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Progesterone Versus Progesterone Plus Dydrogesterone in FET (MiDRONE)

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ClinicalTrials.gov Identifier: NCT03998761
Recruitment Status : Completed
First Posted : June 26, 2019
Last Update Posted : February 24, 2021
Sponsor:
Information provided by (Responsible Party):
Mỹ Đức Hospital

Brief Summary:

Frozen embryo transfer (FET) has been increasing important in IVF. Progesterone is essential for the endometrial secretory transformation, establishment and maintenance of pregnancy. In FET, as there is neither corpus luteum nor the support of hCG, the role of progesterone is even more important to ensure a sufficient luteal phase support.

Vaginal progesterone has been the most common preparation for luteal support in fresh embryo transfer during IVF because of their ease of use and comparable effectiveness compared to intramuscular progesterone. Recently, there was evidence of the considerable variation in uptake, absorption and metabolism of intra-vaginal micronized progesterone. Dydrogesterone alone has described to have similar effectiveness, safety and tolerability prolfiles for luteal phase support compared to vaginal progesterone in luteal phase support for fresh embryo transfer. This prospective study compares the effectiveness of micronized progesterone versus micronized progesterone plus dydrogesterone for luteal phase support in FET.


Condition or disease Intervention/treatment Phase
Infertility Drug: Micronized Progesterone Drug: Micronized progesterone plus dydrogesterone Not Applicable

Detailed Description:

All patients undergoing FET will receive oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day from the second or third day of menses for 6 days. Endometrial thickness will be monitored from day six onwards. From day 8-9 of menses, the estradiol dose could be adjusted from 8mg/day to 16mg/day according the development of the endometrium. Progesterone will be started when endometrial thickness reached 8 mm or more. In the first four months, all the patients will be treated with micronized progesterone. In five months later, the intervention will be changed to micronized progesterone plus dydrogesterone. In the second group of patients, the duration of study will be extended for one month due to the Lunar New Year holiday.

Group 1: Micronized progesterone Patients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening).

Group 2: Micronized progesterone plus dydrogesterone Patients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening) plus dydrogesterone (Duphaston 10mg) at the dose of 10mg twice daily (morning and evening).

In both group, on the day of starting progesterone, the dose of estradiol will be decreased to 8mg/day. A maximum of 2 embryos will be thawed on the day of embryo transfer, which is four days or six days after the start of progesterone depending on day-3 or day-5 embryo transfer. After thawing, surviving embryos will be transferred into the uterus under ultrasound guidance. Estradiol and progesterone will be continued until the day of pregnancy test. If the pregnancy test is positive, the patients will continue to use 800 mg micronized progesterone or 800 mg micronized progesterone plus 20 mg dydrogestetrone, until 7 weeks of gestation.

Blood samples will be obtained at day 4 after the use of progesterone. Serum progesterone will be measured. The blood tests will be taken in the morning, 2-3 h after the dydrogesterone and/or micronized progesterone application.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1364 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Micronized Progesterone Versus Micronized Progesterone Plus Dydrogesterone for Luteal Phase Support in Frozen - Thawed Transfer: a Prospective Cohort Study
Actual Study Start Date : June 26, 2019
Actual Primary Completion Date : January 5, 2021
Actual Study Completion Date : January 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Micronized progesterone
Patients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening).
Drug: Micronized Progesterone
Progesterone will be started when endometrial thickness reached 8 mm or more. Patients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening). A maximum of 2 embryos will be thawed on the day of embryo transfer, which is four days or six days after the start of progesterone depending on day-3 or day-5 embryo transfer. After thawing, surviving embryos will be transferred into the uterus under ultrasound guidance. Estradiol and progesterone will be continued until the day of pregnancy test. If the pregnancy test is positive, the patients will continue to use 800 mg micronized progesterone until 7 weeks of gestation.
Other Name: Cyclogest 400mg

Active Comparator: Micronized progesterone plus dydrogesterone
Patients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening) plus dydrogesterone (Duphaston® 10mg, Abbott) at the dose of 10mg twice daily (morning and evening).
Drug: Micronized progesterone plus dydrogesterone
Progesterone will be started when endometrial thickness reached 8 mm or more. Patients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening) plus dydrogesterone (Duphaston® 10mg, Abbott) at the dose of 10mg twice daily (morning and evening). A maximum of 2 embryos will be thawed on the day of embryo transfer, which is four days or six days after the start of progesterone depending on day-3 or day-5 embryo transfer. After thawing, surviving embryos will be transferred into the uterus under ultrasound guidance. Estradiol and progesterone will be continued until the day of pregnancy test. If the pregnancy test is positive, the patients will continue to use 800 mg micronized progesterone plus 20 mg dydrogestetrone until 7 weeks of gestation.
Other Name: Cyclogest 400 mg + Duphaston 10 mg




Primary Outcome Measures :
  1. Live birth rate [ Time Frame: At least 24 weeks of gestation up to the time of delivery ]
    The birth of at least one newborn after 24 weeks of gestation that exhibits any sign of life such as respiration, heartbeat, umbilical pulsation or movement of voluntary muscles (twin will be a single count).


Secondary Outcome Measures :
  1. The luteal progesterone level [ Time Frame: On day four of the progesterone application ]
    The progesterone level in serum on day four after the progesterone application

  2. The length of luteal phase [ Time Frame: On day sixteen of progesterone application ]
    Starting on the day of progesterone application and ending on the last day prior menses

  3. Positive pregnancy test rate [ Time Frame: On day sixteen of progesterone application ]
    Serum human chorionic gonadotropin level greater than 5 mIU/mL after the completion of the first transfer

  4. Clinical pregnancy rate [ Time Frame: At 7 weeks of gestation ]
    At least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity after the completion of the first transfer

  5. Ongoing pregnancy rate [ Time Frame: At 12 weeks' gestation ]
    Pregnancy with detectable heart rate at 12 weeks' gestation or beyond after the completion of the first transfer.

  6. Implantation rate rate [ Time Frame: At 3 weeks after embryo transferred ]
    The number of gestational sacs per number of embryos transferred after the completion of the first transfer.

  7. Ectopic pregnancy rate [ Time Frame: At 12 weeks of gestation ]
    A pregnancy in which implantation takes place outside the uterine cavity

  8. Miscarriage rate [ Time Frame: At 12 weeks of gestation ]
    Pregnancy loss at < 12 weeks

  9. Multiple pregnancy rate [ Time Frame: At 7 weeks' gestation ]
    Presence of more than one sac at early pregnancy ultrasound (6-8 weeks of gestation)

  10. Gestational diabetes rate [ Time Frame: At 24 weeks of gestation ]
    A type of diabetes that develop during pregnancy

  11. Hypertensive disorder of pregnancy rate [ Time Frame: From 20 weeks of gestation up to at birth ]
    Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia

  12. Antepartum haemorrhage rate [ Time Frame: From 24 weeks of gestation up to at birth ]
    Defined as bleeding from or in to the genital tract, occurring from 24 weeks of pregnancy and prior to the birth of the baby, including placenta previa, placenta accreta and unexplained

  13. Preterm delivery rate [ Time Frame: At birth ]
    Defined as delivery at <24, <28, <32, <37 completed weeks

  14. Birth weight (grams) of singletons and twins [ Time Frame: At birth ]
    Weight of baby born (grams)

  15. Low birth weight rate [ Time Frame: At birth ]
    Weight of baby born < 2500 g at birth

  16. Very low birth weight rate [ Time Frame: At birth ]
    Weight of baby born < 1500 g at birth

  17. High birth weight rate [ Time Frame: At birth ]
    Weight of baby born >4000 gm at birth

  18. Very high birth weight rate [ Time Frame: At birth ]
    Weight of baby born > 4500 gm at birth

  19. Congenital anomaly diagnosed at birth rate [ Time Frame: At birth ]
    Any congenital anomalies detected in baby born

  20. Venous thromboembolism (VTE) rate [ Time Frame: At 7 weeks of gestation ]
    Including deep venous thrombosis and pulmonary embolism

  21. Gastrointestinal disorders rate [ Time Frame: At 7 weeks of gestation ]
    Including nausea, bloating, elevated liver enzymes

  22. Nervous system disorders rate [ Time Frame: At 7 weeks of gestation ]
    Including headache, dizziness

  23. Vaginal discharge rate [ Time Frame: At 7 weeks of gestation ]
    A fluid produced by glands in the vaginal wall and cervix that drains from the opening of the vagina

  24. Vaginal discomfort rate [ Time Frame: At 7 weeks of gestation ]
    Including the symptoms of pain, itching, burning and swelling of vagina and vulva

  25. Vulvovaginal pruritus rate [ Time Frame: At 7 weeks of gestation ]
    Itchiness of the vulva and vagina



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Undergoing frozen embryo transfer
  • Endometrial prepared by exogenous hormonal regimen
  • Permanent resident in Vietnam

Exclusion Criteria:

  • Having > 2 embryo transfer attempts
  • Having embryo(s) from donors cycles
  • Having embryo(s) from IVM
  • Having embryo(s) from PGT/PGS
  • Having endometrial abnormalities: polyp, sub-mucosal fibroid, cesarean scar defects, endometrial hyperplasia, endometrial fluid accumulation, endometrial adhesion.
  • Participating in another IVF study at the same time

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03998761


Locations
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Vietnam
Mỹ Đức Hospital
Ho Chi Minh City, Tan Binh, Vietnam
Sponsors and Collaborators
Mỹ Đức Hospital
Investigators
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Study Chair: Tuong M Ho, MD Hope Research Center
Publications:

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Responsible Party: Mỹ Đức Hospital
ClinicalTrials.gov Identifier: NCT03998761    
Other Study ID Numbers: CS/BVMĐ/19/06
First Posted: June 26, 2019    Key Record Dates
Last Update Posted: February 24, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mỹ Đức Hospital:
FET
Micronized Progesterone
Dydrogesterone
Additional relevant MeSH terms:
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Infertility
Progesterone
Dydrogesterone
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs