Healthy Women Of Childbearing Age Research Articles

CPY27B1-related vitamin D deficiency contributes to the impaired function of CD4+T cells in Recurrent spontaneous miscarriage

The study aimed to explore the relationship between the expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1), vitamin D, and impaired T cell subsets in recurrent spontaneous miscarriage (RSM). A Total of 779 healthy women of childbearing age and 1031 women with a history of RSM were involved in this study. The results of flow cytometry showed that the proportion of Tregs was higher in healthy women than in the women with RSM. For cytokines, the levels of interleukin-17 (IL-17) and interferon-gamma (IFN-γ) were significantly higher in RSM patients than in healthy women, while IL-10 was notably lower in RSM patients. Furthermore, compared to healthy individuals, RSM patients had lower levels of serum 25(OH)D detected by chemiluminescence. The frequency of Tregs was negatively correlated with 25(OH)D. Specifically, for every 10 ng/ml increase in 25(OH)D, the percentage of Tregs increased by 0.58 as calculated. IL-17 and IFN-γ were inversely correlated with 25(OH)D, while the serum interleukin-10 (IL-10) level was positively correlated with 25(OH)D. CYP27B1 was found to be expressed in both cytotrophoblast and extracellular villi trophoblast cells. However, reduced expression of CYP27B1 was observed in the placenta with RSM. Notably, the level of 25(OH)D increased in the supernatant of CYP27B1 knockdown BeWo compared to normal cells, while human chorionic gonadotropin (hCG) was significantly reduced. The hCG secretion of CYP27B1 KO BeWo cells was partially restored after 1,25(OH)2D3 supplementation. In addition, 1,25(OH)2D3 treatment could induce more CD4+ T cells to convert to Foxp3+iTreg, which in turn inhibited the secretion of IL-17, IFN-γ. In summary, this research unveiled a connection between reduced CYP27B1 and vitamin D deficiency in RSM. Our study underscores the potential benefits of vitamin D treatment supplementation in the context of RSM. However, it is important to note that further research is imperative to validate these observations.

Current Diagnostic Possibilities for the Initial Forms of External Endometriosis

Background. Routine use of ultrasound methods does not always allow detecting endometriosis in the early stages. It is necessary to develop more accurate criteria for the diagnosis of endometriosis in its initial stages of development. Objective: to assess ultrasound and biological markers of endometriosis “small” forms of different localization in infertile women.Material and methods. Ultrasound examination of 208 infertile patients with initial stages of external endometriosis (1–15 points by revised American Fertility Society (rAFS) classificatoon) was performed (main group). The control group consisted of 195 healthy women of childbearing age. To verify the diagnosis, it is suggested to use a panel of biomarkers, including interleukins (IL) 1β and 6, CA125, HE4 as well as the ROMA (Risk of Ovarian Malignancy Algorithm) index in the dynamics of the menstrual cycle.Results. On ultrasound scans, 56 (94.9%) patients had small one- and two-sided ovarian cysts corresponding to endometriosis stage 1–2 (rAFS), and in 3 (5.4%) of them, the ultrasound result was questionable. Detectability during the initial ultrasound examination in the Douglas space was 76.9%, in the rest of cases the ultrasound picture was doubtful. Peritoneal endometriosis was detected only in 5 patients. In the remaining cases (88.9%), additional studies were necessary, including surgical (laparoscopy). The average content of CA125 in the main group on days 3–5 of the menstrual cycle was 42.6 (2.1) U/ml, on days 21–23 – 39.6(2.2) U/ml (p=0.32); in the control group, 5.1 (0.4) and 4.8 (0.7) U/ml, respectively (p = 0.71). The increase in CA125 in the main group was almost 8 times higher than in the control group, however, according to the indicators of HE4 and the ROMA index, statistically significant differences in the groups were not obtained. In the dynamics of the menstrual cycle, the content of ILs in the main group significantly decreased by days 21–23 of the cycle, while the content of CA125 and HE4 remained practically unchanged. Such sharp fluctuations of the considered biomarkers were not detected in the control group. However, even on days 21–23 of the cycle, the average content of ILs and CA125 in women of the main group remained statistically significantly higher than in the control group.Conclusion. In infertile women with dubious ultrasound criteria of external endometriosis, the use of IL1β and IL-6, which stimulate the immune inflammatory response, as well as tumor markers CA125, HE4 and ROMA index allows to differentiate the disease in the initial stages.

Relationship between blood uric acid levels and body composition in patients with polycystic ovary syndrome

Objective: To analyze the difference in blood uric acid levels between patients with polycystic ovary syndrome (PCOS) and healthy women of childbearing age, and to investigate the correlation between body composition and blood uric acid levels. Methods: A total of 153 eligible childbearing age patients with PCOS treated at Tianjin Medical University General Hospital from January 2018 to March 2022 were selected, and 153 healthy women with normal menstruation were selected as the control group. Fasting blood uric acid levels were measured by venous blood test, and body composition was measured by a body composition analyzer. Group comparisons were made to analyze the correlation between body composition and blood uric acid levels. Results: The incidence of hyperuricemia was higher in patients with PCOS than that in the control group [30.1% (46/153) vs 2.0% (3/153)], with a statistically significant difference (χ2=44.429, P<0.001). Blood uric acid level was also significantly higher in patients with PCOS than that in the control group [(371±98) vs (265±67) μmol/L; t=11.170, P<0.001]. Among PCOS patients, there were statistically significant differences in weight, body mass index (BMI), body fat mass, skeletal muscle mass, percent body fat, lean body weight, fat mass/lean body weight, percent skeletal muscle, and visceral fat level between the hyperuricemia group and the normal blood uric acid group (all P<0.001), but no significant difference was observed in waist-hip ratio (P=0.348). The following body composition indicators: weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, visceral fat level, lean body weight, and fat mass/lean body weight in all subjects, the PCOS patients and the control group, were positively correlated with blood uric acid levels (all P<0.01). The blood uric acid level in PCOS obese patients was higher than that in non-obese PCOS patients, and the difference was statistically significant [(425±83) vs (336±91) μmol/L; t=6.133, P<0.001]. The blood uric acid level in central obesity PCOS patients was also higher than that in non-central obesity PCOS patients [(385±95) vs (299±79) μmol/L], the difference was statistically significant (t=4.261, P<0.001). The blood uric acid level in normal-weight obese PCOS patients was higher than that in normal-weight non-obese PCOS patients [(333±73) vs (277±54) μmol/L], and the difference was statistically significant (t=2.848, P=0.006). Blood uric acid levels in normal-weight [(315±74) vs (255±67) μmol/L], overweight [(362±102) vs (276±57) μmol/L], and obese PCOS patients [(425±83) vs (303±74) μmol/L] were all higher than those in the corresponding control groups, with statistically significant differences (all P<0.001). Conclusions: PCOS patients have a higher incidence of hyperuricemia than healthy women of childbearing age. Blood uric acid levels are closely correlated with body composition indicators, such as weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, and visceral fat level. Body composition analysis of women with PCOS could help identify potentially obese people more accurately and carry out individualized treatment, thereby reducing the risk of metabolic abnormalities.

Quantitative descriptive study of oxygen saturation in women living at altitudes greater than 2800 M.A.S.L. Huancavelica Peru

The objective of the research work was to determine the oxygen saturation (SpO2) in women of childbearing age who live at altitudes greater than 2800 meters above sea level (m.a.s.l) Huancavelica 2021. The study was observational, prospective, cross-sectional, in 151 healthy women of childbearing age, from 18 to 49 years old, the SpO2 was evaluated, through a pulse oximeter, to all women who attended the consultation between July and August of the year 2021, women without cardiopulmonary pathology were considered within the study group and those who accepted take part. Results: the average of the SpO2, of those who live between 2819 - 3499 m.a.s.l. is 93.72% and between 3500 - 4200 m.a.s.l., it is 90.85%; the minimum SpO2 was 85% and 83% respectively, the maximum SpO2 was 99% in both altitude floors. According to age, 92.91% were between 18 and 19 years old, 93.09% between 20 and 34 years old, and 91.74% between 35 and 49 years old. The average SpO2 of the pregnant women was 92.29% and in the non-pregnant women 92.67%, the minimum SpO2 was 88% and 83% respectively, while the maximum value was the same in both groups 99%. Conclusion: the inhabitants show lower saturations at higher altitudes, and it is observed to decrease after 35 years old, no difference is found between pregnant and non-pregnant women.

Reference Range of Vitamin K Evaluating Indicators in Chinese Childbearing Women.

Vitamin K is an essential fat-soluble vitamin for the human body and its functions, such as promoting blood coagulation, bone health and preventing atherosclerosis, have attracted increasing attention. However, there is no recognized indicator and corresponding reference range for evaluating vitamin K status of different populations at present. The aim of this study is to establish a reference range for vitamin K evaluating indicators in healthy women of childbearing age in China. The population sample in this study was from the Chinese Adult Chronic Disease and Nutrition Surveillance (CACDNS) 2015-2017. A total of 631 healthy women of childbearing age (18-49 years) were included using a series of strict inclusion and exclusion criteria. The concentrations of VK1, MK-4 and MK-7 in serum were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The other commonly-reported indicators evaluating vitamin K nutritional status, including undercarboxylated osteocalcin (ucOC), osteocalcin (OC), matrix Gla protein (MGP), desphosphorylated undercaboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), were measured by enzyme-linked immunosorbent assay (ELISA). The reference range was obtained by calculating the 2.5% to 97.5% interval of the vitamin K evaluating indicators in the reference population. The reference ranges of VK1, MK-4 and MK-7 in serum were 0.21-3.07 ng/mL, 0.02-0.24 ng/mL and 0.12-3.54 ng/mL, respectively. The reference ranges of ucOC, %ucOC, dp-ucMGP and PIVKA-II were 1.09-2.51 ng/mL, 5.80-22.78%, 2.69-5.88 ng/mL and 3.98-8.40 ng/mL, respectively. The cut-off values that can be used to evaluate subclinical vitamin K deficiency were as follows: VK1 < 0.21 ng/mL, MK-7 < 0.12 ng/mL, ucOC > 2.51 ng/mL, %ucOC > 22.78%, dp-ucMGP > 5.88 ng/mL and PIVKA-II > 8.40 ng/mL. The reference range of VK1, MK-4, MK-7 and vitamin K-related indicators for healthy women of childbearing age established in this study could be used to assess the nutritional and health status of this population.

Pregnancy Is Associated with Impaired Transcription of Human Endogenous Retroviruses and of TRIM28 and SETDB1, Particularly in Mothers Affected by Multiple Sclerosis

Accumulating evidence highlights the pathogenetic role of human endogenous retroviruses (HERVs) in eliciting and maintaining multiple sclerosis (MS). Epigenetic mechanisms, such as those regulated by TRIM 28 and SETDB1, are implicated in HERV activation and in neuroinflammatory disorders, including MS. Pregnancy markedly improves the course of MS, but no study explored the expressions of HERVs and of TRIM28 and SETDB1 during gestation. Using a polymerase chain reaction real-time Taqman amplification assay, we assessed and compared the transcriptional levels of pol genes of HERV-H, HERV-K, HERV-W; of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis associated retrovirus (MSRV); and of TRIM28 and SETDB1 in peripheral blood and placenta from 20 mothers affected by MS; from 27 healthy mothers, in cord blood from their neonates; and in blood from healthy women of child-bearing age. The HERV mRNA levels were significantly lower in pregnant than in nonpregnant women. Expressions of all HERVs were downregulated in the chorion and in the decidua basalis of MS mothers compared to healthy mothers. The former also showed lower mRNA levels of HERV-K-pol and of SYN1, SYN2, and MSRV in peripheral blood. Significantly lower expressions of TRIM28 and SETDB1 also emerged in pregnant vs. nonpregnant women and in blood, chorion, and decidua of mothers with MS vs. healthy mothers. In contrast, HERV and TRIM28/SETDB1 expressions were comparable between their neonates. These results show that gestation is characterized by impaired expressions of HERVs and TRIM28/SETDB1, particularly in mothers with MS. Given the beneficial effects of pregnancy on MS and the wealth of data suggesting the putative contribution of HERVs and epigenetic processes in the pathogenesis of the disease, our findings may further support innovative therapeutic interventions to block HERV activation and to control aberrant epigenetic pathways in MS-affected patients.

Fasting Versus Non-Fasting Total Testosterone Levels in Women During the Childbearing Period.

Background Total testosterone in men should be measured in the fasting stateearly in the morning with at least two samples according to guidelines. For women, no such a recommendation is available despite the importance of testosterone in this demographic. The aim of this study is to evaluate the effect of fasting versus non-fasting state on the total testosterone levels in women during the reproductive period. Methods This study was conducted at Faiha Specialized Diabetes, Endocrine and Metabolism Centerin Basrah, (Southern Iraq) betweenJanuary 2022 to November 2022. The total enrolled women were 109; their age was 18-45 years. The presentation was for different complaints; 56 presented for medical consultation with 45 apparently healthy women accompanying the patients as well as eight volunteering female doctors. Testosterone levels were measured by electrochemiluminescence immunoassays using the Roche Cobas e411 platform (Roche Holding, Basel, Switzerland). Two samples were collected from each woman; one was fasting and another was non-fasting the following day, and allsamples were taken before 10 am. Results For all of the participants, the mean ± SD fasting was significantly higher as compared to the non-fasting testosterone (27.39±18.8 ng/dL and 24.47±18.6 ng/dLrespectively,p-value 0.01). The mean fasting testosterone level was also significantly higher in the apparently healthy group, (p-value 0.01). In women who presented with hirsutism, menstrual irregularities and or hair fall, no difference was seen in the testosterone levels between fasting and non-fasting states (p-value 0.4). Conclusion In the apparently healthy women of childbearing age, serum testosterone levels were higher in the fasting versus the non-fasting states. In women who presented with complaints of hirsutism, menstrual irregularities, and or hair fall, the serum testosterone levels were not affected by the fasting states.

Comparison of sexual function in infertile women with polycystic ovary syndrome and endometriosis: A cross-sectional study.

Infertility is one of the issues affecting sexual function (SF). Infertility is also one of the complications of polycystic ovary syndrome (PCOS) and endometriosis. This research seeks to assess and compare SF and the prevalence of sexual dysfunction in infertile women with PCOS and endometriosis. A cross-sectional study was carried out with a sample of 630 (210 infertile women with endometriosis, 210 infertile women with PCOS, and 210 healthy women of childbearing age as the control group). SF was assessed by the female sexual function index (FSFI). Descriptive statistics and inferential statistics were used to analyze the data. The primary outcome measured was FSFI score. Secondary outcome was hospital anxiety and depression scale score. The results showed that the mean score of the total FSFI in the 2 groups of PCOS and endometriosis was lower than the control group (p 0.001). In addition, women with higher education (university education) had a higher total FSFI. Sexual dysfunction rates are high in infertile women with endometriosis and PCOS. Infertility service providers in infertility centers need to pay attention to this issue.

Peculiarities of the clinical course and pathomorphological picture of ovarian endometriosis and adenomyosis in reproductive aged women

Оbjectives: to assess the clinical and pathomorphological features of ovarian endometriosis and adenomyosis in women of reproductive age in order to determine possible causes of fertility disorders and ways to correct them.Materials and methods. 87 patients were examined and divided into 2 groups. The first group included 45 (51.7%) patients with adenomyosis with or without concomitant pathology. The second group included 42 (48.3%) women with ovarian endometriomas. The control group consisted of 30 healthy women of childbearing age who were screened for male infertility.Results. Clinical examination of the patients revealed a high frequency of gynecological (uterine fibroids, endometrial hyperplasia, infertility) and extragenital pathology. Obstetric and gynecological history was burdened by reproductive losses (involuntary and medical abortions, ectopic pregnancy), premature birth, preeclampsia, abnormal uterine and obstetric bleeding, and pelvic surgery. All patients underwent endoscopic treatment (laparoscopy, hysteroscopy). Morphological examination revealed features of the structure of endometrioid cysts, which explains the decrease in ovarian reserve, active adenomyosis, reactive hyperplasia and chronic endometritis, distortion of the uterine cavity by fibroids. This may play an important role in implantation and placentation.Conclusions. Features of morphogenesis of ovarian endometrioma, found by us cystic and glandular-cystic forms may form the basis of endometrial microperforation pathogenesis, development of adhesions of the pelvic organs (in every third woman), ectopic pregnancy, fibrotic adjacent endometrioid tissue and reduction of ovarian reserve. The peculiarities of the uterus histostructure in adenomyosis, frequent combination with uterine fibroids, endometrial hyperplasia, chronic endometritis, ovarian endometriosis, deep infiltrative endometriosis, old age, aggravated obstetric anamnesis and the history of obstetric disorders may be related.

Genital Microbiota of Women From Six Ethnic Groups With and Without Human Papillomavirus Infection in Shangri-La, China.

BackgroundA diversity of microorganisms is associated with human health and exists in a state of dynamic equilibrium. This diversity has direct implications for the assessment of susceptibility to infectious diseases, especially human papillomavirus (HPV) infection.MethodsHere, we investigated the relationships between HPV infection and vaginal, cervical, and gut microbiota composition and assessed the levels of genital immune mediators. We selected a multiethnic area in Yunnan Province, China, to collect samples from healthy women of childbearing age. A total of 82 healthy women of childbearing age were included in this study. Vaginal, cervical, and rectal swabs were collected to analyze the microbial community, and cytokines were analyzed in some samples.FindingsDifferent proportions and types of HPV infection were detected in cervical (44%), vaginal (18%), and rectal (18%) swabs. HPV detected in cervical swabs was generally a high-risk type, while low-risk HPV types were primarily detected in vaginal and rectal swabs. There were some differences in this proportion as well as in the microbial community composition among different ethnic groups. Rectal samples exhibited the highest diversity index, while vaginal samples displayed the lowest diversity index. Lactobacillus dominated most of the vaginal samples, was decreased in HPV-positive samples, and differed among different ethnic groups. However, the sequence proportion of Lactobacillus in the cervix exhibited the opposite trend in those affected by HPV infection. The dynamic balance between the potential pathogens Gardnerella and Lactobacillus determines the health of the female genital system.InterpretationThis study constitutes the first step toward personalized medicine for women’s reproductive health, wherein differences between the genital microbiomes of individuals would be considered in risk assessment and for subsequent disease diagnosis and treatment.

The level distribution of serum AMH in different clinical manifestations of women of childbearing age

To investigate the distribution and diagnostic value of serum anti-Müllerian hormone (AMH) in healthy women of childbearing age, women with polycystic ovary syndrome (PCOS), ovarian dysfunction (DOR) and premature ovarian failure (POF). This study retrospectively selected female patients of childbearing age who were treated in the affiliated Obstetrics and Gynecology Hospital of Fudan University from January to December 2019. According to different clinical manifestations, they were divided into 133 cases in PCOS group, 120 cases in DOR group and 134 cases in POF group. 125 healthy women in the same period were selected as the control group. The values of serum AMH, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) were measured in the four groups. Single sample Kolmogorov-Smirnov test, one-way ANOVA, independent sample t-test, Kruskal-Wallis H test, Mann-Whitney U test, logistic regression analysis and ROC curve were used for comparative analysis. The serum AMH levels of PCOS group, DOR group, POF group and control group were 9.10 (6.67, 11.49) ng/ml, 0.11 (0.05, 0.29) ng/ml, 0.03 (0.02, 0.06) ng/ml and 2.99 (1.57, 4.98) ng/ml, respectively [M(Q1,Q3)], the differences were statistically significant (P<0.001). The basal endocrine levels including E2, FSH, LH and T also had significant differences between groups (P<0.001). The results of multiple comparisons showed that there were significant differences in AMH and LH between DOR, POF and PCOS groups and the control group. The T level of PCOS group was significantly higher than that of the control group, the E2, LH and T levels of DOR group were significantly higher than that of the control group, and the FSH level of POF group was significantly higher than that of the control group (P<0.05). The area under the curve (AUC) of AMH and AMH+LH in the diagnosis of PCOS were 0.905 and 0.922, the sensitivity was 82.7% and 85.0%, and the specificity was 88.0% and 88.8%. The AUC of DOR was 0.861 and 0.971, the sensitivity was 89.0% and 92.5%, and the specificity was 63.0% and 92.0%. The AUC of POF was 0.950 and 0.998, the sensitivity was 98.3% and 99.2%, and the specificity was 75.9% and 97.0%, respectively. The AUC of AMH and AMH+LH combined indexes in the differential diagnosis of DOR and POF were 0.768 and 0.937, the sensitivity was 70.3% and 95.5%, and the specificity was 73.9% and 80.8%.

An Analysis on the Factors for Cervical Insufficiency Causing Adverse Emotions Among Pregnant Women at Different Gestation Phases.

BackgroundTo analyze the anxiety, depression, and related factors among pregnant women with cervical insufficiency, so as to provide a reference for clinical psychological intervention as an adjuvant therapy.MethodsA total of 101 cases in China with cervical insufficiency were included in the observation group by a convenience sampling method, and 114 normal healthy women of childbearing age were selected as the control group. Participants were investigated and observed for anxiety and depression by SAS and SDS, respectively, to analyze the emotional state and influencing factors of the patients with cervical insufficiency. Stratified by the first, second and third trimesters, our study used whether depressive or not and whether anxiety or not as the dichotomous variables. A multivariate Logistic regression was adopted to analyze the influencing factors. Relevant influencing factors were screened out by the forward stepwise method in combination with professional knowledge and the number of variables.ResultsThere were statistical significant differences in SAS and SDS between observation group and control group and the incidence rate of anxiety and depression was higher in pregnant women with CI. Multivariate Logistic regression demonstrated that history of abnormal pregnancy was the main influencing factor for anxiety and depression in the early and middle gestation phases, and cervical insufficiency was the factor influencing the anxiety in early gestation and both anxiety and depression in the late gestation phase.ConclusionCervical insufficiency may have a negative impact on the emotions of pregnant women. Individualized and targeted mental care should be added into clinic work to prevent negative outcomes.

Dynamics of vaginal microbiota in women of reproductive age during the menstrual cycle

Objective: To investigate the dynamic changes of vaginal microbiota in different phases of menstrual cycle in healthy Chinese women of childbearing age. Methods: A total of 11 healthy women of childbearing age with regular menstruation, who had physical examination in the Gynecology Clinic of Beijing Obstetrics and Gynecology Hospital from September to December 2020 were randomly selected as research subjects. Vaginal secretions were collected during menstrual phase (2nd-3rd day), mid-follicular phase (7th-8th day), and mid-luteal phase (21st-22nd day) for microbiota analysis through metagenomic sequencing. Results: (1) Vaginal microbiota species were the most diverse in menstrual phase and the least in follicular phase, observing dominant vaginal bacteria gradually changing to Lactobacillus from menstrual phase to follicular phase and then to luteal phase. (2) The dynamic evolution of vaginal microbiota from menstrual phase to follicular phase and then to luteal phase was divided into: no change in dominant bacteria, replacement of dominant bacteria, changes in the proportion of dominant bacteria, and recurrence of dominant bacteria (non-Lactobacillus-dominance appeared again in luteal phase after returning to normal Lactobacillus-dominance in follicular phase). (3) Prevotella, especially Prevotella_bivia, was significantly higher during menstrual phase. Conclusions: Healthy vaginal microbiota should be relatively stable, but also have the ability of dynamic change and self-recovery. Prevotella plays a central role among opportunistic pathogens in the vagina, whose function remains to be investigated.

Assessment of the Levels of Peripheral Lymphocytes Subpopulation in Healthy Women of Childbearing Age: a Prospective Cohort Study.

To evaluate changes in the levels of the peripheral lymphocyte subpopulation (PBLS) during the menstrual cycle in healthy women of childbearing age (HWOBA), for establishing a normal reference range. Flow cytometric analysis was performed for the assessment of the levels of PBLS during one menstrual cycle in HWOBA. Moreover, ovulation was monitored. The multivariable logistic regression models were used to evaluate the effects of age and body mass index (BMI) on PBLS. The levels of PBLS including CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD16+CD56+ lymphocytes and ratio of Th1/Th2 cells, were relatively stable during the menstrual cycle. However, each increment in age (year) was proportional to a decrease (14%) in the level of CD8+ T cells and an increase (10%) in the level of CD19+ B cells (p < 0.05). Increased BMI was inversely proportional to the level of CD16+CD56+ natural killer (NK) cells. Thus, the normal reference intervals for PBLS in HWOBA were established. The levels of PBLS can be used for daily monitoring of immune status in HWOBA. Notably, age and BMI may affect PBLS level. The normal reference ranges for PBLS levels can provide a basis for the research and treatment of recurrent pregnancy loss.

Confirmation of the cardiac safety of nolasiban in a randomised cohort of healthy female volunteers

Nolasiban is an orally active oxytocin receptor antagonist being developed to increase the efficiency of assisted reproductive technologies. This study evaluated the pharmacokinetics, pharmacodynamics, and cardiac safety of nolasiban in 45 healthy women of child-bearing age. Nolasiban was administered in a fasted state with a standardised lunch served 4.5 h post-dose. Concentration-effect modelling was used to assess the effect of two dosages of nolasiban (900 mg and 1800 mg) on QTc following single-dose administration. We found no significant change in QTc at all tested dosages. Two-sided 90% confidence intervals of geometric mean Cmax for estimated QTc effects of nolasiban were below the threshold of regulatory concern. The sensitivity of the assay to detect small changes in QTc was confirmed by a significant shortening of QTc between 2 and 4 h after consumption of a meal, which served to validate the model. Independent of the nolasiban assessment, this study also explored the effects of sex hormones on ECG parameters, especially QT subintervals. We found a significant relationship between JTpc and oestradiol. Heart rate was negatively correlated with progesterone. This study confirms the cardiovascular safety of nolasiban and describes relationships of sex hormones and ECG parameters.

An observational study of the reactogenicity and immunogenicity of 13-valent pneumococcal conjugate vaccine in women of childbearing age in Papua New Guinea

BackgroundMaternal immunization with pneumococcal conjugate vaccine (PCV) may protect young infants in high-risk settings against the high risk of pneumococcal infections in early life. The aim of this study was to determine the safety and immunogenicity of 13-valent PCV (PCV13) in healthy women of childbearing age in PNG.MethodsAs part of this observational study, 50 non-pregnant women of childbearing age (18-45 yrs. old) living in the highlands of PNG were vaccinated with a single dose of PCV13. Local and systemic reactogenicity were assessed 24–48 h after vaccination. Venous blood samples were collected before and 1 month after vaccination to measure PCV13 serotype-specific IgG antibody concentrations.ResultsNo severe adverse effects were reported during the 1-month follow-up period. IgG antibody concentrations significantly increased after vaccination for all PCV13 serotypes. One month after vaccination IgG antibody levels ≥2.5 μg/mL were reached in at least 75% of women for all PCV13 serotypes, except serotype 3, and ≥ 5 μg/mL in at least 75% of women for 7 serotypes (serotypes 6B, 9 V, 14, 18C, 19A, 19F and 23F).ConclusionPCV13 is safe and immunogenic in women of childbearing age living in a high-risk setting in PNG. This supports the implementation of studies to investigate the safety and immunogenicity of maternal PCV vaccination in high-risk settings as a strategy to protect infants in these settings against the high risk of pneumococcal infections in early life.Trial registrationNCT04183322. Registered 3 December 2019 - Retrospectively registered

Hit Effects On Substrates Oxidation Rates Of Women In Different Phases Of Monthly Ovarian Cycle

The metabolic inflexibility (limitation to respond or adapt to conditional changes in metabolic demand due to dietary patterns, energy availability, or circulating energy substrates) may be associated with variations in estrogen concentrations observed during the monthly ovarian cycle, whereas that apparently healthy women of childbearing age exhibit variation in substrates oxidation rates that may lead to overweight, type II diabetes and other associated conditions. PURPOSE: The aims of this study were to verify and compare the influence of eight treadmill high-intensity interval training (HIT) sessions on carbohydrate and lipid oxidation rates (CHOox and LIPox, respectively) and intensities of ventilatory anaerobic thresholds (VATs) of women in different phases of monthly ovarian cycle. METHODS: Eleven irregularly active women performed incremental treadmill exercise testing followed by submaximal work-rate running for 45min to determine VATs, VO2peak, peak velocity (Vpeak), and substrate oxidation rates, before and after training period, in different phases of their monthly ovarian cycle (“Follicular” phase group, FPG, n=6; “Luteal” phase group, LPG, n=5). The training period consisted of eight HIT sessions, composed each one of eight sets of 60s running at 100%Vpeak interspersed by 75s recovery, every 48h. RESULTS: Our results showed no significant differences in VATs intensities between groups. The comparison between groups showed significant differences in relative energy derived from CHOox pre-post training of the -61.4% and -59.3% respectively, and LIPox pre-post training of the 27.5% and 34.4% respectively. The relative energy derived from CHOox after the training period were 18.9% and 25.5% higher to FPG and LPG, respectively; consequently, the relative energy derived from LIPox after the training period were 8,45% and 3.46% lower to FPG and LPG, respectively. Over the training period, Vpeak was ~13.5 km/h, which produced the relative intensities of ~89%VO2peak e ~93%HRpeak for both groups. CONCLUSION: The monthly ovarian cycle phases promote significant changes on substrates oxidation rates leading to decrease of CHOox. High intensity interval training can minimize the differences observed and constitute an alternative intervention.

Seroprevalence of anti-Parvovirus B19 IgG in childbearing age women in Pleven region (Bulgaria)

Abstract Background Parvovirus B19 is a widespread infection in childhood. Seroprevalence of anti-Parvovirus B19 increases with age and about 60% to 70% of women of childbearing age have serological evidence of past exposure to virus. Diaplacental Parvovirus B19 infection in pregnant women can lead to anaemia, non-immune hydrops fetalis and foetal death. The aim of the study is determining the susceptibility to Parvovirus B19 in childbearing age women. Methods We conducted a prospective seroepidemiological study in which 90 healthy women of childbearing age (19 to 40 years) were tested during the period September-October 2018 in Medical Center “Clinical Institute for Reproductive Medicine”- Pleven, Bulgaria. Participants were surveyed on a voluntary basis. The exclusion criteria were: presence of autoimmune disorder, immunosuppressive states, malignancy and populations at risk such as persons under 18 years of age and pregnant women. The presence of specific Parvovirus B19 IgG was detected using a standardized anti-Parvovirus B19 (IgG) ELISA kit. The demographic and anamnestic data were collected for each participant in Case Report Form. Results The average age of the women was 31.4 ± 4.9 years. Dominating were women with higher education (52.2%) living in urban areas (92.2%). The survey results showed that 37.8% of women were positive for anti-Parvovirus B19 IgG, 61.1% were negative and 1.1% equivocal. Immunty to the virus increased from 27.3% to 45% with age. There was no significant correlation between the presence of antibodies and the demographic factors (living area, education and number of family members). Conclusions The results of this study imply that 61.1% of the childbearing age women in Pleven region are susceptible to infection with Parvovirus B19. Because of the high susceptibility to Parvovirus B19, active monitoring of risk groups pregnant women for the prevention of fetal complications is recommended. Key messages There is no specific treatment or prophylaxis against Parvovirus B19 infection and epidemiological surveillance requires the introduction of effective preventive measures at the public health level. Active monitoring in childbearing age women is necessary to reduce the risk of fetal damage and the cost of healthcare associated with the infection.

Variation of amide proton transfer signal intensity and apparent diffusion coefficient values among phases of the menstrual cycle in the normal uterus: A preliminary study

PurposeTo explore changes in the amide proton transfer (APT) signal intensity (SI) among different phases of the menstrual cycle in healthy young women and to determine whether the APT SI correlates with the apparent diffusion coefficient (ADC). Materials and methodsTwenty healthy women of childbearing age received regular pelvic magnetic resonance imaging (MRI) examinations and APT scans during the menstrual, proliferative and secretory phases of their menstrual cycle. Then, the APT SI and ADC values of the endometrium, myometrium and junctional zone were measured and analyzed to explore the changes during different phases of the menstrual cycle. The Pearson correlation coefficients between the APT SI and ADC were calculated. ResultsBesides the APT SI in the secretory phase, the APT SI and ADC in each menstrual phase were higher in the myometrium and endometrium than in the junctional zone, the APT Si did not differ significantly between the endometrium and myometrium during any phase. In each uterine structure, both the SI and ADC were highest in the secretory phase, second highest in the proliferative phase and lowest in the menstrual phase, but the APT SI did not differ significantly between the menstrual phase proliferative phases. Interindividual variation in APT SI and ADC for a given zone or phase ranged from 1.86% to 2.75% and from 0.37 × 10−3 mm2/s to 0.85 × 10−3 mm2/s, respectively. The Pearson correlation coefficient between APT SI and ADC was 0.481 (P < 0.01). ConclusionWhen the APT SI or ADC values are used to analyze uterine lesions, their changes during the menstrual cycle in childbearing aged women should be considered.

Vitamin D3 induces the expression of membrane progesterone receptors (mPRs) on naive CD4+ T lymphocyte cells in women of reproductive age

ObjectiveVitamin D3 and progesterone (P4) both belong to steroid hormones. These hormones have effects on the function of each other in different ways. The immunomodulatory activity of vitamin D3 and P4 and their role in inducing maternal tolerance for fetus have been shown in various studies. The purpose of this study was to evaluate the effect of vitamin D3 on the expression of membrane progesterone receptors (mPRs) on CD4+ T cells. Materials and methodsNaive CD4+ T cells were isolated from peripheral blood of 38 healthy women of childbearing age. After stimulating by anti-CD3 and anti-CD28 monoclonal antibodies (mAb), these cells were exposed to either various concentrations of vitamin D3 or no exposure at all in a culture medium at 37 °C for 3 days. In the final stage, the mean fluorescence intensity (MFI) of mPRα and mPRβ were evaluated using polyclonal and monoclonal antibodies and several gating strategies on CD4+ T cells. ResultsVitamin D3 significantly increased the expression of mPR α and mPR β on the surface of CD4+ T cells (p ≤ 0.05). ConclusionThe present study demonstrated the potential effect of vitamin D3 on increasing the expression of P4 receptors on CD4+ T cells. This study shows a new aspect of correlation between vitamin D3 and P4 that may influence P4 performance. Therefore, our findings suggest that the appropriate level of this vitamin may affect the optimum P4 immunomodulatory activity during pregnancy.