Infertility
Conditions
Keywords
ICSI, Suboptimal Ovarian Response, rLH
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.
Interventions
DRUGfix dose r-FSH (Gonal-f)
recombinant follicle stimulation
DRUGr-LH supplementation
recombinant luteinizing hormone
DRUGr-FSH (Gonal-f)
recombinant follicle stimulation hormone
Sponsors
Selcuk University
Sisli Hamidiye Etfal Training and Research Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
23 Years to 39 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Fertilization Rate | up to 9 month | fertilization rate used to measure how many oocytes become fertilized by sperm cells |
| Implantation Rates | up to 9 months | Implantation rate is the percentage of embryos which successfully undergo implantation |
| the Number of Oocytes Retrieved | up to 9 month | median number of oocytes retrieved per participant |
| Number of Mature Oocyte | up to 9 month | median number of mature oocytes retrieved per participant |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
fix dose r-FSH (Gonal-f): recombinant follicle stimulation | 52 |
| r-LH Supplementation to r-FSH 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.
r-LH supplementation: recombinant luteinizing hormone | 50 |
| r-FSH (Gonal-f) Group 3: Daily 75 IU/L r-FSH was added to r-FSH treatment until the end of ovarian stimulation.
r-FSH (Gonal-f): recombinant follicle stimulation hormone | 35 |
| Total | 137 |
Baseline characteristics
| Characteristic | r-LH Supplementation to r-FSH | r-FSH (Gonal-f) | Fix Dose r-FSH (Gonal-f) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 35 Participants | 52 Participants | 137 Participants |
| Age, Continuous | 30.3 years STANDARD_DEVIATION 5.1 | 29.4 years STANDARD_DEVIATION 5.1 | 28.7 years STANDARD_DEVIATION 3.9 | 29.5 years STANDARD_DEVIATION 4.7 |
| Region of Enrollment Turkey | 50 participants | 35 participants | 52 participants | 137 participants |
| Sex: Female, Male Female | 50 Participants | 35 Participants | 52 Participants | 137 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Pregnancy Rate
percentage of participants with a pregnancy (a b-HCG determination was obtained and considered positive if the value was greater than 10 mIU/ml)
Time frame: Up to 9 month
Population: In Group 1, transfer procedure could not be performed one patient. In Group 2, the cycle was cancelled in two patients. Oocyte could not be obtained in one patient during OPU. In other 2 patients, transfer couldn't be done. In Group 3 transfer procedure could not be performed in one patient. The pregnancy rates per embryo transfer were calculated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fix Dose r-FSH (Gonal-f) Group 1 | Pregnancy Rate | 64.7 percentage of pregnant participants |
| r-LH Supplementation to r-FSH Group 2 | Pregnancy Rate | 57.8 percentage of pregnant participants |
| r-FSH (Gonal-f) Group 3 | Pregnancy Rate | 32.4 percentage of pregnant participants |
Secondary
Fertilization Rate
fertilization rate used to measure how many oocytes become fertilized by sperm cells
Time frame: up to 9 month
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Fix Dose r-FSH (Gonal-f) Group 1 | Fertilization Rate | 73.1 percentage of fertilized oocytes | 20 |
| r-LH Supplementation to r-FSH Group 2 | Fertilization Rate | 74.9 percentage of fertilized oocytes | 15 |
| r-FSH (Gonal-f) Group 3 | Fertilization Rate | 74.7 percentage of fertilized oocytes | 16 |
Secondary
Implantation Rates
Implantation rate is the percentage of embryos which successfully undergo implantation
Time frame: up to 9 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Fix Dose r-FSH (Gonal-f) Group 1 | Implantation Rates | 34.8 percentage of embryo implantation | 15 |
| r-LH Supplementation to r-FSH Group 2 | Implantation Rates | 36.1 percentage of embryo implantation | 36.1 |
| r-FSH (Gonal-f) Group 3 | Implantation Rates | 15 percentage of embryo implantation | 34.7 |
Secondary
Number of Mature Oocyte
median number of mature oocytes retrieved per participant
Time frame: up to 9 month
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Fix Dose r-FSH (Gonal-f) Group 1 | Number of Mature Oocyte | 8.9 oocytes | Standard Deviation 3.3 |
| r-LH Supplementation to r-FSH Group 2 | Number of Mature Oocyte | 5.5 oocytes | Standard Deviation 2.8 |
| r-FSH (Gonal-f) Group 3 | Number of Mature Oocyte | 5.5 oocytes | Standard Deviation 3 |
Secondary
the Number of Oocytes Retrieved
median number of oocytes retrieved per participant
Time frame: up to 9 month
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Fix Dose r-FSH (Gonal-f) Group 1 | the Number of Oocytes Retrieved | 10.8 oocytes | Standard Deviation 4 |
| r-LH Supplementation to r-FSH Group 2 | the Number of Oocytes Retrieved | 6.6 oocytes | Standard Deviation 3.4 |
| r-FSH (Gonal-f) Group 3 | the Number of Oocytes Retrieved | 6.4 oocytes | Standard Deviation 3.3 |