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IVF: After How Many Tries Should I Give Up?

by Dr. Geoffrey Sher on November 27, 2017

Because of the emotional, physical, and financial toll exacted by IVF, it is preferable that no one undertake a one‑shot attempt. If a couple can only afford one treatment cycle, IVF is probably not the right course of action.  After all, with conventional IVF there is only about one chance in three that it will result in a live birth ‑and a tremendous letdown if it fails. It is thus unreasonable to undergo IVF with the attitude that “if it doesn’t work the first time, we’re giving up.” In vitro fertilization is a gamble even in the best of circumstances.

Statistically speaking, a woman’s under 39 years of age, using her own eggs,  having selected a good IVF program is likely to have a better than 80-90% chance of having a baby within three completed attempts (fresh and frozen transfers), provided that she has adequate ovarian reserve, (the ability to producing several follicles/eggs in response to gonadotropin stimulation), has a fertile male partner (or sperm donor sperm) with access to motile sperm and, has a normal and receptive uterus capable of developing an “adequate uterine lining”. Women of 39-43 years of age, who meet the same criteria, will likely have about half that chance (40%- 45%). When the most “competent” embryos are selected for transfer using a new genetic process known as comparative genomic hybridization (CGH), the birth rate per single, completed IVF cycle is likely to exceed 60% (regardless of the age of the egg provider) and, more than 85% within three such attempts.

Unfortunately, there will inevitably always be some women/couples who in spite of best effort at conventional IVF are destined to remain childless. In my considered opinion, it rarely advisable to undergo IVF more than three IVF attempts using the same approach each time. There is of course one important caveat, namely, that in women where the reason for repeated IVF failure is finally uncovered, it would indeed be justifiable (emotional, physical and financial resources dependent) to continue trying, using a defined and new approach that addresses the reason for prior failures. A specific case that illustrates this point comes to mind. It happened a few years back when a 42 year old Australian patient who had undergone 22 prior failed attempts at IVF elsewhere presented to me for treatment. After discovering a hitherto unrecognized immunologic implantation dysfunction (IID) linked to autoimmune hypothyroidism and activation of uterine natural killer cells (Nka).  I took her through an IVF attempt with her own eggs, but only this time I incorporated selective immunotherapy. She conceived and went on to have a healthy little boy. This case serves to illustrate that the time to stop doing IVF should not only be based on the number of prior failed attempts. The time to stop is when there is no “remediable” explanation for failure.

Older women and those who have diminished ovarian reserve can often benefit from stockpiling their embryos over several successive egg retrievals and then testing these collectively (once) for chromosomal integrity (i.e., “competency”) using CGH. Thereupon one or two “competent” embryos can be transferred at a time with a high expectation of success. This process is called “Embryo Banking” with Staggered IVF” (see elsewhere on this blog). Alternatively, given the low success rate after 43 years of age such women might be advised to rather do egg donor IVF. Here, regardless of the age of the embryo recipient the IVF birth rate after a single attempt is about 60% and better than 85% within three IVF attempts.

When conventional IVF with or without “Embryo Banking” with CGH embryo selection fails to yield a successful outcome, other options such as ovum donation, IVF surrogacy, or adoption should be considered.

Couples who choose to undergo IVF should be encouraged to view the entire procedure with guarded optimism but nevertheless they should be emotionally prepared to deal with the ever‑present possibility of failure. It is important however,  for IVF patients to be made to realize from the outset that an inability to become pregnant should never be considered a reflection on them as individuals.

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  • Jane Doe - May 20, 2018 reply

    Hello Dr. Sher,

    I am a 28 year old female who has undergone 1 retrieval IVF cycle, and two FETs. My husband and I have been together for 9 years, but have only been trying for two. The results of my IVF cycle were three PGS normal embryos (two were discarded for chromosomal abnormalities). I was diagnosed with DOR prior to starting IVF due to my numbers being: FSH: 10.6, and AMH: 0.754.

    For FET#1, we did a BCP, Lupron, estradiol patches and PIO. FET #1 resulted in a chemical pregnancy.

    After FET#1 we did three ERAs which showed that my receptivity window was displaced. We also did a repeat pregnancy loss panel (very basic) which showed that I was heterozygous for both the MTHFR C677T and A1298C variants. We also did a laparoscopy which showed mild endo (which was removed from the uterus but the endo found on the ovaries remained). I’m taking methylfolate based prenatals.

    For FET#2, we introduced prednisone (10 mg), Claritin, Pepcid, Lovenox (40) and an extra day of progesterone per the ERA results, in addition to the existing BCP, Lupron and estradiol patches. I got a much stronger positive pregnancy test this time around, but it still resulted in a chemical pregnancy, with my HCG levels being 25 at 12dp5dt. I was asked to take Estradiol pills vaginally twice a day on 5dp5dt as my estrogen levels were slightly lower (at 110).

    In all four cycles (two FETs and two mock cycles), my lining has not been thicker than 8 mm, but my doctor does not seem to be concerned about it because it is always trilaminar, and they need a minimum of 7mm (which I’ve always met).

    Do you have any recommendations moving forward?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 21, 2018 reply

    Your DOR is one thing, but your failed implantation with euploid embryos is another. The former requires a very individualized and aggressive protoco0l for ovarian stimulation while the latter requires a thorough assessment of both anatomical and immunologic factors that can profoundly affect implantation.

    I think we need to talk. Please call 800-780-7437 and ask Julie to set you up with a Skype consultation ASAP.

    Geoff Sher

  • Erica Devine - May 9, 2018 reply

    I am a 32 year old female with three failed IVF attempts. I have unexplained infertility and hypothyroidism, which runs in my family. Looking at your article on IVF and how many times should I try before you give up, I saw a lady had an immunological response to her embryos. I was wondering if she presented with symptoms? I have found with three day embryos on day 6 and with 5 day embryos on day 2-3, I start to have severe burning/cramping accompanied by severe low back pain and some stabbing pain in my abdominal area. It is the same feeling I have all three times when an embryo is put into me. I have told my family it feels like my uterus is rejecting the embryo and my first fertility specialist did not take me seriously. I have not discussed this with my new fertility clinic.

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - May 9, 2018 reply

    Between 2% and 5% of women of the childbearing age have reduced thyroid hormone activity (hypothyroidism). Women with hypothyroidism often manifest with reproductive failure i.e. infertility, unexplained (often repeated) IVF failure, or recurrent pregnancy loss (RPL). The condition is 5-10 times more common in women than in men. In most cases hypothyroidism is caused by damage to the thyroid gland resulting from of thyroid autoimmunity (Hashimoto’s disease) caused by damage done to the thyroid gland by antithyroglobulin and antimicrosomal auto-antibodies.
    The increased prevalence of hypothyroidism and thyroid autoimmunity (TAI) in women is likely the result of a combination of genetic factors, estrogen-related effects and chromosome X abnormalities. This having been said, there is significantly increased incidence of thyroid antibodies in non-pregnant women with a history of infertility and recurrent pregnancy loss and thyroid antibodies can be present asymptomatically in women without them manifesting with overt clinical or endocrinologic evidence of thyroid disease. In addition, these antibodies may persist in women who have suffered from hyper- or hypothyroidism even after normalization of their thyroid function by appropriate pharmacological treatment. The manifestations of reproductive dysfunction thus seem to be linked more to the presence of thyroid autoimmunity (TAI) than to clinical existence of hypothyroidism and treatment of the latter does not routinely result in a subsequent improvement in reproductive performance.
    It follows, that if antithyroid autoantibodies are associated with reproductive dysfunction they may serve as useful markers for predicting poor outcome in patients undergoing assisted reproductive technologies.
    Some years back, I reported on the fact that 47% of women who harbor thyroid autoantibodies, regardless of the absence or presence of clinical hypothyroidism, have activated uterine natural killer cells (NKa) cells and cytotoxic lymphocytes (CTL) and that such women often present with reproductive dysfunction. We demonstrated that appropriate immunotherapy with IVIG or intralipid (IL) and steroids, subsequently often results in a significant improvement in reproductive performance in such cases.
    The fact that almost 50% of women who harbor antithyroid antibodies do not have activated CTL/NK cells suggests that it is NOT the antithyroid antibodies themselves that cause reproductive dysfunction. The activation of CTL and NK cells that occurs in half of the cases with TAI is probably an epiphenomenon with the associated reproductive dysfunction being due to CTL/NK cell activation that damages the early “root system” (trophoblast) of the implanting embryo. We have shown that treatment of those women who have thyroid antibodies + NKa/CTL using IL/steroids, improves subsequent reproductive performance while women with thyroid antibodies who do not harbor NKa/CTL do not require or benefit from such treatment.

    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 seeking my advice or services, I urge you to contact my concierge, Julie Dahan ASAP to set up a Skype or an in-person consultation with me. You can also contact Julie by phone or via email at 702-533-2691/ Julied@sherivf.com You can also apply online at http://www.SherIVF.com .

    *The 4th edition of my book,”In Vitro Fertilization, the ART of Making Babies” is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

    Geoffrey Sher MD

Alert ! - Dr. Sher will not have access to the internet, and will therefore be out of reach, from June 5 until June 25. Please re-submit this comment after that date. Until then, please explore the Sher IVF website and his Facebook videos archived on his page.

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