Fertilization in VitroNCT03238833
Poor Ovarian Responders Undergoing IVF Using Luteal Ovarian Stimulation Versus Follicular Ovarian Stimulation
A study testing luteal ovarian stimulation and follicular ovarian stimulation in people with Fertilization in Vitro, run by Kaohsiung Veterans General Hospital. at 1 site in Taiwan.
Trial summary
The investigators attempted to compare the clinical outcomes and cumulus genes expression in poor ovarian responders undergoing luteal ovarian stimulation or follicular ovarian stimulation in in vitro fertilization cycles. Read more about this study
- Who is it for?
- Ages 30 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fertilization in Vitro
- What is being tested?
- luteal ovarian stimulation and follicular ovarian stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteTaiwan
- Study dates
- 3 May 2017to 31 Dec 2019
- 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 30 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Poor ovarian responders (PORs) met the Bologna criteria, having at least two of the three following features:
- advanced maternal age (≥ 40 years) or any other risk factor for POR,
- a previous POR (≤ 3 oocytes with a conventional stimulation protocol), and
- an abnormal ovarian reserve test. An abnormal ovarian reserve test was defined as antral follicle count (AFC) < 5 or anti-Müllerian hormone (AMH) < 1 ng/mL in this study.
- Moreover, two episodes of a previous POR after maximal stimulation alone would be sufficient to define a patient as a POR.
Who cannot join
- oophorectomy
- exposure to cytotoxic or pelvic irradiation for malignancy
- taking herbal drugs or other hormonal agents
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital
The investigators attempted to compare the clinical outcomes and cumulus genes expression in poor ovarian responders undergoing luteal ovarian stimulation or follicular ovarian stimulation in in vitro fertilization cycles.
Read the detailed description
Multiple follicular wave theory proposed by Baerwald et al. implied that follicle recruitment may occur in the luteal phase of menstrual cycle. Therefore, luteal phase ovarian stimulation (LPOS) was considered as a potential feasible stimulation method during in vitro fertilization (IVF) cycle. In the beginning, in order to avoid delaying cancer treatment, LPOS was applied for fertility preservation of cancer patients, showing no difference in numbers of oocyte retrieved, mature oocytes and fertilization rate between luteal or follicular phase stimulation. In the recent, LPOS was used for infertility women, suggesting that LPOS owned quite good IVF outcomes. In previous studies, premature luteinizing hormone (LH) surge, a major reason worsening ovarian quality in poor ovarian responders (PORs), was seldom found in LPOS. High progesterone in luteal phase may aid in suppressing premature LH surge. An updated research claimed that numbers of oocyte retrieved, mature oocytes and fertilized oocytes in LPOS significantly increased when compared to follicular ovarian stimulation. Therefore, the investigators presumed that LPOS was a more effective method than follicular stimulation in PORs.
- Conditions
- Fertilization in Vitro
- Being tested
- luteal ovarian stimulation, follicular ovarian stimulation
- Keywords
- In vitro fertilization, Poor ovarian responder, Luteal ovarian stimulation, Antagonist protocol, Cumulus cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
luteal ovarian stimulationOther
In the in vitro fertilization cycle, controlled ovarian stimulation was started since the luteal phase.
follicular ovarian stimulationOther
In the in vitro fertilization cycle, controlled ovarian stimulation was started since the follicular phase.
| Study group | Role | What they receive |
|---|---|---|
| luteal ovarian stimulation | Experimental | The controlled ovarian stimulation in in vitro fertilization cycle was started since luteal phase. Receives: Other: luteal ovarian stimulation |
| follicular ovarian stimulation | Active comparator | The controlled ovarian stimulation in in vitro fertilization cycle was started since early follicular phase phase. Receives: Other: follicular ovarian stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
oocytes and embryos
retrieved oocytes in number, matured oocytes in number, fertilized oocytes in number, day 3 embryos in number, top-quality day 3 embryos in number
Measured: through study completion, an average of 1 year
Secondary outcomes (2)
pregnancy rate
Clinical pregnancy rate
Measured: Pregnancy will be confirmed 4 weeks after embryo transfer.
genes expression
cumulus cells genes expression
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2017
- Study start3 May 2017
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Fertilization in VitroStudies 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
- 96 participants (actual)
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, PhD, Study director, Kaohsiung Veterans General Hospital.Salvatore Giovanni Vitale, M.D., Principal investigator, University of Messina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03238833
- Sponsor's protocol ID
- VGHKS15-CT11-12
- Status last verified
- Feb 2021
- First submitted
- 27 Jul 2017
- Last updated
- 18 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
PubMed 12849812Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8.
PubMed 22068695Bedoschi GM, de Albuquerque FO, Ferriani RA, Navarro PA. Ovarian stimulation during the luteal phase for fertility preservation of cancer patients: case reports and review of the literature. J Assist Reprod Genet. 2010 Aug;27(8):491-4. doi: 10.1007/s10815-010-9429-0. Epub 2010 May 9.
PubMed 20455017von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, Strowitzki T. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009 Oct;92(4):1360-1365. doi: 10.1016/j.fertnstert.2008.08.011. Epub 2008 Oct 18.
PubMed 18930226Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011 Jan;95(1):64-7. doi: 10.1016/j.fertnstert.2010.06.064. Epub 2010 Aug 5.
PubMed 20688325Cakmak H, Rosen MP. Ovarian stimulation in cancer patients. Fertil Steril. 2013 May;99(6):1476-84. doi: 10.1016/j.fertnstert.2013.03.029.
PubMed 23635348Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013 Dec;100(6):1673-80. doi: 10.1016/j.fertnstert.2013.07.1992. Epub 2013 Aug 26.
PubMed 23987516Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23.
PubMed 24161646Martinez F, Clua E, Devesa M, Rodriguez I, Arroyo G, Gonzalez C, Sole M, Tur R, Coroleu B, Barri PN. Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes. Fertil Steril. 2014 Nov;102(5):1307-11. doi: 10.1016/j.fertnstert.2014.07.741. Epub 2014 Aug 22.
PubMed 25154677Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.
PubMed 25444501Li Y, Yang W, Chen X, Li L, Zhang Q, Yang D. Comparison between follicular stimulation and luteal stimulation protocols with clomiphene and HMG in women with poor ovarian response. Gynecol Endocrinol. 2016;32(1):74-7. doi: 10.3109/09513590.2015.1081683. Epub 2015 Sep 15.
PubMed 26370530Wei LH, Ma WH, Tang N, Wei JH. Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol: A retrospective study. Taiwan J Obstet Gynecol. 2016 Feb;55(1):50-4. doi: 10.1016/j.tjog.2015.07.001.
PubMed 26927248Chen YC, Li JY, Li CJ, Tsui KH, Wang PH, Wen ZH, Lin LT. Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study. Int J Med Sci. 2021 Feb 4;18(7):1600-1608. doi: 10.7150/ijms.55955. eCollection 2021.
PubMed 33746576Lin LT, Vitale SG, Chen SN, Wen ZH, Tsai HW, Chern CU, Tsui KH. Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study. Adv Ther. 2018 Jun;35(6):847-856. doi: 10.1007/s12325-018-0713-1. Epub 2018 Jun 4.
PubMed 29869107
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital
- ClinicalTrials.gov ID
- NCT03238833
- Acronym / sponsor ID
- VGHKS15-CT11-12
- Conditions
- Fertilization in Vitro
- Keywords
- In vitro fertilization, Poor ovarian responder, Luteal ovarian stimulation, Antagonist protocol, Cumulus cells
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Kaohsiung Veterans General Hospital.University, hospital or other
- Study start
- 3 May 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 3 Aug 2017 (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.
The investigators attempted to compare the clinical outcomes and cumulus genes expression in poor ovarian responders undergoing luteal ovarian stimulation or follicular ovarian stimulation in in vitro fertilization cycles.
Detailed description
Multiple follicular wave theory proposed by Baerwald et al. implied that follicle recruitment may occur in the luteal phase of menstrual cycle. Therefore, luteal phase ovarian stimulation (LPOS) was considered as a potential feasible stimulation method during in vitro fertilization (IVF) cycle. In the beginning, in order to avoid delaying cancer treatment, LPOS was applied for fertility preservation of cancer patients, showing no difference in numbers of oocyte retrieved, mature oocytes and fertilization rate between luteal or follicular phase stimulation. In the recent, LPOS was used for infertility women, suggesting that LPOS owned quite good IVF outcomes. In previous studies, premature luteinizing hormone (LH) surge, a major reason worsening ovarian quality in poor ovarian responders (PORs), was seldom found in LPOS. High progesterone in luteal phase may aid in suppressing premature LH surge. An updated research claimed that numbers of oocyte retrieved, mature oocytes and fertilized oocytes in LPOS significantly increased when compared to follicular ovarian stimulation. Therefore, the investigators presumed that LPOS was a more effective method than follicular stimulation in PORs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| luteal ovarian stimulation | Experimental | Other: luteal ovarian stimulationThe controlled ovarian stimulation in in vitro fertilization cycle was started since luteal phase. |
| follicular ovarian stimulation | Active comparator | Other: follicular ovarian stimulationThe controlled ovarian stimulation in in vitro fertilization cycle was started since early follicular phase phase. |
Who may qualify
- Ages
- 30 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Poor ovarian responders (PORs) met the Bologna criteria, having at least two of the three following features:
- Moreover, two episodes of a previous POR after maximal stimulation alone would be sufficient to define a patient as a POR.
Key exclusion criteria (3 listed)
- oophorectomy
- exposure to cytotoxic or pelvic irradiation for malignancy
- taking herbal drugs or other hormonal agents
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 |
|---|---|---|
| luteal ovarian stimulationIn the in vitro fertilization cycle, controlled ovarian stimulation was started since the luteal phase. | Other | luteal ovarian stimulation |
| follicular ovarian stimulationIn the in vitro fertilization cycle, controlled ovarian stimulation was started since the follicular phase. | Other | follicular ovarian stimulation |
Primary outcome
oocytes and embryos
Time frame: through study completion, an average of 1 year
retrieved oocytes in number, matured oocytes in number, fertilized oocytes in number, day 3 embryos in number, top-quality day 3 embryos in number
2 secondary outcomes
pregnancy rate
Time frame: Pregnancy will be confirmed 4 weeks after embryo transfer.
genes expression
Time frame: through study completion, an average of 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2021.
- Background: PubMed 12849812Baerwald AR, Adams GP, Pierson RA. A new model for ovarian follicular development during the human menstrual cycle. Fertil Steril. 2003 Jul;80(1):116-22. doi: 10.1016/s0015-0282(03)00544-2.
- Background: PubMed 22068695Baerwald AR, Adams GP, Pierson RA. Ovarian antral folliculogenesis during the human menstrual cycle: a review. Hum Reprod Update. 2012 Jan-Feb;18(1):73-91. doi: 10.1093/humupd/dmr039. Epub 2011 Nov 8.
- Results publication: PubMed 20455017Bedoschi GM, de Albuquerque FO, Ferriani RA, Navarro PA. Ovarian stimulation during the luteal phase for fertility preservation of cancer patients: case reports and review of the literature. J Assist Reprod Genet. 2010 Aug;27(8):491-4. doi: 10.1007/s10815-010-9429-0. Epub 2010 May 9.
- Results publication: PubMed 18930226von Wolff M, Thaler CJ, Frambach T, Zeeb C, Lawrenz B, Popovici RM, Strowitzki T. Ovarian stimulation to cryopreserve fertilized oocytes in cancer patients can be started in the luteal phase. Fertil Steril. 2009 Oct;92(4):1360-1365. doi: 10.1016/j.fertnstert.2008.08.011. Epub 2008 Oct 18.
- Results publication: PubMed 20688325Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011 Jan;95(1):64-7. doi: 10.1016/j.fertnstert.2010.06.064. Epub 2010 Aug 5.
- Results publication: PubMed 23635348Cakmak H, Rosen MP. Ovarian stimulation in cancer patients. Fertil Steril. 2013 May;99(6):1476-84. doi: 10.1016/j.fertnstert.2013.03.029.
- Results publication: PubMed 23987516Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013 Dec;100(6):1673-80. doi: 10.1016/j.fertnstert.2013.07.1992. Epub 2013 Aug 26.
- Results publication: PubMed 24161646Kuang Y, Hong Q, Chen Q, Lyu Q, Ai A, Fu Y, Shoham Z. Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles. Fertil Steril. 2014 Jan;101(1):105-11. doi: 10.1016/j.fertnstert.2013.09.007. Epub 2013 Oct 23.
- Results publication: PubMed 25154677Martinez F, Clua E, Devesa M, Rodriguez I, Arroyo G, Gonzalez C, Sole M, Tur R, Coroleu B, Barri PN. Comparison of starting ovarian stimulation on day 2 versus day 15 of the menstrual cycle in the same oocyte donor and pregnancy rates among the corresponding recipients of vitrified oocytes. Fertil Steril. 2014 Nov;102(5):1307-11. doi: 10.1016/j.fertnstert.2014.07.741. Epub 2014 Aug 22.
- Results publication: PubMed 25444501Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, Shoham Z. Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol). Reprod Biomed Online. 2014 Dec;29(6):684-91. doi: 10.1016/j.rbmo.2014.08.009. Epub 2014 Sep 6.
- Results publication: PubMed 26370530Li Y, Yang W, Chen X, Li L, Zhang Q, Yang D. Comparison between follicular stimulation and luteal stimulation protocols with clomiphene and HMG in women with poor ovarian response. Gynecol Endocrinol. 2016;32(1):74-7. doi: 10.3109/09513590.2015.1081683. Epub 2015 Sep 15.
- Results publication: PubMed 26927248Wei LH, Ma WH, Tang N, Wei JH. Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol: A retrospective study. Taiwan J Obstet Gynecol. 2016 Feb;55(1):50-4. doi: 10.1016/j.tjog.2015.07.001.
- 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, PhD study director
Kaohsiung Veterans General Hospital.
Salvatore Giovanni Vitale, M.D. principal investigator
University of Messina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing luteal ovarian stimulation and follicular ovarian stimulation in people with Fertilization in Vitro, 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 5 inclusion and 3 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: finished, as of the sponsor's last update on 18 Feb 2021. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
oocytes and embryos (time frame: through study completion, an average of 1 year). 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 NCT03238833, which also lists 14 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 Feb 2021.