Comparative Study Between Single Versus Dual Trigger for Poor Responders in GnRH-antagonist ICSI Cycles

Study Overview
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Brief Summary
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All participants started with a combination of recombinant FSH 300 U and urinary Gn 150 U from the 2nd day of the cycle then the dose was adjusted according to the ovarian response From day 6 of the cycle, follow up using transvaginal ultrasound was done either daily or on alternate days according to the ovarian response. When the leading follicle reached 12 mm, GnRH antagonist was started using Cetrotide 0.25 subcutaneously daily till the day of triggering. Triggering was done when at least 3 follicles larger than 14 mm and at least one of them reached a mean diameter of 17 mm or more. At the day of triggering, women were randomized into 2 groups. Group I (single trigger group) that included 80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection. Group II (Dual trigger group) that included 80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection in addition to GnRH agonist triptorelin 0.2 mg subcutaneously. Ovum pickup was done 34 hours after triggering under the guidance of transvaginal ultrasound. ISM1 culture medium was used for oocyte collection and embryo culture. Transabdominal ultrasound guided embryo transfer was done 3 days after oocyte retrieval using Labotect semirigid catheter by the same expert operator Cycle cancellation was done if day 9 folliculometry revealed less than 2 mature follicles, no oocytes were retrieved or if fertilization failed Luteal phase support was started in all women on the day of oocyte retrieval and continued till the day of serum β-hCG assessment (done 14 days after ET) through administration of 400 mg of natural Progesterone twice daily per vagina . In women with +ve serum β-hCG (> 5 mIU/ml), transvaginal ultrasound evaluation was done 4 weeks after ET to confirm the presence and number of intrauterine gestational sacs.

Detailed Description
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All participants started with a combination of recombinant FSH 300 U and urinary Gn 150 U from the 2nd day of the cycle then the dose was adjusted according to the ovarian response evaluated by transvaginal ultrasound and serum E2. Delayed start From day 6 of the cycle, follow up using transvaginal ultrasound was done either daily or on alternate days according to the ovarian response. Ultrasound follow up reported number and size of follicles in each ovary and the endometrial thickness and pattern. When the leading follicle reached 12 mm, GnRH antagonist was started using Cetrotide 0.25 subcutaneously daily till the day of triggering. Triggering was done when at least 3 follicles larger than 14 mm and at least one of them reached a mean diameter of 17 mm or more. At the day of triggering, women were randomized into 2 groups. Group I (single trigger group) that included 80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection. Group II (Dual trigger group) that included 80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection in addition to GnRH agonist triptorelin 0.2 mg subcutaneously. Ovum pickup was done 34 hours after triggering under the guidance of transvaginal ultrasound. ISM1 culture medium was used for oocyte collection and embryo culture. Transabdominal ultrasound guided embryo transfer was done 3 days after oocyte retrieval using Labotect semirigid catheter by the same expert operator Cycle cancellation was done if day 9 folliculometry revealed less than 2 mature follicles, no oocytes were retrieved or if fertilization failed Luteal phase support was started in all women on the day of oocyte retrieval and continued till the day of serum β-hCG assessment (done 14 days after ET) through administration of 400 mg of natural Progesterone twice daily per vagina . In women with +ve serum β-hCG (> 5 mIU/ml), transvaginal ultrasound evaluation was done 4 weeks after ET to confirm the presence and number of intrauterine gestational sacs.

Official Title
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Comparative Study Between Single Versus Dual Trigger for Poor Responders in GnRH-antagonist ICSI Cycles. A Randomized Controlled Study

Conditions
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Assisted Reproduction

Intervention / Treatment
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* Drug: combined oral contaraceptive pills
* Drug: recombinant FSH
* Drug: Urinaru gonadotropin
* Drug: GnRH antagonist
* Drug: Human chorionic gonadotropin
* Drug: GnRH agonist
* Procedure: Ovum pick up
* Procedure: Embryo transfer
* Drug: natural Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women with poor ovarian response candidate for ICSI women with spontaneous normal menstrual cycle normal uterine cavity Exclusion Criteria: women with ovarian cysts endometriosis hydrosalpinx endocrinological disorders as hyperprolactinemia, thyroid or adrenal disorders. Couples with azospermic male partner those with severe uncontrolled medical or metabolic disorders

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: single trigger<br>80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection | Drug: combined oral contaraceptive pills<br>* 1 tablet daily between days 5 and 25 of the cycle before stimulation<br>* Other names: Gynera;Drug: recombinant FSH<br>* 300 U from the 2nd day of the cycle then the dose was adjusted according to the ovarian response evaluated by transvaginal ultrasound and serum E2<br>Drug: Urinaru gonadotropin<br>* 150 U from the 2nd day of the cycle then the dose was adjusted according to the ovarian response evaluated by transvaginal ultrasound and serum E2<br>Drug: GnRH antagonist<br>* 0.25 subcutaneously daily from the day in which the leading follicles reached 12 mm till the day of triggering<br>* Other names: Cetrotide;Drug: Human chorionic gonadotropin<br>* 10,000 IU intramuscular when at least 3 follicles larger than 14 mm and at least one of them reached a mean diameter of 17 mm or more<br>Procedure: Ovum pick up<br>* 34 hours after triggering under the guidance of transvaginal ultrasound<br>Procedure: Embryo transfer<br>* Transabdominal ultrasound guided embryo transfer was done 3 days after oocyte retrieval using Labotect semirigid catheter<br>Drug: natural Progesterone<br>* 400 mg twice daily per vagina<br>* Other names: Prontogest;|
| Active Comparator: Dual trigger<br>80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection in addition to GnRH agonist triptorelin 0.2 mg subcutaneously | Drug: combined oral contaraceptive pills<br>* 1 tablet daily between days 5 and 25 of the cycle before stimulation<br>* Other names: Gynera;Drug: recombinant FSH<br>* 300 U from the 2nd day of the cycle then the dose was adjusted according to the ovarian response evaluated by transvaginal ultrasound and serum E2<br>Drug: Urinaru gonadotropin<br>* 150 U from the 2nd day of the cycle then the dose was adjusted according to the ovarian response evaluated by transvaginal ultrasound and serum E2<br>Drug: GnRH antagonist<br>* 0.25 subcutaneously daily from the day in which the leading follicles reached 12 mm till the day of triggering<br>* Other names: Cetrotide;Drug: Human chorionic gonadotropin<br>* 10,000 IU intramuscular when at least 3 follicles larger than 14 mm and at least one of them reached a mean diameter of 17 mm or more<br>Drug: GnRH agonist<br>* 0.2 mg subcutaneously when at least 3 follicles larger than 14 mm and at least one of them reached a mean diameter of 17 mm or more<br>* Other names: triptorelin;Procedure: Ovum pick up<br>* 34 hours after triggering under the guidance of transvaginal ultrasound<br>Procedure: Embryo transfer<br>* Transabdominal ultrasound guided embryo transfer was done 3 days after oocyte retrieval using Labotect semirigid catheter<br>Drug: natural Progesterone<br>* 400 mg twice daily per vagina<br>* Other names: Prontogest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of mature follicular count | number of follicles larger than 14 mm | 10 - 14 days of the cycle |