Endometriosis is a common gynecologic disorder. The estimated frequency among women of reproductive age is 5%–10% and is particularly frequent among women with pelvic pain and infertility. Around 50% women with pelvic pain suffer from endometriosis. It most commonly affects women in their 20’s and 30’s. This disorder is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. The exact etiology of endometriosis has yet to be elucidated. Mechanistic theories include: the reflux of endometrial tissue through the fallopian tubes at the time of menstruation, coelomic metaplasia, embryonic cell rests, and lymphatic and vascular dissemination. 

The theory of retrograde menstruation (also called the implantation theory or transplantation theory) is the most widely accepted theory for the formation of ectopic endometrium in endometriosis. It suggests that during a woman's menstrual flow, some of the endometrial debris exits the uterus through the fallopian tubes and attaches itself to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as endometriosis. While most women may have some retrograde menstrual flow, typically their immune system is able to clear the debris and prevent implantation and growth of cells from this occurrence. However, in some patients, endometrial tissue transplanted by retrograde menstruation may be able to implant and establish itself as endometriosis. Factors that might cause the tissue to grow in some women but not in others need to be studied, and some of the possible causes below may provide some explanation, e.g., hereditary factors, toxins, or a compromised immune system. It can be argued that the uninterrupted occurrence of regular menstruation month after month for decades is a modern phenomenon, as in the past women had more frequent menstrual rest due to pregnancy and lactation. Retrograde menstruation alone is not able to explain all instances of endometriosis, and it needs additional factors such as genetic or immune differences to account for the fact that many women with retrograde menstruation do not have endometriosis. However, it is generally accepted that endometriosis has a multi-factorial etiology, including genetic, hormonal and immunological factors. Areas commonly affected by endometriosis include the surface of the ovaries and the pelvic peritoneum and can result in pelvic inflammation, adhesions, chronic pain and infertility. Endometrial cells in areas outside the uterus are also influenced by hormonal changes and respond in a way that is similar to the cells found inside the uterus. While endometriosis is a benign lesion, it shares several characteristics with invasive cancer. Similar to cancer, endometriosis has the capacity to invade and spread distantly. Endometriosis can attach to, invade and damage affected tissues. In addition, numerous studies indicate that women with endometriosis have an increased risk of developing epithelial ovarian cancer (EOC).

There is no cure for endometriosis, but it can be treated in a variety of ways, including pain medication, hormonal treatments, and surgery.Tentative evidence suggests that the use of combined oral contraceptives reduces the risk of endometriosis. Exercise and avoiding large amount of alcohol may also be preventative.  

Types of endometriosis - Staging

Surgically, endometriosis can be staged I – IV (Revised Classification of the American Society of Reproductive Medicine). The process is a complex point system that assesses lesions and adhesions in the pelvic organs, but it is important to note staging assesses physical disease only, not the level of pain or infertility. A person with Stage I endometriosis may have little disease and severe pain, while a person with Stage IV endometriosis may have severe disease and no pain or vice versa. In principle the various stages show these findings:

Stage I (Minimal)

Findings restricted to only superficial lesions and possibly a few filmy adhesions (are fibrous bands that form between tissues and organs).

Stage II (Mild)

In addition, some deep lesions are present in the cul-de-sac (recto-uterine pouch - the extension of the peritoneal cavity between the rectum and the posterior wall of the uterus in the female human body).

Stage III (Moderate)

As above, plus presence of endometriomas on the ovary and more adhesions.

Stage IV (Severe)

As above, plus large endometriomas, extensive adhesions.

Even though the endometrioma of the ovary reacts poorly to hormone therapy, nowadays smaller endometriomas (approximately 2-3cm) are not removed surgically to avoid unnecessarily reducing the ovarian reserve.
A larger endometrioma, for example 40-50mm, can be surgically removed if it would constitute an obstacle to the egg collection included in the IVF program.
Ovarian stimulation does not aggravate the course of the endometriosis.
Eliminate the endometrioma with caution in order not to significantly reduce the ovarian reserve.
The worst is repeatedly interfering with the woman's organism and repeatedly operating the consequences of endometriosis.

Associated diseases

Current research has demonstrated an association between endometriosis and certain types of cancers, notably some types of ovarian cancer, non-Hodgkin's lymphoma and brain cancer. Despite similarities in their name and location, endometriosis bears no relationship to endometrial cancer. Endometriosis often also coexists with leiomyoma or adenomyosis, as well as autoimmune disorders.

Complications

Complications of endometriosis include internal scarring, adhesions, many adhezions are called frozen pelvis.

Infertility can be related to scar formation and anatomical distortions due to the endometriosis.It is a mechanical factor.However, endometriosis may also interfere in more subtle ways by biochemical factor. It means cytokines and other chemical agents may be released that interfere with reproduction (low fertilization of oocytes,decreased endometrial receptivity,decreased embryo nidability). Ovarian endometriosis (cysts) can be complicated by its rupture or torsion around own axis. Cysts significantly reduce ovarian tissue - functional parenchyma. Bowel and ureteral obstruction resulting from pelvic adhesions.

Risk factors

The following factors may place you at greater risk for developing endometriosis :

  • early onset of menstruation 
  • not having had children
  • family history of endometriosis 
  • short menstrual cycles 
  • low body mass index (BMI)
  • sedentary lifestyle 
  • age (women between the ages of 25 – 40)

Endometriosis can cause infertility. In endometriosis, there is a risk of female infertility of up to 30% to 50%. The abnormal growth of endometrial tissue with each female hormonal cycle causes adhesions and scars from forming in the organs where it is. This, in the case of the female reproductive organs can be fatal for the smooth passage of the ovum to the uterus.

The mechanisms by which endometriosis may cause infertility is not clearly understood, particularly when the extent of endometriosis is low.

Still possible mechanisms include:

  • Anatomical distortions and adhesions (the fibrous bands that form between tissues and organs following recovery from an injury)
  • The release of factors from endometriotic cysts which are detrimental to gametes or embryos. An endometriotic cyst contains free iron, reactive oxygen species, proteolytic enzymes and inflammatory molecules. Follicular density in tissue surrounding the endometriotic cyst has been consistently shown to be significantly lower than in healthy ovaries, and to a degree that does not appear to be caused merely by the stretching of surrounding tissues owing to the presence of a cyst.

The other way around, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon. For this reason it is preferable to speak of"endometriosis-associated infertility" rather than any definite "infertility caused by endometriosis"  by the same reason that association does not imply causation.

Only surgical treatment has been shown to improve the fertility of patients whose infertility was thought to be due to endometriosis. One study has shown that surgical treatment of endometriosis approximately doubles the fecundity (pregnancy rate).

In younger women with unfulfilled reproductive potential, surgical treatment attempts to remove endometrial tissue and preserving the ovaries without damaging normal tissue.

It is recommended that the small cysts do not operate at all to reduce the valuable ovarian parenchyma.

The use of medical suppression after surgery for minimal/mild endometriosis has not shown benefits for patients with infertility. It is advisable to stimulate the patient immediately after the chirugical exercise in the IVF treatment program. Ovarian stimulation does not aggravate the course of the endometriosis. Use of fertility medication that stimulates ovulation (clomiphene citrate, gonadotropins) combined with intrauterine insemination (IUI) enhances fertility in these patients.

Limited evidence indicates that the use of combined oral contraceptives is associated with a reduced risk of endometriosis.

  • Abdominal pain, fatigue and mood change beginning 1-2 days before menstruation and continuing for duration
  • Cyclical pelvic pain and/or low back pain (unilateral or bilateral) , constant pelvic pain (more serious stage)
  • Infertility - often first diagnosed in women who are seeking treatment for infertility
  • History of ectopic pregnancy or miscarriage
  • Dysmenorrhea (painful menstruation) - commonly identified as the chief complaint if implants are located over the uterosacral ligaments
  • Dyspareunia (painful intercourse) - local adhesions may be irritated by penile penetration
  • Painful defecation - adhesions may be present over the large bowel. As fecal matter moves through the intestines these adhesions can be stretched causing local irritation.
  • Low-grade fever 
  • diarrhea, constipation, rectal bleeding
  • referred pain to the low back/sacral groin, posterior leg, upper abdomen, or lower abdominal suprapubic areas
  • menorrhagia/menometrorrhagia - excessive or occasional heavy periods may be experienced, along with bleeding between periods   
If a woman increases her level of physical activity daily, the amount of pain related with endometriosis may decrease. Medical researchers are uncertain as to the cause of this relationship and have noted that increased exercise does not reduce pain in all women. As in the case of any chronic condition, lifestyle changes like regular movement and consumption of a healthy diet are recommended.

As surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse, many patients began to explore more natural and traditional remedies. In China, treatment of endometriosis using Chinese herbal medicine is routine to alleviate pain, promote fertility, and prevent relapse. However, due to the limited amount intervention studies reported, more rigorous researches are required to accurately assess the type, dose and potential role of Chinese herbal medicine  in treating endometriosis. 

Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. Current treatment of endometriosis is mainly based on surgery (Laparoscopic procedure with laser and/or electrocautery to ablate the lesions and lyse the adhesions, removal of endometriomas, hysterectomy and oophorectomy to prevent cycling) and ovarian suppressive agents (oral contraceptives, progestins, GnRh agonist and androgenic agents).

Pharmacotherapy

Non-steroidal anti- inflammatory agents

With attention to inflammatory nature of endometriosis, for decades non- steroidal anti-inflammatory agents (NSAIDs) such as naproxen and ibuprofen have been administrated for pain control, in endometriosis. These drugs have been reduced prostaglandins (PGs) production, the main stimulator factor in peritoneal nerves and decrease the nociceptor input messenger from the peritoneal endometriotic implants into central nervous system.

Hormones

Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRh antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). 

  1. Continuous oral contraceptive pills – are effective in relieving endometriosis associated pelvic pain, suppress Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) and prevent ovulation
  2. Medroxyprogesterone injections (Depo-Provera) – similar to oral contraceptive
  3. Danazol – a derivative of the synthetic steroid ethisterone that suppresses the production of gonadotropins and has some weak androgenic effects. Although effective for endometriosis, its use is limited by its masculinizing side-effects. Its role as a treatment for endometriosis has been largely replaced by the GnRH agonists.
  4. GnRH agonist (leuprolide, gosarelin) that will negatively feedback to reduce the GnRH secreted also leading to low estrogen, side effects include hot flushes, headaches, and osteoporosis.

Surgical therapy

  1. Laparoscopic procedure with laser and/or electrocautery to ablate the lesions and lyse the adhesions
  2. Removal of endometriomas
  3. Hysterectomy and oophorectomy to prevent cycling

Laparoscopy is nowadays considered best way. Interdisciplinary cooperation with urologists and surgeons is often necessary in the case of urinary tract or intestinal lesions.

Procedures are classified as conservative when reproductive organs are retained, semi - conservative when ovarian function is allowed to continue  and radical surgery.

Conservative therapy consists of the excision of the endometriosis bearing, adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as much as is possible. Laparoscopy, besides being used for diagnosis, can also be an option for surgery. It's considered a "minimally invasive" surgery because the surgeon makes very small openings (incisions) at (or around) the belly button and lower portion of the belly. A thin telescope-like instrument (the laparoscope) is placed into one incision, which allows the doctor to look for endometriosis using a small camera attached to the laparoscope. Small instruments are inserted through the incisions to remove the tissue and adhesions. Because the incisions are very small, there will only be small scars on the skin after the procedure.

Semi-conservative therapy preserves a healthy appearing ovary, very important for women wishing to conceive, but also increases the risk of recurrence and should be performed by a skilled and qualified surgeon.

Radical surgery
Removing the uterus , both ovaries, if possible, all of the endometriosis deposits, including adhesion disruption. It is performed in women who do not plan for pregnancy.

Other options for patients with extreme pain, a presacral neurectomy may be indicated where the nerves to the uterus are cut. However, strong clinical evidence showed that presacral neurectomy is more effective in pain relief if the pelvic pain is midline concentrated, and not as effective if the pain extends to theleft and right lower quadrants of the abdomen.This is because the nerves to betransected in the procedure are innervating the central or the midline regionin the female pelvis. Furthermore, women who had presacral neurectomy have higher prevalence of chronic constipation not responding well to medication treatment because of the potential injury to the parasympathetic nerve in the vicinity during the procedure.

Surgical treatment of deeply infiltrating endometriosis with colorectal involvement belongs to the most difficult surgery, often inoperable matter.

Treatment should be considered individually, respecting the patient's wishes. The most important is the so-called first operation, every other operation (reoperation) leads to a number of problems and is associated with higher morbidity of the patient.

Controlled ovarian hyperstimulation, intrauterine insemination, or in vitro fertilization, are commonly used for endometriosis-associated infertility. Endometriosis impairs the efficacy of in vitro fertilization. IVF makes it possible to combine sperm and eggs in a laboratory and then place the resulting embryos into the woman's uterus. The decision when to apply IVF in endometriosis-associated infertility cases takes into account the age of the patient, the severity of the endometriosis, the presence of other infertility factors, and the results and duration of past treatments.

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Sources

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