Trial Outcomes & Findings for EXpression PRofile Endometrium Samples Study (NCT NCT01210144)
NCT ID: NCT01210144
Last Updated: 2013-12-27
Results Overview
A list of genes based on gene expression profiling carried out on ribonucleic acid (RNA) extracted from endometrial tissue. The expression of messenger ribonucleic acid (mRNA) in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.
TERMINATED
PHASE4
27 participants
Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®
2013-12-27
Participant Flow
A total of 27 participants were enrolled in the study, out of which 2 participants withdrew the consent and 1 participant was excluded since endometrial biopsy was not possible.
Participant milestones
| Measure |
Gonal-f® + Ovitrelle® (Long Agonist Protocol)
Participants received 150 International Units (IU) per day of recombinant human follicle stimulating hormone (r-hFSH, Gonal-f®) subcutaneously (sc) starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 microgram (mcg) recombinant human chorionic gonadotropin alfa (r-hCG alfa, Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles greater than \[\>\] 16 millimeter \[mm\], and with estradiol \[E2\] \>1 microgram per liter \[mcg/L\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation (COS), 0.1 milligram (mg) gonadotropin-releasing hormone (GnRH) agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) as per summary of product characteristics (SmPC), in long agonist protocol.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
11
|
|
Overall Study
COMPLETED
|
10
|
11
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
Reasons for withdrawal
| Measure |
Gonal-f® + Ovitrelle® (Long Agonist Protocol)
Participants received 150 International Units (IU) per day of recombinant human follicle stimulating hormone (r-hFSH, Gonal-f®) subcutaneously (sc) starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 microgram (mcg) recombinant human chorionic gonadotropin alfa (r-hCG alfa, Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles greater than \[\>\] 16 millimeter \[mm\], and with estradiol \[E2\] \>1 microgram per liter \[mcg/L\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation (COS), 0.1 milligram (mg) gonadotropin-releasing hormone (GnRH) agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) as per summary of product characteristics (SmPC), in long agonist protocol.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
|---|---|---|
|
Overall Study
Lack of ovarian response
|
1
|
0
|
|
Overall Study
No fertilization
|
1
|
0
|
|
Overall Study
No transfer
|
1
|
0
|
Baseline Characteristics
EXpression PRofile Endometrium Samples Study
Baseline characteristics by cohort
| Measure |
Gonal-f® + Ovitrelle® (Long Agonist Protocol)
n=13 Participants
Participants received 150 International Units (IU) per day of recombinant human follicle stimulating hormone (r-hFSH, Gonal-f®) subcutaneously (sc) starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 microgram (mcg) recombinant human chorionic gonadotropin alfa (r-hCG alfa, Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles greater than \[\>\] 16 millimeter \[mm\], and with estradiol \[E2\] \>1 microgram per liter \[mcg/L\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation (COS), 0.1 milligram (mg) GnRH agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) as per summary of product characteristics (SmPC), in long agonist protocol.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
n=11 Participants
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
29.8 years
STANDARD_DEVIATION 4.2 • n=5 Participants
|
31.0 years
STANDARD_DEVIATION 4.4 • n=7 Participants
|
30.4 years
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: Data were not analyzed for both agonist and antagonist protocol as total, which was the primary objective, since gene expression of the endometrium could not be performed due to poor quality of biopsy samples and poor recruitment in the study.
A list of genes based on gene expression profiling carried out on ribonucleic acid (RNA) extracted from endometrial tissue. The expression of messenger ribonucleic acid (mRNA) in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: Intention-to-Treat (ITT) population: participants who received at least 1 dose of study drug. "N" (number of participants analyzed) signifies participants evaluable for this measure. Results for both agonist and antagonist protocol are presented as total since assessment of histological pattern for whole study population was the primary objective.
Participants with each histological pattern of endometrium were analyzed. Histological patterns included: Proliferative phase (described as the endometrial on the first two weeks after the menstruation \[or before ovulation\]), Early secretory phase (first step of the secretory phase, located at the Day 16-18 of the cycle) and Intermediate secretory phase (secretory phase located at the Day 20-22 of the cycle and describes endometrial closer to the implantation phase).
Outcome measures
| Measure |
Gonal-f® + Ovitrelle®
n=23 Participants
Participants received 150 IU per day of r-hFSH (Gonal-F®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm \[for both long agonist and multi-dose antagonist protocol\], and with E2\>1 mcg/L \[for long agonist protocol\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation, either 0.1 mg GnRH agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) in long agonist protocol or 0.25 mg GnRH antagonist daily was started from Day 6 of GONAL-f® stimulation treatment in multi-dose antagonist protocol, as per SmPC.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
|---|---|---|
|
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f®
Intermediate secretory phase
|
6 participants
|
—
|
|
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f®
Proliferative phase
|
2 participants
|
—
|
|
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f®
Early secretory phase
|
15 participants
|
—
|
SECONDARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: Data were not analyzed because gene expression of the endometrium could not be performed due to poor quality of biopsy samples and poor recruitment in the study.
A list of genes based on gene expression profiling carried out on RNA extracted from endometrial tissue. The expression of mRNA in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: Data were not analyzed because gene expression of the endometrium could not be performed due to poor quality of biopsy samples and poor recruitment in the study.
A list of genes based on gene expression profiling carried out on RNA extracted from endometrial tissue. The expression of mRNA in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: ITT population included those participants who received at least one dose of study medication. Here "N" (number of participants analyzed) signifies those participants who were evaluable for this measure.
Participants with each histological pattern of endometrium were analyzed. Histological patterns included: Proliferative phase (described as the endometrial on the first two weeks after the menstruation \[or before ovulation\]), Early secretory phase (first step of the secretory phase, located at the Day 16-18 of the cycle), Intermediate secretory phase (secretory phase located at the Day 20-22 of the cycle and describes endometrial closer to the implantation phase).
Outcome measures
| Measure |
Gonal-f® + Ovitrelle®
n=12 Participants
Participants received 150 IU per day of r-hFSH (Gonal-F®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm \[for both long agonist and multi-dose antagonist protocol\], and with E2\>1 mcg/L \[for long agonist protocol\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation, either 0.1 mg GnRH agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) in long agonist protocol or 0.25 mg GnRH antagonist daily was started from Day 6 of GONAL-f® stimulation treatment in multi-dose antagonist protocol, as per SmPC.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
n=11 Participants
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
|---|---|---|
|
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f® and Having Undergone Agonist or Antagonist Protocol
Early secretory phase
|
8 participants
|
7 participants
|
|
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f® and Having Undergone Agonist or Antagonist Protocol
Proliferative phase
|
1 participants
|
1 participants
|
|
Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f® and Having Undergone Agonist or Antagonist Protocol
Intermediate secretory phase
|
3 participants
|
3 participants
|
SECONDARY outcome
Timeframe: Day 5 or 6 (window of implantation) after Oocyte RetrievalPopulation: Data were not analyzed because gene expression of the endometrium could not be performed due to poor quality of biopsy samples and poor recruitment in the study.
A list of genes based on gene expression profiling carried out on RNA extracted from endometrial tissue. The expression of mRNA in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 5 or 6 (window of implantation) after Oocyte RetrievalPopulation: ITT population: participants who received at least one dose of study medication. "N" (number of participants analyzed) signifies participants who were evaluable for this measure. Data were not analyzed for Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol) group because there were no participants without blastocyst transfer in this group.
Participants with each histological pattern of endometrium were analyzed. Histological patterns included: Proliferative phase (described as the endometrial on the first two weeks after the menstruation \[or before ovulation\]), Early secretory phase (first step of the secretory phase, located at the Day 16-18 of the cycle), Intermediate secretory phase (secretory phase located at the Day 20-22 of the cycle and describes endometrial closer to the implantation phase).
Outcome measures
| Measure |
Gonal-f® + Ovitrelle®
n=2 Participants
Participants received 150 IU per day of r-hFSH (Gonal-F®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm \[for both long agonist and multi-dose antagonist protocol\], and with E2\>1 mcg/L \[for long agonist protocol\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation, either 0.1 mg GnRH agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) in long agonist protocol or 0.25 mg GnRH antagonist daily was started from Day 6 of GONAL-f® stimulation treatment in multi-dose antagonist protocol, as per SmPC.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
|---|---|---|
|
Number of Participants With a Specific Histological Pattern of the Endometrium in Participants Without Blastocyst Transfer
Proliferative phase
|
0 participants
|
—
|
|
Number of Participants With a Specific Histological Pattern of the Endometrium in Participants Without Blastocyst Transfer
Early secretory phase
|
0 participants
|
—
|
|
Number of Participants With a Specific Histological Pattern of the Endometrium in Participants Without Blastocyst Transfer
Intermediate secretory phase
|
2 participants
|
—
|
SECONDARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: Data were not analyzed because gene expression of the endometrium could not be performed due to poor quality of biopsy samples and poor recruitment in the study.
A list of genes based on gene expression profiling carried out on RNA extracted from endometrial tissue. The expression of mRNA in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent. Participants with poor response: 5 mature oocytes or less; participants with good response: more than 8 mature oocytes.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®Population: Data for histological pattern of the endometrium in participants with good or poor response to Gonal-f were not summarized because the number of participants in each group with respect to ovarian response were too low.
Participants with each histological pattern of endometrium were analyzed. Histological patterns included: Proliferative phase (described as the endometrial on the first two weeks after the menstruation \[or before ovulation\]), Early secretory phase (first step of the secretory phase, located at the Day 16-18 of the cycle), Intermediate secretory phase (secretory phase located at the Day 20-22 of the cycle and describes endometrial closer to the implantation phase). Participants with poor response: 5 mature oocytes or less; participants with good response: more than 8 mature oocytes.
Outcome measures
Outcome data not reported
Adverse Events
Gonal-f® + Ovitrelle® (Long Agonist Protocol)
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gonal-f® + Ovitrelle® (Long Agonist Protocol)
n=13 participants at risk
Participants received 150 International Units (IU) per day of recombinant human follicle stimulating hormone (r-hFSH, Gonal-f®) subcutaneously (sc) starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 microgram (mcg) recombinant human chorionic gonadotropin alfa (r-hCG alfa, Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles greater than \[\>\] 16 millimeter \[mm\], and with estradiol \[E2\] \>1 microgram per liter \[mcg/L\]). To prevent premature ovulation in participants undergoing a controlled ovarian stimulation (COS), 0.1 milligram (mg) GnRH agonist daily was started after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) as per summary of product characteristics (SmPC), in long agonist protocol.
|
Gonal-f® + Ovitrelle® (Multi-dose Antagonist Protocol)
n=11 participants at risk
Participants received 150 IU per day of r-hFSH (Gonal-f®) sc starting from Day 2 of menstrual cycle until follicles were recruited and developed. Ovulation triggering was performed with a single dose of 250 mcg r-hCG alfa (Ovitrelle®) sc, as soon as follicles satisfied the criteria for follicular development (at least 3 follicles \>16 mm). To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily was started from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.
|
|---|---|---|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
7.7%
1/13 • Up to 15 days after the last Investigational Medicinal Product (IMP) administration or early termination
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerge or worsen relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/11 • Up to 15 days after the last Investigational Medicinal Product (IMP) administration or early termination
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerge or worsen relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/13 • Up to 15 days after the last Investigational Medicinal Product (IMP) administration or early termination
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerge or worsen relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
|
9.1%
1/11 • Up to 15 days after the last Investigational Medicinal Product (IMP) administration or early termination
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerge or worsen relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13 • Up to 15 days after the last Investigational Medicinal Product (IMP) administration or early termination
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerge or worsen relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
|
0.00%
0/11 • Up to 15 days after the last Investigational Medicinal Product (IMP) administration or early termination
An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerge or worsen relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER