Luteal Support in Frozen-Thawed Embryo Transfer Cycles
Condition: Implantation; Placenta; Pregnancy Loss; Frozen Embryo; Luteal Support; Luteal Phase Defect; Assisted Reproduction
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Dydrogesterone 10Mg Tablet (duphaston); Progesterone 50Mg/mL Oil; Crinone 8% Vaginal Gel
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 40 mg daily oral tablets; 100 mg daily intramuscular injections; 180 mg daily vaginal gels
Intervention MeSH terms: Progesterone; Dydrogesterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: progesterone; implantation; pregnancy; abortion