All stages of endometriosis are associated with infertility.
The (cause and effect) nature of the association between minimal (stage I) or mild (stage II) endometriosis and infertility is not clear. A common assumption is that the endometriosis causes the infertility. Some have suggested that it may in fact be that the infertility causes these early stages of endometriosis. There is little scientific data to add strength to either of these positions.
Treatments for infertility associated with endometriosis are controversial. Medical management (such as depo lupron, depo provera, danazol) of endometriosis has not been shown to improve infertility rates. Therefore, fertility specialists often suggest non-medical management of infertility associated with endometriosis.
The surgical treatment of stage III (moderate) or IV (severe) endometriosis has been shown to be (and is generally accepted to be) beneficial in terms of fertility. Anatomic distortions, dense pelvic adhesions or obstructive lesions caused by the chronic inflammation of endometriosis can often be treated effectively with (minimally invasive same day) surgical techniques. Surgical treatment of stage I (minimal) or II (mild) endometriosis has recently (1997) been shown to be beneficial in terms of fertility (overall the available literature is scanty). This study (presented in The New England Journal of Medicine) was of high quality (prospective, randomized, controlled), involved 341 infertile women with stage I or II endometriosis, women were randomized to have laparoscopic “ablation of visible endometriosis” or “diagnostic” laparoscopy only, and there was a (highly) statistically significant (p < .006) increase in percentage of women who became pregnant comparing the operative group (31%) to the diagnostic group (18%). Another common rationale for treating early stage endometriosis associated with infertility is that the severity of disease usually progresses over time and is likely to develop into higher stage endometriosis if not removed.
There does not appear to be a single (all inclusive) explanation for the association between endometriosis and infertility. Therefore, the infertility specialist should always consider various possible contributions from plausible links when deciding on management. These links include (but are not limited to)
- pelvic adhesions and anatomic distortions,
- implants near the site of fertilization which may produce molecular messengers that impact on fertilization
- abnormal ovarian follicular development
Massive dense pelvic adhesions resulting from the chronic irritation and inflammation of endometriosis can obliterate the cul de sac behind the uterus, distort the normal relationship between the ovaries and the fallopian tubes, destroy the delicate fimbrial ends of the fallopian tubes, completely occlude the fallopian tube so that the tube becomes fluid filled (hydrosalpinx), and cover the surface of the ovaries which may result in fibrotic deterioration. Randomized controlled studies have demonstrated a significant improvement in fertility when treating these types of changes surgically (without treatment the pregnancy rate is less than 10% and following surgery the pregnancy rates can rise to greater than 50%).
The small amount of fluid that normally exists within the pelvis is in constant contact with the adnexal organs (fallopian tubes and ovaries). It has been suggested that this fluid may contain some molecular messengers due to the presence of endometriosis that impacts on fertility. Molecular biology research in this area is active and the results are interesting.
One line of research has demonstrated a reduction in both sperm motility (percentage of sperm moving) and sperm velocity in the presence of peritoneal fluid from women with endometriosis (as compared to peritoneal fluid from women without endometriosis).
In rodent research, the injection of (peritoneal) fluid from women with endometriosis into hamster abdomen significantly impaired fertility when compared to the injection of (peritoneal) fluid from women without endometriosis.
Another line of research has looked at the postfertilization (pre-implantation) effects of the peritoneal fluid from women with endometriosis. This research demonstrated that (mouse) embryos developing in culture (such as is done with In Vitro Fertilization) did not reach the later stages of development (blastocyst or hatching stages) as often when co-cultured with (peritoneal) fluid from women with endometriosis as compared to (peritoneal) fluid from women without endometriosis.
An association between endometriosis and poor follicular development (resulting in abnormal steroid hormone production) has been proposed. The research results in this area are often conflicting. Endometriosis is associated with an increased number of prostaglandins, macrophages, activated macrophages, and reactive oxygen groups (such as oxygen free radicals). Various groups have tried to link these molecular increases to ovarian ovulation defects including anovulation, luteal phase defects, and luteinized unruptured follicle syndrome (LUFS) with mixed results. This is presently an exciting area of research that may yield solid clinically relevant results in the near future.
The decision on whether to proceed with endometriosis surgery includes the following considerations, including:
- reportedly there is a good cumulative long term pregnancy rate with untreated stage I and stage II endometriosis, up to 90% in 5 years (compared to a normal fertility rate of 90% in 1 year);
- in patients with endometriosis, COH (controlled ovarian hyperstimulation) and IUIs (intrauterine inseminations) appear to improve the fecundity (rate of pregnancy per cycle) but does not clearly improve the overall cumulative pregnancy rates (which are high if viewed over 5 years).
- endometriosis that causes mechanical interference preventing or limiting the egg and sperm from meeting can be effectively treated surgically. Medical management of endometriosis does not effectively treat anatomic distortions and adhesions;
- when endometriosis must be removed from the ovary, even when deeply invading or causing nonfunctional cysts (called endometriomas), a goal should be to preserve as much ovary as possible since as little as 10% of one ovary may allow fertility
- hormonal (medical) management of endometriosis has no proven value in terms of fertility yet can effectively treat some patients with pain due to endometriosis
- endometriosis tends to recur (return) since the cause (such as retrograde menstruation, vascular or lymphatic dissemination or metaplasia of the coelomic epithelium) of the endometriosis can not be treated. The recurrence rate of endometriosis is unpredictable, but is generally reported in the range of 5-20% per year with a cumulative rate over 5 years of about 40%.
- progressive severe dysmenorrhea (pain during the menses) is typically associated with deep lesions of endometriosis that are often not adequately treated with medication alone
- many patients with infertility and endometriosis have absolutely no dysmenorrhea (possibly due to a reduction in nerve endings that register painful stimuli in the peritoneum of the pelvis), incorrectly feel that the lack of pelvic discomfort means that they do not have significant endometriosis, and continue with their fertility efforts without treatment
- a couple that has not achieved a pregnancy after 2 years of appropriate management following surgical treatment for endometriosis has a poor prognosis in term of fertility
- the most effective long term treatment of endometriosis is removal of the uterus and the ovaries, an undesirable (or unacceptable) option for women interested in reproduction.
- if a patient has decided to undergo radical endometriosis surgery (removal of the uterus and some ovarian tissue) and is younger than 40-45 years of age, leaving an “uninvolved ovary” in place appears to increase the risk for recurrence of endometriosis only slightly. The remaining ovary would then be able to supply the patient with hormones that are beneficial to her until menopause.
- atypical endometriosis has a varied appearance that takes experience to recognize, may be quite active in response to the sex steroid hormones, and should be removed if the decision to treat stage I or II endometriosis surgically has been made. In fact, there is a high rate of endometriosis identified on pathology report in biopsies of normal appearing peritoneum both in women with endometriosis documented elsewhere (up to 40%) and in infertile women without any visible endometriosis (up to 15%).
- when endometriosis is incidentally found in a young woman who is not immediately interested in fertility, placement on birth control pills may be considered if early stage disease (to reduce the progression of the disease) or ovulation suppressing medications if more advanced disease (to reduce the bulk of disease).