Potential anatomical determinants of retrograde menstruation: a comprehensive narrative review.

A century ago, Sampson identified three uterine anatomical structures that may determine the amount of retrograde menstruation and the likelihood of the development of endometriosis: the cervix, the intramural portion of the fallopian tubes, and the myometrium. Critical appraisal was undertaken of data published over the last 40 years on the potential effect of the characteristics of these three anatomical variables on the risk of endometriosis. There is some evidence to support the pathogenic role of the diameter of the cervical canal, stenosis of internal or external orifices, and stiffness of cervical tissue. One study showed a significant association between the morphology of the intramural tubal tract and the frequency of endometriosis. A large body of evidence points to abnormalities of the myometrial structure as the anatomical aberration most consistently associated with endometriosis. These abnormalities have largely been interpreted as signs of early-onset adenomyosis, which may precede endometriosis and even lead to its development by increasing the amount of retrograde menstruation. Future research should aim to verify whether a positive relationship exists between the substantially increased number of ovulatory menses occurring in the decade following menarche, the development of anatomical myometrial abnormalities, changes in the amount of retrograde menstruation over time, and the risk of endometriosis.

The G-Protein-Coupled Estrogen Receptor Selective Agonist G-1 Attenuates Cell Viability and Migration in High-Grade Serous Ovarian Cancer Cell Lines.

The G-protein-coupled estrogen receptor (GPER; G-protein-coupled estrogen receptor 30, also known as GPR30) is a novel estrogen receptor and has emerged as a promising target for ovarian cancer. GPER, a seven-transmembrane receptor, suppresses cellular viability and migration in studied ovarian cancer cells. However, its impact on the fallopian tube, which is the potential origin of high-grade serous (HGSC) ovarian cancer, has not been addressed. This study was conducted to evaluate the relationship of GPER, ovarian cancer subtypes, i.e., high-grade serous cell lines (OV90 and OVCAR420), as well as the cell type that is the potential origin of HGSC ovarian cancer (i.e., the fallopian tube cell line FT190). The selective ligand assessed here is the agonist G-1, which was utilized in an in vitro study to characterize its effects on cellular viability and migration. As a result, this study has addressed the effect of a specific GPER agonist on cell viability, providing a better understanding of the effects of this compound on our diverse group of studied cell lines. Strikingly, attenuated cell proliferation and migration behaviors were observed in the presence of G-1. Thus, our in vitro study reveals the impact of the origin of HGSC ovarian cancers and highlights the GPER agonist G-1 as a potential therapy for ovarian cancer.

Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro.

RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease initiation and progression. Here, we established organoids from primary human FTE and introduced TP53 as well as RAD51D knockdown to enable the exploration of their mutational impact on FTE lesion generation. We observed that TP53 deletion rescued the adverse effects of RAD51D deletion on the proliferation, stemness, senescence, and apoptosis of FTE organoids. RAD51D deletion impaired the homologous recombination (HR) function and induced G2/M phase arrest, whereas concurrent TP53 deletion mitigated G0/G1 phase arrest and boosted DNA replication when combined with RAD51D mutation. The co-deletion of TP53 and RAD51D downregulated cilia assembly, development, and motility, but upregulated multiple HGSOC-associated pathways, including the IL-17 signaling pathway. IL-17A treatment significantly improved cell viability. TP53 and RAD51D co-deleted organoids exhibited heightened sensitivity to platinum, poly-ADP ribose polymerase inhibitors (PARPi), and cell cycle-related medication. In summary, our research highlighted the use of FTE organoids with RAD51D mutations as an invaluable in vitro platform for the early detection of carcinogenesis, mechanistic exploration, and drug screening.

Exploring the presence of markers of decidualization in the fallopian tubes: a systematic review.

The fallopian tubes (FTs) are part of the female upper genital tract. The healthy FT provides the biological environment for successful fertilization and facilitates the subsequent movement of the conceptus to the endometrial cavity. However, when the FT is damaged, as with salpingitis, pyosalpinx, and hydrosalpinx, it may increase the risk of an ectopic pregnancy, a life-threatening condition. Decidualization refers to a multifactorial process by which the endometrium changes to permit blastocyst implantation. The decidualization reaction is vital for endometrial receptivity during the window of implantation. To date, no comprehensive review that collates evidence on decidualization in the human FT has been conducted. Therefore, the aim of this review is to compile the current evidence on cellular decidualization occurring in the healthy and pathological FT in women of reproductive age. A literature search was conducted using five databases and identified 746 articles, 24 of which were analyzed based on inclusion and exclusion criteria. The available evidence indicates that the FT are able to undergo decidual changes under specific circumstances; however, the exact mechanism by which this occurs is poorly understood. Further research is needed to elucidate the mechanism by which decidualization can occur in the FT.

The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial.

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. METHODS: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. DISCUSSION: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. TRIAL REGISTRATION NUMBER: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).

Prospective comparative trial comparing O-RADS, IOTA ADNEX model, and RMI score for preoperative evaluation of adnexal masses for prediction of ovarian cancer.

INTRODUCTION: Preoperative assessment of ovarian tumors to distinguish between benign and malignant is important. At this time, many diagnostic models were available and the popularity of the risk of malignancy index (RMI) in Thailand is still high. The IOTA Assessment of Different NEoplasias in adneXa (ADNEX) model and the Ovarian-Adnexal Reporting and Data System (O-RADS) model were both new models with good performance. OBJECTIVES: The purpose of this study was to compare O-RADS, RMI, and ADNEX models. DESIGN: This diagnostic study was performed using data from the prospective study. METHODS: Data from 357 patients from a previous study were included and calculated using the RMI-2 formula then applied to the O-RADS system and the IOTA ADNEX model. The diagnostic significance of the results was evaluated by receiver operating characteristic (ROC) analysis and pairwise comparison between models was made. RESULTS: The area under the receiver operating characteristic curve (AUC) to distinguish an adnexal mass as a benign or malignant tumor was 0.975 (95% CI, 0.953-0.988) for the IOTA ADNEX model; 0.974 (95% CI, 0.960-0.988) for O-RADS; 0.909 for RMI-2 (95% CI, 0.865-0.952). There were no differences in pairwise AUC comparisons between the IOTA ADNEX and O-RADS models, and both were better than those of RMI-2. CONCLUSIONS: The IOTA ADEX and O-RADS models are excellent tools for distinguishing the adnexal mass in the preoperative assessment and were better than RMI-2. The use of one of these models is recommended.

Trends in female sterilisations in New South Wales, 2010-2019.

BACKGROUND: Female sterilisation remains a common contraceptive method in many countries. AIMS: The aim is to analyse the recent changes in the incidence of female sterilisation in New South Wales (NSW). METHODS: Data were obtained from the NSW Admitted Patients Data Collection for all female patients who had undergone one of the five sterilisation procedures in a public or private hospitals in NSW during 2010 and 2019. Denominators for calculating sterilisation rates were estimated using census and other population data. RESULTS: The number of sterilisation cases dropped from 3407 in 2010 to 2561 in 2019, and the sterilisation rate declined from 22.6 per 10 000 females aged 20-49 in 2010 to 15.4 in 2019. Incidence was at its peak in the 35-39 age group in both years. Indigenous females had higher sterilisation rates than non-Indigenous females born in Australia or overseas. While some foreign-born females had higher sterilisation rates than for those who were in Australia or overseas on average their rates were lower than those who were born in Australia or overseas. There was a clear socio-economic gradient such that females living in the most disadvantaged areas had much higher sterilisation rates than those living in the least disadvantaged areas. The Indigenous, ethnic and socio-economic differences in sterilisation rates persisted in both years of this study. CONCLUSION: Although fertility rates in NSW changed little over the 10-year interval a steady decline in sterilisation occurred, consistent with other forms of contraception (particularly long-acting reversible types) increasing concurrently in popularity.

The cost-effectiveness of transvaginal hydrolaparoscopy versus hysterosalpingography in the work-up for subfertility.

STUDY QUESTION: Is a strategy starting with transvaginal hydrolaparoscopy (THL) cost-effective compared to a strategy starting with hysterosalpingography (HSG) in the work-up for subfertility? SUMMARY ANSWER: A strategy starting with THL is cost-effective compared to a strategy starting with HSG in the work-up for subfertile women. WHAT IS KNOWN ALREADY: Tubal pathology is a common cause of subfertility and tubal patency testing is one of the cornerstones of the fertility work-up. Both THL and HSG are safe procedures and can be used as a first-line tubal patency test. STUDY DESIGN, SIZE, DURATION: This economic evaluation was performed alongside a randomized clinical trial comparing THL and HSG in 300 subfertile women, between May 2013 and October 2016. For comparisons of THL and HSG, the unit costs were split into three main categories: costs of the diagnostic procedure, costs of fertility treatments and the costs for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subfertile women scheduled for tubal patency testing were eligible. Women were randomized to a strategy starting with THL or a strategy starting with HSG. The primary outcome of the study was conception leading to a live birth within 24 months after randomization. The mean costs and outcomes for each treatment group were compared. We used a non-parametric bootstrap resampling of 1000 re-samples to investigate the effect of uncertainty and we created a cost-effectiveness plane and cost-effectiveness acceptability curves. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 149 women to THL and 151 to HSG, and we were able to achieve complete follow-up of 142 versus 148 women, respectively. After the fertility work-up women were treated according to the Dutch guidelines and based on a previously published prognostic model. In the THL group, 83 women (58.4%) conceived a live born child within 24 months after randomization compared to 82 women (55.4%) in the HSG group (difference 3.0% (95% CI: -8.3 to 14.4)). The mean total costs per woman were lower in the THL group compared to the HSG group (THL group €4991 versus €5262 in the HSG group, mean cost difference = -€271 (95% CI -€273 to -€269)). Although the costs of only the diagnostic procedure were higher in the THL group, in the HSG group more women underwent diagnostic and therapeutic laparoscopies and also had higher costs for fertility treatments. LIMITATIONS, REASONS FOR CAUTION: Our trial was conducted in women with a low risk of tubal pathology; therefore, the results of our study are not generalizable to women with high risk of tubal pathology. Furthermore, this economic analysis was based on the Dutch healthcare system, and possibly our results are not generalizable to countries with different strategies or costs for fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: After 2 years of follow-up, we found a live birth rate of 58.4% in the THL group versus 55.4% in the HSG group and a lower mean cost per woman in the THL group, with a cost difference of -€271. The findings of our trial suggest that a strategy starting with THL is cost-effective compared to a strategy starting with HSG in the workup for subfertile women. However, the cost difference between the two diagnostic strategies is limited compared to the total cost per woman in our study and before implementing THL as a first-line strategy for tubal patency testing, more research in other fields, such as patient preference and acceptance, is necessary. STUDY FUNDING/COMPETING INTEREST(S): The authors received no external financial support for the research. B.W.J.M. is supported by an NHMRC Investigator Grant (GNT1176437). B.W.J.M. reports consultancy for ObsEva, Merck KGaA, Guerbet. B.W.J.M. reports receiving travel support from Merck KGaA. C.T.P. reports consultancy for Guerbet, outside of this manuscript. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: NTR3462.

Magnetic resonance imaging characteristics of polypoid endometriosis and review of the literature.

AIM: Polypoid endometriosis is a rare variant of endometriosis and may mimic malignancy. The purpose of this study is to evaluate magnetic resonance (MR) imaging characteristics of polypoid endometriosis for the differential diagnosis with malignancy. METHODS: MR imaging findings of four histologically proven polypoid endometriosis were retrospectively evaluated with the review of the literature. RESULTS: All polypoid endometriosis exhibited high signal intensity on T2-weighted images reflecting abundant dilated endometrial glands. Peritoneal lesions were surrounded by low signal intensity rim represented the "black rim sign" reflecting endometriotic fibrous adhesion. Two cases arising from endometriotic cysts showed transmural extension (peritoneal extension and myometrial infiltration). Endometriotic hemorrhagic foci were demonstrated in four lesions as high signal intensity on T1-weighted images and/or susceptibility-induced signal voids on susceptibility-weighted MR sequence. Diffusion-weighted images showed high signal intensity with relatively high apparent diffusion coefficient (ADC) due to T2 shine-through effect but no diffusion restriction, and dynamic contrast-enhanced (DCE) MR imaging showed gradually increasing contrast-enhancement pattern like benign pathologies. CONCLUSIONS: Polypoid endometriosis may mimic malignancy; however, black rim sign may be a characteristic MR imaging finding for the peritoneal lesions, and no diffusion restriction and gradually increasing contrast-enhancement pattern may reflect its benign nature.

Ovarian cancer risk after salpingectomy for ectopic pregnancy or hydrosalpinx: results of the OCASE nationwide population-based database study.

STUDY QUESTION: What is the effect of salpingectomy for ectopic pregnancy or hydrosalpinx at a young age on ovarian cancer risk compared to no salpingectomy for any reason? SUMMARY ANSWER: We found no significant reduction in ovarian cancer risk after salpingectomy for ectopic pregnancy or hydrosalpinx. WHAT IS KNOWN ALREADY: Salpingectomy may reduce ovarian cancer incidence, although the lag-time between intervention and therapeutic effect remains to be elucidated. STUDY DESIGN, SIZE, DURATION: This nationwide population-based database study uses the Dutch pathology database to identify all women who underwent salpingectomy for ectopic pregnancy or hydrosalpinx between January 1990 and December 2012 and compared ovarian cancer incidence to a control group of women who had a benign dermal nevus removed, matched for age at the time and year of procedure. PARTICIPANTS/MATERIALS, SETTING, METHODS: After selection and manual control of intervention and control group, ovarian cancer incidence was recorded. Hazard ratios (HRs) with 95% CI for the development of ovarian cancer were calculated with Cox regression analyses, both unadjusted and adjusted for age. Subgroup analyses were performed to investigate lag-time between intervention and protective effect. MAIN RESULTS AND THE ROLE OF CHANCE: In all, 18 961 women were included in the intervention group; 17 106 women had a unilateral salpingectomy and 1855 had a bilateral salpingectomy. The control group consisted of 23 686 women. With 14 ovarian cancer cases in the intervention group, the incidence rate (IR) of ovarian cancer was 5.4 (95% CI 3.1-8.9) per 100 000 person-years. In the control group, there were 24 ovarian cancer cases, resulting in an IR of 7.1 (95% CI 4.7-10.5) per 100 000 person-years (P = 0.34). The age-adjusted HR for ovarian cancer was 0.76 (95% CI 0.39-1.47) after salpingectomy. Unilateral salpingectomy resulted in an age-adjusted HR of 0.81 (95% CI 0.41-1.59) and bilateral salpingectomy resulted in an age-adjusted HR of 0.43 (95% CI 0.06-3.16) based on one case. None of our subgroup analysis for lag-time resulted in a significant difference in ovarian cancer incidence between intervention and control group. The difference in ovarian cancer incidence appeared largest in women with at least 8 years of follow-up (P = 0.08). LIMITATIONS, REASONS FOR CAUTION: Due to the young population, ovarian cancer incidence is low, even at the end of follow-up. Furthermore, due to the anonymous nature of the pathology registry, we were unable to adjust for confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: Although results did not reach statistical significance, they add to the available data on ovarian cancer incidence after salpingectomy. Our subgroup analysis suggests there may be no benefit in the first years following salpingectomy. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

Therapeutic effects of hysterosalpingography contrast media in infertile women: what do we know about the H2O in the H2Oil trial and why does it matter?

Recent interest in the use of oil-soluble contrast media (OSCM) for hysterosalpingography (HSG) and other tubal flushing procedures is largely the result of publication of the large, multicentre, randomized controlled H2Oil trial in the New England Journal of Medicine in 2017, addressing the long-held suspicion that pregnancy rates following HSG with OSCM are higher than if a water-soluble contrast media (WSCM) is used. However, the findings of this trial have been compromised by the WSCM selected for comparison with OSCM. The chosen WSCM belongs to a superceded class of ionic media, with an iodine concentration, osmolality and viscosity all lying at the extreme end of the range for water-soluble radiographic contrast. The requirement for safe, cheap, versatile WSCM for intravascular use during computerized tomography, angiography and interventional procedures has resulted in considerable refinement of WSCM, with current widespread use of non-ionic, low osmolality or iso-osmolar WSCM in radiology, including for HSG. However, the use of the earlier ionic, high osmolality agents such as that selected for the H2Oil trial persists for HSG in some centres, despite potential adverse effects on the endometrium and fallopian tubal epithelium compared with more modern, less toxic WSCM. Knowledge of the variety of physical and chemical characteristics of the available WSCM is essential for interpretation of the current literature and establishing the most effective and safe water-soluble agent to use for HSG. Design of future clinical trials to establish the potential superiority of OSCM over WSCM for fertility enhancement must include the use of the readily available, inexpensive modern WSCM. While the fertility rates following OSCM HSG have been shown to be high in women with idiopathic infertility, more robust trials are required before the widespread use of OSCM for HSG or other modalities such as ultrasound and laparoscopy should be adopted.

Impact of severe acute respiratory syndrome coronavirus 2 on ectopic pregnancy management in the United Kingdom: a multicentre observational study.

OBJECTIVE: To describe the impact of coronavirus disease 2019 (COVID-19) on the management of women with ectopic pregnancy. DESIGN: A multicentre observational study comparing outcomes from a prospective cohort during the pandemic [COVID-19-ectopic pregnancy registry (CEPR)] compared with a historical pre-pandemic cohort [non-COVID-19-ectopic pregnancy registry (NCEPR)]. SETTING: Five London university hospitals. POPULATION AND METHODS: Consecutive patients diagnosed clinically and/or radiologically with ectopic pregnancy (March 2020-August 2020) were entered into the CEPR and results were compared with the NCEPR cohort (January 2019-June 2019). An adjusted analysis was performed for potentially confounding variables. MAIN OUTCOME MEASURES: Patient demographics, management (expectant, medical and surgical), length of treatment, number of hospital visits (non-surgical management), length of stay (surgical management) and 30-day complications. RESULTS: Three hundred and forty-one women met the inclusion criteria: 162 CEPR and 179 NCEPR. A significantly lower percentage of women underwent surgical management versus non-surgical management in the CEPR versus NCEPR (58.6%; 95/162 versus 72.6%; 130/179; P = 0.007). Among patients managed with expectant management, the CEPR had a significantly lower mean number of hospital visits compared with NCEPR (3.0, interquartile range [IQR] [3, 5] versus 9.0, [5, 14]; P = <0.001). Among patients managed with medical management, the CEPR had a significantly lower median number of hospital visits versus NCEPR (6.0, [5, 8] versus 9, [6, 10]; P = 0.003). There was no observed difference in complication rates between cohorts. CONCLUSION: Women were found to undergo significantly higher rates of non-surgical management during the COVID-19 first wave compared with a pre-pandemic cohort. Women managed non-surgically in the CPER cohort were also managed with fewer hospital attendances. This did not lead to an increase in observed complication rates. TWEETABLE ABSTRACT: A higher rate of non-surgical management of ectopic pregnancy during the COVID-19 pandemic did not increase complication rates.

Is Chronic Endometritis Associated with Tubal Infertility? A Prospective Cohort Study.

STUDY OBJECTIVE: Chronic endometritis (CE), which often presents asymptomatically, is associated with recurrent pregnancy loss, recurrent implantation failure after in vitro fertilization, and endometriosis. Data connecting CE with fallopian tubal occlusion are limited. The aim was to assess a potential association of CE, defined by the presence of syndecan-1 (CD138)-positive plasma cells in endometrial tissue samples, with fallopian tube patency and other factors for infertility, including endometriosis, adenomyosis, and hydrosalpinges. DESIGN: Prospective, monocentral pilot study. SETTING: Tertiary care center. PATIENTS: A cohort of 100 women who were infertile was enrolled from July 2019 to December 2020. INTERVENTIONS: Hysteroscopy with endometrial biopsy and laparoscopy with chromopertubation. MEASUREMENTS AND MAIN RESULTS: CE was found in 13 women (13.0%) and was associated with endometriosis (p = .034) and unilateral/bilateral fallopian tube blockage (p = .013). In women with endometriosis, the mean number of CD138-positive cells was positively correlated with the revised American Society for Reproductive Medicine score (r = .302, p = .028). In a binary regression model, the presence of a hydrosalpinx on one or both sides (odds ratio 15.308; 95% confidence interval, 1.637-143.189; p = .017) and the finding of CE in the endometrial tissue sample (odds ratio 5.273; 95% confidence interval, 1.257-22.116; p = .023) were significantly associated with fallopian tubal occlusion. CONCLUSION: CE was significantly associated with blockage of the fallopian tubes and endometriosis. Endometriosis stage was associated with the number of CD138-positive cells in endometrial biopsies.

Detection of hysteroscopic fluid in the pouch of Douglas: a prospective cohort study about the predictability of bilateral tubal occlusion.

PURPOSE: To determine whether an increase in cul de sac (CDS) fluid after hysteroscopy is predictive of tubal patency. METHODS: In a prospective clinical cohort study, 115 subfertile women undergoing laparoscopic and hysteroscopic surgery at the Medical University of Vienna were invited to participate. The primary outcome was determining whether an increase in fluid in the pouch of Douglas was reflective of unilateral or bilateral tubal patency. Vaginal sonography before and after hysteroscopy was performed to detect fluid in the pouch of Douglas, directly followed by laparoscopy with chromopertubation. RESULTS: Laparoscopic chromopertubation revealed bilateral Fallopian tube occlusion in 28 women (24.3%). Twenty-seven/40 patients (67.5%) with no fluid shift had bilateral occlusion during the consecutive laparoscopy (p < 0.001). One/75 patients (1.3%) showing a fluid shift had bilateral occlusion (sensitivity of a present fluid shift for uni- or bilateral patency 85.1%, 95% CI: 81.7-99.9, specificity: 96.4%, 95% CI: 75.8-91.8). Intracavitary abnormalities (odds ratio, OR, 0.038; p = 0.030) and adhesions covering one or both tubes (OR 0.076; p = 0.041) increased the risk for a false abnormal result, i.e., uni- or bilateral tubal patency despite the lack of a fluid shift. CONCLUSION: When CDS fluid does not change after hysteroscopy, this is a sensitive test for tubal occlusion and further testing may be warranted. However, if there is an increase in CDS fluid after hysteroscopy, particularly for a patient without fluid present prior, this is both sensitive and specific for unilateral or bilateral tubal patency.

Repeated hyperstimulation affects the ultrastructure of mouse fallopian tube epithelium.

Controlled ovarian hyperstimulation (COH) is routinary used in assisted reproductive technologies (ARTs) to increase the yields of mature oocytes. The possibility that patients with a history of failures or poor-responders may develop side-effects following these treatments is still debated. Epidemiological studies reported controversial results about pregnancy outcome and the risk of developing gynecological cancers. By using a mouse model, here we compared the ultrastructural features of fallopian tubes (FTs) obtained from mice undergoing or not (control, CTR) four (4R) and eight (8R) rounds of gonadotropin stimulation. Although the morphological characteristics of oviductal layers seemed unaffected by repeated treatments, dose-response ultrastructural alterations in the ampulla appeared in the 4R group and even more in the 8R group. The targets were oviductal ciliated (CCs) and non-ciliated (NCCs) cells, which showed damaged mitochondria and glycogen accumulations in the cytoplasm. The drastic reduction of CCs, evident after 4R, was supported by the absence of cilia. After 8R, glycogen granules were significantly reduced and massive degeneration of mitochondria, which appeared swollen and/or vacuolated, occurred in NCCs. Moreover, disintegrated mitochondria were found at the periphery of mitophagic vacuoles with evident signs of cristolysis. The morphometric analysis evidenced a significant increase in the density and frequency of damaged mitochondria after 4R and 8R. The absence of cilia, necessary to sustain oviductal transport of oocytes, spermatozoa and embryos, may originate from either mitochondrial dysfunction or glycogen consumption. These results suggest that repeated COH treatments could induce alterations impairing fertilization and embryo transport toward the uterus.

Assessment of Tubal Patency: A Prospective Comparison of Diagnostic Hysteroscopy and Laparoscopic Chromopertubation.

STUDY OBJECTIVE: To evaluate whether the presence of a visualizable "flow" effect in the fallopian tube ostia in hysteroscopy was predictive of tubal patency. DESIGN: A prospective cohort study. SETTING: In a prospective study, infertile women who underwent surgery because of infertility between March and November 2018 were included. The main outcome parameter was fallopian tube patency assessed by laparoscopic chromopertubation. The predictive parameter tested was the presence of hysteroscopic tube flow. PATIENTS: Seventy-two infertile women. INTERVENTIONS: Combined hysteroscopy and laparoscopy with chromopertubation. RESULTS: One-hundred forty-four fallopian tubes were evaluated, with 88 (61.1%) patent tubes at laparoscopic chromopertubation. A positive hysteroscopic flow effect was recorded for 94 (65.3%) ostia and was accurate in predicting patency (p < .001), with a sensitivity of 85.3% (95% confidence interval [CI], 76.1-91.9) and a specificity of 66.1% (95% CI, 52.2-78.2). A multivariate binary regression model revealed that the presence of a hydrosalpinx (odds ratio = 8.216; 95% CI, 1.062-63.574; p = .044) and peritubal adhesions (odds ratio = 3.439; 95% CI, 1.142-10.353; p = .028) were associated with a false-normal flow result. A hazy hysteroscopic picture was found in 15 of 21 (71.4%) and 5 of 51 (9.8%) cases with and without bilateral tubal occlusion, respectively (p < .001, sensitivity = 71.4% [95% CI, 47.8-88.7], specificity = 90.2% [95% CI, 78.6-96.7]). CONCLUSIONS: The presence of hysteroscopic tubal flow was a reliable indicator of tubal patency. A hydrosalpinx or peritubal adhesions increase the risk for a false-normal result. A hazy hysteroscopic picture suggests bilateral tubal occlusion. Using the hysteroscopic flow effect, one can provide additional information for the patient.

Hysteroscopic Assessment of Tubal Patency: A Randomized Comparison between the Flow and Parryscope Techniques.

STUDY OBJECTIVE: To evaluate the accuracy of the "Parryscope" and "flow" techniques for hysteroscopic assessment of tubal patency. DESIGN: Prospective randomized clinical trial. SETTING: From May to October 2019, women with subfertility undergoing laparoscopic and hysteroscopic surgery at the Medical University of Vienna were invited to participate in the study. The primary outcome was accuracy of Fallopian tube patency relative to the gold standard of laparoscopic chromopertubation. PATIENTS: Sixty women with subfertility. INTERVENTIONS: Hysteroscopy with either the "Parryscope" or the "flow" techniques for tubal assessment, directly followed by laparoscopy with chromopertubation. MEASUREMENTS AND MAIN RESULTS: Hysteroscopic prediction of fallopian tube patency was possible in a statistically significant manner in both study groups (p <0.05). The Parryscope technique achieved higher sensitivity (90.6%, 95% CI: 61.7-98.4) and specificity (100%, 95% CI: 90.0-100.0) than the flow technique (sensitivity: 73.7%, 95% CI: 48.8-90.9 and specificity: 70.7%, 95% CI: 54.5-83.9). CONCLUSION: Using the Parryscope technique to determine if air bubbles traverse the ostia can provide valuable additional information during hysteroscopy and is more accurate in predicting fallopian tubal occlusion than the flow method.

Comparison between magnetic resonance hysterosalpingography and conventional hysterosalpingography: direct visualization of the fallopian tubes using a novel MRI contrast agent mixture.

BACKGROUND: Magnetic resonance hysterosalpingography (MR-HSG) is a promising technique in the work-up of female infertility. Few existing MR-HSG studies focus on the comparison between MR-HSG with gold standard examination. PURPOSE: To compare the diagnostic value of MR-HSG with conventional HSG in patients receiving both exams in one day. MATERIAL AND METHODS: This study included 33 infertile women who completed pelvic MR scanning, HSG, and MR-HSG in that order. A traditional HSG contrast agent (iohexol) and a magnetic resonance imaging (MRI) contrast agent (1 mL gadopentetate dimeglumine (Gd-DTPA) blended with 100 mL iohexol) were used to achieve image enhancement. Inter-observer and inter-modality agreements of HSG and MR-HSG exams were assessed. The results were calculated by using the kappa test. Three radiologists who were blinded to the clinical data independently reviewed the MR images. Extratubal abnormalities were analyzed. RESULTS: A total of 62 fallopian tubes of 33 women were included in the study. MR-HSG imaging findings to depict tubal patency were similar to these of HSG (AUC 0.911, sensitivity 0.821, specificity 1.000, positive predictive values 1.000, and negative predictive values 0.872). Pairwise inter-observer agreement among three observers and inter-modality agreement of the diagnosis were excellent (mean kappa 0.863 and 0.835, respectively). In addition, 29 extratubal abnormalities in 21 patients were found on pelvic MR scanning. CONCLUSION: MR-HSG and HSG demonstrated similar results in assessing tubal patency. Because it offers the comprehensive assessment of female pelvic structures, and avoids ionizing radiation, MR-HSG may be used as an alternative imaging technique for evaluation of female infertility.