Endometriosis & IVF

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 one pregnancy and then battle to conceive again. This is referred to secondary infertility, and endometriosis is the most common 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. In my opinion, 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.