Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth: the Rotterdam Periconception Cohort.

STUDY QUESTION: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? SUMMARY ANSWER: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. WHAT IS KNOWN ALREADY: First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). MAIN RESULTS AND THE ROLE OF CHANCE: Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints ß = 0.017, 95% CI [0.009; 0.025], bifurcation points ß = 0.012, 95% CI [0.006; 0.018], crossing points ß = 0.017, 95% CI [0.008; 0.025], vessel points ß = 0.01, 95% CI [0.002; 0.008], and total vascular length ß = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV ß = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV ß = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV ß = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV ß -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV ß = -48.604 95% CI [-74.246; -22.961])), all P-values < 0.05. After stratification, the associations were observed in natural conceptions specifically. LIMITATION, REASONS FOR CAUTION: Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered at the Dutch Trial Register (NTR6854).

Advances in pathogenesis of preeclampsia.

PURPOSE: Preeclampsia is a major cause of health problems for both pregnant women and unborn babies worldwide. However, the underlying causes of preeclampsia are not fully understood, leading to limited effective treatments. The goal of this study is to enhance our knowledge of its causes, devise prevention strategies, and develop treatments. METHODS: We performed a systematic literature search. Six models regarding the pathogenesis of preeclampsia are discussed in this review. RESULTS: This review focuses on the latest advancements in understanding preeclampsia's origins. Preeclampsia is a complex condition caused by various factors, processes, and pathways. Reduced blood flow and oxygen to the uterus and placenta, heightened inflammatory reactions, immune imbalances, altered genetic changes, imbalanced blood vessel growth factors, and disrupted gut bacteria may contribute to its development. CONCLUSION: Preeclampsia is thought to result from the interplay of these factors.

Maternal supplementation of curcumin-olive oil nanocomposite improves uteroplacental blood flow, placental growth and antioxidant capacity in goats.

This experiment was designed to investigate the impact of curcumin-olive oil nanocomposite (CONC) supplementation on uteroplacental hemodynamics and ultrasonographic measurements as well as maternal oxidative status in midgestating goats. Twelve synchronized pregnant goats (85.58 ± 1.08 days of gestation; mean ± SD) were uniformly assigned to two groups (n = 6/group); the first group received daily oral supplementation of CONC (3 mg/kg body weight; nanocurcumin [NC] group) for 32 days, and the second group was offered physiological saline (control) following the NC group timeline. The goats of both groups were examined at 3-day intervals for middle uterine (MUA) and umbilical (UMA) arteries hemodynamics (pulsatility index [PI], resistive index [RI], systole/diastole [S/D] and blood flow rate [BFR]) and diameters, uteroplacental thickness (UPT), placentomes' diameter (PD) and echogenicity, steroid hormones (progesterone and estradiol 17ß), oxidative biomarkers (total antioxidant capacity [TAC], catalase [CAT], malondialdehyde [MDA]), nitric oxide (NO) and blood cells DNA integrity. The UPT (p = 0.012) and PD (p = 0.021) values were higher in the NC group than in their counterparts' control group (D11-32). There were increases in diameter (p = 0.021 and p = 0.012) and decreases (p = 0.021, p = 0.016 and p = 0.041 [MUA]; p = 0.015, p = 0.023 and p = 0.011 [UMA] respectively) in Doppler indices (PI, RI and S/D) of the MUA and UMA in the NC group compared to the control group (D14-32). On D20-32 (MUA) and D14-32 (UMA), the NC goats had higher BFR than the control group (p = 0.021, 0.018 respectively). The means of blood cells with fragmented DNA were lower (p = 0.022) in the NC group than in the control group on Days 8 and 21 postsupplementation. There were increases in CAT and NO (D20-32; p = 0.022 and p = 0.004 respectively), and TAC (D17-32; p = 0.007) levels in the NC goats compared to the control ones. The NC group had lower (p = 0.029) concentrations of MDA than the control group on Day 20 postsupplementation onward. In conclusion, oral supplementation of CONC improved uteroplacental blood flow and the antioxidant capacity of midgestating goats.

Uterine Immunoprivileged Cells Restore Cardiac Function of Male Recipients After Myocardial Infarction.

It has been documented that the uterus plays a key cardio-protective role in pre-menopausal women, which is supported by uterine cell therapy, to preserve cardiac functioning post-myocardial infarction, being effective among females. However, whether such therapies would also be beneficial among males is still largely unknown. In this study, we aimed to fill in this gap in knowledge by examining the effects of transplanted uterine cells on infarcted male hearts. We identified, based on major histocompatibility complex class I (MHC-I) expression levels, 3 uterine reparative cell populations: MHC-I(neg), MHC-I(mix), and MHC-I(pos). In vitro, MHC-I(neg) cells showed higher levels of pro-angiogenic, pro-survival, and anti-inflammatory factors, compared to MHC-I(mix) and MHC-I(pos). Furthermore, when cocultured with allogeneic mixed leukocytes, MHC-I(neg) had lower cytotoxicity and leukocyte proliferation. In particular, CD8+ cytotoxic T cells significantly decreased, while CD4+CD25+ Tregs and CD4-CD8- double-negative T cells significantly increased when cocultured with MHC-I(neg), compared to MHC-I(mix) and MHC-I(pos) cocultures. In vivo, MHC-I(neg) as well as MHC-I(mix) were found under both syngeneic and allogeneic transplantation in infarcted male hearts, to significantly improve cardiac function and reduce the scar size, via promoting angiogenesis in the infarcted area. All of these findings thus support the view that males could also benefit from the cardio-protective effects observed among females, via cell therapy approaches involving the transplantation of immuno-privileged uterine reparative cells in infarcted hearts.

Early spiral arteriole remodeling in the uterine-placental interface: A rat model.

The mammalian placenta's interface with the parent is a richly vascularized tissue whose development relies upon communication between many different cell types within the uterine microenvironment. The uterine blood vessels of the interface are reshaped during pregnancy into wide-bore, flaccid vessels that convey parental blood to the exchange region of the placenta. Invasive trophoblast as well as parental uterine macrophages and Natural Killer cells are involved in the stepwise remodeling of these vessels and their respective contributions to this crucial process are still being delineated. However, the earliest steps in arteriole remodeling are understudied as they are difficult to study in humans, and other species lack the deep trophoblast invasion that is so prominent a feature of placentation in humans. Here, we further characterize the rat, with deep hemochorial placentation akin to humans, as a model system in which to tease apart the earliest, relatively understudied events in spiral arteriole remodeling. We show that the rat uterine-placental interface increases in size and vascularity rapidly, before trophoblast invasion. The remodeling stages in the arterioles of the rat uterine-placental interface follow a sequence of anatomical changes similar to those in humans, and there are changes to the arterioles' muscular tunica media prior to the marked influx of immune cells. The rat is a tractable model in which to better understand the cell/cell interactions occurring in vivo in an intact tissue microenvironment over time.

A new step-wise surgical technique of knapsack-like uterine compression sutures for intractable postpartum hemorrhage in cesarean section.

BACKGROUND: Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. METHODS: The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. RESULTS: This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. CONCLUSIONS: This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).

Anatomic variation of a duplicated uterine artery.

During the anatomical dissection of the pelvis, a duplication of the uterine artery was identified unilaterally on the left side in a 59-year-old Korean female cadaver. The first uterine artery was found to arise directly from the anterior division of the internal iliac artery and supply the upper uterine body and tube. The second uterine artery shared a common stem with the superior and inferior vesical arteries, supplying the lower uterine body. The external diameter of each uterine artery at its origin on the left side was smaller than that of the right uterine artery. One vaginal artery was identified to arise from the left internal pudendal artery. Embryologically, a duplicated uterine artery could imply the presence of two primordial arteries separately supplying the cranial and caudal parts of the Müllerian duct during the early fetal period. This case of variational anatomy is noteworthy: clinicians could elucidate it and successfully perform uterine artery embolization or hysterectomy with minimal complications.

Treatment of infected placenta accreta in the uterine horn by transabdominal temporary occlusion of internal iliac arteries: A case report and literature review.

RATIONALE: This case report aims to describe the treatment of infected placenta accreta in the uterine horn by transabdominal temporary occlusion of internal iliac arteries. PATIENT CONCERNS: A 29-year-old female patient had a history of retained placenta for 28 days after labor induction in the second trimester of pregnancy because of fetal malformation. DIAGNOSES: Placenta accreta in the uterine horn was diagnosed by 3-dimensional ultrasound and magnetic resonance imaging, and the diagnosis was confirmed during the operation. INTERVENTIONS: Laparotomy was performed to remove the placenta and repair the uterine defect after temporary occlusion of both internal iliac arteries. OUTCOMES: Body temperature and inflammatory markers were elevated at admission but returned to normal on the second day after surgery. Normal menstruation resumed approximately 1 month postoperatively. Ultrasound examination showed that the shape of the uterine cavity was normal. No postoperative complications were observed. LESSONS: Temporary occlusion of the internal iliac artery can help effectively manage infected placenta accreta in the uterine horn.

A spatially resolved timeline of the human maternal-fetal interface.

Beginning in the first trimester, fetally derived extravillous trophoblasts (EVTs) invade the uterus and remodel its spiral arteries, transforming them into large, dilated blood vessels. Several mechanisms have been proposed to explain how EVTs coordinate with the maternal decidua to promote a tissue microenvironment conducive to spiral artery remodelling (SAR)1-3. However, it remains a matter of debate regarding which immune and stromal cells participate in these interactions and how this evolves with respect to gestational age. Here we used a multiomics approach, combining the strengths of spatial proteomics and transcriptomics, to construct a spatiotemporal atlas of the human maternal-fetal interface in the first half of pregnancy. We used multiplexed ion beam imaging by time-of-flight and a 37-plex antibody panel to analyse around 500,000 cells and 588 arteries within intact decidua from 66 individuals between 6 and 20 weeks of gestation, integrating this dataset with co-registered transcriptomics profiles. Gestational age substantially influenced the frequency of maternal immune and stromal cells, with tolerogenic subsets expressing CD206, CD163, TIM-3, galectin-9 and IDO-1 becoming increasingly enriched and colocalized at later time points. By contrast, SAR progression preferentially correlated with EVT invasion and was transcriptionally defined by 78 gene ontology pathways exhibiting distinct monotonic and biphasic trends. Last, we developed an integrated model of SAR whereby invasion is accompanied by the upregulation of pro-angiogenic, immunoregulatory EVT programmes that promote interactions with the vascular endothelium while avoiding the activation of maternal immune cells.

Enhanced myometrial vascularity and AVM: A review on diagnosis and management.

Uterine Arteriovenous malformations (AVM) are vascular disorders characterized by complex high-flow tangles of abnormal vessels connecting arteries and veins with bypassing capillaries. Recently, the terminology applied to describe uterine AVMs has been modified. Most AVMs are acquired. The term enhanced myometrial vascularity (EMV) is used to describe any condition in which any uterine pathology may lead to increased myometrial vascularity regardless of the absence or presence of residual tissue of gestation.

A Vascular Centered Surgical Approach to Radical Hysterectomy: Laparoscopic Anatomy of Pelvic Vascular System Revisited.

OBJECTIVE: As a standard therapy for locally invasive cervical cancer, radical hysterectomy (RH) has been in routine medical practice for more than a century [1]. However, challenges still exist due to the troublesome bleeding during parametrium dissection and resection, which could increase the risk of surgical complications and may probably affect surgical outcomes ultimately [2]. This video illustrated the three-dimensional anatomy of the pelvic vascular system with particular emphasis on "deep uterine vein" and further introduced a vascular-centered surgical approach to performing RH, which could facilitate parametrium dissection with less blood loss and obtain enough resection margins. DESIGN: A step-by-step, narrated video demonstration SETTING: A university hospital INTERVENTIONS: After systemic pelvic lymphadenectomy, ureter was then identified along the medial leaf of the broad ligament. By continuously exploring the pelvic cavity along the ureter, communicating branches of the uterine artery to the ureter, urinary bladder, corpus uteri, uterine cervix, and upper vagina were clearly identified in a cranial to caudal direction, demonstrating the arterial network surrounding the urinary system. Coagulating and cutting these blood vessels could free the ureter from retroperitoneum and subsequently excavate the ureteral tunnel easily. Next, a precise dissection of the area below the ureter revealed the whole distribution of currently named "deep uterine vein". Originated from an internal iliac vein, it is much more like a venous confluence than an accompanying vein, with branches crossing directly into the bladder, dorsally to the rectum, and traveling caudally to the anterolateral side of the uterus and vagina in a crisscross fashion, which mandates us to describe it as pampiniform-like venous plexus instead of "deep uterine vein" due to its anatomical distribution and function. Finally, after complete exposure of venous network, enough extent of parametrium could be adequately separated and resected by accurate coagulation of blood vessels on an individualized requirement. CONCLUSION: Recognizing the precise anatomy of pelvic vascular system, especially the entire distribution of currently named "deep uterine vein" and isolating the venous branches connecting to all three parts of parametrium, are key to the RH procedure. Careful attention to the complex vascular anatomy is critical to reducing intraoperative bleeding and avoiding complications in RH.

Unraveling the mysteries of spiral artery remodeling.

Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to the placenta to nourish the developing fetus. Failure of this process is associated with the pathophysiology of most of the major obstetric complications, including late miscarriage, fetal growth restriction and pre-eclampsia. However, the point at which remodeling 'fails' in these pathological pregnancies is not yet clear. Spiral artery remodeling has predominantly been described in terms of its morphological features, however we are starting to understand more about the cellular and molecular triggers of the different aspects of this process. This review will discuss the current state of knowledge of spiral artery remodeling, in particular the processes involved in loss of the vascular smooth muscle cells, and consider where in the process defects would lead to a pathological pregnancy.

Novel application to evaluate endometrial blood flow using transvaginal superb microvascular imaging: A preliminary study describing physiological changes from ovulation to mid-luteal phase.

INTRODUCTION: We aimed to describe physiological changes in endometrial blood flow (minute arterioles running through the endometrium) from ovulation to the mid-luteal phase using superb microvascular imaging. MATERIAL AND METHODS: The study involved 17 women (median age, 32.5 years; first to third interquartile range, 29.8-40.0 years) with regular menstrual cycles who were managed in our institute from 2020 to 2021. The uterus was delineated at the sagittal section using transvaginal ultrasonography incorporated with superb microvascular imaging. For each participant, a total of 28 cycles were observed; 17 cycles observed within one day of ovulation and the implantation period, 5-7 days (D5-7) after ovulation in the same cycle, and nine cycles in which only ovulation was observed, and two cycles in which only D5-7 was observed. Therefore, 26 and 19 images at ovulation and D5-7, respectively, were acquired. Endometrial blood flow was evaluated by depth of the vascular signal in the endometrium and categorized as follows: signals only in the basal layer of the endometrium (grade 1), reaching up to half the endometrium (grade 2), and covering the whole endometrium (grade 3). Changes in the grade of endometrial blood flow from ovulation to D5-7 after ovulation, and the relationship between the grade of endometrial blood flow and the endometrial thickness on ovulation and D5-7 after ovulation, were analyzed. Statistical significance was set at p < 0.05. RESULTS: The endometrial blood flow from ovulation to D5-7 after ovulation during the same menstrual period showed a downgrade in 14 of 17 cycles (82.3%) and no change in the remaining three cycles (17.6%), indicating a decrease in the endometrial blood flow from ovulation to D5-7 after ovulation (p = 0.001). There were differences between the grade of endometrial blood flow and median endometrial thickness on ovulation (grade 1: 5.9 mm, grade 2: 9.1 mm, and grade 3: 11.2 mm); however, no differences in the endometrial thickness were found between the grades on D5-7 after ovulation. CONCLUSIONS: In the normal menstrual cycle, endometrial blood flow decreased from ovulation to the mid-luteal phase, and the endometrial thickness in the ovulatory phase was related to the endometrial perfusion.

Emergency hysterectomy after 2nd trimester abortion in a patient with placenta accreta spectrum disorder who had four cesarean deliveries.

OBJECTIVE: To perform an emergency hysterectomy by ligation of the uterine arteries before bladder dissection in a patient with placenta accreta spectrum disorder who developed excessive hemorrhage after abortion. CASE REPORT: A patient with four previous cesarean deliveries presented with pelvic pain and excessive vaginal bleeding following a fetal abortion. The patient's hemodynamic status worsened. The patient underwent surgery, and the bladder was densely adherent to the previous incision scar. A classic hysterectomy was performed up to the level of the uterine artery bilaterally. The uterine arteries were then skeletonized and ligated before bladder dissection. The anterior visceral peritoneum was dissected at the isthmic level. The bladder below the adhesion was dissected in the lower uterine segment using a lateral approach. The adhesions were dissected, the bladder was removed from the uterus, and a hysterectomy was performed. CONCLUSION: Obstetricians should be familiar with the dia-gnosis and management of placenta accreta spectrum disorders. In an emergency, the uterine artery could be ligated before bladder dissection. After cessation of bleeding, the bladder could be dissected from the lower uterine segment and a safe hysterectomy could be performed.

Stable adrenomedullin analog mitigates placental ischemia-induced hypertension and fetal growth restriction in rats.

OBJECTIVES: Preeclampsia is a heterogeneous hypertensive disorder of pregnancy. It affects multiorgans and may lead to fetal growth restriction, organ failure, seizure, and maternal death. Unfortunately, current treatments are ineffective at delaying the progression of preeclampsia even for a few days. Clinicians are often forced to deliver preterm fetus if severe preeclampsia occurred early during pregnancy, leading to premature birth-associated complications. Preeclampsia has been associated with defects at the maternal-fetal interface and maternal vascular dysfunction. Of interest, the adrenomedullin peptide and its cognate receptors, calcitonin receptor-like receptor (CLR)/ receptor activity-modifying protein (RAMP) receptor complexes, have been shown to be important regulators of cardiovascular adaptation and feto-placental development during pregnancy. Although the exact role of adrenomedullin-CLR/RAMP signaling in different feto-maternal compartments during pregnancy and how adrenomedullin expression affects preeclampsia development remains to be clarified, we hypothesized that the sustained activation of CLR/RAMP receptors could be a promising strategy to mitigate placental ischemia-associated vascular dysfunction and fetal growth restriction under preeclampsia-like conditions. METHODS: To explore this possibility, we have developed a stable adrenomedullin analog, ADE101, and investigated its effects on human lymphatic microvascular endothelial (HLME) cell proliferation, hemodynamics, and pregnancy outcomes in pregnant rats with reduced uteroplacental perfusion pressure (RUPP) induced by clipping of uterine arteries on gestation day 14. RESULTS: The ADE101 analog has a potent effect on CLR/RAMP2 receptor activation, and an enhanced stimulatory effect on HLME cell proliferation compared to wild-type peptides. ADE101 also exhibits a lasting effect on hemodynamics in normal and hypertensive rats. In addition, studies using the RUPP model showed that ADE101 significantly reduces placental ischemia-induced hypertension and fetal growth restriction in a dose-dependent manner. Infusion of ADE101 increased the weight of fetuses and placentas in RUPP animals to 252% and 202% of that of RUPP controls, respectively. CONCLUSIONS: These data suggested that long-acting adrenomedullin analog could be useful for quenching hypertension as well as the vascular ischemia-associated organ damages in preeclamptic patients.

Accuracy of doppler assessment of the uterine arteries for the diagnosis of pubertal onset in girls: a scoping review.

The uterine artery pulsatility index (PI) assessed by Doppler ultrasound reflects the impedance to the blood flow in the vessel distal to the sampling point. We aimed to assess the accuracy of the uterine artery PI for the diagnosis of puberty in girls. A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with the search terms "puberty" and "Doppler ultrasonography". Studies that included girls aged 0-18 years who underwent pelvic Doppler ultrasound with calculation of uterine artery PI were eligible. Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies included participants from Italy, Brazil, Iran, Belgium and Denmark, and were published between 1996 and 2021. Six studies selected girls who were referred for evaluation of pubertal disorders, while four studies included only healthy girls. Nine studies found a significant difference in Doppler signal pattern and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of puberty, with a sensitivity of 77%-94%, specificity of 85%-100%, and accuracy of 79%-98%. Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of pubertal onset in girls.

Comparison of uterine, endometrial and subendometrial blood flows in predicting pregnancy outcomes between fresh and frozen-thawed embryo transfer after GnRH antagonist protocol: a retrospective cohort study.

This retrospective cohort study aimed to compare endometrial receptivity and pregnancy rate between fresh embryo transfer (ET) and frozen-thawed ET after gonadotrophin-releasing hormone (GnRH) antagonist protocol in normal ovarian responders. The patients were divided into two groups: the fresh ET group and the frozen-thawed ET group. Uterine artery resistance index (RI) and endometrial thickness were lower in the frozen-thawed ET group. The proportion of detectable endometrial-subendometrial flow was significantly higher in the frozen-thawed ET group. There was no significant difference in miscarriage rate between the two groups. Frozen-thawed ET group had a significantly higher CPR (56.0% vs. 48.1%), implantation rate (32.2% vs. 26.4%), and LBR (45.4% vs. 36.5%) than the fresh ET group. In GnRH antagonist protocol, elective frozen-thawed ET should be ideally taken, as this could improve embryo implantation rate, clinical pregnancy rate, and live birth rate, thus presenting an effective strategy to enhance the embryo utilization rate.IMPACT STATEMENTWhat is already known on this subject? The clinical pregnancy rate following fresh embryo transfer (ET) was lower than frozen-thawed ET after GnRH antagonist protocol. IVF success depends on embryo quality, embryo-endometrium interaction and endometrial receptivity. A good blood supply toward the endometrium is generally considered a requirement for implantation.What do the results of this study add? Uterine artery RI and endometrial thickness were significantly lower in the frozen-thawed ET group. The proportion of detectable endometrial-subendometrial flow was significantly higher in the frozen-thawed ET group. Frozen-thawed ET group had a significantly higher clinical pregnancy rate, implantation rate and live birth rate than the fresh ET group after GnRH antagonist protocol.What are the implications of these findings for clinical practice and/or further research? In GnRH antagonist protocol, elective frozen-thawed ET should be ideally taken, as this could improve embryo implantation rate, clinical pregnancy rate and live birth rate, thus presenting an effective strategy to enhance the embryo utilization rate.