Elective Termination Of Pregnancy Research Articles

Prenatal diagnosis and prevalence of critical congenital heart defects: an international retrospective cohort study

ObjectivesTo assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality.SettingFifteen birth defect surveillance...

Proteomic identification of membrane-associated placental protein 4 (MP4) as perlecan and characterization of its placental expression in normal and pathologic pregnancies.

BackgroundMore than 50 human placental proteins were isolated and physico-chemically characterized in the 70–80s by Hans Bohn and co-workers. Many of these proteins turned to have important role in placental functions and diagnostic significance in pregnancy complications. Among these proteins was membrane-associated placental protein 4 (MP4), for which identity or function has not been identified yet. Our aim was to analyze the sequence and placental expression of this protein in normal and complicated pregnancies including miscarriage, preeclampsia and HELLP syndrome.MethodsLyophilized MP4 protein and frozen healthy placental tissue were analyzed using HPLC-MS/MS. Placental tissue samples were obtained from women with elective termination of pregnancy (first trimester controls, n = 31), early pregnancy loss (EPL) (n = 13), early preeclampsia without HELLP syndrome (n = 7) and with HELLP syndrome (n = 8), late preeclampsia (n = 8), third trimester early controls (n = 5) and third trimester late controls (n = 9). Tissue microarrays were constructed from paraffin-embedded placentas (n = 81). Slides were immunostained with monoclonal perlecan antibody and evaluated using light microscopy and virtual microscopy. Perlecan was also analyzed for its expression in placentas from normal pregnancies using microarray data.ResultsMass spectrometry-based proteomics of MP4 resulted in the identification of basement membrane-specific heparan sulfate proteoglycan core protein also known as perlecan. Immunohistochemistry showed cytoplasmic perlecan localization in syncytiotrophoblast and cytotrophoblasts of the villi. Perlecan immunoscore decreased with gestational age in the placenta. Perlecan immunoscores were higher in EPL compared to controls. Perlecan immunoscores were higher in early preeclampsia without and with HELLP syndrome and lower in late preeclampsia than in respective controls. Among patients with preeclampsia, placental perlecan expression positively correlated with maternal vascular malperfusion and negatively correlated with placental weight.ConclusionOur findings suggest that an increased placental perlecan expression may be associated with hypoxic ischaemic injury of the placenta in miscarriages and in early preeclampsia with or without HELLP syndrome.

Endothelin receptor antagonism during preeclampsia: a matter of timing?

Preeclampsia (PE) is a pregnancy complication, featuring elevated blood pressure and proteinuria, with no appropriate treatment. Activation of the endothelin system has emerged as an important pathway in PE pathophysiology based on experimental PE models where endothelin receptor antagonists (ERAs) prevented or attenuated hypertension and proteinuria. Hence, ERAs have been suggested as potential therapy for PE. However, developmental toxicity studies in animals have shown severe teratogenic effects of ERAs, particularly craniofacial malformations. Nonetheless, sporadic cases of pregnancy in women using ERAs to treat pulmonary hypertension have been described. In this review we give an overview of cases describing ERA use in pregnancy and critically address their possible teratogenic effects. A systematic search in literature yielded 18 articles describing 39 cases with ERA exposure during human pregnancy. In most cases there was only exposure in the first trimester, but exposure later or throughout pregnancy was reported in five cases. Elective termination of pregnancy was performed in 12 pregnancies (31%), two ended in a spontaneous miscarriage (5%) and no fetal congenital abnormalities have been described in the remaining cases. These preliminary findings support the idea that ERA treatment for severe, early onset PE might be an option if applied later in pregnancy, when organogenesis is completed to avoid teratogenic risks. However, third trimester toxicology studies are warranted to evaluate drug safety. Subsequently, it remains to be established whether ERA treatment is effective for alleviating maternal symptoms, as demonstrated in preclinical PE models, allowing pregnancy prolongation without leading to adverse neonatal outcomes.

Placental Galectins Are Key Players in Regulating the Maternal Adaptive Immune Response.

Galectins are potent immunomodulators that regulate maternal immune responses in pregnancy and prevent the rejection of the semi-allogeneic fetus that also occurs in miscarriages. We previously identified a gene cluster on Chromosome 19 that expresses a subfamily of galectins, including galectin-13 (Gal-13) and galectin-14 (Gal-14), which emerged in anthropoid primates. These galectins are expressed only by the placenta and induce the apoptosis of activated T lymphocytes, possibly contributing to a shifted maternal immune balance in pregnancy. The placental expression of Gal-13 and Gal-14 is decreased in preeclampsia, a life-threatening obstetrical syndrome partly attributed to maternal anti-fetal rejection. This study is aimed at revealing the effects of Gal-13 and Gal-14 on T cell functions and comparing the expression of these galectins in placentas from healthy pregnancies and miscarriages. First-trimester placentas were collected from miscarriages and elective termination of pregnancies, tissue microarrays were constructed, and then the expression of Gal-13 and Gal-14 was analyzed by immunohistochemistry and immunoscoring. Recombinant Gal-13 and Gal-14 were expressed and purified, and their effects were investigated on primary peripheral blood T cells. The binding of Gal-13 and Gal-14 to T cells and the effects of these galectins on apoptosis, activation marker (CD25, CD71, CD95, HLA-DR) expression and cytokine (IL-1β, IL-6, IL-8, IL-10, IFNγ) production of T cells were examined by flow cytometry. Gal-13 and Gal-14 are primarily expressed by the syncytiotrophoblast at the maternal-fetal interface in the first trimester, and their placental expression is decreased in miscarriages compared to first-trimester controls. Recombinant Gal-13 and Gal-14 bind to T cells in a population- and activation-dependent manner. Gal-13 and Gal-14 induce apoptosis of Th and Tc cell populations, regardless of their activation status. Out of the investigated activation markers, Gal-14 decreases the cell surface expression of CD71, Gal-13 increases the expression of CD25, and both galectins increase the expression of CD95 on T cells. Non-activated T cells produce larger amounts of IL-8 in the presence of Gal-13 or Gal-14. In conclusion, these results show that Gal-13 and Gal-14 already provide an immunoprivileged environment at the maternal-fetal interface during early pregnancy, and their reduced expression is related to miscarriages.

Kisspeptin regulation of human decidual stromal cells motility via FAK-Src intracellular tyrosine kinases.

Can of Clinical Genetics, Maastricht University Medical Centre, Maastricht kisspeptin and its analogues regulate the motility of human decidual stromal cells and what intracellular signaling pathways are involved? Kisspeptin analogue-mediated cell motility in human decidual stromal cells via the focal adhesion kinase (FAK)-steroid receptor coactivator (Src) pathway suggesting that kisspeptin may modulate embryo implantation and decidual programming in human pregnancy. The extravillous trophoblast invades the maternal decidua during embryo implantation and placentation. The motile behavior and invasive potential of decidual stromal cells regulate embryo implantation and programming of human pregnancy. Human decidual stromal cells were isolated from healthy women undergoing elective termination of a normal pregnancy at 6- to 12-week gestation, after informed consent. Kisspeptin analogues were synthetic peptides. Cell motility was estimated by an invasion and migration assay. Immunoblot analysis was performed to investigate the expression of kisspeptin receptor and the effects of kisspeptin analogues on the phosphorylation of FAK and Src. Small interfering RNAs (siRNAs) were used to knock down the expression of kisspeptin receptor, FAK, Src, matrix metallo-proteinases (MMPs) 2 and 9, and extracellular signal-regulated protein kinase (ERK) 1/2. The kisspeptin receptor was expressed in human decidual stromal cells. Kisspeptin agonist decreased, but antagonist increased, cell motility. Kisspeptin agonist decreased the phosphorylation of FAK and Src tyrosine kinases, whereas antagonist increased it. These effects on phosphorylation were abolished by kisspeptin receptor siRNA. The activation of cell motility by kisspeptin analogues was suppressed by siRNA knockdown of endogenous FAK (decreased 66%), Src (decreased 60%), kisspeptin receptor (decreased 26%), MMP-2 (decreased 36%), MMP-9 (decreased 23%), and ERK 1/2 inhibitor (decreased 27%). Human decidual stromal cells were obtained from women having terminations after 6-12weeks of pregnancy and differences in timing could affect their properties. Kisspeptin acting within the endometrium has a potential modulatory role on embryo implantation and decidual programming of human pregnancy. This work was supported by grant NSC-104-2314-B-182A-146-MY2 (to H.-M.W.) from the Ministry of Science and Technology, Taiwan, and grants CMRPG3E0401 and CMRPG3E0402 (to H.-M.W.). This work was also supported by grants from the Canadian Institutes of Health Research to P.C.K.L. P.C.K.L. is the recipient of a Child & Family Research Institute Distinguished Investigator Award. The authors have no conflicts of interest to disclose. N/A.

Loss of Placental P-Glycoprotein May Be a Common Pathophysiologic Pathway for First Trimester Spontaneous Miscarriages.

P-glycoprotein the highly conserved mammalian adenosine triphosphate-binding cassette transmembrane multidrug protein transporter is involved in peri-implantation events and fetal placental development. Greater expression in early versus late pregnancy and localization in both syncytio- and cytotrophoblast indicate that P-glycoprotein transports substances across the uterine epithelium during early pregnancy and protects the conceptus from toxic substances during implantation and early embryogenesis. We hypothesized that P-glycoprotein is involved in the physiologic maintenance of early pregnancy and that P-glycoprotein dysregulation may be involved in early pregnancy pathologies. First trimester dilation and curettage specimens were selected retrospectively from the archives of the Department of Pathology from spontaneous miscarriages (n = 36) and elective termination of pregnancy (n = 20). Two P-glycoprotein specific monoclonal antibodies JSB1and C219 were used on formalin-fixed, paraffin-embedded 5µ tissue sections. The location, intensity, and percentage of P-glycoprotein chorionic villous immunostaining were semiquantitated. Spontaneous miscarriages demonstrated absence or significant reduction in P-glycoprotein compared to elective terminations; 75% (27/36) showed total absence of P-glycoprotein, 19% (7/36) showed only rare villi with discontinuous immunostaining, and 6% (2/36) showed weak immunostaining. In contrast, 90% of elective terminations (18/20) showed positive immunostaining for P-glycoprotein and only 10% (2/20) showed loss of P-glycoprotein expression (P < .0001). We report a dramatic loss/decrease of P-glycoprotein in first trimester spontaneous miscarriages. This finding in conjunction with the known high expression of P-glycoprotein in normal first trimester placental tissues suggests an important role of P-glycoprotein in the maintenance of early pregnancy.

The effects of valproic acid on early pregnancy human placentas: Pilot ex vivo analysis in cultured placental villi

Valproic acid is an established structural and neurodevelopmental teratogen. Recently, we demonstrated that valproate alters the barrier function of perfused term human placentas. Here, we conducted a pilot study to evaluate the effects of subchronic valproate exposure on carrier expression in cultured placental villous explants from early human pregnancies. Placental tissue of gestational age 6-13weeks was collected from elective pregnancy terminations in women without known epilepsy. The effects of valproate (42, 83, or 166μg/mL) on the mRNA expression of 37 major placental carriers and related genes were evaluated by a customized gene expression array (n=5, 5days). Five-day exposure to valproate was associated with high variability in gene expression. However, two main gene clusters were identified, including a cluster of three major folate carriers. Exposure to low therapeutic levels of valproate (42μg/mL) was associated with a tendency toward reduced mRNA expression of genes encoding folate and amino acid and fatty acid carriers (P=0.065, paired analysis). Our initial findings suggest that valproate can affect the function of the human placenta during early pregnancy.

Characteristics of referred patients with twin-twin transfusion syndrome who did not undergo fetal therapy.

Abundant research has reported twin-twin transfusion syndrome (TTTS) outcomes following fetal therapy. Our research describes TTTS patients who did not undergo fetal therapy. Records from TTTS pregnancies evaluated at 16 to 26 gestational weeks were reviewed between January 2006 and March 2017. The study population comprised subjects who did not undergo fetal therapy. Based on initial consultation, patients were grouped as nonsurgical vs surgical candidates. TTTS progression and perinatal outcomes were assessed. Of 734 TTTS patients evaluated, 68 (9.3%) did not undergo intervention. Of these, 62% were nonsurgical candidates and 38% were surgical candidates. Nonsurgical candidates were ineligible for treatment because of fetal demise or maternal factors (placental abruption, severe membrane separation, and preterm labor). Of surgical candidates, 11 underwent expectant management, eight elected pregnancy termination, and seven planned fetal intervention but had a complication before the procedure. TTTS progression occurred in 10 (15.2%) of 66 cases. Neonatal survival in 64 cases was as follows: in 41 (64%), no survivors; in 11 (17.2%), one survivor; and in 12 (18.8%), two survivors. Nine percent of referred TTTS patients did not undergo fetal therapy, with many ineligible because of morbidity between referral and consultation. Studies of TTTS should acknowledge this subgroup and circumstances leading to lack of treatment.

Risk of Congenital Malformations: A Systematic Review

Congenital malformations (CM) are a public health issue, because they cause infant mortality, chronic disease and disability. The origin can be genetic, environmental or unknown causes. Among environmental contaminants, pesticides stand out. Many different causes of malformations have been established. The surveillance of a consecutive population of births, including stillbirths and elective terminations of pregnancy because of fetal anomalies, can identify each infant with malformations and determine the frequency of the apparent etiologies. CM abnormality of structure and, consequently, function of the human body arising during development. This large group of disorders affects almost 5 percent of infants and includes several major groups of conditions.

Direct toxicity of insulin on the human placenta and protection by metformin

To study the effects of insulin and metformin on primary trophoblasts from early pregnancies. Experimental invitro study. Academic research institute. Trophoblasts from healthy patients undergoing first trimester elective termination of pregnancy and primary lung fibroblasts (IMR-90). Culture and treatment with insulin and metformin of primary trophoblasts and primary lung fibroblasts (IMR-90). DNA damage measured by expression of γ-H2AX with immunofluorescence and Western blot. Apoptosis measured by expression of cleaved caspase-3 by Western blot. Cell survival measured by cell proliferation assay. Culture of purified primary trophoblast cells in the presence of insulin at levels as low as 1nM resulted in a 386% increase in the number of cell with elevated γ-H2AX expression, a 66% reduction in cell survival and a marked increase of cleaved caspase-3 expression. Pretreatment of trophoblasts with therapeutic doses of metformin prevented the detrimental effects of insulin. Treatment with insulin and/or metformin had no effects on primary fibroblasts. Elevated insulin levels are directly toxic to first trimester trophoblasts and result in increased DNA damage, apoptosis, and decreased cell survival. These effects are prevented by metformin. Trophoblast cells from early pregnancy are uniquely vulnerable to elevated levels of insulin. These findings, if confirmed invivo, suggest that there may be a role for insulin resistance screening before attempting pregnancy and for focusing on prevention of hyperinsulinemia during early pregnancy.

Concentrations of perfluoroalkyl substances (PFASs) in human embryonic and fetal organs from first, second, and third trimester pregnancies

BackgroundThe persistent environmental contaminants perfluoroalkyl substances (PFASs) have gained attention due to their potential adverse health effects, in particular following early life exposure. Information on human fetal exposure to PFASs is currently limited to one report on first trimester samples. There is no data available on PFAS concentrations in fetal organs throughout all three trimesters of pregnancy. MethodsWe measured the concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), and perfluorohexane sulfonic acid (PFHxS) in human embryos and fetuses with corresponding placentas and maternal serum samples derived from elective pregnancy terminations and cases of intrauterine fetal death. A total of 78 embryos and fetuses aged 7–42 gestational weeks were included and a total of 225 fetal organs covering liver, lung, heart, central nervous system (CNS), and adipose tissue were analyzed, together with 71 placentas and 63 maternal serum samples. PFAS concentrations were assayed by liquid chromatography/triple quadrupole mass spectrometry. ResultsAll evaluated PFASs were detected and quantified in maternal sera, placentas and embryos/fetuses. In maternal serum samples, PFOS was detected in highest concentrations, followed by PFOA > PFNA > PFDA = PFUnA = PFHxS. Similarly, PFOS was detected in highest concentrations in embryo/fetal tissues, followed by PFOA > PFNA = PFDA = PFUnA. PFHxS was detected in very few fetuses. In general, PFAS concentrations in embryo/fetal tissue (ng/g) were lower than maternal serum (ng/ml) but similar to placenta concentrations. The total PFAS burden (i.e. the sum of all PFASs) was highest in lung tissue in first trimester samples and in liver in second and third trimester samples. The burden was lowest in CNS samples irrespective of fetal age. The placenta:maternal serum ratios of PFOS, PFOA and PFNA increased across gestation suggesting bioaccumulation in the placenta. Further, we observed that the ratios were higher in pregnancies with male fetuses compared to female fetuses. ConclusionsHuman fetuses were intrinsically exposed to a mixture of PFASs throughout gestation. The compounds were detected in all analyzed tissues, suggesting that PFASs reach and may affect many types of organs. Collectively, our results demonstrate that PFASs pass the placenta and deposit to embryo and fetal tissues, calling for risk assessment of gestational exposures.

Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance.

Placental infection induces increased levels of pro-inflammatory cytokines, which have been implicated in the pathogenesis of pre-term labor. Endotoxin tolerance is a phenomenon in which exposure to a dose of endotoxin makes tissue less responsive to subsequent exposures. The objective of our study was to determine whether repeated exposure to endotoxin will induce a tolerant phenotype in normal human second-trimester placental tissue. Human second-trimester placental explants from elective termination of pregnancy were cultured and exposed to endotoxin (LPS). After 24hours, the media was collected for analysis, and the explants were re-exposed to LPS after adding fresh media for another 24hours. This process was repeated for a total of 4 LPS doses. The media was collected from each day and analyzed for cytokine levels. The first LPS treatment stimulated the secretion of the pro-inflammatory cytokines IL-1β and TNF-α. However, their production was significantly diminished with repeated LPS doses. Production of the anti-inflammatory cytokines, IL-1ra and IL-10, was also stimulated by the first LPS treatment, but secretion was more gradually and moderately decreased with repeated LPS doses compared to the pro-inflammatory cytokines. The ratios of the anti-inflammatory/pro-inflammatory mediators (IL-1ra/IL-1β and IL-10/TNF-α) indicate a progressively more anti-inflammatory milieu with repeated LPS doses. Repeated LPS exposure of human second-trimester placental tissues induced endotoxin tolerance. We speculate that endotoxin tolerance at the maternal-fetal interface will protect the fetus from exaggerated inflammatory responses after repeated infectious exposure.

Laparoscopic ovariectomy in dogs in late gestation

BackgroundSurgical sterilization of stray dogs is the most widely used technique to control stray dog population. Although ovariectomy is an effective technique for elective sterilization of female dogs, most stray dog population control programs generally utilize ovariohysterectomy for spaying female dogs. In the context of stray dog sterilization, laparoscopic ovariectomy has been utilized and reported to be cost-effective compared to programs utilizing open surgical approaches. However, when pregnant stray dogs are encountered either conventional ovariohysterectomy is performed or surgery is deferred altogether. It is reported that ovariectomy at any stage during canine pregnancy results in fetal resorption or abortion, however, clinical outcomes following laparoscopic ovariectomy in dogs in late gestation have not been previously reported. The purpose of this study was to investigate the outcome of laparoscopic ovariectomy with intra-gestational sac injection (IGSI) of potassium chloride (KCl) in dogs in late gestation.ResultsEight client owned dogs in the gestational age range of 40–50 days underwent laparoscopic ovariectomy with IGSI of KCl. Laparoscopic ovariectomy resulted in decreased serum progesterone from 11.6 ± 2.6 ng/ml on day 0 to 1.3 ± 0.4 ng/ml 24 h’ post-surgery. IGSI of KCl did not result in immediate fetal death and fetal death temporally closely followed the drop in serum progesterone noted 24 h post-ovariectomy. Viscous brown vulvar discharge preceded fetal expulsion by 12 h and all the fetuses were dead when expelled. Uterine evacuation was documented within 45 ± 20 h (1–3.5 days) in all dogs without any clinically significant complications.ConclusionLaparoscopic ovariectomy enables elective termination of pregnancy and simultaneous neutering of dogs in late gestation and has potential applications in high volume stray dog sterilization programs which utilize laparoscopy. Utility of IGSI of KCl in this regard is unclear.

Women’s perspectives on the management and consequences of hyperemesis gravidarum – a descriptive interview study

Objective: Hyperemesis gravidarum (HG) affects 0.3–3% of pregnant women and is a leading cause of hospitalization in early pregnancy. The aim of the study was to investigate women’s treatment and management of HG, as well as the consequences of HG on women’s daily life.Design and setting: A cross-sectional study based on a structured telephone interview and an online questionnaire. Participants were recruited by social media and by the Norwegian patient’s organization for HG.Subjects: Norwegian women that experienced HG.Main outcome measure: Women’s perspectives on management and consequences of HG.Results: The study included 107 women. Maternal morbidity was profound; about 3/4 of participants were hospitalized due to HG, and the majority showed clinical signs of dehydration (79%), ketonuria (75%), and >5% weight loss (84%). Antiemetics were used by >90% and frequently prescribed “as needed”. Metoclopramide (71%) and meclozine (51%) were most commonly used. Participants described HG as having severe psychosocial consequences and profound impact on daily activities. Almost two out of five reported thoughts of elective abortion, and 8 women had at least one elective pregnancy termination due to HG. Overall, 20 women (19%) changed GPs due to dissatisfaction with HG management.Conclusion: Despite the high psychosocial burden and major impact on daily activities, many women with HG reported a lack of support from healthcare professionals and suboptimal management. Greater awareness and knowledge among healthcare professionals is needed to improve care for women with HG.Key PointsThere is a paucity of studies on management and the consequences of HG on women’s daily lives and psychosocial burden. We found that:• Many women described HG as one of their worst life experiences with profound morbidity.• Many women reported suboptimal management of HG and lack of support from healthcare professionals.• Greater understanding of patient perspectives among healthcare professionals is important to improve care and management for HG patients.

Comparison of intravaginal misoprostol and intramuscular carboprost for cervical priming in the first trimester of medical termination of pregnancy

Background: Suction evacuation is a widely used method for elective termination of pregnancy in the first trimester. The step of mechanical cervical dilatation during this procedure is probably the most critical step. Difficult cervical dilatation may cause incomplete evacuation, cervical laceration, and uterine perforation. Prior cervical priming with pharmacological agents like prostaglandin derivatives, although not free from side effects, makes the procedure easier with reduced overall complication rate and hence recommended in several guidelines. Aim: The aim of the study was to compare, two prostaglandin derivatives, intravaginal misoprostol (15-deoxy-16-hydroxy 16-methylprostaglandin E1) with intramuscular carboprost (15-methyl prostaglandin F2α) for cervical priming prior to suction evacuation in the first-trimester termination of pregnancy. Settings and Design: A prospective study was conducted at Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, Maharashtra. Materials and Methods: Eighty women requesting pregnancy termination from 6th to 12th week gestation were randomized into two groups. Two hours prior to suction evacuation, the first group (n = 40) received 400 μg of intravaginal misoprostol, while the second group (n = 40) received 125 μg of intramuscular injection carboprost. The outcomes of both the groups were recorded in terms of baseline cervical dilatation, immediate complications, drug-induced side effects, and patient's acceptability by questionnaire. Results: The “mean baseline cervical dilatation” prior to suction and evacuation in the misoprostol group was 8.11 ± 0.95 mm in the carboprost group was 6.25 ± 0.06 mm which is highly significant (t = 7.02, P 8 mm, compared to 17.5% in carboprost group (P = 0.004). The side effects including nausea, vomiting, and abdominal cramps were more in carboprost group as compared to the misoprostol group. No patient had diarrhea in misoprostol group as against 32.5% in carboprost group (P

470: Comparison of physical examination and ultrasound indicated cerclages between singleton and twin pregnancies

Physical examination indicated cerclage (PEIC) and Ultrasound indicated cerclage (UIC) are well stablished strategies for reducing preterm birth in singleton pregnancies. However, their indication in twin pregnancies is a controversial issue as no data from RCT are available to demonstrate their efficacy. The aim of this study was to compare perinatal outcomes after PEIC and UIC between singleton and twin gestations. Retrospective observational study including patients having PEIC or UIC in Hospital Clinic of Barcelona, from 2007 to 2016. Exclusion criteria were: monochorionic-monoamniotic placentation, major fetal anomalies and elective termination of pregnancy. Wilcoxon-test and Chi-square and Fisher’s exact test were used to compare continuous and categorical variables, respectively. Differences were considered statistically significant when p-value <0.05. 129 women with cercalge were evaluated. 60 women (43 singletons and 17 twins) underwent PEIC, and 2singleton pregnancies were lost to follow-up. 69women (56 singleton and 13 twins) underwent UIC, and 7 (6 singleton and 1 twin) were lost to follow up. Basal characteristics were similar between both PEIC groups, except that there were more twin pregnancies conceived by ART. Between UIC groups, there were more nulliparous and women with a previous preterm birth among twin pregnancies. Perinatal outcomes of PEIC and UIC are shown in Tables 1 and 2, respectively. No significant differences in the perinatal outcomes between singleton and twin pregnancies who underwent PEIC were observed. Regarding UIC, and despite latency to delivery in twins with UIC was significantly shorter compared to singletons, latency to delivery reached a median of 12 weeks. More PPROM and NICU admission were observed in twin pregnancies who underwent a UIC. Outcomes of PEIC were comparable between singleton and twin pregnancies. Outcome of UIC in twins show worse results compared to singletons but latency to delivery is still clinically relevant. Therefore, PEIC and UIC in twin pregnancies deserve further study as they may play a role as a therapeutic approach.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Retained Intrauterine Device (IUD): Triple Case Report and Review of the Literature

Background Throughout the world, intrauterine contraceptive devices (IUDs) are a frequently used, reversible, popular contraceptive method. They are usually placed without major complications. Uterine perforation is a rarely observed complication. Migration of the IUD to the pelvic/abdominal cavity or adjacent structures can occur after perforation. We present 3 cases of uterine perforation, possibly due to scarred myometrium associated with a cesarean delivery. We describe 3 perforations with IUDs lodged in the bladder serosa, the posterior cul-de-sac, and tissue adjacent to the cardinal ligament and external iliac artery. Cases Case 1. 26-year-old, Gravid 4, Para 2113, nonpregnant female with a history of a cesarean delivery underwent placement of an IUD one year after an elective pregnancy termination, presenting with abdominal pain requesting removal of the IUD. On speculum, although the IUD strings were visualized, the IUD could not be removed. Sonogram imaging identified an empty endometrial cavity with the IUD in posterior cul-de-sac. The IUD was removed via laparoscopy. Case 2 34-year-old Gravida 5, Para 4004, at 27 weeks and 3 days gestation, female with history of two previous cesarean deliveries underwent a third cesarean after spontaneous rupture of membranes with comorbid chorioamnionitis. Reproductive history was significant for placement of an IUD that had not been removed or imaged during obstetrical sonograms. The clinical evaluation revealed that the IUD had been spontaneously expelled. On the fifth operative day, the patient is febrile with CT demonstrating the IUD penetrating the anterior surface of bladder. On cystoscopy the bladder mucosa was intact. The IUD was removed via laparotomy with repair of the bladder, serosa, and muscular layer. Case 3 26-year-old, Gravid 4, P3013, nonpregnant female with three previous Cesarean deliveries had an IUD in place. However, with the IUD in situ, the patient conceived and had a spontaneous abortion. After the spontaneous abortion, she presented to clinic to have the IUD removed due to pain that was present since placement. Although the IUD strings were visualized, attempts to remove it were unsuccessful. Imaging identified the IUD outside the uterine cavity. Palpation with a blunt probe laparoscopically revealed a hard object within the adhesion band, close to the cardinal ligament. As per radiology evaluation, IUD was embedded 1cm from the external iliac artery on the right side outside the uterus in the adnexal region. A multidisciplinary procedure with gynecologic-oncologist was scheduled for removal due to the high risk of perioperative bleeding. Conclusion Patients in whom uterine perforation and IUD migration are suspected should have appropriate evaluation that includes transvaginal or transabdominal ultrasound or radiographs to confirm the position of the IUD, regardless of whether they are asymptomatic or present with symptoms. It is particularly important in the presence of a scarred uterus that imaging is used to identify the location of a missing IUD. The uterine scar of a cesarean may facilitate migration of the IUD. Cross sectional imaging, such as CT or MRI scan, may be needed to rule out adjacent organ involvement before surgical removal.

The role of the PD-1/PD-L1 axis in macrophage differentiation and function during pregnancy.

What is the role of the programmed cell death-1 (PD-1)/PD-1 ligand-1 (PD-L1) axis in macrophage polarization during early pregnancy? PD-1 signaling is a major regulator of macrophage differentiation and function, and it is critical for the success of a pregnancy. The predominance of decidual macrophages (DMs) with an M2 phenotype is an important contributor to maternal-fetal tolerance during early pregnancy. Twenty-four women with recurrent miscarriage (RM) and 70 women undergoing elective termination of an early normal pregnancy (NP) were included. Twelve female CBA/J, four male DBA/2, and four male BALB/c mice were included and mating carried out. The 12 CBA/J pregnant mice were then categorized into three groups of four mice: healthy control group CBA/J×BALB/c, abortion-prone pregnant group CBA/J×DBA/2 and normal pregnancies CBA/J×BALB/c treated with anti-PD-1 monoclonal antibodies. The profile of DMs, and the expression of PD-1 and PD-L1 in DMs from women with NP and RM were measured by flow cytometry. PD-L1 expression in human villi was determined by quantitative RT-PCR (qRT-PCR) and western blot. An in vitro model consisting of peripheral CD14+ monocytes isolated from women with NP was used. The profile of differentiated macrophages and their phagocytotic activity were then measured by flow cytometry. The mRNA levels of genes potentially underlying macrophage polarization modulated by PD-1 signaling were determined by qRT-PCR. Twelve pregnant mice were included in our in vivo model and underwent different treatment. The embryo resorption rate, and macrophage profile as well as PD-1 expression in murine spleens and uterus were analyzed by flow cytometry. Compared with NP, women with RM had elevated percentages of M1 DMs (P < 0.01), and reduced frequencies of M2 DMs (P < 0.05), as well as decreased PD-1 protein expression (P < 0.05) in the DMs. In addition, decreased mRNA and protein levels of PD-L1 expression in placental villi were observed in women with RM (P < 0.001). Using in vitro experiments, compared to the control group, we found that PD-1 activation by recombinant human (rh) PD-L1 Fc (human PD-L1 fused to the Fc region of human IgG1) drove the differentiation of macrophages with immuno-modulatory characteristics (P < 0.01). However, PD-1 blockade promoted dominance of the M1 phenotype (P < 0.01). PD-1 polarized macrophages showed enhanced phagocytic activity (P < 0.01), which was decreased with PD-1 blockade (P < 0.001). Furthermore, PD-1 blockade promoted the expression of pro-inflammatory cytokines and interferon regulatory factor (IRF) 5 (P < 0.05), while IRF4 expression was inhibited (P < 0.05). In addition, PD-1 blockade promoted macrophage glycolysis (P < 0.01) and inhibited fatty acid oxidation (P < 0.05). The mRNA expression levels of both phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin and mitogen-activated protein kinase/extracellular signal-regulated kinase/extracellular signal-regulated kinase were upregulated (P < 0.05) with PD-1 blockade during DM metabolic reprogramming. Moreover, in vivo mice data showed that PD-1 blockade or deficiency was associated with decreased M2 percentages at the maternal-fetal interface (P < 0.05) and embryo loss (P < 0.05). N/A. Whether the changes in DM polarization seen in miscarriage tissues are a cause or consequence of the demise of the pregnancy still requires further investigation. In addition, conducting metabolite analysis is required to further measure bioenergetic profiles. This is the first study on the role of the PD-1/PD-L1 axis in macrophage polarization during early pregnancy; such exploration enhances our understanding of the physiology of early pregnancy. Our study also indicates that targeting the PD-1 pathway may represent a novel therapeutic strategy to prevent pregnancy loss. This study was supported by the National Nature Science Foundation of China (No. 81671490) and Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College, HUST (No. 5001519002). None of the authors has any conflict of interest to declare.

Antibodies to Chlamydia trachomatis and reproductive health issues in women with SLE: a case–control study

BackgroundSLE is an autoimmune condition affecting predominantly women. Little is known regarding Chlamydia trachomatis infection in women with SLE, which may drive autoimmunity and contribute to obstetrical and vascular complications.MethodsThis...

Vaginal delivery outcomes of pregnancies following ultrasound-guided high-intensity focused ultrasound ablation treatment for uterine fibroids

Objective: To evaluate the feasibility and safety of vaginal delivery after ultrasound-guided high-intensity focused ultrasound (HIFU) ablation treatment for women with uterine fibroids of child-bearing ages.Methods: A prospective study was conducted on women who underwent ultrasound-guided HIFU therapy for uterine fibroids at the Chinese PLA General Hospital from January 2008 to December 2014. Patients were interviewed yearly to assess their fertility outcomes, including conception method, delivery mode, neonatal outcomes and complications during pregnancy, labor, and delivery.Results: A total of 174 patients with plans for future pregnancy were included, and 88 pregnancies in 81 women occurred. The pregnancy rate was 46.6% (81/174), and the median follow-up time was 76 months. The rate of pregnancies that ended in miscarriages was 10% (9/88), the rate of elective pregnancy termination was 6% (5/88), and 84% (74/88) of the pregnancies resulted in deliveries, with 3 of the 71 women having two deliveries. A cesarean section was requested by 50% (37/74) of the women, and 50% (37/74) opted for a vaginal delivery. Eleven of the 37 pregnancies were scheduled for elective cesarean sections, owing to pregnancy complications; the remaining 26 pregnancies were scheduled for vaginal delivery, and 21 (80.8%) were successful. None of the patients with a vaginal delivery experienced any complications during pregnancy and labor.Conclusions: Ultrasound-guided HIFU ablation could be considered a promising clinical treatment for women with uterine fibroids and plans for future pregnancy, and vaginal delivery after ultrasound-guided HIFU ablation treatment appear to be feasible and safe.