The Evaluation of Recombinant LH Supplementation in Patients With Suboptimal Response to Recombinant FSH Undergoing ICSI

Phase 4

Completed

Interventions: Drug: r-FSH (Gonal-f)
Drug: fix dose r-FSH (Gonal-f)
Drug: r-LH supplementation

Brief Summary: The investigators aimed to evaluate patients who had In-vitro fertilization treatment and who had COH (controlled ovarian hyperstimulation) cycles applying long protocol with GnRH (gonadotropin-releasing hormone) analogue with suboptimal response to the rFSH. The investigators evaluated and compared the addition of rLH, increasing the dose of rFSH and the control groups regarding the results of IVF in these patients.

Detailed Description: 1. Aim

-We aimed to evaluate patients who had In-vitro fertilization treatment and who had COH (controlled ovarian hyperstimulation) cycles applying long protocol with GnRH (gonadotropin-releasing hormone) analogue with suboptimal response to the rFSH. We evaluated and compared the addition of rLH, increasing the dose of rFSH and the control groups regarding the results of IVF in these patients.

2. Material and Methods -Between 01.01.2009-30.04.2011, 137 patients presented with infertility to the unit of Assisted Reproduction Techniques- of the Department of Obstetrics and Gynecology- Meram Medical Faculty- Selcuk University and were planned for ICSI-ET (intracytoplasmic sperm injection-embryo transfer) with normal ovarian function, who had long protocol of GnRH analogue and COH (controlled ovarian hyperstimulation) with rFSH were included in the study. 52 patients were considered responsive to stimulation and composed the normal control group (Group 1). On the 7th day of stimulation transvaginal ultrasonography was carried out. Patients who had at least 6 follicles about 6-10mm but had no follicle above 10mm and E2 (Oestradiol) level of \<250 pg / ml were considered to have suboptimal response to stimulation and were divided into two groups. For Group 2 (n = 50), 75IU / L rLH was added to the treatment, for Group 3 (n = 35), 75IU / L of rFSH was added to the treatment. IVF results were compared between the groups.

Recruitment & Eligibility

Inclusion Criteria

Patients aged 23-39
Body mass index between 18 and 30 kg/m2
Baseline FSH ≤12 IU/l, E2 ≤ 80 pg/ml
The presence of both ovaries and uterine cavity capable of sustaining a pregnancy
Who had regular menstrual cycles (21-35 days) Confirmed absence of pregnancy and sufficient number of antral follicles on the transvaginal US examination on the 3rd day of menstruation
Who were having their first or second IVF trial.

Exclusion Criteria

Grade III-IV endometriosis
Clinically significant condition preventing them from undergoing gonadotrophin treatment
More than two previous assisted cycles
Who had a single ovary
Unexplained gynaecological bleeding
Polycystic ovary or an ovarian cyst of unknown aetiology
Previously diagnosed with a space occupying lesion like submucous myoma , polyps, septum, synechia in the uterine cavity
Have a chromosomal anomaly.

Arm && Interventions

Group	Intervention	Description
r-FSH (Gonal-f)	r-FSH (Gonal-f)	Group 3: Daily 75 IU/L r-FSH was added to r-FSH treatment until the end of ovarian stimulation.
fix dose r-FSH (Gonal-f)	fix dose r-FSH (Gonal-f)	The patients who had normal ovarian response were included as the control group (Group 1). The dose of r-FSH (Gonal-f) was continued for the fix dose until the day of hCG in Group 1
r-LH supplementation to r-FSH	r-LH supplementation	On day 7 of the stimulation, if at least six follicles between 6-10mm were present but there was no follicle over 10 mm on transvaginal ultrasound, E2 level was under 180 pg/ml, it has been considered that the patients had suboptimal response to the stimulation and were divided into Group 2. Group 2 received supplemental r-LH ( Lutropin alpha; Luveris, Merck Serono, France), 75IU/day to r-FSH (Gonal-f) treatment.

Primary Outcome Measures

Name	Time	Method
Pregnancy Rate	Up to 9 month	percentage of participants with a pregnancy (a b-HCG determination was obtained and considered positive if the value was greater than 10 mIU/ml)

Secondary Outcome Measures

Name	Time	Method
Fertilization Rate	up to 9 month	fertilization rate used to measure how many oocytes become fertilized by sperm cells
Number of Mature Oocyte	up to 9 month	median number of mature oocytes retrieved per participant
the Number of Oocytes Retrieved	up to 9 month	median number of oocytes retrieved per participant
Implantation Rates	up to 9 months	Implantation rate is the percentage of embryos which successfully undergo implantation