Endometriosis is a relatively common finding in women of reproductive age. Although it can impair fertility and cause menstrual pain, some women have endometriosis and never know it. There is a significant data base being developed regarding endometriosis, and its relationship to impaired fertility.
I think most people in the Unites States have heard of endometriosis. Not very many know what it is – even women who have endometriosis. It is a fairly common problem, and frequently causes painful menstrual periods. It can impair fertility, but, contrary to what I was taught in the dark ages, does not prevent a woman from becoming pregnant. Also contrary to the archaic teaching of my youth, removing the visible endometriosis does not really restore normal fertility, and pregnancy does not cure endometriosis.
What is endometriosis? Endometriosis is endometrium, uterine lining, growing outside the uterus. The body does not want it there, and tries to get rid of it. The mechanism the body uses to try to get rid of endometriosis is inflammation. If you get a splinter in your finger, you know the skin around it becomes red and is painful. That is inflammation. Inflammation causes pain. Not all women with endometriosis have painful periods. Even though endometriosis can impair fertility, there are a number of women who have had successful pregnancies, even if they have endometriosis. How endometriosis impairs fertility is not fully understood.
How, you ask, does a woman get endometriosis? That is an excellent question. There is not an excellent answer. We actually have 3 theories, each with supporting evidence. Maybe there is more than 1 cause of endometriosis.
In 1921, a professor of OB-GYN at Albany Medical College, John Sampson described endometrium outside the uterus, and called it endometriosis. He hypothesized that its presence was a result of menstrual blood backing up through the fallopian tubes, instead of exiting through the cervix and vagina. It is not uncommon to observe this so called retrograde menstruation. Over the decades, experiments have been performed in animals, causing menstrual flow into the abdominal cavity. Commonly, endometriosis resulted. Retrograde menstruation can certainly explain endometriosis in the pelvis.
Interestingly, retrograde menstruation cannot be the only cause of endometriosis. On rare occasions, endometriosis has been found in the lung and in the brain. In those circumstances, we cannot blame retrograde menstruation. We do know that cells from the uterine cavity can be picked up by the blood stream, and be carried all over the body. Perhaps that could explain endometriosis at distant sites from the uterus. We also have stem cells in our bodies. Stem cells are primitive cells that have the ability to become cells of a multitude of different tissues. A stem cell origin for endometriosis might explain the rare production of endometriosis in men treated for prostate cancer with a potent estrogen, DES. Of course DES is not used, anymore, but before our newer treatment protocols; it was one of the treatments of prostate cancer.
How does endometriosis impair fertility? That is another great question, without a satisfactory answer. Certainly in more advanced stage III and stage IV disease, the scarring (adhesions) caused by endometriosis can interfere with the ability of fallopian tubes to pick up eggs for fertilization. It is more difficult to explain how minimal to mild (Stage I and Stage II) endometriosis impairs fertility. I would like to address possible explanations in our section on the endometrium and implantation of embryos. Also, treatment of endometriosis will be part of another section.
Endometriosis still, to a large extent remains a bit of a puzzling disease. We have learned a great deal about how it can impair fertility, and some things we can do to improve the chances of our patients who have endometriosis. Like almost everything in medicine, it is still a work in progress. There has been extensive evaluation of the environment of the pelvis and uterine cavity of women with endometriosis. In one study performed, it was found that fluid from the pelvic cavity of women with endometriosis contained something, undefined, which is toxic to mouse embryos. Fluid from women who were having tubal ligation performed because they already had all the children they wanted did not contain this apparently toxic, but unknown substance.
In other studies performed over more recent years, it has been discovered that an adhesion molecule, apparently important for an embryo to stick to the uterine lining may not be produced in the endometrium of women with endometriosis. There are actually 4 families of adhesion molecules which allow our cells to stick together, so we do not end up as puddles on the floor. One of these families of adhesion molecules is called integrins. The production of three integrins in the endometrium is apparently regulated by progesterone, the hormone made after ovulation. These integrins come and go at different points in time between ovulation and subsequent menstrual flow. All three are present when an embryo is supposed to implant in the uterus. One of them is present only at that time. Of the 3 things known to impair production of that integrin (ανβ3), one is endometriosis. Since I started treating endometriosis in the sub-set of women who did not make this integrin, my IVF pregnancy rates increased 10 percentage points.
Today, there are only 2 reasons I treat endometriosis. Certainly, I will treat endometriosis in an effort to relieve menstrual pain. The only reason I treat endometriosis in an effort to improve fertility is for women who do not make the ανβ3 integrin. It certainly has decreased the number of patients on whom I perform laparoscopy to try to determine if they do have endometriosis.
How do I treat endometriosis? First, I perform laparoscopy. I need to assure endometriosis is present, and identify its severity. The American Society for Reproductive Medicine, formerly called the American Fertility Society has a staging protocol, which does provide some prognostic information as to the potential for future pregnancy. While performing a laparoscopy, I use a LASER to obliterate endometrial implants large enough to see. There are still microscopic implants. Using a medication called Lupron shuts off estrogen production by the ovaries, depriving endometriosis of a hormone it needs to grow. Unfortunately, many endometriosis implants have the enzyme, aromatase, which allows it to make its own estrogen. Therefore, I add a second medication to block the action of aromatase. It is called Femara. By depriving endometriosis of estrogen, I think of myself as “starving it out”. Yes, there are side effects of medications. Lupron causes menopausal symptoms. Femara has very benign side effects in that a few women may notice a slightly tight sensation in their scalps. I only maintain this regimen for 3 months. The recommended life-time duration of treatment with Lupron is 6 months. Prolonged estrogen deprivation increases the risk of osteoporosis.
The overwhelming number of patients I see are trying to become pregnant. Many of them have endometriosis as a contributing factor to their impaired fertility. Contrary to what I was originally taught, simply treating endometriosis alone does not enhance fertility. During the 1980’s, a number of scientific investigations were performed to try to determine how best to help women with endometriosis conceive. The treatment protocols which far and away provide the best pregnancy rates, and, in some studies, the only ones which significantly improve near term pregnancy rates, involve stimulating ovaries with one of the products which contain the pituitary hormone FSH and then perform intrauterine insemination (IUI). FSH is the hormone which stimulates ovaries to grow follicles, the cystic structures which contain the eggs. The goal is to make 3 to 4 eggs available for fertilization, and maximize the number of sperm near the eggs without removing eggs to the laboratory. Perhaps this strategy improves pregnancy rates because only 30% to, perhaps, only 1/3 of eggs a woman makes are capable of producing a successful pregnancy. Yes, there is a risk of multiple pregnancy. We have about a 10% to 15% twinning rate, and have, over the years, produced a small number of higher order multiple pregnancies. Multiple pregnancy is a very undesirable outcome, since the human uterus was not designed for that. Clearly, if there are other issues, in addition to minimal to mild endometriosis impairing fertility, it may be necessary to perform in vitro fertilization (IVF). Even so, endometriosis may impair production of the adhesion molecule described above, and, therefore, may decrease IVF success rates. Again, in that subset of patients who do not produce the integrin, it is appropriate to treat endometriosis before proceeding to ovulation induction or other treatment.
There is still much to be learned about endometriosis, and the professional literature has new research data published every month. Some of the new information provides some insight into what it is, and how it comes to be. Some provides information with clinical application. Needless to say, we still have much to learn.