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Fresh versus Frozen Embryo Transfer (FET) Enhances IVF Outcome

by Dr. Geoffrey Sher on August 27, 2018

“I am in full agreement with researchers at Cambridge University in the United Kingdom who following a recently published a report on their observation that FET enhances IVF outcome, stated that this could represent one of the most “exciting” IVF revelations of the last  25 years.”

I am often asked by patients whether there is a benefit in doing frozen embryo transfers over fresh embryo transfers and how this decision impacts IVF outcome. Women undergoing IVF usually have one or more fresh embryos transferred within a week of their eggs being harvested following ovarian stimulation with fertility drugs

I have long held that, provided embryos are frozen in their most advanced (blastocyst) stage of development,  that freezing is effected using ultra-rapid vitrification (rather than using previous slow-freezing methods) and optimal technique is employed during the performance of the freezing process, that Frozen Embryo Transfer (FET) will not compromise IVF outcome. It has been my expressed position that while this benefit is least apparent in younger women (<35y) and those who have a normal ovarian reserve, it quite profound when it comes to older women, women who have Diminished Ovarian Reserve (DOR) and women with Polycystic Ovarian Syndrome (PCOS). It is my opinion that this is largely attributable to the fact that the ovaries of the latter group of women have a tendency to over-produce  male hormones (androgens) such as androstenedione and testosterone which reach the ovarian follicles in excess , compromising egg development and maturation thereby  increasing the incidence of egg numerical chromosomal irregularities during meiosis (maturational division) and diminishing the  “competency” to produce viable embryos following fertilization.

A recent study reported from Cambridge in the United Kingdom has now confirmed this observation, reporting a roughly 50% improvement per embryo transferred following FET as compared with fresh embryo transfers.

The reason for the improvement in IVF outcome following FET obviously has little to do with any direct influence of freezing on embryo competency. Rather, it likely is due to targeted and measured hormonal manipulation in preparation for FET improving optimize endometrial receptivity. This likely also serves to explain why older women, women with DOR and those who are high responders (e.g. PCOS) and accordingly have dysfunctional ovarian hormonal production in response to ovarian stimulation with fertility drugs are the ones who are most likely to benefit from more programmed endometrial development.

Regardless however, it should be pointed out that this new revelation showing that FET can only enhance IVF results, should be comforting to those women undergoing FET for other established indications such as: preimplantation genetic screening (PGS) and/or Preimplantation Genetic Diagnosis (PGD), both of which preclude performing embryo transfer in the same cycle as the egg retrieval and  for other embryo recipient situations such as egg donor-IVF, Gestational Surrogacy (GS) and Embryo Adoption (EA).

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  • Eva - September 24, 2018 reply

    Hi Dr Sher,

    My question is do you ever see cases where a fresh transfer could be better than a FET, even if the couple is able to freeze and test embryos?

    I just turned 39, and have been doing fertility treatment for 3 years. My husband is 41 and suffers from MFI. No known female issues other than controlled hashimotos.

    We have done 5 transfers in total. Our first was a failed day 3 transfer. Our second one was a fresh transfer on day 5 and it worked, but ended in mmc at 12 weeks.

    Since then we have done 3 FETs with PGS normal embryos, and all have failed. The first one of those FETS was done with an embryo biopsied and frozen on day 3 and then banked for day 5 transfer. The other two have each been with 3 normal embryos that were biopsied and frozen on day 5.

    Prior to the last FET, a hysteroscopy found a small amount of scar tissue that was removed. The only other main difference between the fresh transfer that worked and these failed FETS was that the fresh transfer had me on dexamethasone from early on during stimulation to around 7 weeks of pregnancy. The FETs were all done with just 4 days of prednisone prior to transfer.

    PGS testing in our most recent cycle resulted in all normal embryos (3/3), and this was after both my husband and myself did 10 weeks of hgh injections prior to retrieval. The previous two cycles in this clinic (where only I did hgh during stimulation) got us 50% normal blasts on each(1/2 and 2/4). So cumulatively we have close to a 70% rate of normal embryos in this current clinic.

    Considering this, would you consider we should go back to trying a fresh transfer, since it worked before? We would test any frozen embryos from the same cycle.
    As a note, the two inital fresh transfers were done when my husband’s counts were far lower, and in a clinic that seemed to have a less advanced lab. (no pgs offered, etc). He had a testicle biopsy done that was used for those two, whereas subsequent cycles were done with a normal semen sample. I’m currently considering switching doctors within my current clinic because they have opened up a branch much closer to me. My main RE is very much against not doing PGS. The new one thinks a fresh transfer is worth a shot since it worked before, and since our abnormal embyros all had the type of abnormalities that would not have ended up in a live birth with an baby with a condition. She told me generally they were the type to not implant at all.

    I’m curious to know if you think some people just respond better to fresh, or maybe some embryos do better if they are never frozen.


    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 24, 2018 reply

    I think we should talk!!

    In my opinion,FET conducted in an IVF center of excellence is always least as good a fresh ET’s…probably better. There is an explanation that needs to be sought for your repeated failures with what sounds like “competent”, PGS-normal embryos having been transferred.

    Whenever a patient fails to achieve a viable pregnancy following embryo transfer (ET), the first question asked is why! Was it simply due to, bad luck?, How likely is the failure to recur in future attempts and what can be done differently, to avoid it happening next time?.
    It is an indisputable fact that any IVF procedure is at least as likely to fail as it is to succeed. Thus when it comes to outcome, luck is an undeniable factor. Notwithstanding, it is incumbent upon the treating physician to carefully consider and address the causes of IVF failure before proceeding to another attempt:
    1. Age: The chance of a woman under 35Y of age having a baby per embryo transfer is about 35-40%. From there it declines progressively to under 5% by the time she reaches her mid-forties. This is largely due to declining chromosomal integrity of the eggs with advancing age…”a wear and tear effect” on eggs that are in the ovaries from birth.
    2. Embryo Quality/”competency (capable of propagating a viable pregnancy)”. As stated, the woman’s age plays a big role in determining egg/embryo quality/”competency”. This having been said, aside from age the protocol used for controlled ovarian stimulation (COS) is the next most important factor. It is especially important when it comes to older women, and women with diminished ovarian reserve (DOR) where it becomes essential to be aggressive, and to customize and individualize the ovarian stimulation protocol.
    We used to believe that the uterine environment is more beneficial to embryo development than is the incubator/petri dish and that accordingly, the earlier on in development that embryos are transferred to the uterus, the better. To achieve this goal, we used to select embryos for transfer based upon their day two or microscopic appearance (“grade”). But we have since learned that the further an embryo has advanced in its development, the more likely it is to be “competent” and that embryos failing to reach the expanded blastocyst stage within 5-6 days of being fertilized are almost invariably “incompetent” and are unworthy of being transferred. Moreover, the introduction into clinical practice about a decade ago, (by Levent Keskintepe PhD and myself) of Preimplantation Genetic Sampling (PGS), which assesses for the presence of all the embryos chromosomes (complete chromosomal karyotyping), provides another tool by which to select the most “competent” embryos for transfer. This methodology has selective benefit when it comes to older women, women with DOR, cases of unexplained repeated IVF failure and women who experience recurrent pregnancy loss (RPL).
    3. The number of the embryos transferred: Most patients believe that the more embryos transferred the greater the chance of success. To some extent this might be true, but if the problem lies with the use of a suboptimal COS protocol, transferring more embryos at a time won’t improve the chance of success. Nor will the transfer of a greater number of embryos solve an underlying embryo implantation dysfunction (anatomical molecular or immunologic).Moreover, the transfer of multiple embryos, should they implant, can and all too often does result in triplets or greater (high order multiples) which increases the incidence of maternal pregnancy-induced complications and of premature delivery with its serious risks to the newborn. It is for this reason that I rarely recommend the transfer of more than 2 embryos at a time and am moving in the direction of advising single embryo transfers …especially when it comes to transferring embryos derived through the fertilization of eggs from young women.
    4. Implantation Dysfunction (ID): Implantation dysfunction is a very common (often overlooked) cause of “unexplained” IVF failure. This is especially the case in young ovulating women who have normal ovarian reserve and have fertile partners. Failure to identify, typify, and address such issues is, in my opinion, an unfortunate and relatively common cause of repeated IVF failure in such women. Common sense dictates that if ultrasound guided embryo transfer is performed competently and yet repeated IVF attempts fail to propagate a viable pregnancy, implantation dysfunction must be seriously considered. Yet ID is probably the most overlooked factor. The most common causes of implantation dysfunction are:
    a. A“ thin uterine lining”
    b. A uterus with surface lesions in the cavity (polyps, fibroids, scar tissue)
    c. Immunologic implantation dysfunction (IID)
    d. Endocrine/molecular endometrial receptivity issues
    Certain causes of infertility are repetitive and thus cannot readily be reversed. Examples include advanced age of the woman; severe male infertility; immunologic infertility associated with alloimmune implantation dysfunction (especially if it is a “complete DQ alpha genetic match between partners plus uterine natural killer cell activation (NKa).
    I strongly recommend that you visit http://www.DrGeoffreySherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

    • The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
    • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
    • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
    • The Fundamental Requirements for Achieving Optimal IVF Success
    • Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
    • Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
    • Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
    • Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
    • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
    • Blastocyst Embryo Transfers should be the Standard of Care in IVF
    • IVF: How Many Attempts should be considered before Stopping?
    • “Unexplained” Infertility: Often a matter of the Diagnosis Being Overlooked!
    • IVF Failure and Implantation Dysfunction:
    • The Role of Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 1-Background
    • Immunologic Implantation Dysfunction (IID) & Infertility (IID): PART 2- Making a Diagnosis
    • Immunologic Dysfunction (IID) & Infertility (IID): PART 3-Treatment
    • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
    • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management 🙁 Case Report)
    • Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
    • Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
    • Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
    • Endometrial Thickness, Uterine Pathology and Immunologic Factors
    • Vaginally Administered Viagra is Often a Highly Effective Treatment to Help Thicken a Thin Uterine Lining
    • Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas:
    • A personalized, stepwise approach to IVF
    • How Many Embryos should be transferred: A Critical Decision in IVF?
    • The Role of Nutritional Supplements in Preparing for IVF
    If you are interested in my advice or medical services, I urge you to contact my patient concierge, ASAP to set up a Skype or an in-person consultation with me. You can also set this up by emailing concierge@sherivf.com or by calling 702-533-2691 and/or 800-780-743. You can also enroll for a consultation with me, online at http://www.SherIVF.com.
    Also, my book, “In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com .

    Geoffrey Sher MD

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