Transvaginal Sonography for the Preoperative Assessment of Parametrial Deep Infiltrating Endometriosis: A Diagnostic Accuracy Study.

OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy for parametria endometriosis (PE) of transvaginal sonography (TVS) performed following a systematic approach for the assessment of the lateral parametria. DESIGN: A diagnostic accuracy study was employed based on a prospective observational design. PARTICIPANTS: All consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020 were considered. SETTING: The study was conducted at endometriosis referral hospitals. METHODS: We prospectively collected clinical, imaging, and surgical data of all consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020. A standardized technique with a systematic approach for the assessment of the lateral parametria following specific anatomic landmarks was used for the TVS. The diagnostic accuracy for PE in TVS was assessed using the intraoperative and pathologic diagnosis of PE as the gold standard. RESULTS: In 476 patients who underwent surgery, PE was identified in 114 out of 476 patients (23.95%): 91 left and 54 right PE out of 476 surgical procedures were identified (19.12% vs. 11.34%; p = 0.001); bilateral involvement in 27.19% (31/114 patients) cases. The sensitivity of TVS for PE was 90.74% (79.70-96.92%, 95% CI) for the right side and 87.91% (79.40-93.81%, 95% CI) for the left side. The specificity was almost identical for both sides (98.58% vs. 98.18%). For the right parametrium, the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 63.82 (28.70-141.90, 95% CI) and 0.09 (0.04-0.22, 95% CI), respectively. On the left parametrium, the PLR and NLR were 48.35 (23.12-101.4, 95% CI) and 0.12 (0.07-0.21, 95% CI), respectively. The diagnostic accuracy for right and left PE was 97.69% (95.90-98.84%, 95% CI) and 96.22% (94.04-97.74%, 95% CI), respectively. LIMITATIONS: The principal limit is the high dependence of TVS on the operator experience. Therefore, although a standardized approach following precise definitions of anatomical landmarks was used, we cannot conclude that the observed accuracy of TVS for PE is the same for all sonographers. In this regard, the learning curve was not assessed. In the case of negative TVS for parametrial involvement with an absent intraoperative suspect, a complete dissection of the parametrium was not performed to avoid surgical complications; therefore, cases of minor PE may be missed, underestimating false negatives. CONCLUSIONS: TVS performed following a systematic approach for assessing the lateral parametria seems to have good diagnostic accuracy for PE with large changes in the posttest probability of parametrial involvement based on the TVS evaluation. Considering the clinical and surgical implications of PE, further studies implementing a standardized approach for assessing the parametrium by TVS are recommended to confirm our observations and implement a standardized protocol in clinical practice.

Progress in the understanding of the pathophysiology of immunologic maladaptation related to early-onset preeclampsia and metabolic syndrome related to late-onset preeclampsia.

Among mammalian species, human reproduction has 2 outstanding features. The human hemochorial placentation is characterized by a very deep endovascular trophoblast invasion in the spiral arteries, reaching deep into the myometrium. This requires an agonistic direct cell-cell interaction between the maternal immune system and semiallogeneic trophoblast. The second feature is preeclampsia, a heterogeneous syndrome, a uniquely human condition. The human female is one of the few mammals exposed to her partner's semen on multiple occasions before conception. Regulatory T cells, especially paternal antigen-specific regulatory T cells, play an important role in the maintenance of pregnancy. Sexual intercourse increases the number of dendritic cells in the uterus that play an important role in the induction of paternal antigen-specific regulatory T cells. Paternal antigen-specific regulatory T cells maintain pregnancy by inducing tolerance. In the decidua basalis of preeclamptic cases, clonal regulatory T cells are reduced; these would normally monoclonally expand to recognize fetal or paternal antigens. Programmed cell death-1 expressed on T cells regulate cytotoxic T-cell activity and protect the fetus against maternal rejection. Programmed cell death-1 expression on clonal cytotoxic T cells is reduced in preeclampsia especially in early-onset preeclampsia, making the fetus and placenta vulnerable to attack by cytotoxic T cells. These phenomena can explain the epidemiologic phenomenon that preeclampsia is more common in couples using condom contraception, with shorter cohabitation periods, first pregnancies, first pregnancies in multiparous women when they change partner, and pregnancies after assisted reproduction using donated gametes. In contrast to its importance in early-onset preeclampsia, shallow trophoblast invasion does not play a role in the development of preeclampsia, that is, immune maladaptation does not seem to be involved. Late-onset preeclampsia (>34 weeks' gestation), representing 80% to 90% of preeclampsia in most developed countries with a "Western lifestyle," is strongly associated with maternal cardiometabolic variables (metabolic syndrome). Although the underlying pathophysiology might be quite different, syncytiotrophoblast stress is the final common pathway leading to the maternal syndrome among the subtypes of preeclampsia by causing an imbalance between proangiogenic factors (placental growth factor and vascular endothelial growth factor) and antiangiogenic factors (soluble fms-like tyrosine kinase-1 and soluble endoglin). Low-dose aspirin, started before 16 week's gestation, will prevent up to 60% of early-onset preeclampsia but will not prevent late-onset preeclampsia. Optimizing prepregnancy weight and controlling gestational weight gain may be the most effective ways to prevent preeclampsia.

Validation of the 34-week gestation as definition of late onset preeclampsia: Testing different cutoffs from 30 to 37 weeks on a population-based cohort of 1700 preeclamptics.

INTRODUCTION: Early onset preeclampsia (EOP) and late onset preeclampsia (LOP) have been differentiated with a cut-point of ≤34 weeks. This classical definition has never been examined with respect to maternal characteristics by different gestational age cut-points. We examined maternal characteristics in a population-based cohort of 1736 preeclamptic deliveries at different gestational age cut-points from 30 to 37 weeks (CO30 to CO37). MATERIAL AND METHODS: Eighteen-year observational population-based historical cohort study (2001-2018). All consecutive births delivered at the Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity. Standardized epidemiological perinatal database. RESULTS: The incidence of EOP was lower in adolescents (1.8% vs 3.5%, odds ratio [OR] 0.50, P = .17). Conversely, the odds of LOP was increased for women over 35, beginning at C030 (OR 1.13, P = .02) and this effect (OR = 1.2) was still detectable at C037 (P = .06). Among primigravid women, the incidence of EOP was lower than LOP (OR ranging from 0.71 to 0.82 for different CO). Conversely, the incidence of LOP was higher (adjusted OR about 2.7 [CO30-CO34] with a rise to 3.3 at CO37 (P < .001). Women with EOP had a lower body mass index (BMI) as compared with LOP at CO34 and CO37. The adjusted OR (per 5 kg/m2 increment) declined from 1.06 to 1.03 from CO30 to C037 in EOP women. Conversely, for LOP, the adjusted odds ratio (aOR) increased from 1.04 to 1.06 from CO30 to CO37 (P < .001). Gestational diabetes mellitus was not associated with LOP at any cut-off (aOR 1.07, NS) but was protective against EOP from CO30 to CO34 (aOR 0.42, 0.61 and 0.73, respectively, P < .001). This protective effect disappeared at CO37. Chronic hypertension and history of preeclampsia were both EOP and LOP risks but with a much stronger effect for EOP (chronic hypertension: aOR 6.0-6.5, history of preeclampsia: aOR 12-17). CONCLUSIONS: The 34th week of gestation appears to provide a reasonable cut-point to differentiate between EOP and LOP. Additional research is needed to better describe the possible differences in the pathophysiology of these different phenotypes.

Ultrasound Differential Diagnosis in Deep Infiltrating Endometriosis of the Urinary Tract.

Endometriosis of the urinary tract is a rare condition that may lead to severe complications. At present, the major challenge appears to be the ultrasound differential diagnosis with diseases that can afflict the ureter and the bladder. Preoperative scan findings were compared with surgical and histologic records. Twenty-three cases were selected as being of interest, as they were referred for suspected endometriosis, whereas second-level ultrasound revealed a different disease in some cases. This case series aims to help in becoming familiar with the possible differential diagnosis of lesions of the urinary tract that resemble endometriosis.

Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials.

PURPOSE: The aim of the present systematic review and meta-analysis was to summarize evidence on the effectiveness of testosterone supplementation for poor ovarian responders (POR) on IVF outcomes. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. METHODS: This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of testosterone administration before/during COS compared with a control group in patients defined as POR. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. Pooled results were expressed as risk ratio (RR) or mean differences (MD) with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroup analysis. All analyses were performed by using the random-effects model. RESULTS: Women receiving testosterone showed higher LBR (RR 2.29, 95% CI 1.31-4.01, p = 0.004), CPR (RR 2.32, 95% CI 1.47-3.64, p = 0.0003), total oocytes (MD = 1.28 [95% CI 0.83, 1.73], p < 0.00001), MII oocytes (MD = 0.96 [95% CI 0.28, 1.65], p = 0.006), and total embryos (MD = 1.17 [95% CI 0.67, 1.67], p < 0.00001) in comparison to controls, with no difference in MR (p = ns). Sensitivity and subgroup analysis did not provide statistical changes to the pooled results. CONCLUSIONS: Testosterone therapy seems promising to improve the success at IVF in POR patients. Further RCTs with rigorous methodology and inclusion criteria are still mandatory.

The PLART study: incidence of preterm labor and adverse pregnancy outcomes after assisted reproductive techniques-a retrospective cohort study.

KEY MESSAGE: Even though assisted reproductive techniques represent one of the greatest achievements in modern medicine, the risk of preterm birth related to these pregnancies is about twice as high. This must be highlighted and further investigated to optimize the management of both mothers and newborns. PURPOSE: The purpose of this study was to compare adverse pregnancy outcomes after assisted reproductive techniques (ART) and spontaneous conceptions, focusing on the incidence of preterm births (PTB) and distinguishing between iatrogenic and spontaneous events. METHODS: This retrospective cohort study analyzed single births of one Italian hospital. The incidence of PTBs in ART pregnancies, divided into iatrogenic procedures, spontaneous preterm labors and preterm premature ruptures of the membranes (pPROMs), was compared with the non-ART control group. The incidence of other adverse pregnancy outcomes and the types of delivery were also reported and compared. RESULTS: Of the 11,769 single births included, 2.39% were conceived by ART. The incidence of PTBs was 4.74% for spontaneous pregnancies and 12.8% for ART pregnancies (aOR 1.93; 95% CI 1.29-2.88). The percentage of iatrogenic procedures was 27.78% in the ART-PTBs' group and 30.88% in the non-ART-PTBs' controls. ART pregnancies showed an increased incidence of pPROMs (6.40% versus 2.41%), preterm labors (2.85% versus 0.93%), hypertensive disorders of the pregnancy (8.19% versus 2.32%), placenta previa (3.20% versus 0.59%), cesarean sections (28.47% versus 16.27%) and vacuum extractions (10.32% versus 5.19%). CONCLUSIONS: Singleton ART pregnancies have a higher risk of PTB which is mostly linked to a higher incidence of pPROMs and spontaneous preterm labor. The concurrency of a demonstrated higher risk of hypertensive gestational disorders and placenta previa suggests that placental development plays an important role in the pathogenesis of PTB.

Randomized Trial on Fast Track Care in Colorectal Surgery for Deep Infiltrating Endometriosis.

STUDY OBJECTIVE: To study the application of a fast-track care protocol in colorectal surgery for deep infiltrating endometriosis. Bowel endometriosis is an infrequent but not rare condition that often needs intestinal surgery and imposes a high economic burden on society. DESIGN: Prospective randomized trial (Canadian Task Force classification I). SETTING: Tertiary referral center. PATIENTS: Two hundred twenty-seven patients with preoperative evidence of bowel endometriosis. INTERVENTIONS: We randomly assigned 227 patients with preoperative evidence of bowel endometriosis to a fast-track protocol (no preoperative bowel preparation, early restoration of diet, no postoperative antibiotics, and early postoperative mobilization) or conventional care for laparoscopic intestinal surgery. Randomization was obtained on a double-blind, date-based schedule, and all procedures were performed by a homogenous group of expert surgeons. Surgical outcomes and a health economic evaluation were assessed. MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital stay. Patient's well-being and intraoperative and postoperative complications up to 30 days after surgery were also assessed. Subsequently, direct medical costs were analyzed. Patients assigned to the fast-track protocol were discharged earlier (median 3 vs 7 days, p < .001) with no significant differences in subjective well-being (p = .55). Operative details, postoperative complications, and need of temporary ileostomy were similar (p = .89) between groups as well as readmission rates within 30 days (p = .69). The application of a fast-track protocol resulted in an overall significant reduction of costs (USD 6699 vs 8674, p < .01), and differences were more evident in cases of protective stoma (7652 vs 8793, p < .05) and surgery with postoperative complications (10 835 vs 14 005, p < .01). CONCLUSION: The application of a fast-track care protocol for laparoscopy in cases of pelvic and intestinal endometriosis does not increase the risk of complications and ensures a reduction of medical costs.

Statistical limits in sonographic estimation of birth weight.

PURPOSE: The accuracy of sonographic estimation of birth weight (EBW) is compromised by the precision of the biometrical measurements and the quality of the algorithms. This prospective study was to evaluate technical aspects to derive new equations for the EBW. METHODS: Three consecutive phases were carried out (1) to recruit a homogenous population, (2) to derive eight new algorithms using a multiple stepwise mathematical/statistical method, and (3) to test the accuracy of the developed equations. Only those patients with a singleton pregnancy who delivered within 48 h from the scan were considered for the analysis. RESULTS: The study population was made of 473 women. Four polynomial, two square root and two logarithmic algorithms were derived from a balanced study group of 200 women selected from the original study population. These formulas were subsequently applied and compared between them and showed a significant correlation with birth weight (p < 0.0001) and satisfactory statistical performances (r > 0.9), nevertheless they performed similarly to other equations previously published. CONCLUSIONS: The present findings define better the limitations associated with the intrinsic properties of algorithms and highlight that the possibility to improve the precision of sonographic measurements remains the only point at issue to increase the accuracy in the prediction of birth weight.

Standard high-resolution pelvic MRI vs. low-resolution pelvic MRI in the evaluation of deep infiltrating endometriosis.

OBJECTIVE: To compare the capabilities of standard pelvic MRI with low-resolution pelvic MRI using fast breath-hold sequences to evaluate deep infiltrating endometriosis (DIE). METHODS: Sixty-eight consecutive women with suspected DIE were studied with pelvic MRI. A double-acquisition protocol was carried out in each case. High-resolution (HR)-MRI consisted of axial, sagittal, and coronal TSE T2W images, axial TSE T1W, and axial THRIVE. Low-resolution (LR)-MRI was acquired using fast single shot (SSH) T2 and T1 images. Two radiologists with 10 and 2 years of experience reviewed HR and LR images in two separate sessions. The presence of endometriotic lesions of the uterosacral ligament (USL), rectovaginal septum (RVS), pouch of Douglas (POD), and rectal wall was noted. The accuracies of LR-MRI and HR-MRI were compared with the laparoscopic and histopathological findings. RESULTS: Average acquisition times were 24 minutes for HR-MRI and 7 minutes for LR-MRI. The more experienced radiologist achieved higher accuracy with both HR-MRI and LR-MRI. The values of sensitivity, specificity, PPV, NPV, and accuracy did not significantly change between HR and LR images or interobserver agreement for all of the considered anatomic sites. CONCLUSIONS: LR-MRI performs as well as HR-MRI and is a valuable tool for the detection of deep endometriosis extension. KEY POINTS: • High- and low-resolution MRI perform similarly in deep endometriosis evaluation • Low-resolution MRI significantly reduces the duration of the examination • Radiologist experience is fundamental for evaluating deep pelvic endometriosis.

Estimation of birthweight by measurement of fetal thigh soft-tissue thickness improves the detection of macrosomic fetuses.

The accuracy of sonographic estimation of birthweight in suspected macrosomic fetuses is compromised by the imprecision of the biometrical measurements. This prospective study evaluated the performance of an equation based on linear measurement of the soft tissue above the external side of the fetal femur. The performance of this algorithm was compared with two classical algorithms. Sonographic measurements were taken within 48 h before of delivery. Sixty-two patients with fetuses with suspected macrosomia were enrolled. The studied formulas were compared between them and showed a significant correlation with birthweight (p < 0.0001) and satisfactory statistical performances (r > 0.9). The new formula showed a reduced standard deviation that means a lower internal error in the prediction. This study supports the potential of this new approach for the estimation of birthweight in large fetuses based on sonographic linear measurements only.

Transvaginal sonography for preoperative assessment of deep endometriosis.

PURPOSE: To determinate transvaginal scan (TVS) accuracy in the preoperative evaluation of deep endometriosis in a large cohort of patients with subsequent laparoscopic assessment. METHODS: A retrospective study was performed in a tertiary referral center for endometriosis. Transvaginal scan reports were retrieved from an electronic database of all patients who underwent laparoscopy for pelvic pain or infertility in 2009. The accuracy of TVS was assessed for 10 different sites of pelvic endometriosis. RESULTS: Four hundred twenty women were included in the study. Sensitivity and specificity of TVS were 61% and 99%, respectively, for bladder endometriosis, 52% and 96% for endometriosis of rectovaginal septum, 65% and 99% for rectum endometriosis, and 69% and 98% for endometriosis of the sigmoid colon. CONCLUSIONS: TVS appears to be useful for the detection of endometriosis located in the bladder and involving the sigmoid colon, the rectovaginal septum, and the rectum.

Placenta and maternal endothelium during preeclampsia: Disruption of the glycocalyx explains increased inositol phosphoglycans and angiogenic factors in maternal blood.

The etiology of the pregnancy syndrome preeclampsia is still unclear, while most hypotheses center on the placenta as the major contributor of the syndrome. Especially changes of the placental metabolism, including the use of glucose to produce energy, are important features. As an example, inositol phosphoglycan P-type molecules, second messengers involved in the glucose metabolism of all cells, can be retrieved from maternal urine of preeclamptic women, even before the onset of clinical symptoms. Alterations in the placental metabolism may subsequently lead to negative effects on the plasma membrane of the placental syncytiotrophoblast. This in turn may have deleterious effects on the glycocalyx of this layer and a disruption of this layer in all types of preeclampsia. The interruption of the glycocalyx in preeclampsia may result in changes of inositol phosphoglycan P-type signaling pathways and the release of these molecules as well as the release of soluble receptors such as sFlt-1 and sEndoglin. The release of placental factors later affects the maternal endothelium and disrupts the endothelial glycocalyx as well. This in turn may pave the way for edema, endothelial dysfunction, coagulation, all typical symptoms of preeclampsia.