Endometriosis and infertility

Last updated

Endometriosis and its complications are a major cause of female infertility. Endometriosis is a dysfunction characterized by the migration of endometrial tissue to areas outside of the endometrium of the uterus. The most common places to find stray tissue are on ovaries and fallopian tubes, followed by other organs in the lower abdominal cavity such as the bladder and intestines. Typically, the endometrial tissue adheres to the exteriors of the organs, and then creates attachments of scar tissue called adhesions that can join adjacent organs together. The endometrial tissue and the adhesions can block a fallopian tube and prevent the meeting of ovum and sperm cells, or otherwise interfere with fertilization, implantation and, rarely, the carrying of the fetus to term.

Contents

Endometriosis is estimated to occur in 1% to 5% of women, with an associated risk of infertility for between 30% and 50% of this population. [1] [2] [3] Endometriosis is commonly classified under the revised American Society for Reproductive Medicine system from minimal endometriosis to severe endometriosis. The therapy and management of endometriosis for infertility is based on the severity of endometriosis. [4]

Diagnosis and classification

Endometriosis often presents with a very diverse array of symptoms, such as dysmenorrhea (pain during menstruation), cyclical pelvic pain (generalized pain in the lower abdomen that predictably worsens with menstruation), dyspareunia (pain during intercourse), or infertility (inability to achieve a pregnancy with unprotected intercourse for > 1 year). One suggested pathophysiologic mechanism involves retrograde menstruation and endometrial interactions with peritoneal inflammatory cytokines that promote ectopic implantation and growth of endometrial tissue outside of the uterus. [5] Most women experience this phenomenon during normal cycles, rendering many susceptible to endometriosis. Up to 4.1% of women undergoing tubal ligation surgeries have visually apparent, but clinically asymptomatic endometrial implantations. [6] The poor correlation between extent of ectopic implantation to symptom severity makes early detection and intervention challenging. Women in which the presenting symptom is infertility often have diagnoses delayed beyond the average window of 25–29 years of age. [6]

The gold standard for diagnosing endometriosis is a diagnostic laparoscopy, a minimally invasive procedure that involves a camera entering the abdominals through a small incision to examine the abdominal cavity for the presence of endometriotic tissue outside of the uterus. Suspect lesions may be further examined microscopically for confirmation, before being classified as: [7]

Upon diagnosis of endometriosis, there are also several classification systems to rate the prognosis. Currently, revised American Society for Reproductive Medicine (rASRM) classification is the most globally accepted and widely used system for the classification of endometriosis. It uses a weighted scoring system, in which values are assigned according to the size and severity of endometriotic adhesions in the ovaries, peritoneum, and fallopian tube. The cumulative score is then ranked as: [8]

Despite being the preferred staging system, each successive stage does not accurately predict the severity of pain an individual will experience or infertility. In fact, there was no difference in observed fertility rates following use of assisted reproductive technology (ART) across rASRM stages. [9] To more accurately predict infertility rates, the development of the Endometriosis Fertility Index (EFI) was proposed in 2010. [10]

Used in conjunction with rASRM, EFI functional scores incorporate patient characteristics to strengthen predictions of infertility, such as age, duration of infertility, and history of prior pregnancy. With 5 possible points derived from surgical findings and 5 possible points from patient characteristics, EFI functional scores range from 0 (worst prognosis, lowest probability of natural pregnancy) to 10 (best prognosis, highest probability of natural pregnancy). [11] Currently, EFI remains the only validated classification system that predicts pregnancy outcomes for patients following laparoscopy for endometriosis. [12] EFI staging is performed as follows:

Endometriosis Fertility Index (EFI): [12]

Estimated percent pregnant using ART by EFI score: [12]

Predicted pregnancy rates by EFI is dependent on functional ova and sperm of both parents, as well as the absence of uterine structural of functional abnormalities. [12] While initial development of this fertility grading score took into account the use of ART (assisted reproductive technology), subsequent studies have shown the scale holds true in the setting of natural forms of conception, such as timed intercourse with ovulation, regardless of ovulation induction methods. When observed over longer periods of time, estimated probabilities for pregnancy were more favorable than originally suggested; therefore, the EFI score likely offers the lower end of fertility expectations and may be used to decide between use of ART or natural methods for conception. [12]

Mechanism

The mechanisms by which endometriosis may cause infertility are not clearly understood, particularly when the extent of endometriosis is low. [13] Proposed mechanisms involve an interplay of genes, hormones, inflammatory and immune mediators. [14] Some examples of pathways are:

For other unknown reasons, endometriosis is more likely to develop in infertile women, and thus be a secondary phenomenon. [21] It is preferable to speak of "endometriosis-associated infertility" rather than any definite "infertility caused by endometriosis" because association does not imply causation. [3]

Management

Medication

In addition to pain control, medical management of endometriosis targets the suppression of hormonally active endometriotic tissue. Standard pharmacotherapy for women diagnosed with endometriosis include: [22]

Other than the analgesics, all these medications attempt to suppress follicle growth, induce amenorrhea, and suppress endometriotic lesions to improve fertility. However, as many of these therapies have contraceptive effects, they are not ideal for women seeking fertility. Instead, they postpone pregnancy and imply side effects. [23]

A second strategy is to stimulate follicle growth and ovulation. Clomiphene citrate, both alone or in combination with gonadotropins, is the most commonly prescribed. Aromatase inhibitors have also been used for follicle stimulation, but their efficacy have not been isolated. [23]

Immunomodulators such as interferon alpha 2 (IFN-α 2) and tumor necrosis factor (TNF)-α inhibitors are being studied in women with severe endometriosis. A study that included nineteen women received Etanercept before an IVF cycle showed a higher pregnancy rate compared to women who were not treated. Further studies still need to be done in order to determine the risk of infectious adverse events. [24]

Surgery

Surgical intervention of endometriosis is indicated for both diagnostic and therapeutic purposes. It can be utilized for the diagnosis and treatment of endometriotic adhesions, as a second-line treatment following the failure or intolerance of pharmacotherapy, or for treatment of infertility in some patients. [25]

The goal of surgical intervention in mild endometriosis is to destroy or remove endometriotic implants, which has been shown to successfully improve fertility. [23] [26] Possible types of surgeries include excision, electrodiathermy, or laser.

The goal of surgical intervention in moderate/severe endometriosis is not only to remove large endometriomas, but also to restore the normal anatomy of the pelvis. [27] However, there are no RCTs comparing these surgeries with medical or non-treatment options. [23] Ideally, surgery would be performed to diagnose while simultaneously treating. This can minimize exposure to multiple surgeries. [28] In cases of severe endometriosis, lesions may or may not be limited to the pelvic area, and may require advanced ultrasound in order to create a more accurate surgical plan. [29]

Compared to hormonal suppression, surgery is more effective at treating infertility in women who suffer from endometriosis, [30] [6] especially for women with mild to moderate endometriosis. [31] While surgery can enhance the chances of conceiving naturally during the 12-18 ensuing months, the removal of ovarian endometriomas may be more risky and cause potential harm on future reproductive success. [30] For this reason, there are certain criteria that a surgeon must take into account beforehand in order to have minimal effect on ovarian reserve. Bilateral versus unilateral cystectomy of endometriomas can reduce ovarian reserve, as well as recurrent endometrioma excisions. [26] Combination of surgery and postoperative hormonal suppression therapy can also reduce the risk of recurring lesions and pain symptoms. [32]

Laparoscopic excision of minimal (rASRM Stage I) endometriomas has been shown to have better health outcomes including shorter postoperative recovery times, shorter hospital stays and decreased hospital costs compared to other endometriosis-associated surgeries. [26] However, the preferred surgical procedure (laparoscopy versus drainage and ablation) has insufficient comparative evidence to guide women planning to have postoperative fertility treatments. [33]

Evidence has shown that preexisting hydrosalpinx is associated with lower fertility rates and reduced success rates for assisted reproductive technologies, the decline attributed to embryotoxic components in the hydrosalpinx fluid. [34] If the hydrosalpinx is significant, it is often recommended to remove the afflicted fallopian tube, preventing such fluid from entering the uterus where it would likely kill any embryo produced by the remaining fallopian tube or by assistive IVF. [35] Hydrosalpinx treatment increases the likelihood of pregnancy, regardless of the treatment modality used. Salpingectomy has been associated with higher rates of clinical pregnancies, implantations and IVF live births, versus other hydrosalpinx treatments. [34]

Intrauterine insemination

In women with minimal to mild endometriosis, as defined by the American Society for Reproductive Medicine, intrauterine insemination is the preferred treatment; however, the effects are modest if used as a monotherapy. [23] The use of fertility medication that stimulates ovulation (clomiphene citrate, gonadotropins) combined with intrauterine insemination (IUI) enhances fertility in this population [3] as does assisted reproduction. [30]

IUI is not given to women with moderate to severe endometriosis due to damage and scarring of the fallopian tubes associated with endometriosis. [36]

In vitro fertilization

In-vitro fertilization (IVF) procedures are effective in improving fertility in many women with endometriosis, especially in those who experience severe endometriosis. [30] [37] Discounting those with damage to the oocytes and embryos, IVF procedures have yielded similar results in increasing fertility among both women with and without endometriosis. [38] [39] IVF makes it possible to combine sperm and eggs in a laboratory and then place the resulting embryos into the uterus. The decision when to apply IVF in endometriosis-associated infertility cases takes into account the age of the individual, severity of the endometriosis, presence of other infertility factors, and the results and duration of past treatments. In ovarian hyperstimulation as part of IVF for 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. [40] On the other hand, when using a GnRH agonist protocol, long-term (three to six months) pituitary down-regulation before IVF for those with endometriosis has been estimated to increase the odds of clinical pregnancy by fourfold. [40]

No difference has been found between surgery (cystectomy or aspiration) versus expectant management, or between ablation versus cystectomy, prior to IVF in women with endometriosis. [40]

Utilizing IVF procedures prior to endometriosis-associated surgery has not been shown to enhance fertility compared to utilizing IVF procedures post-surgery. [38]

Epidemiology

Specific risk factors are still undetermined; however, genetic and environmental factors have been found to be associated with endometriosis, with genetic risk factors accounting for about 51% of endometriosis cases. Genetic risk factors associated with endometriosis include:

Environmental risk factors include:

Early life risk factors found correlated with increased risk for endometriosis include:

Higher physical activity levels and a diet with omega-3 fatty acids may reduce inflammatory markers, and decrease the risk of endometriosis. [44]

Related Research Articles

<span class="mw-page-title-main">Endometrium</span> Inner mucous membrane of the mammalian uterus

The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer thickens and then is shed during menstruation in humans and some other mammals, including apes, Old World monkeys, some species of bat, the elephant shrew and the Cairo spiny mouse. In most other mammals, the endometrium is reabsorbed in the estrous cycle. During pregnancy, the glands and blood vessels in the endometrium further increase in size and number. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus. The speculated presence of an endometrial microbiota has been argued against.

<span class="mw-page-title-main">Endometriosis</span> Disease of the female reproductive system

Endometriosis is a disease of the female reproductive system. It occurs in women and a limited number of female mammals. In endometriosis, cells like those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Lesions can be found on ovaries, fallopian tubes, tissue around the uterus and ovaries (peritoneum), intestines, bladder, and diaphragm; and may also occur in other parts of the body. Symptoms include pelvic pain, heavy and painful periods, pain with bowel movements, painful urination, pain during sexual intercourse and infertility. Nearly half of those affected have chronic pelvic pain, while 70% feel pain during menstruation. Up to half of affected individuals are infertile. About 25% of individuals have no symptoms and 85% of those seen with infertility in a tertiary center have no pain. Endometriosis can have both social and psychological effects.

<span class="mw-page-title-main">Ectopic pregnancy</span> Female reproductive system health issue

Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these symptoms. The pain may be described as sharp, dull, or crampy. Pain may also spread to the shoulder if bleeding into the abdomen has occurred. Severe bleeding may result in a fast heart rate, fainting, or shock. With very rare exceptions, the fetus is unable to survive.

<span class="mw-page-title-main">Tubal ligation</span> Surgical clipping,removal or blocking of the fallopian tubes

Tubal ligation is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus the implantation of a fertilized egg. Tubal ligation is considered a permanent method of sterilization and birth control.

<span class="mw-page-title-main">Asherman's syndrome</span> Medical condition

Asherman's syndrome (AS) is an acquired uterine condition that occurs when scar tissue (adhesions) forms inside the uterus and/or the cervix. It is characterized by variable scarring inside the uterine cavity, where in many cases the front and back walls of the uterus stick to one another. AS can be the cause of menstrual disturbances, infertility, and placental abnormalities. Although the first case of intrauterine adhesion was published in 1894 by Heinrich Fritsch, it was only after 54 years that a full description of Asherman syndrome was carried out by Joseph Asherman. A number of other terms have been used to describe the condition and related conditions including: uterine/cervical atresia, traumatic uterine atrophy, sclerotic endometrium, and endometrial sclerosis.

<span class="mw-page-title-main">Adenomyosis</span> Extension of endometrial tissue into the myometrium

Adenomyosis is a medical condition characterized by the growth of cells that proliferate on the inside of the uterus (endometrium) atypically located among the cells of the uterine wall (myometrium), as a result, thickening of the uterus occurs. As well as being misplaced in patients with this condition, endometrial tissue is completely functional. The tissue thickens, sheds and bleeds during every menstrual cycle.

<span class="mw-page-title-main">Gynecologic ultrasonography</span> Application of medical ultrasonography to the female pelvic organs

Gynecologic ultrasonography or gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs as well as the bladder, the adnexa, and the recto-uterine pouch. The procedure may lead to other medically relevant findings in the pelvis.This technique is useful to detect myomas or mullerian malformations.

<span class="mw-page-title-main">Hydrosalpinx</span> Medical condition

A hydrosalpinx is a condition that occurs when a fallopian tube is blocked and fills with serous or clear fluid near the ovary. The blocked tube may become substantially distended giving the tube a characteristic sausage-like or retort-like shape. The condition is often bilateral and the affected tubes may reach several centimeters in diameter. The blocked tubes cause infertility. A fallopian tube filled with blood is a hematosalpinx, and with pus a pyosalpinx.

Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH levels.

<span class="mw-page-title-main">Fallopian tube obstruction</span> Medical condition

Fallopian tube obstruction, also known as fallopian tube occlusion, is a major cause of female infertility. Blocked fallopian tubes are unable to let the ovum and the sperm converge, thus making fertilization impossible.

The fertiloscope is a type of laparoscope, modified to make it suitable for trans-vaginal application, which is used in the diagnosis and treatment of female infertility.

Ovarian diseases refer to diseases or disorders of the ovary.

Female genital disease is a disorder of the structure or function of the female reproductive system that has a known cause and a distinctive group of symptoms, signs, or anatomical changes. The female reproductive system consists of the ovaries, fallopian tubes, uterus, vagina, and vulva. Female genital diseases can be classified by affected location or by type of disease, such as malformation, inflammation, or infection.

<span class="mw-page-title-main">Endometrioma</span> Medical condition

Endometrioma is the presence of tissue similar to, but distinct from, the endometrium in and sometimes on the ovary. It is the most common form of endometriosis. Endometrioma is found in 17–44% patients with endometriosis.

Reproductive surgery is surgery in the field of reproductive medicine. It can be used for contraception, e.g. in vasectomy, wherein the vasa deferentia of a male are severed, but is also used plentifully in assisted reproductive technology. Reproductive surgery is generally divided into three categories: surgery for infertility, in vitro fertilization, and fertility preservation.

Ovarian pregnancy refers to an ectopic pregnancy that is located in the ovary. Typically the egg cell is not released or picked up at ovulation, but fertilized within the ovary where the pregnancy implants. Such a pregnancy usually does not proceed past the first four weeks of pregnancy. An untreated ovarian pregnancy causes potentially fatal intra-abdominal bleeding and thus may become a medical emergency.

<span class="mw-page-title-main">Endosalpingiosis</span> Medical condition

Endosalpingiosis is a condition in which fallopian tube-like epithelium is found outside the fallopian tube. It is unknown what causes this condition. It is generally accepted that the condition develops from transformation of coelomic tissue. It is often an incidental finding and is not usually associated with any pathology.

Ovarian drilling, also known as multiperforation or laparoscopic ovarian diathermy, is a surgical technique of puncturing the membranes surrounding the ovary with a laser beam or a surgical needle using minimally invasive laparoscopic procedures. It differs from ovarian wedge resection, which involves the cutting of tissue. Minimally invasive ovarian drilling procedures have replaced wedge resections. Ovarian drilling is preferred to wedge resection because cutting into the ovary can cause adhesions which may complicate postoperative outcomes. Ovarian drilling and ovarian wedge resection are treatment options to reduce the amount of androgen producing tissue in women with polycystic ovarian syndrome (PCOS). PCOS is the primary cause of anovulation, which results in female infertility. The induction of mono-ovulatory cycles can restore fertility.

Alan H. DeCherney is an Obstetrician and Gynecologist who specializes in reproductive endocrinology & infertility. He is experienced in reproductive and endocrinology, infertility, and reproductive genetics.

<span class="mw-page-title-main">Prophylactic salpingectomy</span> Surgical technique

Prophylactic salpingectomy is a preventative surgical technique performed on patients who are at higher risk of having ovarian cancer, such as individuals who may have pathogenic variants of the BRCA1 or BRCA2 gene. Originally salpingectomy was used in cases of ectopic pregnancies. As a preventative surgery however, it involves the removal of the fallopian tubes. By not removing the ovaries this procedure is advantageous to individuals who are still of child bearing age. It also reduces risks such as cardiovascular disease and osteoporosis which are associated with removal of the ovaries.

References

  1. Sarria-Santamera A, Orazumbekova B, Terzic M, Issanov A, Chaowen C, Asúnsolo-Del-Barco A (December 2020). "Systematic Review and Meta-Analysis of Incidence and Prevalence of Endometriosis". Healthcare. 9 (1): 29. doi: 10.3390/healthcare9010029 . PMC   7824417 . PMID   33396813.
  2. The Practice Committee of the American Society for Reproductive Medicine (September 2012). "Endometriosis and infertility: a committee opinion" (PDF). Fertility and Sterility . 98 (3): 591–8. doi:10.1016/j.fertnstert.2012.05.031. PMID   22704630.
  3. 1 2 3 Buyalos RP, Agarwal SK (October 2000). "Endometriosis-associated infertility". Current Opinion in Obstetrics & Gynecology . 12 (5): 377–81. doi:10.1097/00001703-200010000-00006. PMID   11111879. S2CID   23855392.
  4. Lee, Dayong; Kim, Seul Ki; Lee, Jung Ryeol; Jee, Byung Chul (2020). "Management of endometriosis-related infertility: Considerations and treatment options". Clinical and Experimental Reproductive Medicine. 47 (1): 1–11. doi:10.5653/cerm.2019.02971. PMC   7127898 . PMID   32088944.
  5. De Ziegler, Dominique (2010). "Endometriosis and infertility: pathophysiology and management". Lancet. 376 (9742): 730–738. doi:10.1016/S0140-6736(10)60490-4. PMID   20801404. S2CID   24508152.
  6. 1 2 3 Wellbery C (October 1999). "Diagnosis and treatment of endometriosis". American Family Physician. 60 (6): 1753–62, 1767–8. PMID   10537390 . Retrieved 19 August 2013.
  7. Kiesel L, Sourouni M (June 2019). "Diagnosis of endometriosis in the 21st century". Climacteric. 22 (3): 296–302. doi:10.1080/13697137.2019.1578743. PMID   30905186. S2CID   85496280.
  8. Haas D, Shebl O, Shamiyeh A, Oppelt P (January 2013). "The rASRM score and the Enzian classification for endometriosis: their strengths and weaknesses". Acta Obstetricia et Gynecologica Scandinavica. 92 (1): 3–7. doi: 10.1111/aogs.12026 . PMID   23061819. S2CID   24608638.
  9. Barbosa, M. A. P.; Teixeira, D. M.; Navarro, P. A. A. S.; Ferriani, R. A.; Nastri, C. O.; Martins, W. P. (September 2014). "Impact of endometriosis and its staging on assisted reproduction outcome: systematic review and meta-analysis: Impact of endometriosis on assisted reproduction outcome". Ultrasound in Obstetrics & Gynecology. 44 (3): 261–278. doi: 10.1002/uog.13366 . PMID   24639087.
  10. Lee SY, Koo YJ, Lee DH (January 2021). "Classification of endometriosis". Yeungnam University Journal of Medicine. 38 (1): 10–18. doi:10.12701/yujm.2020.00444. PMC   7787892 . PMID   32764213.
  11. Tomassetti, C (June 2020). "Why and when you should use the endometriosis fertility index (EFI)". BJOG: An International Journal of Obstetrics & Gynaecology. 127 (7): 810. doi:10.1111/1471-0528.16180. ISSN   1470-0328. PMID   32105389. S2CID   211536693.
  12. 1 2 3 4 5 Adamson, G. David (June 2013). "Endometriosis Fertility Index: is it better than the present staging systems?". Current Opinion in Obstetrics & Gynecology. 25 (3): 186–192. doi:10.1097/GCO.0b013e32836091da. ISSN   1040-872X. PMID   23571831. S2CID   9259934.
  13. Speroff L, Glass RH, Kase NG (1999). Clinical Gynecologic Endocrinology and Infertility (6th ed.). Lippincott Willimas Wilkins. p. 1057. ISBN   978-0-683-30379-7.
  14. Parasar, Parveen; Ozcan, Pinar; Terry, Kathryn L. (March 2017). "Endometriosis: Epidemiology, Diagnosis and Clinical Management". Current Obstetrics and Gynecology Reports. 6 (1): 34–41. doi:10.1007/s13669-017-0187-1. ISSN   2161-3303. PMC   5737931 . PMID   29276652.
  15. Macer ML, Taylor HS (December 2012). "Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility". Obstetrics and Gynecology Clinics of North America. 39 (4): 535–49. doi:10.1016/j.ogc.2012.10.002. PMC   3538128 . PMID   23182559.
  16. 1 2 Filip, Lidia; Duică, Florentina; Prădatu, Alina; Crețoiu, Dragoș; Suciu, Nicolae; Crețoiu, Sanda Maria; Predescu, Dragoș-Valentin; Varlas, Valentin Nicolae; Voinea, Silviu-Cristian (2020-09-09). "Endometriosis Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches". Medicina. 56 (9): 460. doi: 10.3390/medicina56090460 . ISSN   1010-660X. PMC   7559069 . PMID   32916976.
  17. 1 2 Broi, Michele Gomes Da; Ferriani, Rui Alberto; Navarro, Paula Andrea (2019). "Ethiopathogenic mechanisms of endometriosis-related infertility". JBRA Assisted Reproduction. 23 (3): 273–280. doi:10.5935/1518-0557.20190029. ISSN   1518-0557. PMC   6724396 . PMID   31091056.
  18. 1 2 Sanchez AM, Viganò P, Somigliana E, Panina-Bordignon P, Vercellini P, Candiani M (2013). "The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary". Human Reproduction Update. 20 (2): 217–30. doi: 10.1093/humupd/dmt053 . PMID   24129684.
  19. Broi MG, Ferriani RA, Navarro PA (August 2019). "Ethiopathogenic mechanisms of endometriosis-related infertility". JBRA Assisted Reproduction. 23 (3): 273–280. doi:10.5935/1518-0557.20190029. PMC   6724396 . PMID   31091056.
  20. Hill, Christopher J.; Fakhreldin, Marwa; Maclean, Alison; Dobson, Lucy; Nancarrow, Lewis; Bradfield, Alice; Choi, Fiona; Daley, Diandra; Tempest, Nicola; Hapangama, Dharani K. (June 2020). "Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications". Journal of Clinical Medicine. 9 (6): 1905. doi: 10.3390/jcm9061905 . PMC   7355596 . PMID   32570847.
  21. Moen MH (November 1991). "Is a long period without childbirth a risk factor for developing endometriosis?". Human Reproduction. 6 (10): 1404–7. doi:10.1093/oxfordjournals.humrep.a137278. PMID   1770135.
  22. Mounsey, Anne; Wilgus, Alex; Slawson, David C. (2006-08-15). "Diagnosis and Management of Endometriosis". American Family Physician. 74 (4): 594–600. ISSN   0002-838X. PMID   16939179.
  23. 1 2 3 4 5 Tanbo, Tom; Fedorcsak, Peter (June 2017). "Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options". Acta Obstetricia et Gynecologica Scandinavica. 96 (6): 659–667. doi:10.1111/aogs.13082. hdl: 10852/61244 . ISSN   1600-0412. PMID   27998009. S2CID   207028324.
  24. Kolanska, Kamila; Alijotas-Reig, Jaume; Cohen, Jonathan; Cheloufi, Meryem; Selleret, Lise; d'Argent, Emmanuelle; Kayem, Gilles; Valverde, Enrique E.; Fain, Olivier; Bornes, Marie; Darai, Emile (March 2021). "Endometriosis with infertility comprehensive review on the role of immune deregulation and immunomodulation therapy". American Journal of Reproductive Immunology. 85 (3): e13384. doi:10.1111/aji.13384. ISSN   1600-0897. PMID   33278837. S2CID   227315410.
  25. Falcone, Tommaso; Flyckt, Rebecca (March 2018). "Clinical Management of Endometriosis". Obstetrics & Gynecology. 131 (3): 557–571. doi:10.1097/AOG.0000000000002469. ISSN   0029-7844. PMID   29420391. S2CID   3450205.
  26. 1 2 3 Jin, Xingzhong; Ruiz Beguerie, Julieta (September 2014). "Laparoscopic surgery for subfertility related to endometriosis: a meta-analysis". Taiwanese Journal of Obstetrics & Gynecology. 53 (3): 303–308. doi: 10.1016/j.tjog.2013.02.004 . ISSN   1875-6263. PMID   25286781.
  27. Bafort, Celine; Beebeejaun, Yusuf; Tomassetti, Carla; Bosteels, Jan; Duffy, James MN (2020-10-23). Cochrane Gynaecology and Fertility Group (ed.). "Laparoscopic surgery for endometriosis". Cochrane Database of Systematic Reviews. 2020 (10): CD011031. doi:10.1002/14651858.CD011031.pub3. PMC   8428328 . PMID   33095458. S2CID   225051207.
  28. Singh SS, Suen MW (March 2017). "Surgery for endometriosis: beyond medical therapies". Fertility and Sterility. 107 (3): 549–554. doi: 10.1016/j.fertnstert.2017.01.001 . PMID   28189295.
  29. Singh, Sukhbir S.; Suen, Michael W.H. (March 2017). "Surgery for endometriosis: beyond medical therapies". Fertility and Sterility. 107 (3): 549–554. doi: 10.1016/j.fertnstert.2017.01.001 . ISSN   0015-0282. PMID   28189295.
  30. 1 2 3 4 de Ziegler D, Pirtea P, Carbonnel M, Poulain M, Cicinelli E, Bulletti C, et al. (February 2019). "Assisted reproduction in endometriosis". Best Practice & Research. Clinical Endocrinology & Metabolism. 33 (1): 47–59. doi: 10.1016/j.beem.2018.10.001 . PMID   30503728.
  31. Bafort, Celine; Beebeejaun, Yusuf; Tomassetti, Carla; Bosteels, Jan; Duffy, James Mn (2020-10-23). "Laparoscopic surgery for endometriosis". The Cochrane Database of Systematic Reviews. 2020 (10): CD011031. doi:10.1002/14651858.CD011031.pub3. ISSN   1469-493X. PMC   8428328 . PMID   33095458.
  32. Chen I, Veth VB, Choudhry AJ, Murji A, Zakhari A, Black AY, et al. (November 2020). "Pre- and postsurgical medical therapy for endometriosis surgery". The Cochrane Database of Systematic Reviews. 11 (12): CD003678. doi:10.1002/14651858.CD003678.pub3. PMC   8127059 . PMID   33206374.
  33. Hart, Roger J; Hickey, Martha; Maouris, Panos; Buckett, William (2008). "Excisional surgery versus ablative surgery for ovarian endometriomata". Cochrane Database of Systematic Reviews (2): CD004992. doi:10.1002/14651858.CD004992.pub3. PMID   18425908.
  34. 1 2 El-Kharoubi, Amin-Florin (May 2023). Muacevic, Alexander; Adler, John R (eds.). "Tubal Pathologies and Fertility Outcomes: A Review". Cureus. 15 (5): e38881. doi: 10.7759/cureus.38881 . PMC   10184952 . PMID   37197301.
  35. Zaraq Khan; Jeffrey Braverman (February 2024). "Infertility". centerforendo.com. Center for Endometriosis Care. Retrieved 17 February 2024.
  36. Tanbo T, Fedorcsak P (2017). "Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options". Acta Obstetricia et Gynecologica Scandinavica. 96 (6): 659–667. doi:10.1111/aogs.13082. hdl: 10852/61244 . PMID   27998009. S2CID   207028324.
  37. Filip, Lidia; Duică, Florentina; Prădatu, Alina; Crețoiu, Dragoș; Suciu, Nicolae; Crețoiu, Sanda Maria; Predescu, Dragoș-Valentin; Varlas, Valentin Nicolae; Voinea, Silviu-Cristian (2020). "Endometriosis Associated Infertility: A Critical Review and Analysis on Etiopathogenesis and Therapeutic Approaches". Medicina. 56 (9): 460. doi: 10.3390/medicina56090460 . PMC   7559069 . PMID   32916976.
  38. 1 2 Polat, Mehtap; Yaralı, Irem; Boynukalın, Kübra; Yaralı, Hakan (2015). "In Vitro Fertilization for Endometriosis-Associated Infertility". Women's Health. 11 (5): 633–641. doi:10.2217/whe.15.50. hdl: 11655/16713 . PMID   26395161. S2CID   29409251.
  39. Hamdan, M.; Dunselman, G.; Li, T.C.; Cheong, Y. (2015). "The impact of endometrioma on IVF/ICSI outcomes: a systematic review and meta-analysis". Human Reproduction Update. 21 (6): 809–825. doi: 10.1093/humupd/dmv035 . PMID   26168799.
  40. 1 2 3 Farquhar C, Marjoribanks J (2018). "Assisted reproductive technology: an overview of Cochrane Reviews". The Cochrane Database of Systematic Reviews. 2018 (8): CD010537. doi:10.1002/14651858.CD010537.pub5. PMC   6953328 . PMID   30117155.
  41. Ozkan, Sebiha; Murk, William; Arici, Aydin (April 2008). "Endometriosis and infertility: epidemiology and evidence-based treatments". Annals of the New York Academy of Sciences. 1127 (1): 92–100. Bibcode:2008NYASA1127...92O. doi:10.1196/annals.1434.007. ISSN   0077-8923. PMID   18443335. S2CID   6042379.
  42. Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al. (2000). "Endometriosis". Endometriosis in Endotext. MDText.com. PMID   25905227.
  43. Olšarová, Karolína; Mishra, Gita D (2020). "Early life factors for endometriosis: a systematic review". Human Reproduction Update. 26 (3): 412–422. doi: 10.1093/humupd/dmaa002 . PMID   32141508.
  44. Parasar, Parveen; Ozcan, Pinar; Terry, Kathryn L. (March 2017). "Endometriosis: Epidemiology, Diagnosis and Clinical Management". Current Obstetrics and Gynecology Reports. 6 (1): 34–41. doi:10.1007/s13669-017-0187-1. ISSN   2161-3303. PMC   5737931 . PMID   29276652.