Relative Morphokinetics Assessed by Time-Lapse Imaging Are Altered in Embryos From Patients With Endometriosis.

INTRODUCTION: Time-lapse technology allows almost continuous noninvasive assessment of embryonic development. It was shown previously that relative kinetics defining cleavage synchronicity are better predictors of blastocyst quality than absolute time points. This study aims to compare relative kinetics in embryos from patients with and without endometriosis. METHODS: Time-lapse data were collected retrospectively from 596 patients undergoing infertility treatment for in vitro fertilization from January 2011 to July 2016. Four hundred twenty-eight patients with confounding comorbidities (ie, polycystic ovary syndrome, pathological spermiogram in the included cycle, numerical/structural genetic abnormalities, preimplantation genetic screening performed) or incomplete data sets were excluded. Of the 168 included patients, 72 (42.9%) had endometriosis. Indications for in vitro fertilization of controls were tubal factor, unexplained infertility, or prolonged infertility. Relative kinetics were calculated as defined previously: cleavage synchronicity (CS)2-8=((t3-t2) + (t5-t4))/(t8-t2), CS4-8=(t8-t5)/(t8-t4), CS2-4=(t4-t3)/(t4-t2), DNA replication time ratio (DR)=(t3-t2)/(t5-t3). In women with more than one embryo, the median time was analyzed. RESULTS: Median age, body mass index, smoking status, and AMH levels were similar in both groups. Embryos from patients with endometriosis showed poorer relative kinetics. The relative time CS2-8 was decreased in embryos from patients with endometriosis (0.7 [0.0-0.93] vs 0.8 [0.0-0.94], P < .05) and CS4-8 was increased (0.4 [0.0-1.0] vs 0.3 [0.0-1.0], P < .05). The less powerful diagnostic relative kinetic parameters (CS2-4 and DR) were not significantly different. CONCLUSIONS: Embryos from patients with endometriosis presented with altered relative kinetics suggesting poorer embryo quality. These findings support recently published data demonstrating reduced oocyte quality in patients with endometriosis which is one possible explanation for their poor response to fertility treatment.

Endometriosis origin from primordial germ cells.

Endometriosis is defined by the presence of endometrial ectopia. Multiple hypotheses have been postulated to explain the etiology of endometriosis to understand various clinical evidences. The etiology of endometriosis is still unclear.The primary question to understanding the etiology of endometrial ectopia (endometriosis) is determining the origin of eutopic (normally cited) endometrium.According to the new theory, primordial germ cells migrate from hypoblast (yolk sac close to the allantois) to the gonadal ridges. The gonadal ridges which composed of primordial germ cells derive to the: eutopic endometrium, ovary, ovarian ligament and ligamentum teres uteri.There are 2 principal processes in uterine organogenesis: the intersection of gonadal ridges with mesonephral ducts to form the uterine folds with an endometrial cavity and the fusion of the both uterine folds together to form the unicavital (normal) uterus. In the uterine folds there are closer cell-to-cell communications, polypotential germ cells differentiate and grow into myometrium and endometrial layers.Some of the polypotential germ cells fail to reach the ridges and stay in the peritoneal cavity, where they may be transforming into external endometrial heterotopies.The main insight in the etiology of endometriosis is polypotential germ cells origin, which may explain its potency, pathogenesis and expansion.

The Presence of Endometrioma Does Not Impair Time-Lapse Morphokinetic Parameters and Quality of Embryos: A Study On Sibling Oocytes.

OBJECTIVE: To see whether the oocytes retrieved from an ovary with an endometrioma would develop into embryos with aberrant timings of cleavage as assessed using time-lapse monitoring (TLM) and poorer morphologic quality compared with sibling oocytes from the contralateral ovary with no endometrioma in the same patient after intracytoplasmic sperm injection. METHODS: This was an observational prospective study at an in vitro fertilization (IVF) center of a private hospital. It included analysis and comparison of 128 embryos (69 embryos developed from the ovary with endometrioma and 59 embryos from the contralateral ovary without endometrioma serving as controls from a total of 20 women with infertility). Morphology of the embryo was assessed twice (days 3 and 5), again by capturing images with the TLM system. Morphokinetic parameters of embryos and clinical pregnancy rates were recorded separately from ovaries with and without endometrioma and were the primary outcomes of the study. Secondary outcomes included number of retrieved oocytes, number of metaphase II (MII) oocytes, fertilization rates, and conventional morphological classification of embryos. RESULTS: There were no differences in terms of the following time-lapse morphokinetic parameters of embryos. The mean numbers of oocytes and MII oocytes collected from the ovary with the endometrioma were similar to those collected from the contralateral ovary without endometrioma. Fertilization rates and the percentage of embryos with top morphologic quality were also similar. CONCLUSIONS: According to the morphokinetic parameters, this study further strengthens the notion that removal of endometriomas before IVF is not a necessity in terms of better oocyte quality and development.

Fetal endometriosis: a case report.

OBJECTIVE: To report a case of a large fetal pelvic mass diagnosed at 35 weeks' gestation. DESIGN: Report of a unique case of a fetal abdominal mass, emphasizing the wide range of differential diagnoses. Although rare reports of fetal ovarian cysts exist, even fewer describe endometriosis or endometriomas in infants. As of 2014 there have not been any published reports of fetal endometriosis from the United States. SETTING: Large tertiary community hospital. PATIENT(S): An 18-year-old pregnant woman diagnosed with a large fetal pelvic mass at 35 weeks' gestation. INTERVENTION(S): Diagnosis of a fetal abdominal mass at 35 weeks with documented enlargement at 37 weeks leading to delivery, with subsequent removal of the mass on day of life 2. MAIN OUTCOME MEASURE(S): On day of life 2, a pediatric surgeon performed an exploratory laparotomy and left salpingo-oophorectomy. RESULT(S): Final pathology showed a 7.0 × 4.5 cm cyst-like structure consistent with hemorrhagic ovarian cyst wall and focal endometriosis. CONCLUSION(S): It can be very difficult to counsel patients regarding an abdominal mass in their unborn child. These difficulties stem from the large list of differential diagnoses and the range of prognoses they portend. As more and more of these cases appear in the literature, we are able to gain a better understanding of how each of these diagnoses present and appear on imaging, allowing us to provide a more accurate diagnosis and counseling antenatally.

Müllerianosis: four developmental (embryonic) mullerian diseases.

The theory of müllerianosis predicts that embryonic müllerian tissue, misplaced during organogenesis, results in the formation of 4 benign müllerian diseases-developmental adenomyosis, endometriosis, endosalpingiosis, and endocervicosis-(developmental müllerian diseases) that will be identified in human female fetuses, infants, children, adolescents, and adults. Direct evidence is presented to support the existence of developmental adenomyosis, developmental endometriosis, and developmental endocervicosis in human female fetuses along with strong circumstantial evidence supporting the existence of all 4 developmental müllerian diseases in human female infants, children, adolescents, and adults. This evidence throws light upon the pathogenesis of rare müllerian lesions whose pathogenesis remains inexplicable by classical and modern theories. Furthermore, this research has scientific and clinical relevance: scientific relevance because it opens up a new field of comparative research-the 4 developmental müllerian diseases complement the 4 acquired müllerian diseases; clinical relevance because it identifies rare müllerian diseases curable by complete surgical excision.

Embryologic origin of endometriosis: analysis of 101 human female fetuses.

The etiology of endometriosis, a gynecological disease characterized by the presence of endometrial glands and stroma outside the uterine cavity, is still unknown. Our research group has recently demonstrated the presence of ectopic endometrium in human female fetuses at different gestational ages. In this manuscript we describe four new cases of fetal endometriosis found among a series of 52 female fetuses analyzed at autopsy. The anatomical localization of this ectopic endometrium, and its histological and immunohistochemical characteristics are depicted. We suggest that endometriosis is caused by dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis. The clinical and pathological implications of these findings are discussed.

Embarazo ectópico abdominal. Diagnóstico y tratamiento médico con metotrexato / Abdominal pregnancy. Diagnosis and medical treatment with methotrexate

El embarazo ectópico abdominal es uno de los tipos menos frecuentes de embarazos extrauterinos. Está asociado a una alta morbimorbilidad materna y fetal. El diagnóstico de esta entidad es difícil y suele realizarse de forma tardía. Presentamos el caso de una paciente con una gestación ectópica abdominal, diagnosticada mediante ecografía transvaginal, en el primer trimestre de gestación. Se realizó un tratamiento médico con metotrexato hasta la resolución del cuadro. Realizamos una revisión de la literatura científica de los factores de riesgo de embarazo ectópico abdominal, métodos diagnósticos y opciones terapéuticas (AU)

Abdominal pregnancy is a rare form of ectopic pregnancy and is associated with high maternal and fetal morbidity and mortality. The diagnosis of this entity is difficult and is generally delayed. We report the case of a patient with an abdominal pregnancy diagnosed by transvaginal ultrasound in the first trimester of pregnancy. The patient was treated with methotrexate until complete resolution. We provide a review of the literature on the risk factors, diagnostic tests and therapeutic options for abdominal pregnancy (AU)

Pathogenesis of endometriosis.

Many theories have been proffered to explain the histogenesis of endometriosis (Robboy et al., 2009). Generally, they divide into those that favour transplantation of endometrial fragments to ectopic sites, metaplasia of the multipotential celomic peritoneum and induction of undifferentiated mesenchyme in ectopic sites to form endometriotic tissues after exposure to substances released from shed endometrium.

New evidence of the presence of endometriosis in the human fetus.

The aetiology of endometriosis, a gynaecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity, is still open to debate. Research has recently found evidence for endometriosis in human female fetuses at different gestational ages. This paper reports a new case of fetal endometriosis in a 25-week female fetus, deceased due to placental pathology, from a series of 13 female fetuses analysed at autopsy. The exact anatomical localization of this misplaced endometrium, as well as its histopathological and immunohistochemical characteristics are illustrated. The case suggests that endometriosis can be caused by dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis.

The effects of tamoxifen and estradiol on myometrial differentiation and organization during early uterine development in the CD1 mouse.

We used a neonatal mouse model to examine the histogenesis of uterine adenomyosis, and to test whether adenomyosis is due to an abnormality in myometrial differentiation, or in extracellular matrix proteins expression. We also studied the effects of tamoxifen and estradiol on uterine development, myometrial differentiation, and organization. Female CD1 pups were treated with oral tamoxifen (1 mg/kg) (n=27) or estradiol (0.1 mg/kg) (n=24) from age 1 to 5 days. Uteri from control (n=27) and treated mice were obtained on days 2, 5, 10, 15, and 42 of age. We examined the sections histologically, using image analysis and immunohistochemistry for alpha-smooth muscle actin (alpha-SMA), desmin, vimentin, laminin, fibronectin, and estrogen receptor-alpha. Following tamoxifen exposure, all uteri showed adenomyosis by 6 weeks of age (seen as early as day 10). The inner myometrium showed thinning, lack of continuity, disorganization, and bundling. alpha-SMA expression was normal. Desmin expression normally showed a wave of maturation that was absent in tamoxifen-treated mice. In the estradiol group, adenomyosis was not observed. All uterine layers were normally developed, but hypertrophied. The inner myometrium retained its circular arrangement. There was no difference in the localization of laminin or fibronectin between groups (laminin expression was reduced in the tamoxifen treated uteri). Vimentin could not be detected in all groups. Our results suggest that the development of the inner myometrium is particularly sensitive to estrogen antagonism, and can be affected by steroid receptors modulation. Disruption of the inner myometrium may play a role in the development of uterine adenomyosis.

[Endometrioid carcinoma of the prostate: a histogenetic dilemma with therapeutic implications]. / Carcinoma endometrioide de la próstata: un dilema histogenético con implicaciones terapéuticas.

An additional case of endometrioid carcinoma of the prostate is presented. We discuss the origin and significance of this controversial and uncommon tumor type. The different histogenic hypotheses that have been put forward not only imply a distinct embryologic conception but also an appropriate therapeutic approach. The good results achieved by antiandrogen therapy in the case reported herein have prompted us to consider this treatment modality as a valid adjunct to surgery.

Etiology and histogenesis of endometriosis.

Based on the available scientific evidence, the mechanism of developing endometriosis appears to be transplantation of viable endometrial cell fragments shed during menses and regurgitated through the fallopian tubes under the influence of prostaglandin-mediated uterine contractions. As all women apparently retrograde menstruate to some extent, it is not surprising that circumstances which increase the total number of menstrual days experienced have been clinically associated with endometriosis. Similarly, factors which lead to relative uterine outflow obstruction have been associated with a higher incidence of endometriosis. There is virtually no other scientific evidence supporting alternate mechanisms of development of endometriosis. There are many unanswered questions regarding endometriosis including: 1) Are all women equally susceptible to development of the disease? 2) As the clinical presentation and course is extremely variable, what factors influence these events? 3) Does medical suppression of ovulation with oral contraceptives or continuous progestins provide a protective effect? 4) Are there systemic immunologic changes associated with endometriosis? Hopefully, this manuscript will help stimulate the next generation of clinical investigators to address these questions, as they are of paramount importance with this apparently increasingly devastating and frequent clinical disease.

Müllerianosis.

We suggest that müllerianosis is a distinct form of endometriosis, separate in its pathogenesis from transplantation endometriosis of lymphatic, hematogenous, transtubal, or iatrogenic origin, and also distinct from endometriosis of coelomic metaplasia.

Embryologic theory of histogenesis of endometriosis in peritoneal pockets.

A novel presentation of endometriosis is described in which the lesion is identified within the brim or floor of peritoneal pockets located within a crescentic band in the posterior pelvis. The predictability of these peritoneal pockets and their strong association with other anomalies of the Mullerian and urinary tracts raises the possibility of a congenital origin.

[An integrated histogenetic concept of internal and external endometriosis]. / Une conception histogénétique unitaire des endométrioses internes et externes.

The authors have studied the embryology of the uterus and have studied the comparative morphology of the internal foci of endometriosis, as well as the endometrium itself during the menstrual cycle. These studies have led them to think that the foci of endometriosis, whether they are internal or external, come from cells of coelomic mesothelium that persists in the transitional zone between the myometrium and the endometrium of the uterus, or in the mesothelium that covers the ovary, the tube and the pelvis under the stimulus of substances that are present in degenerate endometrial tissues during menstruation. This unitary idea of histogenesis makes it possible to consider under one heading, if not to unite, all endometriosis occurring anywhere according to their histogenic presentation under the same conditions of the tissues that surround them. It also makes it possible to explain the morphological similarity of endometriosis with the endometrium, although the biological behaviour of the two tissues is different. There is therefore a relationship between endometrium and endometriosis but not a filial one.

Endometriosis occurring in leiomyomatosis peritonealis disseminata: ultrastructural study and histogenetic consideration.

Leiomyomatosis peritonealis disseminata is a pseudomalignant condition which mimics disseminated abdominal carcinoma. A new case is reported and compared to the 11 well-documented cases in the literature. All reported patients have experienced a benign clinical course. The peritoneal nodules are composed of histologically benign-appearing smooth-muscle cells, substantiated by electron-microscopic study. The histogenesis of this entity is discussed in the light of our ultrastructural findings and the observation of concurrent endometriosis. The theory of metaplasia of the subcoelomic mesenchyme in the pathogenesis of the leiomyomatous lesions is favored. The serum estrogen levels determined in our patient did not reveal any abnormal change. The inducing factor(s) remain to be identified. Also, an unusual sensitivity of the coelomic tissues in these patients, in response to metaplastic stimuli, is postulated as a possible contributing factor.