Endometriosis

Contributed by Mr Michael Booker, consultant obstetrician & gynaecologist, and fertility specialist at Mayday University Hospital, Croydon.

Section 1 Epidemiology and aetiology

A transvaginal ultrasound can reveal ovarian endometrioma but laparoscopy is the mainstay of diagnosis

A transvaginal ultrasound can reveal ovarian endometrioma but laparoscopy is the mainstay of diagnosis

Endometriosis is one of the most common gynaecological diseases and continues to be the subject of many research articles and clinical guidelines.

There have been recent advances in surgical treatment for patients presenting with pain and those where the primary concern is infertility; this is coupled with a greater understanding of the aetiology of the disease, mechanism of pain, and mechanisms whereby fertility is impaired.

Endometriosis and pain
The differential diagnoses of pelvic pain include many gynaecological conditions and disorders of the GI/urinary tracts musculoskeletal disorders, and psychological/psychiatric conditions.

Typical symptoms are cyclical dysmenorrhoea, deep dyspareunia and dyschezia, but some women present with atypical and non-cyclical pain. Pelvic examination may reveal tender nodularity of the uterosacral ligaments and thickening of the rectovaginal septum.

Transvaginal ultrasound may reveal an ovarian endometrioma. However, operative laparoscopy remains the mainstay of diagnosis and assessment, and laparoscopic surgery can be undertaken at the same time to ablate or excise endometriosis and divide adhesions.

The mechanism for pelvic pain is likely to be irritation or invasion of pelvic vein nerves by infiltrating endometriotic implants, production of substances by the implants and activated macrophages, or bleeding from the implants.

For many patients the decision to recommend laparoscopy will be straightforward, but for others, treatment with NSAIDs and/or the combined oral contraceptive pill (COC) is reasonable if physical examination and ultrasound are negative.

Failure to respond, or relapse on discontinuing treatment should prompt further discussion about laparoscopy.

There can be a reluctance among GPs and gynaecologists to recommend laparoscopy in teenagers who present with pelvic pain that does not respond to conventional medical therapy. A recent review shows that endometriosis will be diagnosed in 70 per cent of these patients.1

Gynaecologists need to be aware of the subtle nature of the disease in younger patients.

A small but important group are teenagers with menstrual outflow obstruction, due to congenital malformations of the genital tract; they tend to have unusually severe endometriosis and need expert management to relieve the obstruction.

Section 2 Surgical treatment

Ovarian endometrioma of left ovary

The same cyst opened, drained and washed out

The American Society of Reproductive Medicine scoring system for endometriosis is widely used: stage I, minimal; stage II, mild; stage III, moderate; stage IV, severe.

All gynaecologists undertaking diagnostic laparoscopy should be aware of this system, and possess the operative skills to proceed with treatment, at least for patients with stage I to early stage III disease.

Ablation vs excision
Ablation with the CO2 and potassium-titanyl-phosphate (KTP) laser, bipolar diathermy, and more recently the helium thermal coagulator, are all popular. Unipolar diathermy is less popular and carries the risk of thermal damage to adjacent structures and normal ovarian tissue.

Excisional surgery is technically more demanding and the results are as good or better, but it runs the risk of trauma to normal tissues and postoperative adhesion formation.

Patient outcomes
Patients with ovarian endometriomas have a better overall outcome in terms of symptom relief and risk of recurrence if cysts are excised rather than ablated.

Clearly, if ablation is undertaken, all areas of the cyst wall need to be treated. Patients with more advanced disease may be recommended a course of medical pre-treatment with gonadotrophin-releasing hormone analogue (GnRHa) injections and referral to an expert.

Input from a colorectal surgeon and/or urologist should be available. Pre-operative MRI with T1 and T2 weighted imaging is recommended for delineating the extent of disease.

Laparoscopic uterosacral nerve ablation has been shown to offer no advantage over conservative surgical techniques.

Total abdominal hysterectomy with bilateral salpingo-oophorectomy is occasionally indicated for patients with advanced disease. Postoperative oestrogen replacement therapy is recommended.

Section 3 Medical treatment
The widespread use of medical therapies has declined as operative laparoscopy and surgical skills and techniques have increased; ablation or resection of endometriosis at the time of the initial laparoscopy means that fewer patients will require medical therapy. There is a wide range of medications to choose from, each with its own individual considerations in terms of length of treatment, suppression of menstruation, efficacy, side-effects and cost.

Recent guidelines reflect the difficulty in interpreting medical literature and, therefore, the use of medical treatment needs to be tailored individually.

NSAIDs are helpful for analgesia but will not suppress menstruation. GI side-effects can be troublesome but, if well-tolerated, NSAIDs can be used long term.

Combined pill
COC preparations are effective for analgesia and can be taken in a tri-cycle regimen to limit the number of menstrual days. The more progestogenic preparations are advocated, but other preparations may be equally effective.

A particular role for the COC pill is as maintenance therapy post-surgery, for patients with endometriosis who do not wish to conceive. Progestogens are effective for pain relief, but side-effects and menstrual irregularity limit compliance over the long term.

Danazol and gestrinone
Danazol was for many years the mainstay of medical treatment. It inhibits ovarian steroidogenesis and increases free testosterone levels. There is subjective and objective evidence for its efficacy, but side-effects (such as androgenic side-effects) can outweigh the benefits.

Gestrinone is broadly similar to danazol, but has simpler dosing (twice a week rather than twice a day). The side-effect profile is similar to danazol.

Helium thermal coagulation of endometrioma

CnRHa injections can lead to loss of bone mineral density

Gonadotrophin-releasing hormone analogues
GnRHa injections produce an initial stimulatory 'flare' response, followed by down-regulation of FSH and LH production and, in turn, marked suppression of ovarian steroidogenesis. They are usually administered monthly in depot injection form.

There is objective and subjective evidence of response, but inevitably these medications cause hypoestrogenic side-effects (hot flushes are almost invariable) and loss of bone mineral density.

This can be alleviated by add-back therapy in the form of tibolone or low-dose estrogen-only HRT, or low-dose continuous combined HRT if treatment is needed for more than a few weeks to prevent endometrial hyperplasia.

Duration of therapy is normally six months, but can be longer for patients with otherwise difficult to treat endometriosis. With long-term therapy, DEXA scans to monitor bone mineral density are recommended.

GnRHa therapy is effective and there is a carry-over effect for a few months post-treatment. However, there is, over time, a high chance of recurrence of symptoms and disease - 53 per cent after two years in one study.2

Medical treatment has been used in combination with surgical treatment to improve response. In theory, pre-surgical treatment inactivates the disease making surgery easier and safer and after surgery, it treats areas that might not have been resected or ablated.

However, most of the medical evidence does not support either strategy and this information should be shared with patients whenever pre- or post-surgical medication is prescribed.

IUD
The levonorgestrel-releasing IUD has been shown to be effective in reducing endometriosis in a third of patients. The device may prove to be useful after conservative surgery for patients not wishing to conceive.

Section 4 Endometriosis and infertility
The treatment of endometriosis-associated infertility raises many questions. Should all infertile women be laparoscoped? How does endometriosis affect fertility? Should it always be treated and how? When is assisted conception indicated?

Pain due to endometriosis can limit coital frequency, ovarian adhesions can inhibit oocyte release and ovarian endometriomas can affect ovarian function, but research indicates that disorders impairing implantation are highly significant,3 and may be the pathways through which endometriosis impairs fertility.

Overall, about half of infertile women have endometriosis, and about half of those with endometriosis will have infertility.

Two randomised controlled trials have shown that operative laparoscopy for early-stage endometriosis improves fertility,4,5 and three studies have shown that surgery for more advanced disease is similarly beneficial.6-8

Another study showed that diagnosing and treating endometriosis in women with previous IVF failure will increase the chance of both natural conception and IVF success.9

If there are clinical grounds for suspecting endometriosis, laparoscopy is indicated.

If not, it should be recommended for women with otherwise unexplained/undiagnosed infertility, particularly if the duration of infertility is prolonged and/or if the patient is 35 or over, and for women who have failed to conceive with assisted conception.

When to refer for IVF
If couples fail to conceive naturally after treatment for endometriosis, ovarian stimulation with either clomifene citrate or gonadotrophins combined with intrauterine insemination will improve fertility.

IVF is indicated if these treatments fail, if the woman has been treated for advanced disease, or if there are additional factors.

Greater awareness of endometriosis should lead to earlier recognition and improved treatment, which will reduce the associated morbidity due to pain and infertility.

Endometriosis always needs to be considered in the infertile couple. Professional bodies have a role in setting standards for the management of women with endometriosis.

References

1. Laufer M, Sanfilippo J, Rose G. Adolescent endometriosis: diagnosis and treatment approaches. J Pediatr Adolesc Gynecol 2003; 16(3 Suppl): S3-11.

2. Walker K, Shaw R. Gonadotrophin-releasing hormone analogues for the treatment of endometriosis: long-term follow-up. Fertil Steril 1993; 59: 511-5.

3. Lessey B, Castelbaum A, Sawin S et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab 1994; 79: 643-9.

4. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. N Engl J Med 1997; 337: 217-22.

5. Parazzini F. Ablation of lesions or no treatment in minimal-mild endometriosis in infertile women. Hum Reprod 1999; 14: 1,332-4.

6. Guzick D, Silliman N, Adamson G et al. Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine's revised classification of endometriosis. Fertil Steril 1997; 67: 822-9.

7. Osuga Y, Koga K, Tsutsumi O et al. Role of laparoscopy in the treatment of endometriosis-associated infertility. Gynecol Obstet Invest 2002; 53 Suppl 1: 33-9.

8. Adamson G, Hurd S, Pasta D, Rodriguez B. Laparoscopic endometriosis treatment: is it better? Fertil Steril 1993; 59: 35-44.

9. Littman E, Giudice L, Lathi R et al. Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles. Fertil Steril 2005; 84: 1,574-8.

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