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

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.

Study Overview

• Status: Unknown
• Conditions: Invitro Fertilizaion
• Intervention / Treatment: Drug: GnRH antagonist; Drug: Gonadotropins; Drug: Human chorionic gonadotropin; Procedure: Embryo transfer; Drug: Progesterone

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 Type: Interventional
• Enrollment (Anticipated): 179
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Radwa Fahmy, MD; Email: radwafahmi@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt, 12111
    • Recruiting
    • Kasr Alainy medical school

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of the retrieved oocytes	number of oocytes retrieved 34 hours after HCG injection	34 hours after HCG injection

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 2, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Progestins; Chorionic Gonadotropin; Cetrorelix; Menotropins; Progesterone
• Other Study ID Numbers: 35

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No