Florida IVF Specialist and New Endometriosis Guidelines

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As a busy practicing IVF specialist I welcome good summaries of useful information.  Endometriosis is a very common affliction.  It is estimated that 15% of the female population has endometriosis while about a third of patients suffering with infertility may have it.  As the years pass, more good information is emerging that has diminished the indications for surgery for the endometriosis patient that is infertile.  Recently, we have learned that patients may gain little from aggressive removal of ovarian endometriosis because that may significantly reduce their ovarian reserve.  More patients are being treated with IVF instead of surgery.  Of course, this approach does not apply to patients that need improvement of significant symptoms like pelvic pain, incapacitating menstrual pain, or painful intercourse.  Below please find and excellent article written for Medcape by Peter Kovacs, MD, PhD summarizing new guidelines from the European Society of Human Reproduction and Embryology.

ESHRE Guideline: Management of Women With Endometriosis

Dunselman GA, Vermeulen N, Becker C, et al

Hum Reprod. 2014;29:400-412

Background

Endometriosis can be diagnosed when endometrial tissue is found in extrauterine locations. It is found in 10%-15% of the general population and in up to one third of the infertile population.[1] There are various theories that attempt to explain its etiology. Some cases can be explained by retrograde menstruation, but metaplasia, hormonal, inflammatory processes, and abnormal cytokine function also seem to play a role.[2]

A wide variety of symptoms may accompany endometriosis. Some women are asymptomatic, whereas others are affected by dysmenorrhea, menorrhagia, dyspareunia, chronic pelvic pain, and urinary and gastrointestinal symptoms. The symptoms typically recur in a cyclic fashion, and an exacerbation can occur around menstruation.

The diagnosis can be suspected on the basis of symptoms but is established when histologic confirmation of endometrial glands and stroma is made from a tissue biopsy sample obtained from an extrauterine location.

Treatment may involve management of the symptoms, medical therapy to suppress endometriosis, and conservative or definitive surgical therapy. The decision is typically made on the basis of the severity of the symptoms, the age of the patient, her wish for future fertility, and potential contraindications to certain therapies.

The Guideline

This guideline is an update of an earlier one aiming to address all important diagnostic and therapeutic issues related to endometriosis.

The authors discuss that various cyclic symptoms and physical findings may raise the possibility of endometriosis, but the gold standard to establish the diagnosis is histologic analysis of tissue samples obtained at the time of surgery. Ultrasonography, MRI, and certain biomarkers may also raise suspicion but should not be used alone to establish diagnosis.

Empirical treatment of pain (without using surgical confirmation) using analgesics or suppressive therapy with oral contraceptive pills (OCPs) may be appropriate for young patients. Hormonal treatment using OCPs, progestins, androgens, and gonadotropin-releasing hormone (GnRH) agonists are all appropriate to manage pain associated with endometriosis. OCPs, especially if use is extended, are appropriate to manage dysmenorrhea and dyspareunia. GnRH agonists with or without hormonal add-back may also be offered to manage painful symptoms.

Surgery and excision or ablation of endometrial implants is also effective to manage endometriosis-associated cyclic symptoms, and providers are encouraged to proceed with removal of endometriosis at the time of diagnosis (“see and treat”). Ovarian endometriomas should be removed by cystectomy, rather than drainage and coagulation, to avoid recurrence. Deep infiltrating endometriosis should be managed by experienced surgeons, because complication rates are high. There is no proven benefit of hormonal treatment as adjuvant therapy to surgery, but nor is there proven harm with this approach. After cystectomy, hormonal therapy may be offered to reduce the risk for recurrence in patients who do not seek immediate conception.

Dietary supplements, transcutaneous nerve stimulation, traditional Chinese medicine, and acupuncture have not shown to be effective for the management of endometriosis.

Medical therapy alone does not improve one’s chance of achieving a pregnancy and should not be offered for this reason. Surgical treatment of early-stage endometriosis improves fertility outcome. Operative laparoscopy can be considered to manage advanced-stage endometriosis (stage III-IV). Before surgical removal of endometriomas, the ovarian reserve should be assessed and the results should be considered. Hormonal treatment after surgical removal of endometriosis has not been shown to improve fertility outcome.

For the infertile patient with early-stage endometriosis (stage I-II), intrauterine insemination can be offered to improve the chance of pregnancy. Success rates of in vitro fertilization seem to be lower among women with endometriosis, but reports are conflicting. GnRH agonist down-regulation for 3-6 months immediately before IVF may improve treatment outcome. The removal of larger endometriomas (> 3 cm) has not been shown to improve IVF outcome, although surgery is recommended to those with painful symptoms. After surgical removal of endometriomas and before IVF is started, hormonal therapy may be considered to reduce the risk for recurrence.

Postmenopausal women with a history of endometriosis should be offered combined hormonal treatment instead of estrogen alone if hormone replacement is needed.

 

Viewpoint

Endometriosis is a rather common, benign gynecologic disease. It is defined as the presence of endometrial tissue outside the uterine cavity. The diagnosis is established by histologic confirmation of both endometrial glands and stroma in tissue specimens obtained at the time of surgery.

Asymptomatic endometriosis does not require surgical treatment, because the natural course of the disease is not known. Patients with recurrent symptoms that are not responsive to medical treatment and significantly affect everyday quality of life may need to be managed with definitive surgery: removal of the uterus and ovaries. For those with less severe symptoms, a wide variety of therapies can be offered.

Medical therapy may involve the use of nonsteroidal anti-inflammatory drugs when the main problem is the cyclic occurrence of painful symptoms. Hormonal therapy that suppresses endometriosis and induces the regression of endometrial tissue has been shown to improve pain, dysmenorrhea, and dyspareunia. OCPs, progestins, androgens, and GnRH agonists can all be considered for this purpose. Deep infiltrating endometriosis often requires surgical management. The procedure should be done by experienced surgeons, as the risk for bladder and bowel injury is relatively high and it may require the resection of the affected bowel segment.

Endometriosis can be detected in up to one third of infertile women.[3,4] Its impact depends on the stage of the disease. Even early-stage endometriosis may lower implantation rates. Surgical treatment of early-stage disease has been shown to improve pregnancy rates.[5] Advanced-stage endometriosis may distort the anatomy and could result in infertility. Surgical correction can be considered, but most of these patients will eventually require IVF. Suppression of endometriosis with a GnRH agonist or extended OCP use improves IVF outcome.

The management of ovarian cysts may pose a clinical dilemma. One the one hand, cysts may lower the response to stimulation, could interfere with successful oocyte collecting during IVF, and may be associated with pain. They may also increase the risk for adnexal torsion during pregnancy when left untreated. On the other hand, even the most careful surgery could negatively affect ovarian reserve when healthy tissue is removed as well. A patient with already compromised ovarian function is likely not to benefit from the surgery. For those without associated symptoms, the removal of endometriomas is not required. Patients with symptoms associated with endometriosis, however, most likely would benefit from surgery before fertility treatment.[6]

Endometriosis is associated with a wide variety of symptoms, and treatment is needed in symptomatic patients. Treatment may involve surgery, medical therapy, or a combination of the two. The treatment has to be individualized to address the patient’s symptoms and her desire for fertility. Treatment should also be determined by assessing the risk/benefit ratios of the various hormonal surgical options.

References

  1. Somigliana E, Infantino M, Benedetti F, Arnoldi M, Calanna G, Ragni G. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins. Fertil Steril. 2006;86:192-196. Abstract
  2. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39:535-549. Abstract
  3. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77:1148-1155. Abstract
  4. Harb HM, Gallos ID, Chu J, Harb M, Coomarasamy A. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG. 2013;120:1308-1320. Abstract
  5. Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337:217-222. Abstract
  6. Garcia-Velasco JA, Somigliana E. Management of endometriomas in women requiring IVF: to touch or not to touch. Hum Reprod. 2009;24:496-501. Abstract