Obesity
Conditions
Brief summary
The aim of the present study is to determine, whether clinical efficacy of 150 mcg of Corifollitropin alfa is the same in normal weighing and obese women. Furthermore, investigators want to determine whether oocytes retrieved from normal weighing and obese women, after COH using 150 mcg of Corifollitropin alfa, are of same quality on the molecular level.
Detailed description
The dosage of Corifollitropin alfa used for controlled ovarian hyperstimulation (COH) is adjusted according to the patient's body weight. Meaning, in women with a body weight ≤ 60 kg, a single dose of 100 mcg of Corifollitropin alfa is administered for COH and in women with a body weight \> 60 kg, a single dose of 150 micrograms of Corifollitropin alfa is administered for COH. These two protocols are comparable in safety and efficacy of follicular stimulation. On the other hand, knowledge about the clinical efficacy of 150 mcg of Corifollitropin alfa in obese women (BMI\>30 kg/m2) is lacking. Cumulus cells (CC) surround the oocyte and bi-directional communication between oocyte and CC is necessary for the development of mature and quality oocytes. It has been proposed, that analysis of genes, expressed in CC, can serve as an objective indicator of the oocyte's maturity and developmental potential. Expression of genes in CC as hyaluronan synthase 2 (HAS2), follicle-stimulating hormone receptor (FSHR), versican (VCAN), progesterone receptor (PR), vascular endothelial growth factor C (VEGFC), serine protease inhibitor E2 (SERPINE2), glutathione peroxidase (GPX3), pentraxin 3(PTX3) was reported to correlate with oocyte maturity and developmental potential. The effect of Corifollitropin alfa on expression of these genes however, is unknown.
Interventions
DRUGElonva
20 obese women will be the study group and 20 normal weighing women will be the control group. Both groups will receive 150 mcg of Elonva for controlled ovarian hyperstimulation (COH). Gonadotropin-releasing hormone (GnRH) antagonist will be used to prevent premature luteinizing hormone (LH) surge. Additional daily doses of 200 IU of recombinant follicle stimulating hormone (rFSH) will be used if necessary. Human chorionic gonadotropin (hCG) will be used for oocyte maturation. 2 mature follicles will be aspirated separately in each patient. Cumulus cell (CC) samples will be collected and stored on -80 oC for subsequent analysis. Clinical and molecular parameters of IVF success will be assessed and compared between the groups. The exclusion criteria will be: polycystic ovary syndrome, severely abnormal sperm parameters, and age \> 38 years.
Sponsors
Merck Sharp & Dohme LLC
University Medical Centre Ljubljana
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No
Inclusion criteria
* BMI \> 30 kg/m2 * BMI 18.5-24.9 kg/m2
Exclusion criteria
* polycystic ovary syndrome, severely abnormal sperm parameters, and age \> 38 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Mature Oocytes | 1 month | Number of mature oocytes obtained was compared between groups |
| Number of Fertilized Oocytes | 1 month | — |
| Number of Frozen Embryos | 1 month | — |
| Biochemical Pregnancy Rate | 1 year | — |
| Number of Oocytes Retrieved Per Patient | 1 month | Number of oocytes obtained in the study group was compared to the number of oocytes obtained in the control group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | 12 months | Expression of some genes that were proposed as biomarkers of oocyte quality was analysed in CC using real-time PCR. Relative expression values of genes were compared between mature oocytes derived from obese women and mature oocytes derived from normal weighing women. |
Countries
Slovenia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Group 35 obese women (BMI ≥ 30 kg/m2) were included to the study group. 150 mcg of Elonva for controlled ovarian hyperstimulation (COH) on day 2 or 3 of menstrual cycle. GnRH antagonist was used to prevent premature LH surge. Additional daily doses of 200 IU of rFSH were used if necessary to achieve optimal ovarian stimulation. hCG was used to induce final oocyte maturation. Follicles were aspirated separately in each patient. Cumulus cells (CC) samples of the first 2 aspirated follicles were collected and stored on -80 oC for subsequent analyses. Clinical IVF parameters were assessed and compared between the groups. Also, gene expression analyses of CC were performed using quantitative real-time PCR.
Inclusion criteria for the study group were: first or second IVF cycle, BMI ≥ 30 kg/m2, tubal factor of infertility, normal partner's spermiogram. | 35 |
| Control Group 35 normal weighing women (BMI 19 - 24.9 kg/m2) were included to the study group. 150 mcg of Elonva for controlled ovarian hyperstimulation (COH) on day 2 or 3 of menstrual cycle. GnRH antagonist was used to prevent premature LH surge. Additional daily doses of 200 IU of rFSH were used if necessary to achieve optimal ovarian stimulation. hCG was used to induce final oocyte maturation. Follicles were aspirated separately in each patient. Cumulus cells (CC) samples of the first 2 aspirated follicles were collected and stored on -80 oC for subsequent analyses. Clinical IVF parameters were assessed and compared between the groups. Also, gene expression analyses of CC were performed using quantitative real-time PCR.
Inclusion criteria for the control group were: first or second IVF cycle, normal BMI (19 - 24.9 kg/m2), tubal factor of infertility and normal partner's spermiogram.
s. | 35 |
| Total | 70 |
Baseline characteristics
| Characteristic | Study Group | Control Group | Total |
|---|---|---|---|
| Age, Customized Age | 30.3 Years STANDARD_DEVIATION 3.9 | 31.5 Years STANDARD_DEVIATION 3.6 | 30.9 Years STANDARD_DEVIATION 3.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 35 Participants | 70 Participants |
| Region of Enrollment Slovenia | 35 Participants | 35 Participants | 70 Participants |
| Sex/Gender, Customized Women | 35 Participants | 35 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
Biochemical Pregnancy Rate
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Biochemical Pregnancy Rate | 18 Biochemical pregnancies |
| Control Group | Biochemical Pregnancy Rate | 18 Biochemical pregnancies |
p-value: 0.4Regression, Logistic
Primary
Number of Fertilized Oocytes
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Number of Fertilized Oocytes | 206 Fertilized oocytes |
| Control Group | Number of Fertilized Oocytes | 207 Fertilized oocytes |
p-value: 0.3Regression, Logistic
Primary
Number of Frozen Embryos
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Number of Frozen Embryos | 45 Frozen embryos |
| Control Group | Number of Frozen Embryos | 49 Frozen embryos |
p-value: 0.9Regression, Logistic
Primary
Number of Mature Oocytes
Number of mature oocytes obtained was compared between groups
Time frame: 1 month
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study Group | Number of Mature Oocytes | 269 Mature oocytes |
| Control Group | Number of Mature Oocytes | 319 Mature oocytes |
p-value: 0.5Regression, Logistic
Primary
Number of Oocytes Retrieved Per Patient
Number of oocytes obtained in the study group was compared to the number of oocytes obtained in the control group
Time frame: 1 month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Number of Oocytes Retrieved Per Patient | 11.3 Oocytes | Standard Deviation 7.5 |
| Control Group | Number of Oocytes Retrieved Per Patient | 12.4 Oocytes | Standard Deviation 7.4 |
p-value: 0.9Regression, Logistic
Secondary
Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level
Expression of some genes that were proposed as biomarkers of oocyte quality was analysed in CC using real-time PCR. Relative expression values of genes were compared between mature oocytes derived from obese women and mature oocytes derived from normal weighing women.
Time frame: 12 months
Population: Gene expression in cumulus cells surrounding mature oocytes was analyzed using quantitative polymerase chain reaction (qPCR). We analyzed 53 CC samples in the Study group and 56 CC samples in Control group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Progesterone receptor (PGR) | 2.52 Arbitrary units (Relative expression) | Standard Deviation 1.73 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Pentraxin 3 (PTX3) | 1.49 Arbitrary units (Relative expression) | Standard Deviation 1.37 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Serpin Family E Member 2 (SERPINE2) | 0.83 Arbitrary units (Relative expression) | Standard Deviation 0.75 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Follicle stimulating hormone receptor (FSHR) | 1.29 Arbitrary units (Relative expression) | Standard Deviation 1.58 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Glutathione peroxidase (GPX3) | 0.66 Arbitrary units (Relative expression) | Standard Deviation 1.31 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Hyaluronan Synthase 2 (HAS2) | 1.02 Arbitrary units (Relative expression) | Standard Deviation 0.78 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Versican (VCAN) | 5.40 Arbitrary units (Relative expression) | Standard Deviation 4.66 |
| Study Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Vascular endothelial growth factor C (VEGFC) | 0.79 Arbitrary units (Relative expression) | Standard Deviation 0.46 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Vascular endothelial growth factor C (VEGFC) | 0.84 Arbitrary units (Relative expression) | Standard Deviation 0.42 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Progesterone receptor (PGR) | 1.31 Arbitrary units (Relative expression) | Standard Deviation 0.9 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Glutathione peroxidase (GPX3) | 0.33 Arbitrary units (Relative expression) | Standard Deviation 0.25 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Pentraxin 3 (PTX3) | 0.63 Arbitrary units (Relative expression) | Standard Deviation 0.58 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Versican (VCAN) | 5.09 Arbitrary units (Relative expression) | Standard Deviation 5.6 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Serpin Family E Member 2 (SERPINE2) | 0.61 Arbitrary units (Relative expression) | Standard Deviation 0.43 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Hyaluronan Synthase 2 (HAS2) | 0.96 Arbitrary units (Relative expression) | Standard Deviation 0.71 |
| Control Group | Real-time PCR Analysis of Genes That Were Proposed as Biomarkers of Oocyte Quality to Determine Effect of Corifollitropin Alpha on Oocyte Quality on Molecular Level | Follicle stimulating hormone receptor (FSHR) | 1.2 Arbitrary units (Relative expression) | Standard Deviation 1.15 |