level of FSH (< 12 IU/mL)
  • normal body mass index (BMI = kg/m2 < 28)
  • poor or hyporesponse in a previous cycle according to Bologna criteria

Exclusion Criteria:

  • Azoospermia
  • Endometriosis
  • recurrent abortion
  • recurrent failures after IVF

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
apoptosis of cumulus cell
Time Frame: 1 year
The apoptosis of cumulus cells has been investigated by "in situ" fluorescent TUNEL assay. The measure of apoptosis is the percentage of apoptotic cells on the total of cells analyzed. Usually a rate less than 15% in considered normal
1 year

Collaborators and Investigators

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

Sponsor

Centro di Biologia della Riproduzione, Palermo, Italy

Investigators

  • Principal Investigator: Giovanni Ruvolo, Biologist, Centro di Biologia della Riproduzione, Palermo, Italy

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

January 1, 2012

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

May 27, 2013

First Submitted That Met QC Criteria

June 5, 2013

First Posted (Estimate)

June 7, 2013

Study Record Updates

Last Update Posted (Estimate)

June 7, 2013

Last Update Submitted That Met QC Criteria

June 5, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • apoptosis2013

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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