Growth Hormone for Poor Responders in in Vitro Fertilization (IVF)
Condition: Infertility; Poor Ovarian Reserve
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine if growth hormone given 4 weeks before as well as
      during a cycle of in vitro fertilization will improve outcomes in women who have had previous
      failure with IVF treatment cycles using high doses of follicle stimulating medications and
      had a poor response (less than 6 follicles).
    

Detailed description: 
      Growth hormone (GH; Saizen®) is indicated for the treatment of growth hormone deficiency in
      both children and adults, as well as for Turner's Syndrome, chronic renal failure, and
      children born short for gestational age.

      In animal studies, growth hormone has been shown to be important in early antral follicle
      recruitment, subsequent follicular growth, and oocyte maturation. Together with insulin-like
      growth factor-1 (IGF-1), growth hormone is essential early on in the recruitment of
      primordial follicles in the growing pool (Slot et al 2006, Wandji et al 1992, Donadeu &
      Peterson 2008, Scaramuzi et al 2006, Liu et al, 1998).

      Two recent meta-analyses have concluded that the addition of growth hormone during the
      ovarian stimulation phase of in vitro fertilization (IVF) cycles in poor responders will
      result in an increased probability of clinical pregnancy (Kolibianakas et al, 2009 and Ahmad
      et al, 2009). However, these studies have investigated the role of growth hormone in IVF when
      starting growth hormone injections with the initiation of gonadotropin stimulation. This may
      be too late to show an effect as GH may have more of an impact in the month prior to
      stimulation when primordial follicles are in the recruitment phase. Adding growth hormone in
      the month prior to stimulation with gonadotropins, as well as during stimulation phase may
      improve IVF outcomes by increasing the number of antral follicles that are recruited in the
      month prior to a stimulated cycle, and may ultimately improve the response to gonadotropin
      stimulation.

      Starting growth hormone prior to stimulation has been studied in one previous publication
      (Kucuk et al, 2008), and showed that by starting growth hormone on day 21 of the menstrual
      cycle preceding gonadotropin stimulation, and continuing co-treatment with growth hormone
      until human chorionic gonadotropin (hCG) trigger resulted in a significantly higher number of
      fertilized oocytes when compared to a control group receiving no growth hormone (4.4 +/-1.8
      vs 1.5 +/-0.9; p<0.001).

      The addition of growth hormone to an IVF treatment protocol is directed at those infertile
      women who have previously undergone an IVF cycle on maximal doses of gonadotropins with a
      poor ovarian response. This study is aimed at improving IVF success in this population of
      women at the Ottawa Fertility Centre.

      The purpose of this study is to determine if the addition of growth hormone both in the month
      prior to gonadotropin stimulation and during the active phase of stimulation, will result in
      an increased number of mature oocytes retrieved in previously poor responders during an IVF
      cycle.
    

Intervention name(s): Growth Hormone; Patch protocol
Intervention type(s): Drug; Drug
Intervention description(s): Subjects in this trial will use a 3.33mg vial (1 vial =10 IU) by daily subcutaneous injection. This will start on day 1 of the menstrual cycle preceding the stimulation phase of an IVF cycle, and will continue until the day of the human chorionic gonadotropin (hCG) trigger (approximately 5-6 weeks); Group A (n=10; control group) will receive "patch protocol": 100ug estrogen patch (Estradot), Gonadotropin releasing hormone (GnRH) antagonist (Cetrotide; 0.25mg/d), gonadotropin stimulation 412 IU recombinant follicle stimulating hormone (r-FSH; Gonal F) and 150 IU of recombinant luteinizing hormone (r-LH; Luveris). With 3 or more follicles at mean diameter equal to or greater than 17mm, urinary human chorionic gonadotropin (u-hCG) 10,000 IU self-injected to complete final maturation of oocytes. Egg retrieval will occur 36 hours after hCG injection. Eggs fertilized by standard IVF or intra-cytoplasmic sperm injection (ICSI) depending on semen parameters. Embryos cultured to day 2 and the best 2-4 will be transferred back under ultrasound guidance. Surplus embryos will be frozen as per clinic protocol. Luteal support: Endometrin 100mg vaginally three times daily, starting on the day of egg retrieval and continuing until menses or positive serum beta-hCG, then stopped.
Other intervention name(s): Saizen (Somatoptropin; Human growth hormone)
Intervention MeSH terms: Hormones
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: in vitro fertilization; IVF; poor responder; growth hormone; Poor responders to in vitro fertilization treatments