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

Invitro Fertilization Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03118830
• Other study ID #: 164
• Status: Completed
• Phase: Phase 4
• First received: April 3, 2017
• Last updated: November 3, 2017
• Start date: April 21, 2017
• Est. completion date: November 3, 2017

Study information

• Verified date: November 2017
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 204
• Est. completion date: November 3, 2017
• Est. primary completion date: November 1, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Invitro Fertilization

Intervention

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.
• 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 .
• 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.

Locations

Country	Name	City	State
Egypt	Ahmed Maged	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	clinical pregnancy rate	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)	4 weeks after embryo transfer
Secondary	chemical pregnancy rate	POSITIVE pregnancy testing of HCG exceeding 50 mIU	14 days after embryo transfer
Secondary	abortion rate	termination of pregnancy before 12 weeks of gestational age	12 weeks of gestational age
Secondary	Ovarian hyperstimulation syndrome	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	7 days after HCG administration
Secondary	Late Ovarian hyperstimulation syndrome	OHSS manifestation 12 to 17 days following HCG administration	12 to 17 days following HCG administration