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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,364
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.
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.
Mỹ Đức Hospital
Ho Chi Minh City, Tan Binh, Vietnam
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).
Time frame: At least 24 weeks of gestation up to the time of delivery
The luteal progesterone level
The progesterone level in serum on day four after the progesterone application
Time frame: On day four of the progesterone application
The length of luteal phase
Starting on the day of progesterone application and ending on the last day prior menses
Time frame: On day sixteen of progesterone application
Positive pregnancy test rate
Serum human chorionic gonadotropin level greater than 5 mIU/mL after the completion of the first transfer
Time frame: On day sixteen of progesterone application
Clinical pregnancy rate
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
Time frame: At 7 weeks of gestation
Ongoing pregnancy rate
Pregnancy with detectable heart rate at 12 weeks' gestation or beyond after the completion of the first transfer.
Time frame: At 12 weeks' gestation
Implantation rate rate
The number of gestational sacs per number of embryos transferred after the completion of the first transfer.
Time frame: At 3 weeks after embryo transferred
Ectopic pregnancy rate
A pregnancy in which implantation takes place outside the uterine cavity
Time frame: At 12 weeks of gestation
Miscarriage rate
Pregnancy loss at \< 12 weeks
Time frame: At 12 weeks of gestation
Multiple pregnancy rate
Presence of more than one sac at early pregnancy ultrasound (6-8 weeks of gestation)
Time frame: At 7 weeks' gestation
Gestational diabetes rate
A type of diabetes that develop during pregnancy
Time frame: At 24 weeks of gestation
Hypertensive disorder of pregnancy rate
Comprising pregnancy induced hypertension (PIH); pre-eclampsia (PET) and eclampsia
Time frame: From 20 weeks of gestation up to at birth
Antepartum haemorrhage rate
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
Time frame: From 24 weeks of gestation up to at birth
Preterm delivery rate
Defined as delivery at \<24, \<28, \<32, \<37 completed weeks
Time frame: At birth
Birth weight (grams) of singletons and twins
Weight of baby born (grams)
Time frame: At birth
Low birth weight rate
Weight of baby born \< 2500 g at birth
Time frame: At birth
Very low birth weight rate
Weight of baby born \< 1500 g at birth
Time frame: At birth
High birth weight rate
Weight of baby born \>4000 gm at birth
Time frame: At birth
Very high birth weight rate
Weight of baby born \> 4500 gm at birth
Time frame: At birth
Congenital anomaly diagnosed at birth rate
Any congenital anomalies detected in baby born
Time frame: At birth
Venous thromboembolism (VTE) rate
Including deep venous thrombosis and pulmonary embolism
Time frame: At 7 weeks of gestation
Gastrointestinal disorders rate
Including nausea, bloating, elevated liver enzymes
Time frame: At 7 weeks of gestation
Nervous system disorders rate
Including headache, dizziness
Time frame: At 7 weeks of gestation
Vaginal discharge rate
A fluid produced by glands in the vaginal wall and cervix that drains from the opening of the vagina
Time frame: At 7 weeks of gestation
Vaginal discomfort rate
Including the symptoms of pain, itching, burning and swelling of vagina and vulva
Time frame: At 7 weeks of gestation
Vulvovaginal pruritus rate
Itchiness of the vulva and vagina
Time frame: At 7 weeks of gestation
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.