Poor Ovarian Responders Undergoing IVF Using Luteal Ovarian Stimulation Versus Follicular Ovarian Stimulation

NCT ID: NCT03238833

Last Updated: 2021-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-03

Study Completion Date

2019-12-31

Brief Summary

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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

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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

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Fertilization in Vitro

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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luteal ovarian stimulation

The controlled ovarian stimulation in in vitro fertilization cycle was started since luteal phase.

Group Type EXPERIMENTAL

luteal ovarian stimulation

Intervention Type OTHER

In the in vitro fertilization cycle, controlled ovarian stimulation was started since the luteal phase.

follicular ovarian stimulation

The controlled ovarian stimulation in in vitro fertilization cycle was started since early follicular phase phase.

Group Type ACTIVE_COMPARATOR

follicular ovarian stimulation

Intervention Type OTHER

In the in vitro fertilization cycle, controlled ovarian stimulation was started since the follicular phase.

Interventions

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luteal ovarian stimulation

In the in vitro fertilization cycle, controlled ovarian stimulation was started since the luteal phase.

Intervention Type OTHER

follicular ovarian stimulation

In the in vitro fertilization cycle, controlled ovarian stimulation was started since the follicular phase.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Poor ovarian responders (PORs) met the Bologna criteria, having at least two of the three following features:

1. advanced maternal age (≥ 40 years) or any other risk factor for POR,
2. a previous POR (≤ 3 oocytes with a conventional stimulation protocol), and
3. 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.

Exclusion Criteria

* oophorectomy
* exposure to cytotoxic or pelvic irradiation for malignancy
* taking herbal drugs or other hormonal agents
Minimum Eligible Age

30 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Kaohsiung Veterans General Hospital.

OTHER

Sponsor Role lead

Responsible Party

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Li-Te Lin

Department of Obstetrics and Gynecology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kuan-Hao Tsui, PhD

Role: STUDY_DIRECTOR

Kaohsiung Veterans General Hospital.

Salvatore Giovanni Vitale, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Messina

Locations

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Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Site Status

Countries

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Taiwan

References

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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.

Reference Type BACKGROUND
PMID: 12849812 (View on PubMed)

Baerwald 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.

Reference Type BACKGROUND
PMID: 22068695 (View on PubMed)

Bedoschi 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.

Reference Type RESULT
PMID: 20455017 (View on PubMed)

von 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.

Reference Type RESULT
PMID: 18930226 (View on PubMed)

Maman 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.

Reference Type RESULT
PMID: 20688325 (View on PubMed)

Cakmak H, Rosen MP. Ovarian stimulation in cancer patients. Fertil Steril. 2013 May;99(6):1476-84. doi: 10.1016/j.fertnstert.2013.03.029.

Reference Type RESULT
PMID: 23635348 (View on PubMed)

Cakmak 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.

Reference Type RESULT
PMID: 23987516 (View on PubMed)

Kuang 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.

Reference Type RESULT
PMID: 24161646 (View on PubMed)

Martinez 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.

Reference Type RESULT
PMID: 25154677 (View on PubMed)

Kuang 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.

Reference Type RESULT
PMID: 25444501 (View on PubMed)

Li 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.

Reference Type RESULT
PMID: 26370530 (View on PubMed)

Wei 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.

Reference Type RESULT
PMID: 26927248 (View on PubMed)

Chen 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.

Reference Type DERIVED
PMID: 33746576 (View on PubMed)

Lin 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.

Reference Type DERIVED
PMID: 29869107 (View on PubMed)

Other Identifiers

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VGHKS15-CT11-12

Identifier Type: -

Identifier Source: org_study_id

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