Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer

Capsule:
Frozen embryo transfer is now competitive with fresh transfer and may be superior in some cases. Numerous factors should be considered when deciding between them.

Authors:
Bruce S. Shapiro, M.D., Ph.D., Said T. Daneshmand, M.D., Forest Garner, M.S., Martha Aguirre, Ph.D., Cynthia Hudson, M.S.

Volume 102, Issue 1, Pages 3-9

Abstract:
Recent dramatic increases in success rates with frozen–thawed embryo transfer (FET) are encouraging, as are numerous findings of several reduced risks with FET when compared with fresh transfer. These reduced risks include low birth weight and prematurity, among others. However, FET is also associated with increased risks of macrosomia and large for gestational age. There have been reports of greater implantation and pregnancy rates with FET than with fresh autologous embryo transfer, suggesting superior endometrial receptivity in the absence of ovarian stimulation. As cryo-technology evolves, there is potential for further increase in FET success rates, but for now it may be best to follow an individualized approach, balancing fresh transfer and embryo cohort cryopreservation options while considering patient characteristics, cycle parameters, and clinic success rates.

  • Mete Isikoglu

    “Is it too early for a major change?
    A critical objection to the freeze all policy”

    In Vitro Fertilization (IVF) has created an opportunity for numerous couples who
    would otherwise never have had a chance to get pregnant. Subsequently, embryo cryopreservation and frozen embryo transfer (FET) was successfully introduced into all IVF programs from mid 1980s (1). The rationale on which freezing the surplus embryos is based is essentially to avoid repeating all the stressful and expensive steps of an IVF procedure in case of implantation failure with the fresh embryo transfer. If the outcome of the fresh embryo transfer is a healthy delivery, then the frozen embryos are available for a future sibling conception. Another less common indication for embryo freezing is in case of impending severe ovarian hyperstimulation syndrome
    (OHSS) in which all embryos are frozen. Similar situations arise in case of
    fluid collection in endometrial cavity, endometrial bleeding or related
    infrequent problems. All these indications for freezing all or super-numerary embryos
    are consistent with the statements of Declaration of Helsinki (2.).

    Recent argument regarding “freezing all the embryos routinely or not” is limited to
    comparison of the implantation rates, live birth rates and maternal, fetal or
    neonatal parameters between the “all freeze” and the “fresh transfer” groups.
    Indeed, another critical point with utmost importance must be the long term outcome
    of these individuals.

    In my opinion, the following aspect should be the focus of debate in the issue of
    freezing all embryos routinely:

    The first successful frozen IVF baby was born in 1984. Hence, the oldest frozen IVF
    individuals are in their early thirties. Thus, no comment on any theoretical
    long term risk (e.g. any cognitive disorder or neoplastic disease) can be done.
    Declaration of Helsinki draws a strict frame regarding any unproven
    interventions by stating that “In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an unproven intervention if in the
    physician’s judgement it offers hope of saving life, re-establishing health or
    alleviating suffering. This intervention should subsequently be made the object
    of research, designed to evaluate its safety and efficacy. In all cases, new
    information must be recorded and, where appropriate, made publicly available”
    (2). Although frozen embryo transfer is proven to be able to result in a healthy delivery, the long term outcome is not available yet which means long term safety has not been proven. Instead of taking any more risks of disturbing the embryo by encountering the physical stress of freeze/thaw procedure, it seems wiser to do fresh embryo transfers.
    This is a point of debate if one freezes all the embryos routinely for elective
    FET. Hence, “freeze all policy” should be scuritinized regarding its
    consistency with the statements of Declaration of Helsinki.

    Then another question comes up: From the ethical point of view, is it really justifiable to freeze all the embryos routinely if no risk factor for severe OHSS or endometrial problems exist at all?

    Taking into consideration the drawbacks enumerated above, the “all freeze” policy should not be performed liberally just based on the encouraging implantation rates of
    cryopreservation/frozen embryo transfer program of any particular IVF center. Besides,
    advantages of frozen embryo transfer regarding maternal and neonatal parameters
    still await randomized controlled trials (3).
    In conclusion, efforts for switching to milder stimulation protocols and working
    towards ideal laboratory conditions may be the key factors in order to improve
    the outcome measures while waiting for the long term results of frozen
    individuals.

    References:

    1.Zeilmaker
    GH, Alberda AT, van Gent I, Rijkmans CM, Drogendijk AC.Two pregnancies
    following transfer of intact frozen-thawed embryos. Fertil Steril.
    1984;42(2):293-6.

    2.WMA Declaration of Helsinki – Ethical
    Principles for Medical Research Involving Human Subjects. Formun Üstü

    Adopted by
    the 18th World Medical Association General Assembly, Helsinki, Finland, June
    1964 the latest amendment was done by the: 64th WMA General Assembly, Fortaleza,
    Brazil, October 2013

    3.Evans J, Hannan NJ, Edgell TA, Vollenhoven BJ, Lutjen PJ, Osianlis T, Salamonsen LA, Rombauts LJ. Fresh versus frozen embryo transfer: backing clinical decisions with
    scientific and clinical evidence. Hum Reprod Update. 2014 Nov-Dec;20(6):808-21.
    doi: 10.1093/humupd/dmu027. Epub 2014 Jun 10.

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