Clinical trial NCT03118830: Long Protocol and Freeze All Embryos vs Antagonist Protocol With Fresh Embryo Transfer in PCOS Patients Undergoing ICSI
Official title: Long Protocol and Freeze All Embryos vs Antagonist Protocol With Fresh Embryo Transfer in PCOS Patients Undergoing ICSI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Invitro Fertilization
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2017-04-18
Enrollment: 204
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: clinical pregnancy rate
timeFrame: 4 weeks after embryo transfer
Secondary outcomes:
measure: chemical pregnancy rate
timeFrame: 14 days after embryo transfer
measure: abortion rate
timeFrame: 12 weeks of gestational age
measure: Ovarian hyperstimulation syndrome
timeFrame: 7 days after HCG administration
measure: Late Ovarian hyperstimulation syndrome
timeFrame: 12 to 17 days following HCG administration
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ahmed Maged
Study officials:
affiliation: Kasr Alainy medical school
name: Ahmed Maged, MD
role: PRINCIPAL_INVESTIGATOR
References: