Failed IVF: Could a Thin Uterine Lining Be the Problem?

18 Apr

When a couple facing infertility makes the decision to embark upon a treatment of IVF at Sher Fertility New York, if they ultimately fail to meet with success it is usually attributable to a paucity of healthy embryos to work with. Healthy embryos are those that are, at a minimum, chromosomally normal, or “euploid”. Creating such embryos gets more difficult as a woman ages due to a natural fragility of eggs that only grows more problematic with time.

But what about those couples that transfer very healthy appearing embryos (i.e. those that have reached the expanded blastocyst stage) that still do not conceive? These developmentally normal embryos have a higher chance to be euploid certainly, but it is not a guarantee. This leads some to genetically screen their embryos to more fully understand what they are capable of producing. Such screening involves an embryo biopsy on day 3 or day 5 of its development and then a chromosomal numerical assessment through a technique called CGH. Embryos that look developmentally appropriate and test normal via the CGH technique have minimally about a 65% chance of making a baby. This is about as good as one’s starting materials can ever be.

But what about those couples who on one or more occasions transfer such good quality, normal testing embryos but still fail to implant? Should we just ascribe it to bad luck and keep transferring? I recommend that when such a scenario occurs, before more transfers are done, the uterine environment should be strongly considered as the source of failure and deserves more scrutiny and attention.

Does the lining of the uterus (endometrium) achieve an adequate thickness?

If the substrate for implantation is not adequate, the embryo may fail to implant or fail to thrive if it does. We like to see the lining at a minimum of 9mm thick. A trilaminar appearance is reassuring, but is not a mandate for a good outcome. Certainly if the lining is less than 7mm we think a fresh transfer is going to be compromised and will vitrify our embryos until we can get the lining better in the context of a frozen transfer. Data supports the use of vaginal sildenafil (Viagra) as one means to enhance the lining, presumably working through the enhancement of blood flow to the pelvic organs. Sometimes by merely increasing the duration of estrogen exposure, as can only be done in the context of a frozen embryo transfer, one can enhance the lining thickness. Finally, a hysteroscopy to look into the uterine cavity directly is worth considering as the presence of scarring might be the reason for the thin lining. Such scarring can often be cured through careful resection at the time of hysteroscopy.

Is the lining (endometrium) receptive?

We know from years of studying the physiology of early pregnancy that a uterine “window of implantation” exists in which there is a relatively brief period of time during a woman’s menstrual cycle in which her uterine lining will be receptive to an embryo. Embryos placed into the uterine cavity before or after this period won’t implant. Protein secretion in the endometrial cells is altered in response to the post-ovulatory hormonal changes that occur (the main one being a surge in progesterone) and it is this new protein profile that characterizes the “window of implantation”. For example, a protein called cyclin is markedly diminished while another protein called integrin is markedly increased. Occasionally the normal protein fluctuations that engender receptivity in the lining do not occur despite what appears to be a perfectly normal hormonal pattern during natural or medicated treatment cycles. To diagnose such issues, a protein analysis of lining samples obtained via endometrial biopsy can be performed. The reasons for a receptivity failure can be mysterious, but such aberrations tend to be more frequent in women with inflammation of the endometrial lining (endometritis), endometriosis, or tubal disease. Therefore treatments including antibiotics, a lowering of estrogen influence (as with long-acting Lupron or the aromatase inhibitor letrozole), or surgical removal of dysfunctional tubes (hydrosalpingectomy) can be very helpful. In the context of a fresh IVF cycle, it is important to measure progesterone levels during the later days of stimulation. Premature increases of progesterone can sometimes occur and when present can shift the window of implantation. This leads to embryos which are no longer developmentally in sync with their lining. Freezing all the embryos and performing a later frozen embryo transfer should be considered when there are progesterone elevations greater than 2.5 ng/mL before egg retrieval.

What else can be done for the seemingly refractory uterine lining?

Recent data has accrued for some newer techniques that have been postulated to help implantation. One technique is called an “endometrial scratch biopsy” in which the lining of the uterus is biopsied about a month before transfer, not strictly for diagnostic purposes, but rather merely to irritate the lining a bit. Such a thing sounds very counter-productive, but nonetheless the data show otherwise, and this effect has been attributed to the fact that an irritated lining secretes many proteins and growth factors that may prove chemically alluring to the embryo. Another potentially promising technique is the injection of a dilute amount of hCG directly into the uterine cavity a short while before an embryo transfer. A recent study (Reproductive Biology and Endocrinology 2014, 12:9) demonstrated an increase in the implantation rate from 36% to 52%, and such an improvement has been attributed to the ability of hCG to influence inflammatory factors and blood vessel development in the lining. These techniques require further corroboration but appear promising and we shall follow the literature closely to see if they deserve more application.

Dr. Drew Tortoriello is a physician with Sher Fertility New York, NY.

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9 Comments

  • celeste Madhere says:

    I am having an issue with my lining now. I am consistently taking lupron, i tried 5 Estries a day and made it to 7, but once I started the ghonal F my lining reduced to a 5. Now I am on 4 patches a day and my lining won’t go past 6.7. We are going to try IUI one more time, but my doctor is looking like there is no hope for my lining and I refuse to give up. There has to be another option. They don’t want to do IVF because if we can’t make my lining thick enough what would be the point. They want to put me on blood thinners, but I would like to try Viagra before going that route.

    I’m on the wait list for Dr. T for an approintment. This process has definitely been trying, especially with a lining that won’t cooperate. Everything else is fine…just this stupid lining!

    Tired of my lining,

    Celeste

    • Geoffrey Sher says:

      The cause of a thin lining needs to be evaluated. It could be the fertility medication itself (especiallyb if you are using clomiphene repeatedly or it can be due to trauma to the basal endometrium (post inflammatory).

      Please go to the home page of this blog, http://www.IVFauthority.com . When you get there look for a “search bar” in the upper right hand column. Then type in the following subjects into the bar, click and this will take you to all the relevant articles I posted there.

      1. “An Individualized Approach to Ovarian stimulation” (posted on November 22nd, 2010)

      2. Ovarian Stimulation for IVF: The most important determinant of IVF Outcome” (Nov. 2103)

      3. “Agonist/Antagonist Conversion Protocol”

      4. “Embryo Implantation………” (Part-1 and Part- 2—-Posted August 2012)

      5. “Endometrial Thickness and IVF”

      Consider calling 800-780-7437 or 702-699-7437 to arrange a Skype with me so we can discuss your case in detail.

      Finally, perhaps you would be interested in accessing my new book (recently released). It is the 4th edition (and a re-write) of “In Vitro Fertilization: The ART of Making Babies”. The book is available through “Amazon.com” as a down-load or in book form. It can also be obtained from most bookstores.

      Geoff Sher

      P.S: Please go to http://www.youtube.com/watch?v=Vp3GYuqn2eM&feature=youtu.be
      To view a video-tutorial by Linda Vignapiano RN, Clinical Manager at SIRM-Las Vegas.

  • Marina says:

    I have a hysteroscopy to remove a small polyp. I have a retroverted uterus. Since I experienced OHSS during IVF I have an FET coming up. Is it common for women to NOT respond to estrace? I have no reason to think I wouldn’t but I just was wondering how common cancellatons are. I am 27 with no known fertility problems (MFI).