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

• ClinicalTrials.gov Identifier: NCT03484611
• Recruitment Status: Unknown
• First Posted: April 2, 2018
• Last Update Posted: April 2, 2018
• Sponsor: Cairo University
• Information provided by (Responsible Party): Ahmed Maged, Cairo University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Invitro Fertilizaion	Drug: GnRH antagonist; Drug: Gonadotropins; Drug: Human chorionic gonadotropin; Procedure: Embryo transfer; Drug: Progesterone	Not Applicable

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 179 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Prediction of Metaphase II Oocytes According to Different Levels of Serum AMH in Poor Responders Using the Antagonist Protocol
• Actual Study Start Date: January 2013
• Estimated Primary Completion Date: April 2018
• Estimated Study Completion Date: April 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: AMH < 0.3 ng/ml; Poor ovarian responders according to ESHRE consensus with serum AMH < 0,3 ng/ml	Drug: 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; Other Name: cetrorelix; Drug: Gonadotropins; started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU; Other Name: Human menopausal gonadotropin; Drug: Human chorionic gonadotropin; 10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more; Other Name: HCG; Procedure: 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); Drug: Progesterone; vaginal prontogest 400 mg twice daily
Active Comparator: 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	Drug: 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; Other Name: cetrorelix; Drug: Gonadotropins; started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU; Other Name: Human menopausal gonadotropin; Drug: Human chorionic gonadotropin; 10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more; Other Name: HCG; Procedure: 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); Drug: Progesterone; vaginal prontogest 400 mg twice daily
Active Comparator: AMH > 0.7 to 1 ng/ml; Poor ovarian responders according to ESHRE consensus with serum AMH 0.7 to 1 ng/ml	Drug: 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; Other Name: cetrorelix; Drug: Gonadotropins; started on day 2 of the menstrual cycle until the day of HCG administration(choriomon,IBSA10000IU)with starting dose 300IU to 450IU; Other Name: Human menopausal gonadotropin; Drug: Human chorionic gonadotropin; 10000 IU is given to induce final oocytes maturation when at least 2 follicles reached 14 mm or more; Other Name: HCG; Procedure: 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); Drug: Progesterone; vaginal prontogest 400 mg twice daily

Outcome Measures

Primary Outcome Measures :

1. Number of the retrieved oocytes [ Time Frame: 34 hours after HCG injection ]
   number of oocytes retrieved 34 hours after HCG injection

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Ahmed Maged, MD; +2001005227404; prof.ahmedmaged@gmail.com

Contact: Radwa Fahmy, MD; radwafahmi@yahoo.com

Locations

Egypt

Kasr Alainy medical school; Recruiting

Cairo, Egypt, 12111

Contact: Ahmed Maged, MD 01005227404 prof.ahmedmaged@gmail.com

Sponsors and Collaborators

Cairo University

Investigators

• Principal Investigator: Ahmed Maged, MD; professor

More Information

• Responsible Party: Ahmed Maged, professor, Cairo University
• ClinicalTrials.gov Identifier: NCT03484611
• Other Study ID Numbers: 35
• First Posted: April 2, 2018
• Last Update Posted: April 2, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:

Chorionic Gonadotropin; Cetrorelix; Menotropins; Progesterone; Progestins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Hormone Antagonists