Endometriosis and Infertility: Common Misconceptions

22 May
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Endometriosis is one of the most common conditions associated with infertility. I say “associated with” rather than “causing” infertility because in many cases, it can be an ( added) contributing factor to another underlying issue that is the root cause of a woman’s infertility.

Many times, women are given an oversimplified picture of the correlation between endometriosis and infertility – in essence, that:

  • The primary effect of endometriosis is that it impedes the eggs from reaching the fallopian tubes…

and therefore,

  • That the severity of infertility is directly proportionate to the anatomical severity of the endometriosis itself.

This gross over-simplification and erroneous view is often used to justify the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis that such “treatment” can evoke a cure of the infertility.

It is indeed indisputable that even the mildest form of endometriosis can compromise fertility. It is equally true that mild to moderate endometriosis is by no means a cause of absolute “sterility”.

When compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about three to four times less likely to have a successful pregnancy. Two important reasons for such reduction in fertility potential are:

  1. Endometriosis is associated with the release of local pelvic “toxins” that significantly reduce the fertilization potential of eggs as they pass via the pelvic cavity from the ovary to the awaiting sperm in the outer fallopian tube
  2. Given that the origins of endometriosis almost certainly also involve an abnormal immune response of the uterine lining, many such women tend to reject the embryo (fertilized egg) as it attempts to gain attachment to the uterine wall (endometrium).

The reason that women with mild to moderate endometriosis have a much poorer reproductive performance has less to do with ovulation dysfunction or anatomical disease than the two factors mentioned above. Therefore, it should come as no surprise that the use of fertility drugs, surgery (to ablate small endometriotic deposits and free pelvic adhesions), as well as treatment by intrauterine insemination (IUI) which do not address the primary causes, are unlikely to provide any improvement in pregnancy rate over no treatment at all.

Of course, there are women with mild to moderate endometriosis who are under 35 years and who, in spite of such barriers to fertility, do conceive following fertility hormone therapy, intrauterine insemination (IUI) or surgery. But these women should realize that they probably became pregnant in spite of – rather than due to – such treatment. Then, there is the danger that women who conceive in spite of mild to moderate endometriosis might be lulled into a false sense of complacency, thinking that because they were able to achieve a pregnancy once, they will have no problem doing so again. In reality, the achievement of a viable pregnancy by a woman with mild/moderate endometriosis (by whatever means), does not improve her chances or provide assurance that she will be able to do so again.

Younger women (under 30 yrs.) with mild/moderate pelvic endometriosis (who have patent fallopian tubes, are ovulating normally, and have fertile male partners), have about a 30-40% chance of having a baby within 3 years. Accordingly, they would be fully justified in taking a “wait and see” approach, avoiding surgery, fertility drugs and intrauterine insemination (none of which, in my opinion, is likely to improve their chance of a successful pregnancy over no treatment at all). However, if they prefer to take a more active approach to conception, their best bet is In Vitro Fertilization. The nature of the IVF procedure allows eggs to be removed without their being exposed to the “toxic” pelvic environment. The eggs are then fertilized outside the body and transferred as embryos to the uterus. This nullifies one of the major factors in endometriosis-related infertility.

In addition to this toxic “peritoneal factor” present in all women with endometriosis, our research has shown that up to 1/3 of women with endometriosis (regardless of severity) have an immunologic barrier to implantation. That is, the body’s natural immune response rejects the embryo as a foreign body before it can implant in the uterus. This population of women is not generally able to conceive until the immunologic problem has been diagnosed and suppressed through selective immunotherapy.

It therefore behooves all women with endometriosis who are planning to have a family to be thoroughly tested for immunologic factors including Antiphospholipid Antibodies (APA) and Natural Killer cell activation (NKa). These tests should only be performed by a reproductive immunology reference lab. To my knowledge, no more than a half dozen exist in the United States that are capable of performing these tests with the required sensitivity.

Given the effect of the biological clock, women over 35 years of age who have endometriosis-related infertility need to be very proactive, as they do not have time to waste. Such women should, in my opinion, do IVF as a first line approach.

In the absence of clear evidence of immunologic implantation dysfunction (increased NK cell activity), I often recommend a conservative approach in women under 35 years (who potentially can afford the time to wait). However, it is my opinion that regardless of age, women who have increased NK cell activity should undergo IVF accompanied by immunotherapy with Intralipid (and sometimes with heparin, Clexane or Lovenox added ). Without such treatment, they are not likely to conceive regardless of the treatment approach.


  • Hiral says:

    I have IID, (normal embryo did not implant) and was diagonised with endometriosis stage 4 (now excised) after failed IVF. But my APA is normal. I wonder if absence of APA still can cause implantation failure in case of stage 4 endo. Also do you think now that my endometriosis is excised, i could try naturally? (I am DOR too) or would Heparin help me?

    • Geoffrey Sher says:

      No! You need to be tested for activated NK cells using the K-562 target cell test (Google and contact Reprosource Lab in Boston, MA).You will need IVF and my suggestion is that if you have DOR, you should use a very strategic, individualized protocol for ovarian stimulation. Additionally, you need to consider “Embryo Banking” and “Staggered IVF” to make hay while the sun still shines…see below.

      Endometriosis is a condition where the uterine lining (endometrium) grows on pelvic structures outside the uterine cavity. In early stage- endometriosis there is usually little, if any, visible evidence of anatomical distortion sufficient to compromise the release of an egg (ovulation) or its transportation from the ovary to the fallopian tube. In contrast, more advanced endometriosis, is characterized by the presence of pelvic adhesions sufficient to distort normal pelvic anatomy and interfere with fertilization as well as egg/embryo transportation mechanisms.
      While it is tempting to conclude that normally ovulating women with mild to moderate endometriosis would have no difficulty in conceiving if their anatomical disease is addressed surgically or that endometriosis-related infertility is confined to cases with more severe anatomical disease…nothing could be further from the truth.
      The natural conception rate for healthy ovulating women in their early 30’s (who are free of endometriosis) is about 15% per month of trying and 70% per year of actively attempting to conceive. Conversely, the conception rate for women of a comparable age who have mild or moderate pelvic endometriosis (absent or limited anatomical disease) is about 5-6% per month and 40% after 3 years of trying. The reduced conception rate in women with endometriosis can, in large part be explained by:
      • Toxins in the peritoneal fluid: It is very common for women with mild endometriosis to do exactly this…have 1 pregnancy and then battle to conceive again. This is referred to 2ndary infertility and Endometriosis is the commonest cause I know of. The explanation is that all women with endometriosis (regardless of its severity) have” toxic factors” in their pelvic peritoneal fluid. Eggs, as they pass from the ovary (ies) to the Fallopian tube(s) to reach the awaiting sperm, become exposed to these “toxins” which renders the egg envelopment (zona pellucida) resistant to sperm penetration. This reduces fertilization potential by a factor of at least 3 or 4. This means that if, in the absence of endometriosis, an egg has a 15% chance of being fertilized and thereupon resulting in a baby, that same egg, in a woman with endometriosis would have no more than a 5% chance. Thus if the overall chance of a having a baby per year of actively trying is about 12% then the chance in a woman with mild endometriosis (of the same age) would probably be no more than 3-4%. Only IVF or ICSI which by their very nature involve extracting eggs before they are released (ovulated) in to the “toxic peritoneal environment” can bypass this effect. This explains why a women with endometriosis who is lucky enough to become pregnant on her own or following the use of fertility drugs (with or without intrauterine insemination), often experiences secondary infertility later in her reproductive career. It also helps explain why normally ovulating women with endometriosis and patent Fallopian tubes do not benefit significantly from intrauterine insemination, with or without the use of fertility drugs, or from surgery to remove endometriotic lesions (since many endometriotic deposits are non-pigmented, thus invisible to the naked eye and cannot be removed surgically). In such cases only IVF improves the chance of a baby per month of trying. Simply put…. if a normally ovulating woman who has mild to moderate endometriosis conceives following IUI, surgery or the use of fertility drugs, it is probably in spite of (rather than due) to such treatments.
      • Immunologic Implantation failure: We have previously reported that >50%% of women with endometriosis (regardless of severity) have antiphospholipid antibodies (APA) in their blood. Also, and perhaps much more significant, is the fact that, approximately one third of women who have endometriosis (regardless of severity) show evidence of increased NK cell activity. In such cases there is a high likelihood of early or later IID. In the case of early IID, rejection occurs prior to embryo attachment to the uterine wall, usually even before the pregnancy hormone, hCG can be detected in the woman’s blood. Strictly speaking, rather than suffering from “true infertility” such women are experiencing are having “mini miscarriages “which occur so early on that the women does not even realize that she conceived in the first place. In the case of the latter (later implantation failure), poor implantation might manifest as a miscarriage. It is not certain whether APA’s themselves cause implantation failure. We believe that they could be “markers”, pointing to those women who are at increased risk of immunologic implantation failure. Selective immunomodulation with heparin (for the APA) and/or Intralipid/steroid therapy can often effectively counter immunologic implantation failure and lead to successful AR-induced pregnancies in women who have APA and/or increased NK cell/CTL activation.
      • Endometriomas: These are cystic lesions within the ovary that result from the accumulation of “menstrual blood” which is produced by the endometrial lining that lines these “cysts”. Decomposition of this blood causes the blood to become like molten chocolate in color and consistency. Hence the name “chocolate cysts’. Endometriomas can activate the surrounding ovarian connective tissue (stroma) leading to the excess production of male hormones (androgens)such as testosterone. This can compromise egg production and quality in the affected ovary. In our opinion, any ovarian endometrioma that is more than 1cm in size should be removed. The traditional way of doing this is surgically. A few years ago, we introduced “sclerotherapy”. This is, a relatively non-invasive, safe and effective outpatient method to permanently eliminate endometriomas without surgery being required.Sclerotherapy for ovarian endometriomas involves needle aspiration of the liquid content of the endometriotic cyst, followed by the injection of 4-5% tetracycline into the cyst cavity. Treatment results in disappearance of the lesion within 6-8 weeks, in more than 75% of cases so treated. Ovarian sclerotherapy can be performed under local anesthesia or under general anesthesia. It has the advantage of being an ambulatory office- based procedure, at low cost, with a low incidence of significant post-procedural pain or complications and the avoidance of the need for laparoscopy or laparotomy
      • Adhesions and Scar tissue: Endometriosis and/or its surgical treatment can result in adhesions and/or scarring. This can compromise tubal function and can as a very late manifestation of endometriosis block the tubes. Scarring can also compromise blood flow to the ovaries and result in reduced ovarian reserve and resistance to ovarian stimulation with fertility drugs. Please go to the home page of 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. “Immunologic Implantation Dysfunction” (posted on May, 10th and on May 16th respectively.

      5. “Thyroid Autoimmune Disease and IVF”

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

      7. “Traveling for IVF from Out of State/Country– The Process at SIRM-Las Vegas” (posted on March, 21st 2012)

      8.“A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)

      9. “IVF success: Factors that influence outcome”

      10. “Use of the Birth Control Pill in 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.

      Important Announcement:

      Dr Al Peters (Medical Director at SIRM-New Jersey), and I ,recently established the “SIRM Reproductive Immunology Forum(SRIF) which will provide a venue where you can address and hopefully find solutions to problems relating to Immunologic Implantation dysfunction (IID) that often manifest with “Unexplained” infertility, IVF Failure and Recurrent Pregnancy Loss (RPL..

      To this end we established http://www.InfertilityImmunology.com , a dedicated website where you can:
      • Register with SIRF
      • Request and receive (free of charge) a PDF copy of our book: “Unexplained” Infertility and Miscarriage : The Immunologic Link”
      • Be kept abreast of what is current in the IID arena
      • Post questions for Dr Peters and I to respond to and,
      • Interact with other patients on a separate discussion board dedicated to this.

      We look forward to hearing from you!

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