Progesterone Versus Progesterone Plus Dydrogesterone in FET

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.

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