Prediction of Metaphase II Oocytes According to Different Levels of Serum AMH in Poor Responders Using the Antagonist Protocol

NCT ID: NCT03484611

Last Updated: 2018-04-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 179 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2018-04-30

Brief Summary

A multicentric study looked into 179 poor responders who underwent antagonist protocol in ICSI cycles Gonadotrophines is started on day 2 with HMG until the day of HCG administration with starting dose 300IU to 450IU,with no pretreatment with OCPs or progestogens or estrogen.

GNRH antagonist (cetrorelix 0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration Ovarian ultrasound scans were performed using a 5.0-9.0 MHZ multi frequency trans vaginal probe to assess the ovarian response till the mature follicles reach18-20mm when hCG administration 10000 IU is given to induce final oocytes maturation , serum E2 is done on day of HCG trigger.

Trans vaginal ultrasound-guided oocyte retrieval is performed 34-36 hours after hCG injection.

Ultrasound -guided fresh embryo transfer is performed on day 3 or 5 after fertilization.

Progesterone support of luteal phase was commenced on the day of ovum pick up using prontogest 400 mg twice daily.

Detailed Description

A multicentric study looked into 179 poor responders who underwent antagonist protocol in ICSI cycles

Induction of ovulation cycle:

1. Gonadotrophines is started on day 2with HMG(merional, IBSA) ,until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU,with no pretreatment with OCPs or progestogens or estrogen.

2. GNRH antagonist (cetrorelix 0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration

3. Ovarian ultrasound scans were performed using a 5.0-9.0 MHZ multi frequency trans vaginal probe (mindrayDP-5) to assess the ovarian response till the mature follicles reach18-20mm when hCG administration 10000 IU is given to induce final oocytes maturation , serum E2 is done on day of HCG trigger.

4. Trans vaginal ultrasound-guided oocyte retrieval is performed 34-36 hours after hCG injection.

5. Ultrasound -guided fresh embryo transfer is performed on day 3 or 5 after fertilization. . Embryo transfer was performed under abdominal ultrasound guide for proper embryo placement to the mid-uterine cavity. 0ne to three grade 1 or 2 embryos were transferred on day 3 after oocyte retrieval. The quality of the embryos were graded as 1,2,3 (1 being the best and 3 being the worst) based on the number of cells, degree of fragmentation and regularity. Embryo transfer was performed with a Wallace catheter (Smith Medical International Ltd, Hythe, Kent, UK). Progesterone support of luteal phase was commenced on the day of ovum pick up using prontogest 400 mg twice daily (IBSA, institut Biochemique,Switzerland).

Conditions

Invitro Fertilizaion

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

AMH < 0.3 ng/ml

Poor ovarian responders according to ESHRE consensus with serum AMH \< 0,3 ng/ml

Group Type: ACTIVE_COMPARATOR

GnRH antagonist

Intervention Type: DRUG

0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration

Gonadotropins

Intervention Type: DRUG

started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU

Human chorionic gonadotropin

Intervention Type: DRUG

10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more

Embryo transfer

Intervention Type: PROCEDURE

0ne to three grade 1 or 2 embryos were transferred on day 3 after oocyte retrieval. Embryo transfer was performed with a Wallace catheter (Smith Medical International Ltd, Hythe, Kent, UK)

Progesterone

Intervention Type: DRUG

vaginal prontogest 400 mg twice daily

AMH 0.3 to 0.7 ng/ml

Poor ovarian responders according to ESHRE consensus with serum AMH 0.3 to 0.7 ng/ml

Group Type: ACTIVE_COMPARATOR

GnRH antagonist

Intervention Type: DRUG

0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration

Gonadotropins

Intervention Type: DRUG

started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU

Human chorionic gonadotropin

Intervention Type: DRUG

10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more

Embryo transfer

Intervention Type: PROCEDURE

0ne to three grade 1 or 2 embryos were transferred on day 3 after oocyte retrieval. Embryo transfer was performed with a Wallace catheter (Smith Medical International Ltd, Hythe, Kent, UK)

Progesterone

Intervention Type: DRUG

vaginal prontogest 400 mg twice daily

AMH > 0.7 to 1 ng/ml

Poor ovarian responders according to ESHRE consensus with serum AMH 0.7 to 1 ng/ml

Group Type: ACTIVE_COMPARATOR

GnRH antagonist

Intervention Type: DRUG

0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration

Gonadotropins

Intervention Type: DRUG

started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU

Human chorionic gonadotropin

Intervention Type: DRUG

10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more

Embryo transfer

Intervention Type: PROCEDURE

0ne to three grade 1 or 2 embryos were transferred on day 3 after oocyte retrieval. Embryo transfer was performed with a Wallace catheter (Smith Medical International Ltd, Hythe, Kent, UK)

Progesterone

Intervention Type: DRUG

vaginal prontogest 400 mg twice daily

Interventions

GnRH antagonist

0,25mg s.c, cetrotide, serono laboratories, Aubonne Switzerland) is given using flexible protocol, it is given when at least one follicle reaches size 14 mm to prevent premature lutenization ,until the day of hCG administration

Intervention Type: DRUG

Gonadotropins

started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU

Intervention Type: DRUG

Human chorionic gonadotropin

10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more

Intervention Type: DRUG

Embryo transfer

0ne to three grade 1 or 2 embryos were transferred on day 3 after oocyte retrieval. Embryo transfer was performed with a Wallace catheter (Smith Medical International Ltd, Hythe, Kent, UK)

Intervention Type: PROCEDURE

Progesterone

vaginal prontogest 400 mg twice daily

Intervention Type: DRUG

Other Intervention Names

cetrorelix; Human menopausal gonadotropin; HCG

Eligibility Criteria

Inclusion Criteria

• 3- On antagonist protocol 4- Poor responder according to ESHRE consensus; in which at least 2 of the following should be present:
• Advanced maternal age (≥ 40 years old) or any other risk factor
• A previous poor ovarian response (cycles cancelled or ≤ 3 oocytes with a conventional protocol)
• An abnormal ovarian reserve test (ORT); antral follicle count (AFC) < 5-7 follicles or anti-mullerian hormone (AMH) ≤0.5- 1.1 ng/ml NB: In the absence of advanced maternal age or abnormal ORT, two previous episodes of poor ovarian response after maximal stimulation patients are also considered poor responders according to ESHRE consensus.
• Presence and Adequate visualization of both ovaries
• Uterine cavity within normal anatomy

Exclusion Criteria

Any factor which may affect reproductive outcome other than that the patient is a poor responder will be excluded from the study, like:

1. Severe male factor .

2. Uterine factor (eg: fibroid, polyp, Ashermann, .. etc)

3. Immunological disorder (eg: SLE, APS, … etc)

4. Thyroid or adrenal dysfunction

5. Neoplasia (especially: hypothalamic, pit, ovarian)

6. Women diagnosed with PCOS according to Rotterdam criteria

7. Hydrosalpinx that hasn't been surgically removed or ligated. 8 . Untreated hyperprolactinemia 9 . Abnormal bleeding disorder

10.Hepatic or renal dysfunction 11.Hypersenstivity to study medication ( GNRH antagonist) 12.Need to take medication that can influence ovarian stimulation 13.Endometriosis grade 3 or 4 14.Ovarian cyst> 10 cm.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Ahmed Maged

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ahmed Maged, MD

Role: PRINCIPAL_INVESTIGATOR

professor

Locations

Kasr Alainy medical school

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Ahmed Maged, MD

Role: CONTACT

prof.ahmedmaged@gmail.com

+2001005227404

Radwa Fahmy, MD

Role: CONTACT

radwafahmi@yahoo.com

Facility Contacts

Ahmed Maged, MD

Role: primary

prof.ahmedmaged@gmail.com

01005227404

Other Identifiers

35

Identifier Type: -

Identifier Source: org_study_id