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

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

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.

Study Overview

• Status: Completed
• Conditions: Assisted Reproduction
• Intervention / Treatment: Drug: combined oral contaraceptive pills; Drug: recombinant FSH; Drug: Urinaru gonadotropin; Drug: GnRH antagonist; Drug: Human chorionic gonadotropin; Procedure: Ovum pick up; Procedure: Embryo transfer; Drug: natural Progesterone; Drug: GnRH agonist

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 12151
    • Kasr Alainy medical school

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: single trigger; 80 women who received triggering in the form of 10,000 IU of HCG intramuscular injection	Drug: combined oral contaraceptive pills; 1 tablet daily between days 5 and 25 of the cycle before stimulation; Other Names: Gynera; Drug: recombinant FSH; 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; Drug: Urinaru gonadotropin; 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; Drug: GnRH antagonist; 0.25 subcutaneously daily from the day in which the leading follicles reached 12 mm till the day of triggering; Other Names: Cetrotide; Drug: Human chorionic gonadotropin; 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; Procedure: Ovum pick up; 34 hours after triggering under the guidance of transvaginal ultrasound; Procedure: Embryo transfer; Transabdominal ultrasound guided embryo transfer was done 3 days after oocyte retrieval using Labotect semirigid catheter; Drug: natural Progesterone; 400 mg twice daily per vagina; Other Names: Prontogest
Active Comparator: Dual trigger; 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; 1 tablet daily between days 5 and 25 of the cycle before stimulation; Other Names: Gynera; Drug: recombinant FSH; 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; Drug: Urinaru gonadotropin; 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; Drug: GnRH antagonist; 0.25 subcutaneously daily from the day in which the leading follicles reached 12 mm till the day of triggering; Other Names: Cetrotide; Drug: Human chorionic gonadotropin; 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; Procedure: Ovum pick up; 34 hours after triggering under the guidance of transvaginal ultrasound; Procedure: Embryo transfer; Transabdominal ultrasound guided embryo transfer was done 3 days after oocyte retrieval using Labotect semirigid catheter; Drug: natural Progesterone; 400 mg twice daily per vagina; Other Names: Prontogest; Drug: GnRH agonist; 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; Other Names: triptorelin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cairo University

Publications and helpful links

General Publications

• Maged AM, Ragab MA, Shohayeb A, Saber W, Ekladious S, Hussein EA, El-Mazny A, Hany A. Comparative study between single versus dual trigger for poor responders in GnRH-antagonist ICSI cycles: A randomized controlled study. Int J Gynaecol Obstet. 2021 Mar;152(3):395-400. doi: 10.1002/ijgo.13405. Epub 2020 Oct 22.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2016
• Primary Completion (Actual): June 2, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 2, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Luteolytic Agents; Progestins; Triptorelin Pamoate; Chorionic Gonadotropin; Cetrorelix; Progesterone; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: 58

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No