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2 2024-07-24, 1403/05/03 309533
1 2023-03-16, 1401/12/25 259214
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  • Protocol summary

    Therefore, the aim of this study is to investigate the effect of astaxanthin on the oxidative stress and inflammatory cytokines markers in follicular fluid and assisted reproductive technology results in patients with poor ovarian response.
    Therefore, the aim of this study is to investigate the effect of astaxanthin on assisted reproductive technology results and the oxidative stress and inflammatory cytokines markers and cell free DNA in patients with poor ovarian response.
    هدف این مطالعه بررسی اثر آستازانتین بر شاخص¬های استرس اکسیداتیو و سایتوکین¬های التهابی در مایع فولیکولی و نتایج تکنولوژی کمک باروری (Assisted Reproductive Technology (ART)) در بیماران با پاسخ ضعیف تخمدان (POR) می باشد.
    هدف این مطالعه بررسی اثر آستازانتین بر نتایج تکنولوژی کمک باروری (Assisted Reproductive Technology (ART)) و شاخص¬های استرس اکسیداتیو و سایتوکین¬های التهابی و cell-free DNA (مارکر آپوپتوز) در بیماران با پاسخ ضعیف تخمدان (POR) می باشد.
    Two arm parallel group, Triple-Blind, Randomized control trial and outcome assessment Randomization will be in the form of blocking. 40 patients with poor ovarian response will enter the project. Patients will be randomly divided into two groups: group one will receive 12 mg of astaxanthin (2 capsules) per day and group two will receive placebo capsules for 8 weeks.
    Two arm parallel group, Triple-Blind, Randomized control trial and outcome assessment Randomization will be in the form of blocking. 60patients with poor ovarian response will enter the project. Patients will be randomly divided into two groups: group one will receive 12 mg of astaxanthin (2 capsules) per day and group two will receive placebo capsules for 8 weeks.
    این کارآزمایی بالینی دارای گروه کنترل و استازانتین، با گروه های موازی ، سه سویه کور ، تصادفی سازی به صورت بلوک بندی، فاز 3 بر روی 40 بیمار با پاسخ ضعیف تخمدان انجام می شود. برای تصادفی سازی از فانکشن rand نرم افزار اکسل استفاده شد. گروه درمان با استازانتین، 12 میلی-گرم آستازانتین در روز (3 کپسول 4mg آستازانتین در روز) و گروه کنترل، کپسول پلاسبو (3 کپسول پلاسبو در روز) را به مدت 8 هفته دریافت می¬کنند (101).
    این کارآزمایی بالینی دارای گروه کنترل و استازانتین، با گروه های موازی ، سه سویه کور ، تصادفی سازی به صورت بلوک بندی، فاز 3 بر روی 60 بیمار با پاسخ ضعیف تخمدان انجام می شود. برای تصادفی سازی از فانکشن rand نرم افزار اکسل استفاده شد. گروه درمان با استازانتین، 12 میلی-گرم آستازانتین در روز (3 کپسول 4mg آستازانتین در روز) و گروه کنترل، کپسول پلاسبو (3 کپسول پلاسبو در روز) را به مدت 8 هفته دریافت می¬کنند (101).
    Inclusion criteria: (i) advanced maternal age (>40 years), (ii) a previous poor response, defined as ≤3 oocytes retrieved after a standard ovarian stimulation, (iii) or an abnormal ovarian reserve test (AFC < 5–7 follicles and/or AMH < 1.1 ng/mL). Exclusion criteria: including history of ovarian surgery, autoimmune or endocrine disease, severe male factor infertility
    The inclusion criteria were: age > 35 years, and poor ovarian reserve (anti-müllerian hormone (AMH) < 1.2 ng/ml, or antral follicle count (AFC) < 5) (indicating low prognosis group 4 following the POSEIDON stratification) (24). Exclusion criteria: including history of ovarian surgery or chemotherapy, autoimmune or endocrine disease, severe male factor infertility
    معیارهای ورود: (i) سن بالای مادر(>40 سال)، (ii) پاسخ ضعیف قبلی، یعنی پس از تحریک تخمدانی استاندارد، ≤3 اووست بازیابی شود، (iii) یا یک آزمایش ذخیره تخمدانی غیرطبیعی (تعداد فولیکول¬های آنترال < 5–7 فولیکول و/یا anti-Mullerian hormone (AMH) < 1.1 ng/mL). معیارهای خروج: سابقه جراحی تخمدان، بیماری خودایمنی یا اندوکرین، ناباروری شدید با عامل مردانه
    معیارهای ورود شامل: سن بالای ۳۵ سال و ذخیره تخمدانی پایین (هورمون آنتی مولرین (AMH) کمتر از ۱.۲ نانوگرم در میلیلیتر یا شمارش فولیکولهای آنترال (AFC) کمتر از ۵) (که نشاندهنده گروه ۴ با پیشآگهی ضعیف طبق طبقهبندی POSEIDON) بود. معیار های خروج: سابقه جراحی تخمدان یا شیمیدرمانی، اختلالات غدد درونریز ، اختلالات خودایمنی، اندومتریوز، ناباروری شدید مردان
    1- The following markers will be checked in follicular fluid: MDA, SOD, TAC, IL-6, IL-8, VEGF, Cell free DNA 2- Consequences of ART: Evaluation of the number of antral follicles, number of retrieved oocytes, oocyte and embryo quality, fertilization rate, chemical pregnancy rate
    1- ART outcomes: Evaluation of the number of MII oocytes & retrieved oocytes, number & quality of embryos, fertilization rate, chemical & clinical pregnancy rate 2- Evaluation of MDA, SOD, TAC, IL-6, IL-8, VEGF in serum and follicular fluid, & Cell-free DNA levels in follicular fluid.
    1- مارکر های زیر در مایع فولیکی بررسی خواهند شد: MDA, SOD, TAC, IL-6, IL-8, VEGF, Cell free DNA 2- پیامد های َART: ارزیابی تعداد فولیکول های آنترال، تعداد اووسیت¬های بازیابی شده، ارزیابی کیفیت تخمک و جنین، نرخ لقاح، میزان بارداری شیمیایی
    1- پیامد های َART ارزیابی تعداد تخمک های MII، تعداد اووسیت¬های بازیابی شده، تعداد جنین ها، کیفیت جنین ها، نرخ لقاح، میزان بارداری شیمیایی و بارداری کلینیکی، نرخ کنسل شدن سیکل ها، 2- پیامد های ثانویه: سنجش سطح MDA, SOD, TAC, IL-6, IL-8, VEGF در مایع فولیکولی و سرم و سنجش Cell free DNA در مایع فولیکولی
  • General information

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    The precise age range under study was determined to ensure the homogeneity of the patient population with poor ovarian response. The selected age range was 36-41 years, corresponding to group 4 of the POSEIDON classification. Additionally, modifying certain variables such as adding variables that include the cycle cancellation rate and the dosage of ovarian stimulation medications which is important in patients with poor ovarian response.
    empty
    تعیین محدوده ی سنی دقیق مورد مطالعه که به منظور همگن سازی جمعیت بیماران مبتلا به پاسخ ضعیف تخمدانی بازه سنی 36-41 سال که منطبق با گروه 4 طبقه بندی POSEIDONمی باشد انتخاب شدند و همچنین تغییر برخی متغیر ها نظیر اضافه کردن متغیر هایی شامل نرخ کنسل شدن سیکل ها و دوز دارو های تحریک تخمدانی که در بیماران با پاسخ ضعیف تخمدان دارای اهمیت می باشد.
    POR will be diagnosed based on Blogna criteria and having at least two of the following three criteria: (i) advanced maternal age (>40 years),
    (ii) a previous poor response, defined as ≤3 oocytes retrieved after a standard ovarian stimulation,
    (iii) or an abnormal ovarian reserve test (antral follicle count (AFC) < 5–7 follicles and/or anti-Mullerian hormone (AMH) < 1.1 ng/mL).
    The couple should be a candidate for ICSI
    and do not have any history of male factor infertility.
    POR will be diagnosed based on PSEIDON: (i) age > 35 years,
    (ii) anti-Mullerian hormone (AMH) < 1.2 ng/mL or antral follicle count (AFC) < 5
    The couple should be a candidate for ICSI
    تشخیص POR بر اساس معیارهای Blogna و با داشتن حداقل دو مورد از سه معیار زیر صورت خواهد گرفت: (i) سن بالای مادر(>40 سال)،
    (ii) پاسخ ضعیف قبلی، یعنی پس از تحریک تخمدانی استاندارد، ≤3 اووست بازیابی (retrieved) شود،
    (iii) یا یک آزمایش ذخیره تخمدانی غیرطبیعی (تعداد فولیکول های آنترال (antral follicle count (AFC)) < 5–7 فولیکول و/یا هورمون آنتی¬مولریان anti-Mullerian hormone (AMH) < 1.1 ng/mL)،
    کاندید ICSI باشد،
    زوجین هیچ سابقه ای از ناباروری با عامل مردانه نداشته باشند.
    تشخیص POR بر اساس معیارهای POSEIDON : (i) سن بالای مادر(>35 سال)،
    (ii) anti-Mullerian hormone (AMH) < 1.2 ng/mL یا تعداد فولیکول های انترال کمتر از 5 عدد (antral follicle count (AFC) < 5)
    کاندید ICSI باشد،
    including pregnancy,
    history of ovarian surgery,
    autoimmune or endocrine disease (diabetes, thyroid dysfunction, presence of anti-thyroid antibody or polycystic ovary),
    hyperprolactinemia,
    severe endometriosis (stages III and IV based on AFS-rAFS classification of endometriosis),
    recurrent Spontaneous miscarriage,
    ovarian tumor,
    chromosomal defect,
    uterine disorder,
    more than 3 previous IVF cycles,
    severe male factor infertility (especially non-obstructive azoospermia),
    history of taking drugs that affect ovarian function such as steroids and OCP.
    Also, people who have used antioxidant supplements or drugs affecting the hormonal profile 6 months before the start of the plan will not be included in the plan.
    including spontaneous pregnancy,
    history of ovarian surgery,
    autoimmune or endocrine disease (diabetes, thyroid dysfunction, presence of anti-thyroid antibody or polycystic ovary),
    hyperprolactinemia,
    severe endometriosis (stages III and IV based on AFS-rAFS classification of endometriosis),
    recurrent Spontaneous miscarriage,
    ovarian tumor,
    chromosomal defect,
    uterine disorder,
    more than 3 previous IVF cycles,
    severe male factor infertility (especially non-obstructive azoospermia),
    history of taking drugs that affect ovarian function such as steroids and OCP.
    Also, people who have used antioxidant supplements, vitamins or drugs affecting the hormonal profile 3 months before the start of the plan will not be included in the plan.
    have any history of male factor infertility.
    شامل حاملگی،
    سابقه جراحی تخمدان،
    بیماری خودایمنی یا اندوکرین (دیابت، اختلال عملکرد تیروئید، حضور انتی-بادی ضد تیرئید یا تخمدان پلی¬کیستیک)،
    هایپرپرولاکتینمی،
    اندومتریوز شدید (stages III and IV بر اساسAFS-rAFS classification of endometriosis)،
    سقط مکرر خود به خودی،
    تومور تخمدان،
    نقص کروموزومی،
    اختلال رحمی،
    بیشتر از 3 سیکل IVF قبلی،
    ناباروری شدید با عامل مردانه (به ویژه آزواسپرمی غیر انسدادی)،
    سابقه مصرف داروهایی که روی عملکرد تخمدان اثر می¬گذارند نظیر استروئیدها و OCP، می¬باشد.
    همچنین افرادی که ۶ ماه قبل از شروع طرح مکمل¬های آنتی¬اکسیدانی یا داروهای مؤثر بر پروفایل هورمونی استفاده کرده¬اند نیز وارد طرح نخواهند شد.
    شامل حاملگی خود به خودی،
    سابقه جراحی تخمدان،
    بیماری خودایمنی یا اندوکرین (دیابت، اختلال عملکرد تیروئید، حضور انتی-بادی ضد تیرئید یا تخمدان پلی¬کیستیک)،
    هایپرپرولاکتینمی،
    اندومتریوز شدید (stages III and IV بر اساسAFS-rAFS classification of endometriosis)،
    سقط مکرر خود به خودی،
    تومور تخمدان،
    نقص کروموزومی،
    اختلال رحمی،
    بیشتر از 3 سیکل IVF قبلی،
    ناباروری شدید با عامل مردانه (به ویژه آزواسپرمی غیر انسدادی)،
    سابقه مصرف داروهایی که روی عملکرد تخمدان اثر می¬گذارند نظیر استروئیدها و OCP، می¬باشد.
    همچنین افرادی که 3 ماه قبل از شروع طرح مکمل¬های آنتی¬اکسیدانی، ویتامین یا داروهای مؤثر بر پروفایل هورمونی استفاده کرده¬اند نیز وارد طرح نخواهند شد.
    سابقه ای از ناباروری با عامل مردانه.
  • Primary outcomes

    #1
    Malondialdehyde (MDA)
    number of MII oocytes
    Malondialdehyde (MDA)
    تعداد تخمک های MII
    8 weeks after the intervention
    8 weeks after the start of the intervention
    8 هفته پس از اتمام مداخله
    8 هفته پس از آغاز مداخله
    Spectrophotometry
    stereo microscope
    Spectrophotometry
    میکروسکوپ استریو
    #2
    Superoxide dismutase (SOD)
    Number of retrieved oocytes
    Superoxide dismutase (SOD)
    تعداد تخمک های بازیابی شده
    8 weeks after the intervention
    8 weeks after the start of the intervention
    8 هفته پس از اتمام مداخله
    8 هفته پس از آغاز مداخله
    Spectrophotometry
    میکروسکوپ استریو
    Spectrophotometry
    میکروسکوپ استریو
    #3
    Total antioxidant capacity (TAC)
    Oocyte maturity rate (MII %)
    Total antioxidant capacity (TAC)
    نرخ بلوغ تخمک
    8 weeks after the intervention
    8 weeks after the start of the intervention
    8 هفته پس از اتمام مداخله
    8 هفته پس از آغاز مداخله
    Spectrophotometry
    میکروسکوپ استریو
    Spectrophotometry
    میکروسکوپ استریو
    #4
    IL-6
    Total gonadotrophin doses
    IL-6
    دوز کلی گنادوتروپین تجویز شده
    8 weeks after the intervention
    During the ovarian stimulation cycle
    8 هفته پس از اتمام مداخله
    در طول مدت سیکل تحریک تحمدانی
    ELISA kit
    The prescribed medication dosage is reported in IU (International Units).
    کیت الایزا
    دوز داروی تجویز شده بر اساس واحد بین المللی (IU) گزارش می شود
    #5
    IL-8
    rFSH doses
    IL-8
    دوز rFSH تجویز شده
    8 weeks after the intervention
    During the ovarian stimulation cycle
    8 هفته پس از اتمام مداخله
    در طول مدت سیکل تحریک تحمدانی
    ELISA kit
    The prescribed medication dosage is reported in IU (International Units).
    کیت الایزا
    دوز داروی تجویز شده بر اساس واحد بین المللی (IU) گزارش می شود
    #6
    VEGF
    HMG doses
    VEGF
    دوز HMG تجویز شده
    8 weeks after the intervention
    During the ovarian stimulation cycle
    8 هفته پس از اتمام مداخله
    در طول مدت سیکل تحریک تحمدانی
    ELISA kit
    The prescribed medication dosage is reported in IU (International Units).
    کیت الایزا
    دوز داروی تجویز شده بر اساس واحد بین المللی (IU) گزارش می شود
    #7
    Cell free DNA
    number of embryos
    Cell free DNA
    تعداد جنین ها
    8 weeks after the intervention
    8 weeks and 3 days after the start of the intervention
    8 هفته پس از اتمام مداخله
    8 هفته و 3 روز بعد از آغاز مداخله
    Real time pcr
    stereo microscope
    Real time pcr
    میکروسکوپ استریو
    #8
    basal FSH
    Quality of embryos
    basal FSH
    کیفیت جنین ها
    before the beginning of the intervention
    8 weeks and 3 days after the start of the intervention
    قبل از شروع مداخله
    8 هفته و 3 روز بعد از آغاز مداخله
    ELISA kit
    stereo microscope
    کیت الایزا
    میکروسکوپ استریو
    #9
    basal LH
    Antral follicular count
    basal LH
    تعداد فولیکول های انترال
    before the beginning of the intervention
    before the start of the intervention and 8 weeks after the start of the intervention
    قبل از شروع مداخله
    قبل از آغاز مداخله و 8 هفته بعد از آغاز مداخله
    ELISA kit
    vaginal sonography
    کیت الایزا
    سونوگرافی واژینال
    #10
    Estradiol
    fertilization rate
    Estradiol
    نرخ لقاح
    before the beginning of the intervention
    8 weeks and 1 day after the start of the intervention (1 day after oocyte pick up)
    قبل از شروع مداخله
    8 هفته و یک روز بعد از آغاز مداخله (یک روز بعد از پانکچر)
    ELISA kit
    stereo microscope
    کیت الایزا
    میکروسکوپ استریو
    #11
    Progestrone
    chemical pregnancy rate
    Progestrone
    نرخ بارداری شیمیایی
    before the beginning of the intervention
    14 days after embryo transfer
    قبل از شروع مداخله
    14 روز بعد از انتقال جنین
    ELISA kit
    beta-HCG blood test
    کیت الایزا
    تست خون beta-HCG
    #12
    AMH
    clinical pregnancy rate
    AMH
    نرخ بارداری کلینیکی
    before the beginning of the intervention
    6-8th week of gestational age
    قبل از شروع مداخله
    هفته 6-8 بارداری
    ELISA kit
    pregnancies showing confirmed clinical markers on ultrasound (like gestational sac and heart rate)
    کیت الایزا
    بارداریهایی که نشانگرهای بالینی تایید شده در سونوگرافی (مانند کیسه بارداری و ضربان قلب) را نشان میدهند
    #13
    Antral Follicle Count
    Cycle cancellation rate
    Antral Follicle Count
    نرخ کنسل شدن سیکل ها
    before the beginning of the intervention
    8 weeks after the start of the intervention
    قبل از شروع مداخله
    8 هفته بعد از آغاز مداخله
    vaginal sonography
    Percentage of cycles canceled before OPU per the number of started cycles
    سونوگرافی واژینال
    درصد نسبت سیکل های لغو شده قبل از پانکچر به تعداد سیکل های شروع شده
    #14
    empty
    number of transferred embryos
    empty
    تعداد جنین های انتقال داده شده
    empty
    after the embryo transfer
    empty
    بعد از انتقال جنین
    empty
    number of embryos
    empty
    تعداد جنین ها
  • Secondary outcomes

    #1
    Number and quality of oocytes
    malondialdehyde [MDA] levels in follicular fluid
    تعداد و کیفیت تخمک ها
    malondialdehyde [MDA] در مایع فولیکولی
    8 weeks after the intervention
    8 weeks after the start of the intervention
    8 هفته بعد از اتمام مداخله
    8 هفته بعد از آغاز مداخله
    Counting, light microscope
    ELISA Kit
    شمارش و میکروسکوپ نوری
    کیت الایزا
    #2
    Number and quality of embryos
    superoxide dismutase [SOD] levels in follicular fluid
    تعداد و کیفیت جنین ها
    superoxide dismutase [SOD] در مایع فولیکولی
    8 weeks and 3 days after the intervention
    8 weeks after the start of the intervention
    8 هفته و 3 روز بعد از اتمام مداخله
    8 هفته بعد از آغاز مداخله
    Counting, light microscope
    ELISA Kit
    شمارش و میکروسکوپ نوری
    کیت الایزا
    #3
    Antral Follicle Count
    total antioxidant capacity [TAC] levels in follicular fluid
    تعداد فولیکول های انترال
    total antioxidant capacity [TAC] در مایع فولیکولی
    8 weeks after the intervention
    8 weeks after the start of the intervention
    8 هفته بعد از اتمام مداخله
    8 هفته بعد از آغاز مداخله
    Vaginal sonography
    ELISA Kit
    سونوگرافی واژینال
    کیت الایزا
    #4
    fertility rate
    interleukin-6 [IL-6] levels in follicular fluid
    نرخ لقاح
    interleukin-6 [IL-6] در مایع فولیکولی
    8 weeks and 1 day after the intervention (1 day after oocyte pick up)
    8 weeks after the start of the intervention
    8 هفته و 1 روز بعد از اتمام مداخله (یک روز بعد از پانکچر)
    8 هفته بعد از آغاز مداخله
    light microscope
    ELISA Kit
    میکروسکوپ نوری
    کیت الایزا
    #5
    Chemical pregnancy
    interleukin-8 [IL-8] interleukin-6 [IL-6]
    بارداری شیمیایی
    interleukin-8 [IL-8] در مایع فولیکولی
    14 days after embryo transfer
    8 weeks after the start of the intervention
    14 روز بعد از انتقال جنین
    8 هفته بعد از آغاز مداخله
    beta-hCG blood test
    ELISA Kit
    تست خون beta-hCG
    کیت الایزا
    #6
    empty
    vascular endothelial growth factor [VEGF] interleukin-6 [IL-6]
    empty
    vascular endothelial growth factor [VEGF] در مایع فولیکولی
    empty
    8 weeks after the start of the intervention
    empty
    8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا
    #7
    empty
    cell-free DNA interleukin-6 [IL-6]
    empty
    cell-free DNA در مایع فولیکولی
    empty
    8 weeks after the start of the intervention
    empty
    8 هفته بعد از آغاز مداخله
    empty
    qPCR
    empty
    qPCR
    #8
    empty
    malondialdehyde [MDA] levels in serum
    empty
    malondialdehyde [MDA] در سرم
    empty
    before the start of the intervention and 8 weeks after the intervention
    empty
    قبل از شروع مداخله و 8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا
    #9
    empty
    superoxide dismutase [SOD] levels in serum
    empty
    superoxide dismutase [SOD] در سرم
    empty
    before the start of the intervention and 8 weeks after the intervention
    empty
    قبل از شروع مداخله و 8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا
    #10
    empty
    total antioxidant capacity [TAC] levels in serum
    empty
    total antioxidant capacity [TAC] در سرم
    empty
    before the start of the intervention and 8 weeks after the intervention
    empty
    قبل از شروع مداخله و 8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا
    #11
    empty
    interleukin-6 [IL-6] levels in serum
    empty
    interleukin-6 [IL-6] در سرم
    empty
    before the start of the intervention and 8 weeks after the intervention
    empty
    قبل از شروع مداخله و 8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا
    #12
    empty
    interleukin-8 [IL-8] levels in serum
    empty
    interleukin-8 [IL-8] در سرم
    empty
    before the start of the intervention and 8 weeks after the intervention
    empty
    قبل از شروع مداخله و 8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا
    #13
    empty
    vascular endothelial growth factor [VEGF] levels in serum
    empty
    vascular endothelial growth factor [VEGF] در سرم
    empty
    before the start of the intervention and 8 weeks after the intervention
    empty
    قبل از شروع مداخله و 8 هفته بعد از آغاز مداخله
    empty
    ELISA Kit
    empty
    کیت الایزا

Protocol summary

Study aim
Therefore, the aim of this study is to investigate the effect of astaxanthin on assisted reproductive technology results and the oxidative stress and inflammatory cytokines markers and cell free DNA in patients with poor ovarian response.
Design
Two arm parallel group, Triple-Blind, Randomized control trial and outcome assessment Randomization will be in the form of blocking. 60patients with poor ovarian response will enter the project. Patients will be randomly divided into two groups: group one will receive 12 mg of astaxanthin (2 capsules) per day and group two will receive placebo capsules for 8 weeks.
Settings and conduct
The location of the experiment: Tehran University of Medical Sciences. Sampling location: Omid fertility center. This clinical trial is a randomized, triple-blind placebo-controlled trial. In any clinical trial, three groups can influence the results of the study, these three groups are 1- the participants in the research, 2- the implementers of the plan, 3- the evaluators or others who analyze the obtained data. If blinding is done for all three groups involved, it is called a triple-blind study.
Participants/Inclusion and exclusion criteria
The inclusion criteria were: age > 35 years, and poor ovarian reserve (anti-müllerian hormone (AMH) < 1.2 ng/ml, or antral follicle count (AFC) < 5) (indicating low prognosis group 4 following the POSEIDON stratification) (24). Exclusion criteria: including history of ovarian surgery or chemotherapy, autoimmune or endocrine disease, severe male factor infertility
Intervention groups
Astaxanthin consumer. Placebo consumer.
Main outcome variables
1- ART outcomes: Evaluation of the number of MII oocytes & retrieved oocytes, number & quality of embryos, fertilization rate, chemical & clinical pregnancy rate 2- Evaluation of MDA, SOD, TAC, IL-6, IL-8, VEGF in serum and follicular fluid, & Cell-free DNA levels in follicular fluid.

General information

Reason for update
The precise age range under study was determined to ensure the homogeneity of the patient population with poor ovarian response. The selected age range was 36-41 years, corresponding to group 4 of the POSEIDON classification. Additionally, modifying certain variables such as adding variables that include the cycle cancellation rate and the dosage of ovarian stimulation medications which is important in patients with poor ovarian response.
Acronym
IRCT registration information
IRCT registration number: IRCT20230223057510N1
Registration date: 2023-03-16, 1401/12/25
Registration timing: prospective

Last update: 2024-07-28, 1403/05/07
Update count: 1
Registration date
2023-03-16, 1401/12/25
Registrant information
Name
Anahid Shafie
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8826 0049
Email address
shafie-a@alumnus.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-04-04, 1402/01/15
Expected recruitment end date
2024-01-05, 1402/10/15
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The Effect of Astaxanthin Administration on Oxidative Stress Markers and Inflammatory Cytokines in the Follicular Fluid of Patients with Poor Ovarian Response: A Triple-Blind, Randomized control trial
Public title
The Effect of Astaxanthin Administration on poor Ovarian Response
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
POR will be diagnosed based on PSEIDON: (i) age > 35 years, (ii) anti-Mullerian hormone (AMH) < 1.2 ng/mL or antral follicle count (AFC) < 5 The couple should be a candidate for ICSI
Exclusion criteria:
including spontaneous pregnancy, history of ovarian surgery, autoimmune or endocrine disease (diabetes, thyroid dysfunction, presence of anti-thyroid antibody or polycystic ovary), hyperprolactinemia, severe endometriosis (stages III and IV based on AFS-rAFS classification of endometriosis), recurrent Spontaneous miscarriage, ovarian tumor, chromosomal defect, uterine disorder, more than 3 previous IVF cycles, severe male factor infertility (especially non-obstructive azoospermia), history of taking drugs that affect ovarian function such as steroids and OCP. Also, people who have used antioxidant supplements, vitamins or drugs affecting the hormonal profile 3 months before the start of the plan will not be included in the plan. have any history of male factor infertility.
Age
From 36 years old to 41 years old
Gender
Female
Phase
3
Groups that have been masked
  • Participant
  • Care provider
  • Investigator
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 60
Randomization (investigator's opinion)
Randomized
Randomization description
Eligible patients will be randomly assigned to the study after visiting the gynecology clinic. Randomization will be in the form of blocking in such a way that the method of replacement blocks is used within each floor. The blocks will be binary, consisting of AB and BA. The randomization tool will be a table of random numbers, that using the sequence AB for numbers zero through 4 in the random number table and the sequence BA for 5 to 9.It should be noted that the letter A means the intervention group and the letter B means the control group For hiding we use concealment allocation in a way that before the individual is assigned, the assigned group is not specified. In this method, each of the random sequences created on a cards are placed in the closed envelopes. In order to maintain a random sequence, the envelopes are numbered in the same way on the outer surface. Finally, the lids of the envelopes are glued and placed inside a box, respectively. At the time of registration of participants, based on the order of entry of the eligible participants in the study, one of the closed envelopes will be opened and the assigned group of the participant will be revealed.
Blinding (investigator's opinion)
Triple blinded
Blinding description
This study will be a three-way blind and the patient, researcher and statistical analyst of the patients' group therapy have no information and the decoder is outside the research team. The drug under study (Astaxanthin) and placebo in a completely similar shape and appearance, each of which is in the same bottle instead of the drug will be provided to the subjects based on random allocation. It should be noted that the drug content of each The bottles are code-tagged on the bottles by the by someone outside the research team consultant and the research team is not aware of their interpretation.
Placebo
Used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
research ethics committees of scholl of medicine- Tehran university of medical sciences
Street address
Building no.1, Northern gate of the university, Poursina St. Qods St. Enqelab St
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2023-01-01, 1401/10/11
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1401.636

Health conditions studied

1

Description of health condition studied
Poor ovarian response
ICD-10 code
E28.8
ICD-10 code description
Other ovarian dysfunction: Poor ovarian response

Primary outcomes

1

Description
number of MII oocytes
Timepoint
8 weeks after the start of the intervention
Method of measurement
stereo microscope

2

Description
Number of retrieved oocytes
Timepoint
8 weeks after the start of the intervention
Method of measurement
میکروسکوپ استریو

3

Description
Oocyte maturity rate (MII %)
Timepoint
8 weeks after the start of the intervention
Method of measurement
میکروسکوپ استریو

4

Description
Total gonadotrophin doses
Timepoint
During the ovarian stimulation cycle
Method of measurement
The prescribed medication dosage is reported in IU (International Units).

5

Description
rFSH doses
Timepoint
During the ovarian stimulation cycle
Method of measurement
The prescribed medication dosage is reported in IU (International Units).

6

Description
HMG doses
Timepoint
During the ovarian stimulation cycle
Method of measurement
The prescribed medication dosage is reported in IU (International Units).

7

Description
number of embryos
Timepoint
8 weeks and 3 days after the start of the intervention
Method of measurement
stereo microscope

8

Description
Quality of embryos
Timepoint
8 weeks and 3 days after the start of the intervention
Method of measurement
stereo microscope

9

Description
Antral follicular count
Timepoint
before the start of the intervention and 8 weeks after the start of the intervention
Method of measurement
vaginal sonography

10

Description
fertilization rate
Timepoint
8 weeks and 1 day after the start of the intervention (1 day after oocyte pick up)
Method of measurement
stereo microscope

11

Description
chemical pregnancy rate
Timepoint
14 days after embryo transfer
Method of measurement
beta-HCG blood test

12

Description
clinical pregnancy rate
Timepoint
6-8th week of gestational age
Method of measurement
pregnancies showing confirmed clinical markers on ultrasound (like gestational sac and heart rate)

13

Description
Cycle cancellation rate
Timepoint
8 weeks after the start of the intervention
Method of measurement
Percentage of cycles canceled before OPU per the number of started cycles

14

Description
number of transferred embryos
Timepoint
after the embryo transfer
Method of measurement
number of embryos

Secondary outcomes

1

Description
malondialdehyde [MDA] levels in follicular fluid
Timepoint
8 weeks after the start of the intervention
Method of measurement
ELISA Kit

2

Description
superoxide dismutase [SOD] levels in follicular fluid
Timepoint
8 weeks after the start of the intervention
Method of measurement
ELISA Kit

3

Description
total antioxidant capacity [TAC] levels in follicular fluid
Timepoint
8 weeks after the start of the intervention
Method of measurement
ELISA Kit

4

Description
interleukin-6 [IL-6] levels in follicular fluid
Timepoint
8 weeks after the start of the intervention
Method of measurement
ELISA Kit

5

Description
interleukin-8 [IL-8] interleukin-6 [IL-6]
Timepoint
8 weeks after the start of the intervention
Method of measurement
ELISA Kit

6

Description
vascular endothelial growth factor [VEGF] interleukin-6 [IL-6]
Timepoint
8 weeks after the start of the intervention
Method of measurement
ELISA Kit

7

Description
cell-free DNA interleukin-6 [IL-6]
Timepoint
8 weeks after the start of the intervention
Method of measurement
qPCR

8

Description
malondialdehyde [MDA] levels in serum
Timepoint
before the start of the intervention and 8 weeks after the intervention
Method of measurement
ELISA Kit

9

Description
superoxide dismutase [SOD] levels in serum
Timepoint
before the start of the intervention and 8 weeks after the intervention
Method of measurement
ELISA Kit

10

Description
total antioxidant capacity [TAC] levels in serum
Timepoint
before the start of the intervention and 8 weeks after the intervention
Method of measurement
ELISA Kit

11

Description
interleukin-6 [IL-6] levels in serum
Timepoint
before the start of the intervention and 8 weeks after the intervention
Method of measurement
ELISA Kit

12

Description
interleukin-8 [IL-8] levels in serum
Timepoint
before the start of the intervention and 8 weeks after the intervention
Method of measurement
ELISA Kit

13

Description
vascular endothelial growth factor [VEGF] levels in serum
Timepoint
before the start of the intervention and 8 weeks after the intervention
Method of measurement
ELISA Kit

Intervention groups

1

Description
Intervention group: in this group patients, will receive 12 mg of astaxanthin capsules per day (in 3 capsules of 4mg a day) for 8 weeks. The appearance of placebo and astaxanthin capsules are completely similar in terms of color, shape, size and packaging, and patients will not know the contents of the package until the end of the project.
Category
Treatment - Drugs

2

Description
Control group: in this group, patients will receive placebo capsules (3 capsules per day) for 8 weeks. The appearance of placebo and astaxanthin capsules are completely similar in terms of color, shape, size and packaging, and patients will not know the contents of the package until the end of the project.
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Omid fertility clinic
Full name of responsible person
Dr. Ashraf Alyasin
Street address
Baharestan street
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 7767 0696
Fax
Email
omidivf@yahoo.com

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr Akbar Fotoohi
Street address
6th floor of Research and Technology Vice-Chancellor, Central Organization of the University, corner of Qods St, Keshavarz Blvd, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 8163 3619
Email
tums_edu@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Fardin Amidi
Position
professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Poursina St. School of Medicine, Tehran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 6405 3411
Email
amidifardin@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Fardin Amidi
Position
professor
Latest degree
Ph.D.
Other areas of specialty/work
Anatomy
Street address
Poursina St. School of Medicine, Tehran University of Medical Sciences
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 6405 3411
Email
amidifardin@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Anahid Shafie
Position
PhD candidate of reproductive biology
Latest degree
Master
Other areas of specialty/work
Reproductive Biology
Street address
Poursina St. School of Medicine, Tehran University of Medical Sciences, Anatomy department
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 6405 3404
Fax
Email
shafie.a1996@gmail.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
All data obtained in the research will be published in one of the valid and related scientific journals.
When the data will become available and for how long
2025
To whom data/document is available
Researchers working in academic institutions
Under which criteria data/document could be used
The data of this study can be used as an adjuvant therapy in patients with poor ovarian response underwent IVF/ICSI.
From where data/document is obtainable
Anahid Shafie
What processes are involved for a request to access data/document
By sending an email to the corresponding author.
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