EXpression PRofile Endometrium Samples Study

NCT01210144 | Terminated Phase 4 Results

• 2 other identifiers: IMP 283642007-003938-41
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase IV, pilot, open-label, national, multi-centric study planned to determine the gene expression profiles and histologic changes of the endometrial tissue before and after stimulation with Gonal-f®. Physicians are interested in identifying predictive genetic markers in assisted reproductive technologies (ART) in addition to the clinical predictive factors already known. Among those predictive factors, the state of the endometrium is considered as an important implantation determining factor for which pharmacogenomic research is of great interest. The direct benefits of this study will be to know whether the endometrial gene expression profile is modified in response to stimulation treatment and have an impact or not on the endometrial tissue receptivity. The potential benefits of this study could be to assess the therapy optimization based on individual treatment response and gene expression profile compared to group treatment response in infertile women and prediction of response to therapy based on gene expression profiling before and after Gonal-f® stimulation in infertile women.

Conditions

In Vitro Fertilization

Keywords

Infertility; Gonal-f; gene expression; Assisted Reproductive Technologies; Follitropin alfa; endometrium

Outcome Measures

Primary Outcomes (2)

• Gene Expression of the Endometrium Following 1 Cycle With Gonal-f®

  A list of genes based on gene expression profiling carried out on ribonucleic acid (RNA) extracted from endometrial tissue. The expression of messenger ribonucleic acid (mRNA) in endometrial tissue was measured by using microarrays such as the Affymetrix® GeneChip HG-U133 plus 2.0 array or equivalent.

  Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®

• Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f®

  Participants with each histological pattern of endometrium were analyzed. Histological patterns included: Proliferative phase (described as the endometrial on the first two weeks after the menstruation \[or before ovulation\]), Early secretory phase (first step of the secretory phase, located at the Day 16-18 of the cycle) and Intermediate secretory phase (secretory phase located at the Day 20-22 of the cycle and describes endometrial closer to the implantation phase).

  Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®

Secondary Outcomes (7)

• Gene Expression of the Endometrium in Participants With or Without Blastocyst Transfer

  Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®

• Gene Expression of the Endometrium Following 1 Cycle With Gonal-f® in Participants Having Undergone Agonist or Antagonist Protocol

  Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®

• Number of Participants With a Specific Histological Pattern of the Endometrium Following 1 Cycle With Gonal-f® and Having Undergone Agonist or Antagonist Protocol

  Day of Oocyte Retrieval (36 +/- 2 hours post r-hCG administration) after COS by Gonal-f®

• Gene Expression in Participants Without Blastocyst Transfer

  Day 5 or 6 (window of implantation) after Oocyte Retrieval

• Number of Participants With a Specific Histological Pattern of the Endometrium in Participants Without Blastocyst Transfer

  Day 5 or 6 (window of implantation) after Oocyte Retrieval

Study Arms (2)

Gonal-f® + Ovitrelle® + Long Agonist Protocol

EXPERIMENTAL

Drug: Gonal -f® [r-hFSH]; Drug: Ovitrelle® [r-hCG alfa]; Drug: Gonadotropin-releasing hormone (GnRH) Agonist

Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol

EXPERIMENTAL

Drug: Gonal -f® [r-hFSH]; Drug: Ovitrelle® [r-hCG alfa]; Drug: Gonadotropin-releasing hormone (GnRH) Antagonist

Interventions

Gonal -f® [r-hFSH] DRUG

On Day 2 of the menstrual cycle, a pre-defined fixed dose of 150 International Units (IU) per day of recombinant human follicle stimulating hormone (r-hFSH) will be administered until follicles are recruited and developed.

Also known as: Gonal-f®, Follitropin Alfa

Gonal-f® + Ovitrelle® + Long Agonist Protocol; Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol

Ovitrelle® [r-hCG alfa] DRUG

Ovulation triggering will be performed using a single injection of 250 microgram (mcg) recombinant human chorionic gonadotropin (r-hCG) alfa as soon as follicles satisfy the criteria for follicular development, that is at least 3 follicles greater than (\>) 16 millimeter (mm), and with estradiol (E2) \> 1 microgram per liter (mcg/L) if gonadotropin releasing hormone (GnRH) agonist will be used.

Also known as: Ovitrelle®, Ovidrel®

Gonal-f® + Ovitrelle® + Long Agonist Protocol; Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol

Gonadotropin-releasing hormone (GnRH) Agonist DRUG

To prevent premature ovulation in participants undergoing a controlled ovarian stimulation (COS), 0.1 milligram (mg) GnRH agonist daily will be given after endometrial biopsy, 7 days after the peak day of luteinizing hormone (Day LH + 7) as per summary of product characteristics (SmPC), in long agonist protocol.

Gonal-f® + Ovitrelle® + Long Agonist Protocol

Gonadotropin-releasing hormone (GnRH) Antagonist DRUG

To prevent premature ovulation in participants undergoing a COS, 0.25 mg GnRH antagonist daily will be given from Day 6 of Gonal-f® stimulation treatment as per SmPC, in multi-dose antagonist protocol.

Gonal-f® + Ovitrelle® + Multi-dose Antagonist Protocol

Eligibility Criteria

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

You may qualify if:

• Infertile female or infertile male. Infertile female means diverse infertility etiologies including tubal disease (excepting hydrosalpinx) and so called "unexplained infertility"
• Suitable for ART: IVF undergoing first or second attempt, ICSI undergoing first attempt
• years old, body mass index (BMI) less than or equal to 27 kilogram per square meter (kg/m\^2), non smoking
• Normal ovarian status (FSH less than or equal to 9.45 International Units per Liter \[IU/L\], E2 less than or equal to 40 picogram per milliliter \[pg/mL\], Anti-Mullerian Hormone \[AMH\] greater than or equal to 18 picomole/liter \[pmol/L\]; within normal laboratory range values, normal ovaries sonography and uterine echo doppler)
• No history of active genito-urinary infection
• Normal thyroid function (or adequate substitution for at least 3 months)
• Negative cervical papanicolaou test within the last 12 months prior to study entry
• No hormonal therapy, including gonadotropins and progesterone, for at least 2 months prior to the study
• In couple with female infertility, male partner with normal sperm or moderate oligoasthenospermia in semen analysis and negative semen culture less than 6 months at the study entry
• Willingness and ability to comply with the protocol for the duration of the study
• Written informed consent prior to any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care

You may not qualify if:

• Subjects with ongoing pregnancy, any pregnancy within 3 months prior to study entry, or any contraindication to pregnancy or carrying pregnancy to term
• Subjects with uterine malformation, diethylstilbestrol syndrome, adenomyosis, synechia
• Subjects with history of previous OHSS
• Subjects with polycystic ovarian syndrome (PCOS) according to the revised Rotterdam Consensus 2003
• Subjects with extra-uterine pregnancy during the previous 3 months
• Subjects with recurrent miscarriages (early or late, more than 2)
• Subjects having known infection with human immunodeficiency virus (HIV), hepatitis B or C virus, for subject or partner
• Subjects with abnormal gynecological bleeding of undetermined origin
• Subjects with history of major thromboembolic disease
• Subjects with endometriosis
• Subjects with presence or history of malignant tumors and related treatment
• Subjects with clinically significant systemic disease or clinically significant abnormal hematology, chemistry, or urinalysis results at screening
• Subjects with known allergy or hypersensitivity to Gonal-f® or Ovitrelle®
• Subjects with any active substance abuse or history of drug, medication or alcohol abuse in the past 5 years
• Subjects who have participated within 3 months prior to study entry in another clinical trial

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono S.A.S, France: collaborator

Study Sites (1)

Research Site

Paris, France

Location

MeSH Terms

Conditions

Infertility

Interventions

Glycoprotein Hormones, alpha Subunit; follitropin alfa; Chorionic Gonadotropin; Ovidrel; Gonadotropin-Releasing Hormone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Luteinizing Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Thyrotropin; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Neuropeptides; Oligopeptides; Nerve Tissue Proteins

Limitations and Caveats

Gene expression of the endometrium could not be analyzed due to poor quality of biopsy samples (poor mRNA quality) and poor recruitment in the study.

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2010
• First Posted: September 28, 2010
• Study Start: August 1, 2008
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: December 27, 2013
• Results First Posted: November 14, 2012

Record last verified: 2013-12

Locations

FR (1)