Clinical trial NCT03998761: Progesterone Versus Progesterone Plus Dydrogesterone in FET
Official title: Micronized Progesterone Versus Micronized Progesterone Plus Dydrogesterone for Luteal Phase Support in Frozen - Thawed Transfer: a Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Keywords: FET
Micronized Progesterone
Dydrogesterone
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2019-06-26
Enrollment: 1364
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Live birth rate
timeFrame: At least 24 weeks of gestation up to the time of delivery
Secondary outcomes:
measure: The luteal progesterone level
timeFrame: On day four of the progesterone application
measure: The length of luteal phase
timeFrame: On day sixteen of progesterone application
measure: Positive pregnancy test rate
timeFrame: On day sixteen of progesterone application
measure: Clinical pregnancy rate
timeFrame: At 7 weeks of gestation
measure: Ongoing pregnancy rate
timeFrame: At 12 weeks' gestation
measure: Implantation rate rate
timeFrame: At 3 weeks after embryo transferred
measure: Ectopic pregnancy rate
timeFrame: At 12 weeks of gestation
measure: Miscarriage rate
timeFrame: At 12 weeks of gestation
measure: Multiple pregnancy rate
timeFrame: At 7 weeks' gestation
measure: Gestational diabetes rate
timeFrame: At 24 weeks of gestation
measure: Hypertensive disorder of pregnancy rate
timeFrame: From 20 weeks of gestation up to at birth
measure: Antepartum haemorrhage rate
timeFrame: From 24 weeks of gestation up to at birth
measure: Preterm delivery rate
timeFrame: At birth
measure: Birth weight (grams) of singletons and twins
timeFrame: At birth
measure: Low birth weight rate
timeFrame: At birth
measure: Very low birth weight rate
timeFrame: At birth
measure: High birth weight rate
timeFrame: At birth
measure: Very high birth weight rate
timeFrame: At birth
measure: Congenital anomaly diagnosed at birth rate
timeFrame: At birth
measure: Venous thromboembolism (VTE) rate
timeFrame: At 7 weeks of gestation
measure: Gastrointestinal disorders rate
timeFrame: At 7 weeks of gestation
measure: Nervous system disorders rate
timeFrame: At 7 weeks of gestation
measure: Vaginal discharge rate
timeFrame: At 7 weeks of gestation
measure: Vaginal discomfort rate
timeFrame: At 7 weeks of gestation
measure: Vulvovaginal pruritus rate
timeFrame: At 7 weeks of gestation
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Mỹ Đức Hospital
state: Tan Binh
Study officials:
affiliation: Hope Research Center
name: Tuong M Ho, MD
role: STUDY_CHAIR
References:
citation: 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.
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