The Outcome of Two Protocols Used to Prepare Endometrium for Frozen Embryo Transfer
Condition: Infertility; Infertility, Female; Infertility, Male
MeSH terms: Infertility; Infertility, Female; Infertility, Male
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a RCT to test the outcome of two protocols used for preparation of the endometrium
      for frozen blastocyst embryo transfer
    

Detailed description: 
      Receptive endometrium and a good quality embryo at the blastocyst developmental stage are
      prerequisites for a successful implantation to occur. Blastocyst freezing techniques and
      survival have witnessed huge improvements in the last years. Trials to improve the outcome of
      frozen embryo transfer (FET) are not to be stopped. The transfer of a good quality blastocyst
      represents a vital part of the process. Optimization of endometrial receptivity and
      implantation is an everlasting challenge.

      Hormone replacement therapy (HRT) is now proven to be successful for preparation of the
      endometrium to receive the vitrified warmed embryos. Most HRT protocols give estradiol (E2)
      first to reach a satisfactory endometrial thickness, then followed by progesterone to mimic
      the natural cycles. E2 is mostly given for 10 to 14 days and this duration might be prolonged
      to reach a satisfactory endometrial thickness without adversely affecting the outcome.
      Trans-vaginal ultrasound assessment of the endometrial thickness before the start of P
      supplementation has been traditionally used to predict FET cycle outcome. Clinical pregnancy
      rates (CPR) and live birth rates (LBR) were found to decrease for each millimetre of
      endometrial thickness below 7 mm. Endometrial thickness however of 9 mm was reported to be
      among major factors affecting LBR after FET in a large set of data.

      Further, there is a recent concept that endometrial compaction (decreased thickness) between
      the end of estrogen phase and the day of ET has favorable impact on the outcome of FET.
      Different modalities were proposed to enhance endometrial compaction. One of these modalities
      was to decrease the dose of estrogen so as to change the estrogen- progesterone ratio as well
      as help in preventing further endometrial growth.

      Aromatase inhibitor (AI) can be used to decrease estrogen before starting P supplementation.
      Additionally, there were also reports that their use had been associated with improved
      implantation. It appears interesting to combine the easy scheduled HRT protocol with
      aromatase inhibitor to maximize FET outcome.

      This proposed protocol has not been tested before. In current study, HRT plus AI will be
      compared with HRT only. In both groups, daily intramuscular P will be given for luteal
      support as it was shown to give the highest ongoing pregnancy rate in FET cycles.

      We did a secondary follow up analysis of some exploratory outcomes (not preregistered). These
      outcomes were analyzed after publication and they include Live birth rate, implantation rate,
      hypertensive disorders of pregnancy, large for gestation and congenital anomalies. The
      results of these outcomes are planned to be presented elsewhere. For openness and
      transparency, we felt the importance to report this follow up in the registry.
    

Intervention name(s): Estradiol Valerate; Progesterone; Aromatase inhibitor
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 2mg three times daily; 100 mg daily intramuscular; 2.5 mg twice daily for 5 days
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Progesterone; Aromatase Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment