PooR Embryo Yield Cleavage Stage Versus blaStocyst Embryo Transfer (PILOT STUDY)
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional

Summary: 
      The purpose of this small-scale pilot study (10 patients) is to test the study protocol for
      an RCT comparing IVF outcomes between day 3 and day 5 embryo transfer in patients with five
      or fewer embryos in a fresh embryo transfer in vitro fertilization (IVF) cycle. Information
      derived from this RCT would allow us to maximize the chances of success for these patients
      undergoing IVF.
    

Detailed description: 
      Embryos created with assisted reproductive technology (ART, e.g. in vitro fertilization
      (IVF)) are commonly transferred into a woman's uterus at either the cleavage stage (day 3
      after egg retrieval) or blastocyst stage (day 5 after egg retrieval). Until recently, most
      IVF cycles transferred embryos at the cleavage stage. However, with improvements in in vitro
      culture technique there has been a steady shift in practice to transfer embryos at the
      blastocyst stage (day 5 after egg retrieval) as this timing is about the same as when embryos
      reach the endometrial cavity in natural conception.

      There now is a general consensus that, for good prognosis patients, those with a high embryo
      from the IVF cycle, it is beneficial to transfer the embryo on day 5 rather than day 3. The
      rationale for this is to allow for self-selection of embryos, meaning those that develop to
      blastocyst in vitro are more likely to be viable in vivo and result in a viable pregnancy. In
      addition, transferring an embryo on day 5 improves uterine/embryonic synchronicity and
      thereby improves outcomes. This allows the transfer of fewer embryos and decreases the
      likelihood of multiples (twins, triplets, etc.).

      As a result, day 5 transfer has become standard of care for good prognosis patients in the
      United States. The American Society of Reproductive Medicine1 issued a committee opinion in
      2013 to this effect stating that in "good prognosis" patients, blastocyst transfer results in
      a significant increase in live birth rates compared to transfer of an equal number of
      cleavage stage embryos (50.5% vs. 30.1%, P< .01)2-5. In addition, for unselected and poor
      prognosis patients, no high-quality studies have evaluated whether blastocyst transfer
      increases live birth rates when compared to cleavage stage transfer.

      It is possible that the attrition of day 3 embryos in vivo is lower than the attrition in
      vitro and that day 5 transfer leads to loss of embryos that may have survived in vivo. In
      addition, women undergoing blastocyst culture are expected to have a higher incidence of
      cycle cancellation due to failure of the embryo to develop to a blastocyst6 and of having
      fewer embryos cryopreserved (frozen)7. Because of this, in Europe and Asia, day 3 transfer is
      the most common practice.

      On the other hand, transferring embryos on day 3 decreases our ability to select the best
      embryo, increases laboratory costs and may increase multiple pregnancy rates as, typically,
      more embryos are transferred at this time. In addition, in vivo, day 3 embryos are in transit
      through the fallopian tube during natural conception and are exposed to a different
      developmental and nutritional environment than day 3 IVF embryos transferred into the uterine
      cavity. Thus, it is possible that exposing day 3 embryos to the physiologically premature
      uterine environment (particularly one that has been subjected to superovulation and thus high
      levels of estrogen) increases embryo attrition compared to day 5 transfer, particularly in
      poor prognosis patients.

      Therefore, a clinical dilemma exists for poor prognosis patients (those with ≤5 embryos
      available on day 1 after egg retrieval). Currently, many practices in the United States
      transfer embryos from these patients on day 3 due to the risk of not having embryos available
      to transfer on day 5. Any remaining embryos are then frozen if they meet criteria on day 5/6.

      Retrospective data from Boston IVF, BIDMC's affiliated infertility treatment center,
      demonstrates that the live birth rate per transfer among poor prognosis patients is 18% among
      those who have a cleavage stage transfer and 38% among those who have a blastocyst transfer.

      At Boston IVF, about 35% of patients have a day 3 embryo transfer, which is consistent with
      national trends. For a patient undergoing an IVF cycle at Boston IVF, a physician may choose
      to transfer an embryo on day 3 or day 5 or allow the laboratory to make that decision, based
      on the number of embryos the patient has on day 1 after egg retrieval and the patient's age.
      This decision typically is made prior to the IVF cycle. As demonstrated above, pregnancy
      rates are far lower in the cleavage stage transfer group and there is the possibility that,
      within a select cohort of these patients, we are unrealistically raising patient's
      expectations of a live birth.

      The purpose of this study is to compare IVF outcomes among poor prognosis patients (≤5
      embryos with two pronuclei) who have a day 3 transfer to those who have a day 5 transfer.
    

Intervention name(s): day 3 uterine transfer; day 5 uterine transfer
Intervention type(s): Procedure; Procedure
Intervention description(s): uterine transfer of embryo on day 3 after fertilization (cleavage stage); uterine transfer of embryo on day 5 after fertilization (blastocyst stage)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: non-inferiority
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: cleavage embryo; blastocyst; embryo transfer; in vitro fertilization