Clinical trial NCT01204840: Growth Hormone for Poor Responders in in Vitro Fertilization (IVF)
Official title: Co-treatment With Recombinant Growth Hormone (GH) in Poor Responders Treated by in Vitro Fertilization (IVF-ET)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infertility
Poor Ovarian Reserve
Keywords: in vitro fertilization
IVF
poor responder
growth hormone
Poor responders to in vitro fertilization treatments
Lead sponsor: Ottawa Fertility Centre
Sponsor class: OTHER
Collaborators: name: EMD Serono
First posted: 2010-09-17
Enrollment: 38
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* less than 42 years of age
* previous IVF cycle with high doses of gonadotropins (defined as greater than or equal to 400 IU/day)
* produced less than 6 follicles greater than or equal to 15mm

Exclusion Criteria:

* any known contraindications to the approved fertility drugs as per the Canadian Product Monographs
* any contraindications to growth hormone, pregnancy (to be ruled out and documented before GH treatment), or are at risk for gestational diabetes

Primary outcomes:
measure: number of mature oocytes retrieved
timeFrame: 8-12 weeks from IVF start date
Secondary outcomes:
measure: duration of stimulation
timeFrame: 8-12 weeks from IVF start date
measure: gonadotropin requirements
timeFrame: 8-12 weeks from IVF start date
measure: number of cumulus-oocyte complexes retrieved
timeFrame: 8-12 weeks from IVF start date
measure: number of fertilized oocytes
timeFrame: 8-12 weeks from IVF start date
measure: proportion of patients reaching embryo transfer
timeFrame: 8-12 weeks from IVF start date
measure: implantation rate
timeFrame: 8-12 weeks from IVF start date
measure: clinical pregnancy rate
timeFrame: 8-12 weeks from IVF start date
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: Ottawa Fertililty Centre
state: Ontario
Study officials:
affiliation: Ottawa Fertility Centre
name: Arthur Leader, BSc., MD, FRCSC
role: PRINCIPAL_INVESTIGATOR
References: