Controlled Ovarian StimulationNCT01510054
Endometrial Luteal Phase Characteristics and Luteal Phase Support in Controlled Ovarian Stimulation Protocols With GnRH Antagonists:Focusing on MicroRNA
An observational study of Controlled Ovarian Stimulation, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 31 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Controlled Ovarian Stimulation
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2002to Nov 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 31 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: 30 emdometrial biopsy from oocyte donors
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins at Green Spring Station
Lutherville, Maryland, 21093
About this study
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
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.
Read more
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.
- Conditions
- Controlled Ovarian Stimulation
- Keywords
- miRNA in endometrium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| steroid support | Endometrial biopsies from subjects of with or without luteal phase steroid support will be compared for miRNA expression |
What is being measured
The primary outcome is the main question the study is designed to answer.
microRNA expression in human endometrium after IVF
Measured: Up to 4 years are estimated for the study to be completed including all measures.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2012 (estimated)
- Study startJul 2002
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Controlled Ovarian StimulationStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yulian Zhao, Ph.D, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01510054
- Sponsor's protocol ID
- IISP 38749
- Status last verified
- Jul 2025
- First submitted
- 22 Dec 2011
- Last updated
- 23 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01510054
- Acronym / sponsor ID
- IISP 38749
- Conditions
- Controlled Ovarian Stimulation
- Keywords
- miRNA in endometrium
- Study type
- Observational
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Jul 2002
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 13 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| steroid support | – | –Endometrial biopsies from subjects of with or without luteal phase steroid support will be compared for miRNA expression |
Who may qualify
- Ages
- 21 to 31 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- 30 emdometrial biopsy from oocyte donors
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (6 listed)
- Women with a body mass index exceeding 28 kg/m2,
- history of:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
microRNA expression in human endometrium after IVF
Time frame: Up to 4 years are estimated for the study to be completed including all measures.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yulian Zhao, Ph.D principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Controlled Ovarian Stimulation, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
microRNA expression in human endometrium after IVF (time frame: Up to 4 years are estimated for the study to be completed including all measures.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2025.