Long Protocol and Freeze All Embryos vs Antagonist Protocol With Fresh Embryo Transfer in PCOS Patients Undergoing ICSI

• ClinicalTrials.gov Identifier: NCT03118830
• Recruitment Status: Completed
• First Posted: April 18, 2017
• Last Update Posted: November 7, 2017
• Sponsor: Cairo University
• Information provided by (Responsible Party): Ahmed Maged, Cairo University

Study Description

Brief Summary:

Patients will be divided into two groups Group A; patients using long protocol and freeze all embryos Group B; patients using antagonist protocol with fresh embryo transfer Patients will be carefully chosen according to a strict inclusion and exclusion criteria after meticulous revision of patient files.

In the long protocol, daily SC injection of Triptorelin :Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day according to women age, day 3 FSH,AMH and previous gonadotropin response then adjustment of the dose according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.

Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when 2 or more follicles have 18 mm as a mean diameter .

Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg (Cetrotide, Merck Serono, Darmstadt, Germany) started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l . Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done.

Condition or disease	Intervention/treatment	Phase
Invitro Fertilization	Drug: Triptorelin; Drug: cetrorelix; Drug: Recombinant Follicle Stimulating Hormone	Phase 4

Detailed Description:

Patients will be divided into two groups Group A; patients using long protocol and freeze all embryos Group B; patients using antagonist protocol with fresh embryo transfer Patients will be carefully chosen according to a strict inclusion and exclusion criteria after meticulous revision of patient files.

In the long protocol, daily SC injection of Triptorelin :Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day according to women age, day 3 FSH,AMH and previous gonadotropin response then adjustment of the dose according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.

Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when 2 or more follicles have 18 mm as a mean diameter .

Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg (Cetrotide, Merck Serono, Darmstadt, Germany) started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l . Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done.

Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no adequate follicular growth (<3 mature follicles),if no oocytes were retrieved on ovum pick up,or if failure of fertilization occurred. If signs of early OHSS were observed at 3rd day of ovum pickup ,cancellation of ET was done with elective embryo cryopreservation as it may end with life-threatening OHSS . ET was cancelled also if any criteria of hospital admission was found

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long Protocol and Freeze All Embryos vs Antagonist Protocol With Fresh Embryo Transfer in PCOS Patients Undergoing ICSI
• Actual Study Start Date: April 21, 2017
• Actual Primary Completion Date: November 1, 2017
• Actual Study Completion Date: November 3, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Long GnRH agonist; daily SC injection of Triptorelin :Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l with either HMG or rFSH in a starting dose of 150-300 IU/day	Drug: Triptorelin; daily SC injection of Triptorelin 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering.; Other Name: Decapeptyl; Drug: Recombinant Follicle Stimulating Hormone; Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done.; Other Name: Gonal-f
Active Comparator: GnRH antagonist; Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l. Daily sc rFSH injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done	Drug: cetrorelix; Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l .; Other Name: Cetrotide; Drug: Recombinant Follicle Stimulating Hormone; Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done.; Other Name: Gonal-f

Outcome Measures

Primary Outcome Measures :

1. clinical pregnancy rate [ Time Frame: 4 weeks after embryo transfer ]
   The detection of fetal cardiac activity within a gestational sac on ultrasonography examinationenlargement (<12 cm in average diameter), ascitis in moderate form and clinical evidence of ascites and/or hydrothorax, haemoconcentration and significant ovarian enlargement (>12 cm in average diameter)

Secondary Outcome Measures :

1. chemical pregnancy rate [ Time Frame: 14 days after embryo transfer ]
   POSITIVE pregnancy testing of HCG exceeding 50 mIU
2. abortion rate [ Time Frame: 12 weeks of gestational age ]
   termination of pregnancy before 12 weeks of gestational age
3. Ovarian hyperstimulation syndrome [ Time Frame: 7 days after HCG administration ]
   evaluated by the British fertility society criteria, the Canadian Fertility and Andrology Society ( CFAS) and the Society of obstetrics and Gynecology of Canada (SOGC); [Mild OHSS; Abdominal bloating, Mild abdominal pain, Ovarian size usually < 8 cm. Moderate OHSS; Moderate abdominal pain, Nausea with/without vomiting, Ultrasound evidence of ascites and Ovarian size usually 8-12 cm. Severe OHSS; Clinical ascites (occasionally pleural effusion), Oliguria, Hemoconcentration with hematocrit (> 45%), Hypoproteinemia and Ovarian size usually > 12 cm. Critical OHSS; Tense ascites or large pleural effusion, Hematocrit (> 55%) White cell count > 25 000/L, anuria, Thromboembolism or Acute respiratory distress syndrome
4. Late Ovarian hyperstimulation syndrome [ Time Frame: 12 to 17 days following HCG administration ]
   OHSS manifestation 12 to 17 days following HCG administration

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 39 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. PCOS diagnosed by Roterdam criteria
2. Protocol used for ovulation induction either long procol with freeze all embryos vs antagonist with fresh embryo transfer
3. BMI less than 30
4. ALL patients receiving adjuvant drugs for prevention of OHSS in the form of metformin, cabergoline as well as prophylactic hysteril , low dose asprin and LMW heparin following oocyte retrieval on a routine basis

Exclusion criteria;

1. PCOS on long protocol with fresh embryo transfer and those on antagonist protocol with freezing all embryo
2. BMI more than 30
3. PCOS patients not given adjuvant drugs in prophylaxis of OHSS
4. Antagonist cases receiving agonist as trigger instead of HCG
5. PCOS receiving more than 5000 IU HCG as trigger
6. PCOS undergoing costing during ovulation induction
7. PCOS with known medial problems as diabetes or hypertension

Contacts and Locations

Locations

Egypt

Ahmed Maged

Cairo, Egypt, 12151

Sponsors and Collaborators

Cairo University

Investigators

• Principal Investigator: Ahmed Maged, MD; Kasr Alainy medical school

More Information

• Responsible Party: Ahmed Maged, Professor, Cairo University
• ClinicalTrials.gov Identifier: NCT03118830
• Other Study ID Numbers: 164
• First Posted: April 18, 2017
• Last Update Posted: November 7, 2017
• Last Verified: November 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Triptorelin Pamoate; Cetrorelix; Hormones; Follicle Stimulating Hormone; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Fertility Agents, Female; Fertility Agents; Hormone Antagonists