Linda C. Giudice
Linda C. Giudice
MD, PhD, University of California, San Francisco

Endometriosis and Infertility

Approximately 12% of women have impaired fertility, and about 7% of couples have infertility. In women, the leading causes are increasing age, disorders of ovulation (hormonal imbalance), anatomic abnormalities (e.g., blocked fallopian tubes) and endometriosis. In couples, about 1/3 of infertility is due to female factors, 1/3 to male factors, and 1/3 to both, and in about 10% a cause cannot be found – meaning it is “unexplained”.
Many causes of infertility are discussed in detail in other articles on this website. This article focuses on endometriosis – what it is, how it impacts fertility, methods to diagnose and treat it, and pregnancy outcomes in women with disease.

What is endometriosis?

Endometriosis is a common disorder, occurring in 10-15% of reproductive age women and in up to 30-50 % of women with infertility and/or chronic pelvic pain. Both genetic and environmental factors contribute to risk of developing the disease. In endometriosis, cells similar to those in the uterine lining (endometrium) are found outside their normal location – mainly in the pelvis, on the ovaries or as ovarian endometriomas (collections of endometrial cells in the ovary), on the bladder and bowel or outside the abdominal cavity. When a woman gets her menstrual period, most menstrual blood and endometrial tissue cells and fragments flow into the vagina, and then out of the body. At the same time, most women will have some “back flow” through the fallopian tubes (retrograde menstruation). Most women have no issue with this, but for the 10-15% of women who have endometriosis, we think there is an impaired ability of the immune system in the pelvis to effectively clear the cells and debris. The blood and tissue cells then land in the pelvis where they can attach and invade onto the pelvic organs and cause inflammation and pain.

How can endometriosis affect fertility?

Inflammation in the pelvis that is caused by the tissue cells outside the uterus of women with endometriosis can affect egg quality and sperm function and result in scarring of the fallopian tubes and other structures, thus impairing fertility. When the endometriosis directly affects the ovaries (ovarian endometriomas), they may respond less well to hormonal stimulation during IVF treatment to produce eggs. This is likely to be due to inflammation in the ovary from the endometriosis tissue affecting egg quality. Moreover, the lining of the uterus of women with endometriosis also has inflammation, which might make embryo implantation more difficult. Thus, pelvic inflammation and scarring (fibrosis) in women with endometriosis can result in infertility, and can also result in painful periods (dysmenorrhea) and/or chronic pelvic pain. Note that most women who have endometriosis have pain and/or infertility, but not all do. Why this is so is not well understood.

Diagnosing endometriosis

Endometriosis will be considered if a women reports to her health care provider that she has a family history of endometriosis, severely painful periods since they first started, increasing in magnitude over time and worsening chronic pelvic pain not due to bowel or bladder disorders, infections or pelvic scarring due to other conditions (e.g., previous surgery).

The gold standard to diagnose endometriosis is surgery – usually laparoscopy – where suspected disease is biopsied (a small piece of the suspicious tissue is taken) and confirmed by histology (under the microscope). Once endometriosis detected, it is surgically removed. This often results in decreased pelvic inflammation pain and sometimes improves fertility. Sometimes medications are needed to keep the disease at bay, although most of these are counterproductive to trying to conceive (see below).

A doctor diagnosing endometriosis

There is much research ongoing to develop non-surgical tests to diagnose endometriosis. Recent studies show that the endometrium of some women with endometriosis has altered levels of certain proteins that are needed for normal endometrial function and embryo attachment/implantation. Preliminary studies suggest that the levels of these proteins are returned to normal after surgical removal of the disease or with medical therapies and that the chance of an embryo successfully implanting into the uterus then increases.

Treating endometriosis

Pain associated with endometriosis is treated with combined oral contraceptives, progestins alone (oral, implants, intrauterine devices), or medications to lower estrogen levels, e.g., GnRH (gonadotropin releasing hormone) analogues. These approaches, while usually effective for pain relief, can have significant side effects that may result in patients stopping them and are counterproductive for trying to conceive.

Surgical treatment of endometriosis can be helpful for some scar tissue removal and also can lower pelvic and endometrial inflammation, making the uterus a better environment for embryo implantation (see above). By far, ovarian stimulation with intrauterine insemination (IUI) is an excellent treatment for endometriosis-related infertility, as is IVF. It is not clear if removing asymptomatic ovarian endometriomas prior to attempting pregnancy is the best treatment option. This is because removing large endometriomas (>3-5 cm in diameter) can further lower the ovarian reserve (make the ovaries less responsive to IVF stimulation). When women have symptoms associated with ovarian endometriomas (like pain), however, surgically removal is a good option (not drained because then they will quickly reoccur). Some women benefit from pre-treatment with progestins or GnRH analogues prior to IVF cycles if their previous cycles have been unsuccessful and endometriosis is suspected or proven.

A woman can get pregnant after diagnosed with endometriosis

Pregnancy outcomes in women with endometriosis

While the data are controversial, most studies support that when women with endometriosis do conceive, either naturally or through assisted reproductive approaches, they are at increased risk of miscarriage, ectopic pregnancy, pre-term birth, and pre-eclampsia. Thus, health care providers would do well to be aware of a patient’s history of having had endometriosis before pregnancy and possible increased risks during pregnancy (as above).

Sometimes pain symptoms get better during pregnancy, although they tend to recur over time. Fertility does not seem to be augmented by having had a previous successful pregnancy.

Conclusions

Most women who have endometriosis and infertility have successful outcomes with ovarian stimulation/IUI or IVF.

Notably, in the Society for Assisted Reproductive Technologies (SART) database, endometriosis diagnosis occurs in < 3% of cycles annually. Since laparoscopy is not part of the infertility workup, the diagnosis of endometriosis is likely significantly under-reported. We are hopeful that non-surgical approaches that are being developed to diagnose endometriosis will help patients and their health care providers to optimize therapies for infertility and for pain due to this complex disease.