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Progesterone Versus Progesterone Plus Dydrogesterone in FET

Not Applicable
Completed
Conditions
Infertility
Interventions
Registration Number
NCT03998761
Lead Sponsor
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
1364
Inclusion Criteria
  • Undergoing frozen embryo transfer
  • Endometrial prepared by exogenous hormonal regimen
  • Permanent resident in Vietnam
Read More
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
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Micronized progesterone plus dydrogesteroneMicronized progesterone plus dydrogesteronePatients 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).
Micronized progesteroneMicronized ProgesteronePatients will receive micronized progesterone (Cyclogest® 400mg; Actavis) at the dose of 400mg twice daily (morning and evening).
Primary Outcome Measures
NameTimeMethod
Live birth rateAt 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
NameTimeMethod
The luteal progesterone levelOn day four of the progesterone application

The progesterone level in serum on day four after the progesterone application

Gestational diabetes rateAt 24 weeks of gestation

A type of diabetes that develop during pregnancy

Antepartum haemorrhage rateFrom 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

Ectopic pregnancy rateAt 12 weeks of gestation

A pregnancy in which implantation takes place outside the uterine cavity

Birth weight (grams) of singletons and twinsAt birth

Weight of baby born (grams)

Low birth weight rateAt birth

Weight of baby born \< 2500 g at birth

Gastrointestinal disorders rateAt 7 weeks of gestation

Including nausea, bloating, elevated liver enzymes

Vulvovaginal pruritus rateAt 7 weeks of gestation

Itchiness of the vulva and vagina

The length of luteal phaseOn day sixteen of progesterone application

Starting on the day of progesterone application and ending on the last day prior menses

Very high birth weight rateAt birth

Weight of baby born \> 4500 gm at birth

Venous thromboembolism (VTE) rateAt 7 weeks of gestation

Including deep venous thrombosis and pulmonary embolism

Positive pregnancy test rateOn day sixteen of progesterone application

Serum human chorionic gonadotropin level greater than 5 mIU/mL after the completion of the first transfer

Ongoing pregnancy rateAt 12 weeks' gestation

Pregnancy with detectable heart rate at 12 weeks' gestation or beyond after the completion of the first transfer.

Miscarriage rateAt 12 weeks of gestation

Pregnancy loss at \< 12 weeks

Multiple pregnancy rateAt 7 weeks' gestation

Presence of more than one sac at early pregnancy ultrasound (6-8 weeks of gestation)

Hypertensive disorder of pregnancy rateFrom 20 weeks of gestation up to at birth

Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia

High birth weight rateAt birth

Weight of baby born \>4000 gm at birth

Clinical pregnancy rateAt 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

Implantation rate rateAt 3 weeks after embryo transferred

The number of gestational sacs per number of embryos transferred after the completion of the first transfer.

Preterm delivery rateAt birth

Defined as delivery at \<24, \<28, \<32, \<37 completed weeks

Very low birth weight rateAt birth

Weight of baby born \< 1500 g at birth

Congenital anomaly diagnosed at birth rateAt birth

Any congenital anomalies detected in baby born

Nervous system disorders rateAt 7 weeks of gestation

Including headache, dizziness

Vaginal discharge rateAt 7 weeks of gestation

A fluid produced by glands in the vaginal wall and cervix that drains from the opening of the vagina

Vaginal discomfort rateAt 7 weeks of gestation

Including the symptoms of pain, itching, burning and swelling of vagina and vulva

Trial Locations

Locations (1)

Mỹ Đức Hospital

🇻🇳

Ho Chi Minh City, Tan Binh, Vietnam

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