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

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ClinicalTrials.gov Identifier: NCT01872247
Recruitment Status : Completed
First Posted : June 7, 2013
Last Update Posted : June 7, 2013
Sponsor:
Information provided by (Responsible Party):
Centro di Biologia della Riproduzione, Palermo, Italy

Brief Summary:

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


Condition or disease
Infertility

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


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Study Type : Observational
Actual Enrollment : 61 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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
Study Start Date : January 2012
Actual Primary Completion Date : June 2013
Actual Study Completion Date : June 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility




Primary Outcome Measures :
  1. 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



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Ages Eligible for Study:   30 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Infertile women after 2 years of failed spontaneous conception
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01872247


Locations
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Italy
Centro di Biologia della Riproduzione
Palermo, Italy, 90141
Sponsors and Collaborators
Centro di Biologia della Riproduzione, Palermo, Italy
Investigators
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Principal Investigator: Giovanni Ruvolo, Biologist Centro di Biologia della Riproduzione, Palermo, Italy