Poor Ovarian Stimulation Response in In Vitro Fertilization (IVF) Program

NCT02640976 | Completed Early Phase 1 DMC

• 1 other identifier: BC (705)
• Study Type: interventional
• Target: 216
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study is to assess the role of AMH in prediction of poor ovarian response as well as the relation between ESR2 (+1730G\>A) (rs4986938), FSHR p.Thr307Ala (c.919A\>G, rs6165) and FSHR p.Asn680Ser (c.2039A\>G, rs6166) SNPs and the poor response in Egyptian women undergoing IVF procedure. Discovering the genetic variants associated with ovarian response is an important step towards individualized pharmacogenetic protocols of ovarian stimulation.

Conditions

Infertility

Keywords

in vitro fertilization; controlled ovarian hyperstimulation; poor ovarian response; estrogen receptor 2 gene polymorphism; follicle stimulating hormone receptor gene polymorphism; anti-mullerian hormone

Outcome Measures

Primary Outcomes (1)

• number of oocytes collected

  when at least 3 follicles will reach 17 mm in diameter, ovulation will be triggered by a single intra-muscular injection of 10,000 IU of hCG \[Choriomon® 5000 IU ampoules, IBSA institut\]. 36 hours later, oocyte retrieval will be performed and will be guided by transvaginal ultrasound.

  3 weeks from of start of ICSI cycle

Secondary Outcomes (1)

• Detection of the single nucleotide polymorphisms ESR2(+1730G>A) (rs4986938), FSHR p.Thr307Ala (c.919A>G, rs6165) and FSHR p.Asn680Ser (c.2039A>G, rs6166) SNPs will be performed using the TaqMan system by real-time polymerase chain reaction (PCR)

  Within 1 week

Other Outcomes (2)

• Laboratory analysis of basal follicle stimulating hormone level for each individual will be measured by enzyme-linked immunosorbent assay (ELISA)

  Done within 3 months preceeding the ICSI cycle

• Laboratory analysis of anti-mullerian hormone level (AMH) will be measured by ELISA technique for each individual.

  Done within 3 months preceeding the ICSI cycle.

Study Arms (2)

Poor responders

ACTIVE COMPARATOR

This group will include women who underwent IVF/ICSI cycle and produced 4 oocytes or less. intervention: 1. fixed daily morning dose of Human menopausal gonadotrophin (HMG) Merional® intra-muscular injection ,starting on cycle day 2 and will be maintained for 9-11 days according to each individual ovarian response,at a dose of (300 IU). 2. On cycle day 7, the GnRH antagonist Cetrorelix 0.25 mg Cetrotide® will be introduced as daily subcutaneous injections and continued till the day of ovulation triggering. 3. Finally, when at least 3 follicles will reach 17 mm in diameter, ovulation will be triggered by a single intra-muscular injection of 10,000 IU of Human chorionic gonadotrophin (hCG) Choriomon®.

Drug: Human menopausal gonadotrophin (HMG); Drug: GnRH antagonist Cetrorelix; Drug: Human chorionic gonadotrophin (hCG)

Good responders

ACTIVE COMPARATOR

This group will include women who produced (5 or more oocytes) after COH. Intervention: 1. fixed daily morning dose of Human menopausal gonadotrophin (HMG) Merional® intra-muscular injection ,starting on cycle day 2 and will be maintained for 9-11 days according to each individual ovarian response,at a dose of (225 IU) for participants with AMH levels \> 1.5 ng/ml and/or FSH levels ≤ 8 mIU/ml 2. On cycle day 7, the GnRH antagonist Cetrorelix 0.25 mg Cetrotide® will be introduced as daily subcutaneous injections and continued till the day of ovulation triggering. 3. When at least 3 follicles will reach 17 mm in diameter, ovulation will be triggered by a single intra-muscular injection of 10,000 IU of Human chorionic gonadotrophin (hCG) Choriomon®.

Drug: Human menopausal gonadotrophin (HMG); Drug: GnRH antagonist Cetrorelix; Drug: Human chorionic gonadotrophin (hCG)

Interventions

Human menopausal gonadotrophin (HMG) DRUG

\[Merional® 75 IU ampoules, IBSA institut\]

Also known as: Merional®

Good responders; Poor responders

GnRH antagonist Cetrorelix DRUG

\[Cetrotide® 0.25 mg syringes, Merck Serono\]

Also known as: Cetrotide®

Good responders; Poor responders

Human chorionic gonadotrophin (hCG) DRUG

\[Choriomon® 5000 IU ampoules, IBSA institut\]

Also known as: Choriomon®

Good responders; Poor responders

Eligibility Criteria

• Age: 25 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women at or under the age of 35 years.
• Normal thyroid stimulating hormone and prolactin levels.
• Normal ovulatory cycles (25-35 interval days), together with proven patent fallopian tubes at hysterosalpingography or laparoscopy done within six cycles preceding the ICSI cycle.
• Presence of both ovaries with normal findings as assessed by trans-vaginal ultrasound and laparoscopy.
• All male partners had a normal semen analysis according to WHO criteria (WHO, 2010), done within 6 months preceding the ICSI cycle

You may not qualify if:

• Chronic medical disorders such as diabetes.
• Previous inadequate response to ovulation induction.
• Polycystic ovary syndrome.
• Women who performed ovarian surgery and cases of endometriosis diagnosed by laparoscopy or suspected by ultrasound or CA-125 assay.
• Abnormal pelvic pathology or congenital anomalies.

Sponsors & Collaborators

• Cairo University: lead

Related Publications (1)

• Motawi TMK, Rizk SM, Maurice NW, Maged AM, Raslan AN, Sawaf AH. The role of gene polymorphisms and AMH level in prediction of poor ovarian response in Egyptian women undergoing IVF procedure. J Assist Reprod Genet. 2017 Dec;34(12):1659-1666. doi: 10.1007/s10815-017-1013-4. Epub 2017 Aug 19.

  PMID: 28825151 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Menotropins; hMG-IBSA; cetrorelix; Chorionic Gonadotropin

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Biological Products; Complex Mixtures; Placental Hormones; Pregnancy Proteins; Proteins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Demonstrator at faculty of pharmacy Cairo university biochemistry department

Study Record Dates

• First Submitted: December 16, 2015
• First Posted: December 29, 2015
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: August 1, 2015
• Last Updated: December 29, 2015

Record last verified: 2015-12

Data Sharing

• IPD Sharing: Will share