Assessment of vaginal and endometrial microbiota by real-time PCR in women with unexplained infertility.

AIM: Microbiota of the reproductive tract may be associated with unexplained infertility in women. We aimed to determine the derangements of vaginal and endometrial microbiota related to unexplained infertility by real-time polymerase chain reaction (real-time PCR) microbiota analyses of vaginal and endometrial samples of the unexplained infertility patients and fertile women. MATERIALS AND METHODS: Twenty-six women with unexplained infertility and 26 age-matched fertile women were included. Vaginal and endometrial samples were obtained in the mid-menstrual cycle for analysis by quantitative real-time PCR method. RESULTS: The proportion of lactobacilli-impaired microbiota was significantly higher in the vaginal samples of unexplained infertility patients (76.9% vs. 26.9%; p < 0.001). Those with impaired lactobacilli microbiota of vaginal samples had an increased risk of 9.048 times for infertility than those with normal lactobacilli microbiota. In addition, the mean lactobacilli/total bacterial mass (TBM) ratio in the vaginal samples was significantly lower in the unexplained infertility patients (38.2% vs.76.3%; p = 0.001). CONCLUSION: The present study results supported the role of vaginal and endometrial microbiota derangements in unexplained infertility. Many time-consuming and invasive methods are currently used in the diagnosis of infertility. Our study showed that the quantitative determination of lactobacilli/TBM ratio in vaginal specimens, a less invasive and easily obtainable method, could be used as a diagnostic test during the workup of couples with unexplained infertility.

Prediction of gestational diabetes mellitus and perinatal outcomes by plasma zonulin levels.

PURPOSE: Zonulin has been shown to be associated with many metabolic disorders, including type 2 diabetes mellitus, metabolic syndrome, and obesity. In this study, we aimed to evaluate the association between maternal plasma zonulin levels and gestational diabetes mellitus (GDM) and its perinatal outcomes. MATERIALS: A total of 100 pregnant women, 56 with GDM and 44 controls, were included in this prospective case-control study. Maternal plasma zonulin levels were evaluated in each trimester. The association between zonulin levels and GDM, body mass index (BMI) and adverse perinatal outcomes was evaluated. The GDM predictability of zonulin levels for each trimester was analyzed with the receiver operator curve (ROC). RESULTS: Plasma zonulin levels were significantly higher in pregnant with GDM in all trimesters (p < 0.001; for all). Optimum cut-off values of plasma zonulin levels in predicting GDM: first trimester: 6.27 ng/mL, second trimester: 12.71 ng/mL, and third trimester: 18.38 ng/mL. BMI was significantly higher in pregnant women with GDM (30.5 vs 26.1; p < 0.001). Zonulin levels were significantly higher in pregnant women with GDM with overweight BMI [≥ 25-30 (kg/m2)] in all trimesters (p < 0.05; for all). Zonulin levels were significantly higher in pregnant women with composite adverse outcomes that included at least one of neonatal intensive care unit (NICU) admission, meconium-stained amniotic fluid, and 1st minute APGAR score < 7. CONCLUSION: Increased maternal plasma zonulin levels were associated with increased risk of GDM and adverse perinatal outcomes. Zonulin may be a potential marker to predict GDM risk and perinatal outcomes.

Derangements of vaginal and cervical canal microbiota determined with real-time PCR in women with recurrent miscarriages.

Balanced vaginal microbiota and, as a continuum, cervical canal microbiota help prevent reproductive disorders, including recurrent miscarriage (RM). In a significant proportion of couples with RM, routine diagnostic workup cannot find any manageable cause, leading to a requirement for new diagnostic tools. In the present study, we determined the quantitative composition of the microbiota of the vagina and cervical canal, assessed by real-time polymerase chain reaction, in women with RM. It also evaluated their derangements related to the pathogenesis of RM, and thus the suitability of this test as a diagnostic tool for managing RM. Vaginal and cervical canal specimens of 25 women with RM and 25 healthy volunteers were collected. The test results revealed information about the total vaginal bacterial biomass by measuring the abundance of Lactobacillus spp.; other bacteria; and pathogens, including Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma (urealyticum + parvum), and Candida spp. Overall, the findings of this study implied the abundance of Lactobacillus spp. decreased in women with RM with an increase in the abundance of other microorganisms in accordance with the reduction in the abundance of Lactobacillus spp. due to aerobic vaginitis and bacterial vaginosis. Vaginal and cervical canal microbiota need to be considered during the diagnostic workup of women with RM.IMPACT STATEMENTWhat is already known on this subject? Recurrent miscarriage (RM) is a well-known reproductive disorder. Its diagnostic workup is not successful in determining the underlying problem in many cases. Hence, novel diagnostic tools based on real-time polymerase chain reaction (PCR) are needed for evaluating reproductive microbiota, which are considerably reliable, to satisfy the expectations of women with RM.What do the results of this study add? Overall, the decrease in the abundance of Lactobacillus spp. was found to be related to RM, and the patterns of the presence of other microorganisms were in accordance with the reduction in the abundance of Lactobacillus spp. These findings suggested an important role of vaginal and cervical canal microbiota in the pathogenesis of RM.What are the implications of these findings for clinical practice and/or further research? Additional research is warranted to elucidate the functional impact of altered components of the microbiota of vaginal and cervical canals on the physiology of the local cervical canal and its participation in the microbiota of the endometrial cavity, especially regarding unsuccessful pregnancies as a result of the disturbed physiology of the local endometrial microenvironment. However, possible applications of real-time PCR-based tests for the screening of subclinical infections in clinical practice require the performance of further investigations in patients with RM.

Lifesaving dose increment of cabergoline in life-threatening spontaneous ovarian hyperstimulation syndrome resistant to all interventions.

OBJECTIVE: Spontaneous ovarian hyperstimulation syndrome (SOHSS) is an extremely rare complication that deserves a multidisciplinary approach together with a thorough investigation for the correct diagnosis of the underlying pathology. The aim of this study was to present a case of severe SOHSS resistant to all interventions and to discuss the available interventions to overcome such a rare and serious clinical situation. CASE REPORT: We report a case of severe, life-threatening spontaneous OHSS with a normal nine weeks singleton pregnancy in a 25-year-old nulliparous woman, which resulted with pregnancy termination and continuation of disease progression until the dose of cabergoline was increased to 1.5 mg/day. CONCLUSION: This case report emphasizes that patients with life-threatening SOHSS resistant to all medical and surgical interventions may benefit from higher doses of cabergoline. Although spontaneous OHSS is extremely rare, it is potentially a life-threatening clinical entity in its severe form and needs time management and detailed examination of the underlying causes.

Zonulin as a potential biomarker for diminished ovarian reserve: A prospective study.

Objective: The purpose of this research is to investigate the relationship between zonulin levels and diminished ovarian reserve (DOR), and to evaluate the potential role of autoimmunity in the development of DOR. The study contributes to the understanding of the pathogenesis of DOR, which can be an unexpected diagnosis often associated with infertility and unpleasant physical symptoms in women. Materials and Methods: This cross-sectional study was conducted by scanning 224 patients. The demographic characteristics of the patients were recorded. Antral follicle counts of the patients were determined by ultrasound, and Anti-Mullerian hormone (AMH) levels were examined. Follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, AMH measurement, and antral follicle counts were made on the 2nd or 3rd day of menstrual bleeding. The zonulin levels of the participants were measured by the ELISA method. The patients were divided into two groups according to the presence of DOR. The patients' demographic characteristics and hormone levels were compared between these two groups, serum zonulin levels were examined, and the relationship between other hormone parameters and zonulin was investigated. Results: When the median ages of the patients in both groups were compared, the median age of patients with DOR was 38 years, significantly higher (p<0.001) than the median age of those without DOR, which was 27 years. The median zonulin levels of both groups were compare; it was observed that it was 19.71 ng/mL in the group with DOR and 11.03 ng/mL without DOR, and a statistically significant difference was found between the zonulin levels of the patients in both groups (p<0.001). A moderate inverse correlation (p<0.001) between patients' zonulin and AMH levels, and a moderate correlation between FSH levels (p<0.001). Conclusion: In conclusion, zonulin levels of patients with DOR were higher than women without DOR. Evaluation of zonulin levels may also be considered during the diagnosis of DOR.

Perinatal and neonatal outcomes of adolescent pregnancies over a 10-year period.

OBJECTIVES: Poor overall neonatal outcomes, small neonatal head circumference, neonatal hypoglycemia, need for Neonatal Intensive Care Unit and late-onset neonatal sepsis are more common in adolescents. The aim of this study is to draw attention to the outcomes of adolescent pregnancies. MATERIAL AND METHODS: This retrospective study was conducted in adolescent singleton pregnancies with maternal age < 15 years (n = 20, group 1), 16-19 years (n = 1929, group 2), and 20 years (n = 866, group 3). Age, gravidity, parity, and body mass index (BMI) measurements of mothers; mode of delivery, maternal and neonatal outcomes were evaluated and compared. RESULTS: The rate of preterm birth, postpartum hemorrhage, asymmetrical intra-uterine growth restriction (IUGR, as 3% percentile), macrosomia, and height of newborn of Group 3 was significantly higher. The rate of asymmetrical IUGR (as 10% percentile) was significantly lower in Group 3. The rate of severe preeclampsia and cesarean section was significantly higher in Group 3. The rate of Small for Gestational Age newborn, neonatal hypoglycemia, and late-onset neonatal sepsis was significantly higher in Group 1. CONCLUSIONS: Neonatal problems with poor obstetric outcomes are common in adolescent pregnant women, so that a family planning and baby care social trainings are important in achieving good long-term maternal and neonatal outcomes.

Relationship between serum cadherin 6 and 11 levels and severe and early-onset preeclampsia: A pilot study.

Objective: Preeclampsia is a highly morbid disease of placental origin, life-threatening condition for both a pregnant woman and her fetus. Cadherin 6 and 11 are adhesion molecules that play an important role in trophoblastic development and placentation. In our study, we investigated the change in serum cadherin 6 and 11 levels in pregnant women with preeclampsia. Materials and Methods: Pregnant women with preeclampsia were selected and compared with healthy women (as a control group) for a one-year study. The serum alanine aminotransferase, aspartate aminotransferase, and cadherin levels 6 and 11 of participants were analyzed and compared. Results: A total of 189 pregnant women were subdivided into 2 groups as preeclamptic (n=94) and women with healthy pregnancy (n=95). The cadherin 6 and cadherin 11 levels of the preeclamptic patients were significantly higher than those in the control group (p=0.001), and they were found to be significantly higher mainly in patients with early-onset and severe preeclampsia group (p=0.001). The cut-off cadherin 6 and 11 values for severe preeclampsia were found as 98.174 ng/mL and 1.92 ng/mL; with sensitivity of 88.3% and 84% respectively (p=0.001). Conclusion: The data analysis showed elevated serum cadherin 6 and 11 levels associated with the severity and early onset of pre-eclampsia. Serum cadherin 6 and 11 levels can be a candidate marker for the prediction of preeclampsia.

Oocyte maturation abnormalities - A systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina.

A small proportion of infertile women experience repeated oocyte maturation abnormalities (OMAS). OMAS include degenerated and dysmorphic oocytes, empty follicle syndrome, oocyte maturation arrest (OMA), resistant ovary syndrome and maturation defects due to primary ovarian insufficiency. Genetic factors play an important role in OMAS but still need specifications. This review documents the spectrum of OMAS and to evaluate the multiple subtypes classified as OMAS. In this review, readers will be able to understand the oocyte maturation mechanism, gene expression and their regulation that lead to different subtypes of OMAs, and it will discuss the animal and human studies related to OMAS and lastly the treatment options for OMAs. Literature searches using PubMed, MEDLINE, Embase, National Institute for Health and Care Excellence were performed to identify articles written in English focusing on Oocyte Maturation Abnormalities by looking for the following relevant keywords. A search was made with the specified keywords and included books and documents, clinical trials, animal studies, human studies, meta-analysis, randomized controlled trials, reviews, systematic reviews and options written in english. The search detected 3,953 sources published from 1961 to 2021. After title and abstract screening for study type, duplicates and relevancy, 2,914 studies were excluded. The remaining 1,039 records were assessed for eligibility by full-text reading and 886 records were then excluded. Two hundred and twenty seven full-text articles and 0 book chapters from the database were selected for inclusion. Overall, 227 articles, one unpublished and one abstract paper were included in this final review. In this review study, OMAS were classified and extensively evaluatedand possible treatment options under the light of current information, present literature and ongoing studies. Either genetic studies or in vitro maturation studies that will be handled in the future will lead more informations to be reached and may make it possible to obtain pregnancies.

Midregional pro-adrenomedullin and matrix metalloproteinase-2 levels in intrauterine growth restriction and small gestational age pregnancies: biochemical diagnostic difference.

OBJECTIVE: Midregional pro-adrenomedullin (MR-proADM) and matrix metalloproteinase-2 (MMP-2) are such proteins, that decreased levels are demonstrated in defective placental functions, as preeclampsia. The aim of the study is to compare maternal serum MR-proADM and MMP-2 levels across pregnancies with intrauterine growth restriction (IUGR), small for gestational age (SGA) and appropriate for gestational age (AGA), to biochemical screen the difference between SGA and IUGR. MATERIALS AND METHODS: 180 pregnant women were enrolled in a cross-sectional study: sixty pregnancies diagnosed for IUGR were included in group 1 (IUGR group), sixty pregnancies with SGA were in Group 2 (SGA group) and sixty pregnancies diagnosed for AGA, as control group. Maternal venous blood samples were collected at the time of enrollment, to assess serum MR-proADM and MMP-2 levels, by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean maternal serum MR-proADM and MMP-2 levels were lower in the IUGR group than in the SGA and AGA groups (p < .001 and p < .001). Maternal serum MR-proADM and MMP-2 cutoffs of 29.985 pg/mL and 1.875 ng/mL were found to be optimal to distinguish IUGR, with sensitivity of 98.3% and 98.3%, specificity of 83.3% and 89.2%, respectively. CONCLUSION: Maternal serum MR-proADM and MMP-2 levels were significantly lower in pregnancies with IUGR. Maternal serum MR-proADM and MMP-2 measurements could be used to distinguish IUGR pregnancies from SGA pregnancies.

Morbidly adherent placenta and cesarean section methods. A retrospective comparative multicentric study on two different skin and uterine incision.

OBJECTIVES: Morbidly adherent placenta (MAP) is one of leading causes of maternal mortality, with an increasing rate because of repeated cesarean sections (CS). The primary objective of this study is to compare two techniques of skin and uterine incisions in patients with MAP, evaluating the maternal fetal impact of the two methods. Retrospective multicentric cohort study. MATERIAL AND METHODS: A total of 116 women with MAP diagnosis were enrolled and divided in two groups. Group one, comprised of 81 patients, abdominal entry was performed by Pfannenstiel skin incision plus an upper transverse lower uterine segment (LUS) incision (transverse-transverse), which was 2-3 cm above the MAP border, with the uterus in the abdomen. In group two, comprised of 35 patients, abdominal entry was performed by an infra-umbilical midline abdominal incision, by vertical-vertical technique, and the pregnant uterus was incised by a midline incision (vertical) from the fundus till the border of the MAP. Total surgery time, blood loss, blood product consumption, total hospital stay, cosmetic outcomes, and postoperative complications were investigated. RESULTS: Total time of surgery was significantly shorter in group 1 (p < 0.05). Intraoperative blood loss was higher in group 2. Difference between preoperative and postoperative Hb and Htc levels were 3.30 ± 1.04 and 12.99 ± 5.07 respectively (p = 0.012; p = 0.033). The use of erythrocyte suspension (ES), fresh frozen plasma (FFP), and cryoprecipitate and thrombocyte suspension (TS) were found to be significantly lower in patients of group 1than vertical-vertical group (p = 0.008, p = 0.009, p = 0.001, p = 0.001, respectively). There was no difference in terms of total length of hospital stay between groups. CONCLUSIONS: In a subgroup of patients diagnosed for MAP, the transverse-transverse incision resulted in less bleeding, less blood and blood product use, and had better cosmetic results than vertical-vertical incision. Moreover, the total time of surgery, crucial for MAP patients, seems to be shorter also in transverse-transverse incision than in vertical-vertical incision.

Bladder filling before accreta surgery is a very effective method for preventing bladder injury: a retrospective cohort study.

OBJECTIVES: The aim of this study is to show whether bladder filling with saline before percreta surgery diminish the rate of bladder injuries or not. A secondary aim was to check the operative and postoperative outcomes between the cases of filled and unfilled bladder in placenta accreta surgery. METHODS: This retrospective multicentric cohort study involved 88 patients who were diagnosed with placenta accreta and underwent cesarean hysterectomy between 1 January 2009 and 1 January 2019. Women who had cesarean hysterectomies due to the indication of placenta accreta and did not have bladder filling were used as the control group. RESULTS: Eighty-eight women met the inclusion criteria. Forty-nine of the cases, the bladder was filled with saline solution before the operation, whereas in 39 the bladder was not filled. Intraoperative bladder injury occurred less in patients with preoperative filled bladders than in patients with unfilled bladders (p = .015; p < .05). There was a statistically significant difference between the duration of surgery according to bladder inflation (p = .001; p < .01); in the filled bladder group, the operation time was shorter than in the unfilled group. CONCLUSIONS: Filling the bladder with 200 ml saline solution before starting a cesarean section is an easy and useful technique that can reduce the possibility of bladder injury in placenta accreta surgery.

A Comparative Multicentric Study on Serosal and Endometrial Myomectomy During Cesarean Section: Surgical Outcomes.

OBJECTIVE: This multi-center study aims to determine the efficiency and safety of endometrial myomectomy (EM) for the removal of uterine fibroids during cesarean section (CS). METHODS: Retrospective review of 360 women diagnosed for fibroids during pregnancy. They all delivered by CS between 2014 and 2019. The study groups included 118 women who only underwent EM, 120 women who only had subserosal myomectomy by traditional technique and 122 women with fibroids who decided to avoid cesarean myomectomy, as control group. They were analyzed and compared the surgical outcomes. RESULTS: The EM, subserosal myomectomy and control groups were statistically (p > 0.05) similar for to age, body mass index (BMI), gravidity, parity, gestational age at delivery, indications for CS, number of excised fibroids, size of the largest myoma. Postoperative hemoglobin values and ? (?) hemoglobin concentrations were lower in SM group (10.39gr/dl vs 9.98 gr/dl vs 10.19 - 1.44 gr/dl vs 1.90 gr/dl vs 1.35; p = 0.047, p = 0.021; respectively) Hybrid fibroids were significantly more frequent in the EM group than subserosal myomectomy and control groups (respectively, 33.1% vs 23.3% vs 27.0%, p = 0.002). Surgery time was significantly longer in the subserosal myomectomy group than EM and control groups (respectively, 46.53 min vs 37.88 min vs 33.86 min, p = 0.001). Myomectomy took significantly longer time in the subserosal myomectomy than EM group (13.75 min vs 8.17 min, p = 0.001). CONCLUSIONS: Endometrial myomectomy is a feasible choice for treatment of fibroids during CS, and, basing on our results could be an alternative to traditional cesarean subserosal myomectomy.

Predictive value of early second trimester maternal serum cyclophilin A concentrations in women complicated with preeclampsia: a preliminary case-control study.

OBJECTIVE: To investigate cyclophilin A in early second trimester of pregnancy before the onset of preeclampsia. METHODS: In this prospective case-control study, 51 pregnant women whose serum were collected and stored and who developed preeclampsia in later follow-up and 41 pregnant women as control group were included. RESULTS: Maternal serum cyclophilin A levels in the study group who developed preeclampsia in later follow-up were significantly higher than those of normal healthy pregnant women. CONCLUSION: Cyclophilin A may be a valuable predictor for pregnant women who subsequently develop preeclampsia in their pregnancies.