Progesterone Versus Progesterone Plus Dydrogesterone in FET

NCT03998761 | Completed

• 1 other identifier: CS/BVMĐ/19/06
• Study Type: interventional
• Target: 1,364
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility

Keywords

FET; Micronized Progesterone; Dydrogesterone

Outcome Measures

Primary Outcomes (1)

• Live birth rate

  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).

  At least 24 weeks of gestation up to the time of delivery

Secondary Outcomes (25)

• The luteal progesterone level

  On day four of the progesterone application

• The length of luteal phase

  On day sixteen of progesterone application

• Positive pregnancy test rate

  On day sixteen of progesterone application

• Clinical pregnancy rate

  At 7 weeks of gestation

• Ongoing pregnancy rate

  At 12 weeks' gestation

Study Arms (2)

Micronized progesterone

ACTIVE COMPARATOR

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

Drug: Micronized Progesterone

Micronized progesterone plus dydrogesterone

ACTIVE COMPARATOR

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

Interventions

Micronized Progesterone DRUG

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.

Also known as: Cyclogest 400mg

Micronized progesterone

Micronized progesterone plus dydrogesterone DRUG

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.

Also known as: Cyclogest 400 mg + Duphaston 10 mg

Micronized progesterone plus dydrogesterone

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (1)

Mỹ Đức Hospital

Ho Chi Minh City, Tan Binh, Vietnam

Location

Related Publications (9)

• Barbosa MW, Silva LR, Navarro PA, Ferriani RA, Nastri CO, Martins WP. Dydrogesterone vs progesterone for luteal-phase support: systematic review and meta-analysis of randomized controlled trials. Ultrasound Obstet Gynecol. 2016 Aug;48(2):161-70. doi: 10.1002/uog.15814. Epub 2016 Jul 8.

  PMID: 26577241 BACKGROUND

• Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, Chen ZJ, Kahler E, Pexman-Fieth C, Tournaye H. Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod. 2018 Dec 1;33(12):2212-2221. doi: 10.1093/humrep/dey306.

  PMID: 30304457 BACKGROUND

• Griesinger G, Blockeel C, Tournaye H. Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil Steril. 2018 May;109(5):756-762. doi: 10.1016/j.fertnstert.2018.03.034.

  PMID: 29778368 BACKGROUND

• Tournaye H, Sukhikh GT, Kahler E, Griesinger G. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017 May 1;32(5):1019-1027. doi: 10.1093/humrep/dex023.

  PMID: 28333318 BACKGROUND

• Wang Y, He Y, Zhao X, Ji X, Hong Y, Wang Y, Zhu Q, Xu B, Sun Y. Crinone Gel for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Prospective Randomized Clinical Trial in the Chinese Population. PLoS One. 2015 Jul 29;10(7):e0133027. doi: 10.1371/journal.pone.0133027. eCollection 2015.

  PMID: 26222435 BACKGROUND

• Wei D, Liu JY, Sun Y, Shi Y, Zhang B, Liu JQ, Tan J, Liang X, Cao Y, Wang Z, Qin Y, Zhao H, Zhou Y, Ren H, Hao G, Ling X, Zhao J, Zhang Y, Qi X, Zhang L, Deng X, Chen X, Zhu Y, Wang X, Tian LF, Lv Q, Ma X, Zhang H, Legro RS, Chen ZJ. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019 Mar 30;393(10178):1310-1318. doi: 10.1016/S0140-6736(18)32843-5. Epub 2019 Feb 28.

  PMID: 30827784 BACKGROUND

• Yanushpolsky E, Hurwitz S, Greenberg L, Racowsky C, Hornstein M. Crinone vaginal gel is equally effective and better tolerated than intramuscular progesterone for luteal phase support in in vitro fertilization-embryo transfer cycles: a prospective randomized study. Fertil Steril. 2010 Dec;94(7):2596-9. doi: 10.1016/j.fertnstert.2010.02.033. Epub 2010 Mar 27.

  PMID: 20347079 BACKGROUND

• Labarta E, Mariani G, Holtmann N, Celada P, Remohi J, Bosch E. Low serum progesterone on the day of embryo transfer is associated with a diminished ongoing pregnancy rate in oocyte donation cycles after artificial endometrial preparation: a prospective study. Hum Reprod. 2017 Dec 1;32(12):2437-2442. doi: 10.1093/humrep/dex316.

  PMID: 29040638 BACKGROUND

• Yovich JL, Conceicao JL, Stanger JD, Hinchliffe PM, Keane KN. Mid-luteal serum progesterone concentrations govern implantation rates for cryopreserved embryo transfers conducted under hormone replacement. Reprod Biomed Online. 2015 Aug;31(2):180-91. doi: 10.1016/j.rbmo.2015.05.005. Epub 2015 May 18.

  PMID: 26099447 BACKGROUND

MeSH Terms

Conditions

Infertility

Interventions

Progesterone; Dydrogesterone

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Pregnadienes

Study Officials

• Tuong M Ho, MD

  Hope Research Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: June 26, 2019
• Study Start: June 26, 2019
• Primary Completion: January 5, 2021
• Study Completion: January 31, 2021
• Last Updated: February 24, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)