First-trimester Miscarriage Research Articles

The role of polycystic ovary syndrome in reproductive and metabolic health: overview and approaches for treatment.

Polycystic ovary syndrome (PCOS) is a condition with a range of reproductive and metabolic features that affects 4–18% of reproductive-age women, depending on the diagnostic criteria used (1,2). PCOS typically involves hormonal imbalances, insulin resistance, and metabolic abnormalities, which significantly increase the risk of infertility, type 2 diabetes, and cardiovascular disease (CVD) (3) and affect quality of life (4). Women with PCOS suffer from greater body dissatisfaction and are also at increased risk of mood, generalized anxiety, and eating disorders (2,5,6). Despite its prevalence and implications for reproductive, metabolic, and psychological health, PCOS is underdiagnosed, in part because of the diversity of phenotypes manifested by this condition. PCOS is the most common cause of anovulatory infertility; ∼ 90–95% of anovulatory women seeking treatment for infertility have PCOS (7). Women may learn they have PCOS only after seeking infertility treatment. Most women with PCOS have elevated levels of luteinizing hormone and reduced levels of follicle-stimulating hormone (FSH), coupled with elevated levels of androgens and insulin (8). These imbalances can manifest as oligomenorrhea or amenorrhea (infrequent or lack of menstruation). Underproduction of estrogen and overproduction of androgens (testosterone, dehydroepiandrosterone, and androstenedione) by the ovaries can result in a number of additional clinical features, including tiny cysts on the surface of the ovaries (polycysts) and hair and skin symptoms (9). Women with PCOS who become pregnant are at higher risk than those without PCOS of developing gestational diabetes mellitus or suffering a first-trimester spontaneous abortion (2,9). Insulin resistance with compensatory hyperinsulinemia affects ∼ 65–70% of women with PCOS (10). An estimated 30–40% of PCOS patients have impaired glucose tolerance (IGT), and 7.5–10% have type 2 diabetes (7,9). Conversely, the prevalence of PCOS is elevated among women who have already been diagnosed with …

The obesity-related FTO gene variant associates with the risk of recurrent miscarriage.

To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage. Candidate gene association study. Human Genetics Unit, Colombo, Sri Lanka. A total of 202 Sinhalese women with two or more first-trimester miscarriages and no living children (cases) and 202 age- and ethnicity-matched women with no history of miscarriage and having two or more living children (controls). Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing. The prevalence of the single nucleotide polymorphism in cases and controls. The mean age of the women in the recurrent miscarriage group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the recurrent miscarriage group, 140 (69.3%) had experienced three or more first-trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single nucleotide polymorphism were increased in women in the recurrent miscarriage group compared with the control group. The obesity-related FTO rs9939609 single nucleotide polymorphism associates with recurrent miscarriage. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The single nucleotide polymorphism may be useful in predicting the risk of recurrent miscarriage.

Pregnancy outcome after electrosurgical cervical cone biopsy using Fischer cone biopsy excisor

Objective: To evaluate the pregnancy outcomes of all patients who underwent electrosurgical cone biopsy of the cervix between January 2000 and December 2011 and subsequently became pregnant.Study design: Retrospective cohort study.Settings: District General Hospital in the North East of England.Methods: Patients were identified from the local colposcopy electronic data, Hospital Episode Statistics and Maternity electronic data. Data were collected on a pro forma with two sections: (1) treatment section and (2) pregnancy section. In the treatment section, year and indication for treatment, volume of cervix removed, histological results and marginal status of specimen were documented. In the pregnancy section, time interval between treatment and pregnancy, pre-treatment obstetric history, cervical length measurements, cervical suture, gestation and mode of delivery and neonatal outcome were documented. Data were analysed using SPSS.Results: 25 women achieved 47 pregnancies after electrosurgical cone biopsy treatment. Most common indication for cone biopsy was glandular neoplasia accounting for nearly half of the procedures; 21.2% of pregnancies ended in first-trimester miscarriages. The preterm delivery rate (<37 weeks) was 19.4%. Volume of cervix excised was significantly greater in women who delivered preterm compared to women who delivered at term (p = 0.028). The rate of preterm delivery was significantly higher in post treatment pregnancies when compared to pregnancies before treatment in the same women (p = 0.02). The preterm delivery in post-treatment pregnancies was not related to the time interval between treatment and pregnancy (p = 0.54). There was no significant difference in miscarriage rates in pre- and post-treatment pregnancies (p = 0.98).Conclusion: Electrosurgical cone biopsy of cervix is associated with increased risk of preterm labour that is related to the volume of cervix excised.

Complete trisomy 9 with unusual phenotypic associations: Dandy-Walker malformation, cleft lip and cleft palate, cardiovascular abnormalities

ObjectiveTrisomy 9 is a rare chromosomal abnormality usually associated with first-trimester miscarriage; few fetuses survive until the second trimester. We report two new cases of complete trisomy 9 that both present unusual phenotypic associations, and we analyze the genetic pathway involved in this chromosomal abnormality. Case reportThe first fetus investigated showed Dandy-Walker malformation, cleft lip, and cleft palate) at the second trimester scan. Cardiovascular abnormalities were characterized by a right-sided, U-shaped aortic arch associated with a ventricular septal defect (VSD). Symmetrical intrauterine growth restriction and multicystic dysplastic kidney disease were associated findings. The second fetus showed a dysmorphic face, bilateral cleft lip, hypoplastic corpus callosum, and a Dandy-Walker malformation. Postmortem examination revealed cardiovascular abnormalities such as persistent left superior vena cava draining into the coronary sinus, membranous ventricular septal defect, overriding aorta, pulmonary valve with two cusps and three sinuses, and the origin of the left subclavian artery distal to the junction of ductus arteriosus and aortic arch. ConclusionComplete trisomy 9 may result in a wide spectrum of congenital abnormalities, and the presented case series contributes further details on the phenotype of this rare aneuploidy.

Polymorphisms in the fibrinolytic pathway genes and the risk of recurrent spontaneous abortion

Impaired fibrinolytic activity is implicated in the pathogenesis of recurrent spontaneous abortion (RSA). This case-control study assessed the prevalence of polymorphisms in fibrinolytic system genes in RSA. Cases comprised 202 Sinhalese women who had experienced at least two first-trimester spontaneous abortions and had no living children; controls were 202 women with no history of spontaneous abortion and two or more living children. The groups were matched for age and ethnicity. DNA was genotyped using the Sequenom MassARRAY system. The PLAUR rs4251923 A (OR 95% CI 2.3 [1.3 to 4.0]), SERBP2 rs6098 A (OR 95% CI 1.4 [1.1 to 1.9]) and SERBP2 rs6103 C alleles (OR 95% CI 1.4 [1.1 to 1.9]) were increased in the RSA group compared with controls. The prevalence of PLAUR rs4251923/ SERBP2 rs6098/ SERBP2 rs6103 GG/AA/CC (OR 95% CI 2.4 [1.2 to 4.9], GA/GA/GC(OR 95% CI 3.9 [1.3 to 11.2]), GA/AA/CC (OR 95% CI 2.9 [1.0 to 8.6] and GA/GG/GG (OR 95% CI 21.3 [1.1 to 410.3]) genotypes were also increased in cases. Polymorphisms in the fibrinolytic system genes are associated with RSA in Sinhalese women. These likely impair implantation.

Interaction of decidual CD56+ NK with trophoblast cells during normal pregnancy and recurrent spontaneous abortion at early term of gestation.

The immunological paradox of pregnancy, when maternal immune system recognizes but does not reject the semiallogenic foetus, is not yet fully understood. The aim of this work was to detail the mechanisms of the interaction of decidual CD56+ NK, infiltrating the maternal part of placenta, and trophoblast cells of foetal origin. Samples of the endometrial tissue from 13 healthy non-pregnant women, 37 placentas, obtained after medical abortion of viable pregnancy at 7-10weeks of gestation, and 26 samples of placentas from first-trimester recurrent spontaneous abortion (RSA) were used as the material for investigation. Phenotype of NK was assessed by flow cytometry. The influence of trophoblast cells upon IFNγ and GrB mRNAs expression by dNK was investigated by RT-PCR. The influence of dNK upon trophoblast cells migration and invasion was studied using collagen and Matrigel systems. In RSA group comparing to the normal pregnancy, the decrease of dNK with inhibitory receptors (NKG2A) and elevation of activated dNK were seen. In normal pregnancy, but not in RSA, trophoblast cells increased the expression of IFNγ and GrB mRNAs by CD56+ dNK. Both in normal and RSA pregnancy, dNK inhibited the migration and invasion of trophoblast cells. Initially, low invasive and migration capacities of trophoblast cells were seen during RSA. Thus, unbalanced activation of dNK can lead to the impairment of dNK and trophoblast cells interaction during RSA.

Fausses couches du premier trimestre : bénéfices et risques des alternatives thérapeutiques

The objective of this review was to assess early and late benefits and harms of different management options for first-trimester miscarriage. Surgical uterine evacuation remains the most effective and the quickest method of treatment. Depending on the clinical situation, medical treatment using misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) does not increase the risk of complications, neither haemorrhagic nor infectious. However, these alternatives generally require longer outpatient follow-up, which leads to more prolonged bleeding and not planned surgical procedures.

Müllerian duct anomalies diagnosed by saline contrast sonohysterography: prevalence in a general population

To estimate the prevalence of uterine müllerian duct anomalies in a general population. Cross-sectional study. University hospital in collaboration with the Danish Civil Registry. A total of 1,654 women randomly recruited from a general population; 686 women were eligible and accepted inclusion (429 pre- and 257 postmenopausal). Saline contrast sonohysterography (SCSH) was finally performed in 622 women (aged 20-74 years) (the procedure was impossible owing to cervical stenosis in 58, contraindicated in 2, other patient-related factors in 4). The shape of the uterus was dynamically evaluated in the transversal and longitudinal planes during SCSH and classified in accordance with American Fertility Society as normal, arcuate, septate (partial, complete), bicorn (partial, complete), or unicorn. History of previous miscarriage and menstrual cycle was obtained by a questionnaire. Prevalence of müllerian anomalies, miscarriage, and oligomenorrhea. The overall prevalence of müllerian anomalies was 9.8% (61 of 622) (95% confidence interval [CI] 7.5-12.1). The majority had arcuate uteri (n=42, 6.8%), 17 partial septate (2.7%), 1 complete septate (1.6%), and 1 unicorn uterus (1.6%). Müllerian anomalies were significantly more frequently diagnosed in nulliparous (20% [26 of 128]) compared with parous women (7% [35 of 494]). Müllerian anomalies were more frequent in women with oligomenorrhea compared with women with normal menstrual periods (19% [15 of 79] vs. 10% [34 of 339]). One first-trimester miscarriage or multiple miscarriages (more than one) were not significantly more frequent in premenopausal women with müllerian anomalies compared with women with normal-shaped uteri (24% [6 of 25] vs. 22% [57 of 265]). In a general population examined by SCSH the prevalence of Müllerian anomalies is estimated at 9.8%. Müllerian anomalies were more frequent in nulliparous women. Both impaired fertility and a pregnancy-associated modulation of the uterine corpus are among explanations. Müllerian anomalies were associated with oligomenorrhea in premenopausal women. In this general population there was no association between miscarriage and müllerian anomalies; however, the number of cases was limited.

Maternal serum disintegrin and metalloprotease protein-12 in early pregnancy as a potential marker of adverse pregnancy outcomes.

ObjectivesThe aim of this study was to determine whether the concentration of disintegrin and metalloprotease protein12 (ADAM12) in first trimester maternal serum can be used as a marker for first-trimester complete spontaneous abortions, missed abortions, ectopic pregnancies and hydatidiform moles.MethodsThe maternal serum concentrations of ADAM12 were measured in the range of 5–9+6 weeks of gestation using an automated AutoDelfia immunoassay platform in 9 cases of complete spontaneous abortion, 27 cases of missed abortions, 56 cases of ectopic pregnancies, 12 cases of hydatidiform moles, and 100 controls. Logistic regression analysis was used to determine significant factors for predicting adverse pregnancy outcomes in early pregnancy. Screening performance was assessed using receiver operating characteristic curves.ResultsTwo hundred and four women were enrolled in the study. In the control group, the level of ADAM12 increased with gestational age. The median ADAM12 levels in the spontaneous abortion (0.430 MoM), ectopic pregnancy (0.460 MoM) and hydatidiform mole (0.037 MoM) groups were lower than that in the control group, while the median ADAM12 level in the missed abortion group (1.062 MoM) was not significant from the controls (1.002 MoM). Logistic regression analysis demonstrated that the level of ADAM12 in maternal serum facilitated the detection of ectopic pregnancies (OR = 0.909; 95% CI = 0.841∼0.982) and complete spontaneous abortion (OR = 0.863; 95% CI = 0.787∼0.946).ConclusionsIn complete spontaneous abortion and ectopic pregnancy, ADAM12 maintained at low levels in early pregnancies, and there were significant differences compared to normal pregnancies. ADAM12 is a promising marker for the diagnosis of complete spontaneous abortion and ectopic pregnancy in symptomatic women, and under certain conditions, ADAM12 can diagnose ectopic pregnancy and spontaneous abortion before an ultrasonographic detection of the conditions.

Hypothyroidism and first-trimester spontaneous miscarriages

Objective: To evaluate the association between hypothyroidism and first-trimester spontaneous miscarriages and to explain the mechanism. Materials and Methods: Patients admitted between October and May 2011 with threatened miscarriage in the first trimester were analyzed and levels of progesterone and thyroid hormones as T3, T4, and thyroid-stimulating hormone (TSH) were estimated. Once hypothyroidism was diagnosed, patients were treated with sodium levothyroxine (LT4) as substitution and outcomes were observed. Results: Measurement of progesterone was useful for predicting the outcome of threatened miscarriage The results showed that progesterone (P) = 14.74 ng/ml is selected as predictive value to judge whether the fetal treatment was successfully or not. When serum P value is above 14.74 ng/ml before treatment, it may favour a miscarriage, if the serum P value is below 14.74 ng/ml, miscarriage is unlikely; its sensitivity and specificity are high. The risk for miscarriage in patients diagnosed with hypothyroidism in which LT4 substitution was similar to the level observed in the controls, and P between the two groups had no distinct difference. The mechanism explaining the risk of miscarriage increased by thyroid disorders remains unclear, which needs advanced research. Conclusion: Screening of thyroid disorders has important clinical significance in early pregnancy, and substitution of LT4 to those who are in the early pregnancy with hypothyroidism could reduce the risk of miscarriage.

The cost-effectiveness of introducing manual vacuum aspiration compared with dilatation and curettage for incomplete first-trimester miscarriages at a tertiary hospital in Manzini, Swaziland

Background. Despite proven efficacy of manual vacuum aspiration (MVA) for incomplete miscarriages its use is low in Swaziland, including Raleigh Fitkin Memorial (RFM) Hospital, Manzini. Uncertainty about the cost implications of introducing MVA to replace dilatation and curettage (D&C) is probably the major obstacle to change. Aim. To evaluate the cost-effectiveness of introducing MVA as an evacuation method for first-trimester incomplete miscarriages, as well as assess the implications of the introduction of MVA for the entire post-miscarriage care budget at RFM Hospital. Methods. The methods comprised cost-effectiveness and budget-impact analyses from a healthcare perspective based on a theoretical cohort. Clinical outcomes data for procedures were obtained from the relevant literature. Costs were collated from prospective suppliers and then compared for the two treatment modalities. Future numbers of annual evacuations were extrapolated from previous annual figures. First-trimester miscarriages were in turn extrapolated from proportions found in previous studies. Total budgets were calculated under the current scenario, as well as if MVA was introduced. Results. With initial capital costs of ZAR11 093.00, introduction of MVA for first-trimester incomplete abortions would cut post-miscarriage care costs by 34.7%. MVA would cost ZAR819.86 per procedure, while D&C costs ZAR1 255.40 per procedure. An estimated 26 MVA procedures done instead of D&Cs would compensate for the initial capital investment. Introduction of MVA into the post-miscarriage care programme would save the hospital about ZAR516 115.30 annually, with clinical outcomes at least similar to D&C. Conclusions. MVA should be considered as the first option in first-trimester post-miscarriage care.

Hypoxia-Inducible Factor 1α Expression in Chorionic Tissue and Decidua of Women with Spontaneous Abortion at the First Trimester of Pregnancy

Oxygen-regulated genes expression has important role in pre-implantation embryonic metabolism regulation. Hypoxia Inducible Factor (HIF) regulated by hypoxia oxygen tension is crucial for placenta development. But the data about its role in spontaneous abortion is very poor. Thus, we aimed to determine an expression level of HIF-1α in chorionic tissue and decidua at pregnancy. Samples of chorionic tissue and decidua were taken after surgical termination of normally progressing pregnancies in 5-9 week of gestation (n = 8) and spontaneous abortion in 5-9 week of gestation (n = 9). HIF-1α expression was analyzed using semi-quantitative reverse transcription-polymerase chain reaction. Compared with decidual tissue, the expression of HIF-1α was increased in chorionic tissue in condition of normally progressing pregnancy. HIF-1α expression in samples of both tissues is equal in spontaneous abortion. In same time the expression of HIF-1α was decreased (1,5 fold) in chorionic tissue for spontaneous abortion compared with control group. The results demonstrated that low HIF-1α expression level in chorionic tissue can be associated with spontaneous abortion in first trimester of pregnancy.

Pregnancy Loss Managed by Cervical Dilatation and Curettage Increases the Risk of Spontaneous Preterm Birth

Women with a history of 1 or 2 miscarriages or terminations of pregnancy have not been considered to be at risk of adverse pregnancy outcomes in subsequent pregnancies. However, few studies have examined the association between previous pregnancy loss and adverse pregnancy outcomes in subsequent pregnancies; results in the available studies are mixed. It has been suggested that previous use of cervical dilatation and curettage (D&C) for management of first-trimester miscarriage or termination may adversely affect outcomes in subsequent pregnancies. The aim of this prospective cohort study was to determine whether women with a previous miscarriage or termination of pregnancy are at increased risk of spontaneous preterm birth and to determine whether any increased risk is associated with previous use of cervical D&C. Prospective data were obtained for 5575 healthy nulliparous women with singleton pregnancies who were enrolled from 2004 to 2011 in the Screening for Pregnancy Endpoints (SCOPE) study. The primary study outcome was spontaneous preterm birth (spontaneous onset of preterm labor or preterm premature rupture of membranes resulting in preterm birth at less than 37 weeks’ gestation). Secondary outcomes examined included preterm premature rupture of membrane, small for gestational age, birth weight, placental abruption, and preeclampsia. Comparison groups were women with previous pregnancy loss (miscarriage or termination) and women with no previous pregnancy loss (control). Among the 5575 women in the study, 4331 (78%) had no previous pregnancy loss, 974 (17.5%) had 1 early previous pregnancy loss, 249 (4.5%) had 2, and 21 (0.5%) had 3 or 4 losses. A single pregnancy loss was not associated with a significant increase in adverse pregnancy outcomes, whereas 2 to 4 previous losses had an increased risk of spontaneous preterm birth (adjusted odds ratio [aOR], 2.12; 95% confidence interval [CI], 1.55–2.90) and/or placental abruption (aOR, 2.30; 95% CI, 1.36–3.89) compared with no previous pregnancy loss. The use of cervical D&C to manage a single previous miscarriage or termination of pregnancy was associated with an increased risk of spontaneous preterm birth (aOR,1.64; 95% CI, 1.08–2.50; 6% absolute risk and aOR, 1.83; 95% CI, 1.35–2.48; 7% absolute risk, respectively) compared with no previous pregnancy loss. In contrast, use of a nonsurgical method for management of a single previous miscarriage or termination did not increase the risk of adverse outcomes in a subsequent pregnancy (aOR, 0.86 [95% CI, 0.38–1.94; 3.4% absolute risk]; and aOR, 0.87 [95% CI, 0.69–1.12; 3.8% absolute risk], respectively). These findings indicate that a single pregnancy loss managed by cervical D&C is associated with an increased risk of spontaneous preterm birth and/or placental abruption. In contrast, a single pregnancy loss managed nonsurgically does not increase the risk, but 2 to 4 losses are associated with increased risk. Further prospective studies are needed to confirm these data and to determine whether nonsurgical management in this population should be preferable to surgical treatment.

IUD in first-trimester abortion: immediate intrauterine contraceptive devices insertion vs delayed insertion following the next menstruation bleeding

Approximately 21 days after an abortion, ovulation occurs in 50 % of women. Installation of an IUD directly after induced or spontaneous abortion offers immediate contraceptive protection. The purpose of the present study was to weigh up contraceptive safety and adverse reactions of IUD inserted directly after first-trimester abortion under general or paracervical anesthesia as against the fitting of IUD in the days of the next menstrual cycle without anesthesia. During the period May 1987 to October 2010, 73 women (Group A) underwent an immediate post-abortion insertion IUD after a first-trimester spontaneous or induced abortion under general or local paracervical anesthesia and 69 participants (Group B) received IUD during the next menstrual cycle without anesthesia. Questionnaires were completed by all the women of the study with respect to the effects of IUD. The women were examined every 3 months for 1 year after the fitting of the IUD in the out-patient department of the University Obstetrics Gynecological Department of Alexandroupolis, Democritus University of Thrace, Greece. The demographic characteristics of the women of the two groups were similar. The age of the women ranged between 19 and 44 years, while 61.98 % were women with one or two children and 38.02 % were women with three or more children. During the first menstrual cycles, with the exception of vaginal hemorrhages (5 %) and adnexitis (1 %), no serious adverse reactions were noted. During the transvaginal ultrasonography checks in both groups, no observation was made of any dislocation of the IUD, except for two cases in the subgroup of those women with paracervical anesthesia and one case in the women of Group B. As concerns the questionnaire with regard to the women's subjective evaluation of IUD, satisfactory answers were given. There were no differences between the two groups either with respect to the security of the supplied contraceptive methods or to the development of side effects.

Value of histopathologic examination of uterine products after first-trimester miscarriage.

The main rationale of routine histopathologic examination of products after first-trimester miscarriages is to detect an ectopic pregnancy or a molar pregnancy, which require further management. An alternative approach is to examine the products only when there is a definite indication. As there is no agreement, we aimed to study whether routine histopathological examination of tissues obtained after first-trimester miscarriage is of any clinical value in our populations. Medical records of all (558) patients with a diagnosis of first-trimester miscarriage over 4 years (2007–2010) at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were reviewed. Histopathologic examination confirmed products of conception in 537 (96.2%) patients, no products of conception in 17 (3%) patients, molar pregnancy in 2 (0.4%) patients, and decidual tissues without chorionic villi (Arias-Stella reaction) in 2 (0.4%) patients. After clinical correlation, only one unsuspected partial molar pregnancy was diagnosed by histopathology examination. Conclusion is that it does not appear reasonable to perform histopathological examination routinely after all first-trimester miscarriages in our studied population. We recommend that histopathological examination be performed in select instances: when the diagnosis is uncertain, when fewer tissues have been obtained during surgery, when unexpected pathology was seen, when ultrasound suggests a molar pregnancy, or when patients are considered at high risk for trophoblastic disease.

Fetal–maternal communication: the role of Notch signalling in embryo implantation

The establishment of a successful pregnancy requires the implantation of a competent blastocyst into a 'receptive' endometrium, facilitating the formation of a functional placenta. Inadequate or inappropriate implantation and placentation is a major reason for infertility and is thought to lead to first-trimester miscarriage, placental insufficiency and other obstetric complications. Blastocyst-endometrial interactions are critical for implantation and placental formation. The Notch signalling family is a receptor-ligand family that regulates cellular processes as diverse as proliferation, apoptosis, differentiation, invasion and adhesion. Notch signalling is achieved via cell-cell interaction; thus, via Notch, cells can have direct effects on the fate of their neighbours. Recently, a number of studies have identified Notch receptors and ligands in the endometrium, blastocyst and placenta. This review collates current knowledge of this large receptor-ligand family and explores the role of Notch signalling during implantation and placentation, drawing on information from both human and animal studies. Overall, the evidence suggests that Notch signalling is a critical component of fetal-maternal communication during implantation and placentation and that abnormal Notch expression is associated with impaired placentation and pre-eclampsia.

Exposure to ambient air pollutants and spontaneous abortion

This study aimed to evaluate the correlation between ambient concentrations of air pollutants and first-trimester spontaneous abortion. This was a retrospective case–control study, which was conducted on 296 women from June 2010 to February 2011 in Tehran, Iran. Cases were 148 women who experienced a spontaneous abortion before 14 weeks of gestation while the controls were 148 pregnant women after 14 weeks of gestation and groups were matched on sociodemographics and obstetrics characteristics. The samples were recruited randomly from 10 hospitals. In total, pollutants concentrations were collected at 29 stations hourly throughout the study area. We estimated the mean exposure for each participant and investigated the association between spontaneous abortion and ambient pollutants. Findings demonstrated that the average of ambient air pollutants in the cases was significantly higher than in the controls (P < 0.05). The odd ratios of abortion in the areas with higher concentrations of CO, NO₂, O₃ and PM₁₀ were 1.98, 0.96, 0.94 and 1.01, respectively (P < 0.05). Also, the model showed that there was no significant association between prenatal exposures to SO₂ and abortion (P > 0.05). Our findings suggest that pregnant women exposed to ambient air pollutants may be at increased risk of spontaneous abortion. Confirmation by further research is needed.

Obscure effect of aneuploidy on embryo morphology

In this issue, Fragouli et al. report the results obtainedbyexamining a total of 1213 embryos by combining comprehensive chromosome analysis with a systematic assessment of embryo morphology. At the cleavage stage, chromosome abnormalities were common even amongst embryos assigned the best morphological scores, indicating that aneuploidy has little effect on microscopic appearance during the first days of development. At the blastocyst stage on the other hand, aneuploidies were found to be significantly less common among embryos of optimal morphological quality, while such abnormalities were overrepresented amongst embryos considered to be of poor morphology. However, many blastocysts affected by forms of aneuploidy with the greatest capacity to produce clinical pregnancies, such as trisomy 21, were indistinguishable from euploid embryos. Therefore this large study illustrates that embryo selection based on morphological criteria is not efficient enough. The aimof selectionduring thepreimplantation stage is to improve the success rate of ART. However, success can be defined in many different ways: as an increase of the implantation rate, as a decrease of themiscarriage rate, as an increase of the clinical pregnancy rate, as an increase of the live birth rate, as the prevention of chromosomally abnormal newborns and as a decrease of the time to pregnancy. This means that, at least in theory, an efficient selection system might have a lot of success. However, it should be based on aneuploidy detection, since chromosome abnormalities are the predominant cause of all these clinical problems, both in natural conceptions as well as after assisted reproduction (Macklon et al., 2002). About 42% of all oocytes exposed to natural fertilization survive until after implantation, and only 31%will lead to a live birth. The miscarriage rate causing the difference between both figures mainly depends on the maternal age because of aneuploidy oocytes originating at maternal meiosis I. Recently a meta-analysis was performed to obtain a more precise evaluation of the risk of embryonic chromosomal abnormalities in first-trimester miscarriage after ART in which a total of 15 studies were included. No statistical difference was found in risk of chromosomally abnormal miscarriage compared with natural conception and the different types of ART utilized, whereas the risk of fetal aneuploidy significantly increased with maternal age ≥35 (Qin et al., 2013). Already during preimplantation development the potential of human embryos depends on their chromosomal constitution. Themajority of all normal embryos reach the blastocyst stage,while this is the case in only a minority of chromosomally abnormal embryos (Sandalinas et al., 2001). Since trisomies and triploidies are much more viable than monosomies andmore complex aneuploidies, humanmiscarriage in the first trimester mainly results from embryos with extra chromosomes (Simpson, 2007). However, during the first trimester the behaviour of individual human autosomal trisomies is very variable. Trisomy 1 has hardly ever been observed in a clinically recognized pregnancy. Trisomy 16 on the other hand is the most frequently occurring abnormality. From the start, the survival of the latter does not seem to be compromised but before fetal development starts the loss of these embryos is complete. Aminority of the autosomal trisomies 13, 18 and 21 only are compatible with post-natal life. They undergo a continuous and differential prenatal loss as was shown for trisomies 18 and 21 by a Kaplan–Meier analysis (Won et al., 2005). Therefore, the finding of Fragouli and colleagues that it is difficult to prevent the transfer of these abnormalities on the basis of morphology is not surprising, although this has been the selection method of choice since the introduction of assisted reproduction. It is clear that a more proper selection system should be based on other aspects than morphology or better than morphology only. However, which other selection methods should be considered? In general one can make a distinction between molecular methods and time-lapse systems. In all cases conclusions about the potential use of these should be based on RCT results, which are hardly available. Genomic, transcriptomic and proteomic analysis can only be based on embryonic material obtained by invasive procedures such as polar body, cleavage stageor trophectodermbiopsy.As an alternative for noninvasive molecular studies, it has also been suggested that the use of differential metabolomic markers found in spent media from preimplantation embryos could be a feasiblemethod for the detection of aneuploidies before embryo transfer (Sanchez-Ribes et al., 2012). The most promising non-invasive strategy at present seems to be the combined evaluation of morphology and developmental kinetics using time-lapse imaging (Montag et al., 2013). Promising supplementary models of embryo selection based on time-dependent markers have been proposed and are currently being verified in prospective trials (Herrera and Meseguer, 2013). Until the results of the on-going RCTs available selection for aneuploidy will remain obscure.

Expectant versus surgical management of first-trimester miscarriage: a randomised controlled study

The aim of this study is to compare the efficacy and safety of expectant management with surgical management of first-trimester miscarriage. This randomised prospective study was conducted in the Gynaecology Department at University of Saarland Hospital, Germany between February 2011 and April 2012. A total of 234 women were recruited following diagnosis of the first-trimester incomplete or missed miscarriage and randomised into two groups: 109 women were randomised to expectant management (group I), and 125 women to surgical management (groupII). All women were examined clinically and sonographically during the follow-up appointments at weekly intervals for up to 4 weeks as appropriate. The outcome measures were: efficacy, short-term complications and duration of vaginal bleeding and pain. Of 234 eligible women, 17 were lost to follow-up, and the remaining 217 women were analysed. The baseline characteristics were similar in both groups. The total success rate at 4 weeks was lower for expectant than for surgical management (81.4 vs 95.7 %; P = 0.0029). The type of miscarriage was a significant factor affecting the success rate. For missed miscarriage, the success rates for expectant versus surgical management were 75 and 93.8 %, respectively. For women with incomplete miscarriage, the rates were 90.5 and 98 %. No differences were found in the number of emergency curettages between the two study groups. The duration of bleeding was significantly more in the expectant than the surgical management (mean 11 vs 7 days; P < 0.0001). The duration of pain was also more in the expectant than the surgical group (mean 8.1 vs 5.5 days; P < 0.0001). The total complication rates were similar in both groups (expectant 5.9 % vs surgical group 6.1 %; P = 0.2479). However, the pelvic infection was significantly lower in the expectant than the surgical group (1.9 vs 3.5 %, respectively; P = 0.0146). Expectant management of clinically stable women with first-trimester miscarriage is safe and effective and avoids the need for surgery and the subsequent risk of anaesthesia in about 81.4 % of cases, and has lower pelvic infection rate than surgical curettage. However, surgical management is more successful, and with a shorter duration of bleeding and pain. Therefore, the patient's preference should be considered in the counselling process.

Reliability of 46,XX results on miscarriage specimens: a review of 1,222 first-trimester miscarriage specimens

To examine the rate of maternal contamination in miscarriage specimens. Retrospective review of 1,222 miscarriage specimens submitted for chromosome testing with detection of maternal cell contamination (MCC). Referral centers requesting genetic testing of miscarriage specimens at a single reference laboratory. Women with pregnancy loss who desire complete chromosome analysis of the pregnancy tissue. Analysis of miscarriage specimens using single-nucleotide polymorphism (SNP) microarray technology with bioinformatics program to detect maternal cell contamination. Chromosome content of miscarriages and incidence of 46,XX results due to MCC. Of the 1,222 samples analyzed, 592 had numeric chromosomal abnormalities, and 630 were normal 46,XX or 46,XY (456 and 187, respectively). In 269 of the 46,XX specimens, MCC with no embryonic component was found. With the exclusion of maternal 46,XX results, the chromosomal abnormality rate increased from 48% to 62%, and the ratio for XX to XY results dropped from 2.6 to 1.0. Over half of the normal 46,XX results in miscarriage specimens were due to MCC. The use of SNPs in MCC testing allows for precise identification of chromosomal abnormalities in miscarriage as well as MCC, improving the accuracy of products of conception testing.