Endometriosis and Infertility
Endometriosis was a puzzling disease when first described by pathologist Rokitansky in 1860. Though we now have a clearer understanding of some aspects of the biology of this disease, it still remains largely a mystery 150 years later.
Endometriosis affects about 5 million women in the U.S. Of women with infertility, approximately 25% are diagnosed with endometriosis. The symptoms fall into two categories: 1) pelvic pain, most significantly with menses, and 2) infertility. The definitive method to diagnose this disease is surgery. A laparoscopy is performed to obtain tissue biopsies of typical peritoneal lesions (peritoneum is the internal layer overlaying pelvic organs including the uterus, fallopian tubes and ovaries); and confirm the presence of endometrial glands in those biopsies. The American Fertility Society has created a classification scheme which grades the disease (Grade I-IV).
It is important to understand that there is not necessarily a correlation between pelvic pain and the severity (or grade) of the disease. Another method for presumptively diagnosing endometriosis is with ultrasound, if the patient has endometriosis ovarian cysts (endometriomas), or with MRI if one there is endometriosis growth in the uterine muscle layer (adenomyosis). A diagnosis of even minimal to mild endometriosis (stage I and II) can have significant consequences on fertility success rates. A fertile 30 year old woman has about a 25% chance of pregnancy per month (fecundity rate). A patient diagnosed with minimal to mild endometriosis has about a 3% monthly fecundity rate (1, 2, 3). If surgery is performed to dissect and remove the visible endometriosis lesions, the fecundity rate improves to 6%; but this is still much lower than the 25% afforded a fertile 30 year old. If that same patient undergoes ovarian stimulation and insemination cycles, her monthly fecundity rate increases to 11% (4). If the combination of ovarian stimulation/IUI treatment is going to increase chances of pregnancy, results are usually seen within the first 3-4 treatment cycles. Undergoing additional IUI cycles is not typically beneficial, and proceeding to in-vitro fertilization (IVF) treatment would be the next step. For patients with severe endometriosis, gonadotropin/IUI therapy is of minimal assistance. Most patients with moderate to severe endometriosis (stage III and IV) will need to pursue IVF therapy (5).
IVF studies from the 80s and 90s indicate that patients with endometriosis have a slightly lower chance of achieving a pregnancy than patients with other infertility diagnoses (6). With current IVF laboratory techniques and current ovarian stimulation strategies, this difference will probably disappear—but up-to-date studies are needed as proof. When assessing if the lower pregnancy rate is because of a uterine or ovarian issue, it appears that the uterus of endometriosis patients is effective in providing a supportive environment for the embryo to attach (7). However, the oocytes (eggs) from endometriosis patients, particularly those with endometriomas, seem to have some compromised quality (8). This lower egg quality seems to lead to less healthy and effective embryos, and therefore overall lower pregnancy rates. We clearly understand that strategies of suppressing endometriosis growth by using medications such as birth control pills, Danazol, Lupron or others, does not lead to improved pregnancy rates (9). The concept of a fertility "rebound" post-medical suppression has been proven false over-and-over again. These strategies only lose potentially precious time for the patient. Similar strategies of using medical suppression post surgical removal of endometriosis also fail to improve fecundity rates. The best approach is to move forward with an appropriate form of fertility treatment as soon as the patient desires fertility.
How to treat endometriomas has been debated, but we now have some studies to guide us. Collectively these studies indicate that patients who have undergone surgery for their endmetrioma(s) have the same IVF outcomes as those where the endometrioma(s) was left alone (10). We feel that the patient’s current clinical situation should be scrutinized carefully before recommending ovarian surgery for a patient who is seeking fertility. With surgical removal of an endometioma (ovarian cystectomy), we know that the ovary where surgery is performed will have fewer eggs and less normal ovarian tissue post surgery (11). This implies that we will have a lower chance of gathering eggs in an IVF cycle. Additionally, the patient will have a greater chance of having an elevated FSH after a cystectomy procedure, especially if she undergoes cystectomies of both ovaries (11). The risk of premature ovarian failure (POF or premature menopause) for a patient undergoing cystectomies of both ovaries for endometriomas is about 2% (12).
Historically the strategy for treating endometriosis has been to surgically remove or hormonally suppress its growth with various medications. As we better understand the biology of this disease, we can use more targeted therapies which interrupt the biochemical pathways that promote the growth of endometriosis lesions: aromatase inhibitors, estrogen and progesterone receptor blockers, angiogenesis inhibitors, etc. All of these types of medications are being studied in endometriosis patients. The future may hold some promising new medical options.
In summary, endometriosis clearly affects fecundity rates, even with minimal and mild disease. Using hormonal medications to suppress endometriosis provides no improvement in pregnancy rates, and surgical intervention provides minimal improvement. Most patients will need to pursue fertility treatment. For patients with moderate to severe disease, they most often will need to pursue IVF. For patients with endometriomas, careful consideration has to be given to all factors (age, assessment of egg quality, prior fertility treatment, etc.). The patient needs to be fully counseled prior to surgery, including risk of diminished ovarian quality (DOR) and premature menopause (POF). Patients with adenomyosis seem to have impaired implantation rates, and those with severe adenomyosis may need to consider a gestational carrier. Having a clear understanding of endometriosis as it impacts fertility, and having realistic expectations with each treatment type is most important when choosing fertility treatment options.
-- Isabelle Ryan, M.D. References
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- Marcoux et al, NEJM 1997; Jul 24; 337(4):269-70
- Parazzini, Hum Reprod 1999; 14(5):1332-4
- Tummon et al, Fertil Streil 1997; 68(1):8-12
- Dmowsky et al, Fertil Steril 78:750 2002
- Barnhart et al, Fertil Steril 2002; 77:1148-1155
- Diaz et al, Fertil Steril 2000; 74:31-34
- Simon et al, Hum Reprod 1994; 9, 725-9
- Hughes et al, Cochrane Database Syst Rev 2007; 3:CD000155
- Tsoumpou et al, Fertil Steril 2009; 92, 75-87
- Li et al, Fertil Steril 2009; 92(4):1428-35
- Busacca et al, Obstet Gynecol 2006; (195), 4
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