Optimal Length of Progesterone Supplementation Before the Transfer of Cryopreserved(Frozen)-Thawed Embryos in an Artificial Cycle With Exogenous Estrogen and Progesterone.
Condition: Cryopreservation; Embryo Implantation; Progesteron
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of the study is to determine whether 5 or 7 days of progesterone supplementation
      before transfer of a day 5 cryopreserved thawed embryos in an artificial cycle results in a
      significant higher pregnancy rate.
    

Detailed description: 
      Cryopreserved-thawed embryos are often replaced in an artificial cycle, in which the
      endometrium is prepared by exogenous estrogen and progesterone with or without the use of
      GnRH agonist downregulation. The correct duration for exposure to progesterone is still not
      well established. To date, there are no prospective randomized trials available, comparing
      different durations of progesterone supplementation before the date of transfer, with regard
      to treatment outcome (Nawroth).

      The purpose is to transfer the embryo during the 'window of implantation', what is defined as
      the period during which the uterus is receptive for implantation of the free-lying
      blastocyst. This has been a subject of debate since many years (Bourgain et al, 2007).

      Succesful implantation requires a co-ordinated series of events allowing a timely dialogue
      between a receptive endometrium and the intrusive blastocyst (Tabibzadeh, 1998). The period
      of receptivity is thought to be 3 days in human (Rogers et al, 1989; Yoshinaga, 1988;
      Psychoyos, 1993; Harper, 1992). It is suggested that blastocyst apposition begins about day
      LH+6 and is completed by day LH+10 (Lessey, 2000).

      A number of structural and functional endometrial changes have been suggested to play a role
      in the implantation process: the formation of luminal epithelial pinopodes (Enders et al,
      1973), expression of adhesion molecules and growth factors and cytokines (Lessey, 2000). Most
      of them are related directly or indirectly to progesterone secretion and influence on the
      endometrium.

      In the Centre of Reproductive Medicine of the Brussels University Hospital, we start
      progesterone supplementation 7 days before the transfer of a day 5 embryo. In order to mimic
      the natural cycle, since progesterone starts to rise 2 to 3 days before ovulation, due to the
      LH-stimulated production by the peripheral granulosa cells (Speroff). In fresh IVF-cycles,
      progesterone is started from the day of oocyte retrieval. HCG administration in fresh cycles
      will lead to an increase in progesterone levels and therefore, endometrium will progress
      quickly, compared with frozen-thawed cycles which are hormone supplemented (Nawroth).

      Our approach in artificial FrET cycles results in a pregnancy rate of 26%.

      In other centres, progesterone supplementation is generally started 5 days before the embryo
      transfer. Recent studies show pregnancy rates up to 40.5% (Givens CR et al, 2009), using this
      approach.

      In this trial, we want to determine the optimal duration of progesterone supplementation.
    

Intervention name(s): Progesterone
Intervention type(s): Drug
Intervention MeSH terms: Progesterone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment