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Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF

Primary Purpose

Infertility

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Tamoxifen
Clomiphene
Sponsored by
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility focused on measuring tamoxifen, clomiphene, mild stimulation, poor ovarian response, clinical pregnancy rate

Eligibility Criteria

37 Years - 42 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. age between 37 and 42;
  2. BMI≤23kg/m2;
  3. ≤3 oocytes with a conventional stimulation protocol;
  4. AFC<5 follicles or AMH<1.1 ng/ml on the day 1 to 5 of the menses;
  5. Cause of Infertiity: tubal factor, male factor, diminished ovarian reserve.

Exclusion Criteria:

  1. endormetrial polyp, endormetrial cancer,intrauterine adhesions,uterine fibroids that affects uterine cavity
  2. Endometriosis, adenomyosis
  3. The diameter of Hydrosalpinx >2cm

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    tamoxifen

    clomiphene

    Arm Description

    All patients will have serum hormone examination and be monitored by transvaginal ultrasound for ovaries on the day 3 of the menses（D3）.Patients in the tamoxifen group will take 20 mg of tamoxifen oral tablets daily from D3 for 5 days.All patients will check serum E2 and be monitored by transvaginal ultrasound for the mean follicular diameter and endometrial thickness on the day 8 of the cycle. The investigators will add HMG and GnRH-ant according to follicular diameter,E2 and LH. Human chorionic gonadotropin(hCG) (5000-10000 IU IM) will be given when one follicle measured at least 18 mm is found. IVF or ICSI will be performed 34-36 h after hCG administration. All patients will receive luteal phase support with progesterone 60 mg im qd for 2 weeks.

    All patients will have serum hormone examination and be monitored by transvaginal ultrasound for ovaries on the day 3 of the menses（D3）.Patients in clomiphene group will take 100 mg of CC oral tablets daily from D3 for 5 days.All patients will have sexual hormone determination and be monitored by transvaginal ultrasound for the mean follicular diameter and endometrial thickness on the day 8 of the cycle.The investigators will add HMG and GnRH-ant according to follicular diameter,E2 and LH. Human chorionic gonadotropin(hCG) (5000-10000 IU IM) will be given when one follicle measured at least 18 mm is found. IVF or ICSI will be performed 34-36 h after hCG injection. All patients will receive luteal phase support with progesterone 60 mg im qd for 2 weeks.

    Outcomes

    Primary Outcome Measures

    clinical pregnancy rate

    Secondary Outcome Measures

    cycle cancellations for thin endrometrial thickness
    endrometrial pattern and thickness on the day of HCG administration
    the number of follicular diameter≥10mm and sexual hormone test on the HCG day

    Full Information

    First Posted
    February 20, 2016
    Last Updated
    February 23, 2016
    Sponsor
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Collaborators
    Sun Yat-sen University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02690870
    Brief Title
    Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF
    Official Title
    Comparison of Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF: a Prospective Cohort Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2016
    Overall Recruitment Status
    Unknown status
    Study Start Date
    January 2017 (undefined)
    Primary Completion Date
    May 2018 (Anticipated)
    Study Completion Date
    March 2019 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Collaborators
    Sun Yat-sen University

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this prospective cohort study is to compare IVF outcome between tamoxifen and clomiphene citrate in mild stimulation.
    Detailed Description
    The reported prevalence of poor ovarian responders amongst patients undergoing IVF-ET is 9%-24%, and morbidity must be higher nowadays. For these women, Mild stimulation has been an important ovulation induction protocol. Clomiphene citrate(CC) and tamoxifen(TMX) are commonly used in mild stimulation protocol. It's reported that CC has adverse effect on growth of endrometrium and results in thin endrometrium(≤7mm) which maybe affect pregnancy rate. However, TMX has estrogen-like effect on the endrometrium that may be helpful to increase endormetrial thickness. The reported results about comparing CC with TMX showed that they had similar ovulation rate. Prospective study is necessary to confirm whether TMX is superior to CC on the IVF outcome.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Infertility
    Keywords
    tamoxifen, clomiphene, mild stimulation, poor ovarian response, clinical pregnancy rate

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    210 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    tamoxifen
    Arm Type
    Experimental
    Arm Description
    All patients will have serum hormone examination and be monitored by transvaginal ultrasound for ovaries on the day 3 of the menses（D3）.Patients in the tamoxifen group will take 20 mg of tamoxifen oral tablets daily from D3 for 5 days.All patients will check serum E2 and be monitored by transvaginal ultrasound for the mean follicular diameter and endometrial thickness on the day 8 of the cycle. The investigators will add HMG and GnRH-ant according to follicular diameter,E2 and LH. Human chorionic gonadotropin(hCG) (5000-10000 IU IM) will be given when one follicle measured at least 18 mm is found. IVF or ICSI will be performed 34-36 h after hCG administration. All patients will receive luteal phase support with progesterone 60 mg im qd for 2 weeks.
    Arm Title
    clomiphene
    Arm Type
    Active Comparator
    Arm Description
    All patients will have serum hormone examination and be monitored by transvaginal ultrasound for ovaries on the day 3 of the menses（D3）.Patients in clomiphene group will take 100 mg of CC oral tablets daily from D3 for 5 days.All patients will have sexual hormone determination and be monitored by transvaginal ultrasound for the mean follicular diameter and endometrial thickness on the day 8 of the cycle.The investigators will add HMG and GnRH-ant according to follicular diameter,E2 and LH. Human chorionic gonadotropin(hCG) (5000-10000 IU IM) will be given when one follicle measured at least 18 mm is found. IVF or ICSI will be performed 34-36 h after hCG injection. All patients will receive luteal phase support with progesterone 60 mg im qd for 2 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Tamoxifen
    Other Intervention Name(s)
    CAS RN：10540-29-1
    Intervention Description
    Patients in the tamoxifen group will take 20 mg of tamoxifen oral tablets daily from day 3 of the menses for 5 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Clomiphene
    Other Intervention Name(s)
    clomiphene citrate
    Intervention Description
    Patients in clomiphene group will take 100 mg of CC oral tablets daily from day 3 of the menses for 5 days.
    Primary Outcome Measure Information:
    Title
    clinical pregnancy rate
    Time Frame
    four weeks after embryo transfer
    Secondary Outcome Measure Information:
    Title
    cycle cancellations for thin endrometrial thickness
    Time Frame
    on the HCG day
    Title
    endrometrial pattern and thickness on the day of HCG administration
    Time Frame
    on the HCG day
    Title
    the number of follicular diameter≥10mm and sexual hormone test on the HCG day
    Time Frame
    on the HCG day

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    37 Years
    Maximum Age & Unit of Time
    42 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: age between 37 and 42; BMI≤23kg/m2; ≤3 oocytes with a conventional stimulation protocol; AFC<5 follicles or AMH<1.1 ng/ml on the day 1 to 5 of the menses; Cause of Infertiity: tubal factor, male factor, diminished ovarian reserve. Exclusion Criteria: endormetrial polyp, endormetrial cancer,intrauterine adhesions,uterine fibroids that affects uterine cavity Endometriosis, adenomyosis The diameter of Hydrosalpinx >2cm
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Haiyan LIN
    Phone
    0018615913154456
    Email
    linhaiyan_818@163.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Qingxue ZHANG
    Organizational Affiliation
    Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Yes
    Citations:
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    11334921
    Citation
    Boostanfar R, Jain JK, Mishell DR Jr, Paulson RJ. A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction. Fertil Steril. 2001 May;75(5):1024-6. doi: 10.1016/s0015-0282(01)01749-6.
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    Revelli A, Casano S, Salvagno F, Delle Piane L. Milder is better? Advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization. Reprod Biol Endocrinol. 2011 Feb 16;9:25. doi: 10.1186/1477-7827-9-25.
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    Badawy A, Gibreal A. RETRACTED: Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial. Eur J Obstet Gynecol Reprod Biol. 2011 Nov;159(1):151-154. doi: 10.1016/j.ejogrb.2011.07.015. Epub 2011 Aug 9. No abstract available.
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    PubMed Identifier
    18616885
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    Reynolds K, Khoury J, Sosnowski J, Thie J, Hofmann G. Comparison of the effect of tamoxifen on endometrial thickness in women with thin endometrium (<7mm) undergoing ovulation induction with clomiphene citrate. Fertil Steril. 2010 Apr;93(6):2091-3. doi: 10.1016/j.fertnstert.2009.08.038. Epub 2009 Sep 22.
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    Brinton LA, Westhoff CL, Scoccia B, Lamb EJ, Trabert B, Niwa S, Moghissi KS. Fertility drugs and endometrial cancer risk: results from an extended follow-up of a large infertility cohort. Hum Reprod. 2013 Oct;28(10):2813-21. doi: 10.1093/humrep/det323. Epub 2013 Aug 13.
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    Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF

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