Clinical Review
Endometriosis and pain: Expert answers to 6 questions targeting your management options
Experts address the nuances of endometriosis-associated pain and describe a multipronged approach to keep it at bay
Although endometriosis and infertility are clearly linked—in life as well as the medical literature—no causal relationship has been established. Nevertheless, data suggest that 25% to 50% of infertile women have endometriosis, and that as many as 30% to 50% of women who have endometriosis are infertile.1
Among the mechanisms that have been proposed to explain this link are:
- distorted pelvic anatomy
- endocrine and ovulatory abnormalities
- impaired implantation
- impaired quality of the oocyte and embryo
- altered peritoneal function
- altered hormonal and cell-mediated function
- abnormal uterotubal transport.2
Recent studies by Kao and colleagues and Giudice and colleagues have led to new findings in regard to endometriosis and infertility, says Ceana Nezhat, MD.3,4 Dr. Nezhat is Director of the Nezhat Medical Center in Atlanta, Georgia, and Medical Director of Training and Education at Northside Hospital in Atlanta. “These researchers have discovered that endometriosis causes changes to the endometrium that contribute to infertility.”
“There are no studies that have specifically assessed whether one anatomic site is associated with increased infertility over another,” says Tommaso Falcone, MD. “However, it is assumed that disease that involves the tubes and ovaries would impede fertility the most. Adhesive disease and endometriomas around the tubes and ovaries are associated with a worsening prognosis. Although peritoneal disease probably influences fertility solely on the basis of inflammation, disease around the tubes and ovaries is thought to have a mechanical effect as well.” Dr. Falcone is Professor and Chair of Obstetrics and Gynecology at the Cleveland Clinic in Cleveland, Ohio.
“Endometriosis is a chronic and heterogeneous disease process,” says Stephanie J. Estes, MD, Director of Robotic Surgical Services and Associate Professor, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, at Penn State Hershey Medical Center in Hershey, Pennsylvania.
“It is likely that no single site is the causative factor,” Dr. Estes says. “Endometriosis alters prostaglandins, cytokines, and proteases that may adversely affect eggs, sperm, or embryo development. In addition, altered endometrial receptivity may play a role. It has been shown that, when donor oocytes from women with endometriosis are transferred to women without endometriosis, there are lower implantation rates and poorer embryo quality.”5
Does it follow, then, that eradication of endometriosis improves fertility?
The answer is not clear. Rather, it depends on a number of variables, including the stage of the disease, its location, the presence of symptoms, and more.
“The approach for endometiosis-associated infertility is completely different from the approach for pain,” says Dr. Nezhat. “In a patient with pain, complete eradication of endometriosis is necessary. However, when addressing infertility, a surgeon must be cautious in the vicinity of the reproductive organs, even if a multistage approach is required. Fertility preservation is the goal.6,7 However, thorough treatment of endometriosis improves fertility rates even in cases of failed in vitro fertilization” (IVF).8
In this article, the focus is on 6 critical questions concerning endometriosis and infertility, including the role of medical therapy, when surgery is indicated, and whether an endometrioma warrants removal or referral for IVF.
In Part 1 of this 3-part series, which appeared in the April 2015 issue of OBG Management, the subject was diagnosis of endometriosis. In Part 2, which appeared in May 2015, the focus was endometriosis and pain.
1. Is there a role for medical therapy?
In women who have endometriosis-related infertility, medical therapy does not appear to produce any benefit. In its committee opinion on the subject, the American Society for Reproductive Medicine (ASRM) states as much: “There is no evidence that medical treatment of endometriosis improves fertility.”2
In fact, observes Dr. Estes, trials of medical treatment, involving such medications as combined estrogen-progestin therapy, danazol, progestins, or gonadotropin-releasing hormone (GnRH) agonists, may cause an unnecessary “delay in the use of more effective treatments that could result in pregnancy.”
Dr. Nezhat believes that medical therapy is effective in patients who have adenomyosis in addition to endometriosis. “Three months of treatment with a GnRH agonist will improve fertility rates in these patients,” he says.
“Medical treatments inhibit ovulation,” notes Dr. Estes. “These therapies have no role in pretreatment of patients with endometriosis prior to infertility treatment. On the other hand, medical therapy with GnRH agonists for 3 to 6 months prior to an IVF cycle does result in increased pregnancy rates.”9
2. What is the role of clomiphene and intrauterine insemination?
Should women who have endometriosis, open fallopian tubes, and infertility be treated with clomiphene and intrauterine insemination (IUI) prior to a cycle of IVF?
“This is a complex question,” says Dr. Estes, “as clinical parameters such as age, symptoms, duration of infertility, and the ability to proceed with IVF are important, as well as stage of disease.”
