Clinical Outcomes in WHO Type I Anovulatory Women Using r-hFSH+r-hLH in a 2:1 Ratio or hMG-HP
Condition: Hypogonadotropic Hypogonadism
MeSH terms: Hypogonadism
Study type: Interventional

Summary: 
      The aim of the study is to compare the efficacy and safety of r-hFSH+r-hLH in a 2:1 ratio
      with human Menopausal Gonadotropin Highly Purified (hMG-HP), in WHO type I anovulation, HH
      women.

      This open-label monocentric, randomized comparative trial, to receive the two different
      standard clinical practice treatments:

        -  1 vial of Pergoveris: (vial/powder 150 International unit (IU) r-hFSH+ 75IU r-hLH)

        -  2 vials of Menopur: (vials/powder hMG 75IU).

      Follicular development were monitored until the protocol hCG requirement is met and a single
      injection of hCG was administered.

      Main Outcome Measures were follicular development i.e. follicle ≥ 17 millimeters (mm),
      pre-ovulatory E2 ≥ 400 picomole/Liter (pmol/L) and mid-luteal phase Progesterone (P4) ≥ 25
      nanomole/Liter (nmol/L).
    

Detailed description: 
      World Health Organization (WHO) type I hypogonadotropic anovulation (hypogonadotropic
      hypogonadism, HH) is a rare alteration of the reproductive system with absent or decreased
      function of the gonads, caused by congenital, including genetic, or acquired reduced
      hypothalamic or pituitary activity. This results in abnormally low serum levels of Follicular
      Stimulation Hormone (FSH) and Luteinizing Hormone (LH) and negligible oestrogen (E2)
      activity.

      The most convenient treatment is daily injections of exogenous gonadotropins that has been
      proven to be effective.

      Patients lacking an effective hypothalamic-pituitary activity (WHO type I anovulation) do not
      produce sufficient threshold levels of endogenous LH, which is required to obtain optimal
      follicular development and steroidogenesis when treated with FSH alone. Therefore a
      combination therapy with adequate doses of both FSH and LH in an optimal ratio is required in
      order to restore fertility.

      The LH activity could be produced by LH itself or by human Chorionic Gonadotropin (hCG) and
      the two gonadotropins are available to be used in the WHO type I patients in two different
      formulations both in indication for this type of patients. It would be worth of interest to
      assess if these two different formulations could elicit the same clinical outcomes in
      standard clinical practice or not.

      The aim of the study is to compare the efficacy and safety of recombinant human FSH and
      recombinant human LH (r-hFSH+r-hLH) in a 2:1 ratio with human Menopausal Gonadotropin Highly
      Purified (hMG-HP), containing LH-like activity, in women with severe LH and FSH deficiency
      (WHO type I anovulation, HH).

      All patients were diagnosed with HH according to a negative progesterone (P4) challenge test,
      serum LH<1.2 IU/L and FSH <5 IU/L, a transvaginal ultrasound showing a uterus with a midline
      echo, no ovarian tumor or cyst and ≤ 13 small follicles (mean diameter ≤ 10millimeters (mm))
      on the largest section through each ovary, a Body Mass Index (BMI) between 18 and 32
      Kilograms for square meters(Kg/m2), and no systemic diseases.

      In this open-label monocentric, randomized comparative trial, patients was randomized in two
      arms in 1:1 ratio, to receive the two different standard clinical practice treatments:

        -  1 vial of Pergoveris: (vial/powder 150 International Units (IU) r-hFSH+ 75IU
           r-hLH)stimulation day 1 until required hCG level is met. The dose can be adjusted at
           stimulation Day 6 according to subject ovarian response and standard clinical practice

        -  2 vials of Menopur: (vial/powder hMG containing 75IU FSH + 75IU LH-like activity).
           stimulation day 1 until required hCG level is met. The dose can be adjusted at
           stimulation Day 6 according to subject ovarian response and standard clinical practice
           Follicular development were monitored according clinical practice by ultrasound (US)
           and/or estradiol (E2) levels, until the protocol hCG requirement is met (i.e., at least
           one follicle greater than or equal to 17 mm). After this, a single injection of hCG was
           administered in order to induce final oocyte maturation.

      Main Outcome Measures were ovulation induction as measured by follicular development i.e.
      follicle ≥ 17 mm, pre-ovulatory E2 ≥ 400 picomole/Liter (pmol/L) and mid-luteal phase
      Progesterone ≥ 25 nanomole/Liter (nmol/L). Secondary efficacy endpoints included estradiol
      levels/follicle at mid-cycle, number of follicles at mid-cycle and pregnancy rate (PR).

      Drug safety was assessed by monitoring adverse events and the incidence of local reactions
      after drug injection at local site. Ovarian hyperstimulation syndrome (OHSS) was assessed and
      recorded according to Golan classification According to this protocol, patients were
      initially treated for one cycle. If consenting, patients who did not become pregnant during
      the first cycle were treated for a further optional one or two series of cycles with the same
      criteria of randomization, i.e. maintaining the same treatment as the previous cycle.
    

Intervention name(s): Pergoveris: 150IU r-hFSH + 75IU r-hLH; Menopur: HMG-HP (150 IU)
Intervention type(s): Drug; Drug
Intervention description(s): Fixed formulation of two recombinant gonadotropins; Human Menopausal Gonadotropin is an urinary estract from menopausal women containing 150IU of FSH and 150 IU of LH-like activity (HCG)
Other intervention name(s): Pergoveris; Menopur
Intervention MeSH terms: Menotropins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Luteinizing Hormone; Hypogonadotropic Hypogonadism; Ovulation Induction; Chorionic Gonadotropin