Endometrial Luteal Phase Characteristics and Luteal Phase Support in Controlled Ovarian Stimulation Protocols With GnRH Antagonists:Focusing on MicroRNA

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01510054
Recruitment Status : Withdrawn
First Posted : January 13, 2012
Last Update Posted : April 3, 2015
Information provided by (Responsible Party):
Yulian Zhao, Johns Hopkins University

Brief Summary:

MiRNAs are single-stranded small non-coding RNAs that act on specific mRNAs to regulate the gene expression. Studies have suggested that miRNAs influence cellular activities in the uterus, including cell differentiation and embryo implantation.

In assisted reproductive cycles, controlled ovarian stimulation (COS) results in supraphysiological steroid levels and is associated with very low luteinizing hormone concentration during the luteal phase, the peri-implantation and implantation period. Luteal phase support, administration of medication aimed at supporting the implantation process, has been a routine practice in in vitro fertilization (IVF) clinics. Luteal phase support with steroid hormone has been found to improve pregnancy rates when human menopausal gonadotropins were used in conjunction with GnRH agonists for ovarian stimulation and IVF. Reports on effect of steroid supplementation in GnRH antagonist protocols are limited.

The proposed project is an extension of our previous study on Endometrial Luteal Phase Characteristics and Luteal Phase Support in Controlled Ovarian Hyperstimulation Protocols with Gonadotropin Releasing Hormone Antagonists. The significance of this study is based on the importance of luteal phase endometrial after COS for the process of implantation. The availability of oocycte donors in assisted reproduction technology programs offers a unique opportunity to study the impact of different stimulation protocols on the quality of the luteal phase. In addition, the oocyte donor model may allow us to evaluate the impact of different luteal support protocols directly on the endometrial preparation by histological as well as biochemical markers.

Study design: Study subjects underwent ovarian stimulation according to a gonadotropin/GnRH antagonist protocol. All donors had a baseline measurement of serum follicle stimulating hormone (FSH) and estradiol levels on the second day of their menstrual cycles. Provided serum FSH levels were less than 10mIU/ml and E2 levels were less than 60pg/ml, ovarian stimulation was initiated with recombinant FSH. The daily dose was adjusted according to follicular development by serial transvaginal ultrasound and serum E2 response. A daily evening dose of ganirelix acetate was initiated on the 6th day of stimulation and continued through the day of human chorionic gonadotropin administration. When at least three follicles reached a mean diameter of 18mm, ovulation was triggered with a single dose of Human chorionic gonadotropin (hCG). Sonographically guided transvaginal oocyte retrieval was performed 34-36 hours after the hCG administration.

Thirty endometrial biopsies from oocyte donors on their COS cycles will be used for the study. Study subjects have been randomized into 4 groups. Grp 1: day of retrieval, did not receive any luteal-phase support, which serves as base line; grp2: 3, 5 and 10 days after retrieval with no luteal phase support, which serves as control; grp3: 3, 5 and 10 days after retrieval, luteal phase support with progesterone in the form of vaginal suppositories starting from the day after retrieval; grp4: daily oral dose of 2 mg 17β-estradiol in addition to the micronized progesterone. Immediately after the endometrial biopsy all specimens were stored in liquid nitrogen tanks at -196°C.

Total RNA will be isolated and microarray will be performed using an Illumina miRNA expression panel. Array results will be compiled and analyzed focusing on the following aspects: the target genes of prominent miRNAs, miRNA profile in relation to target gene pathways; miRNA expression profile in relation to endometrial dating and status; effect of luteal phase support on miRNA expression after ovarian stimulation. Minimum of 3 miRNA arrays will be run for each sample for the purpose of statistical analysis. A total of 30 arrays will be needed for all samples from all groups.

In this study, the investigators pose three questions: 1) How many and what types of miRNAs are in the endometrium during ovarian stimulation? This is to identify miRNAs and associated target genes that are relevant for endometrium receptivity; 2) Do levels of miRNA expression change during the luteal phase, or during the window of implantation? This is to examine the dynamics of miRNAs that are associated with remodeling process of endometrium; and 3) Do luteal phase support alter miRNA expression in the luteal phase? This is to investigate the steroid effect on miRNA regulation. The investigators hypothesize that many critical genes related to implantation are regulated by miRNAs. This research effort will potentially advance our knowledge of endometrial characteristics after COS and the impact of sex steroid supplementation. Overall the study should help better understand the genetic control of implantation. Completion of this study may also provide measurable scientific evidence and useful information for the management of IVF cycles.

Condition or disease
Controlled Ovarian Stimulation

Study Type : Observational
Actual Enrollment : 0 participants
Official Title: Endometrial Luteal Phase Characteristics and Luteal Phase Support in Controlled Ovarian Stimulation Protocols With Gonadotropin Releasing Hormone (GnRH) Antagonists: Focusing on MicroRNA Identification and Expression
Study Start Date : July 2002
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

steroid support
Endometrial biopsies from subjects of with or without luteal phase steroid support will be compared for miRNA expression

Primary Outcome Measures :
  1. microRNA expression in human endometrium after IVF [ Time Frame: Up to 4 years are estimated for the study to be completed including all measures. ]

Biospecimen Retention:   Samples With DNA
endometril tissue

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 31 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
30 emdometrial biopsy from oocyte donors

Inclusion Criteria:

  • 21 to 31 years of age female who underwent a standard screening protocol for oocyte donation, in accordance with the recommendations of the American Society for Reproductive Medicine.

Exclusion Criteria:

  • Women with a body mass index exceeding 28 kg/m2,
  • history of:

    • pelvic inflammatory disease,
    • sexually transmitted diseases,
    • reproductive tract pathology, or
    • other systemic diseases or conditions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01510054

United States, Maryland
Johns Hopkins at Green Spring Station
Lutherville, Maryland, United States, 21093
Sponsors and Collaborators
Johns Hopkins University
Principal Investigator: Yulian Zhao, Ph.D Johns Hopkins University

Responsible Party: Yulian Zhao, Associate Professor, Johns Hopkins University Identifier: NCT01510054     History of Changes
Other Study ID Numbers: IISP 38749
First Posted: January 13, 2012    Key Record Dates
Last Update Posted: April 3, 2015
Last Verified: April 2015

Keywords provided by Yulian Zhao, Johns Hopkins University:
miRNA in endometrium