Immunological effects of human decidual mesenchymal stem cells in spontaneous and recurrent abortions.

The aim of this study was to evaluate the immunological activities of human decidual mesenchymal stem cells (MSCs) on proliferation, apoptosis and percentage of regulatory T cells (Treg) in abortions and to investigate whether these activities differ in spontaneous abortions (SA) and recurrent abortions (RA). This prospective cohort study included women who had a first-trimester abortion between 2019 and 2022. Women with uterine anomaly, endocrinological disease, known autoimmune or thrombophilic disease, and fetal chromosomal abnormality in abortion material were excluded. Decidual MSCs isolated from abortion materials were classified as spontaneous abortion-MSCs (SA-MSCs) and recurrent abortion-MSCs (RA-MSCs). Peripheral blood mononuclear cells were isolated from venous blood and co-cultured with SA-MSCs and RA-MSCs. The effects of MSCs on proliferation and apoptosis of lymphocytes, and Tregs levels were compared between SA-MSCs and RA-MSCs groups. Thirty cases (15 SA-MSCs and 15 RA-MSCs) were included in the study. The presence of MSC in co-cultures increased percentage of Treg cells while reducing proliferation and apoptosis compared to those without MSCs (p < 0.0001, p < 0.0001 and p < 0.0001). The increase in percentage of Treg cells and the reduction in apoptosis were significantly lower in the RA-MSCs group compared to the SA-MSCs group (p < 0.0001 and p < 0.001, respectively). Although the proliferation reducing effect of the presence of MSCs was lower in the RA-MSCs group compared to the SA-MSCs group, the difference was not significant (p = 0.07). MSCs contribute to maternal immunotolerance to semi-allogeneic fetus by suppressing proliferation and apoptosis, and increasing percentage of Treg cells. However, the immunoregulatory effects of MSCs are lower in RA compared to SA.

The outcome of two SMA cases treated with nusinersen at seven hours and at three days of life: the earliest ever.

New molecular therapies are available for the treatment of spinal muscular atrophy (SMA) but early intervention is required. We report two cases that were diagnosed prenatally, where treatment with nusinersen was initiated within 7 h and three days respectively. The children were followed up for 13 months and almost six years respectively. Both children have developed within entirely normal centiles, indicating that initiating treatment immediately after birth, as in these cases, is essential for a good outcome.

Accurate interpretation of thyroid dysfunction during pregnancy: should we continue to use published guidelines instead of population-based gestation-specific reference intervals for the thyroid-stimulating hormone (TSH)?

BACKGROUND: Considering the changes in thyroid physiology associated with pregnancy and poor outcomes related to abnormal maternal thyroid function, international guidelines recommend using population-based trimester-specific reference intervals (RIs) for thyroid testing. If these RIs are not available in the laboratory, implementing recommended fixed cut-off values globally is still controversial. To address this issue, we aimed to establish appropriate RI of thyroid-stimulating hormone (TSH) in pregnant Turkish women for our laboratory and compare the prevalence of thyroid dysfunction based on the established and recommended criteria. METHODS: Of 2638 pregnant women, 1777 women followed in the obstetric outpatient were enrolled in the reference interval study after applying exclusion criteria related to medical and prenatal history. A retrospective study was conducted by collecting data from July 2016 to March 2019. Serum TSH was measured by UniCel DxI 800 Immunoassay System (Beckman Coulter Inc., Brea, CA, USA). The study design relied on two approaches in order to classify pregnant women: trimester-specific and subgroup-specific; the latter involved dividing each trimester into two subgroups: T1a, T1b, T2a, T2b, T3a, T3b. The lower and upper limits of the RIs were derived by the parametric method after normalizing the data distribution using the modified Box-Cox power transformation method. RESULTS: The lowest TSH value was detected at 8-12 weeks in early pregnancy, and the median value of TSH in the T1b subgroup was significantly lower than the T1a subgroup (P < 0.05). TSH levels showed a gradual trend of increase along with the pregnancy and increased significantly in the T2a, T2b, and T3b subgroups compared to the preceding subgroups (P < 0.05). Compared to the diagnostic criteria recommended by American Thyroid Association (ATA), the prevalence of thyroid dysfunction was significantly different from the established trimester- and subgroup-specific RIs throughout the pregnancy (P < 0.001). CONCLUSIONS: We conclude that establishing gestation- and laboratory-specific RIs, especially for TSH, is essential for diagnosing thyroid disorders in pregnancy, and the recommended universal cut-off values, which may contribute to the risk of a misdiagnosis or a missed diagnosis, should be taken with caution in the clinical setting. However, regarding the fluctuation of thyroid function tests throughout pregnancy, trimester-specific RIs are insufficient, and implementing split phases is required.

Polymicrobial bacteremia due to Lactobacillus jensenii and Veillonella montpellierensis in a pregnant patient; case report and review of literature.

Prompt and accurate diagnosis of polymicrobial bacteremia, which causes the difficulty in anti-infective treatments, poor treatment outcome and high mortality, is essential for initiating effective antimicrobial therapy. Here we present a case of bacteremia caused by two types of uncommon bacteria, Lactobacillus jenseniand and Veillonella montpellierensis in a 29-year-old pregnant woman at 33 weeks of gestation with anemia due to iron deficiency. She had no comorbidity or other chronic illnesses and was successfully treated with appropriate antibiotic use.

Meckel-Gruber Syndrome: Clinical and Molecular Genetic Profiles in Two Fetuses and Review of the Current Literature.

Background: Meckel-Gruber syndrome (MKS; OMIM No. 249000) is a rare, in utero lethal disease characterized by occipital encephalocele, polycystic kidneys, and polydactyly. Methodology and Results: In this study, two fetuses diagnosed as having MKS in the prenatal period were evaluated on the basis of ultrasonographic findings, postmortem autopsy findings, and molecular genetic analyses. Using exome sequencing analyses a novel homozygous frameshift variant (NM_015631: c.530delA, p.Lys177Argfs*47) was detected at exon 4 of TCTN3 gene in case 1, and a novel homozygous synonymous variant (NM_025114: c.180G>A, p Lys60Lys) was detected at exon 3 of CEP290 gene in case 2. Case 1 is the first reported case in the literature, which showed the typical MKS clinical feature with a novel frameshift variation in the TCTN3 gene. The variant in case 2 is the first reported synonymous variant of CEP290 gene in the literature, which has been shown to affect splicing in a functional study at the RNA level. Conclusion: TCTN3 gene variants that were rarely associated with the typical MKS phenotype and all cases with these variations have been discussed in the context of genotype-phenotype. The detection of the first synonymous variant of CEP290 gene and the demonstration of its effect on splicing by a functional study are likely to contribute to the molecular etiology of MKS.

What do expectant parents know about antenatal ultrasound screening?

Objective: We aimed to investigate and compare the background knowledge and attitudes of pregnant women and their partners about antenatal ultrasound scans.Materials and methods: A cross-sectional survey was conducted in a university perinatology clinic. Pregnant women and their partners who underwent the first trimester ultrasound scan or the second trimester anomaly scan were invited to complete a questionnaire which contained items on their sociodemographic characteristics, knowledge, and attitude.Results: In total, 500 eligible expectant mothers and their partners (220 in the first trimester and 280 in the second trimester) were recruited. The knowledge and attitude of expectant mothers and fathers were statistically similar. Working status, education level, and presence of chronic disease were the factors affecting the number of correct answers in both expectant mothers and fathers. The knowledge levels of both the expectant mothers and fathers were similar in the first and second trimesters.Conclusions: Pregnant women's and their partners' attitudes and knowledge on antenatal ultrasound scans were similar and generally satisfactory.

Can first trimester maternal serum follistatin like 3 levels predict developing gestational diabetes mellitus?

PURPOSE: The purpose of this study is to determine whether the first trimester maternal serum levels of follistatin like 3 (FSTL3) are altered in patients who develop gestational diabetes mellitus (GDM). METHODS: This is a prospective nested case-control study that included 170 singleton pregnant women recruited in their first trimester. All women were followed up until the delivery and 144 of them completed the study. The maternal serum levels of FSTL3 were measured at 11-14 weeks of gestation. The GDM-affected women (n = 19) were compared with the GDM-free control women (n = 125) for potential serum biomarkers including the FSTL3 levels. RESULTS: There were no significant differences in maternal age, maternal pre-pregnancy body mass index, and neonatal birth weight between the GDM group and the GDM-free control group. Women with GDM had significantly greater weight gain during pregnancy than the women without GDM. Serum concentration of glycosylated hemoglobin was significantly higher in women with GDM. There were no significant differences in serum FSTL3 levels (p = 0.578) between the GDM group and the GDM-free control group. CONCLUSIONS: Our results suggest that the first trimester maternal serum FSTL3 levels are not altered in women who develop GDM and thus do not support the use of serum FSTL3 levels for early prediction of GDM.

Epithelioid trophoblastic tumor.

OBJECTIVE: To describe a case of epithelioid trophoblastic tumor (ETT) in a postmenopausal woman, which had several peculiar features that differentiate it from previously reported ETTs. CASE REPORT: ETT of the uterus is a rare form of trophoblastic tumor with only 100 cases distinguished until now. Our case differs from the previously reported ones due to its several exceptional features. Our patient had no history of trophoblastic or gynecological disease; is postmenopausal; had endocervical extension from the beginning; recurrences and metastasis at follow up; and had a high Ki-67 index and a normal beta-human chorionic gonadotropin value. CONCLUSION: Because precise differential diagnosis will alter the therapeutic approach and prognosis, it is necessary for treating physicians to be aware of these unusual presentations.

Purse-string double-layer closure: a novel technique for repairing the uterine incision during cesarean section.

AIM: To compare the classical double-layer uterine closure to a double-layer purse-string uterine closure (Turan technique) in cesarean section regarding short- and long-term results. METHODS: Patients were randomized into either the double-layer purse-string uterine closure arm (study group, 84 patients) or the classical double-layer uterine closure arm (control group, 84 patients). For short-term comparison, a detailed transvaginal ultrasound examination was planned in all patients 6 weeks after the operation and a wedge-shaped defect in the uterine incision scar was accepted as uterine scar defect and recorded. For the long-term comparison, subsequent pregnancies of these patients were followed up for any complication. RESULTS: The number of patients with ultrasonographically visible uterine scar defect was 12 (23.5% of all scar defects) in the study group whereas it was 39 (76.5% of all scar defects) in the control group (P < 0.001, χ(2) = 15.42). Demographic data, operation time, hospitalization time, preoperative and postoperative hemoglobin values were not significantly different between the groups. During the 2-year of the follow-up period, five patients in the study group and six patients in the control group became pregnant again. No complication during their pregnancies and second cesarean operation were encountered. CONCLUSION: With the Turan technique, the uterine incision length becomes shorter, and the frequency of uterine scar defect is lower regarding short-term results. More data is needed for long-term results. ClinicalTrials.gov NCT01287611.

Comparing the effects of intrauterine progestin system and oral progestin on health-related quality of life and Kupperman index in hormone replacement therapy.

AIM: The aim of this study was to compare the effects of intrauterine-system-releasing 20 µg daily of levonorgestrel (LNG IUS) plus 1 mg 17 beta-estradiol daily, orally with combined oral pill containing 1 mg 17 beta-estradiol/2 mg drospirenone daily as hormone replacement therapy, on health-related quality of life (HRQoL) and climacteric symptoms in postmenopausal women. MATERIALS AND METHODS: A 6-month prospective clinical trial was conducted at the Department of Obstetrics and Gynecology, Dr Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey. Ninety postmenopausal women were accepted to be part of the study. The Euro Quality of Life-5 Dimensions (EQ-5D) and Euro Quality of Life Visual Analogue Scale (EQ VAS) indexes for HRQoL and Kupperman indexes were compared between two groups of patients. RESULTS: Kupperman indexes of both treatment groups decreased gradually over 6 months, but indexes decreased significantly more in the group with intrauterine-system-releasing 20 µg daily of levonorgestrel. Elevations were observed in EQ-5D indexes and VAS values of both groups. EQ VAS values significantly increased in the group on intrauterine progestogen system. Similar changes were observed in the EQ-5D indexes of both groups. CONCLUSION: A hormone replacement therapy regimen that includes an intrauterine progestin system decreased climacteric symptoms and increased HRQoL in postmenopausal women during a follow-up period of 6 months. The extent of the relief of symptoms was greater in this group than in women receiving oral combined hormone replacement therapy. It seems therefore that the intrauterine progestin system could represent a method of choice for endometrial suppression in women using estrogen replacement therapy with distinct advantages over systemically administered progestogens, which have been the subject of considerable debate as reported in the recent literature.

The effectiveness of bilateral hypogastric artery ligation for obstetric hemorrhage in three different underlying conditions and its impact on future fertility.

OBJECTIVE: To evaluate the effectiveness of bilateral hypogastric artery ligation (BHAL) according to the underlying cause and future fertility in these women. METHOD: Fifty-eight women who underwent BHAL operation in our department between 1997 and 2008 were further divided into three subgroups in accordance with the underlying disease. Group 1: Severe preeclampsia with coagulapathy (n:24). Group 2: Postpartum hemorrhage (PPH) due to uterine atony (n:24). Group 3: Massive hemorrhage due to inadequate surgical control of bleeding and/or uterine rupture (n:10). Effectiveness of BHAL according to the underlying cause and future fertility after BHAL were evaluated. RESULTS: Success rate of BHAL was found to be 87.9% (51 out of 58 patients). Complication rates of the groups were 25%, 12.5%, and 10%, respectively. There was one maternal death in each group. Mean hospital stay, blood and blood products transfusion need were similar for all groups. Thirty women out of 58 had desired future fertility, and 17/30 (56.7%) of them became pregnant within less than 1 year. CONCLUSION: BHAL is a safe, effective, life-saving procedure in controlling massive PPH. It preserves future fertility and must be the first choice operation for PPH in young women whichever the underlying condition is.

Raloxifene: is it really effective on mood changes in postmenopausal osteopenic women?

OBJECTIVE: To investigate the effect of raloxifene therapy on menopausal symptoms, depression and anxiety scores using Kupperman's Scale, Hamilton Depression Rating Scale (HDRS) and Beck Anxiety Rating Scale (BARS) in osteopenic postmenopausal women. METHODS: This was a prospective, randomised, parallel and open labeled clinical study. One-hundred thirty-two postmenopausal osteopenic women with natural menopause enrolled into the study. One-hundred twenty-four of them completed the study. Group I patients were treated with oral raloxifene (60 mg/day), Group II patients were treated with oral calcium supplementation (1000 mg/day) for 3 months. The patient's menopausal, depressive and anxiety symptoms were assessed by using Kupperman's Scale, HDRS and BARS, before and at the end of treatment. For statistical analysis unpaired t, ANOVA, RM-ANOVA, MANCOVA, Pearson correlation tests were used. Statistical significance level was established at p < 0.05. RESULTS: Baseline Kupperman's Scale, HDRS and BARS scores were not different among two groups. At the end of 3 months of therapy, there was improvement in menopausal symptoms, depression and anxiety scores within both groups. When we compared change of scores before and after the treatment; group I scores were better than group II scores. CONCLUSION: Our results suggest that raloxifene may have a positive effect on mood in osteopenic postmenopausal women.

Effectiveness of short-term maintenance treatment with cabergoline in microadenoma-related and idiopathic hyperprolactinemia.

OBJECTIVE: This study aimed to determine the effectiveness of short-term maintenance treatment with cabergoline and to find out minimum effective dosage of cabergoline during maintenance treatment for patients with microadenoma-related and idiopathic hyperprolactinemia. STUDY DESIGN: Cabergoline was administered orally at a dose of 0.5 mg twice per week to 164 de novo hyperprolactinemic patients until serum prolactin level normalized. After this initial treatment phase, patients started on maintenance phase for which they were previously randomized. No maintenance treatment (Group I, n = 36) or cabergoline 0.5 mg (Group II, n = 46), 0.25 mg (Group III, n = 39), 0.125 mg (Group IV, n = 43) was administered twice per week for 8 weeks as maintenance treatment. Then, maintenance phase was finalized and patients were followed up for 6 months. Mean serum prolactin levels through maintenance treatment phase and follow-up period were assessed between groups and within groups. RESULTS: Except for group I, all the groups showed a similar pattern with fast decrease of serum prolactine level during maintenance phase and slower increase during the follow-up period. Notably, the average prolactin level was significantly lower at the last follow-up visit than at the diagnosis time in all of the groups. Stable normoprolactinemia of the groups at the end of follow-up period were 47.2, 37, 48.7, and 34.9%, respectively. CONCLUSIONS: The results indicate that short maintenance treatment in idiopathic and microadenoma-related hyperprolactinemia seems as effective as long maintenance treatment in the present study. But, further studies with larger study population and longer follow-up period are needed to make a decision about early treatment withdrawal. Also, during the maintenance treatment administration of medicine to patients should be tapered down to the lowest dose that will maintain prolactin levels normal.

The relationship between unexplained elevated serum markers in triple test, uterine artery Doppler measurements and adverse pregnancy outcome.

OBJECTIVE: To investigate the relationship between adverse pregnancy outcomes and unexplained elevations of second trimester maternal serum human chorionic gonadotropin (hCG), alpha fetoprotein (AFP) levels and uterine artery Doppler measurements. METHODS: A total of 144 women between 16-20 weeks of gestation that applied to our clinic for triple test were enrolled into the study. Study group consisted of 84 pregnant women with hCG and/or AFP levels > or =2 MoM. Control group comprised of 60 pregnant women with hCG and AFP levels <2 MoM. Study group was further subdivided into 3 subgroups: Subgroup I; only AFP> or =2 MoM (n=30), subgroup II; only hCG > or =2 MoM (n=64) and subgroup III; both AFP and hCG > or =2 MoM (n=10). RESULT: Operative delivery rate (p = 0.0017), overall complication rate (p=0.0002), bilateral early diastolic notch presence rate (p = 0.015) were high and mean birth weight was low (p=0.045) in the study group. In subgroup I patients, low birth weight [LBW] (p = 0.0008), preterm delivery (p = 0.0001), preeclampsia (p = 0.003) and preterm premature rupture of membranes [PPROM] (p = 0.012) rates were high. In subgroup II patients, only small for gestational age baby [SGA] (p = 0.016) rate was high. In subgroup III patients LBW (p = 0.009), preterm delivery (p = 0.0001) and PPROM (p = 0.01) rates were high. According to Doppler velocimetry studies, bilateral early diastolic notch presence rate was high (p = 0.015) in the study group. CONCLUSION: Patients with high AFP levels and bilateral uterine artery diastolic notch presence, are candidates for pregnancy complications and these groups of patients should be followed up more intensively.

Successful pregnancy in a patient with portal hypertension secondary to portal vein thrombosis due to essential thrombocythaemia: a rare case.

Essential thrombocythaemia (ET) is a disease characterized by an increased platelet count, megakaryocytic hyperplasia and a hemorrhagic or thrombotic tendency. Pregnancy in patients with ET can have a favorable outcome. However, ET has also been reported to complicate pregnancy by recurrent abortions, intrauterine death, and fetal growth retardation due to placental infarctions. ET has an unusual prevalence of intraabdominal (hepatic, portal and mesenteric) vein thrombosis, especially in young patients, which can lead to portal hypertension. There are ample cases in the literature of both essential thrombocytosis complicating pregnancy and portal hypertension complicating pregnancy, but the coincidence of both conditions appears to be unique. In this case report, we report a successful pregnancy in a patient with a prior diagnosis of essential thrombocytosis with remote secondary portal vein thrombosis and portal hypertension (PH).

Successful management of uterine prolapse during pregnancy with vaginal pessary: a case report.

UNLABELLED: We present a case of uterine prolapse complicating a second trimester pregnancy which was managed successfully with a vaginal pessary. CASE: A 19 year-old primigravid woman referred to the obstetric emergency unit at the 16th week of gestation complaining of uterine prolapse. A silicone ring-shaped middle-size vaginal pessary was placed into the vagina. On each control visit, when the vaginal pessary was removed, the uterine prolapse still persisted until birth. The patient gave birth at 38(th) week by spontaneous vaginal delivery to a healthy baby. After birth, with uterine contractions, uterine prolapse regressed progressively. CONCLUSION: The management and treatment of uterine prolapse in pregnancy should be individualized depending on the patient's preference. A vaginal pessary may be helpful to avoid complications of this condition and should be considered during patient counseling.

Transvaginal sonography, sonohysterography, and hysteroscopy for investigation of focal intrauterine lesions in women with recurrent postmenopausal bleeding after dilatation & curettage.

PURPOSE: To determine the diagnostic accuracy of different diagnostic methods (blind dilatation & curettage (D&C), transvaginal ultrasonography (TVS), sonohysterography (SH), and hysteroscopy) compared with gold standard (hysteroscopic biopsy's histopathologic result) in diagnosis of focal intrauterine lesions of recurrent postmenopausal bleeding. METHODS: 36 postmenopausal women with recurrent vaginal bleeding after a normal D&C results were enrolled into the study. TVS, SH, hysteroscopy were performed on all patients. Outcomes of blind D&C, TVS, SH, and hysteroscopy were compared with results of gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) were calculated. RESULTS: Blind D&C sensitivity, specificity, PPV, and NPV were 47, 68, 57, 59%, respectively in comparison with gold standard. Blind D&C fails to diagnose 70% of all focal intracavitary lesions. TVS sensitivity, specificity, PPV, NPV were 63, 78, 89, 41%, respectively. SH yielded better results; with 93% sensitivity, 56% specificity, 86% PPV, and 71% NPV. Hysteroscopy sensitivity, specificity, PPV, and NPV were 100, 44, 84, 100%, respectively. CONCLUSIONS: In experienced hands, SH can be an initial evaluation method of uterine cavity for detecting focal lesions in women with recurrent postmenopausal bleeding.

Pregnancy complicated with chronic myelogeneous leukemia (CML) successfully treated with imatinib: a case report.

Pregnancy and cancer is a complex situation. The coincidence of chronic myelogeneous leukemia (CML) and pregnancy is an uncommon event, in part because CML occurs mostly in older age groups. The management of CML during pregnancy is a difficult problem because of the potential effects of the therapy on the mother and fetus. Imatinib is a relatively new drug in this era and it induces dramatic hematologic and cytogenetic responses in CML but it is not recommended for use during pregnancy or if the patient plans to conceive. In the literature there are very few reports of outcome of pregnancy conceived while on imatinib. In this report, we describe a successful pregnancy and labor under treatment of imatinib in a patient who was diagnosed with CML at the beginning of her pregnancy.

Imperforate hymen: a new benign reason for highly elevated serum CA 19.9 and CA 125 levels.

Imperforate hymen is a urogenital tract anomaly that represents the most frequent congenital malformation of the female genital tract. CA 19-9 and CA 125 are widely used as tumor markers, however several benign conditions are also known to increase serum CA 19-9 and CA 125 levels. According to classical textbook knowledge, imperforate hymen is not listed under the benign conditions that increase serum CA 19-9 and CA 125 levels. In this case report we describe a relation between imperforate hymen and elevated serum CA 19-9 and CA 125 levels.