Endometriosis: Symptoms, Causes, Treatment Options and Fertility Outlook

In short: Endometriosis is the growth of tissue like the lining of the uterus outside the uterus, on the ovary, fallopian tube, bladder or bowel. It affects 10–15% of women of reproductive age, and 35–50% of them have difficulty conceiving. Symptoms are severe pain during periods and intercourse, heavy periods and pelvic pain. It is treated with painkillers and hormones, or by laparoscopic surgery, according to the case.

It is a condition where tissue similar to the endometrium grows outside the uterus, most commonly on the ovaries and the lining of the pelvis (peritoneum) behind and beside the uterus, less often on the bowel and bladder, and rarely far from the pelvis in the lung, skin, and other regions of the body, but it is a non-cancerous condition.

This tissue continues to respond to hormonal signals, specifically estrogen from the ovaries each month which stimulate it to grow, and when the estrogen level drops, the tissue bleeds, after which an inflammatory process and adhesions occur. Over time, bleeding into endometriosis on the ovary can form a cyst filled with old blood (an endometrioma or chocolate cyst).

This disease affects 10-15% of premenopausal women, and it is a common cause of pelvic pain and infertility. About 35-50% of women with this disease have difficulty in getting pregnant due to adhesions and distorted pelvic anatomy, inflammation in the pelvis that affects eggs, sperm and embryos, and reduced egg reserve when there are ovarian endometriomas or after ovarian surgery.

Symptoms of Endometriosis:

1- The most common symptom is painful menstrual cycles.

2- Dyspareunia

3- Menorrhagia

4- Pelvic pain and backache

5-Dyschesia & rectal bleeding in cases of colonic endometriosis

6- Nausea & vomiting and abdominal cramps in endometriosis of the small intestine

7- Hematuria and frequency in endometriosis of the urinary bladder

Causes of Endometriosis:

Causes of this disease are still unknown, but some researchers believe endometriosis is due to an immune system problem or hormonal imbalance. Others believe endometriosis is a genetic condition. Studies found an increased risk (5-7%) in women with family history of this disease.

Theories of causation of Endometriosis include:-

· Retrograde menstruation

· Lymphatic and vascular dissemination

· Coelomic metaplasia

Stages of endometriosis:

Endometriosis lesions can look different at surgery:

1-Microscopic endometriosis: In this stage, the peritoneum appears normal macroscopically, and lesions are identified using electron microscopy. The endometrial deposits contain endometrial gland and stroma.

2-Early active endometriosis:

It appears as vesicles, papules; maybe solid or fluid-filled and highly vascular and non-fibrotic-containing glands in the proliferative or secretory phase.

3-Advanced active endometriosis:

Present as pigmented hemorrhagic and fibrotic endometriotic deposits known as classic lesions.

4-Healed endometriosis:

Appears as white nodules or flattened fibrotic scar-containing glands only.

Note: in clinical practice today, doctors stage endometriosis at surgery using the revised ASRM system (stage I minimal, II mild, III moderate, IV severe) and the #Enzian system for deep disease. The stage does not predict how much pain a woman feels.

Risk factors for Endometriosis:

. Early first period, short menstrual cycles and heavy or long periods

. Family history

. Age 30 – 44 years

. Alcohol – caffeine intake

. Low body weight (lower body mass index)

Prevention of Endometriosis:

There is no known way to prevent this disease, but some believe women having more than one child and having children early in life develop a certain level of protection against the disease and women with a long-term use of birth control pills are less likely to develop endometriosis.

Complications of Endometriosis:

1- Infertility

2- Intestinal obstruction

3- Ureteric obstruction

4- Secondary infection of the endometriotic lesions

5- Rupture of endometrioma.

Investigations of Endometriosis:

1- Laparoscopy : - previously considered the gold standard; today it is used mainly when scans are normal but symptoms persist or medical treatment fails, or when surgery is planned anyway. Up to 50% of women with pelvic pain and dysmenorrhoea have endometriosis diagnosed at laparoscopy. Treatment can often be started based on symptoms and scans without first doing a laparoscopy.

2- Ultrasonography : - transvaginal ultrasound by an experienced doctor is the first-line test; it detects endometriomas and deep endometriosis of the bowel, bladder and rectovaginal septum, but a normal scan does not exclude small superficial spots.

3- MRI: - detects endometrioma, ovarian adhesions, and extra peritoneal masses and detects invasion to bowel, bladder, and rectovaginal septum.

4- Blood test CA 125: This protein increases in patients with severe endometriosis but also increases in ovarian cancer and peritonitis. It is not a sensitive test since it cannot detect the disease in early stages, and it is not specific, so it should not be used to diagnose endometriosis or to follow the response to treatment.

Treatment of Endometriosis:

There is no definite cure for this disease, but several options are available.

Medical Treatment of Endometriosis

. (NSAIDS) non- steroidal anti- inflammatory drugs such as ibuprofen are helpful in reducing the severity of dysmenorrhoea.

. Combined oral contraceptive pills

Three packs of pills taken continuously are helpful in decreasing the number and frequency of the menstrual cycles, thus causing atrophy of the endometriotic spots.

. Progestogen

Such as dienogest, desogestrel, the levonorgestrel-releasing IUD (Mirena), or medroxyprogesterone given continuously; they produce pseudo-decidualization in endometriotic lesions and are a first-line treatment, but may cause irregular (breakthrough) bleeding, weight gain and mood changes.

. Danazol

This drug has androgenic effects (acne, weight gain, hirsutism and possibly permanent deepening of the voice), so it is rarely used today and only when other treatments are unsuitable.

. GnRH agonists

Present as nasal spray, subcutaneous, or intramuscular injection. These drugs cause down-regulation of pituitary function, which suppresses ovarian steroid production and induces pseudo-menopause. Their side effects include hot flushes, atrophic vaginitis, and bone pain unless they are given with hormone replacement therapy as ADD-BACK THERAPY. Newer oral GnRH antagonists (such as relugolix combination therapy) are also available for endometriosis pain. Giving GnRH agonists for several months before IVF has not been proven to improve the chance of a live birth, so it is not routinely recommended.

Surgical Treatment of Endometriosis

The surgery aims to palliate symptoms, increase fertility, remove endometriotic implants, and delay recurrence of the disease.

Conservative surgery done with laparoscopy is a diagnostic as well as a therapeutic procedure used to remove endometriotic lesions by laser or diathermy and adhesolysis. This type of treatment reduces the need for open surgery in young women who seek future pregnancies.

Radical surgery

This is reserved for cases with severe symptoms and progressive disease or women who have completed their families. Such procedures include hysterectomy and bilateral salpingo – oophorectomy. Nearly 12% of all endometriosis patients require radical surgery.

Endometriosis surgery is more effective in treating severe cases than a mild or minimal disease.

In minimal or mild disease, removing the endometriosis during laparoscopy modestly improves the chance of natural pregnancy compared with laparoscopy alone. Surgery on ovarian endometriomas can reduce the egg reserve, so it should be planned carefully in women wishing to conceive.

Endometriosis and Assisted reproduction techniques:-

Endometriosis patients with long-term infertility can benefit from assisted reproduction techniques in overcoming their infertility.

Older studies suggested that pretreatment with LH RH analogues improves fertilization and implantation, especially in severe forms, but current evidence has not confirmed a higher live birth rate. For this reason, long pre-treatment with LH RH analogues before IVF is not routinely recommended; it may be considered individually, for example in severe pain.

In cases of mild endometriosis with open tubes, intrauterine insemination (IUI) with ovarian stimulation can be a useful option; if this fails, or in moderate to severe disease, IVF or ICSI is recommended.

In endometriosis, there is a risk for spontaneous abortion.

Abortion rates are 11.7% in mild endometriosis and 13.6% in moderate forms of the disease regardless of the stimulation protocol used.

Current studies show that the risk of miscarriage in women with endometriosis is only slightly higher than in other women.

Endometriosis in menopause

Post-menopausal endometriosis is one of the most unusual facets of endometriosis. About 2-5% of women with endometriosis have symptoms after the menopause, more often in the years immediately following the menopause.

Clinical presentations:-

-Metrorrhagia

-If you find the enlarged uterus which may be fixed, it raises the suspicion of endometrial cancer.

-Pelvic mass

The association of post-menopausal endometriosis and neoplasia is possible. The transformation of an endometriotic lesion to malignancy occurs in 0.7-1% mostly on the ovary, but can also take place in the recto vaginal septum and colon.

Causes:-

Active endometriosis

It indicates that estrogens are still being produced in the body or are supplied exogenously as in cases of:

1- Women on HRT.

2- Patients taking Tamoxifen.

3- Obese women in whom peripheral androgens are converted to estrogens.

4- Secretory ovarian tumors.

Hormone-independent endometriotic lesions in which the receptor level is much lower in the lesion than in the endometrium and not influenced by hormonal variation as the endometrium, so it gives rise to severe and extensive clinical forms requiring surgery (hysterectomy with removal of both ovaries and the endometriosis). If menopausal hormone therapy is needed afterwards, continuous combined estrogen-progestogen (or tibolone) is preferred, and estrogen alone should be avoided, even after hysterectomy.

Dr Najeeb Layyous F.R.C.O.G

Consultant Obstetrician, Gynecologist and Infertility Specialist