Increased Oocyte DeathNCT06315777
GREM1, HAS2 and PTGS2 Gene Expression Following the in Vitro Maturation (IVM)
A study testing cumulus cell oocytes complex (COC) among women with poor ovarian reserve in people with Increased Oocyte Death and in Vitro Maturation, run by National University of Malaysia at 1 site in Malaysia.
Trial summary
Poor ovarian reserve (POR) is an adverse prognostic factor for In-Vitro Fertilization (IVF) success. Numerous established data showed low live birth rates per IVF cycle; 6 to 10%, including the usage of In-Vitro Maturation (IVM). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Increased Oocyte Death, in Vitro Maturation, GREM1 Gene Mutation
- What is being tested?
- cumulus cell oocytes complex (COC) among women with poor ovarian reserve
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteMalaysia
- Study dates
- 1 Jul 2021to 31 Jul 2024
- Phase
- Interventional
- 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 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- women underwent IVF with normal and Poor ovarian reserve based on the Bologna criteria( anti-Müllerian hormone (AMH) below 0.5-1.1 ng/ml]).
Who cannot join
- Male factor infertility (to reduce bias for embryo quality factor)
- Not agree to participate.
Trial locations and contacts
1 site in 1 country.
Malaysia1 site, 1 recruiting
- Recruiting
Advanced Reproductive Centre
Kuala Lumpur, Kuala Lumpur, 56000
Muhammad Azrai AA Abu, +60196410944, azraiabu1983@gmail.com
About this study
Official title: Elucidating the GREM1, HAS2 and PTGS2 Gene Expression as Oocytes Development Competency Markers Among Women With Poor Ovarian Reserve (POR) Following the in Vitro Maturation (IVM)
Poor ovarian reserve (POR) is an adverse prognostic factor for In-Vitro Fertilization (IVF) success. Numerous established data showed low live birth rates per IVF cycle; 6 to 10%, including the usage of In-Vitro Maturation (IVM). In Malaysia, POR incidence increases mainly from cancer survival, endometriosis, and autoimmune diseases women; therefore, IVM implementation is paramount. In the molecular level, the low competence oocytes showed a low expression of GREM1, HAS2 and PTGS2 in human cumulus cells, thus leading to poor oocyte quality(OQ). Various IVM media had been formulated to enhance the competency and quality of the oocytes to date. Therefore, our study aims to elucidate the GREM1, HAS2 and PTGS2 gene expression as oocyte developmental competency markers among POR women following IVM and tailored to the IVF outcome.
Read the detailed description
In this study, we will follow up the normal and POR women. The discarded product - cumulus cell will be used in this study for evaluation following the standard IVF cumulus-oocyte-complex denudation. We will develop the In-Vitro Model to assess the expression of GREM1, HAS2, and PTGS2 in normal and POR women first. Subsequently, these gene expressions will be reassessed again via clinical model using IVF-IVM cumulus cell comparing the both groups to elucidate the modifying of oocytes quality following IVM. The cumulus cell RNA will be extracted,and the cDNA will be synthesized and quantitated. The RT-PCR standard curves will be produced, and the concentration range of these genes will be generated and quantified. The OQ, embryo morphology scoring, fertilization rates, and live birth rates will be recorded and compared. We anticipate a higher gene expression associated with good OQ thus better fertilization and live birth rate.
Therefore, this research will understand the impact of IVM in oocytes competency, aiming to improve the fertility rate among POR women in Malaysia.
- Being tested
- cumulus cell oocytes complex (COC) among women with poor ovarian reserve
- Keywords
- cumulus cell, GREM 1 gene expression, HAS 2 gene expression, PTGS 2 gene expression, oocyte quality, in vitro maturation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cumulus cell oocytes complex (COC) among women with poor ovarian reserveGenetic
level of expression of Gremlin-1 (GREM1), Hyaluronic acid synthetase-2 (HAS2), and Prostaglandin-endoperoxide synthase-2 (PTGS2) in cumulus cell oocytes complex (COC) among women with poor ovarian reserve were analyzed
| Study group | Role | What they receive |
|---|---|---|
| normal cumulus cell oocytes complex | Experimental | women with normal ovarian reserve will be utilized and analyse the cumulus cell as a baseline Receives: Genetic: cumulus cell oocytes complex (COC) among women with poor ovarian reserve |
What is being measured
The primary outcome is the main question the study is designed to answer.
normal ovarian reserve
the regulation of Gremlin-1 (GREM1), Hyaluronic acid synthetase-2 (HAS2), and Prostaglandin-endoperoxide synthase-2 (PTGS2) in normal cumulus cell oocytes complex (COC).
Measured: for 1 year duration
poor ovarian reserve
the level of expression of Gremlin-1 (GREM1), Hyaluronic acid synthetase-2 (HAS2), and Prostaglandin-endoperoxide synthase-2 (PTGS2) in cumulus cell oocytes complex (COC) among women with poor ovarian reserve
Measured: for 1 year duration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2024
- Study start1 Jul 2021
- Primary completion1 Jul 2024 (estimated)
- Study completion31 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Increased Oocyte DeathStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University of Malaysia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Azrai Abu, National University of Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06315777
- Sponsor's protocol ID
- FRGS/1/2021/SKK01/UKM/02/1
- Status last verified
- Mar 2024
- First submitted
- 12 Mar 2024
- Last updated
- 18 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rouhollahi Varnosfaderani S, Hajian M, Jafarpour F, Ghazvini Zadegan F, Nasr-Esfahani MH. Granulosa secreted factors improve the developmental competence of cumulus oocyte complexes from small antral follicles in sheep. PLoS One. 2020 Mar 17;15(3):e0229043. doi: 10.1371/journal.pone.0229043. eCollection 2020.
PubMed 32182244Anderson RA, Sciorio R, Kinnell H, Bayne RA, Thong KJ, de Sousa PA, Pickering S. Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy. Reproduction. 2009 Oct;138(4):629-37. doi: 10.1530/REP-09-0144. Epub 2009 Jul 14.
PubMed 19602522McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE, Amato P, Matzuk MM. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod. 2004 Dec;19(12):2869-74. doi: 10.1093/humrep/deh535. Epub 2004 Oct 7.
PubMed 15471935Russell DL, Robker RL. Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum Reprod Update. 2007 May-Jun;13(3):289-312. doi: 10.1093/humupd/dml062. Epub 2007 Jan 22.
PubMed 17242016Demiray SB, Goker ENT, Tavmergen E, Yilmaz O, Calimlioglu N, Soykam HO, Oktem G, Sezerman U. Differential gene expression analysis of human cumulus cells. Clin Exp Reprod Med. 2019 Jun;46(2):76-86. doi: 10.5653/cerm.2019.46.2.76. Epub 2019 Jun 1.
PubMed 31181875Karakaya C, Guzeloglu-Kayisli O, Uyar A, Kallen AN, Babayev E, Bozkurt N, Unsal E, Karabacak O, Seli E. Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells. Fertil Steril. 2015 Jun;103(6):1469-76.e1-3. doi: 10.1016/j.fertnstert.2015.02.035. Epub 2015 Apr 22.
PubMed 25910568
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidating the GREM1, HAS2 and PTGS2 Gene Expression as Oocytes Development Competency Markers Among Women With Poor Ovarian Reserve (POR) Following the in Vitro Maturation (IVM)
- ClinicalTrials.gov ID
- NCT06315777
- Acronym / sponsor ID
- FRGS/1/2021/SKK01/UKM/02/1
- Keywords
- cumulus cell, GREM 1 gene expression, HAS 2 gene expression, PTGS 2 gene expression, oocyte quality, in vitro maturation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National University of MalaysiaUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 1 Jul 2024 (estimated)
- Study completion
- 31 Jul 2024 (estimated)
- First posted
- 18 Mar 2024 (actual)
- 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.
Poor ovarian reserve (POR) is an adverse prognostic factor for In-Vitro Fertilization (IVF) success. Numerous established data showed low live birth rates per IVF cycle; 6 to 10%, including the usage of In-Vitro Maturation (IVM). In Malaysia, POR incidence increases mainly from cancer survival, endometriosis, and autoimmune diseases women; therefore, IVM implementation is paramount. In the molecular level, the low competence oocytes showed a low expression of GREM1, HAS2 and PTGS2 in human cumulus cells, thus leading to poor oocyte quality(OQ). Various IVM media had been formulated to enhance the competency and quality of the oocytes to date. Therefore, our study aims to elucidate the GREM1, HAS2 and PTGS2 gene expression as oocyte developmental competency markers among POR women following IVM and tailored to the IVF outcome.
Detailed description
In this study, we will follow up the normal and POR women. The discarded product - cumulus cell will be used in this study for evaluation following the standard IVF cumulus-oocyte-complex denudation. We will develop the In-Vitro Model to assess the expression of GREM1, HAS2, and PTGS2 in normal and POR women first. Subsequently, these gene expressions will be reassessed again via clinical model using IVF-IVM cumulus cell comparing the both groups to elucidate the modifying of oocytes quality following IVM. The cumulus cell RNA will be extracted,and the cDNA will be synthesized and quantitated. The RT-PCR standard curves will be produced, and the concentration range of these genes will be generated and quantified. The OQ, embryo morphology scoring, fertilization rates, and live birth rates will be recorded and compared. We anticipate a higher gene expression associated with good OQ thus better fertilization and live birth rate.
Therefore, this research will understand the impact of IVM in oocytes competency, aiming to improve the fertility rate among POR women in Malaysia.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| normal cumulus cell oocytes complex | Experimental | Genetic: cumulus cell oocytes complex (COC) among women with poor ovarian reservewomen with normal ovarian reserve will be utilized and analyse the cumulus cell as a baseline |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- women underwent IVF with normal and Poor ovarian reserve based on the Bologna criteria( anti-Müllerian hormone (AMH) below 0.5-1.1 ng/ml]).
Key exclusion criteria (2 listed)
- Male factor infertility (to reduce bias for embryo quality factor)
- Not agree to participate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cumulus cell oocytes complex (COC) among women with poor ovarian reservelevel of expression of Gremlin-1 (GREM1), Hyaluronic acid synthetase-2 (HAS2), and Prostaglandin-endoperoxide synthase-2 (PTGS2) in cumulus cell oocytes complex (COC) among women with poor ovarian reserve were analyzed | Genetic | normal cumulus cell oocytes complex |
Primary outcome
normal ovarian reserve
Time frame: for 1 year duration
the regulation of Gremlin-1 (GREM1), Hyaluronic acid synthetase-2 (HAS2), and Prostaglandin-endoperoxide synthase-2 (PTGS2) in normal cumulus cell oocytes complex (COC).
poor ovarian reserve
Time frame: for 1 year duration
the level of expression of Gremlin-1 (GREM1), Hyaluronic acid synthetase-2 (HAS2), and Prostaglandin-endoperoxide synthase-2 (PTGS2) in cumulus cell oocytes complex (COC) among women with poor ovarian reserve
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- Results publication: PubMed 32182244Rouhollahi Varnosfaderani S, Hajian M, Jafarpour F, Ghazvini Zadegan F, Nasr-Esfahani MH. Granulosa secreted factors improve the developmental competence of cumulus oocyte complexes from small antral follicles in sheep. PLoS One. 2020 Mar 17;15(3):e0229043. doi: 10.1371/journal.pone.0229043. eCollection 2020.
- Results publication: PubMed 19602522Anderson RA, Sciorio R, Kinnell H, Bayne RA, Thong KJ, de Sousa PA, Pickering S. Cumulus gene expression as a predictor of human oocyte fertilisation, embryo development and competence to establish a pregnancy. Reproduction. 2009 Oct;138(4):629-37. doi: 10.1530/REP-09-0144. Epub 2009 Jul 14.
- Results publication: PubMed 15471935McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE, Amato P, Matzuk MM. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod. 2004 Dec;19(12):2869-74. doi: 10.1093/humrep/deh535. Epub 2004 Oct 7.
- Results publication: PubMed 17242016Russell DL, Robker RL. Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum Reprod Update. 2007 May-Jun;13(3):289-312. doi: 10.1093/humupd/dml062. Epub 2007 Jan 22.
- Results publication: PubMed 31181875Demiray SB, Goker ENT, Tavmergen E, Yilmaz O, Calimlioglu N, Soykam HO, Oktem G, Sezerman U. Differential gene expression analysis of human cumulus cells. Clin Exp Reprod Med. 2019 Jun;46(2):76-86. doi: 10.5653/cerm.2019.46.2.76. Epub 2019 Jun 1.
- Results publication: PubMed 25910568Karakaya C, Guzeloglu-Kayisli O, Uyar A, Kallen AN, Babayev E, Bozkurt N, Unsal E, Karabacak O, Seli E. Poor ovarian response in women undergoing in vitro fertilization is associated with altered microRNA expression in cumulus cells. Fertil Steril. 2015 Jun;103(6):1469-76.e1-3. doi: 10.1016/j.fertnstert.2015.02.035. Epub 2015 Apr 22.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing cumulus cell oocytes complex (COC) among women with poor ovarian reserve in people with Increased Oocyte Death and in Vitro Maturation, run by National University of Malaysia at 1 site in Malaysia.
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 2 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: status not confirmed, as of the sponsor's last update on 18 Mar 2024. 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 Malaysia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
normal ovarian reserve (time frame: for 1 year duration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06315777, which also lists 6 linked publications.
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 18 Mar 2024.