Growth Hormone for Poor Responders in in Vitro Fertilization (IVF)

Infertility Clinical Trial

Official title:

Co-treatment With Recombinant Growth Hormone (GH) in Poor Responders Treated by in Vitro Fertilization (IVF-ET)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01204840
• Other study ID #: OFC-001
• Status: Completed
• Phase: Phase 2
• First received: September 14, 2010
• Last updated: June 29, 2015
• Start date: September 2010
• Est. completion date: May 2015

Study information

• Verified date: June 2015
• Source: Ottawa Fertility Centre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 41 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Poor Ovarian Reserve

Intervention

Drug:
• Growth Hormone
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)
• Patch protocol
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.

Locations

Country	Name	City	State
Canada	Ottawa Fertililty Centre	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Fertility Centre	EMD Serono

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of mature oocytes retrieved		8-12 weeks from IVF start date	No
Secondary	duration of stimulation		8-12 weeks from IVF start date	No
Secondary	gonadotropin requirements		8-12 weeks from IVF start date	No
Secondary	number of cumulus-oocyte complexes retrieved		8-12 weeks from IVF start date	No
Secondary	number of fertilized oocytes		8-12 weeks from IVF start date	No
Secondary	proportion of patients reaching embryo transfer		8-12 weeks from IVF start date	No
Secondary	implantation rate		8-12 weeks from IVF start date	No
Secondary	clinical pregnancy rate		8-12 weeks from IVF start date	No

External Links

•   Ottawa Fertility Centre webpage