Effects of Recombinant LH in Patients With Repeated Implantation Failure
Condition: Female Infertility; Female Subfertility
MeSH terms: Infertility; Infertility, Female
Study type: Interventional

Summary: 
      Pregnancy rates fall dramatically in women after 35 years undergoing to IVF or ICSI. While
      ovarian aging obviously plays the major role in this phenomenon, over suppression of
      endogenous LH concentrations with GnRH agonists or antagonists-an integral part of standard
      IVF/ ICSI protocols-may also play a pivotal role.

      Assisted reproduction technology protocols using GnRH agonists have been considered as the
      standard protocol during the last two decades, but the use of GnRH antagonists offers the
      opportunity to control the endogenous LH surge in a rapid and more convenient way.

      LH plays a key role in the intermediate-late phases of folliculogenesis. The presence of
      receptors for LH in cumulus granulosa cells and its correlation with oocyte maturation has
      been demonstrated. Although ovarian stimulation is efficiently achieved in most cases by the
      administration of exogenous FSH alone, specific subgroups of women may benefit from LH
      activity supplementation during ovarian stimulation. Some authors have found improved outcome
      with LH activity supplementation in advanced reproductive age women.

      LH has a number of roles in follicular development, induction of ovulation, completion of
      meiosis I, early luteinization and the production of progesterone.

      The efficacy of recombinant human follicle-stimulating hormone (r-hFSH) for ovarian
      stimulation is well established however, the role of supplementary recombinant human
      luteinizing hormone (r-hLH) is less clear.

      Aim of the present study is to evaluate If adding rLH in the late phase of stimulation can
      benefit in some patient awith repeated implantation failure.
    

Detailed description: 
      Study Design, Size and Duration

      The study was conducted at the - Bio fertility IVF Center, Rome, Italy, on infertile couples
      due to male factor undergoing ICSI treatment.

      The study was reviewed and approved by the institutional review board at the - Biofertilty
      IVF Center.

      All patients undergoing ICSI and participating in the study gave informed consent.

      Patients included in the study had regular spontaneous menstrual cycles (26-39 days) and were
      aged < 42 years.

      All patients had acceptable follicular phase serum concentrations of FSH (≤10IU/L), LH
      (<10IU/L) and oestradiol (<60pg/ml), body mass index (BMI) ≤ 30 kg/m2, presence of both
      ovaries and normal uterine cavity.

      Only patients with repeated implantation failure in at least two previous IVF cycles were
      included.

      Patients were excluded from the study if they had any clinically significant systemic
      disease, polycystic ovarian syndrome (PCOS), a previous history of severe ovarian
      hyperstimulation syndrome (OHSS), abnormal gynaecological bleeding of unknown origin, a
      previous history of intolerance to any of the agents used in the study.

      This was a prospective, randomized study.

      All patient sighed a detailed informed consent.

      The study is in accordance to the GCP guidelines

      They were randomly divided into two groups (A and B).

      All patients were stimulated in GnRH antagonist flexible protocol cycles using rFSH started
      on day 2 of a spontaneous or induced cycle. HCG (10000 iu ) was administered by I.M route
      when at least 2 folliclesreached 18 mm in diameter.

      Group A included 29 women stimulated with rFSH supplemented by rLH in the late follicular
      phase started at the same time of starting the antagonist administration.

      Those patients received 75 iu of rLH (Luveris serono) daily and 150 iu about 12 hours before
      triggering ovulation with HCG while Group B included 32 women who were stimulated with
      recombinant FSH (gonal F serono) only. The oocytes were decumulated and assessed for the
      maturation two hours after pick up which was done 36 hours after hcg injection. Mature oocyte
      should have an intact first polar body and homogeneously fine granular and light-colored
      ooplasm

      The rate of metaphase II oocytes was calculated and the MII oocytes were assessed for
      cytoplasmic morphology and maturity. MII oocytes with a light color and fine homogeneous
      granulate ooplasm were considered oocytes normal morphology and classified as oocytes that
      have completed their cytoplasmic maturation.

      Embryo transfer was done after 2 days of icsi. Pregnancy test was done after 12 days and
      clinical pregnancy and number of gestional sacs were assured after 2 weeks of positive
      pregnancy test with presence of featal heart beats. The mean, SD, T-test and Chi square test
      were used for statistic calculations of the results.
    

Intervention name(s): rFSH + r-LH in combination; rFSH alone
Intervention type(s): Drug; Drug
Intervention description(s): 29 women stimulated with rFSH supplemented by rLH in the late follicular phase started at the same time of starting the antagonist administration.; 32 women who were stimulated with recombinant FSH alone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment