Materiały źródłowe

• #1 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Ectopic pregnancy occurs at a rate of 19.7 cases per 1,000 pregnancies in North America and is a leading cause of maternal mortality in the first trimester. […] Ectopic pregnancy is any pregnancy in which the fertilized ovum implants outside the intrauterine cavity. More than 95 percent of ectopic pregnancies occur in the fallopian tubes. […] The mechanism can be anatomic (e.g., scarring that blocks transport of the egg) or functional (e.g., impaired tubal mobility). […] In the general population, pelvic inflammatory disease is the most common risk factor for ectopic pregnancy. […] Previous ectopic pregnancy becomes a more significant risk factor with each successive occurrence. […] Endometriosis, tubal surgery and pelvic surgery result in pelvic and tubal adhesions and abnormal tubal function.

• #2 Ectopic pregnancy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-024-00579-x

  Ectopic pregnancy, defined as the implantation of a developing pregnancy outside of the endometrial cavity of the uterus, is the leading cause of early-pregnancy maternal mortality. […] The majority of ectopic pregnancies implant in a fallopian tube. […] Acute complications may include rupture of the fallopian tube or rupture of ectopic pregnancy, haemorrhage and hypovolaemic shock, or occur secondary to treatments such as emergency surgery or blood transfusions, and ultimately increase the risk of maternal death. […] Over the last four decades, the foundations of non-invasive diagnosis have been transvaginal sonography and serum -human chorionic gonadotropin, with diagnostic laparoscopy as a confirmatory test if surgical treatment is planned. […] Once diagnosed, ectopic pregnancy can be managed expectantly, treated medically with methotrexate or managed surgically.

• #3 Ectopic pregnancy – Wikipedia

  https://en.wikipedia.org/wiki/Ectopic_pregnancy

  Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. […] Risk factors for ectopic pregnancy include pelvic inflammatory disease, often due to chlamydia infection; tobacco smoking; endometriosis; prior tubal surgery; a history of infertility; and the use of assisted reproductive technology. […] The exact mechanism through which chlamydia increases the risk of ectopic pregnancy is uncertain, though some research suggests that the infection can affect the structure of fallopian tubes. […] Tubal pregnancy is when the egg is implanted in the fallopian tubes. Hair-like cilia located on the internal surface of the fallopian tubes carry the fertilized egg to the uterus. […] As cilia degenerate, the amount of time it takes for the fertilized egg to reach the uterus will increase.

• #4 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Physiologically, egg cell is fertilized in the ampulla portion of the fallopian tube, subsequently blastocyst travels down the salpinx to the implantation area. Any impinging with the normal function of the fallopian tube during this step can lead to the development of an ectopic pregnancy. […] We differentiate between EP that arise in the uterine adnexa and abdominal pregnancies. Embryo transportation to the endometrium usually protects human fallopian tube from ectopic implantation. Hormones have a great influence on tubal muscles causing erroneous transit of the embryo. This transportation involves a substantial change of tubal smooth muscle cells state and mainly a modification of oviductal ciliary beat and muscle contractions. Predominantly in the ampullary-isthmic and utero-tubal junction of the salpinx, estrogens produce a sphincter-like response while progestins relax these zones. Further studies must investigate even other hormones role. In fact, prostaglandins, catecholamines, oxytocin could have a main role in embryo transport. Ectopic implantation is more frequent when a chromosomal defect which cause abnormal development is present. Inflammation has a key role in this process, that’s why pre-existent tubal disease is a major factor for EP development.

• #5 Ectopic Pregnancy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539860/

  Ectopic pregnancy occurs when a fertilized egg implants outside the uterus, most commonly in the fallopian tube. […] Most ectopic pregnancies (approximately 97%) occur within the fallopian tube, commonly linked to underlying fallopian tube abnormalities. […] For a tubal ectopic pregnancy, damage to the fallopian tubes, usually secondary to inflammation, induces tubal dysfunction, which can result in the retention of an oocyte or embryo within the tube. […] Several local factors can induce inflammation, including toxic, infectious, immunologic, and hormonal etiologies. […] An upregulation of proinflammatory cytokines occurs following tubal damage; this subsequently promotes embryo implantation, invasion, and angiogenesis within the fallopian tube. […] Chlamydia trachomatis infection results in the production of interleukin 1 by tubal epithelial cells; this is a vital indicator for embryo implantation within the endometrium. […] Cilia beat frequency is also negatively affected by smoking and infection.

• #6 Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2817566/

  Ectopic pregnancy, a worldwide health problem, is potentially life-threatening and occurs in approximately 1.52% of all pregnancies in the western world; however, the precise mechanisms underlying the initiation and development of tubal ectopic pregnancy are unknown. […] Tubal abnormalities and dysfunction, such as altered contractility or abnormal ciliary activity, have been speculated to lead to tubal ectopic pregnancy. […] Our understanding of the mechanisms which contribute to tubal ectopic pregnancy in humans may be enhanced through further study of these KO mouse models. […] Abnormalities in the structure and function of the Fallopian tube can interfere with the gamete/early embryo transport process and lead to tEP; however, the molecular mechanisms underlying this interference are not well characterized.

• #7 Ectopic Pregnancy: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/2041923-overview

  An ectopic pregnancy requires the occurrence of 2 events: fertilization of the ovum and abnormal implantation. Many risk factors affect both events; for example, a history of major tubal infection decreases fertility and increases abnormal implantation. […] Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers or delays the migration of the fertilized ovum to the endometrial cavity can predispose a woman to ectopic gestation. […] The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection; however, most patients presenting with an ectopic pregnancy have no identifiable risk factor. […] Cigarette smoking has been shown to be a risk factor for ectopic pregnancy development. Studies have demonstrated an elevated risk ranging from 1.6 to 3.5 times that of nonsmokers.

• #8 Ectopic Pregnancy: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/2041923-overview

  An ectopic pregnancy requires the occurrence of 2 events: fertilization of the ovum and abnormal implantation. Many risk factors affect both events; for example, a history of major tubal infection decreases fertility and increases abnormal implantation. […] Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers or delays the migration of the fertilized ovum to the endometrial cavity can predispose a woman to ectopic gestation. […] The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection; however, most patients presenting with an ectopic pregnancy have no identifiable risk factor. […] Cigarette smoking has been shown to be a risk factor for ectopic pregnancy development. Studies have demonstrated an elevated risk ranging from 1.6 to 3.5 times that of nonsmokers.

• #9 Ectopic Pregnancy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539860/

  Ectopic pregnancy occurs when a fertilized egg implants outside the uterus, most commonly in the fallopian tube. […] Most ectopic pregnancies (approximately 97%) occur within the fallopian tube, commonly linked to underlying fallopian tube abnormalities. […] For a tubal ectopic pregnancy, damage to the fallopian tubes, usually secondary to inflammation, induces tubal dysfunction, which can result in the retention of an oocyte or embryo within the tube. […] Several local factors can induce inflammation, including toxic, infectious, immunologic, and hormonal etiologies. […] An upregulation of proinflammatory cytokines occurs following tubal damage; this subsequently promotes embryo implantation, invasion, and angiogenesis within the fallopian tube. […] Chlamydia trachomatis infection results in the production of interleukin 1 by tubal epithelial cells; this is a vital indicator for embryo implantation within the endometrium. […] Cilia beat frequency is also negatively affected by smoking and infection.

• #10 Ectopic Pregnancy: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/2041923-overview

  Ectopic pregnancy is the result of a flaw in human reproductive physiology that allows the conceptus to implant and mature outside the endometrial cavity, which ultimately ends in the death of the fetus. Without timely diagnosis and treatment, ectopic pregnancy can become a life-threatening situation. […] In ectopic pregnancy, the gestation grows and draws its blood supply from the site of abnormal implantation. As the gestation enlarges, it creates the potential for organ rupture, because only the uterine cavity is designed to expand and accommodate fetal development. Ectopic pregnancy can lead to massive hemorrhage, infertility, or death. […] The faulty implantation that occurs in ectopic pregnancy occurs because of a defect in the anatomy or normal function of either the fallopian tube, the ovary, or the uterus. Reflecting this, most ectopic pregnancies are located in the fallopian tube; the most common site is the ampullary portion of the tube, where over 80% of ectopic pregnancies occur.

• #11 Understanding the mechanisms of human tubal ectopic pregnancies: new evidence from knockout mouse models

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2817566/

  The deletion of CB1 or Dicer1 in mice results in the retention of an oocyte/embryo within the Fallopian tube and may provide clues for tubal abnormality-induced tEP in humans. […] It is possible that the molecular mechanisms involved in tubal transport may be different in mice and humans, thus, not all of the information gained from mouse models may be applicable to human disease. […] Mechanisms regulating ciliary beating and smooth muscle activity are complex, and they can be either coordinately or independently responsible for different stages of tubal transport. […] Therefore, extensive studies of temporal changes in the gene expression and in cell-specific signalling pathways in the Fallopian tube will be essential in order to understand the contribution of each of these factors to tubal function.

• #12 Ectopic pregnancy – Wikipedia

  https://en.wikipedia.org/wiki/Ectopic_pregnancy

  Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. […] Risk factors for ectopic pregnancy include pelvic inflammatory disease, often due to chlamydia infection; tobacco smoking; endometriosis; prior tubal surgery; a history of infertility; and the use of assisted reproductive technology. […] The exact mechanism through which chlamydia increases the risk of ectopic pregnancy is uncertain, though some research suggests that the infection can affect the structure of fallopian tubes. […] Tubal pregnancy is when the egg is implanted in the fallopian tubes. Hair-like cilia located on the internal surface of the fallopian tubes carry the fertilized egg to the uterus. […] As cilia degenerate, the amount of time it takes for the fertilized egg to reach the uterus will increase.

• #13 Diagnosis and Management of Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2014/0701/p34.html

  Ectopic pregnancy affects 1% to 2% of all pregnancies and is responsible for 9% of pregnancy-related deaths in the United States. […] Ectopic pregnancy, a high-risk condition in which a fertilized ovum implants outside the uterine cavity, affects 1% to 2% of all pregnancies and poses a significant threat to women of reproductive age. It is the leading cause of maternal death during the first trimester of pregnancy and is responsible for 9% of pregnancy-related deaths in the United States. […] Transport of the fertilized ovum through the fallopian tube is controlled by a combination of smooth muscle contractions and ciliary beating. Conditions that damage the integrity of the tube and impair these functions are risk factors for ectopic pregnancy. […] The most common symptoms of an unruptured ectopic pregnancy are first-trimester bleeding and abdominal pain.

• #14 Ectopic pregnancy – Wikipedia

  https://en.wikipedia.org/wiki/Ectopic_pregnancy

  Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. […] Risk factors for ectopic pregnancy include pelvic inflammatory disease, often due to chlamydia infection; tobacco smoking; endometriosis; prior tubal surgery; a history of infertility; and the use of assisted reproductive technology. […] The exact mechanism through which chlamydia increases the risk of ectopic pregnancy is uncertain, though some research suggests that the infection can affect the structure of fallopian tubes. […] Tubal pregnancy is when the egg is implanted in the fallopian tubes. Hair-like cilia located on the internal surface of the fallopian tubes carry the fertilized egg to the uterus. […] As cilia degenerate, the amount of time it takes for the fertilized egg to reach the uterus will increase.

• #15 Ectopic Pregnancy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539860/

  Ectopic pregnancy occurs when a fertilized egg implants outside the uterus, most commonly in the fallopian tube. […] Most ectopic pregnancies (approximately 97%) occur within the fallopian tube, commonly linked to underlying fallopian tube abnormalities. […] For a tubal ectopic pregnancy, damage to the fallopian tubes, usually secondary to inflammation, induces tubal dysfunction, which can result in the retention of an oocyte or embryo within the tube. […] Several local factors can induce inflammation, including toxic, infectious, immunologic, and hormonal etiologies. […] An upregulation of proinflammatory cytokines occurs following tubal damage; this subsequently promotes embryo implantation, invasion, and angiogenesis within the fallopian tube. […] Chlamydia trachomatis infection results in the production of interleukin 1 by tubal epithelial cells; this is a vital indicator for embryo implantation within the endometrium. […] Cilia beat frequency is also negatively affected by smoking and infection.

• #16 Ectopic Pregnancy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539860/

  Ectopic pregnancy occurs when a fertilized egg implants outside the uterus, most commonly in the fallopian tube. […] Most ectopic pregnancies (approximately 97%) occur within the fallopian tube, commonly linked to underlying fallopian tube abnormalities. […] For a tubal ectopic pregnancy, damage to the fallopian tubes, usually secondary to inflammation, induces tubal dysfunction, which can result in the retention of an oocyte or embryo within the tube. […] Several local factors can induce inflammation, including toxic, infectious, immunologic, and hormonal etiologies. […] An upregulation of proinflammatory cytokines occurs following tubal damage; this subsequently promotes embryo implantation, invasion, and angiogenesis within the fallopian tube. […] Chlamydia trachomatis infection results in the production of interleukin 1 by tubal epithelial cells; this is a vital indicator for embryo implantation within the endometrium. […] Cilia beat frequency is also negatively affected by smoking and infection.

• #17 Ectopic Pregnancy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539860/

  Ectopic pregnancy occurs when a fertilized egg implants outside the uterus, most commonly in the fallopian tube. […] Most ectopic pregnancies (approximately 97%) occur within the fallopian tube, commonly linked to underlying fallopian tube abnormalities. […] For a tubal ectopic pregnancy, damage to the fallopian tubes, usually secondary to inflammation, induces tubal dysfunction, which can result in the retention of an oocyte or embryo within the tube. […] Several local factors can induce inflammation, including toxic, infectious, immunologic, and hormonal etiologies. […] An upregulation of proinflammatory cytokines occurs following tubal damage; this subsequently promotes embryo implantation, invasion, and angiogenesis within the fallopian tube. […] Chlamydia trachomatis infection results in the production of interleukin 1 by tubal epithelial cells; this is a vital indicator for embryo implantation within the endometrium. […] Cilia beat frequency is also negatively affected by smoking and infection.

• #18 Methotrexate in the Management of Ectopic Pregnancy: A Comparative Review of Single-Dose Versus Multi-Dose Protocols | Auctores

  https://www.auctoresonline.org/article/methotrexate-in-the-management-of-ectopic-pregnancy-a-comparative-review-of-single-dose-versus-multi-dose-protocols

  Ectopic pregnancy ruptures account for five percent to ten percent of all pregnancy-related deaths and are the primary reason for maternal mortality throughout the first trimester of pregnancy, with a rate of nine percent to fourteen percent. An ectopic pregnancy is a gestational sac that implants somewhere other than the uterus. The implantation of an embryo outside the uterus, usually in the fallopian tube, is the essence of ectopic pregnancy. To aid in the passage of an egg and embryo by the fallopian tubes, smooth muscle contraction and ciliary beat have been used. Damage to the fallopian tubes, typically caused by inflammation, can lead to tubal dysfunction and the retention of an embryo or ovum. […] After tubal injury, pro-inflammatory cytokines have been upregulated, which facilitates angiogenesis, invasion, and embryo implantation in the fallopian tube. When tubal epithelial cells are infected with Chlamydia trachomatis, they produce interleukin-1, which is an essential marker for the implantation of embryos in the endometrium. Additionally, interleukin-1 plays a part in the recruitment of neutrophils downstream, which exacerbates the damage to the fallopian tubes.

• #19 Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy

  https://www.mdpi.com/1422-0067/23/7/3490

  Inflammation induction can also be caused by B-cell activation factor (BAFF), which regulates acquired and innate immune responses. Increased BAFF expression with simultaneous increases in IL-6 and TNF-alpha levels was observed in patients with TEP. […] This review provides an initial summary of the common features of the pathophysiology of endometriosis and EP. It is still unclear how strongly the two conditions are connected to each other and how. We presented studies that showed similarities for both pathologies. The fact is that both endometriosis and EP are associated with the inflammatory environment, the Wnt/β-catenin pathway, and hormonal regulation that to date seems to be most important and well-documented common molecular mechanisms of both diseases.

• #20 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Physiologically, egg cell is fertilized in the ampulla portion of the fallopian tube, subsequently blastocyst travels down the salpinx to the implantation area. Any impinging with the normal function of the fallopian tube during this step can lead to the development of an ectopic pregnancy. […] We differentiate between EP that arise in the uterine adnexa and abdominal pregnancies. Embryo transportation to the endometrium usually protects human fallopian tube from ectopic implantation. Hormones have a great influence on tubal muscles causing erroneous transit of the embryo. This transportation involves a substantial change of tubal smooth muscle cells state and mainly a modification of oviductal ciliary beat and muscle contractions. Predominantly in the ampullary-isthmic and utero-tubal junction of the salpinx, estrogens produce a sphincter-like response while progestins relax these zones. Further studies must investigate even other hormones role. In fact, prostaglandins, catecholamines, oxytocin could have a main role in embryo transport. Ectopic implantation is more frequent when a chromosomal defect which cause abnormal development is present. Inflammation has a key role in this process, that’s why pre-existent tubal disease is a major factor for EP development.

• #21 Prioritization of Susceptibility Genes for Ectopic Pregnancy by Gene Network Analysis

  https://www.mdpi.com/1422-0067/17/2/191

  Ectopic pregnancy is a very dangerous complication of pregnancy, affecting 1%–2% of all reported pregnancies. […] The pathogenesis of ectopic pregnancy in humans is not fully understood. It has been suggested that both impaired embryo transport in the Fallopian tube and abnormal tubal environment may contribute to the pathogenesis of ectopic pregnancy. […] The inflammatory environment may also provide necessary pro-implantation factors with roles in the establishment of Fallopian tube receptivity for the retained embryo. […] There has been little success in identifying functionally important genes in the pathogenesis of ectopic pregnancy. […] Using text mining data and gene network information as input, we developed a random walk–based algorithm named TM-rank to prioritize ectopic pregnancy–related genes.

• #22 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Physiologically, egg cell is fertilized in the ampulla portion of the fallopian tube, subsequently blastocyst travels down the salpinx to the implantation area. Any impinging with the normal function of the fallopian tube during this step can lead to the development of an ectopic pregnancy. […] We differentiate between EP that arise in the uterine adnexa and abdominal pregnancies. Embryo transportation to the endometrium usually protects human fallopian tube from ectopic implantation. Hormones have a great influence on tubal muscles causing erroneous transit of the embryo. This transportation involves a substantial change of tubal smooth muscle cells state and mainly a modification of oviductal ciliary beat and muscle contractions. Predominantly in the ampullary-isthmic and utero-tubal junction of the salpinx, estrogens produce a sphincter-like response while progestins relax these zones. Further studies must investigate even other hormones role. In fact, prostaglandins, catecholamines, oxytocin could have a main role in embryo transport. Ectopic implantation is more frequent when a chromosomal defect which cause abnormal development is present. Inflammation has a key role in this process, that’s why pre-existent tubal disease is a major factor for EP development.

• #23 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Physiologically, egg cell is fertilized in the ampulla portion of the fallopian tube, subsequently blastocyst travels down the salpinx to the implantation area. Any impinging with the normal function of the fallopian tube during this step can lead to the development of an ectopic pregnancy. […] We differentiate between EP that arise in the uterine adnexa and abdominal pregnancies. Embryo transportation to the endometrium usually protects human fallopian tube from ectopic implantation. Hormones have a great influence on tubal muscles causing erroneous transit of the embryo. This transportation involves a substantial change of tubal smooth muscle cells state and mainly a modification of oviductal ciliary beat and muscle contractions. Predominantly in the ampullary-isthmic and utero-tubal junction of the salpinx, estrogens produce a sphincter-like response while progestins relax these zones. Further studies must investigate even other hormones role. In fact, prostaglandins, catecholamines, oxytocin could have a main role in embryo transport. Ectopic implantation is more frequent when a chromosomal defect which cause abnormal development is present. Inflammation has a key role in this process, that’s why pre-existent tubal disease is a major factor for EP development.

• #24 Ectopic Pregnancy: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/2041923-overview

  Ovulation induction with clomiphene citrate or injectable gonadotropin therapy has been linked to a 4-fold increase in the risk of ectopic pregnancy in a case-control study. […] The highest rate of ectopic pregnancy occurs in women aged 35-44 years. A 3- to 4-fold increase in the risk of developing an ectopic pregnancy exists compared with women aged 15-24 years. One proposed explanation suggests that aging may result in a progressive loss of myoelectrical activity in the fallopian tube; myoelectrical activity is responsible for tubal motility.

• #25 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Physiologically, egg cell is fertilized in the ampulla portion of the fallopian tube, subsequently blastocyst travels down the salpinx to the implantation area. Any impinging with the normal function of the fallopian tube during this step can lead to the development of an ectopic pregnancy. […] We differentiate between EP that arise in the uterine adnexa and abdominal pregnancies. Embryo transportation to the endometrium usually protects human fallopian tube from ectopic implantation. Hormones have a great influence on tubal muscles causing erroneous transit of the embryo. This transportation involves a substantial change of tubal smooth muscle cells state and mainly a modification of oviductal ciliary beat and muscle contractions. Predominantly in the ampullary-isthmic and utero-tubal junction of the salpinx, estrogens produce a sphincter-like response while progestins relax these zones. Further studies must investigate even other hormones role. In fact, prostaglandins, catecholamines, oxytocin could have a main role in embryo transport. Ectopic implantation is more frequent when a chromosomal defect which cause abnormal development is present. Inflammation has a key role in this process, that’s why pre-existent tubal disease is a major factor for EP development.

• #26 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Poole et al. found that the most of EP cases are caused by tubal insult after surgery, infection and smoking. A third of the possible causes remain unknown. Risk of EP increases with pelvic infections number, but this factor contributes less to ectopic implant risk than smoking. […] Between infective agent, chlamydia seems to have a key role like demonstrated in many studies. Even assisted reproductive technologies (ARTs) increase the risk. In fact, age, tubal infections, intra-fallopian transfer, fresh embryo-transfers (ETs), day of ET, number of ETs and intrauterine hormonal environment have an impact on EP rate. […] This rate lowers when frozen embryos are transferred compared with fresh embryo due to the influence of no-medication versus medicated cycle on endometrial receptivity. An interesting explanation for this could be the increased uterine muscles fibers activity in stimulated cycles. This raises in uterine contractility favor embryo migration into the fallopian tubes and decrease uterine implantation rate.

• #27 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Poole et al. found that the most of EP cases are caused by tubal insult after surgery, infection and smoking. A third of the possible causes remain unknown. Risk of EP increases with pelvic infections number, but this factor contributes less to ectopic implant risk than smoking. […] Between infective agent, chlamydia seems to have a key role like demonstrated in many studies. Even assisted reproductive technologies (ARTs) increase the risk. In fact, age, tubal infections, intra-fallopian transfer, fresh embryo-transfers (ETs), day of ET, number of ETs and intrauterine hormonal environment have an impact on EP rate. […] This rate lowers when frozen embryos are transferred compared with fresh embryo due to the influence of no-medication versus medicated cycle on endometrial receptivity. An interesting explanation for this could be the increased uterine muscles fibers activity in stimulated cycles. This raises in uterine contractility favor embryo migration into the fallopian tubes and decrease uterine implantation rate.

• #28 Review of Ectopic Pregnancy treatment for IVF patients

  https://www.immunologyresearchjournal.com/articles/review-of-ectopic-pregnancy-treatment-for-ivf-patients.html

  Ectopic pregnancy (EP) is an abnormal pregnancy described by the implantation of a fertilized ovum in a location outside the uterine cavity. It represents 1-2% of pregnancies in the general population and 2-5% in patients undergoing IVF. […] Several theories suggest that abnormal fallopian tube pathology interferes with embryo transport, such as ciliary dysfunction, myosalpinx spasm secondary to prostaglandin release or incomplete relaxation, leading to EP. Another common explanation is the chronic inflammation or infection after pelvic inflammatory disease affecting tubal patency. […] Abnormal tubal pathology is thought to be the most common cause of EP both in naturally conceived pregnancies and in pregnancies resulted from IVF- embryo transfer. Several studies have shown that additional mechanisms are involved in EPs occurring in IVF patients, as no transport of the fertilized ovum occurs along the fallopian tube. Such mechanisms include the overexpression of the adhesion molecule E-cadherin in the tubal implantation sites of EPs resulting from IVF treatment compared to natural conceptions.

• #29 Review of Ectopic Pregnancy treatment for IVF patients

  https://www.immunologyresearchjournal.com/articles/review-of-ectopic-pregnancy-treatment-for-ivf-patients.html

  In addition, controlled ovarian hyperstimulation (COH) leads to hormonal changes that affect the expression of signaling molecules (cytokines, chemokines etc.) disrupting the interaction among embryo, fallopian tube and endometrium. It is proposed that immunologic changes have also been associated with an increased risk of EP.

• #30 Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy

  https://www.mdpi.com/1422-0067/23/7/3490

  Inflammation induction can also be caused by B-cell activation factor (BAFF), which regulates acquired and innate immune responses. Increased BAFF expression with simultaneous increases in IL-6 and TNF-alpha levels was observed in patients with TEP. […] This review provides an initial summary of the common features of the pathophysiology of endometriosis and EP. It is still unclear how strongly the two conditions are connected to each other and how. We presented studies that showed similarities for both pathologies. The fact is that both endometriosis and EP are associated with the inflammatory environment, the Wnt/β-catenin pathway, and hormonal regulation that to date seems to be most important and well-documented common molecular mechanisms of both diseases.

• #31 Ectopic pregnancy and epithelial to mesenchymal transition: is there a link? in: Reproduction Volume 161 Issue 3 (2021)

  https://rep.bioscientifica.com/view/journals/rep/161/3/REP-20-0542.xml

  Ectopic pregnancy (EP) is defined as the implantation of an embryo outside of the uterus and is a leading cause of first trimester maternal mortality and morbidity. This article discusses a possible role for epithelial to mesenchymal transition in the pathogenesis of EP, given the notable similarity of protein expression between the two processes. […] Epithelial to mesenchymal transition (EMT) is a biological process whereby epithelial cells undergo loss of polarity and cell-cell adhesion, then adopt mesenchymal characteristics such as migration, invasion and resistance to apoptosis. […] Here, we put forward the hypothesis that tEP occurs as a result of EMT in the epithelial cells lining the Fallopian tube, with these changes enabling ectopic embryo implantation. […] There are many similarities in protein expression between EMT and tEP including integrins, Wnt, Mucin-1 (MUC-1), E-cadherin, signal transducer and activator of transcription (STAT3), and matrix metalloproteases (MMPs).

• #32 Ectopic pregnancy and epithelial to mesenchymal transition: is there a link? in: Reproduction Volume 161 Issue 3 (2021)

  https://rep.bioscientifica.com/view/journals/rep/161/3/REP-20-0542.xml

  Ectopic pregnancy (EP) is defined as the implantation of an embryo outside of the uterus and is a leading cause of first trimester maternal mortality and morbidity. This article discusses a possible role for epithelial to mesenchymal transition in the pathogenesis of EP, given the notable similarity of protein expression between the two processes. […] Epithelial to mesenchymal transition (EMT) is a biological process whereby epithelial cells undergo loss of polarity and cell-cell adhesion, then adopt mesenchymal characteristics such as migration, invasion and resistance to apoptosis. […] Here, we put forward the hypothesis that tEP occurs as a result of EMT in the epithelial cells lining the Fallopian tube, with these changes enabling ectopic embryo implantation. […] There are many similarities in protein expression between EMT and tEP including integrins, Wnt, Mucin-1 (MUC-1), E-cadherin, signal transducer and activator of transcription (STAT3), and matrix metalloproteases (MMPs).

• #33 Ectopic pregnancy and epithelial to mesenchymal transition: is there a link? in: Reproduction Volume 161 Issue 3 (2021)

  https://rep.bioscientifica.com/view/journals/rep/161/3/REP-20-0542.xml

  Similar to the process of EMT, 1-integrin is upregulated in the endometrial luminal epithelium during implantation in intrauterine pregnancy and has also been noted to be increased in the cytoplasm of Fallopian tube epithelial cells in tEP. […] In summary, EMT is likely a common process in the Fallopian tube, which could explain the pathophysiology of EP, providing a unifying mechanism behind multiple risk factors for tEP.

• #34 Ectopic pregnancy and epithelial to mesenchymal transition: is there a link? in: Reproduction Volume 161 Issue 3 (2021)

  https://rep.bioscientifica.com/view/journals/rep/161/3/REP-20-0542.xml

  Ectopic pregnancy (EP) is defined as the implantation of an embryo outside of the uterus and is a leading cause of first trimester maternal mortality and morbidity. This article discusses a possible role for epithelial to mesenchymal transition in the pathogenesis of EP, given the notable similarity of protein expression between the two processes. […] Epithelial to mesenchymal transition (EMT) is a biological process whereby epithelial cells undergo loss of polarity and cell-cell adhesion, then adopt mesenchymal characteristics such as migration, invasion and resistance to apoptosis. […] Here, we put forward the hypothesis that tEP occurs as a result of EMT in the epithelial cells lining the Fallopian tube, with these changes enabling ectopic embryo implantation. […] There are many similarities in protein expression between EMT and tEP including integrins, Wnt, Mucin-1 (MUC-1), E-cadherin, signal transducer and activator of transcription (STAT3), and matrix metalloproteases (MMPs).

• #35 Role of telocytes in the pathogenesis of ectopic pregnancy

  https://www.europeanreview.org/article/27754

  Increased telocyte count in the fallopian tube may decrease tubal motility and may affect the transfer of the blastocyst to the uterus and possibly contribute to the pathogenesis of EP. […] The homogenous distribution of telocytes in the mucosa and muscular layers of the control group, changed to heterogeneous localization the EP group. […] Immunohistochemical staining with vimentin, S100A, c-Kit and CD34, revealed increased telocyte counts in the muscular layer and serosa of the tubal tissues of EP.

• #36 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Ectopic pregnancy occurs at a rate of 19.7 cases per 1,000 pregnancies in North America and is a leading cause of maternal mortality in the first trimester. […] Ectopic pregnancy is any pregnancy in which the fertilized ovum implants outside the intrauterine cavity. More than 95 percent of ectopic pregnancies occur in the fallopian tubes. […] The mechanism can be anatomic (e.g., scarring that blocks transport of the egg) or functional (e.g., impaired tubal mobility). […] In the general population, pelvic inflammatory disease is the most common risk factor for ectopic pregnancy. […] Previous ectopic pregnancy becomes a more significant risk factor with each successive occurrence. […] Endometriosis, tubal surgery and pelvic surgery result in pelvic and tubal adhesions and abnormal tubal function.

• #37

  https://journals.lww.com/armh/fulltext/2016/04020/histomorphology_of_fallopian_tubes_in_ectopic.9.aspx

  Ectopic pregnancy can present as an acute life-threatening emergency when it ruptures and accounts for about 10% of all maternal mortalities. The fallopian tube is the most common site for ectopic pregnancy (90-95%). […] Ectopic tubal pregnancy is the most common cause of hematosalpinx. […] Chronic salpingitis due to chronic PID has been documented as one of the most important risk factors in the development of ectopic pregnancy. […] The risk of ectopic is known to increase 7-fold after an episode of acute salpingitis. […] One of the other causes for chronic salpingitis, especially in India, is genital TB. […] Since ectopic pregnancy is one of the most serious complications of PID, the identification of features of chronic salpingitis with subsequent treatment reduces the risk of a recurrent ectopic. […] The most serious clinical and pathological complications of SIN are infertility and a strong association with ectopic pregnancy. […] Histopathological examination of the resected fallopian tubal ectopics can provide an insight into the etiopathogenesis of ectopic pregnancy.

• #38 Ectopic pregnancy – Wikipedia

  https://en.wikipedia.org/wiki/Ectopic_pregnancy

  Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. […] Risk factors for ectopic pregnancy include pelvic inflammatory disease, often due to chlamydia infection; tobacco smoking; endometriosis; prior tubal surgery; a history of infertility; and the use of assisted reproductive technology. […] The exact mechanism through which chlamydia increases the risk of ectopic pregnancy is uncertain, though some research suggests that the infection can affect the structure of fallopian tubes. […] Tubal pregnancy is when the egg is implanted in the fallopian tubes. Hair-like cilia located on the internal surface of the fallopian tubes carry the fertilized egg to the uterus. […] As cilia degenerate, the amount of time it takes for the fertilized egg to reach the uterus will increase.

• #39 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Ectopic pregnancy occurs at a rate of 19.7 cases per 1,000 pregnancies in North America and is a leading cause of maternal mortality in the first trimester. […] Ectopic pregnancy is any pregnancy in which the fertilized ovum implants outside the intrauterine cavity. More than 95 percent of ectopic pregnancies occur in the fallopian tubes. […] The mechanism can be anatomic (e.g., scarring that blocks transport of the egg) or functional (e.g., impaired tubal mobility). […] In the general population, pelvic inflammatory disease is the most common risk factor for ectopic pregnancy. […] Previous ectopic pregnancy becomes a more significant risk factor with each successive occurrence. […] Endometriosis, tubal surgery and pelvic surgery result in pelvic and tubal adhesions and abnormal tubal function.

• #40 Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy

  https://www.mdpi.com/1422-0067/23/7/3490

  Endometriosis is a common inflammatory disease characterized by the presence of endometrial cells outside the uterine cavity. Its pathogenesis covers a wide range of abnormalities, including adhesion, proliferation, and cell signaling disturbances. One of the most serious complications of endometriosis is an ectopic pregnancy (EP). Currently, the exact mechanism explaining this phenomenon is unknown; therefore, there are no effective methods of prevention. It is assumed that the pathogenesis of EP is influenced by abnormalities in the contraction of the fallopian tube muscles, the mobility of the cilia, and in the fallopian microenvironment. Endometriosis can disrupt function on all three levels and thus contribute to the implantation of the embryo beyond the physiological site. […] The mechanism leading to an EP is not fully understood. Most of the data come from in vitro studies as ectopic pregnancy is rare in animals and it is difficult to develop such a model. However, it can be assumed that the passage of the oocyte and later the embryo along the fallopian tube is influenced by three main components: ciliary movement, contractility of the fallopian tubes, and tubal fluid. All of these phenomena occur due to the paracrine relationship between the epithelium and endothelium of the fallopian tube, the immune system, and the embryo.

• #41 Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy

  https://www.mdpi.com/1422-0067/23/7/3490

  Endometriosis is a common inflammatory disease characterized by the presence of endometrial cells outside the uterine cavity. Its pathogenesis covers a wide range of abnormalities, including adhesion, proliferation, and cell signaling disturbances. One of the most serious complications of endometriosis is an ectopic pregnancy (EP). Currently, the exact mechanism explaining this phenomenon is unknown; therefore, there are no effective methods of prevention. It is assumed that the pathogenesis of EP is influenced by abnormalities in the contraction of the fallopian tube muscles, the mobility of the cilia, and in the fallopian microenvironment. Endometriosis can disrupt function on all three levels and thus contribute to the implantation of the embryo beyond the physiological site. […] The mechanism leading to an EP is not fully understood. Most of the data come from in vitro studies as ectopic pregnancy is rare in animals and it is difficult to develop such a model. However, it can be assumed that the passage of the oocyte and later the embryo along the fallopian tube is influenced by three main components: ciliary movement, contractility of the fallopian tubes, and tubal fluid. All of these phenomena occur due to the paracrine relationship between the epithelium and endothelium of the fallopian tube, the immune system, and the embryo.

• #42 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Cigarette smoking has an independent and dose-related effect on the risk of ectopic pregnancy. […] The potential advantages are the avoidance of surgery and its concomitant hazards, the preservation of tubal patency and function, and a lower cost. […] Methotrexate inhibits the synthesis of purines and pyrimidines. Thus, it interferes with DNA synthesis and cell multiplication. Rapidly dividing cells are most vulnerable to methotrexate. This accounts for the drug’s effect on trophoblastic tissue, as well as its side effects on the buccal and intestinal mucosa, urinary bladder, bone marrow and skin. […] The laparoscope has virtually eliminated the need for laparotomy.

• #43

  https://link.springer.com/article/10.1007/s43032-022-00947-6

  In the past few decades, the smoking rate of women of childbearing age has increased. […] Epidemiological data has repeatedly shown that smoking women have an increased risk of various reproductive diseases, including ectopic pregnancy (EP), decreased fertility, adverse pregnancy outcomes, and failure of assisted reproduction. […] This paper reviews the roles of the fallopian tube in gametes and embryo transportation, and the possible mechanism tobacco smoke contributes to tubal EP. […] A possible signal pathway might be a model to develop intervention of EP for pregnant women exposed to smoking. […] Cotinine exposure increases Fallopian tube PROKR1 expression via nicotinic AChRalpha-7: a potential mechanism explaining the link between smoking and tubal ectopic pregnancy. […] Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy.

• #44 Ectopic Pregnancy: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/2041923-overview

  An ectopic pregnancy requires the occurrence of 2 events: fertilization of the ovum and abnormal implantation. Many risk factors affect both events; for example, a history of major tubal infection decreases fertility and increases abnormal implantation. […] Multiple factors contribute to the relative risk of ectopic pregnancy. In theory, anything that hampers or delays the migration of the fertilized ovum to the endometrial cavity can predispose a woman to ectopic gestation. […] The most logical explanation for the increasing frequency of ectopic pregnancy is previous pelvic infection; however, most patients presenting with an ectopic pregnancy have no identifiable risk factor. […] Cigarette smoking has been shown to be a risk factor for ectopic pregnancy development. Studies have demonstrated an elevated risk ranging from 1.6 to 3.5 times that of nonsmokers.

• #45 Ectopic Pregnancy | Calgary Guide

  https://calgaryguide.ucalgary.ca/ectopic-pregnancy/ectopic-pregnancy-1/

  Ectopic Pregnancy: Pathogenesis and Clinical Findings In vitro fertilization Tubal disorders leading to infertility and unknown procedural causes Previous ectopic pregnancy Underlying tubal disorder leading to previous ectopic Pelvic inflammatory disease (PID) Endometriosis Tubal surgery or disorders Age 35 Risk factor accumulation over time Smoking Impairment in tubal motility; impaired immunity (risk factor for PID) Tubal scarring leading to adhesions, obstruction, and alteration of tubal function […] Ectopic Pregnancy: Implantation of developing blastocyst outside the uterine cavity, most commonly in fallopian tube (other locations: interstitial cornual cervical ovarian abdominal) Embryo releases human chorionic gonadotropin (-hCG), which supports corpus luteum to continue producing progesterone […] Pregnancy cannot survive without the uterine endometrium […] Cessation of human chorionic gonadotropin (-hCG) release from embryo -hCG plateaus or decreases […] Positive -hCG, but rising 2000 + absence of intrauterine pregnancy.

• #46 Ectopic Pregnancy: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/2041923-overview

  Ovulation induction with clomiphene citrate or injectable gonadotropin therapy has been linked to a 4-fold increase in the risk of ectopic pregnancy in a case-control study. […] The highest rate of ectopic pregnancy occurs in women aged 35-44 years. A 3- to 4-fold increase in the risk of developing an ectopic pregnancy exists compared with women aged 15-24 years. One proposed explanation suggests that aging may result in a progressive loss of myoelectrical activity in the fallopian tube; myoelectrical activity is responsible for tubal motility.

• #47 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Ectopic pregnancy occurs at a rate of 19.7 cases per 1,000 pregnancies in North America and is a leading cause of maternal mortality in the first trimester. […] Ectopic pregnancy is any pregnancy in which the fertilized ovum implants outside the intrauterine cavity. More than 95 percent of ectopic pregnancies occur in the fallopian tubes. […] The mechanism can be anatomic (e.g., scarring that blocks transport of the egg) or functional (e.g., impaired tubal mobility). […] In the general population, pelvic inflammatory disease is the most common risk factor for ectopic pregnancy. […] Previous ectopic pregnancy becomes a more significant risk factor with each successive occurrence. […] Endometriosis, tubal surgery and pelvic surgery result in pelvic and tubal adhesions and abnormal tubal function.

• #48 Ectopic pregnancy pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Ectopic_pregnancy_pathophysiology

  The most common site of ectopic pregnancies is in the Fallopian tubes (80% ampullar). […] hCH levels in an ectopic pregnancy are usually lower than in uterine pregnancies. […] No visible intruterine transvaginal utrasonography with a serum hCG higher than 2000 mIU/ml is indicateive of an ectopic pregnancy. […] Damage to the cilia or blockage of the Fallopian tubes is likely to lead to an ectopic pregnancy. […] A common cause of Fallopian tubes occlusion and damage to cilia is by scaring of tissues after pelvic inflammatory disease (PID). […] Tubal ligation can predispose to ectopic pregnancy, variably increasing the risk depending on the method used. […] A history of ectopic pregnancy increases the risk of future occurrences in about 10%. […] In vitro fertilization is used for patients with damaged tubes, which are an inherent risk factor for ectopic pregnancy.

• #49 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Some authors explain the twin EP as a mere result of a bilateral ovulation. Just like in singleton EP, fallopian tube is the most common site. […] Among EP risk factors Intrauterine device with progestogen (IUDs) were one of the principal subjects of investigation. […] Like has been largely demonstrated, IUD use does not increase risk of an abnormal pregnancy implantation. […] But as Iavazzo et al. illustrated in a 2008 review, results are conflicting and if an IUD is inside uterine cavity, possibilities of an EP are higher. […] Some studies have found that EP incidence rate among women using a low-dose hormonal IUD was higher than in women using other types of hormonal contraception. […] Like demonstrated in a systematic review by Callahan et al., progestin-only implant or injectable contraception substantially reduces their risk of pregnancy and, thus, EP.

• #50 Ectopic Pregnancy: An Overview

  https://www.imrpress.com/journal/CEOG/49/12/10.31083/j.ceog4912262/htm

  Some authors explain the twin EP as a mere result of a bilateral ovulation. Just like in singleton EP, fallopian tube is the most common site. […] Among EP risk factors Intrauterine device with progestogen (IUDs) were one of the principal subjects of investigation. […] Like has been largely demonstrated, IUD use does not increase risk of an abnormal pregnancy implantation. […] But as Iavazzo et al. illustrated in a 2008 review, results are conflicting and if an IUD is inside uterine cavity, possibilities of an EP are higher. […] Some studies have found that EP incidence rate among women using a low-dose hormonal IUD was higher than in women using other types of hormonal contraception. […] Like demonstrated in a systematic review by Callahan et al., progestin-only implant or injectable contraception substantially reduces their risk of pregnancy and, thus, EP.

• #51 70 Basic icons by Xicons.co

  https://ectopic.org.uk/reasons-for-an-ectopic-pregnancy/intrauterine-devices-and-ectopic-pregnancy

  Unfortunately, IUCDs can fail in around 1% of cases and do come with a risk of pregnancy. […] If you do get pregnant with an IUCD, it is more likely to be an ectopic pregnancy. This is because IUCDs are so effective at preventing pregnancies in the uterus, if a pregnancy does occur, it is more likely to occur outside of the uterus. […] The IUCD does not directly cause ectopic pregnancy; rather, it prevents typical intrauterine pregnancies (normally-sited), but it does not prevent ectopic pregnancies. Copper IUCDs are thought to also increase the risk of ectopic pregnancy by causing inflammation in the Fallopian tubes. […] A review of IUCD safety and efficacy stated that ectopic pregnancies affect 2 in 10,000 women with hormonal IUCDs, and 5 in 10,000 copper IUCD users, each year. […] Though an IUCD does increase the chance of a pregnancy being ectopic while it is in place, there is no increased risk of ectopic pregnancy after IUCD removal. […] The recommended treatments for ectopic pregnancy with an IUCD in the UK are surgical or medical treatments. […] Case studies have shown that the most effective way of managing an ectopic pregnancy with an IUCD is surgery.

• #52 Methotrexate in the Management of Ectopic Pregnancy: A Comparative Review of Single-Dose Versus Multi-Dose Protocols | Auctores

  https://www.auctoresonline.org/article/methotrexate-in-the-management-of-ectopic-pregnancy-a-comparative-review-of-single-dose-versus-multi-dose-protocols

  Methotrexate is a medication used in the treatment of ectopic pregnancy, which is a condition where a fertilized egg implants and grows outside the uterine cavity, usually in a fallopian tube. The mechanism of action of methotrexate in this context includes several key aspects: Methotrexate is a folic acid antagonist. It inhibits the enzyme dihydrofolate reductase, which is crucial for the synthesis of nucleotides, the building blocks of DNA and RNA. By blocking this enzyme, methotrexate impairs the production of DNA and RNA, leading to reduced cellular proliferation. […] Ectopic pregnancy involves the growth and division of trophoblastic cells (the cells that form the outer layer of the placenta). Methotrexate disrupts the proliferation of these cells by interfering with their ability to synthesize DNA and RNA, which ultimately leads to the termination of the ectopic pregnancy. […] Methotrexate may also induce apoptosis (programmed cell death) in rapidly dividing cells. This contributes to the resolution of the ectopic pregnancy by causing the death of the trophoblastic cells that are growing abnormally.

• #53 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Cigarette smoking has an independent and dose-related effect on the risk of ectopic pregnancy. […] The potential advantages are the avoidance of surgery and its concomitant hazards, the preservation of tubal patency and function, and a lower cost. […] Methotrexate inhibits the synthesis of purines and pyrimidines. Thus, it interferes with DNA synthesis and cell multiplication. Rapidly dividing cells are most vulnerable to methotrexate. This accounts for the drug’s effect on trophoblastic tissue, as well as its side effects on the buccal and intestinal mucosa, urinary bladder, bone marrow and skin. […] The laparoscope has virtually eliminated the need for laparotomy.

• #54 Methotrexate in the Management of Ectopic Pregnancy: A Comparative Review of Single-Dose Versus Multi-Dose Protocols | Auctores

  https://www.auctoresonline.org/article/methotrexate-in-the-management-of-ectopic-pregnancy-a-comparative-review-of-single-dose-versus-multi-dose-protocols

  Methotrexate is a medication used in the treatment of ectopic pregnancy, which is a condition where a fertilized egg implants and grows outside the uterine cavity, usually in a fallopian tube. The mechanism of action of methotrexate in this context includes several key aspects: Methotrexate is a folic acid antagonist. It inhibits the enzyme dihydrofolate reductase, which is crucial for the synthesis of nucleotides, the building blocks of DNA and RNA. By blocking this enzyme, methotrexate impairs the production of DNA and RNA, leading to reduced cellular proliferation. […] Ectopic pregnancy involves the growth and division of trophoblastic cells (the cells that form the outer layer of the placenta). Methotrexate disrupts the proliferation of these cells by interfering with their ability to synthesize DNA and RNA, which ultimately leads to the termination of the ectopic pregnancy. […] Methotrexate may also induce apoptosis (programmed cell death) in rapidly dividing cells. This contributes to the resolution of the ectopic pregnancy by causing the death of the trophoblastic cells that are growing abnormally.

• #55 Diagnosis and Management of Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2014/0701/p34.html

  Transvaginal ultrasonography is the recommended imaging technique for patients with suspected ectopic pregnancy. […] When transvaginal ultrasonography is nondiagnostic, the beta subunit of human chorionic gonadotropin (-hCG) discriminatory level may be useful. This is the value above which an intrauterine pregnancy should be visualized by ultrasonography. In a patient with a -hCG value above this level, failure to visualize an intrauterine pregnancy strongly suggests ectopic pregnancy. […] Medical management is cost-effective and avoids the risk of morbidity associated with surgery and anesthesia. Methotrexate, a folic acid antagonist that inhibits DNA synthesis and cell replication, was first used to treat ectopic pregnancy in 1982 and is now the agent most commonly used for medical treatment. The mechanism of action is to selectively kill cytotrophoblasts (the rapidly dividing cells at the fallopian tube implantation site), which the body then spontaneously resorbs.

• #56 Ectopic pregnancy: models and medical management

  https://era.ed.ac.uk/handle/1842/40637

  This mirrors the in vivo situation where ectopic implantation occurs in a minority of pregnancies. Manipulation of this system could offer new insights into the pathogenesis of ectopic pregnancy. […] It is widely presumed that the mechanism of action of methotrexate in ectopic pregnancy is inhibition of DNA synthesis, as is the case where it is used at a 20-fold higher dose in the treatment of certain cancers. […] In contrast, persistently high methotrexate concentrations, which more closely replicate cancer therapy, were able to inhibit DNA synthesis. […] What role this may have in treatment of ectopic pregnancy requires future investigation. […] This pre-clinical study suggests that GnRHR antagonists could have utility as a future treatment for ectopic pregnancy. […] In conclusion, this thesis describes a novel in vitro model of ectopic pregnancy; identifies that the mechanism of action of methotrexate in ectopic pregnancy is not as presumed, perhaps explaining its limited efficacy; and that pre-clinical study of GnRHR antagonists suggest they may represent a promising new medical treatment for ectopic pregnancy.

• #57 Ectopic Pregnancy | AAFP

  https://www.aafp.org/pubs/afp/issues/2000/0215/p1080.html

  Cigarette smoking has an independent and dose-related effect on the risk of ectopic pregnancy. […] The potential advantages are the avoidance of surgery and its concomitant hazards, the preservation of tubal patency and function, and a lower cost. […] Methotrexate inhibits the synthesis of purines and pyrimidines. Thus, it interferes with DNA synthesis and cell multiplication. Rapidly dividing cells are most vulnerable to methotrexate. This accounts for the drug’s effect on trophoblastic tissue, as well as its side effects on the buccal and intestinal mucosa, urinary bladder, bone marrow and skin. […] The laparoscope has virtually eliminated the need for laparotomy.

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