Random-start Ovarian Stimulation in Egg-donors (ROSE) | NCT02821819

Random-start Ovarian Stimulation in Egg-donors (ROSE) | NCT02821819 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Random start ovarian stimulation	Experimental	Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at luteinizing hormone (LH) peak +3,+5,+7,+9 or +11. They will receive urinary follicle stimulating hormone (FSH) 150-225 International units / daily (IU/d) and five days later the gonadotropin-releasing hormone (GnRH) antagonist: cetrorelix acetate 0,25 mg/d will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later. Interventions: Random start ovarian stimulation Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonists: Cetrorelix 0,25 mg/d GnRH agonist for triggering: Triptorelin 0,2 mg single dose	Other: Random start ovarian stimulation Drug: Gonadotrophins Drug: GnRH antagonist Drug: GnRH agonist

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Random start ovarian stimulation	Other	Egg-donors will start ovarian stimulation randomly at different moments throughout the menstrual cycle.	Random start ovarian stimulation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Mature Eggs	When collected, eggs retain numerous cells (granulosa or cumulus cells) surrounding the oocyte; this structure is termed as the cumulus oocyte complex (COC). Few hours later (2-4 hs), the oocyte is denuded from these cumulus cells, allowing for a clearer observation of the maturity status (presence or absence of a metaphase II) of the oocyte. The percentage of mature eggs represents the proportion resulting from dividing the total number of COCs collected by the number of metaphase II oocytes and multiplied by 100.	Up to 24 hours from the oocyte collection

Measure	Description	Time Frame
Fertilization Rate	Percentage of properly fertilized eggs after microinjection (ICSI) method	24 hours after day of oocyte collection

Contacts/Locations Module

Name	Affiliation	Role
Juan C Castillo, Md. PhD.	Instituto Bernabeu	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Instituto Bernabeu		Alicante		03016	Spain

Label	URL
Setting	View source
Reference	View source

Arm/Group Information

ID	Title	Description
FG000	Random Start Ovarian Stimulation	Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at luteinizing hormone (LH) peak +3,+5,+7,+9 or +11. They will receive urinary follicle stimulating hormone (FSH) 150-225 International units / daily (IU/d) and five days later the gonadotropin-releasing hormone (GnRH) antagonist will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later. Interventions: Random start ovarian stimulation Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonists: Cetrorelix 0,25 mg/d GnRH agonist for triggering: Triptorelin 0,2 mg single dose Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonist: Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation GnRH agonist: GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00015 subjects
COMPLETED		FG00014 subjects
NOT COMPLETED		FG0001 subjects

Type	Comment	Reasons
Protocol Violation		FG0001 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Random Start Ovarian Stimulation	Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at LH peak +3,+5,+7,+9 or +11. They will receive urinary FSH 150-225 IU/d and five days later cetrorelix acetate 0,25 mg/d will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later. Interventions: Random start ovarian stimulation Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonists: Cetrorelix 0,25 mg/d GnRH agonist for triggering: Triptorelin 0,2 mg single dose Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonist: Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation GnRH agonist: GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Mature Eggs

When collected, eggs retain numerous cells (granulosa or cumulus cells) surrounding the oocyte; this structure is termed as the cumulus oocyte complex (COC). Few hours later (2-4 hs), the oocyte is denuded from these cumulus cells, allowing for a clearer observation of the maturity status (presence or absence of a metaphase II) of the oocyte. The percentage of mature eggs represents the proportion resulting from dividing the total number of COCs collected by the number of metaphase II oocytes and multiplied by 100.

Posted

Mean

Standard Deviation

Percentage of mature eggs

Up to 24 hours from the oocyte collection

ID	Title	Description
OG000	Random Start Ovarian Stimulation	Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at LH peak +3,+5,+7,+9 or +11. They will receive urinary FSH 150-225 IU/d and five days later cetrorelix acetate 0,25 mg/d will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later. Interventions: Random start ovarian stimulation Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonists: Cetrorelix 0,25 mg/d GnRH agonist for triggering: Triptorelin 0,2 mg single dose Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonist: Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation GnRH agonist: GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Random Start Ovarian Stimulation	Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at LH peak +3,+5,+7,+9 or +11. They will receive urinary FSH 150-225 IU/d and five days later cetrorelix acetate 0,25 mg/d will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later. Interventions: Random start ovarian stimulation Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonists: Cetrorelix 0,25 mg/d GnRH agonist for triggering: Triptorelin 0,2 mg single dose Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonist: Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation GnRH agonist: GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Dr. Juan Carlos Castillo	Instituto Bernabeu	+34650562634		jcastillo@institutobernabeu.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 3, 2019	Feb 3, 2019	Prot_SAP_000.pdf

ID	Term
D007246	Infertility

ID	Term
D000091662	Genital Diseases
D000091642	Urogenital Diseases

Intervention Browse Module

ID	Term
D010062	Ovulation Induction
D006062	Gonadotropins
C092464	LHRH, Ac-Nal(1)-Cpa(2)-Trp(3)-Arg(6)-Ala(10)-
D007987	Gonadotropin-Releasing Hormone

ID	Term
D027724	Reproductive Techniques, Assisted
D012099	Reproductive Techniques
D013812	Therapeutics
D008919	Investigative Techniques

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000	The sample size was calculated assuming a non-inferiority margin of 5 eggs and a standard deviation (SD) of 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60).	t-test, 1 sided		0.8	a priori threshold for statistical significance: <0.05	Mean Difference (Final Values)	18	Standard Deviation	8.1	1-Sided								Non-Inferiority	The sample size was calculated assuming a non-inferiority margin of 5 eggs SD 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60).	Since the number of collected eggs constitutes the main outcome of the study, the sample size was calculated assuming a non-inferiority margin of 5 eggs with an standard deviation of 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60). Statistical analysis was performed using t-student test for continuous variables and chi-square test for categorical parameters. A P value of <.05 was considered significant.
OG000	The sample size was calculated assuming a non-inferiority margin of 5 eggs SD 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60). Statistical analysis used t-student test for continuous variables and chi-square test for categorical parameters.	Chi-squared		0.8	a priori threshold for statistical significance: <0.05	Mean Difference (Final Values)	82			2-Sided								Non-Inferiority	The sample size was calculated assuming a non-inferiority margin of 5 eggs SD 6.7. A unilateral alpha level of 0.05 was stablished. With the aim to show that the difference in the mean number of collected eggs will not exceed 5, a statistical power of 80% required 30 patients per group (1:1 allocation, total sample: 60). Statistical analysis used t-student test for continuous variables and chi-square test for categorical parameters.

Secondary

Fertilization Rate

Percentage of properly fertilized eggs after microinjection (ICSI) method

Posted

Median

Standard Deviation

Percentage of properly fertilized eggs

24 hours after day of oocyte collection

ID	Title	Description
OG000	Random Start Ovarian Stimulation	Egg-donors will be assigned to random start ovarian stimulation: During follicular phase starting at day 5,7,9,11 or 13 of the menstrual cycle and during luteal phase at LH peak +3,+5,+7,+9 or +11. They will receive urinary FSH 150-225 IU/d and five days later cetrorelix acetate 0,25 mg/d will be added until achieving criteria for receiving triptorelin 0,2 mg to induce final follicular maturation. Egg collection will take place 36 hours later. Interventions: Random start ovarian stimulation Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonists: Cetrorelix 0,25 mg/d GnRH agonist for triggering: Triptorelin 0,2 mg single dose Gonadotrophins: Urinary FSH 150-225 IU/d GnRH antagonist: Cetrorelix acetate 0,25 mg/d starting five days after ovarian stimulation GnRH agonist: GnRH agonist triggering with triptorelin 0,2 mg for final follicular maturation.

Units	Counts
Participants	OG00014

Title

Denominators