Luteal Support in Frozen-Thawed Embryo Transfer Cycles

This study evaluates the clinical efficacy of 3 different luteal phase support in patients undergoing frozen-thawed embryo transfer cycles. Endometrium preparation will be hormone replacement in all cycles. Starting from day 11, group 1 will receive 100 mg micronized progesterone parenteral daily injections, group 2 will receive 90 mg bioadhesive gel vaginal twice daily and group 3 will receive 40 mg oral dydrogesterone daily tablets.

In natural pregnancy, successful implantation and pregnancy necessitates well-functioning corpus luteum. Luteal phase support (LPS) is critical in assisted conception cycles particularly for replacement frozen embryo transfer cycles owing to lack of corpus luteum. 3 different LPS options have been suggested:

* Progesterone in oil (intramuscular injections) is rapidly absorbed after i.m. injection and high progesterone plasma concentrations are reached after approximately 2h. Despite satisfactory plasma levels, the possible side-effects of pain and swelling are limiting the use.
* Vaginal application of progesterone is widely accepted with satisfactory endometrial levels and patient convenience. However, increased vaginal discharge and possible vaginal irritation are the most common side effects.
* Oral administration of synthetic progesterone (dydrogesterone) would offer a convenient way of progesterone administration. Better bioavailability than natural progesterone and less cost makes dydrogesterone preferable. Also, good quality evidence revealed satisfactory outcomes in fresh embryo transfer cycles. However, there is lack of good quality evidence for dydrogesterone as a LPS in frozen-thawed cycles.

The investigator's aim is to compare 3 widely used LPS in frozen-thawed embryo transfer cycles.

Following allocation of the subjects, hormone replacement will be scheduled for the endometrial preparation. Briefly; On day 2 of menstrual bleeding, endometrial preparation with oral estradiol (E2) (2 mg twice daily) will be initiated. Approximately 10 days after initiation of E2 administration, the subject will undergo a transvaginal ultrasound examination to assess endometrial development and serum progesterone (P) level will be checked. Once the subject achieved a trilaminar endometrium with a thickness of \>7 mm with serum P levels \<1.5 ng/ml, she will start the progesterone treatment to which she will be randomized to one of the 3 arms. After 3 days of P treatment along with E2 pills, cleavage embryo transfer will be performed. If the subject will receive blastocyst, 5 days of P treatment will be scheduled.

If these criteria were not met at the first evaluation, she will allowed up to 10 additional days (20 days total) of estrogen stimulation.

Eligibility Criteria:
Inclusion Criteria:

* woman aged 20-40 years
* Having available blastocyst(s) cryopreserved by vitrification method.

Exclusion Criteria:

* requirement for fresh embryo(s);
* presence of any clinically relevant systemic disease contraindicated for assisted reproduction or pregnancy
* history of more than three failed cycles of IVF
* history of recurrent abortions
* allergy history for relevant drugs
* body mass index of \<18 or \>38 kg/m2 at screening
* current breastfeeding or pregnancy
* refusal or inability to comply with the requirements of the protocol for any reason, including scheduled clinic visits and laboratory tests
* trophectoderm or blastomere biopsy of the blastocyst(s) to be transferred