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MARCH 10, 2022

Endometriosis and Infertility: A Review

FACTS Spotlight: Endometriosis Awareness Month

By Abigail Agbabiaka

 

Editor’s Note: This review of endometriosis and infertility incorporates the medical applications of charting the female cycle with fertility awareness-based methods (FABMs) to diagnose and/or manage endometriosis. It was written by Abigail Agbabiaka and summarizes an article [1] titled, “Endometriosis and Infertility: How and When to Treat?” It was published in Frontiers in Surgery in 2014 by Fadhlaoui et al.

Introduction

Endometriosis is an inflammatory condition characterized by the growth of ectopic endometrial tissue outside of the uterine cavity.[1] The lesions start as surface implants but can infiltrate deeper as the disease progresses.[2] The condition affects up to 10% of women of reproductive age and the incidence increases to 50% in women with infertility.[2] Clinical features of endometriosis may include chronic pelvic pain, dysmenorrhea, deep dyspareunia, period-related dyschezia, and infertility, among others.

Endometriosis reduces fertility from 15-20% in healthy couples to 2-10%.[1] As of the publication of Fadhlaoui et al’s article,[1] no strong evidence-based consensus existed on how to treat infertility due to endometriosis. Their article, summarized below, reviews the evidence related to medical and surgical treatment as well as assisted reproductive technologies (ART), and highlights how and when to treat infertility related to endometriosis.

Infertility and Endometriosis

The cause of infertility and subfertility in endometriosis is not fully understood. Current theories suggest the inflammatory environment caused by pro-inflammatory molecules, estradiol, and progesterone has a negative effect on gametes, embryos, tubal motility, follicular development, implantation, and sperm survivability.[1] In more severe disease, structural abnormalities caused by adhesions and endometriomas affect oocyte release, sperm movement, and tubal transport.[1]

Medical Treatment

Medical treatment for endometriosis involves suppression of the natural menstrual cycle with oral contraceptive pills (OCPs), gonadotropin releasing hormone (GnRH) agonists or medroxyprogesterone acetate. These treatments can be effective for symptoms such as relieving pain; however, they do not treat the root cause or prevent progression of the disease. In fact, a study showed a correlation between prolonged OCP use and more advanced endometriosis.[3] A meta-analysis showed medical hormonal treatment does not improve fertility rates when taken independently or in combination with surgery. Based on this evidence, it is not recommended to use hormonal treatment prior to surgery for endometriosis to improve fertility.[1]

Staging and Surgical Treatment Considerations

Surgical treatment involves removal of endometriotic implants and reconstruction of normal pelvic anatomy via laparoscopy. Surgery has been shown to improve pregnancy rates as well as relieve pelvic pain, dysmenorrhea, and dyschezia.[4] The risks associated with surgery must be considered, including infection, bleeding, damage to surrounding organs such as the bladder and intestines, and adhesions that may worsen fertility.

Surgery has been shown to improve pregnancy rates as well as relieve pelvic pain, dysmenorrhea, and dyschezia.

Endometriosis can be classified using the revised American Society of Reproductive Medicine (rASRM) staging based on endometriosis size, location, and infiltration.[2] Stages I and II indicate minimal and mild disease, respectively. Studies have shown that removal of endometriotic implants in Stage I and II causes a statistically significant increase in live birth rate and ongoing pregnancy.[1]

Stage III and IV disease represents moderate and severe endometriosis, respectively, and lacks high-quality evidence from randomized controlled trials concerning the benefits of surgical treatment. However, prospective cohort studies have shown a significant improvement in pregnancy rates post-surgery compared to conservative management.[1] The positive effect of surgery on pregnancy outcome is seen soon after initial surgery, before adhesion reoccurrence affects tubal motility. If surgery is unsuccessful in promoting pregnancy, subsequent surgical attempts are not likely to be beneficial. Therefore, the role of multiple surgeries to improve fertility in endometriosis appears limited, whereas initial surgery may be beneficial.

Ovarian endometriomas, colloquially known as chocolate cysts, are cysts formed from endometriotic implants in the ovaries. These cysts are associated with decreased ovarian reserve and fertility.[5] The European Society of Human Reproduction and Embryology (ESHRE) recommends that endometriomas > 3cm should be excised rather than ablated. Excision is associated with increased pregnancy rates[1] and allows for a histological diagnosis, which is the gold standard. Excision involves removal of the endometrial cells from the affected area, whereas ablation relies on heat to destroy the endometrial cells.

Assisted Reproductive Technologies

Assisted-reproductive technologies (ART) include intra-uterine insemination (IUI) and in vitro fertilization (IVF). ART is an invasive but, at times, effective choice for individuals trying to conceive. However, compared to other causes of infertility, endometriosis negatively impacts ART success rate.

A study showed live birth rates are five times higher with IUI; however, the effectiveness of IUI is reduced by up to 30% in women with unexplained infertility.[1] The evidence surrounding IVF is more complicated. Studies have shown that severe endometriosis was associated with worse IVF outcomes compared to mild disease. Yet, conflicting evidence shows no statically significant difference between endometriosis stage and IVF outcomes.[1]

Fertility Awareness-Based Methods: A Modern Approach

Fertility awareness-based methods use observations and biomarkers such as cervical mucus, basal body temperature, and urinary hormones to monitor reproductive health, and to diagnose and manage common women’s health conditions. This is a safe and effective approach that empowers and educates women about their physiology and reproductive health.

There are multiple advantages of using FABMs in endometriosis, including:

  • Achieving an earlier diagnosis. Endometriosis is significantly underdiagnosed, with a delay to diagnosis of twelve years, on average.[6] Charting the female cycle with FABMs can reveal clues, such as spotting seen late in the luteal phase, that may raise suspicion and hasten the diagnosis of endometriosis. This is an invaluable benefit.
  • Identifying comorbidities. The use of FABMs may aid clinicians in identifying coexisting medical conditions. For instance, women with endometriosis are more likely to also have polycystic ovarian syndrome (PCOS).[7]
  • Monitoring treatment effect. Charting symptoms enables FABM users to objectively monitor the impact of treatment.
  • Recognizing symptom patterns. Knowing when you may feel particular symptoms based on patterns noted on prior cycles means you can anticipate and treat preemptively.

Endometriosis can affect hormone levels, and these changes may be reflected in the female chart in various ways, including irregular bleeding, long or short luteal phases, limited mucus cycles, heavy bleeding with clots, premenstrual spotting, the presence of pain, and more. NaProTechnology, which incorporates the FABM known as the Creighton Model, uses surgery to remove endometriotic tissue while eliminating adhesive disease, one of the common complications of surgical treatment.

Conclusion

The effect of endometriosis on fertility is multifactorial. Similarly, a combination of treatments is beneficial to increase pregnancy and live birth rates among women with endometriosis. Active treatment is often more beneficial to improving fertility compared to conservative management. Surgical treatment and ART generally have a positive effect on fertility. Incorporating FABMs into the treatment of endometriosis places women in the center of their care to make informed decisions.


[1] Fadhlaoui A, Bouquet de la Jolinière J, Feki A. Endometriosis and Infertility: How and When to Treat?. Frontiers in Surgery. 2014;1.

[2] Zondervan K, Becker C, Missmer S. Endometriosis. New England Journal of Medicine. 2020;382(13):1244-1256.

[3] Chapron C, Lafay-Pillet M, Monceau E, Borghese B, Ngô C, Souza C et al. Questioning patients about their adolescent history can identify markers associated with deep infiltrating endometriosis. Fertility and Sterility. 2011;95(3):877-881.

[4] Yeung P, Sinervo K, Winer W, Albee R. Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary?. Fertility and Sterility. 2011;95(6):1909-1912.e1.

[5] The Effect of Surgery for Endometriomas on Fertility. BJOG: An International Journal of Obstetrics & Gynaecology. 2017;125(6):e19-e28.

[6] Hadfield R, Mardon H, Barlow D, Kennedy S. Delay in the diagnosis of endometriosis: a survey of women from the USA and the UK. Human Reproduction. 1996;11(4):878-880.

[7] Holoch K, Savaris R, Forstein D, Miller P, Higdon H, Likes C et al. Coexistence of polycystic ovary syndrome and endometriosis in women with infertility. Journal of Endometriosis. 2014;6(2):79-83.

About the Author


Abigail Agbabiaka

Abigail Agbabiaka wrote this review while on the FACTS elective as a fifth-year medical student at Cardiff University, Wales. She has an intercalated Bachelor of Science degree in Medical Sciences with Endocrinology from Imperial College, London. She learned about the role of FABMs in restorative reproductive women’s healthcare while on the FACTS elective and hopes to specialize in endocrinology.



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