Endometriosis and Infertility

Endometriosis – What is it?

Endometriosis can be an overwhelming diagnosis. It is an often a painful and life altering condition in which endometrial tissue, which normally lines the uterus, develops outside of the uterine cavity in abnormal locations such as the ovaries, fallopian tubes, and abdominal cavity.1 This tissue responds during the menstrual normal cycle but cannot be shed out of the body.

Although some women may not have any symptoms, many suffer from pain and infertility. ASRM (American Society for Reproductive Medicine) estimates up to 10% of all women have endometriosis though African-American women are less likely to be diagnosed than Caucasian women. ASRM also indicates that risk factors include low body mass index (BMI), alcohol use and smoking.2 It is still under debate about whether endometriosis causes infertility, it has been estimated that 30% to 50% of infertile women have endometriosis.3 Staging of the disease is used to describe the severity of the case and is often used by physicians to develop a treatment or surgical plan.

The staging of endometriosis helps physicians takes into consideration the location of the abnormal tissue growth, the extent, and the depth and seriousness of the endometrial scar tissue and cysts that are present.4 The four stages of endometriosis are described as: Stage 1-Minimal, Stage 2-Mild, Stage 3-Moderate or Stage 4-Severe. The scoring system correlates with pregnancy success and if surgery may help your chances of getting pregnant naturally.5

Diagnosis of endometriosis

A patient usually has different goals associated with pursuing a diagnosis of endometriosis. The first goal of a diagnosis of endometriosis can be pain management. This goal usually begins with a conversation with the patient’s primary gynecologist. Usually the patient has such pain that it is interfering with their quality of life and they are compelled to have a conversation with their provider. This provider will attempt to diagnose or stage and then can progressively offer management strategies based on the severity of the disease. The second goal of many women seeking an endometriosis diagnosis can be for fertility success or because they are trying to get pregnant. Again, many of these women start with their primary OB/GYN provider to and are given a stage.

Each of these goals have very different timelines and motivations for treatments. Sometimes accelerated family building and even the end of family building can be advantageous because it can lead to treatment options that help with pain and health management. Some pain management treatments reduce or eliminate fertility. It is important for a patient to communicate the primary goal of her treatment so that her provider can prioritize her care and give her appropriate treatment options.

The diagnosis of endometriosis typically occurs when a women first approaches her doctor usually describing pelvic or abdominal pain. This pain can occur in the time around her menstrual cycle or sex. The physician may perform a comprehensive verbal, physical, MRI, and/or ultrasound examination trying to determine the cause of the discomfort. Other women who are already experiencing infertility may have their provider find and cyst or endometrioma on their ovary. The only way to have a true diagnosis is to have laparoscopic surgery and look for endometriosis using a camera or a tissue sample.

This surgery is minimally invasive and uses small instruments inserted through incisions in the abdominal area to view and possibly remove adhesions. It is usually a procedure that allows a patient to go home later that day with few risks or complications. Also, microscopic evaluation of tissue samples might be needed if a visual diagnosis cannot be made during surgery.6 7 But in a woman that has possible asymptomatic endometriosis that is causing her infertility actually establishing a diagnosis might be less important that seeking treatment for her infertility because no staging system has been proposed yet that correlates well to the chance of conception following treatment.8 9

Treatments: Infertility or Pain Management?

Much of the surgical treatment for endometriosis is for pain therapy and there is no evidence that treatment improves fertility. In fact, as discussed above many treatments inhibit ovulation so a women pursuing pregnancy must consider her options carefully. ASRM states the women’s age, duration of infertility, ability to undergo IVF-ET (In Vitro Fertilization-Embryo Transfer), family history and pelvic pain should be taken into consideration when considering treatment options.10 Doctors have limited data from randomized controlled trials and observational data is conflicting so there is no clear treatment path.

The reason endometriosis causes infertility is still under debate. Doctors propose a few different theories but none have been proven to be the cause. These theories include altered pelvic anatomy, peritoneal fluid, antibodies, endocrine levels or ovulation, implantation, or fallopian tube transport.

One of the theories of why women with endometriosis experience infertility is because of an altered pelvic anatomy. Since endometriosis can cause adhesions, or scar tissue that causes organs to stick together, problems can occur when the egg is released from the ovary and adhesions can also interfere with the fallopian tube capturing the egg for fertilization and transport to the uterus. If the egg does not fertilize or if a fertilized embryo does not transport properly to the uterus a normal pregnancy can not result.

It has also been proven there is an increase in amount and change of the content of peritoneal fluid in women with endometriosis. This peritoneal fluid is made in the abdominal cavity and is used to lubricate the organs. Specifically, the increase amount and increased concentrations of inflammatory cytokines in the serum of women with endometriosis. Inflammatory cytokines are signaling molecules that are secreted by cell types that promote inflammation. An increased amount of inflammatory cytokines indicate that inflammation is present or results from endometriosis.11

Another possible cause of infertility for women who are diagnosed with endometriosis is the possibility that increased inflammation and scar tissue may have resulted in the body issuing an immune response to the pelvic area and causing antibody formation. Antibody formation can interfere with the uterine receptivity and negatively affect embryo implantation. There have been studies that have seen an increase in autoantibodies to endometrial (uterine) antigens in some women with endometriosis.12

Proper endocrine or hormone levels are needed for ovulation. Ovulation is a very synchronized system where different areas of the brain and body chemically communicate to result in a series of events that put the egg and sperm in the fallopian tube for fertilization and transport. It has been proposed, but not yet proven, that endometriosis can cause problems with that ovulatory system. Ovulation system problems from endometriosis can be from abnormal hormone levels that interfere with follicle growth, rupture, or maturation. There is also evidence that endometriosis can also interfere with the hormone progesterone which sustains a healthy early pregnancy 13 14 and can result in lack of implantation, miscarriage or loss of the pregnancy.

Endometriosis and IVF

Age is an important factor in deciding which endometriosis treatment path to follow. After the age of 35 there is a very reduced chance of pregnancy and increased rate of miscarriage. That means that the older an infertile woman is with endometriosis, the more aggressive her infertility treatment should be. For Stage 1 or 2 women that do not experience symptoms are not encouraged to have laparoscopy surgery only to increase the likelihood of pregnancy. For a women with Stage 3 or 4 endometriosis laparoscopy or laparotomy are recommended or IVF. For women who are not symptomatic and pursuing IVF there is not sufficient evidence that removal of your endometrioma will improve IVF success using ICSI (Intra-Cytoplasmic Sperm Injection) unless it is > 4cm.

For women that have an endometrioma > 4 cm surgery may improve access to follicles, improve ovarian response or even just used to gather tissue to confirm diagnosis but there is also a risk that extensive ovarian surgery could reduce the ovary’s ability to respond to IVF stimulation medication 15 16 17 18 19 20. Other possible benefits to surgical removal of endometriosis in the ovary is to prevent spontaneous rupture, detection of occult malignancy21, preventing progression of disease and possibility of contaminating of follicular fluid with endometriosis.

For a woman that has a Stage 3 or 4 diagnosis and already had an operation, researchers have observed that IVF-ET is a better treatment option than another surgery, but additional randomized trials are needed to confirm this observation. The general consensus amongst providers is that in patients with moderate to severe endometriosis (Stage 3 or 4) if the initial surgery fails to restore fertility than IVF is an effective alternative.

Varying levels of infertility are options for the endometriosis patient. According to ASRM when a woman is under 35 a “wait and see” or super-ovulation (SO) or intra-uterine inseminations (IUI) may be a first line of therapy. SO or IUI in combination with clomiphene citrate after surgically corrected endometriosis have sometimes been shown to be more effective than timed intercourse. 22 But for women over 35 more aggressive treatment is warranted and SO/IUI and IVF with ICSI may be considered. If a woman has had surgery for endometriosis and has failed to conceive, IVF-ET is an effective option resulting in sometimes as high as 70% pregnancy rates after two cycles. 23

To decide what the best individualized treatment options are best for you and your partner, it is recommended to make a consultation with a reproductive endocrinologist (RE) or specialist. This specialist will review your and your partner’s medical history, fertility status and order testing. Based on the information they gather, they will typically give recommendations on what your treatment options are. Many RE’s also review success rates, costs and invasiveness of each option.

Endometriosis and Pregnancy

Finally, if pregnancy is achieved it is important that a patient discloses their endometriosis diagnosis to their OB/GYN doctor. Women with endometriosis have increased pregnancy complications when compared to women without endometriosis and your provider may choose to monitor the pregnancy closer 24 with the goal of a healthy mother and baby!

Resources:

1 https://www.asrm.org/topics/topics-index/endometriosis/

2 Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM,
Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. Am J Epidemiol 2004;160:
784–96.

3 https://www.reproductivefacts.org/news-and-publications/patient-fact-sheets-and-booklets/documents/fact-sheets-and-info-booklets/endometriosis_infertility.pdf

4 https://endometriosisnews.com/endometriosis-stages/

5 https://www.endofound.org/endometriosis-stages

6 Parazzini F. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo Studio dell’Endometriosi. Hum Reprod 1999;14:1332–4.

7 American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997;67:817–21

8 Schenken RS. Modern concepts of endometriosis. Classification and its consequences for therapy. J Reprod Med 1998;43:269–75.

9 Adamson GD, Pasta DJ. Endometriosis fertility index: the new, validated
endometriosis staging system. Fertil Steril 2010;94:1609–15.

10 https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/practice-guidelines/for-members/endometriosis_and_infertility_a_committee_opinion-pdfmembers.pdf

11 https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/practice-guidelines/for-members/endometriosis_and_infertility_a_committee_opinion-pdfmembers.pdf

12 Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril 2001;75:1–10

13 Cahill DJ, Wardle PG, Maile LA, Harlow CR, Hull MG. Ovarian dysfunction in endometriosis-associated and unexplained infertility. J Assist Reprod Genet 1997;14:554–7.

14 Cunha-Filho JS, Gross JL, Bastos de Souza CA, Lemos NA, Giugliani C,Freitas F, et al. Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis. J Assist Reprod Genet 2003;20: 117–21.

15 Thomas EJ, Cooke ID. Successful treatment of asymptomatic endometriosis: does it benefit infertile women? Br Med J 1987;294:1117–9.

16 Hull ME, Moghissi KS, Magyar DF, Hayes MF. Comparison of different treatment modalities of endometriosis in infertile women. Fertil Steril 1987;47:40–4.

17 Crosignani PG, Vercellini P, Biffignandi F, Costantini W, Cortesi I, Imparato E. Laparoscopy versus laparotomy in conservative surgical treatment for severe endometriosis. Fertil Steril 1996;66:706–11.

18 Chapron C, Vercellini P, Barakat H, Vieira M, Dubuisson JB. Management of ovarian endometriomas. Hum Reprod Update 2002;8:591–7.

19 Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. Large ovarian endometriomas. Hum Reprod 1996;11:641–6.

20 Pagidas K, Falcone T, Hemmings R, Miron P. Comparison of reoperation for moderate (stage III) and severe (stage IV) endometriosis-related infertility with in vitro fertilization-embryo transfer.

21 Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, et al.
Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 2012;13:285–94

22 Deaton JL, Gibson M, Blackmer KM, Nakajima ST, Badger GJ, Brumsted JR. A randomized, controlled trial of clomiphene citrate and intrauterine insemination in couples with unexplained infertility or surgically corrected endometriosis. Fertil Steril 1990;54:1083–8

23 https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/practice-guidelines/for members/endometriosis_and_infertility_a_committee_opinion-pdfmembers.pdf

24 https://www.sciencedirect.com/science/article/pii/S0015028216628406

About the Author

Ashley Wong

Ashley Wong

Ashley Wong lives in Minnesota where she works as embryologist and lab supervisor for Midwest Center for Reproductive Health. She is married and a mother of three children. She has an extensive working history in the human embryology field. Ashley trained at the University of Minnesota holding both a Bachelor of Science and a Master of Science degree. In addition, she has a Technical Supervisor Certificate from the American Association of Bioanalysts and is a member of ASRM, College of Reproductive Biology (CRB) and the Society of Reproductive Biologists and Technologist (SRBT). Ashley describes her fertility career as extremely gratifying and what brings her joy and love. She hopes to inspire her patients as she helps them create a family of their own. Twitter: @MNEmbryologist, LinkedIn >>>

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