Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis.

Endometriosis is a chronic disease in which the endometrium cells are located outside the uterine cavity. The aim of this study was to evaluate circulating 20S proteasome and 20S immunoproteasome levels in plasma and peritoneal fluid in women with and without endometriosis in order to assess their usefulness as biomarkers of disease. Concentrations were measured using surface plasmon resonance imaging biosensors. Patients with suspected endometriosis were included in the study-plasma was collected in 112 cases and peritoneal fluid in 75. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group (confirmed endometriosis) and a control group (patients without endometriosis). Proteasome and immunoproteasome levels in both the plasma (p = 0.174; p = 0.696, respectively) and the peritoneal fluid (p = 0.909; p = 0.284, respectively) did not differ between those groups. There was a statistically significant difference in the plasma proteasome levels between patients in the control group and those with mild (Stage I and II) endometriosis (p = 0.047) and in the plasma immunoproteasome levels in patients with ovarian cysts compared to those without (p = 0.017). The results of our study do not support the relevance of proteasome and immunoproteasome determination as biomarkers of the disease but suggest a potentially active role in the pathogenesis of endometriosis.

Targeted gene expression profiling for accurate endometrial receptivity testing.

Expressional profiling of the endometrium enables the personalised timing of the window of implantation (WOI). This study presents and evaluates a novel analytical pipeline based on a TAC-seq (Targeted Allele Counting by sequencing) method for endometrial dating. The expressional profiles were clustered, and differential expression analysis was performed on the model development group, using 63 endometrial biopsies spanning over proliferative (PE, n = 18), early-secretory (ESE, n = 18), mid-secretory (MSE, n = 17) and late-secretory (LSE, n = 10) endometrial phases of the natural cycle. A quantitative predictor model was trained on the development group and validated on sequenced samples from healthy women, consisting of 52 paired samples taken from ESE and MSE phases and five LSE phase samples from 31 individuals. Finally, the developed test was applied to 44 MSE phase samples from a study group of patients diagnosed with recurrent implantation failure (RIF). In validation samples (n = 57), we detected displaced WOI in 1.8% of the samples from fertile women. In the RIF study group, we detected a significantly higher proportion of the samples with shifted WOI than in the validation set of samples from fertile women, 15.9% and 1.8% (p = 0.012), respectively. The developed model was evaluated with an average cross-validation accuracy of 98.8% and an accuracy of 98.2% in the validation group. The developed beREADY screening model enables sensitive and dynamic detection of selected transcriptome biomarkers, providing a quantitative and accurate prediction of endometrial receptivity status.

Circulating miR-3613-5p but not miR-125b-5p, miR-199a-3p, and miR-451a are biomarkers of endometriosis.

OBJECTIVE: This study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis. STUDY DESIGN: Patients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves. RESULTS: MiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05). CONCLUSION: Circulating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= -0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

Personalized embryo transfer (pET) guided by endometrial receptivity (ER) assessment - a possibility to increase effectiveness of IVF procedures. Review of available methods.

The continuous development of assisted reproductive techniques (ART) implies the search for solutions that could increase the effectiveness ofavailable methods. In the context of in vitro fertilization (IVF), a significant proportion of failures are due to unsuccessful embryo transfers. At this stage the most important issue is proper dialogue between implanting embryo and the maternal endometrium. Therefore, it seems justified to assess endometrial receptivity (ER), defined as the tissue's ability to accept an embryo to attach and invade into the mucosa. Window of implantation (WOI), is a certain period in which implantation of the properly developed embryo is possible. The cause of endometrial receptivity disorders is believed to be the disturbed expression of cytokines and endometrial surface proteins, the presence of which has been proven in commonly diagnosed diseases such as endometriosis or chronic endometritis. Despite many years of research on endometrial receptivity, the area of ​​diagnostic methods enabling clinical monitoring of ER still remains undeveloped. The aim of this study is to review the utility of selected markers and the available methods of ER assessment, ranging from noninvasive ultrasound, through endometrial fluid analysis, to genomic studies based on endometrial biopsy, in order to increase the effectiveness of IVF. Such an approach could potentially be a significant step towards personalizing medical procedures especially in patients diagnosed with repeated implantation failure (RIF).

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening.

INTRODUCTION: Extreme levels of either PAPP-A or free ß-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. METHODS: A total number of 8591 patients with singleton pregnancies between 11 + 0-13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free ß-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. RESULTS: Values of PAPP-A ≥ 2,0 MoM and free ß-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free ß-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free ß-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free ß-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free ß-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DISCUSSION: Pregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free ß-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free ß-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.

Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 µg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 µg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

Enlarged Abdominal Lymph Node as a Cause of Polyhydramnios in the Course of Congenital Neonatal Leukaemia: A Case Report and Review of the Literature on Foetal Abdominal Tumours with Coexisting Polyhydramnios.

Polyhydramnios represents a complication found in 0.2-2% of pregnancies, and it is usually diagnosed between 31 and 36 weeks of pregnancy. Although most cases of polyhydramnios are idiopathic, maternal diabetes or foetal malformations constitute frequent causes of the excessive accumulation of the amniotic fluid. Considering the latter, polyhydramnios may rarely be caused by foetal abdominal tumours, with the incidence rate of 2-14 cases per 100,000 live births. Congenital neonatal leukaemia (CNL) is a rare disease with a reported incidence rate of 5-8.6 cases per million live births. In the prenatal period, the ultrasound abnormalities associated with CNL include hepatomegaly and splenomegaly. In this paper, we presented a case of polyhydramnios caused by mechanical pressure on the foetal gastrointestinal tract by an enlarged lymph node in the course of CNL, as well as reviewing the available literature on foetal abdominal tumours with concurrent polyhydramnios.

A Six-Year Gynecological Follow-Up of Immunosuppressed Women with a High-Risk Human Papillomavirus Infection.

Immunocompromised women are at an increased risk of developing malignancies, especially those that are viral-induced, such as invasive cervical cancer caused by the human papillomavirus (HPV). The aim of the study was to describe gynecological follow-up of women undergoing chronic immunosuppressive therapy for various reasons (e.g., kidney/liver transplant, systemic lupus erythematosus), diagnosed with a high-risk HPV (hrHPV) infection based on a self-sampling test. Twenty-six hrHPV-positive women were invited to take part in a gynecological follow-up, including a visual assessment of the anogenital region, two-handed gynecological examination, and cervical cytology as well as a colposcopy and cervical biopsy when necessary. Four women declined taking part in the study. Over six years of observation, low-grade squamous intraepithelial lesions (LSIL) were detected at least once in 7/22 women (31.8%), and a cervical intraepithelial lesion 1 (CIN 1) histopathologic result was obtained five times in 3/22 women. No cases of high-grade squamous intraepithelial lesions, CIN 2/3, or invasive cervical cancers were observed. Loop electrosurgical excision procedure (LEEP) was performed in three patients. As immunocompromised women are prone to persistent hrHPV infections, they should be under strict gynecological supervision because only vigilant surveillance enables fast detection and treatment of early dysplasia and, therefore, provides a chance for the reduction of the cervical cancer burden.

Management Options for Fetal Bronchopulmonary Sequestration.

To evaluate the prenatal course and perinatal outcome of fetuses with bronchopulmonary sequestration (BPS) managed expectantly or using minimally invasive methods. This was a retrospective study of 29 fetuses with suspected BPS managed between 2010 and 2021 in three fetal medicine centers in Poland. Medline was searched to identify cases of BPS managed expectantly or through minimally-invasive methods. In 16 fetuses with BPS, there was no evidence of cardiac compromise. These fetuses were managed expectantly. Thirteen hydropic fetuses with BPS qualified for intrauterine intervention: a thoraco-amniotic shunt (TAS) was inserted in five fetuses, laser coagulation of the feeding vessel was performed in seven cases, and one fetus had combined treatment. In the combined data from the previous and the current study of various percutaneous interventions for BPS associated with hydrops, the survival rate was 91.2% (31/34) for TAS, 98.1% (53/54) for laser coagulation, and 75% (3/4) for intratumor injection of sclerosant. After taking into account cases with available data, the rate of preterm birth before 37 weeks in the group treated with laser coagulation was 14.3% (7/49) compared to 84.6% (22/26) in the group treated with TAS. The need for postnatal sequestrectomy was lower in the group of fetuses treated with laser coagulation 23.5% (12/51) in comparison to fetuses treated with TAS 84% (21/26). In fetuses with BPS without hydrops, progression of the lesion's volume, leading to cardiac compromise, is unlikely. In hydropic fetuses with BPS, intrauterine therapy using minimally invasive methods prevents fetal demise. Both, the rate of preterm birth and the need for postnatal surgery is significantly lower in the group treated with laser coagulation compared to the group treated with TAS.

Hyperthyroidism secondary to a hydatidiform mole.

The case presented in the article is that of a 47-year-old female patient with hyperthyroidism induced by a hydatidiform mole. Attention was drawn to the necessity of preparing the patient for a procedure with drugs that stabilize the hormonal activity of the thyroid. The removal of the hydatidiform mole resulted in gradual normalization of thyroid hormone levels. The trophoblast has a hormonal activity, secrete hCG (human chorionic gonadotropin).The hCG partial structural homology causes affinity to the TSH (thyroid stimulating hormone) receptor. The higher the weight of the trophoblast, the higher the production and concentration of hCG in the blood. Therefore, gestational trophoblastic disease may be accompanied by hyperthyroidism. The problem is frequently described, however, due to the risk of developing thyroid storm, it cannot be overlooked [1].

Intrauterine fetoscopic closure of myelomeningocele: Clinical case and literature review.

OBJECTIVE: Spina bifida (SB) is a congenital birth defect defined as a failure of the neural tube formation during the embryonic development phase. Fetoscopic repair of SB is a novel treatment technique that allows to close spinal defect early and prevent potential neurological and psychomotor complications. CASE REPORT: We present a case report of a 32-year-old-multigravida whose fetus was diagnosed with lumbosacral myelomeningocele at 23rd week. Fetoscopic closure of MMC was performed at 26 weeks. At 32 weeks, due to premature amniorrhexis and placental abruption, an emergency C-section was performed. Newborn's psychomotor development was within normal limits. CONCLUSION: Although intrauterine treatment has an increased risk of premature labor, placental abruption, prenatal closure is associated with improved postnatal psychomotor development. Prenatal surgery decreases the risk of Arnold-Chiari II malformation development and walking disability. Fetoscopic closure of SB is becoming a choice for treatment with beneficial outcomes for mother and fetus.

Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia.

BACKGROUND: Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking. METHODS: In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women. RESULTS: The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09). CONCLUSIONS: In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).

Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS: In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS: In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS: This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).

Evaluation of a real-time optoelectronic method in the diagnostics of CIN over four years of observations.

Cervical cancer is considered to be particularly amenable to prevention and highly treatable in its early stages. The real-time optoelectronic method of cervix examination seemed to be very promising in the detection of cervical squamous intraepithelial lesions and demonstrated relatively good efficacy. Although this method was introduced into clinics almost 10 years ago, it has not found its place in diagnostic schemes. At the moment, cytological smears and HPV detection with genotyping are still essential. TruScreen seems to be a slightly forgotten test. The aim of the study was to evaluate the efficacy and accuracy of TruScreen in detecting cervical pathology: CIN and cervical cancer confirmed with a histopathological diagnosis in comparison with other methods-cytology and colposcopy over four years of observations. The study was conducted on 130 women with abnormal Pap smear results. We can conclude that a real-time optoelectronic method like TruScreen can be useful as an effective initial cervical cancer screening in developing countries, possibly in combination with other methods. The combination of cytology and TruScreen examination may help clinicians to take decision about the next diagnostics steps (e.g. colposcopy) and contribute to better primary screening for cervical cancer.

Prolactin secretion pattern among female flight attendants.

OBJECTIVES: Epidemiological observations indicate that female flight attendants are exposed to some reproductive and endocrine system disturbances. The aim of the study was to determine the incidence of hyperprolactinemia among female flight attendants, and to identify factors affecting the secretion of prolactin in female flight attendants working within 1 time zone as well as on long-distance flights. MATERIAL AND METHODS: The cross-sectional study covered 103 women aged 23-46 years. The study group (I) was divided into 2 subgroups: subgroup Ia comprising female flight attendants flying within 1 flight zone, and subgroup Ib composed of female flight attendants working on long-distance flights. The control group (II) included women of reproductive age who sought medical assistance due to marital infertility in whom the male factor was found to be responsible for problems with conception in the course of the diagnostic process. The assessment included: age, the body mass index, menstrual cycle regularity, the length of service, the frequency of flying, the prolactin, estradiol and progesterone concentrations, and the result of endometrial biopsy. Descriptive and inferential statistics methods were used to compile the data. RESULTS: The incidence of hyperprolactinemia in the female flight attendants (46%) was significantly higher than in the control group (9%), p < 0.001. Differences between subgroups Ia and Ib regarding individual concentrations were not statistically significant (p = 0.425). Hyperprolactinemia among the female flight attendants working ≥15 years is present slightly more often than in those working <15 years: 46% vs. 45% (p > 0.05). No significant difference was revealed in the secretion of prolactin between the study participants spending <60 h/month flying and those spending ≥60 h/month flying (p > 0.05). CONCLUSIONS: Hyperprolactinemia is more common in female flight attendants than in the general population. High values of prolactin concentration in flight attendants are rarely manifested in clinical symptoms. The frequency of flying and the length of service do not affect the development of hyperprolactinemia or the mean prolactin concentration. Int J Occup Med Environ Health. 2021;34(3):351-61.

Longitudinal changes in maternal left atrial volume index and uterine artery pulsatility indices in uncomplicated pregnancy.

BACKGROUND: Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. OBJECTIVE: This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. STUDY DESIGN: Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free ß-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). RESULTS: Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). CONCLUSION: Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.