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Early-Endometriosis-related Infertility: Ovulation Induction and Reproductive Surgery vs. IVF

by Dr. Geoffrey Sher on August 20, 2017

Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).

All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.

The annual birth rate for normally ovulating women, free of any pelvic pathology (including mild endometriosis), who are having regular intercourse with fertile male partners, timed to coincide with ovulation differs with the age of the woman. For women under 35yrs it is about 80%.For those 35-40yrs of age, is about 50-60% and for women in their early 40’s the comparable annual rate is approximately 20-25% In contrast women in similar age categories who have even the mildest degree of endometriosis can expect a 3-4 fold reduction in annual birth rate.

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.” Rather, 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:

  • The existence of endometriotic deposits in the pelvis is associated (in all cases) with the presence “toxins” in the pelvic secretions. This significantly reduces the fertilization potential of eggs as they pass from the ovary to the fallopian tube via the pelvic cavity, and…..
  • In about one third (1/3) of cases, endometriosis almost certainly involves an immune implantation dysfunction (IID), such that the uteri of such women tends to reject the embryo (fertilized egg) as it attempts to gain attachment to the uterine lining (endometrium).

What about Surgery, ovulation induction with fertility agents and intrauterine (artificial) insemination- IUI for treating women who have early endometriosis?

All women with endometriosis have toxins in their pelvic secretions that, compromise the ability of sperm to fertilize eggs that pass through this environment from the ovary (ies) to reach sperm in the fallopian tube(s).This dramatically reduces fertilization potential of such eggs (by a factor of 4-6 fold) It serves to explain why potentially all women with endometriosis have reduced fecundity (reproductive potential) and. It also serves to explain why the use of tubal surgery, fertility drugs and/or intrauterine insemination (IUI) will likely not improve fecundity over no treatment at all and why in normally ovulating women, when pregnancy ensues following such approaches it in all likelihood occurred  in spite of, rather than due to such treatment. The only way to avoid this effect is through by-passing this toxic pelvic environment by extracting the eggs before they are exposed to the toxic pelvic secretions…IOW, IVF.

Endometriosis and an immunologic implantation dysfunction (IID):

The second factor that must be carefully evaluated in women with early endometriosis is the possibility that she might have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). Accordingly, in my opinion, all women who have symptoms suggestive of endometriosis (heavy and painful menstruation, pain with ovulation, pain with deep penetration during intercourse, unexplained infertility and failure to conceive after repeated attempts at IUI or IVF) should be tested for NKa using the K-562 target cell test and if this indicated NKa, the treatment would involve Intralipid infusions, steroids and possible heparinoids (e.g. Clexane and Lovenox). Tests for IID should only be done in a reproductive immunology reference lab capable of performing these tests with the required sensitivity currently exist in the U.S.A. There are to my knowledge fewer than a half dozen such reference laboratories in the United states..

How should fertility treatment be planned for in women with Early Endometriosis?

Since in the absence of an IID, women ovulating women who have early endometriosis (and fertile partners) can and do conceive spontaneously albeit much more difficult to succeed. Thus, since alternatives such as ovulation induction, surgery and/or IUI offer little if any advantage over no treatment at all, younger women (under 35y) who have no diminished ovarian reserve (normal AMH) and no IID, can elect to take a “wait and see approach for a year or two at which time if no pregnancy occurs IVF would become the treatment of choice. However, if there is an associated IID or a male infertility component to boot, they are best advised to go directly to IVF which is much likely to be successful”. However, if such women, in addition have diminished ovarian reserve (such that time3 might be running out on their fecundity), and IID or a concomitant male factor component they Are best advised to go directly to IVF.

Older women (over 35yrs) who have endometriosis-related infertility, do not have time to waste, and should, in my opinion, regard IVF as a first line approach, regardless of their immunologic status.

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  • Katie - September 14, 2017 reply

    Hi Dr Sher
    I (30 y/o) suspect I may have endo (24 day cycles, lots of clots, painful ovulation) but my RE and gyno both say definitely not based on clear ultrasounds/HSG. I’ve read that endo can only be truly diagnosed by a lap so how can they conclude this?

    Dr. Geoffrey Sher

    Dr. Geoffrey Sher - September 15, 2017 reply

    You can suspect endometriosis based upon symptoms but unless you do open surgery,laparoscopy or identify an endometrioma by Ultrasound or MRI, you cannot make a definitive diagnosis.

    Endometriosis is a condition that occurs when the uterine lining (endometrium) grows not only in the interior of the uterus but in other areas, such as the fallopian tubes, ovaries and the bowel. Endometriosis is a complex condition where, the lack or relative absence of an overt anatomical barrier to fertility often belies the true extent of reproductive problem(s).
    All too often the view is expounded that the severity of endometriosis-related infertility is inevitably directly proportionate to the anatomical severity of the disease itself, thereby implying that endometriosis causes infertility primarily by virtue of creating anatomical barriers to fertilization. This over-simplistic and erroneous view is often used to support the performance of many unnecessary surgeries for the removal of small innocuous endometriotic lesions, on the basis of such “treatment” evoking an improvement in subsequent fertility.
    It is 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”.
    Rather, when compared with normally ovulating women of a similar age who do not have endometriosis, women with mild to moderate endometriosis are about four to six times less likely to have a successful pregnancy.
    Endometriosis often goes unnoticed for many years. Such patients are frequently, erroneously labeled as having “unexplained infertility”, until the diagnosis is finally clinched through direct visualization of the lesions at the time of laparoscopy or laparoscopy. Not surprisingly, many patients with so called “unexplained” infertility, if followed for a number of years, will ultimately reveal endometriosis.

    Women who have endometriosis are much more likely to be infertile. There are several reasons for this:

    • First-Ovulation Dysfunction: In about 25 – 30% of cases, endometriosis is associated with ovulation dysfunction. Treatment requires controlled ovarian stimulation (COS). The problem is that the toxic pelvic environment markedly reduces the likelihood that anything other than IVF will enhance pregnancy potential.
    • Second- Toxic Pelvic environment that compromises Fertilization Endometriosis is associated with the presence of toxins in peritoneal secretions while it is tempting to assert 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. As sperm and egg(s) travel towards the fallopian tubes they are exposed to these toxins which compromise the fertilization process. In fact it has been estimated that there is a 5-6 fold reduction in fertilization potential because of these toxins which cannot be eradicated. Frankly, it really does not matter whether an attempt is made to remove endometriosis deposits surgically as this will not improve pregnancy potential. The reason is that for every deposit observed, there are numerous others that are in the process of developing and are not visible to the naked eye and whether visible or not, such translucent deposits still produce toxins. This also explains why surgery to remove visible endometriosis deposits, controlled ovarian stimulation with or without intrauterine insemination will usually not improve pregnancy potential. Only IVF, through removing eggs before they are exposed to the toxic pelvic environment, fertilizing them in-vitro and then transferring the embryos to the uterus represents the only way to enhance pregnancy potential.
    • Third-Pelvic adhesions and Scarring: In its most severe form, endometriosis is associated with scarring and adhesions in the pelvis, resulting in damage to, obstruction or fixation of the fallopian tubes to surrounding structures, thereby preventing the union of sperm and eggs.
    • Fourth-Ovarian Endometriomas, Advanced endometriosis is often associated with ovarian cysts (endometriomas/chocolate cysts) that are filled with altered blood and can be large and multiple. When these are sizable (>1cm) they can activate surrounding ovarian connective tissue causing production of excessive male hormones (androgens) such as testosterone and androstenedione. Excessive ovarian androgens can compromise egg development in the affected ovary (ies) resulting in an increased likelihood of numerical chromosomal abnormalities (aneuploidy) and reduced egg/embryo competency”. In my opinion large ovarian endometriomas need to be removed surgically or rough sclerotherapy before embarking on IVF.
    • Fifth- Immunologic Implantation Dysfunction (IID). Endometriosis, regardless of its severity is associated with immunologic implantation dysfunction linked to activation of uterine natural killer cells (NKa) and cytotoxic uterine lymphocytes (CTL) in about 30 of cases. This is diagnosed by testing the woman’s blood for NKa using the K-562 target cell test or by endometrial biopsy for cytokine analysis, and, for CTL by doing a blood immunophenotype. These NKa attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in death of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or even an early miscarriage. . As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.

    Advanced Endometriosis: In its most advanced stage, anatomical disfiguration is causally linked to the infertility. In such cases, inspection at laparoscopy or laparoscopy will usually reveal severe pelvic adhesions, scarring and “chocolate cysts”. However, the quality of life of patients with advanced endometriosis is usually so severely compromised by pain and discomfort, that having a baby is often low on the priority list. Accordingly, such patients are usually often more interested in relatively radical medical and surgical treatment options (might preclude a subsequent pregnancy), such as removal of ovaries, fallopian pubis and even the uterus, as a means of alleviating suffering.

    Moderately Severe Endometriosis. These patients have a modest amount of scarring/ adhesions and endometriotic deposits which are usually detected on the ovaries, fallopian tubes, bladder surface and low in the pelvis, behind the uterus. In such cases, the fallopian tubes are usually opened and functional.

    Mild Endometriosis: These patients who at laparoscopy or laparotomy are found to have no significant distortion of pelvic anatomy are often erroneously labeled as having “unexplained” infertility. To hold that the there can only infertility can only be attributed to endometriosis if significant anatomical disease can be identified, is to ignore the fact that, biochemical, hormonal and immunological factors profoundly impact fertility. Failure to recognize this salient fact continues to play havoc with the hopes and dreams of many infertile endometriosis patients.

    TREATMENT:
    The following basic concepts apply to management of endometriosis-related infertility:

    1. Controlled Ovulation stimulation (COS) with/without intrauterine insemination (IUI): Toxins in the peritoneal secretions of women with endometriosis exert a negative effect on fertilization potential regardless of how sperm reaches the fallopian tubes. This helps explain why COS with or without IUI will usually not improve the chances of pregnancy (over no treatment at all) in women with endometriosis. IVF is the only way by which to bypass this problem.
    2. Laparoscopy orLaparotomy Surgery aimed at restoring the anatomical integrity of the fallopian tubes does not counter the negative influence of toxic peritoneal factors that inherently reduce the chances of conception in women with endometriosis four to six fold. Nor does it address the immunologic implantation dysfunction (IID) commonly associated with this condition. Pelvic surgery is relatively contraindicated for the treatment of infertility associated with endometriosis, when the woman is more than 35 years of age. With the pre-menopause approaching, such women do not have the time to waste on such less efficacious alternatives. In contrast, younger women who have time on their side might consider surgery as a viable option. Approximately 30 -40 percent of women under 35 years of age with endometriosis will conceive with in two to three years following corrective pelvic surgery.
    3. Sclerotherapy for ovarian endometriomas.: About 10 years ago I introduced “sclerotherapy”, 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 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
    4. The role of selective immunotherapy Women with antiphospholipid antibodies (APA’s) experience improved IVF birth rates when heparinoids (Clexane/Lovenox) is administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy.
    a. About Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating activated natural killer cells (NKa). This effect is enhanced through the concomitant administration of corticosteroids such as dexamethasone, prednisone, and prednisolone which enhance the therapeutic effect by suppressing cytotoxic/activated T-lymphocytes (CTL). This effect of IL might is likely due to its ability to
    5. In vitro fertilization is the treatment of choice for women with endometriosis. This is especially true for women more than 35 years of age or where surgery and treatment with fertility agents has proven to be unsuccessful. We anticipate that approximately 75 percent of such women will achieve the birth of one or more babies within three IVF attempts performed.
    6.
     suppresses pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. In-vitro testing has shown that IL successfully and completely down-regulates activated natural killer cells (NKa) within 2-3 weeks in 78% of women experiencing immunologic implantation dysfunction. In this regard it is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.

    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 .
    *FYI
    The 4th edition of my newest 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.

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