Effect of Ovarian Stimulation With r-hLH/r-hFSH,r-hFSH and hMG in Reducing Apoptosis Rate in Cumulus Cells of Patients Undergoing ICSI
Condition: Infertility
MeSH terms: Infertility
Study type: Observational

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
    

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
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Infertile women after 2 years of failed spontaneous conception