Unrecognized ConditionNCT06546774
The Effect of Melatonin Supplementation on Cumulus Cells and IVF Outcomes
A study testing Melatonin in people with Unrecognized Condition, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.
Trial summary
This study investigates the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. Read more about this study
- Who is it for?
- Ages 35 to 45 years, women only
- Conditions the study is for
- Unrecognized Condition
- What is being tested?
- Melatonin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 May 2021to 31 Dec 2025
- 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 35 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Age 35-45 years
- BMI 18-30 kg/m2
- planning to undergo IVF cycles
Who cannot join
- Primary ovarian insufficiency
- history of oophorectomy
- receiving oocyte donation
- Chromosome anomaly
- Congenital uterine anomaly
- Severe intrauterine adhesion
- Malignancy
- Using hormone therapy or supplements in recent 3 months
Trial locations and contacts
1 site in 1 country.
Kuan-Hao Tsui contact
Taiwan1 site, 1 recruiting
- Recruiting
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
Kaohsiung City, 886
Kuan-Hao Tsui, +886-7-3422121, lllee23@vghks.gov.tw
Li-Te Lin
About this study
Official title: The Effect of Melatonin Supplementation on Cumulus Cells and Reproductive Outcomes in Older Women Undergoing IVF Cycles
This study investigates the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. Cumulus cells will be collected after oocyte retrieval, and IVF outcomes will be assessed.
Read the detailed description
Aging in female reproductive cells, particularly cumulus granulosa cells, is associated with various dysfunctions that compromise fertility. Melatonin, a hormone primarily produced by the pineal gland, is renowned for its multifaceted roles in regulating physiological processes, including sleep-wake cycles, immune function, and antioxidative defense. Melatonin's antioxidant action is mediated through direct scavenging of free radicals, upregulation of antioxidant enzymes, and improvement of mitochondrial efficiency. These properties make melatonin a promising candidate for mitigating the adverse effects of aging on cellular function. This study aims to explore the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. In the control group, patients will proceed directly to IVF cycles without melatonin supplementation. Cumulus cells will be collected after oocyte retrieval, and gene expression will be measured. Additionally, clinical pregnancy rate, live birth rate, and miscarriage rate between the two groups will be evaluated.
- Conditions
- Unrecognized Condition
- Being tested
- Melatonin
- Keywords
- Melatonin, Cumulus cells, In vitro fertilization, Old women, Infertility
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDietary supplement
In the study group, patients will receive melatonin supplementation for at least two months prior to IVF cycles
| Study group | Role | What they receive |
|---|---|---|
| Melatonin group | Experimental | Patients received melatonin supplementation for at least a two-month period prior to IVF cycles Receives: Dietary Supplement: Melatonin |
| Control group | No intervention | Patients did not receive melatonin supplementation and proceeded directly to IVF cycles |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate (%)
a viable infant after 24 weeks of gestation
Measured: through study completion, an average of 4 year
oxygen consumption rate of mitochodria (%)
to assess mitocondrial function in cumulus cells
Measured: through study completion, an average of 4 year
mRNA levels of cumulus cell genes
to assess cumulus cells gene expression analysis
Measured: through study completion, an average of 4 year
Secondary outcomes (3)
Clinical pregnancy rate (%)
the presence of a fetal heartbeat detected via transvaginal sonography at 6-7 weeks of gestation
Measured: through study completion, an average of 4 year
Ongoing pregnancy rate (%)
the continuation of the pregnancy beyond 12 weeks of gestation
Measured: through study completion, an average of 4 year
Amount of ATP production (moles/min) of mitochodria
to assess mitocondrial function in cumulus cells
Measured: through study completion, an average of 4 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start1 May 2021
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Unrecognized ConditionStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kaohsiung Veterans General Hospital.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li-Te Lin, Kaohsiung Veterans General Hospital.
- Investigators
- Kuan-Hao Tsui, Study director, Kaohsiung Veterans General Hospital.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06546774
- Sponsor's protocol ID
- KSVGH21-CT1-43
- Status last verified
- Aug 2024
- First submitted
- 1 Aug 2024
- Last updated
- 13 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kandil OM, Rahman SMAE, Ali RS, Ismail EA, Ibrahim NM. Effect of melatonin on developmental competence, mitochondrial distribution, and intensity of fresh and vitrified/thawed in vitro matured buffalo oocytes. Reprod Biol Endocrinol. 2024 Apr 5;22(1):39. doi: 10.1186/s12958-024-01209-7.
PubMed 38580962Navid S, Saadatian Z, Talebi A. Assessment of developmental rate of mouse embryos yielded from in vitro fertilization of the oocyte with treatment of melatonin and vitamin C simultaneously. BMC Womens Health. 2023 Oct 4;23(1):525. doi: 10.1186/s12905-023-02673-w.
PubMed 37794412He C, Wang J, Zhang Z, Yang M, Li Y, Tian X, Ma T, Tao J, Zhu K, Song Y, Ji P, Liu G. Mitochondria Synthesize Melatonin to Ameliorate Its Function and Improve Mice Oocyte's Quality under in Vitro Conditions. Int J Mol Sci. 2016 Jun 14;17(6):939. doi: 10.3390/ijms17060939.
PubMed 27314334Yang M, Tao J, Chai M, Wu H, Wang J, Li G, He C, Xie L, Ji P, Dai Y, Yang L, Liu G. Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results. Molecules. 2017 Nov 27;22(12):2059. doi: 10.3390/molecules22122059.
PubMed 29186876Zhao XM, Wang N, Hao HS, Li CY, Zhao YH, Yan CL, Wang HY, Du WH, Wang D, Liu Y, Pang YW, Zhu HB. Melatonin improves the fertilization capacity and developmental ability of bovine oocytes by regulating cytoplasmic maturation events. J Pineal Res. 2018 Jan;64(1). doi: 10.1111/jpi.12445. Epub 2017 Oct 11.
PubMed 28833478Dai X, Lu Y, Zhang M, Miao Y, Zhou C, Cui Z, Xiong B. Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and Juno to promote sperm binding and fusion. Hum Reprod. 2017 Mar 1;32(3):598-606. doi: 10.1093/humrep/dew362.
PubMed 28137755Miao Y, Zhou C, Bai Q, Cui Z, ShiYang X, Lu Y, Zhang M, Dai X, Xiong B. The protective role of melatonin in porcine oocyte meiotic failure caused by the exposure to benzo(a)pyrene. Hum Reprod. 2018 Jan 1;33(1):116-127. doi: 10.1093/humrep/dex331.
PubMed 29112712Zhang M, Dai X, Lu Y, Miao Y, Zhou C, Cui Z, Liu H, Xiong B. Melatonin protects oocyte quality from Bisphenol A-induced deterioration in the mouse. J Pineal Res. 2017 Apr;62(3). doi: 10.1111/jpi.12396. Epub 2017 Mar 1.
PubMed 28178360Wei D, Zhang C, Xie J, Song X, Yin B, Liu Q, Hu L, Hao H, Geng J, Wang P. Supplementation with low concentrations of melatonin improves nuclear maturation of human oocytes in vitro. J Assist Reprod Genet. 2013 Jul;30(7):933-8. doi: 10.1007/s10815-013-0021-2. Epub 2013 Jun 6.
PubMed 23737216Bao Z, Li G, Wang R, Xue S, Zeng Y, Deng S. Melatonin Improves Quality of Repeated-Poor and Frozen-Thawed Embryos in Human, a Prospective Clinical Trial. Front Endocrinol (Lausanne). 2022 May 13;13:853999. doi: 10.3389/fendo.2022.853999. eCollection 2022.
PubMed 35634513Nishihara T, Hashimoto S, Ito K, Nakaoka Y, Matsumoto K, Hosoi Y, Morimoto Y. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014 May;30(5):359-62. doi: 10.3109/09513590.2013.879856. Epub 2014 Mar 17.
PubMed 24628045Eryilmaz OG, Devran A, Sarikaya E, Aksakal FN, Mollamahmutoglu L, Cicek N. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J Assist Reprod Genet. 2011 Sep;28(9):815-20. doi: 10.1007/s10815-011-9604-y. Epub 2011 Jul 12.
PubMed 21748445Batioglu AS, Sahin U, Gurlek B, Ozturk N, Unsal E. The efficacy of melatonin administration on oocyte quality. Gynecol Endocrinol. 2012 Feb;28(2):91-3. doi: 10.3109/09513590.2011.589925. Epub 2011 Jul 20.
PubMed 21770829Jahromi BN, Sadeghi S, Alipour S, Parsanezhad ME, Alamdarloo SM. Effect of Melatonin on the Outcome of Assisted Reproductive Technique Cycles in Women with Diminished Ovarian Reserve: A Double-Blinded Randomized Clinical Trial. Iran J Med Sci. 2017 Jan;42(1):73-78.
PubMed 28293053Hu KL, Ye X, Wang S, Zhang D. Melatonin Application in Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of Randomized Trials. Front Endocrinol (Lausanne). 2020 Mar 27;11:160. doi: 10.3389/fendo.2020.00160. eCollection 2020.
PubMed 32292388
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Melatonin Supplementation on Cumulus Cells and Reproductive Outcomes in Older Women Undergoing IVF Cycles
- ClinicalTrials.gov ID
- NCT06546774
- Acronym / sponsor ID
- KSVGH21-CT1-43
- Conditions
- Unrecognized Condition
- Keywords
- Melatonin, Cumulus cells, In vitro fertilization, Old women, Infertility
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Kaohsiung Veterans General Hospital.University, hospital or other
- Study start
- 1 May 2021 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 9 Aug 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.
This study investigates the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. Cumulus cells will be collected after oocyte retrieval, and IVF outcomes will be assessed.
Detailed description
Aging in female reproductive cells, particularly cumulus granulosa cells, is associated with various dysfunctions that compromise fertility. Melatonin, a hormone primarily produced by the pineal gland, is renowned for its multifaceted roles in regulating physiological processes, including sleep-wake cycles, immune function, and antioxidative defense. Melatonin's antioxidant action is mediated through direct scavenging of free radicals, upregulation of antioxidant enzymes, and improvement of mitochondrial efficiency. These properties make melatonin a promising candidate for mitigating the adverse effects of aging on cellular function. This study aims to explore the effects of melatonin supplementation on cumulus cell gene expression and in vitro fertilization (IVF) outcomes in women over 35 years old. In the study group, patients will receive melatonin supplementation for at least two months prior to their IVF cycles. In the control group, patients will proceed directly to IVF cycles without melatonin supplementation. Cumulus cells will be collected after oocyte retrieval, and gene expression will be measured. Additionally, clinical pregnancy rate, live birth rate, and miscarriage rate between the two groups will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin group | Experimental | Dietary Supplement: MelatoninPatients received melatonin supplementation for at least a two-month period prior to IVF cycles |
| Control group | No intervention | –Patients did not receive melatonin supplementation and proceeded directly to IVF cycles |
Who may qualify
- Ages
- 35 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age 35-45 years
- BMI 18-30 kg/m2
- planning to undergo IVF cycles
Key exclusion criteria (8 listed)
- Primary ovarian insufficiency
- history of oophorectomy
- receiving oocyte donation
- Chromosome anomaly
- Congenital uterine anomaly
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 |
|---|---|---|
| MelatoninIn the study group, patients will receive melatonin supplementation for at least two months prior to IVF cycles | Dietary supplement | Melatonin group |
Primary outcome
Live birth rate (%)
Time frame: through study completion, an average of 4 year
a viable infant after 24 weeks of gestation
oxygen consumption rate of mitochodria (%)
Time frame: through study completion, an average of 4 year
to assess mitocondrial function in cumulus cells
mRNA levels of cumulus cell genes
Time frame: through study completion, an average of 4 year
to assess cumulus cells gene expression analysis
3 secondary outcomes
Clinical pregnancy rate (%)
Time frame: through study completion, an average of 4 year
Ongoing pregnancy rate (%)
Time frame: through study completion, an average of 4 year
Amount of ATP production (moles/min) of mitochodria
Time frame: through study completion, an average of 4 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Results publication: PubMed 38580962Kandil OM, Rahman SMAE, Ali RS, Ismail EA, Ibrahim NM. Effect of melatonin on developmental competence, mitochondrial distribution, and intensity of fresh and vitrified/thawed in vitro matured buffalo oocytes. Reprod Biol Endocrinol. 2024 Apr 5;22(1):39. doi: 10.1186/s12958-024-01209-7.
- Results publication: PubMed 37794412Navid S, Saadatian Z, Talebi A. Assessment of developmental rate of mouse embryos yielded from in vitro fertilization of the oocyte with treatment of melatonin and vitamin C simultaneously. BMC Womens Health. 2023 Oct 4;23(1):525. doi: 10.1186/s12905-023-02673-w.
- Results publication: PubMed 27314334He C, Wang J, Zhang Z, Yang M, Li Y, Tian X, Ma T, Tao J, Zhu K, Song Y, Ji P, Liu G. Mitochondria Synthesize Melatonin to Ameliorate Its Function and Improve Mice Oocyte's Quality under in Vitro Conditions. Int J Mol Sci. 2016 Jun 14;17(6):939. doi: 10.3390/ijms17060939.
- Results publication: PubMed 29186876Yang M, Tao J, Chai M, Wu H, Wang J, Li G, He C, Xie L, Ji P, Dai Y, Yang L, Liu G. Melatonin Improves the Quality of Inferior Bovine Oocytes and Promoted Their Subsequent IVF Embryo Development: Mechanisms and Results. Molecules. 2017 Nov 27;22(12):2059. doi: 10.3390/molecules22122059.
- Results publication: PubMed 28833478Zhao XM, Wang N, Hao HS, Li CY, Zhao YH, Yan CL, Wang HY, Du WH, Wang D, Liu Y, Pang YW, Zhu HB. Melatonin improves the fertilization capacity and developmental ability of bovine oocytes by regulating cytoplasmic maturation events. J Pineal Res. 2018 Jan;64(1). doi: 10.1111/jpi.12445. Epub 2017 Oct 11.
- Results publication: PubMed 28137755Dai X, Lu Y, Zhang M, Miao Y, Zhou C, Cui Z, Xiong B. Melatonin improves the fertilization ability of post-ovulatory aged mouse oocytes by stabilizing ovastacin and Juno to promote sperm binding and fusion. Hum Reprod. 2017 Mar 1;32(3):598-606. doi: 10.1093/humrep/dew362.
- Results publication: PubMed 29112712Miao Y, Zhou C, Bai Q, Cui Z, ShiYang X, Lu Y, Zhang M, Dai X, Xiong B. The protective role of melatonin in porcine oocyte meiotic failure caused by the exposure to benzo(a)pyrene. Hum Reprod. 2018 Jan 1;33(1):116-127. doi: 10.1093/humrep/dex331.
- Results publication: PubMed 28178360Zhang M, Dai X, Lu Y, Miao Y, Zhou C, Cui Z, Liu H, Xiong B. Melatonin protects oocyte quality from Bisphenol A-induced deterioration in the mouse. J Pineal Res. 2017 Apr;62(3). doi: 10.1111/jpi.12396. Epub 2017 Mar 1.
- Results publication: PubMed 23737216Wei D, Zhang C, Xie J, Song X, Yin B, Liu Q, Hu L, Hao H, Geng J, Wang P. Supplementation with low concentrations of melatonin improves nuclear maturation of human oocytes in vitro. J Assist Reprod Genet. 2013 Jul;30(7):933-8. doi: 10.1007/s10815-013-0021-2. Epub 2013 Jun 6.
- Results publication: PubMed 35634513Bao Z, Li G, Wang R, Xue S, Zeng Y, Deng S. Melatonin Improves Quality of Repeated-Poor and Frozen-Thawed Embryos in Human, a Prospective Clinical Trial. Front Endocrinol (Lausanne). 2022 May 13;13:853999. doi: 10.3389/fendo.2022.853999. eCollection 2022.
- Results publication: PubMed 24628045Nishihara T, Hashimoto S, Ito K, Nakaoka Y, Matsumoto K, Hosoi Y, Morimoto Y. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014 May;30(5):359-62. doi: 10.3109/09513590.2013.879856. Epub 2014 Mar 17.
- Results publication: PubMed 21748445Eryilmaz OG, Devran A, Sarikaya E, Aksakal FN, Mollamahmutoglu L, Cicek N. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J Assist Reprod Genet. 2011 Sep;28(9):815-20. doi: 10.1007/s10815-011-9604-y. Epub 2011 Jul 12.
- Individual participant dataSharing planned: No
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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.
Kuan-Hao Tsui contact
Kuan-Hao Tsui study director
Kaohsiung Veterans General Hospital.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Melatonin in people with Unrecognized Condition, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.
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 3 inclusion and 8 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 13 Aug 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 Taiwan. 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?
Contact Li-Te Lin (+88673464027, litelin1982@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate (%) (time frame: through study completion, an average of 4 year). The study lists 3 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 NCT06546774, which also lists 16 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 13 Aug 2024.