Efficacy and Safety of R-hLH (Luveris ®) Priming Prior to R-HFSH Treatment in Infertile Women Undergoing IVF-ET
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 4

Summary: 
      In programmes of IVF, normal women undergo controlled ovarian stimulation using exogenous FSH
      injections to obtain multiple eggs. The process results in eggs of mixed quality with a broad
      range of developmental and implantation potential.

      The aim of the study was to determine whether, treatment with recombinant human LH prior to
      the FSH injections can improve outcome for women undergoing IVF. High grade embryos implant
      with a higher frequency and baby delivery rate than poor quality embryos. The mature oocyte
      is the most important determinant of embryo quality. Early follicles, containing immature
      eggs, have LH receptors in the theca cells that surround the follicle, and LH stimulates
      these cells to produce factors essential for normal follicular development.

      The intent of the study was to use recLH treatment prior to recFSH to treat a cohort of
      follicles, so that they can all mature together, thus increasing the proportion of high grade
      oocytes and their subsequent embryos
    

Detailed description: 
      Normal women undergoing IVF (Total n = 146; GRI n = 43) were recruited in 4 centres in 3
      countries, and all were started on treatment with a depo GnRH-agonist to suppress endogenous
      gonadotropin secretion. Block randomisation lead to a distribution 71 untreated cases and 75
      cases treated with rec-hLH (Luveris,[Serono]; 300IU/d) for 7 days. On the following days
      recombinant follicle stimulating hormone (rec-hFSH) stimulation of the ovaries was initiated
      using Gonal-f (150IU/d) for approximately 12 days.

      HCG (3500IU) was given when >2 mature follicles were seen by ovarian ultrasound, and oocytes
      (eggs) were fertilized in vitro after collection between 36 and 38h after the injection.
      Embryos were scored for quality, and a maximum of 2 embryos were transferred 2 or 3 days
      later.

      Results During Luveris treatment the LH concentration was increased by approximately 3 IU/L,
      but there was no change in the hormone profiles of androgens or estrogens in blood samples
      measured in a central laboratory. Both groups of patients showed an increase in the
      circulating anti-mullerian hormone, although there was no difference between the groups.

      The Luveris treated group showed a significant (p=0.007) increase in the number of small
      antral follicles, but to a degree that was not different from the control group.

      During rec-hFSH stimulation, there was no difference in the duration of FSH injections
      required or the total dose, or the total number of follicles seen, or the hormone profiles
      observed.

      The Luveris pre-treated group showed a slight (not significant) increase in oocyte yield. In
      this group there was a significant increase in the normally fertilized embryo yield (no
      treatment mean = 5.1; Luveris treatment mean = 7.0: p= 0.038).

      Discussion The observations of negligible effects of LH upon the hormone profiles may be
      explained by the fact that the hormone concetrations were at the lower limit of sensitivity
      of the assay methods, and they do not preclude an effect within the follicles. We did observe
      effects upon follicular development in the ultrasound profiles. Effects upon hormone profiles
      may require both hormones (LH and FSH) to be present at the same time (instead of in
      sequence).

      The small effect of the pre-treatment upon normal embryo yield may be an important
      observation.

      Conclusion These results demonstrate that treating follicles with LH prior to FSH, may lead
      to the development of more viable follicles than with FSH treatment alone. This should lead
      to improved regimes of ovarian stimulation and improve the outcome potential for women
      undergoing IVF.

      Future Research Exploration of this phenomenon will be required in order to maximise any
      potential benefit from the process. There are numerous sub-groups of patients who may
      possibly benefit, including poor responding patients, but further data are required.
    

Intervention name(s): recombinant human LH
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ovarian follicle; Thecal cells; Androgens; FSH sensitivity