Can endometriosis effect fertility?
Endometriosis and infertility
Surgery is more effective for infertility than medicinal intervention in endometriosis. One study has shown that surgical treatment of endometriosis approximately doubles the fecundity (pregnancy rate). The use of medical suppression after surgery for minimal/mild endometriosis has not shown benefits for patients with infertility. Use of fertility medication that stimulates ovulation (clomiphene citrate, gonadotropins) combined with intrauterine insemination (IUI) enhances fertility in these patients.
Endometrial hyperplasia
Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of the progesterone-like hormones which ordinarily counteract estrogen's proliferative effects on this tissue. This may occur in a number of settings, including obesity, polycystic ovary syndrome, estrogen producing tumours (e.g. granulosa cell tumour) and certain formulations of estrogen replacement therapy. Endometrial hyperplasia is a significant risk factor for the development or even co-existence of endometrial cancer, so careful monitoring and treatment of women with this disorder is essential.
Endometriosis
Complications of endometriosis include internal scarring, adhesions, pelvic cysts, chocolate cysts of ovaries, ruptured cysts, and bowel and ureter obstruction resulting from pelvic adhesions. Endometriosis-associated infertility can be related to scar formation and anatomical distortions due to the endometriosis.
Coelomic epithelium
The coelomic metaplasia theory provides a theory for the pathology of endometriosis (a condition where endometrial tissue grows outside the uterus). The coelomic epithelium develops into: peritoneum, pleura and the surface of the ovary. This combines retrograde and metaplasia and can explain the distant sites of endometriosis.
Lipiodol
Recently there has been an increasing interest in the use of Lipiodol as a therapeutic agent in the management of unexplained infertility, using a procedure called Lipiodol flushing. There have been a small number of studies that suggest that flushing the media through the tubes gives a short-term rise in fecundity in patients with unexplained infertility. A systematic review has suggested a significant increase in fertility, especially in those women who have endometriosis when using Lipiodol flushing.
Endometrium
If there is inadequate stimulation of the lining, due to lack of hormones, the endometrium remains thin and inactive. In humans, this will result in amenorrhea, or the absence of a menstrual period. After menopause, the lining is often described as being atrophic. In contrast, endometrium that is chronically exposed to estrogens, but not to progesterone, may become hyperplastic. Long-term use of oral contraceptives with highly potent progestins can also induce endometrial atrophy.
Adenomyosis
The pathogenesis of adenomyosis still remains unclear, but the functioning of the inner myometrium, also called the junction zone (JZ), is believed to play a major role in the development of adenomyosis. It is also a matter of discussion whether the link between reproductive disorders and major obstetrical disorders also lies here. Parity, age, and previous uterine abrasion increase the risk of adenomyosis. Hormonal factors such as local hyperestrogenism and elevated levels of s-prolactin as well as autoimmune factors have also been identified as possible risk factors. As both the myometrium and stroma in an adenomyosis affected uterus show significant differences from those of a non-affected uterus, a complex origin that includes multifactorial changes on both genetic and biochemical levels is likely.
Round ligament pain
Several cases of inguinal endometriosis, that infiltrates the round ligament of the uterus have been reported in fertile, non-pregnant women. In the majority of these cases, diagnosis was problematic. In some cases, definitive diagnosis of round ligament endometriosis was only possible during exploratory surgery.
Thoracic endometriosis
Thoracic endometriosis affects women aged 15–54, who are between menarche and menopause. It can affect their qualify of life, with catamenial pneumothorax being the most common presentation.
Thoracic endometriosis
The endometrium, the tissue that normally lines the female uterus, undergoes changes with each menstrual cycle. At the end of each cycle and after the lining has thickened in preparation for hosting a fertilised ovum, it sloughs off, detaches, and is expelled through the cervix and vagina in the process of menstruation. In endometriosis, some endometrial tissue is found in other parts of the body; most often the pelvis and abdomen, the central nervous system, the nasal passages, skin and thorax. At these other 'ectopic' sites, endometrium tissue still responds to hormones with normal cyclical changes - bleeding roughly every 28 days.
Decidualization
Abnormalities in decidualization have been implicated in diseases such as endometriosis, in which impaired decidualization leads to ectopic uterine tissue growth. Lack of decidualization has also been linked to higher rates of miscarriage.
Endometrium
Chorionic tissue can result in marked endometrial changes, known as an Arias-Stella reaction, that have an appearance similar to cancer. Historically, this change was diagnosed as endometrial cancer and it is important only in so far as it should not be misdiagnosed as cancer.Thin endometrium may be defined as an endometrial thickness of less than 8 mm. It usually occurs after menopause. Treatments that can improve endometrial thickness include Vitamin E, L-arginine and sildenafil citrate.
Fertility testing
Hysteroscopy is used to diagnose the presence of a number of conditions which may affect fertility, such as uterine fibroids, Asherman's syndrome, and bicornate uterus. It involves the insertion of an endoscope to produce images of the inside of the uterus.
Carlos Simon (gynaecologist)
Since 1991 he has contributed with his pioneering works to the research and clinical solution of the problems that produce infertility which is suffered by the 10% of the couples in reproductive age in the world. He has worked on the clinical demonstration and molecular mechanisms which control the deleterious effect of the high levels of oestradiol hormone changing the regular clinical practice and initiating the concept of “mild stimulation”. By employing the technique of microarrays he identified the transcriptomic sequences of the genes involved in the human endometrial receptivity, by publishing his discoveries in 20 papers as the first or last author, the former is the most quoted in the scientific journal Molecular Human Reproduction. The clinical translation of his results has led in a patent about the creation of a customized array named endometrial receptivity array (ERA) for the molecular diagnosis of the endometrial receptivity in infertile patients (Díaz-Gimeno P, et al. Fertil Steril. 2011). All the same, he has created a data base bank with free access about the endometrial receptivity managed by the University of Valencia. Finally thanks to the funding of an excellence project PROMETEO to research the origin of the endometrial stem cells in human, he has been the first scientific in discovering that the endometrial stem cells isolated are able to reconstruct the human endometrium.
Endometriosis
There is an association between endometriosis and certain types of cancers, notably some types of ovarian cancer, non-Hodgkin's lymphoma and brain cancer. Endometriosis is unrelated to endometrial cancer.
Menopause
Women who have a functional disorder affecting the reproductive system (e.g., endometriosis, polycystic ovary syndrome, cancer of the reproductive organs) can go into menopause at a younger age than the normal timeframe. The functional disorders often significantly speed up the menopausal process.
Endometriosis
Rectovaginal or bowel endometriosis affects approximately 5-12% of women with endometriosis, and can cause severe pain with bowel movements.
Endometriosis
Individual genomic changes (found by genotyping including genome-wide association studies) that have been associated with endometriosis include:
Female infertility
Usually reproductive endocrinology & infertility medical practices do not see women for general maternity care. The practice is primarily focused on helping their women to conceive and to correct any issues related to recurring pregnancy loss.
There is no unanimous definition of female infertility, because the definition depends on social and physical characteristics which may vary by culture and situation. NICE guidelines state that: "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner." It is recommended that a consultation with a fertility specialist should be made earlier if the woman is aged 36 years or over, or there is a known clinical cause of infertility or a history of predisposing factors for infertility. According to the World Health Organization (WHO), infertility can be described as the inability to become pregnant, maintain a pregnancy, or carry a pregnancy to live birth.
A clinical definition of infertility by the WHO and ICMART is “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.” Infertility can further be broken down into primary and secondary infertility. Primary infertility refers to the inability to give birth either because of not being able to become pregnant, or carry a child to live birth, which may include miscarriage or a stillborn child.
Repeated implantation failure
Two genes have been identified to assist in the development and receptivity of the uterus and endometrium, Hoxa10 and Hoxa11. Hoxa10 has been shown to change the upper uterine segment into oviduct-like structures, creating a smaller uterus that appears normal. Embryo transfer into the lower uterine segment does not allow for implantation, so the Hoxa10 gene has multiple effects throughout the uterus. Hoxa11 mutations alter the endometrial gland development and reduce the secretion of Leukaemia-Inhibitory factor (LIF) which is required for implantation.
Fibroids are benign tumours found in the smooth muscle of the uterus, they are often asymptomatic but can cause pelvic pain. They effect implantation rates by altering the shape and cytokine composition of the uterus. Removal of submucosal fibroids has shown to increase implantation rates.
Linda Griffith
Griffith currently directs the Center for Gynepathology Research (CGR) at MIT, which she launched in 2009 together with Dr. Keith Isaacson, Director of the Newton-Wellesley Hospital Center for Minimally Invasive Gynecology Surgery. The public launch featured a passionate talk by the celebrity host of Bravo's Top Chef, Padma Lakshmi, who suffered for over a decade with endometriosis before being diagnosed. Lakshmi co-founded the Endometriosis Foundation of America (EFA) to raise awareness of the disease, especially among college students. Lakshmi's experience underscored that of Griffith's own 16-year-old niece, who was diagnosed with endometriosis after suffering years of debilitating pain, which had been attributed to "stress" instead of to a treatable disease. The average delay between onset of symptoms and diagnosis of endometriosis is about ten years; Griffith's niece was diagnosed with less delay only because a family member with the disease insisted she see a gynecological surgeon who specializes in treating endometriosis. The CGR now has over 10 participating faculty at MIT and collaborates with surgeons and scientists in Brazil, Singapore, and across the US. Griffith was honored at the EFA's annual Blossom Ball in NYC in 2010 for her efforts to raise awareness about endometriosis among scientists and engineers.
Asherman's syndrome
Depending on the degree of severity, AS may result in infertility, repeated miscarriages, pain from trapped blood, and future obstetric complications If left untreated, the obstruction of menstrual flow resulting from adhesions can lead to endometriosis in some cases.
Endometriosis
The rate of recurrence of endometriosis is estimated to be 40-50% for adults over a 5-year period. The rate of recurrence has been shown to increase with time from surgery and is not associated with the stage of the disease, initial site, surgical method used, or post-surgical treatment.
Hormone replacement therapy
While combined estrogen–progestogen supplementation has been linked to an increased incidence of endometrial cancer, the specific subtype is usually stage I, or "in situ", and has extremely low morbidity and mortality, and studies in American women have shown the tumor to not have propensity for growth into the myometrium or parametrial soft tissues. When seen in the context of all cause mortality, women who take estrogen and develop endometrial cancer have higher survival rates than women who do not take hormonal therapy at all, which was due to the preventive effect of HRT on hip fractures.
Endometriosis
The underlying process that causes endometriosis may not cease after a surgical or medical intervention. Studies have shown that endometriosis recurs at a rate of 20 to 40 percent within five years following conservative surgery,
unless hysterectomy is performed or menopause reached. Monitoring of women consists of periodic clinical examinations and sonography.
Uterine fibroid
While fibroids are common, they are not a typical cause for infertility, accounting for about 3% of reasons why a woman may not be able to have a child. The majority of women with uterine fibroids will have normal pregnancy outcomes. In cases of intercurrent uterine fibroids in infertility, a fibroid is typically located in a submucosal position and it is thought that this location may interfere with the function of the lining and the ability of the embryo to implant.
Endometriosis and infertility
In-vitro fertilization (IVF) procedures are effective in improving fertility in many women with endometriosis. 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. In ovarian hyperstimulation as part of IVF in women with endometriosis, using a standard GnRH agonist protocol has been found to be equally effective in regard to using a GnRH antagonist protocol in terms of pregnancy rate. On the other hand, when using a GnRH agonist protocol, long-term (three to six months) pituitary down-regulation before IVF for women with endometriosis has been estimated to increase the odds of clinical pregnancy by fourfold.
Kathryn B. H. Clancy
Clancy's fertility research focuses on menstruation and variability in endometrial function. Clancy's early published research demonstrated that, contrary to previous belief, menstruation does not increase risk for iron-deficiency anemia. Instead, Clancy and colleagues show that a thicker endometrium is associated with greater iron reserves amongst healthy women. Clancy's later studies focus on rural Polish populations. Clancy explores potential variation amongst endometrial function, or the functions of the inner mucous membrane layer of the uterus. Her research finds that endometrial thickness is negatively correlated over the latter phase of the menstrual cycle (the luteal phase).
Ectopic pregnancy
Women with pelvic inflammatory disease (PID) have a high occurrence of ectopic pregnancy. This results from the build-up of scar tissue in the Fallopian tubes, causing damage to cilia. If however both tubes were completely blocked, so that sperm and egg were physically unable to meet, then fertilization of the egg would naturally be impossible, and neither normal pregnancy nor ectopic pregnancy could occur. Intrauterine adhesions (IUA) present in Asherman's syndrome can cause ectopic cervical pregnancy or, if adhesions partially block access to the tubes via the ostia, ectopic tubal pregnancy. Asherman's syndrome usually occurs from intrauterine surgery, most commonly after D&C. Endometrial/pelvic/genital tuberculosis, another cause of Asherman's syndrome, can also lead to ectopic pregnancy as infection may lead to tubal adhesions in addition to intrauterine adhesions.
Dydrogesterone
Endometriosis is a chronic disease which can cause severe, progressive, and at times, incapacitating dysmenorrhea, pelvic pain, dyspareunia and infertility. Dydrogesterone relieves pain without inhibiting ovulation, so that patients are able to become pregnant during treatment. Dydrogesterone is particularly suitable in cases where the woman desires to become pregnant and to prevent bleeding problems. Dydrogesterone results in statistically significant reductions in the symptoms pelvic pain, dysmenorrhea and dyspareunia after the first treatment cycle for the treatment of post-laparoscopic endometriosis. The amount and duration of menstrual bleeding is also significantly reduced, and from the end of the third month onwards, bleeding was considered normal in the majority of patients. Improvement of endometriosis was observed in 71% of patients and cure in 21%.
Endometrial cancer
Risk factors for endometrial cancer include obesity, diabetes mellitus, breast cancer, use of tamoxifen, never having had a child, late menopause, high levels of estrogen, and increasing age. Immigration studies (migration studies), which examine the change in cancer risk in populations moving between countries with different rates of cancer, show that there is some environmental component to endometrial cancer. These environmental risk factors are not well characterized.
Endometriosis
Other symptoms include diarrhea or constipation, chronic fatigue, nausea and vomiting, headaches, low-grade fevers, heavy and/or irregular periods, and hypoglycemia.
Adenomyosis
Adenomyosis is a benign but often progressing condition. It is advocated that adenomyosis poses no increased risk for cancer development. However, both entities could coexist and the endometrial tissue within the myometrium could harbor endometrioid adenocarcinoma, with potentially deep myometrial invasion. As the condition is estrogen-dependent, menopause presents a natural cure. Ultrasound features of adenomyosis will still be present after menopause. People with adenomyosis are also more likely to have uterine fibroids or endometriosis.
Endometriosis Society of India
Endometriosis Society of India is a voluntary non-profit organisation that works to create awareness about endometriosis, training caregivers and service providers for better management of the condition and promoting research about endometriosis. Endometriosis is a benign yet progressive disease where the tissue that normally grows within the uterus grows outside of it – like on the ovaries, fallopian tubes or the external uterus. Its main symptoms are pelvic pain and infertility.
Endometriosis
Several studies have investigated the potential link between exposure to dioxins and endometriosis, but the evidence is equivocal and potential mechanisms are poorly understood. A 2004 review of studies of dioxin and endometriosis concluded that "the human data supporting the dioxin-endometriosis association are scanty and conflicting", and a 2009 follow-up review also found that there was "insufficient evidence" in support of a link between dioxin exposure and women developing endometriosis. A 2008 review concluded that more work was needed, stating that "although preliminary work suggests a potential involvement of exposure to dioxins in the pathogenesis of endometriosis, much work remains to clearly define cause and effect and to understand the potential mechanism of toxicity".
Diana Falzone
In January 2017, Falzone wrote an article published on the Fox News website revealing that she suffered from endometriosis, a condition that rendered her infertile: "It was just days after my 33rd birthday when my doctor delivered the worst news of my life: I will likely never have a child and fulfill my greatest wish of being a mother... When hit with the news that I am infertile, I could not stop crying. And not only was it very unlikely I’d ever conceive, my health was in jeopardy." Falzone alleges that she sought Fox News' approval to publish an article before publication.
Endometrium
Observation of the endometrium by transvaginal ultrasonography is used when administering fertility medication, such as in in vitro fertilization. At the time of embryo transfer, it is favorable to have an endometrium of a thickness of between 7 and 14 mm with a "triple-line" configuration, which means that the endometrium contains a hyperechoic (usually displayed as light) line in the middle surrounded by two more hypoechoic (darker) lines. A "triple-line" endometrium reflects the separation of the stratum basalis and functionalis layers, and is also observed in the periovulatory period secondary to rising estradiol levels, and disappears after ovulation.
Reproductive technology
Assisted reproductive technology (ART) is the use of reproductive technology to treat low fertility or infertility. ART is currently the only form of reproductive technology in clinical use, and is more effective in those suffering from ovulatory disorders or endometriosis (those without a functional uterus, for example, for the time being can only conceive through surrogacy methods). Examples of ART include "in vitro" fertilization and its possible expansions, including:
Persistent organic pollutant
The same study in 2002 with evidence of a link from POPs to endocrine disruption also linked low dose exposure of POPs to reproductive health effects. The study stated that POP exposure can lead to negative health effects especially in the male reproductive system, such as decreased sperm quality and quantity, altered sex ratio and early puberty onset. For females exposed to POPs, altered reproductive tissues and pregnancy outcomes as well as endometriosis have been reported.
Endometriosis
There are multiple causes of pain. Endometriosis lesions react to hormonal stimulation and may "bleed" at the time of menstruation. The blood accumulates locally if it is not cleared shortly by the immune, circulatory, and lymphatic system. This may further lead to swelling, which triggers inflammation with the activation of cytokines, which results in pain. Another source of pain is the organ dislocation that arises from adhesion binding internal organs to each other. The ovaries, the uterus, the oviducts, the peritoneum, and the bladder can be bound together. Pain triggered in this way can last throughout the menstrual cycle, not just during menstrual periods.
Endometritis
Acute Endometritis is characterized by infection. The organisms most often isolated are believed to be because of compromised abortions, delivery, medical instrumentation, and retention of placental fragments. There is not enough evidence for the use of prophylactic antibiotics to prevent endometritis after manual removal of placental in vaginal birth. Histologically, neutrophilic infiltration of the endometrial tissue is present during acute endometritis. The clinical presentation is typically high fever and purulent vaginal discharge. Menstruation after acute endometritis is excessive and in uncomplicated cases can resolve after 2 weeks of clindamycin and gentamicin IV antibiotic treatment.
Abayomi Ajayi
Abayomi is the country representative for Endometriosis Support Group. He has appeared on numerous television and radio programs He has also appeared on different television and radio channels talking and educating people about infertility. Abayomi is an advocate for helping couples with infertility and speaks on the topic on the programme Nordica Fertility Center on STV today.
Endometrial cancer
Genetic disorders can also cause endometrial cancer. Overall, hereditary causes contribute to 2–10% of endometrial cancer cases. Lynch syndrome, an autosomal dominant genetic disorder that mainly causes colorectal cancer, also causes endometrial cancer, especially before menopause. Women with Lynch syndrome have a 40–60% risk of developing endometrial cancer, higher than their risk of developing colorectal (bowel) or ovarian cancer. Ovarian and endometrial cancer develop simultaneously in 20% of people. Endometrial cancer nearly always develops before colon cancer, on average, 11 years before. Carcinogenesis in Lynch syndrome comes from a mutation in MLH1 and/or MLH2: genes that participate in the process of mismatch repair, which allows a cell to correct mistakes in the DNA. Other genes mutated in Lynch syndrome include MSH2, MSH6, and PMS2, which are also mismatch repair genes. Women with Lynch syndrome represent 2–3% of endometrial cancer cases; some sources place this as high as 5%. Depending on the gene mutation, women with Lynch syndrome have different risks of endometrial cancer. With MLH1 mutations, the risk is 54%; with MSH2, 21%; and with MSH6, 16%.
Endometriosis and infertility
In younger women with unfulfilled reproductive potential, surgical treatment attempts to remove endometrial tissue and preserving the ovaries without damaging normal tissue.
Stenosis of uterine cervix
Cervical stenosis may impact natural fertility by impeding the passage of semen into the uterus. In the context of infertility treatments, cervical stenosis may complicate or prevent the use of intrauterine insemination (IUI) or in vitro fertilization (IVF) procedures.
Neuroangiogenesis
Endometriosis is a common gynaecological disease caused by endometrial tissue implanting outside the uterus, a symptom of which is chronic pelvic pain. The formation, growth and persistence of these implants are dependent upon angiogenesis to increase the supply of blood vessels. The resulting increase in blood flow may correlate directly with pain symptoms. One possible explanation for this is the simultaneous growth of neurons into these areas alongside blood vessels through neuroangiogenesis.
Elagolix
Elagolix is used in the treatment of moderate to severe pain associated with endometriosis in premenopausal women. Endometriosis is a condition in which the endometrium, the inner lining of the uterus, grows outside of the uterus into surrounding tissues and causes symptoms such as pelvic pain and infertility. Around 10% of women may be affected by endometriosis. Elagolix significantly decreases symptoms of dysmenorrhea (menstrual pelvic pain), non-menstrual pelvic pain, and dyspareunia (pain during sexual intercourse) in women with endometriosis. The medication is used at a lower dosage of 150 mg once per day or at a higher dosage of 200 mg twice per day, depending on the severity of symptoms.
LENG9
Analysis of endometrial receptivity using miRNA of receptive and prereceptive endometrium from fertile women also indicated significant up-regulation of miR-30d. Consequently, the induced expression of LENG9 from miR-30d transfection suggests a possible relationship between the LENG9 gene and female fertility functions.
Myocardial infarction
Endometriosis in women under the age of 40 is an identified risk factor.
Infertility
For women, problems with fertilisation arise mainly from either structural problems in the Fallopian tube or uterus or problems releasing eggs. Infertility may be caused by blockage of the Fallopian tube due to malformations, infections such as chlamydia or scar tissue. For example, endometriosis can cause infertility with the growth of endometrial tissue in the Fallopian tubes or around the ovaries. Endometriosis is usually more common in women in their mid-twenties and older, especially when postponed childbirth has taken place.
Tubal factor infertility
Tubal factor infertility can be due to Chlamydia infection and testing for Chlamydia antibodies is one diagnostic tool. A "Mycoplasma genitalium" infection has also been linked to TFI. Women have difficulty getting pregnant or carrying a baby to term due to the buildup of scar tissue in the Fallopian tubes causing damage to the cilia on the epithelial cells. TFI can also be due to endometriosis.
Dienogest
Dienogest is described as "special" progestogen, possessing low or moderate antigonadotropic efficacy but strong or very strong endometrial efficacy. Specifically in relation to endometrial activity, dienogest is said to be one of the strongest progestogens available. The high endometrial activity of dienogest underlies its ability to stabilize the menstrual cycle when combined with either ethinylestradiol or estradiol valerate in birth control pills, and also its use in the treatment of endometriosis. The combination of most other progestins with estradiol as birth control pills failed due to a high incidence of irregular menstrual bleeding. This is a property that ethinylestradiol does not share with estradiol, because of its resistance to metabolism in the endometrium and hence its greater relative effects in this part of the body. In contrast to other progestins, due to its high endometrial efficacy, the combination of dienogest with estradiol valerate in birth control pills is able to prevent breakthrough bleeding, and is uniquely able to treat heavy menstrual bleeding. The absence of withdrawal bleedings, otherwise known as "silent menstruations", also may occur.
Endometriosis
55% to 100% of women develop adhesions following pelvic surgery, which can result in infertility, chronic abdominal and pelvic pain, and difficult reoperative surgery. Trehan's temporary ovarian suspension, a technique in which the ovaries are suspended for a week after surgery may be used to reduce the incidence of adhesions after endometriosis surgery.
KLF15
In rodents KLF15 appears to control the actions of estradiol and progesterone in the endometrium by inhibiting the production of MCM2, a protein involved in DNA synthesis raising the possibility of preventing or treating endometrial and breast cancer and other diseases related to estrogen by promoting the action of KLF15.
Endometrosis
Endometrosis is a chronic degenerative syndrome of the lining of the uterus (the endometrium) in mares. The cause is unknown, but the severity of endometrosis increases in parallel with the age and number of pregnancies of the mare. Endometrosis is confirmed by histological examination of an endometrial biopsy, which shows degeneration of blood vessels in the endometrium, and fibrosis of the tissue, along with the development of endometrial cysts. These changes cause subfertility; in pregnant mares, the changes in the endometrium can cause the placenta to fail, leading to miscarriage of the foal. Foals which are delivered at full term may be underdeveloped (dysmature). No effective treatment is known.
Worldwide Endometriosis March
The first Worldwide EndoMarch took place on March 13, 2014, and occurred in approximately 43 countries, with a flagship event held on the National Mall in Washington, D.C. Multiple medical societies and medical schools co-sponsored the event, including the American Medical Association, American College of Obstetricians and Gynecologists, American Society of Reproductive Medicine, Society of Laparoendoscopic Surgeons, International Federation of Gynecology and Obstetrics, Royal College of Obstetricians and Gynecologists, the European Society of Human Reproduction and Embryology, The National Infertility Association, Howard University, and the World Symposium on Endometriosis and Oncofertility. Several U.S. public figures attended the first Washington, D.C. EndoMarch, including Oracle Co-CEO Safra Catz, Grammy-winning singer-songwriter Sheryl Crow, Law and Order SVU Actress Stephanie March, MSNBC News reporter Mika Brzezinski, and TV Political Analyst Michelle Bernard. Public figures from other countries have also supported the international marches.
Endometrial cancer
Estrogen replacement therapy during menopause when not balanced (or "opposed") with progestin is another risk factor. Higher doses or longer periods of estrogen therapy have higher risks of endometrial cancer. Women of lower weight are at greater risk from unopposed estrogen. A longer period of fertility—either from an early first menstrual period or late menopause—is also a risk factor. Unopposed estrogen raises an individual's risk of endometrial cancer by 2–10 fold, depending on weight and length of therapy. In trans men who take testosterone and have not had a hysterectomy, the conversion of testosterone into estrogen via androstenedione may lead to a higher risk of endometrial cancer.
Endometriosis
Retrograde menstruation alone is not able to explain all instances of endometriosis, and additional factors such as genetic or immune differences need to be invoked to account for the fact that many women with retrograde menstruation do not have endometriosis. In addition, endometriosis has shown up in people who have never experienced menstruation including men, fetuses, and prepubescent girls. Further detracting from the retrograde menstruation theory are cases of endometriosis showing up in the brain and lungs. This theory has numerous other associated issues.
Endometriosis
Some factors associated with endometriosis include:
Elagolix
Because combined birth control pills and other forms of combined birth control contain an estrogen, and because elagolix treats endometriosis by decreasing estrogen levels in the endometrium, these form of hormonal birth control are likely and expected to decrease the effectiveness of elagolix in the treatment of this condition. The effect of progestogen-only birth control on the effectiveness of elagolix in endometriosis is unknown. However, progestogens are antiestrogenic in the uterus, and high-dose progestin therapy is known to be effective in the treatment of endometriosis similarly to GnRH antagonists. On the basis of limited clinical research, combined birth control pills have also been found to be effective in the treatment of endometriosis, but are likely not as effective as GnRH modulator monotherapy. It is advised that women use non-hormonal methods of birth control during elagolix therapy and for one week following discontinuation of elagolix.
Cécile Réal
Endodiag specializes in endometriosis which occurs when small pieces of the lining of the womb migrate to other parts of the body. The cells cause pain and can lead to infertility. It is not unusual for diagnosis to take up to nine years. The company is developing methods to improve diagnosis with tools such as EndoGram, based on biopsy, and EndoDiag, relying on a simple blood test.
Human reproductive ecology
Fertility is influenced by fecundity, but has additional factors that can increase or decrease an individual's lifetime reproductive success. The inter-birth interval, the amount of time between a woman's births, impacts a woman's total fertility. This amount of time varies cross-culturally, as well as varies with different environmental constraints. Many cultures practice conscious birth spacing to adhere to the desired length of time between pregnancies, or desired number of children. Environmental concerns like fetal loss, lack of resource access, and disease may all impact fertility for females or males.
Endometrium
About 20,000 protein coding genes are expressed in human cells and some 70% of these genes are expressed in the normal endometrium. Just over 100 of these genes are more specifically expressed in the endometrium with only a handful genes being highly endometrium specific. The corresponding specific proteins are expressed in the glandular and stromal cells of the endometrial mucosa. The expression of many of these proteins vary depending on the menstrual cycle, for example the progesterone receptor and thyrotropin-releasing hormone both expressed in the proliferative phase, and PAEP expressed in the secretory phase. Other proteins such as the HOX11 protein that is required for female fertility, is expressed in endometrial stroma cells throughout the menstrual cycle. Certain specific proteins such as the estrogen receptor are also expressed in other types of female tissue types, such as the cervix, fallopian tubes, ovaries and breast.
Endometriosis
There are public figures who speak out about their experience with endometriosis including Whoopi Goldberg, Mel Greigs, and Julianne Hough.
Endometritis
In human medicine, pyometra (also a veterinary condition of significance) is regarded as a form of chronic endometritis seen in elderly women causing stenosis of the cervical os and accumulation of discharges and infection. Symptom in chronic endometritis is blood stained discharge but in pyometra the patient complaints of lower abdominal pain.
Endometrium
In humans, the cycle of building and shedding the endometrial lining lasts an average of 28 days. The endometrium develops at different rates in different mammals. Various factors including the seasons, climate, and stress can affect its development. The endometrium itself produces certain hormones at different stages of the cycle and this affects other parts of the reproductive system.
Mucin 4
MUC-4 is also relevant to several other disease conditions. Polymorphisms in the MUC4 gene have been found to play a role in the progression of endometriosis and related infertility, as well as dysplastic cervical disorders. MUC-4 also has important roles in inflammatory bowel disease such as Crohn's disease and is found to be overexpressed in ulcerative colitis.
Oophorectomy
Oophorectomy for endometriosis is used only as last resort, often in conjunction with a hysterectomy, as it has severe side effects for women of reproductive age. However, it has a higher success rate than retaining the ovaries.
Ovarian disease
There is no exact cause of endometriosis.
Endometrioma
Laser surgery and cauterization are considered to be far less effective and only burn the top layer of endometrial tissue, allowing for the endometrioma and endometriosis to grow back quickly. Likewise, endometrioma drainage or sclerotherapy are somewhat controversial technique for removing endometriomas with varied degrees of success. Conservative surgery can be performed to preserve fertility in younger patients but as earlier stated can have the effect of raising FSH values and making the ovaries less productive, especially if functional ovarian tissue is removed in the surgical process.
Fertility testing
Laparoscopy is used to examine the interior of the abdomen. It can be used to establish patency of the fallopian tubes, and is especially suitable for the diagnosis of endometriosis.
Endometrial cancer
Smoking and the use of progestin are both protective against endometrial cancer. Smoking provides protection by altering the metabolism of estrogen and promoting weight loss and early menopause. This protective effect lasts long after smoking is stopped. Progestin is present in the combined oral contraceptive pill and the hormonal intrauterine device (IUD). Combined oral contraceptives reduce risk more the longer they are taken: by 56% after four years, 67% after eight years, and 72% after twelve years. This risk reduction continues for at least fifteen years after contraceptive use has been stopped. Obese women may need higher doses of progestin to be protected. Having had more than five infants (grand multiparity) is also a protective factor, and having at least one child reduces the risk by 35%. Breastfeeding for more than 18 months reduces risk by 23%. Increased physical activity reduces an individual's risk by 38–46%. There is preliminary evidence that consumption of soy is protective.
Endometritis
Endometritis is inflammation of the inner lining of the uterus (endometrium). Symptoms may include fever, lower abdominal pain, and abnormal vaginal bleeding or discharge. It is the most common cause of infection after childbirth. It is also part of spectrum of diseases that make up pelvic inflammatory disease.
Endometritis is divided into acute and chronic forms. The acute form is usually from an infection that passes through the cervix as a result of an abortion, during menstruation, following childbirth, or as a result of douching or placement of an IUD. Risk factors for endometritis following delivery include Caesarean section and prolonged rupture of membranes. Chronic endometritis is more common after menopause. The diagnosis may be confirmed by endometrial biopsy. Ultrasound may be useful to verify that there is no retained tissue within the uterus.
Treatment is usually with antibiotics. Recommendations for treatment of endometritis following delivery includes clindamycin with gentamicin. Testing for and treating gonorrhea and chlamydia in those at risk is also recommended. Chronic disease may be treated with doxycycline. Outcomes with treatment are generally good.
Rates of endometritis are about 2% following vaginal delivery, 10% following scheduled C-section, and 30% with rupture of membranes before C-section if preventative antibiotics are not used. The term "endomyometritis" may be used when inflammation of the endometrium and the myometrium is present. The condition is also relatively common in other animals such as cows.
Uterine fibroid
Aromatase inhibitors have been used experimentally to reduce fibroids. The effect is believed to be due partially by lowering systemic estrogen levels and partially by inhibiting locally overexpressed aromatase in fibroids. However, fibroid growth has recurred after treatment was stopped. Experience from experimental aromatase inhibitor treatment of endometriosis indicates that aromatase inhibitors might be particularly useful in combination with a progestogenic ovulation inhibitor.
Endometriosis
There are many findings of altered gene expression and epigenetics, but both of these can also be a secondary result of, for example, environmental factors and altered metabolism. Examples of altered gene expression include that of miRNAs.
Endometrial cancer
Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.
Approximately 40% of cases are related to obesity. Endometrial cancer is also associated with excessive estrogen exposure, high blood pressure and diabetes. Whereas taking estrogen alone increases the risk of endometrial cancer, taking both estrogen and a progestogen in combination, as in most birth control pills, decreases the risk. Between two and five percent of cases are related to genes inherited from the parents. Endometrial cancer is sometimes loosely referred to as "uterine cancer", although it is distinct from other forms of uterine cancer such as cervical cancer, uterine sarcoma, and trophoblastic disease. The most frequent type of endometrial cancer is endometrioid carcinoma, which accounts for more than 80% of cases. Endometrial cancer is commonly diagnosed by endometrial biopsy or by taking samples during a procedure known as dilation and curettage. A pap smear is not typically sufficient to show endometrial cancer. Regular screening in those at normal risk is not called for.
The leading treatment option for endometrial cancer is abdominal hysterectomy (the total removal by surgery of the uterus), together with removal of the fallopian tubes and ovaries on both sides, called a bilateral salpingo-oophorectomy. In more advanced cases, radiation therapy, chemotherapy or hormone therapy may also be recommended. If the disease is diagnosed at an early stage, the outcome is favorable, and the overall five-year survival rate in the United States is greater than 80%.
In 2012, endometrial cancers newly occurred in 320,000 women and caused 76,000 deaths. This makes it the third most common cause of death in cancers which only affect women, behind ovarian and cervical cancer. It is more common in the developed world and is the most common cancer of the female reproductive tract in developed countries. Rates of endometrial cancer have risen in a number of countries between the 1980s and 2010. This is believed to be due to the increasing number of elderly people and increasing rates of obesity.
Vaginal bleeding or spotting in women after menopause occurs in 90% of endometrial cancer. Bleeding is especially common with adenocarcinoma, occurring in two-thirds of all cases. Abnormal menstrual cycles or extremely long, heavy, or frequent episodes of bleeding in women before menopause may also be a sign of endometrial cancer.
Endometrium
The normal dominance of Lactobacilli in the vagina is seen as a marker for vaginal health. However, in the uterus this much lower population is seen as invasive in a closed environment that is highly regulated by female sex hormones, and that could have unwanted consequences. In studies of endometriosis "Lactobacillus" is not the dominant type and there are higher levels of "Streptococcus" and "Staphylococcus" species. Half of the cases of bacterial vaginitis showed a polymicrobial biofilm attached to the endometrium.
Endometriosis
It can affect any female, from premenarche to postmenopause, regardless of race or ethnicity or whether or not they have had children. It is primarily a disease of the reproductive years. Incidences of endometriosis have occurred in postmenopausal women, and in less common cases, girls may have endometriosis symptoms before they even reach menarche.
Lactational amenorrhea
Although the first post-partum cycle is sometimes anovulatory (reducing the likelihood of becoming pregnant again before having a post-partum period), subsequent cycles are almost always ovulatory and therefore must be considered fertile. For women exclusive breastfeeding ovulation tends to return after their first menses after the 56 days postpartum time period. Supplementing nutritional intake can lead to an earlier return of menses and ovulation then exclusive breastfeeding. Nursing more frequently for a shorter amount of time was shown to be more successful in prolonging amenorrhea then nursing longer but less frequently. The continuing of breastfeeding, while introducing solids after 6 months, to 12 months were shown to have an efficiency rate of 92.6 – 96.3 percent in pregnancy prevention. Because of this some women find that breastfeeding interferes with fertility even after ovulation has resumed.
Endometrial arteries
In the endometrium there are straight and serial arteries. Straight arteries specifically branch to the base of the endometrium therefore supplying blood to the base of the endometrium. Spiral arteries supply blood to the rest of the endometrium. They grow rapidly, covering much of the space of the endometrium and end up coiled. When hormones levels are low, the endometrial arteries react by becoming narrow. Endometrial arteries supply blood to the endometrium but are also beneficial during pregnancy. When a female is pregnant a placenta develops. The baby receives blood, nutrients and oxygen via the umbilical cord which is attached to the placenta. Between the placenta and the myometrium are intervillous spaces where the endometrial arteries supply blood to. The placenta has villous trees which allow for blood to circulate and then be transported to the baby via the placenta.
Artificial insemination
There are a number of reasons why a woman with a male partner would use artificial insemination to achieve pregnancy. For example, a woman's immune system may be rejecting her partner's sperm as invading molecules. Women who have issues with the cervix – such as cervical scarring, cervical blockage from endometriosis, or thick cervical mucus – may also benefit from artificial insemination, since the sperm must pass through the cervix to result in fertilization.
Female infertility
A woman's fertility is affected by her age. The average age of a girl's first period (menarche) is 12-13 (12.5 years in the United States, 12.72 in Canada, 12.9 in the UK), but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year. A woman's fertility peaks in the early and mid 20s, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced age depend on many factors, including the general health of a woman and the fertility of the male partner.
Endometrioma
Laparoscopic surgical approaches include excision of ovarian adhesions and of endometriomas. Endometriomas frequently require surgical removal and excision is considered to be superior in terms of permanent removal of the disease and pain relief. Surgery can sometimes have the effect of improving fertility but can have the adverse effect of leading to increases in cycle day 2 or 3 FSH for many patients.
SGK
Deregulated expression of SGK1 in the endometrium has been implicated in cases of infertility or recurrent miscarriage in humans, and SGK1 expression in the endometrium also affects fertility in mice.
Endometriosis
Endometriosis recurrence following conservative surgery is estimated as 21.5% at 2 years and 40-50% at 5 years.
Haemolacria
Acute haemolacria can occur in fertile women and seems to be induced by hormones, similarly to what happens in endometriosis.
Dioxins and dioxin-like compounds
The Endometriosis Research Center (ERC) has testified before the California State Legislature concerning Assembly Bill 2820 [Cardoza, D-Merced] that, "feminine hygiene products (i.e. tampons) do indeed test positive for Dioxin. Dioxin, in turn, is a well-documented catalyst for Endometriosis - and the effects of Dioxin are cumulative; able to be measured as much as 20 or 30 years after exposure." The ERC also references an independent study that found, in an assessment of four brands of tampons and four brands of baby diapers, dioxins "were present at detectable concentrations in all samples." The presence of this toxin in tampons may be linked to endometriosis because dioxins last a long time in the body; they are chemically stable and can be absorbed by fat tissue, where they are then stored in the body. Their half-life in the body is estimated to be 7 to 11 years.
Estradiol
Certain gynecological conditions are dependent on estrogen, such as endometriosis, leiomyomata uteri, and uterine bleeding.
Endometriosis
While there is no cure for endometriosis, there are two types of interventions; treatment of pain and treatment of endometriosis-associated infertility. In many women, menopause (natural or surgical) will abate the process. In women in the reproductive years, endometriosis is merely managed: the goal is to provide pain relief, to restrict progression of the process, and to restore or preserve fertility where needed. In younger women, surgical treatment attempts to remove endometrial tissue and preserve the ovaries without damaging normal tissue.
Endometrium
An endometrial thickness of less than 7 mm decreases the pregnancy rate in in vitro fertilization by an odds ratio of approximately 0.4 compared to an EMT of over 7 mm. However, such low thickness rarely occurs, and any routine use of this parameter is regarded as not justified.
Health in Australia
In 2011, endometriosis was estimated to affect 550,000 women and girls in Australia, with estimated direct costs fof $6 billion per annum for medical and surgical treatments of adult women and $600 million per annum for medical and surgical treatments of girls. Between the ages of 15 to 49 years, approximately 1 in 10 women are affected by it, a higher incidence than conditions such as breast cancer, prostate cancer, diabetes and AIDS combined within that age range. Working women are estimated to lose 11 hours per week due to absenteeism and presenteeism. In addition, there are the indirect costs and the general loss of quality of life due to the debilitating pain. Such indirect costs include welfare payments for disability and unemployment, expenditure on complementary medication and therapies, and the medical costs of treating consequential issues of mental health and infertility caused by endometriosis. Endometriosis usually first presents symptoms during adolescence but there is an average of 8 years from first symptoms to diagnosis, due to parents and general practitioners "discrediting" the pelvic pain as being a "normal" aspect of the menstrual cycle, while employed women encounter negativity by employers towards women perceived to have menstrual irregularities.
Endometriosis and infertility
In endometriosis, there is a risk of female infertility of up to 30% to 50%.
Endometriosis
A hysterectomy (removal of the uterus) can be used to treat endometriosis in women who do not wish to conceive. However, this should only be done when combined with removal of the endometriosis by excision, as if endometriosis is not also removed at the time of hysterectomy, pain may persist.
Adenomyosis
Adenomyosis can only be cured definitively with surgical removal of the uterus. As adenomyosis is responsive to reproductive hormones, it reasonably abates following menopause when these hormones decrease. In women in their reproductive years, adenomyosis can typically be managed with the goals to provide pain relief, to restrict progression of the process, and to reduce significant menstrual bleeding.
Broadly speaking, surgical management of adenomyosis is split into two categories: uterine-sparing and non-uterine-sparing procedures. Uterine-sparing procedures are surgical operations that do not include surgical removal of the uterus. Some uterine-sparing procedures have the benefit of improving fertility or retaining the ability to carry a pregnancy to term. In contrast, some uterine-sparing procedures worsen fertility or even result in complete sterility. The impact of each procedure on a woman's fertility is of particular concern and typically guides the selection. Non-uterine-sparing procedures, by definition, include surgical removal of the uterus and consequently they will all result in complete sterility.
Hysterectomy, or surgical removal of the uterus, has historically been the primary method of diagnosing and treating adenomyosis. It was especially popular in women who had completed their childbearing or in cases where fertility was not desired. Today, there are many more medical and surgical interventions available. These treatments, such as hormonal therapy and endometrial ablation, have significantly reduced the number of women who require a hysterectomy. That being said, hysterectomies remain as the final treatment option for women in whom the other treatments have failed. Typically viewed as definitive treatment for the bleeding and pelvic pain associated with adenomyosis, a hysterectomy will always result in sterility and cessation of menstrual bleeding. Pelvic pain, on the other hand, can persist after a hysterectomy in as many as 22% of women.
Endometriosis
A 20-year study of 12,000 women with endometriosis found that women under 40 who are diagnosed with endometriosis are 3 times more likely to have heart problems than their healthy peers.
Endometrial cancer
The few contraindications to surgery include inoperable tumor, massive obesity, a particularly high-risk operation, or a desire to preserve fertility. These contraindications happen in about 5–10% of cases. Women who wish to preserve their fertility and have low-grade stage I cancer can be treated with progestins, with or without concurrent tamoxifen therapy. This therapy can be continued until the cancer does not respond to treatment or until childbearing is done. Uterine perforation may occur during a D&C or an endometrial biopsy. Side effects of surgery to remove endometrial cancer can specifically include sexual dysfunction, temporary incontinence, and lymphedema, along with more common side effects of any surgery, including constipation.
VEZT
Endometriosis is a gynaecological disorder affecting 1 in 10 women in their reproductive years globally. This disorder occurs when endometrial tissue which grows inside the lining of the uterus grows on the outer surface of the uterus. The predominant symptoms of this are pelvic pain and infertility, however 25% of women who are inflicted with the disease may show none of these symptoms. Whilst the disease is usually non-fatal, it can have prolonged social and psychological effects on women and thus degrades their quality of life. Whilst the causes of the disease are still unclear, a certain number of genes have been linked to being a contributing factor for the disease. Of these, mutations in the VEZT gene have been identified by various Genome-wide association studies (GWAS). The VEZT gene is a complex gene, however it is known that the single nucleotide polymorphism (SNP) rs10859871 at locus 12q22 has been highly linked to being a genetic cause of endometriosis in women. An SNP is simply a variation that occurs in a single nucleotide in a specific region of a gene. Vezatin, the protein encoded by the VEZT gene is seen abundantly in endometrial and myometrial tissue, with localisation of the protein being both cytoplasmic and nuclear. This result was concurrent with previous literature stating the prominent role of vezatin in the regulation and maintenance of adherens junctions. This specific SNP is proven to cause an increase in vezatin expression within the endometrial cells, thus posing as a risk factor in the pathogenesis of endometriosis. Vezatin expression is also greater in ectopic endometrium as opposed to eutopic. Furthermore, vezatin expression is significantly increased in glandular endometrium during the secretory phase of the menstrual cycle. This result in conjunction with the finding that other adherens junction components also increase expression suggests that this process may be occurring in response to fluctuating progesterone levels. However, the mechanism of increased vezatin expression leading to the formation of ectopic endometrial tissues is unknown. Furthermore, there is much more scientific study required to directly link mutations in the VEZT gene to a direct cause of endometriosis.
Endometriosis
Surgically, endometriosis can be staged I–IV by the revised classification of the American Society of Reproductive Medicine from 1997. 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 a 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:
Endometriosis
Also, endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the central nervous system, potentially producing a variety of individual differences in pain that can, in some women, become independent of the disease itself. Nerve fibres and blood vessels are thought to grow into endometriosis lesions by a process known as neuroangiogenesis.
Endometrium
The endometrial lining undergoes cyclic regeneration. Humans, apes, and some other species display the menstrual cycle, whereas most other mammals are subject to an estrous cycle. In both cases, the endometrium initially proliferates under the influence of estrogen. However, once ovulation occurs, the ovary (specifically the corpus luteum) will produce much larger amounts of progesterone. This changes the proliferative pattern of the endometrium to a secretory lining. Eventually, the secretory lining provides a hospitable environment for one or more blastocysts.
Endometrial cancer
Most of the risk factors for endometrial cancer involve high levels of estrogens. An estimated 40% of cases are thought to be related to obesity. In obesity, the excess of adipose tissue increases conversion of androstenedione into estrone, an estrogen. Higher levels of estrone in the blood causes less or no ovulation and exposes the endometrium to continuously high levels of estrogens. Obesity also causes less estrogen to be removed from the blood. Polycystic ovary syndrome (PCOS), which also causes irregular or no ovulation, is associated with higher rates of endometrial cancer for the same reasons as obesity. Specifically, obesity, type II diabetes, and insulin resistance are risk factors for Type I endometrial cancer. Obesity increases the risk for endometrial cancer by 300–400%.