Endometriosis and Its Impact on Pregnancy Outcomes and IVF Success

Endometriosis is a chronic gynecological condition characterized by the presence of endometrial-like tissue outside the uterine cavity, commonly affecting the ovaries, fallopian tubes, and pelvic lining. It is a highly prevalent condition, affecting approximately 10% of women of reproductive age globally  . Endometriosis has long been associated with pain, infertility, and impaired reproductive outcomes. While the precise etiology of endometriosis remains unclear, the impact of the condition on fertility and pregnancy is widely documented. This article provides a comprehensive exploration of how endometriosis affects natural conception, pregnancy outcomes, and success rates in assisted reproductive technologies (ART), specifically in vitro fertilization (IVF).

Pathophysiology of Endometriosis in Relation to Reproduction

Endometriosis is a multifactorial disease, with immunologic, hormonal, and genetic factors playing roles in its pathogenesis . The ectopic endometrial tissue responds to the hormonal changes of the menstrual cycle, leading to inflammation, fibrosis, and the formation of adhesions and cysts, often referred to as “chocolate cysts” when they involve the ovaries (endometriomas). This chronic inflammatory state creates a hostile environment for fertility by disrupting ovulatory function, altering tubal motility, and impairing sperm-egg interaction, thus hindering natural conception.

Impact of Endometriosis on Natural Conception

Several mechanisms contribute to the reduced fertility in women with endometriosis. These include anatomical distortions caused by adhesions, impaired folliculogenesis, altered ovarian reserve, and immune dysregulation that interferes with embryo implantation .

Severe endometriosis, particularly in stage III and IV disease (according to the revised American Society for Reproductive Medicine classification), can lead to the formation of adhesions that distort the pelvic anatomy, impairing the function of the fallopian tubes . This can prevent the transport of sperm and eggs, obstructing natural conception. Even in milder cases, microadhesions may disrupt the release of eggs from the ovaries or hinder sperm transport, further complicating fertility.

Endometriomas, which are cysts that form on the ovaries, can lead to a reduction in ovarian reserve and negatively impact oocyte quality . Surgical interventions to remove endometriomas may further reduce ovarian reserve, particularly if significant ovarian tissue is inadvertently excised during the procedure. As a result, women with endometriosis, especially those with endometriomas, may experience a decline in their ovarian reserve at a younger age compared to women without endometriosis .

Endometriosis is also characterized by a heightened inflammatory response in the peritoneal cavity, with elevated levels of pro-inflammatory cytokines, growth factors, and activated macrophages. These immune factors can create a hostile environment for sperm and embryos, inhibiting sperm motility, fertilization, and implantation . The altered immune environment in women with endometriosis may also lead to reduced implantation rates and increased rates of early pregnancy loss.

When women with endometriosis achieve pregnancy, either naturally or through assisted reproductive techniques, they face a higher risk of complications during pregnancy compared to the general population. These complications include preterm birth, placenta previa, miscarriage, preeclampsia, and small-for-gestational-age (SGA) infants  . The severity of endometriosis and its associated comorbidities may contribute to the increased risk of adverse pregnancy outcomes.

Several studies have reported an increased risk of miscarriage in women with endometriosis, particularly in those with more severe disease . The exact mechanisms underlying this increased risk are not fully understood but are thought to be related to altered uterine receptivity, abnormal placental development, and immune dysfunction. The chronic inflammatory state associated with endometriosis may lead to impaired trophoblast invasion, a critical process for the establishment of a healthy pregnancy .

Women with endometriosis are also at a significantly higher risk of preterm birth, even after adjusting for other risk factors . Placenta previa, a condition in which the placenta covers the cervix, is also more common in pregnancies affected by endometriosis . These placental abnormalities may arise from the inflammatory environment in the uterus, which can affect the normal invasion and development of the placenta, leading to complications such as preeclampsia and fetal growth restriction .

Endometriosis and Assisted Reproductive Technology (ART)

Many women with endometriosis turn to ART, particularly IVF, when they are unable to conceive naturally. However, the impact of endometriosis on IVF success rates is a subject of ongoing research, with mixed results depending on the severity of the disease and the presence of comorbid conditions.

The success of IVF in women with endometriosis varies according to the stage of the disease, the presence of endometriomas, and other factors such as ovarian reserve and age. Studies generally suggest that women with endometriosis have lower implantation rates, lower clinical pregnancy rates, and lower live birth rates compared to women without endometriosis undergoing IVF. Women with severe endometriosis (stage III/IV) tend to have the poorest outcomes, as the anatomical distortions, adhesions, and damage to the ovaries and fallopian tubes are more pronounced . In contrast, women with minimal or mild endometriosis (stage I/II) may have IVF success rates comparable to women without the condition .

One of the key factors affecting IVF success in women with endometriosis is the quality and quantity of oocytes retrieved during stimulation. Studies have shown that women with endometriosis often have fewer oocytes retrieved compared to those without the condition, even when ovarian reserve markers such as anti-Müllerian hormone (AMH) and antral follicle count (AFC) are within normal ranges . Furthermore, the quality of the oocytes may be compromised by the inflammatory environment, leading to reduced fertilization rates and poorer embryo quality .

The presence of endometriomas can further complicate IVF outcomes. While surgery to remove endometriomas is sometimes performed prior to IVF to improve ovarian access and reduce inflammation, the procedure itself may decrease ovarian reserve, particularly if the cyst is large or if ovarian tissue is removed along with the cyst wall . In cases where endometriomas are left untreated, they may impede the ability to retrieve oocytes from the affected ovary and may contribute to a lower response to ovarian stimulation .

Role of Medical Treatment Prior to IVF

Hormonal suppression of endometriosis prior to IVF can improve outcomes by reducing inflammation and allowing the ovaries to respond better to stimulation . Gonadotropin-releasing hormone (GnRH) agonists are commonly used for this purpose, and several trials have shown that women treated with these agents prior to IVF have improved pregnancy and live birth rates compared to those who do not receive pretreatment .

Endometriosis significantly affects reproductive outcomes, both in terms of natural conception and pregnancy success through ART, such as IVF. The disease creates a hostile reproductive environment through anatomical distortions, impaired ovarian function, and immune dysregulation. Women with endometriosis are at increased risk for adverse pregnancy outcomes, including miscarriage, preterm birth, and placental complications. In IVF, women with endometriosis often experience lower oocyte retrieval rates, poorer embryo quality, and reduced implantation rates. Treatment strategies to optimize IVF success in women with endometriosis remain an area of active investigation, and personalized approaches that consider the severity of the disease and individual patient characteristics are essential for improving outcomes.

References
1. Giudice LC. Endometriosis. N Engl J Med. 2010;362(25):2389-2398.
2. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244-1256.
3. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-279.
4. Holoch KJ, Lessey BA. Endometriosis and infertility. Clin Obstet Gynecol. 2010;53(2):429-438.
5. Johnson NP, Hummelshoj L. Consensus on current management of endometriosis. Hum Reprod. 2013;28(6):1552-1568.
6. Somigliana E, Infantino M, Benedetti F, et al. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins. Fertil Steril. 2006;86(1):192-196.
7. Vercellini P, Somigliana E, Vigano P, et al. Surgery for endometriosis-associated infertility: a concise review of the evidence. Fertil Steril. 2009;91(1):13-20.
8. Khan KN, Kitajima M, Hiraki K, et al. Role of prostaglandin E2 in endometriosis: novel insights into the pathophysiology and therapeutic implications. Hum Reprod Update. 2015;21(5):625-645.
9. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511-519.
10. Horne AW, Saunders PTK. Inflammation and endometriosis: potential roles in pain and infertility. J Endometriosis Pelvic Pain Disord. 2013;5(2):75-83.
11. Muzii L, Di Tucci C, Achilli C, et al. Laparoscopic management of endometriosis and its impact on fertility. Womens Health (Lond). 2015;11(1):151-158.
12. Saraswat L, Ayansina DT, Cooper KG, et al. Pregnancy outcomes in women with endometriosis: a national record linkage study. BJOG. 2017;124(3):444-452.
13. Harb HM, Gallos ID, Chu J, et al. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG. 2013;120(11):1308-1320.
14. Hamdan M, Dunselman G, Li TC, et al. The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis. Hum Reprod Update. 2015;21(6):809-825.
15. Benaglia L, Somigliana E, Iemmello R, et al. Endometriosis and IVF: are agonists mandatory before IVF? J Minim Invasive Gynecol. 2015;22(3):380-386.
16. Nezhat C, Vasioukhin V, Nezhat F. Ovarian reserve following endometrioma surgery: a review. Minerva Ginecol. 2014;66(6):553-561.
17. De Ziegler D, Borghese B, Chapron C. Endometriosis and infertility: pathophysiology and management. Lancet. 2010;376(9742):730-738.
18. Santulli P, Lamau MC, Marcellin L, et al. Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation for infertility. Hum Reprod. 2016;31(8):1765-1775.
19. Gupta S, Harlev A, Agarwal A, et al. Endometriosis and oxidative stress: potential implications for fertility and assisted reproductive technologies. Gynecol Obstet Invest. 2008;65(4):239-247.
20. Shmorgun D, Claman P; Reproductive Endocrinology and Infertility Committee, et al. The diagnosis and management of endometriosis: a committee opinion. J Obstet Gynaecol Can. 2010;32(7):S1-S32.
21. Stephansson O, Falconer H, Ludvigsson JF, et al. Endometriosis and the risk of preterm birth. Obstet Gynecol. 2009;114(4):830-837.
22. Farland LV, Horne AW, Missmer SA. Association of endometriosis with adverse pregnancy outcomes. Obstet Gynecol Clin North Am. 2020;47(1):145-154.
23. Eisenberg VH, Weil C, Chodick G, et al. Epidemiology of endometriosis: a large population-based database study in a 2 million member health care provider. Am J Obstet Gynecol. 2018;218(2):210.e1-210.e7.
24. Nezhat C, Nezhat F, Nezhat C. Laparoscopic treatment of ovarian endometriomas: predictors of success and pregnancy outcome. Am J Obstet Gynecol. 1994;170(6):1695-1701.