Progestin Primed Double Stimulation Protocol Versus Flexi... | NCT04537078

NCT04537078

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

The study will be conducted on 90 infertile women indicated for ICSI with criteria of poor ovarian response defined by Bologna criteria All participants will be informed about the nature of the study and informed consent will be taken from all of them.

Group 1:45 patients will be given the progestin primed double stimulation protocol.

Group 2: 45 patients will be given the flexible GnRh antagonist follicular controlled ovarian stimulations will be done in 2 cycles.

Written informed consents will be obtained from all participants who accept to participate in the research protocol.

Work up:

Complete history taking and full assessment of different infertility factors.
Hormonal investigations
- FSH, LH, E2, Prolactin
- AMH, TSH
Basal transvaginal ultrasound

Clinical and embryological procedures:

Group 1:

I. The follicular phase of the double stimulation protocol

luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week (0.03 mg ethinyl estradiol, gestodene 0.075 mg, Gynera tab, Bayer Pharma AG., Berlin, Germany).
Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts.
Dydrogesterone (Duphaston, Abbott company, Illinois, United states) at 20 mg/day will be started from the first day of the ovulation induction.
Patient response will be monitored by:
1. Transvaginal follicular scanning and the dose of the gonadotropins will be modified according to the response.
2. Serum estradiol.
3. Serum progesterone and LH on the day of triggering.
GnRh agonist triggering (Decapeptyl, Ferring, SAINT-PREX Switzerland) in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter.
Oocyte pickup will be done 36 hours after GnRh administration with precaution of leaving the follicles measuring 11 mm or less.
After the pick-up, oocytes will be denuded. The denuded oocytes are then assessed for nuclear status. Mature oocytes will be used for ICSI.

II. The luteal phase of the double stimulation protocol

Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started the next day after the previous oocyte pickup simultaneously with Dydrogesterone (Duphaston, Abbott company, Illinois, United states) at 20 mg/day.

The rest will be as the follicular phase.

III. Fertilization and embryo quality:

The fertilization check, which will be performed 16 to 20 hours after ICSI. The resultant embryos will be scored, and they will be vitrified for subsequent transfer.

IV. Embryo transfer

- Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets); Bayer, Germany) daily. From Day 10 onwards, endometrium growth will be monitored by transvaginal ultrasound. When endometrial thickness ≥ 7 mm. Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be initiated and Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.

V. Luteal support - Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be continued until pregnancy testing 18 days after embryo transfer. The pregnant cases will continue the luteal support till the 12 weeks of gestation.

Group 2:

VI. The flexible GnRH antagonist protocol controlled ovarian stimulation This controlled ovarian stimulation will be done twice in two different cycles

In each cycle:

luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week (0.03 mg ethinyl estradiol, gestodene 0.075 mg , Gynera tab, Bayer Pharma AG., Berlin, Germany).
Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts.
GnRH antagonist ( Cetrotide , Merck Serono, Darmstadt, Germany) will be given daily as the biggest oocyte reaches size 14 mm.
Patient response will be monitored by:
1. Transvaginal follicular scanning and the dose of the gonadotropins will be modified according to the response.
2. Serum estradiol.
3. Serum progesterone on the day of triggering.
GnRh agonist triggering (Decapeptyl, Ferring, Saint-Prex Switzerland) in a dose of 2 ampules 0.2 mg will be administered when leading follicle >18 mm in diameter. While in the second cycle HCG triggering (Choriomon, IBSA, Lugano, Switzerland) in a dose of 10,000 IU will be administered when the leading follicle >18 mm in diameter.
Oocyte pickup will be done 36 hours after GnRh administration.
After the pick-up, oocytes will be denuded. The denuded oocytes are then assessed for nuclear status. Mature oocytes will be used for ICSI.

VII. Fertilization and embryo quality:

The fertilization check, which will be performed 16 to 20 hours after ICSI. The resultant embryos will be scored.

Embryos of the first cycle will be vitrified while embryos of the second cycle will be freshly transferred unless there is excess for vitrification for subsequent trials of transfer.

VIII. Embryo transfer

- Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be initiated on the day of the oocyte pick up of the second cycle. Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.

IX. Luteal support Progesterone administration (as 800 mg/day vaginal suppositories per day and 100 mg ampule IM every other day) will be continued until pregnancy testing 18 days after embryo transfer. The pregnant cases will continue the luteal support till the 12 weeks of gestation.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
the progestin primed double stimulation group	Active Comparator	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	Drug: Duphaston Drug: Gonadotropin Drug: Decapeptyl Drug: Combined Oral Contraceptive Drug: Cyclo-Progynova Drug: progesterone
the flexible GnRh antagonist	Active Comparator	This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle >18 mm in diameter. While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle >18 mm in diameter. Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Duphaston	Drug	will be used for pituitary suppression in the first arm:20 mg/day will be started from the first day of the ovulation induction in the follicular phase and in the luteal phase will be started the next day after oocyte pickup at 20 mg/day.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
the Number of M2 Oocytes Retrieved	it is the number of M2 oocytes retrieved that were being assessed after denudation	1-2 hours after oocyte retrieval
the Fertilization Rate	percentage transformation of micro injected oocytes into two pronuclei. it is done 16 to 20 hours after microinjection of the oocytes by the sperms	16 to 20 hours after microinjection of the oocytes with the sperms
the Resultant Embryos Number	it is the resultant embryos number counted day 3 or 4 or 5 after fertilization	the embryos number counted day 3 or 4or 5 after fertilization
the Implantation Rate	it is calculated as the number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos at the 6 th week of pregnancy and then multiplied by 100	at the 6 th week of pregnancy
the Clinical Pregnancy Rate.	percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy	at the 6 th weeks of pregnancy

Secondary Outcomes

Measure	Description	Time Frame
the Difference in the Ongoing Pregnancy Rate in Both Protocols.	Assessing the difference in the ongoing pregnancy rate when the pregnancy had completed ≥20 weeks of gestation	At the 20 th week of gestation
the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Days of Controlled Ovarian Hyperstimulation

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Aly A Hussein, Ass.lecturer	Elshatby University hospital	Principal Investigator
Sherif S Gaafar, Professor	Elshatby University hospital	Principal Investigator

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23271957	Background	Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med. 2012;9(12):e1001356. doi: 10.1371/journal.pmed.1001356. Epub 2012 Dec 18.
25362088	Background	Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HW. Can you ever collect too many oocytes? Hum Reprod. 2015 Jan;30(1):81-7. doi: 10.1093/humrep/deu272. Epub 2014 Oct 31.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

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 26, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

Drug: Gonadotropin
Drug: Cetrotide Injectable Product
Drug: Decapeptyl
Drug: Chorionic Gonadotropin
Drug: Combined Oral Contraceptive
Drug: Cyclo-Progynova
Drug: progesterone

the progestin primed double stimulation group

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.
BG001	the Flexible GnRh Antagonist	This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle >18 mm in diameter. While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle >18 mm in diameter. Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00041 BG00142 BG00283

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00034.05± 5 BG00135.48± 6.99 BG00234.77± 6.09

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00041 BG00142 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Egypt

Title	Measurements
	BG00041 BG00142 BG002

duration of infertility

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	BG0005(3 to 6) BG0015(2 to 8) BG002

previous ICSI trials

Number

participants

Title

Denominators

Categories

had no previous ICSI trials

Title	Measurements
	BG00022 BG00126 BG002

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

the Number of M2 Oocytes Retrieved

it is the number of M2 oocytes retrieved that were being assessed after denudation

Posted

Median

Inter-Quartile Range

oocytes

1-2 hours after oocyte retrieval

ID	Title	Description
OG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.
OG001	the Flexible GnRh Antagonist Group	This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle >18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified . While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle >18 mm in diameter. Oocyte pickup will be done 36 hours after GnRh administration . embryos of the second cycle will be freshly transferred unless there is excess so being verified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.

Units	Counts
Participants	OG00041 OG00142

Title

Denominators

Categories

Title	Measurements
	OG0006(3 to 7) OG0014.5(3 to 8)

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 OG001		Wilcoxon (Mann-Whitney)		0.254		Median Difference (Final Values)	1.5			2-Sided								Other

Primary

the Fertilization Rate

percentage transformation of micro injected oocytes into two pronuclei. it is done 16 to 20 hours after microinjection of the oocytes by the sperms

Posted

Median

Inter-Quartile Range

percentage of transformation

16 to 20 hours after microinjection of the oocytes with the sperms

ID	Title	Description
OG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.

Primary

the Resultant Embryos Number

it is the resultant embryos number counted day 3 or 4 or 5 after fertilization

Posted

Median

Inter-Quartile Range

number of embryos

the embryos number counted day 3 or 4or 5 after fertilization

ID	Title	Description
OG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.
OG001

Primary

the Implantation Rate

it is calculated as the number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos at the 6 th week of pregnancy and then multiplied by 100

Posted

Median

Inter-Quartile Range

percentage

at the 6 th week of pregnancy

ID	Title	Description
OG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.

Primary

the Clinical Pregnancy Rate.

percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy

Posted

Number

percentage of participants

at the 6 th weeks of pregnancy

ID	Title	Description
OG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.
OG001

Secondary

the Difference in the Ongoing Pregnancy Rate in Both Protocols.

Assessing the difference in the ongoing pregnancy rate when the pregnancy had completed ≥20 weeks of gestation

Posted

Number

percentage of participants

At the 20 th week of gestation

ID	Title	Description
OG000	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer.Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.
OG001

Secondary

the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Days of Controlled Ovarian Hyperstimulation

the total number of days of the controlled ovarian hyperstimulation in both follicular and luteal phase of the progestin primed double stimulation protocol are studied so as to asses the difference between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Posted

Median

Inter-Quartile Range

number of days

From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation

ID	Title	Description
OG000	the Follicular Phase of the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration. The resultant embryos will be scored, and they will be vitrified for subsequent transfer

Secondary

the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Total Dosage of Gonadotropins Used in the Controlled Ovarian Hyperstimulation

Assessing the difference between the follicular phase and the luteal phase of the progestin primed double stimulation protocol regarding the total dosage of gonadotropins used in the controlled ovarian hyperstimulation so as to the difference between the two phases

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Posted

Median

Inter-Quartile Range

From the first day of ovarian stimulation till the last day of ovarian stimulation in each phase ,the follicular and the luteal, of stimulation

ID	Title	Description
OG000	the Follicular Phase of the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration. The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001

Secondary

the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Number of M2 Oocytes Retrieved

it is the number of M2 oocytes retrieved that were being assessed after denudation so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Posted

Median

Inter-Quartile Range

number of oocytes

1-2 hours after oocyte retrieval

ID	Title	Description
OG000	the Follicular Phase of the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration. The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001	the Luteal Phase of the Progestin Primed Double Stimulation Group

Secondary

the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Fertilization Rate.

percentage of transformation of micro injected oocytes into two pronuclei at 16 -20 hours after microinjection of the oocytes by the sperms so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Posted

Median

Inter-Quartile Range

percentage

16 to 20 hours after microinjection of the oocytes with the sperms

ID	Title	Description
OG000	the Follicular Phase of the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001	the Luteal Phase of the Progestin Primed Double Stimulation Group

Secondary

the Difference Between the Follicular Phase and the Luteal Phase of the Progestin Primed Double Stimulation Protocol Regarding the Resultant Embryos Number

the resultant embryos number are counted day 3 or 4 or 5 after fertilization so as to the difference between the results between the two phases, the follicular phase and the luteal phase of the progestin primed double stimulation protocol

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Posted

Median

Inter-Quartile Range

number of embryos

the embryos number counted day 3 or 4or 5 after fertilization

ID	Title	Description
OG000	the Follicular Phase of the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001	the Luteal Phase of the Progestin Primed Double Stimulation Group

Secondary

Assessing the Difference Between the Follicular Phase of the Progestin Primed Double Stimulation Protocol and the First Round of the Conventional GnRH Antagonist Protocol Regarding the Number of M2 Oocytes Retrieved .

it is the number of M2 oocytes retrieved that were being assessed after denudation.so as to study the effect of the progestin used on the ovarian response in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group

the progestin primed dual stimulation group are subdivided into the follicular phase stimulation and the luteal phase stimulation so as to study the difference between both phases

Posted

Median

Inter-Quartile Range

number of oocytes

1-2 hours after oocyte retrieval

ID	Title	Description
OG000	The Follicular Phase of the Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001	the First Round of the Conventional GnRH Antagonist Group

Secondary

it is percentage transformation of micro injected oocytes into two pronuclei.so as to study the effect of the progestin used on the ovarian response and its results in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group

Posted

Median

Inter-Quartile Range

percentage

16 to 20 hours after microinjection of the oocytes by the sperms

ID	Title	Description
OG000	The Follicular Phase of the Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001	the First Round of the Conventional GnRH Antagonist Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle >18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified

Secondary

it is the number of the resultant embryos counted at day 3 or 4 or 5 after fertilization.so as to study the effect of the progestin used on the ovarian response and the resultant embryos number in poor ovarian responders, we have compared the follicular phase of the dual stimulation group and first follicular wave of the flexible antagonist group

Posted

Mean

Standard Deviation

percentage

at day 3 or 4or 5 after fertilization

ID	Title	Description
OG000	The Follicular Phase of the Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration . The resultant embryos will be scored, and they will be vitrified for subsequent transfer
OG001	the First Round of the Conventional GnRH Antagonist Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle >18 mm in diameter.Oocyte pickup will be done 36 hours after GnRh administration. Embryos of the first cycle will be vitrified

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	the Progestin Primed Double Stimulation Group	luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Duphaston at 20 mg/day will be started from the first day of the ovulation induction.Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering .Then, Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. Starting from the next menstrual cycle Day 3, patients will receive oral estradiol valerate (Cyclo-Progynova (white tablets) daily.When endometrial thickness ≥ 7 mm.Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage.	0	41	0	41	12	41
EG001	the Flexible GnRh Antagonist	This step will be done twice in two different cycles In each cycle: luteal phase priming using combined contraceptive pills from day 21 of the previous cycle for one week by Gynera tab. Controlled ovarian hyper-stimulation using antagonist protocol will be used. Stimulation with 225-375 IU of gonadotropins will be started day 2-3 of menses after vaginal ultrasound confirming the absence of ovarian cysts. Cetrotide ampule will be given daily as the biggest oocyte reaches size 14 mm. Decapeptyl ampules 0.2 mg will be administered when leading follicle >18 mm in diameter. While in the second cycle HCG triggering (Choriomon)in a dose of 10,000 IU will be administered when the leading follicle >18 mm in diameter. Embryo transfer will be scheduled on Day 3, 4 or 5 with maximum number of 3 class A embryos whether of cleavage or blastocyst stage that will be a mixture of the thawed embryos of the first cycle and fresh embryos of the second cycle.	0	42	0	42	10	42

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
nausea and abdominal distention	Gastrointestinal disorders	Systematic Assessment	EG00015 events5 affected41 at risk EG00112 events5 affected42 at risk
pelvic pain	Reproductive system and breast disorders	Systematic Assessment	EG00010 events3 affected41 at risk EG0018 events3 affected42 at risk
headache	Nervous system disorders	Systematic Assessment	EG00010 events4 affected41 at risk EG0015 events2 affected42 at risk

First MCP Posted Date

ID	Term
D007247	Infertility, Female

Ancestor Terms

ID	Term
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases
D007246	Infertility

ID	Term
D004394	Dydrogesterone
D006062	Gonadotropins
D008596	Menotropins
D017329	Triptorelin Pamoate
D006063	Chorionic Gonadotropin
D003277	Contraceptives, Oral, Combined
D011374	Progesterone

Ancestor Terms

ID	Term
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D006065	Gonadotropins, Pituitary
D010908	Pituitary Hormones, Anterior
D010907	Pituitary Hormones
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D001688	Biological Products
D045424	Complex Mixtures
D007987	Gonadotropin-Releasing Hormone
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D009479	Neuropeptides
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins
D010926	Placental Hormones
D011257	Pregnancy Proteins
D004338	Drug Combinations
D004364	Pharmaceutical Preparations
D003276	Contraceptives, Oral
D003271	Contraceptive Agents, Female
D003270	Contraceptive Agents
D012102	Reproductive Control Agents
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D045506	Therapeutic Uses
D011282	Pregnenediones
D011283	Pregnenes
D003339	Corpus Luteum Hormones
D042341	Gonadal Hormones
D045167	Progesterone Congeners
D012739	Gonadal Steroid Hormones

Controlled ovarian hyper-stimulation the next day after the previous oocyte pickup simultaneously with Duphaston. .Decapeptyl in a dose of 2 ampules of 0.2 mg will be administered when leading follicle >18 mm in diameter for triggering.Oocyte pickup will be done 36 hours after GnRh administration The resultant embryos will be scored, and they will be vitrified for subsequent transfer