Management of intrauterine adhesions using human amniotic mesenchymal stromal cells to promote endometrial regeneration and repair through Notch signalling.

Intrauterine adhesions (IUAs) severely hamper women's reproductive functions. Human amniotic mesenchymal stromal cell (hAMSC) transplantation is effective in treating IUAs. Here, we examined the function of Notch signalling in IUA treatment with hAMSC transplantation. Forty-five Sprague-Dawley female rats were randomly divided into the sham operation, IUA, IUA + E2, IUA + hAMSCs and IUA + hAMSCs + E2 groups. After IUA induction in the rats, hAMSCs promoted endometrial regeneration and repair via differentiation into endometrial epithelial cells. In all groups, the expression of key proteins in Notch signalling was detected in the uterus by immunohistochemistry. The results indicated Notch signalling activation in the hAMSCs and hAMSCs + E2 groups. We could also induce hAMSC differentiation to generate endometrial epithelial cells in vitro. Furthermore, the inhibition of Notch signalling using the AdR-dnNotch1 vector suppressed hAMSC differentiation (assessed by epithelial and mesenchymal marker levels), whereas its activation using the AdR-Jagged1 vector increased differentiation. The above findings indicate Notch signalling mediates the differentiation of hAMSCs into endometrial epithelial cells, thus promoting endometrial regeneration and repair; Notch signalling could have an important function in IUA treatment.

Morphological and functional assessment of the uterus: "one-stop shop imaging" using a compressed-sensing accelerated, free-breathing T1-VIBE sequence.

BACKGROUND: The combination of motion-insensitive, high-temporal, and spatial resolution imaging with evaluation of quantitative perfusion has the potential to increase the diagnostic capabilities of magnetic resonance imaging (MRI) in the female pelvis. PURPOSE: To compare a free-breathing compressed-sensing VIBE (fbVIBE) with flexible temporal resolution (range = 4.6-13.8 s) with breath-hold VIBE (bhVIBE) and to evaluate the potential value of quantifying uterine perfusion. MATERIAL AND METHODS: A total of 70 datasets from 60 patients (bhVIBE: n = 30; fbVIBE: n = 40) were evaluated by two radiologists. Only temporally resolved reconstruction (fbVIBE) was performed on 30 of the fbVIBE datasets. For a subset (n = 10) of the fbVIBE acquisitions, a time- and motion-resolved reconstruction (mrVIBE) was evaluated. Image quality (IQ), artifacts, diagnostic confidence (DC), and delineation of uterine structures (DoS) were graded on Likert scales (IQ/DC/DoS: 1 (non-diagnostic) to 5 (perfect); artifacts: 1 (no artifacts) to 5 (severe artifacts)). A Tofts model was applied for perfusion analysis. Ktrans was obtained in the myometrium (Mm), junctional zone (Jz), and cervix (Cx). RESULTS: The median IQ/DoS/DC scores of fbVIBE (4/5/5 κ >0.7-0.9) and bhVIBE (4/4/4; κ = 0.5-0.7; P > 0.05) were high, but Artifacts were graded low (fbVIBE/bhVIBE: 2/2; κ = 0.6/0.5; P > 0.05). Artifacts were only slightly improved by the additional motion-resolved reconstruction (fbVIBE/mrVIBE: 2/1.5; P = 0.08); fbVIBE was preferred in most cases (7/10). Significant differences of Ktrans values were found between Cx, Jz, and Mm (0.12/0.21/0.19; P < 0.05). CONCLUSION: The fbVIBE sequence allows functional and morphological assessment of the uterus at comparable IQ to bhVIBE.

Purulent vaginal discharge diagnosed in pasture-based Holstein-Friesian cows at 21 days postpartum is influenced by previous lactation milk yield and results in diminished fertility.

In a subset of dairy cows, prolonged pathological uterine inflammation results in purulent vaginal discharge (PVD), which can have negative consequences for both fertility and milk production. However, unlike for intensive systems, analysis of the effects of PVD in predominantly pasture-based herds is limited. The objective of this study was to assess the effect of PVD in spring-calving, pasture-based dairy cows on production and reproduction indices, stratified according to previous full-lactation milk yield. We assessed clinical disease as defined by vaginal mucus score (VMS) in 440 Holstein-Friesian cows from 5 farms. Cows were categorized as healthy (VMS 0) or having PVD (VMS 1-3) at 21 d postpartum. We recorded 305-d milk, milk protein, and milk fat yields (kg) before and after disease diagnosis, as well as fertility data, such as services per conception and the calving-conception period (CCP). Using SAS 9.4 (SAS Institute Inc., Cary, NC), we analyzed data using PROC MIXED, PROC PHREG, and PROC LOGISTIC to determine the least squares means differences and hazard and odds ratios between the groups, respectively. Overall, a 60% prevalence of PVD was recorded at 21 d postpartum. Milk yield and milk constituents were similar between all VMS categories and between healthy cows and cows with PVD. Although cows in the 4 VMS categories had statistically similar CCP, cows with PVD had a significantly longer CCP than healthy cows on average (9 d). The hazard ratio for cows with PVD was 0.66, indicating a 34% higher risk of a prolonged CCP than healthy cows. Odds ratio analysis determined that cows with PVD were 3 times more likely not to conceive at all, twice as likely not to conceive at first service, twice as likely not to conceive by 100 d postpartum, and 3 times more likely to fail to conceive before 150 d postpartum compared with healthy cows. Cows were retrospectively categorized as having low or high milk yield, based on whether they were above or below the median 305-d milk yield of the study population (6,571 kg) in the lactation before vaginal mucus scoring. Based on a univariate odds ratio, high-yield cows were 1.6 times more likely to present with PVD in the subsequent lactation. The number of services per conception did not differ between healthy and PVD cows in the low- and high-yield groups. In the high-yield group, cows with PVD were 4.9 times more likely not to conceive, 2.7 times more likely to require multiple services to conceive, 2.1 times more likely to remain not pregnant by 100 d postpartum, and 4.4 times more likely to remain not pregnant by 150 d postpartum. The CCP was also significantly longer in cows with PVD than their healthy counterparts (115.9 ± 4.9 and 104 ± 7.4 d, respectively). In conclusion, PVD significantly increased the CCP in all cows, but to a greater extent in cows with a high milk yield in the lactation before disease diagnosis.

The pathophysiology of the septate uterus: a systematic review.

BACKGROUND: Little is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus. OBJECTIVES: We explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects. SEARCH STRATEGY: We performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018. SELECTION CRITERIA: We selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated potentially eligible papers. MAIN RESULTS: Thirty-eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall. CONCLUSIONS: We found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum. TWEETABLE ABSTRACT: In women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.

Junctional zone endometrium alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment.

PURPOSE OF REVIEW: To investigate the JZE alterations in gynecological and obstetrical disorders and impact on diagnosis, prognosis and treatment. RECENT FINDINGS: JZE was found to be significantly extended in patients with endometriosis, leading to the conclusion that endometriosis is a primary disease of the uterus, much like adenomyosis. Statistical correlation was then demonstrated between the severity of endometriosis and the depth of the adenomyosis infiltrates, hence the thickening of the JZE. Stem cells, predominantly found in the JZE were also found in histological sections of leiomyoma, suggested to be the origin of leiomyoma. This reservoir of JZE stem cells is influenced by different stressors leading to their differentiation into leiomyoma, endometriosis, adenomyosis or endometrial cancer, according to the stressor. The variability in presentation was hypothesized to be connected to genetic and epigenetic factors. JZE was also suggested to act as a barrier, stopping endometrial carcinoma cells invasion and metastasis. In addition, JZE plays a major role in conception, pregnancy and postpartum. SUMMARY: JZE is an important anatomical landmark of the uterus contributing to normal uterine function under the influence of ovarian hormones. Alterations of the JZE thickness and contractility can be used as pathognomonic clinical markers in infertility and chronic pelvic pain, for subendometrial and myometrial disorders, for example, adenomyosis and fibroids. Prospective randomized control trials will clarify the diagnostic steps, imaging modalities to follow and probably triage the patients between medical and surgical treatments.

A model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes.

Bacterial infection of the uterus causes clinical endometritis in 15 to 20% of postpartum dairy cows and reduces fertility, even after the resolution of disease. However, it is difficult to disentangle the mechanisms linking reduced fertility with endometritis because cows have multiple confounding postpartum conditions. The aim of the present experiment was to develop an in vivo model of clinical endometritis in Holstein heifers using pathogenic Escherichia coli and Trueperella pyogenes. Estrous cycles of heifers were synchronized using a 5-d Co-Synch protocol, and subsequently received exogenous progesterone to elevate circulating progesterone at the time of uterine infusion. Endometrial scarification was performed before uterine infusion of live pathogenic Escherichia coli and Trueperella pyogenes, or sterile vehicle. Effects of infusion were evaluated by measuring rectal temperature, plasma haptoglobin, hematology, grading pus in the vaginal mucus, quantifying 16S rRNA in vaginal mucus, and transrectal ultrasonography. Bacterial infusion increased the median vaginal mucus to grade 2 by d 3 postinfusion, and to grade 3 from d 4 to 6 postinfusion. Control heifers maintained a median vaginal mucus grade ≤1 from d 1 to 6. Transrectal ultrasound revealed the accumulation of echogenic fluid in the uterus of heifers following bacterial infusion, which was absent in control heifers. Total 16S rRNA in vaginal mucus was elevated in bacteria-infused heifers compared with control heifers at d 5. Rectal temperature was increased in bacteria-infused heifers. Plasma haptoglobin, general health, and appetite did not differ between groups. As indicated by increased vaginal mucus grade after bacterial infusion and absence of systemic signs of illness, this model successfully induced symptoms resembling clinical endometritis in virgin Holstein heifers. The model allows the isolation of effects of uterine disease on fertility from confounding factors that can occur during the postpartum period in dairy cows.

Characteristics of midluteal phase uterine artery hemodynamics in patients with recurrent pregnancy loss.

AIM: To study the association in resistance to uterine artery blood flow and recurrent pregnancy loss (RPL) and find its potential influencing factors. METHODS: A retrospective study was conducted in 870 RPL and 237 non-RPL patients visiting to the Clinic from January 2014 to February 2018. All participants underwent comprehensive examinations and were scanned by transvaginal Doppler ultrasonography during the midluteal phase to measure the pulsatility index (PI), resistance index (RI) and systolic/diastolic ratio (S/D) values of the left and right main uterine arteries. P value less than 0.05 was considered statistically significant. RESULTS: The mean PI, RI and S/D values for uterine arteries were significantly higher in RPL patients than in non-RPL patients (P < 0.001). When subjects were grouped according to the different etiologies of RPL, significant higher indices of uterine arteries were found in RPL patients with antiphospholipid syndrome (P < 0.001), autoimmune diseases (P < 0.001), endocrinological abnormalities (P < 0.05), thrombophilia (P < 0.001), uterine anomalies (P < 0.01) and unexplained RPL (P < 0.001). No differences were found between patients with chromosomal anomalies and uterine arteries blood flow (P > 0.05). In RPL patients, mean PI, mean RI and mean S/D values shows no difference among groups (P > 0.05). The Similar results were observed in age and number of spontaneous abortion (P > 0.05). CONCLUSION: Impaired uterine artery blood perfusion may be an underlying pathology to RPL, and it can be used as an independent risk factor for pregnancy failure.

CLINICAL VALUE OF TRANSVAGINAL ULTRASONOGRAPHY IN COMPARISON TO HYSTEROSCOPY WITH HISTOPATHOLOGIC EXAMINATION IN DIAGNOSING ENDOMETRIAL ABNORMALITIES.

The aim of our retrospective study was to compare the performance of transvaginal sonography in relation to histologic diagnosis of samples obtained by hysteroscopy through analysis of data collected over 16 years. Data on suspected formation of endometrial polyp or submucosal fibroid found on ultrasound examination were extracted. The study included a total of 3679 women examined during the 2000-2015 period. All women underwent ultrasound examination preoperatively for better planning the type and scope of operation to be performed. The study included only women with samples for histopathologic analysis collected during the operation. Ultrasound diagnosis of polyps compared with histology showed 89.6% sensitivity and 39.1% specificity. For submucosal myomas, sensitivity was 69.2% and specificity 91.3%. In conclusion, ultrasound is not reliable method for definitive diagnosis but it is an excellent orientation method.

Congenital Uterine Malformation by Experts (CUME): better criteria for distinguishing between normal/arcuate and septate uterus?

OBJECTIVES: To assess the level of agreement between experts in distinguishing between septate and normal/arcuate uterus using their subjective judgment when reviewing the coronal view of the uterus from three-dimensional ultrasound. Another aim was to determine the interobserver reliability and diagnostic test accuracy of three measurements suggested by recent guidelines, using as reference standard the decision made most often by experts (Congenital Uterine Malformation by Experts (CUME)). METHODS: Images of the coronal plane of the uterus from 100 women with suspected fundal internal indentation were anonymized and provided to 15 experts (five clinicians, five surgeons and five sonologists). They were instructed to indicate whether they believed the uterus to be normal/arcuate (defined as normal uterine morphology or not clinically relevant degree of distortion caused by internal indentation) or septate (clinically relevant degree of distortion caused by internal indentation). Two other observers independently measured indentation depth, indentation angle and indentation-to-wall-thickness (I:WT) ratio. The agreement between experts was assessed using kappa, the interobserver reliability was assessed using the concordance correlation coefficient (CCC), the diagnostic test accuracy was assessed using the area under the receiver-operating characteristics curve (AUC) and the best cut-off value was assessed using Youden's index, considering as the reference standard the choice made most often by the experts (CUME). RESULTS: There was good agreement between all experts (kappa, 0.62). There were 18 septate and 82 normal/arcuate uteri according to CUME; European Society of Human Reproduction and Embryology (ESHRE)-European Society for Gynaecological Endoscopy (ESGE) criteria (I:WT ratio > 50%) defined 80 septate and 20 normal/arcuate uteri, while American Society for Reproductive Medicine (ASRM) criteria defined five septate (depth > 15 mm and angle < 90°), 82 normal/arcuate (depth < 10 mm and angle > 90°) and 13 uteri that could not be classified (referred to as the gray-zone). The agreement between ESHRE-ESGE and CUME was 38% (kappa, 0.1); the agreement between ASRM criteria and CUME for septate was 87% (kappa, 0.39), and considering both septate and gray-zone as septate, the agreement was 98% (kappa, 0.93). Among the three measurements, the interobserver reproducibility of indentation depth (CCC, 0.99; 95% CI, 0.98-0.99) was better than both indentation angle (CCC, 0.96; 95% CI, 0.94-0.97) and I:WT ratio (CCC, 0.92; 95% CI, 0.90-0.94). The diagnostic test accuracy of these three measurements using CUME as reference standard was very good, with AUC between 0.96 and 1.00. The best cut-off values for these measurements to define septate uterus were: indentation depth ≥ 10 mm, indentation angle < 140° and I:WT ratio > 110% . CONCLUSIONS: The suggested ESHRE-ESGE cut-off value overestimates the prevalence of septate uterus while that of ASRM underestimates this prevalence, leaving in the gray-zone most of the uteri that experts considered as septate. We recommend considering indentation depth ≥ 10 mm as septate, since the measurement is simple and reliable and this criterion is in agreement with expert opinion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Therapeutic strategies involving uterine stem cells in reproductive medicine.

PURPOSE OF REVIEW: The current review provides an update on recent advances in stem cell biology relevant to female reproduction. RECENT FINDINGS: Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted. Recruitment of stem cells from outside of the uterus occurs in setting of increased demand such as ischemia or injury. Bone marrow-derived multipotent stem cells are recruited to the uterus by estrogen or injury-induced expression of the chemokine CXCL12. In the setting of overwhelming injury, especially in the setting of low estrogen levels, there may be insufficient stem cell recruitment to adequately repair the uterus resulting in conditions such as Asherman syndrome or other endometrial defects. In contrast, excessive recruitment of stem cells underlies endometriosis. Enhanced understanding of stem-cell mobilization, recruitment, and engraftment has created the possibility of improved therapy for endometrial defects and endometriosis through enhanced manipulation of stem-cell trafficking. Further, the normal endometrium is a rich source of multipotent stem cells that can be used for numerous applications in regenerative medicine beyond reproduction. SUMMARY: A better understanding of reproductive stem-cell biology may allow improved treatment of endometrial disease such as Asherman syndrome and other endometrial receptivity defects. Inhibiting stem-cell mobilization may also be helpful in endometriosis therapy. Finally, endometrial derived multipotent stem cells may play a crucial role in cell therapy for regenerative medicine.

No. 249-Asymptomatic Endometrial Thickening.

OBJECTIVE: To formulate clinical recommendations for the assessment of endometrial thickening when it is found on ultrasound in a postmenopausal patient without bleeding. OUTCOMES: Ensure that women with asymptomatic thickening and endometrial polyps found on ultrasound are managed appropriately. EVIDENCE: Published literature was retrieved through searches of English language articles from the EMBASE, Cochrane, and PubMed databases for relevant peer-reviewed articles dating from 1970 to 2009, using appropriate controlled vocabulary (e.g., "asymptomatic endometrial thickness," "endometrial cancer," "postmenopausal bleeding," "transvaginal ultrasonography," "endometrial biopsy" and "endometrial polyp"). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to April 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The level of evidence was determined according to the criteria established by the Canadian Task Force on Preventive Health Care (Table 1). Recommendations are ranked according to this method. BENEFITS, HARMS, AND COSTS: It is anticipated that the adoption of these recommendations would save postmenopausal women unnecessary anxiety, pain, and risk of procedural complication. It is also expected to decrease the cost to the health system by eliminating unnecessary interventions.

Histologic Funisitis and Likelihood of Intrauterine Inflammation or Infection: A Case-Control Study.

OBJECTIVE: The objective of this study was to ascertain the likelihood of isolated maternal fever and suspected intrauterine inflammation or infection or both (Triple I) among cases of histologic chorioamnionitis with funisitis (HCF) at term. STUDY DESIGN: In this case-control study, placental pathology records were reviewed to identify term singleton laboring patients with HCF. Controls (1:1) were matched for gestational age. RESULTS: During the 6-month period, there were 2,399 term deliveries of laboring women. Of 1,552 (65%) term placentas examined, 4% (n = 60) had HCF.Features of Triple I were significantly more common among cases than controls: (1) isolated maternal fever of ≥100.4°F, twice, at least 30 minutes apart (p = 0.014); (2) fever with fetal tachycardia (p = 0.029); 3) fever with either fetal tachycardia or white blood cell count greater than 15,000 per mm3 (p = 0.034). The feature of Triple I with the highest sensitivity at 10% (95% confidence intervals [CI] 4-21%) was isolated maternal fever using ≥100.4°F on two occasions. The specificity for all features was consistently 100% (95% CI 91-100%). CONCLUSION: To our knowledge, this is the first report on HCF and Triple I features. Though the sensitivity of Triple I to identify HCF is low, specificity is excellent.

Impact of opportunistic salpingectomy on anti-Müllerian hormone in patients undergoing laparoscopic hysterectomy: a multicentre randomised controlled trial.

OBJECTIVE: The aim of the study was to investigate whether opportunistic salpingectomy has any deleterious effects on ovarian reserve and increases surgical risk in patients undergoing laparoscopic hysterectomy. DESIGN: A multicentre, randomised controlled trial. SETTING: Three university hospitals in Korea. POPULATION: Sixty-eight patients undergoing laparoscopic hysterectomy for the treatment of symptomatic benign uterine diseases. METHODS: Patients were randomised to undergo either opportunistic salpingectomy (n = 34) or no salpingectomy (n = 34) during laparoscopic hysterectomy. MAIN OUTCOME MEASUREMENTS: The primary and secondary outcome measures were the change of ovarian reserve, determined by the rate of decline in anti-Müllerian hormone (AMH) level from before surgery to 3 months post-surgery and surgical outcomes, respectively. RESULTS: Baseline demographic and clinical characteristics were similar between the two groups. There was also no difference in operative outcomes such as operative time, operative bleeding, or complications between the two groups. In both groups, postoperative AMH levels were significantly lower than preoperative AMH levels (both, P < 0.01). The decline rate in AMH was 12.5% (interquartile range 0.8-60.9%) in the opportunistic salpingectomy group and 10.8% (interquartile range 6.9-27.4%) in the no salpingectomy group, with no significant difference between both groups (P = 0.898). CONCLUSIONS: Opportunistic salpingectomy at the time of laparoscopic hysterectomy did not have any negative effects on ovarian reserve or increased surgical risk. TWEETABLE ABSTRACT: Opportunistic salpingectomy did not have any negative effects on ovarian reserve or increased surgical risk.

Promoting awareness of neonatal menstruation.

Neonatal uterine bleeding (NUB) has been carefully studied in the past through case reports, small series, clinical cohort studies, pathology investigations of fetal and neonatal. Following a historical recount, this review summarizes biological mechanisms conditioning NUB, starting from the persistence till birth of an 'ontogenetic progesterone resistance' (OPR), causing decreased responsiveness of target tissues to bioavailable progesterone. Several pregnancy-related conditions, such as preeclampsia, fetal growth restriction, prematurity, post-maturity and even Rhesus or ABO incompatibility, influence the occurrence of NUB. It seems therefore that the phenomenon is precipitated by chronic fetal distress. When present, OPR may persists until telarche; as a consequence, if pregnancy occurs in early teenage, the disorder known as "defective deep placentation" may ensue, increasing the risk of obstetrical syndromes. In the presence of NUB, retrograde shedding into the peritoneal cavity of endometrial stem/progenitor and niche cells may occur. There, given the right environment, these cells can survive and become activated at the time of telarche, causing the specific phenotype of early-onset endometriosis. In conclusion, neonatal menstruation is a fetal distress indicator and can alter the incidence of a variety of pathological conditions later in life. For this reason, it should be carefully recorded and the parents informed.

Strategies to manage refractory endometrium: state of the art in 2016.

The endometrium is one of a number of factors involved in achieving optimal outcomes after assisted reproductive treatment. Owing to its "passive" growth following adequate ovarian stimulation, it has received virtually no attention. Only when either endometrial thickness or ultrasonographic pattern seem inadequate have different strategies been assessed to try to improve it, especially in those cases where it seems difficult or impossible to make it grow. The objective of this review is to summarize the different strategies that have been investigated in patients with inadequate endometrium, to attempt to provide solid evidence of therapies that may be beneficial and to move away from empirism. A review of the existing literature was performed by searching MEDLINE, EMBASE, Cochrane library and Web of Science for publications in English related to refractory endometrium. Most current treatments are based on anecdotal cases and not on solid data, although worldwide many doctors and patients use them. In conclusion, this review found that it is not easy to provide a pragmatic, evidence-based approach to help physicians and patients confused by the available data on how to improve a poor endometrium. Honest balanced information provided to our patients is the best that we can do.

Carryover effect of postpartum inflammatory diseases on developmental biology and fertility in lactating dairy cows.

The objective of this series of studies was to investigate the effects of inflammatory diseases occurring before breeding on the developmental biology and reproductive responses in dairy cows. Data from 5 studies were used to investigate different questions associating health status before breeding and reproductive responses. Health information for all studies was composed of the incidence of retained fetal membranes, metritis, mastitis, lameness, and respiratory and digestive problems from parturition until the day of breeding. Retained placenta and metritis were grouped as uterine disease (UTD). Mastitis, lameness, digestive and respiratory problems were grouped as nonuterine diseases (NUTD). Study 1 evaluated the effect of disease before artificial insemination (AI), anovulation before synchronization of the estrous cycle, and low body condition score at AI on pregnancy per AI, as well as their potential interactions or additive effects. Study 2 investigated the effect of site of inflammation (UTD vs. NUTD) and time of occurrence relative to preantral or antral stages of ovulatory follicle development, and the effect of UTD and NUTD on fertility responses of cows bred by AI or by embryo transfer. Study 3 evaluated the effect of disease on fertilization and embryonic development to the morula stage. Study 4 evaluated the effect of disease on preimplantation conceptus development as well as secretion of IFN-τ and transcriptome. Study 5 investigated the effect of diseases before AI on the transcript expression of interferon-stimulated genes in peripheral blood leukocytes during peri-implantation stages of conceptus development after first AI postpartum. Altogether, these studies demonstrated that inflammatory disease before breeding reduced fertilization of oocytes and development to morula, and impaired early conceptus development to elongation stages and secretion of IFN-τ in the uterine lumen. Diseases caused inflammation-like changes in transcriptome of conceptus cells, increased risk of pregnancy loss, and reduced pregnancy or calving per breeding. Moreover, the effects on reproduction were independent of cyclic status before synchronization of the estrous cycle and body condition score at breeding, which all had additive negative effects on fertility of dairy cows. Occurrence of disease at preantral or at antral stages of ovulatory follicle development had similar detrimental effects on pregnancy results. The carryover effects of diseases on developmental biology might last longer than 4 mo. Reduced oocyte competence is a likely reason for carryover effects of diseases on developmental biology, but impaired uterine environment was also shown to be involved.

Laparoscopic supracervical hysterectomy with transcervical morcellation: our experience.

STUDY OBJECTIVE: To present our experience with laparoscopic supracervical hysterectomy with transcervical morcellation (LSH-TM). DESIGN: A retrospective observational study (Canadian Task Force Classification III). SETTING: Gynecologic Department at Brunico Hospital, Brunico, Italy. PATIENTS: Three hundred sixty-five patients affected by gynecologic benign diseases who underwent LSH-TM. INTERVENTIONS: A minimally invasive surgical technique for supracervical hysterectomy that involves extraction of the morcellated uterus through the cervical canal. MEASUREMENTS AND MAIN RESULTS: We performed LSH-TM successfully in 365 patients; the mean (standard deviation) operating time was 72.24 (23.21) minutes. We registered no intraoperative complications. The main postoperative complications resulted in 2 cases of second-look laparoscopy because of internal bleeding, 5 cases of asymptomatic hematoma around the cervical stump, and 7 cases of pelvic pain. CONCLUSION: Our experience shows that LSH-TM is a safe and easy to perform technique and that it ensures minimal blood loss.

Subendometrial blood flow changes by 3-dimensional power Doppler ultrasound after hysteroscopic lysis of severe intrauterine adhesions: preliminary study.

OBJECTIVE: To evaluate the changes in subendometrial blood flow and endometrial volume after hysteroscopic lysis of severe intrauterine adhesions (IUAs). DESIGN: A pilot observational study. Forty infertile women with severe IUAs served as their own controls and were included in this study only once, to avoid selection bias. INTERVENTION: Three-dimensional power Doppler ultrasound was performed in all patients 1 day before hysteroscopic lysis of severe IUA, and repeated 1 month later, to assess subendometrial blood flow [as measured by vascularization index (VI), flow index (FI), and vascularization flow index (VFI)] and endometrial volume. Main outcome measures were subendometrial blood flow (VI, FI, VFI) and endometrial volume. RESULTS: There were statistically significant postoperative increases in endometrial volume, VI, FI, and VFI. Subendometrial blood flow improved in 14 women (35%), and menstrual improvement occurred in 15 women (37.5%). CONCLUSION: Hysteroscopic lysis of severe IUAs improves subendometrial blood flow, with subsequent increases in endometrial volume.

Intrauterine endometriotic cyst at the site of previous cesarean scar; scar endometriosis.

Uterine scar endometriosis is an extremely rare entitiy. As the surgical procedures of the uterus increases through time, scar endometriosis may be diagnosed more often in the future. A case of uterine scar endometriosis is presented with complaints of menstruation lasting one day with associated pelvic pain. When a cystic mass in the site of previous surgery is diagnosed, scar endometriosis must be considered.

Endometrial beta3 integrin profile reflects endometrial receptivity defects in women with unexplained recurrent pregnancy loss.

BACKGROUND: The pathophysiology of recurrent pregnancy loss (RPL) is still unknown in 50% of the cases. Herein we measure the expression of beta3 integrin subunit, a well-known implantation marker, in women with or without RPL and correlate it with the histological dating of the endometrial tissue. METHODS: LH-timed endometrial biopsies were obtained from cases (RPL; n = 21, age 33.9+/-4.7) and healthy controls (n = 29; age 29.8+/-4.1) during the mid-secretory phase (post ovulatory day: 8 to 10). Endometrial samples were timed histologically according to Noyes' criteria and underwent immunohistochemical staining for beta3 integrin expression. For statistical analysis the semi-quantitative HSCORE was assessed. Type I (beta3 negative in an out-of-phase endometrium) and Type II defect (beta3 negative in an in-phase endometrium) were also analysed. Statistical analysis was done with Student t-test, Mann Whitney U test, ANCOVA and chi square for trend. Significance was set as P < 0.05. RESULTS: The mean (SD) age in controls was lower compared to cases [(29.8 (4.1) vs. 33.9 (4.7) - P = 0.001; Student t-test)]. The median (range) expression of beta3 integrin in controls and cases was 1.94 (0 to 3.5) vs. 0.82 (0 to 3.6), respectively (P = 0.001; Mann Whitney U test). Significance was still significant after adjusting for age (P = 0.03;ANCOVA). The normal positive staining > =0.7 of beta3 integrin subunit and in-phase endometrium was seen in 24 out of 29 (82.8%) controls, but in only 6 out of 21 (28.6%) of cases with RPL; Type I and II defects were seen in 10.3 and 6.9% of controls, while present in 52.4 and 19.1% of cases, respectively (P = 0.0005; chi-square). CONCLUSIONS: Women with unexplained RPL had significantly reduced integrin expression compared to controls. Our findings underline the need for further molecular analysis of endometrial tissue in affected women.