Elsevier

The Lancet

Volume 376, Issue 9742, 28 August–3 September 2010, Pages 730-738
The Lancet

Review
Endometriosis and infertility: pathophysiology and management

https://doi.org/10.1016/S0140-6736(10)60490-4Get rights and content

Summary

Endometriosis and infertility are associated clinically. Medical and surgical treatments for endometriosis have different effects on a woman's chances of conception, either spontaneously or via assisted reproductive technologies (ART). Medical treatments for endometriosis are contraceptive. Data, mostly uncontrolled, indicate that surgery at any stage of endometriosis enhances the chances of natural conception. Criteria for non-removal of endometriomas are: bilateral cysts, history of past surgery, and altered ovarian reserve. Fears that surgery can alter ovarian function that is already compromised sparked a rule of no surgery before ART. Exceptions to this guidance are pain, hydrosalpinges, and very large endometriomas. Medical treatment—eg, 3–6 months of gonadotropin-releasing hormone analogues—improves the outcome of ART. When age, ovarian reserve, and male and tubal status permit, surgery should be considered immediately so that time is dedicated to attempts to conceive naturally. In other cases, the preference is for administration of gonadotropin-releasing hormone analogues before ART, and no surgery beforehand. The strategy of early surgery, however, seems counterintuitive because of beliefs that milder non-surgical options should be offered first and surgery last (only if initial treatment attempts fail). Weighing up the relative advantages of surgery, medical treatment and ART are the foundations for a global approach to infertility associated with endometriosis.

Introduction

Endometriosis, an enigmatic disease characterised by development of endometrial tissue outside of the uterus, causes pain and infertility.1, 2, 3, 4 A good correlation exists between amount, type, and location of endometriotic lesions and the painful symptoms encountered.5 By contrast, links between endometriosis and infertility are less clear, even though the association is clinically recognised.6 The prevailing vision today is that infertility in endometriosis is multifactorial, with many ways identified by which endometriosis possibly interferes with reproduction.

After touching on the pathophysiological background of endometriosis and infertility, we will assess the respective values of surgery and medical treatments. By medical treatments we mean the various agents proposed for treatment of endometriosis (all block ovarian function but by different means). Today, drugs mainly amount to agonists of gonadotropin-releasing hormone, oral contraceptives, and other hormone treatments (ie, progestins only). These, however, do not encompass the various assisted reproductive technologies (ART), such as ovarian stimulation, which is used for augmentation of fertility and is sometimes undertaken for endometriosis. When surgery and medical treatments fail, or natural conception is impossible because of coexisting tubal disease or altered male characteristics, reversion to ART is necessary. Such techniques include in-vitro fertilisation (IVF) and its variant for male factor infertility, intracytoplasmic sperm injection. Hence, we will also highlight how medical and surgical treatments of endometriosis affect the outcome of ART. Finally, having laid the foundation for a global approach to infertility associated with endometriosis, we will sketch a practical algorithm for guidance of clinical management.

Section snippets

Pathophysiology

Figure 1 summarises possible mechanisms by which endometriosis could affect fertility. These processes are described below, according to whether they take place in the pelvic cavity, ovaries, or uterus.

The compounding role of pain

In women with endometriosis, pelvic pain and, particularly, dyspareunia affect a couple's ability to have regular sexual intercourse and, thus, will compound infertility problems. The primary cause of pain is deep infiltrating endometriotic lesions that penetrate the muscularis propria of surrounding organs (such as the bladder or rectum).74 However, whether deep infiltrating endometriosis hinders fertility directly is unclear.75 Practically speaking, the presence of pain strongly weighs in

Natural conception

To date, all forms of medical treatment available for endometriosis block ovarian function and are, thus, contraceptive (eg, danazol, gonadotropin-releasing hormone analogues, progestins, and oral contraceptives). These agents are effective on pain77 and reduce the risk of recurrence of symptoms after surgery.78 Contrary to earlier beliefs, however, fecundity does not rebound on termination of treatment.75, 79 Medical treatments are, thus, not indicated for infertility associated with

Management of infertility

Figure 2 outlines primary variables to be taken into account during treatment of infertility associated with endometriosis. The proposed strategy represents the essence of a global approach that combines respective advantages of surgery and ART, and it accords with guidelines of the European Society of Human Reproduction and Embryology105 and American Society for Reproductive Medicine.106 Surgery should be offered early in the course of endometriosis, when infertility is at the workup stage,

Conclusion

The cause of infertility associated with endometriosis remains elusive, with current findings suggesting a multifactorial mechanism. The respective advantages of surgery, medical treatment, and ART intertwine complexly in women with these disorders. This intricate medley mandates a global approach to optimise every option. Indeed, only such a strategy can oppose a situation that still too often prevails, when the main reason for choice of surgery or ART stems from the primary activity of the

Search strategy and selection criteria

We searched PubMed for work published in English since Jan 1, 2004, grouping the keywords “endometriosis” and “fertility”. This strategy yielded 602 hits, which we screened for relevance from the abstract, ultimately retaining 127 reports for full review. Next, we used 34 key articles to screen for related work on PubMed, which yielded 64 further reports. The keywords “endometriomas”, “anti mullerian hormone/(AMH)”, “antral follicle count”, “inflammation”, “pelvic fluid”, and “endometrial

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