Imbalance of the Gut Microbiota May Be Associated with Missed Abortions: A Perspective Study from a General Hospital of Hunan Province.

OBJECTIVE: To conduct a preliminary investigation that shows the possible correlation between the change of gut microbiota and missed abortions (MAs), which further provides a new potential insight for the prevention and therapy of MAs. METHOD: One hundred women, including 50 patients with MAs (case group) and 50 normal pregnant women (control group), were enrolled in the study. Fecal specimens were collected in the first trimester. Bacterial DNA was extracted, hybridized with primers of specific genes, and then detected by bacterial chip. The composition and the relative abundance of the gut microbiota were compared and analyzed. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis was used to explore the relative pathways. RESULTS: (1) The α-diversity and ß-diversity of the gut microbiota in patients with MAs were significantly lower than that those in normal pregnant women (P < 0.05). At the phylum level, Firmicutes, Proteobacteria, Actinomycetes, and Bacteroidetes accounted for the main proportion of intestinal flora in the 2 groups. Only Actinobacteria was high in the case group. Significant differences were found between the two groups at the phylum level (P < 0.05). Prevotella, Lactobacillus, and Paracoccus were significantly more abundant in the control group than in the case group at the genus level (P < 0.05). (2) KEGG pathway enrichment analysis found significant differences in 27 signaling pathways and metabolic pathways between the two groups of differentially expressed genes (all adjusted P < 0.05). (3) The positive rate of M. hominins (MH) detection in the control group was significantly higher in the MA group (χ 2 = 7.853, P = 0.004). CONCLUSION: The high abundance of Actinobacteria in the MA group was the first time found and reported in the study. The dysbiosis of the gut microbiota correlates with MAs. This study provided insights into the potential change of gut microbiota of MAs and the potential underlying mechanisms through certain impaired lipid metabolism and aroused inflammation pathways. Comprehensive insights regarding gut microbiota may facilitate improved understanding and the development of novel therapeutic and preventive strategies for MAs.

A survey of influencing factors of missed abortion during the two-child peak period.

This study aimed to investigate the influencing factors of missed abortion during the two-child peak period in China. 220 pregnant women were divided into observation (presence of missed abortion, 100 cases) and control group (no presence of missed abortion, 120 cases). The single factor analysis of clinical data showed that, advanced age, premarital examination, genitalia abnormality, luteal insufficiency, spouse semen abnormality, mycoplasma infection, chlamydia infection, sexually transmitted diseases, perm or dyeing hair in pregnancy, radiation overload, primipara, spontaneous abortion history, smoking, drinking and overly intimate with pets had significant difference between observation and control group (p < .05). The logistic regression analysis results showed that, the advanced age, genital abnormality, luteal insufficiency, spouse sperm abnormality, pregnancy infection, primipara, spontaneous abortion history and bad life habits were the main risk factors of missed abortion. In the intervention for prevention of missed abortion, these factors should be paid more attention.Impact statementWhat is already known on this subject? There are many complex factors affecting the embryonic development and causing the missed abortion.What do the results of this study add? The advanced age, genital abnormality, luteal insufficiency, spouse sperm abnormality, pregnancy infection, primipara, spontaneous abortion history and bad life habits are the main risk factors of missed abortion.What are the implications of these findings for clinical practice and/or further research? These findings can provide a theoretical basis for the further prevention of missed abortion.

The risk of missed abortion associated with the levels of tobacco, heavy metals and phthalate in hair of pregnant woman: A case control study in Chinese women.

To assess the association between exposure to the tobacco, heavy metals and phthalate on early pregnancy and missed abortion.42 women with missed abortion and 57 matched controls (women with normal pregnancies) were recruited between March and May 2012, from the Department of Gynecology and Obstetrics, First Affiliated Hospital of Guangxi Medical University and the People Hospital of Guangxi Zhuang Autonomous Region. The questionnaire survey was carried on to learn about the basic conditions, as well as smoking history of all participants. The levels of tobacco, heavy metal, and phthalate exposure were compared between the 2 groups by measuring nicotine, cocaine, cadmium (Cd), manganese (Mn), plumbum (Pb) and dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), di-2-ethyl hexyl phthalate (DEHP) in the hair samples.Out results showed that significant differences in age (P = .042), premarital examination (P = .041), passive smoking (P = .021), and heavy metal exposure (P = .022) were found in the case group compared to the control. In addition, the concentration of nicotine (P = .037), cotinine (P = .018), Cd (P = .01), Pb (P = .038) and DEHP (P = .001) in the hair were significantly higher in the case group. Furthermore, logistic analysis revealed that age [Odds Ratio (OR) 1.172, 95% confidence interval (CI) 1.036-1.327], Cd (OR 8.931, 95% CI 2.003-39.811), Cotinine (OR 4.376, 95% CI 1.159-16.531), DEHP (OR 1.863, 95% CI 1.103-3.146) were important factors contributing to the missed abortion (P < .05).It was demonstrated that high gestational age, passive smoking, heavy metals, and the phthalate exposure were the risk factors for missed abortion, while the premarital health examination was a protective factor. Avoiding these harmful substances before getting pregnant and during the early stages of pregnancy, might help prevent missed abortions.

Neoadjuvant chemotherapy followed by large cone resection as fertility-sparing therapy in stage IB cervical cancer.

BACKGROUND: Standard treatment of cervical cancer FIGO stage IB1 is a radical hysterectomy with pelvic lymphadenectomy. As the number of patients with a preserved fertility wish has increased, the need for fertility sparing surgery emerges. In this study we discuss 11 patients with cervical carcinoma stage IB treated with neoadjuvant chemotherapy followed by large cone resection. METHODS: In this retrospective study we included 10 patients with FIGO stage IB1 and 1 patient with IB2 cervical cancer, who first received a pelvic lymphadenectomy followed by neoadjuvant chemotherapy and conization. Paclitaxel-ifosfamide-carboplatin or a combination of paclitaxel-carboplatin was used as neoadjuvant chemotherapy. RESULTS: Complete response after chemotherapy was observed in 64%, partial response in 27% and 9% had progressive disease. All patients with response underwent a conization, with no residual disease on pathology in 80%. Patients with residual disease were treated by radical hysterectomy. In 9 patients fertility sparing surgery could be performed and 6 (67%) got pregnant. Five patients had 7 children and two patients had four missed abortions. Two premature deliveries at 32 and 33weeks were described, both in the same patient. Recurrence was observed in one patient that was treated with simple hysterectomy followed by radiochemotherapy. Median follow up time is 58months with all patients alive and no evidence of disease until now. CONCLUSIONS: Neoadjuvant chemotherapy followed by conization seems to be a promising new fertility sparing treatment modality in patients with cervical carcinoma stage IB1, but further studies with larger populations should confirm these data.

A comparison of the molecular distribution of proangiogenic factors in endometrium of missed abortions and of voluntary first trimester termination cases.

OBJECTIVE: The authors aimed to evaluate the angiogenic changes that occur in the cases with missed abortions compared with the voluntary termination of pregnancy as control group, with this controlled clinical study. MATERIALS AND METHODS: The study included fifteen healthy volunteer women with unwanted pregnancy less than 10th gestational week in an academic research environment. The patients were 19 women between 6th and 11th gestational weeks diagnosed with missed abortion as the patient group. Immunohistochemistry was utilized to examine temporal and spatial expression of vascular endothelial growth factor (VEGF) and their two receptors: VEGF-R1 (Flt-1) and VEGF-R2 (Flk-1/KDR), and Trombospondin-1, eNOS, iNOS, and HIF-1α in the both deciduas and placenta of the both groups. RESULTS: This study discovered the significant difference (p < 0.005) between the groups of controlled and missed abortion in the decidual and placental cell components, and has put forward that thrombospondin and iNOS have an impact on abortion through antiangiogenic effect in cases of missed abortions. CONCLUSIONS: The potential role of molecules affecting angiogenesis in the etiology of missed abortion has been evaluated and the authors aimed for this to be a guide for studies on further treatments and on the prevention of the development of missed abortions.

Coxsackievirus B infection is highly related with missed abortion in Korea.

PURPOSE: This study investigated the possible relationship between viral infection and first trimester pregnancy loss. MATERIALS AND METHODS: A prospective study was performed on 51 gravidas with missed abortion, fetal anomaly, pre-term delivery, and full-tem delivery at Hanyang University Hospital. Enteroviruses were detected by semi-nested reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in abortive tissues and placentas. Enterovirus serotypes were confirmed by genome sequencing. Herpesviruses were detected by PCR. RESULTS: Coxsackievirus B3 (CVB3) was detected in 8 of 14 missed abortion cases, 1 of 27 full-term cases, and none of the 9 pre-term cases. Coxsackievirus B1 (CVB1) was detected in an encephalocele case. Herpes simplex virus type 1 was found in 4 full-term cases, 3 pre-term cases, and none of the missed abortion cases. CONCLUSION: The prevalence of CVB3 was significantly higher in missed abortion cases compared to full-term or pre-term delivery cases. CVB infection may therefore be an important etiological agent of missed abortion.

Infertility following retained products of conception: is it the surgical procedure or the presence of trophoblastic tissue?

OBJECTIVE: To compare the reproductive outcome of women who underwent re-evacuation of the uterine cavity due to suspected retained products of conception (RPOC) and in whom trophoblastic tissue was confirmed by histopathologic examination to those with negative pathologic findings. STUDY DESIGN: We retrospectively reviewed all cases of women who underwent uterine re-evacuation due to suspected RPOC between January 2000 and December 2010. Reproductive outcomes were compared between women in whom trophoblastic tissue was confirmed by histopathologic examination and those with negative pathologic findings. RESULTS: A total of 240 patients underwent uterine re-evacuation due to suspected RPOC, of whom 162 (67.5%) had pathological examination positive for RPOC, and 78 (32.5%) had pathologically negative RPOC. The rate of a new infertility problem following resection of a positive pathologic finding was significantly higher compared with a negative finding (P=0.029). The mean time to conception was significantly longer after resection of a positive pathologic finding compared with a negative finding (P<0.001). A significantly higher rate of hypomenorrhea/amenorrhea was found following resection of a positive pathologic finding compared with a negative finding (P=0.017). CONCLUSION: RPOC-associated infertility is primarily related to the presence of trophoblastic tissue rather than the surgical intervention per se in the gravid uterus.

Autoamputed uterus within pelvic cavity: a tale of negligence.

At maternity worldwide we recognize the complexity and interlinking nature of the many different factors which can prevent women and girls from being able to have access to high quality maternal and family planning care. Our integrated maternal health approach draws on the Three Delays Model which recognizes the different barriers women face in achieving the timely and effective medical care needed to prevent deaths occurring in pregnancy and childbirth. The three delay model proposed by Main in 1993 depicts the roles of communities and the health system as emergency service to protect safe motherhood. The model shows that the result of an obstetric emergency is influenced by factors which govern the decision to seek care, reaching the medical facility and receiving adequate treatment. The three delays break the use of emergency obstetrics care facilities. The article flushes the neglected tragic view of young women for all three delays suffering from septic abortion even at tertiary level care. In our study the substandard management is focused causing the woman to loss her reproductive life.

Common stress and serum cortisol and IL-12 levels in missed abortion.

To investigate stress levels, serum cortisol levels, and changes in IL-12 concentration in patients with missed abortion. Patients with missed abortion (n = 48) were age and gestational age-matched with normal early pregnancy cases (n = 48). All subjects completed a stress evaluation survey questionnaire about common stressors. Venous blood samples were collected at 07.00 hours, and serum cortisol and IL-12 concentrations were measured by electrochemiluminescence immunoassay and ELISA methods, respectively. Missed abortion patients demonstrated a significantly higher number of common stressors and higher serum cortisol levels compared to controls (both p < 0.05). Dilation and curettage did not lead to significant differences in serum cortisol and IL-12 levels (p > 0.05). Stress and immunity alterations of the immune system may contribute to the aetiology of missed abortion.

[Forensic medical assessment of the origin of the missed early post-traumatic abortions].

The objective of the present study was to develop an algorithm for the forensic medical assessment of the origin of the missed early post-traumatic abortions. The analysis of the available data on the main variants of traumatic pregnancy interruption was carried out. Diagnostic features of the missed early post-traumatic abortions are considered along with the possible errors in the use of the current approaches to forensic medical assessment of their origin. The proposed algorithm for the forensic medical assessment of the origin of the missed early post-traumatic abortions takes into consideration the specific features of the objects of interest and includes the analysis of the results of ultrasonic studies of the uterine cavity and histological investigations of the scraps of endometrial tissue. Absolute and probabilistic criteria for spontaneous and traumatic origin of the missed early post-traumatic abortions. The proposed algorithm is recommended for the use in routine clinical practice for the elucidation of the causes of the missed early post-traumatic abortions.

[Cervical pregnancy: a rare case of reimplantation after abortion. A case report]. / La réimplantation cervicale de la grossesse, une complication méconnue des interruptions volontaires de grossesse. À propos d'un cas.

Cervical pregnancy is a rare form of ectopic pregnancy defined by the implantation of the blastocyst in the cervical canal. Most of the cervical pregnancies have been reported in patients with a history of vacuum curettage or caesarean section. The authors report a case of cervical pregnancy occurred after a failure of medical abortion. A literature review discusses the possibility of a cervical secondary implantation and describes the management of such pregnancies.

Investigation of systemic inflammatory response in first trimester pregnancy failure.

BACKGROUND: The contribution of local and systemic inflammation to the pathophysiology of sporadic first trimester miscarriages remains unclear. The objective of this study was to investigate the inflammatory response in the circulation of women presenting with first trimester miscarriage. METHODS: Levels of tumour necrosis factor alpha (TNFα), TNF receptors 1 and 2, interferon gamma (IFNγ), interleukin (IL)-6 and IL-10 were assayed using cytometric bead arrays in plasma samples from 29 euploid and 21 aneuploid missed miscarriages, 35 normal pregnant controls and 31 non-pregnant women (NPW). Whole blood flow cytometry was carried out with samples from 17 euploid and 16 aneuploid miscarriages, 18 pregnant controls and 13 NPW. RESULTS: The plasma of women with euploid miscarriage contained significantly higher circulating levels of TNFα (P < 0.005), IFNγ (P < 0.005), IL-6 (P < 0.005) and IL-10 (P < 0.01) than that of pregnant controls, irrespective of gestational age. Significantly (P < 0.05) higher TNF-R1 levels at 6-9 weeks, and significantly higher TNFα/IL-6 (P < 0.001) and significantly lower TNFα/IL-10 (P < 0.001) and IFNγ/IL-10 (P < 0.001) ratios at 10-14 weeks, were also found in euploid miscarriage cases compared with pregnant controls. TNFα/IL-10 ratio in plasma was significantly (P < 0.05) lower in miscarriages with an abnormal karyotype than those with normal karyotype. Normal pregnant women had a significantly higher plasma level of IFNγ (P < 0.01) and IFNγ/IL-10 ratio (P < 0.005), a significantly (P < 0.005) lower TNF-R1 level, and a significant (P < 0.05) increase in stimulated TNFα in monocytes, compared with NPW. CONCLUSIONS: Our data confirm that there is an inflammatory reaction in normal pregnancy compared with the non-pregnant state, which may be disrupted during miscarriage.

Retained fetal bones two years after midtrimester dilation and evacuation: a case report.

BACKGROUND: Retained fetal parts is an uncommon but recognized complication of pregnancy termination. A case of retained fetal bones, 2 years after midtrimester dilation and evacuation (D&E), is described and utilized as a nidus for literature search and discussion of clinical presentation variations. CASE: A 27-year-old woman, G2, P1, A1, presented complaining of a 2-year history of vaginal discharge. After visiting several healthcare providers and receiving ultrasound evaluations followed by courses of antibiotics and oral contraceptives, the patient's symptoms persisted. Subsequent hysteroscopy revealed fragments of immature bone. Symptoms resolved after hysteroscopic removal of the bone fragments. CONCLUSION: Retained fetal parts can present with a variety of clinical symptoms and signs, including chronic pelvic pain, vaginal discharge, and secondary infertility. When symptoms are nonspecific, the condition can mimic other gynecologic conditions. Multiple case reports have described postabortal removal of retained fetal bone at varying time intervals from the antecedent D&E, ranging from days to years. The symptomatic presentation can be temporally remote from the antecedent abortion, and symptoms can mimic other common gynecologic conditions. The entity presents the gynecologist with diagnostic and therapeutic challenges.

Post-abortion hysteroscopy: a method for early diagnosis of congenital and acquired intrauterine causes of abortions.

OBJECTIVE: Recurrent pregnancy loss is often defined as three or more consecutive pregnancy losses but there are no strict criteria for initiation of investigations after a miscarriage. We compared the frequency of uterine anomalies diagnosed by hysteroscopy following one, two and three or more miscarriages. STUDY DESIGN: In our study 151 patients underwent diagnostic hysteroscopy following a missed or an incomplete abortion. Uterine septum, subseptum, arcuate uterus, and uterine hypoplasia are classified as congenital uterine anomalies and polyps, synechia, and submucous myomas are classified as acquired uterine abnormalities. RESULTS: 151 Patients were enrolled in the study. The pregnancy numbers of the patients varied between 1 and 12. Sixty nine (46%) of the patients had one miscarriage, 42 (28%) had two miscarriages and 40 (26%) had three or more miscarriages. Diagnostic hysteroscopy revealed normal uterine cavity in 61.1% of the patients, congenital uterine anomalies in 20.4% and acquired uterine pathologies in 18.5%. Among the congenital anomalies, 14 (9.3%) were uterine septum, 10 (6.6%) were subseptate uterus, 4 (2.6%) were arcuate uterus and 3 (1.9%) were uterine hypoplasia. Among acquired abnormalities 14 (9.3%) were uterine synechia, 12 (7.9%) were endometrial polyps, and 2 (1.3%) were submucous myoma. Among patients who had one miscarriage 64.1% had a normal uterine cavity, 18.2% had congenital abnormalities and 17.7% had acquired uterine pathologies. Of patients with two miscarriages, 52% had a normal uterine cavity, 21.9% had congenital anomalies and 26.1% had acquired uterine pathology. In the three or more miscarriage group, 58.4% had normal uterine cavity, 25.3% had congenital anomalies, and 16.3% had acquired uterine pathology. We did not find any statistically significant difference between the number of miscarriages and pathologic diagnostic hysteroscopy findings. CONCLUSIONS: Post-abortion office hysteroscopy is a simple and efficient tool in the early diagnosis of congenital and acquired uterine pathologies. Diagnostic hysteroscopy can be performed after the first miscarriage in order to determine congenital and acquired uterine pathologies, with regard to the patient's age and anxiety level.

"See and treat" hysteroscopy after missed abortion.

A prospective study was conducted on the incidence of intrauterine pathology after missed abortion diagnosed and treated by hysteroscopy. A hysteroscopy was performed in 100 women four to 12 weeks after a dilatation and curettage for missed abortions. Uterine malformations were found in 12 patients, intrauterine adhesions in seven and submucous myoma in two cases. As a side finding four cases of asymptomatic retained products of conception were found. Most cases of the intrauterine pathology were treated instantly by hysteroscopy, "see and treat" regimen was preferred. Post-missed abortion-hysteroscopy is a simple and useful method for early diagnosis and treatment of congenital and acquired intrauterine pathology.

Exposure to polycyclic aromatic hydrocarbons and missed abortion in early pregnancy in a Chinese population.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete burning of fossil fuels, wood, and tobacco products. High PAH exposure has been associated with low birth weight, intrauterine growth restriction, and preterm birth, but little is known about its impact on adverse outcomes in early pregnancy such as in-utero fetal death. OBJECTIVES: To examine associations between exposure to PAHs and missed abortion in which the embryo has died but a miscarriage has not yet occurred during early pregnancy in a Chinese population in Tianjin. METHODS: A case-control study was conducted from April to November, 2007 in Tianjin, China. Cases experienced a missed abortion while controls underwent elective abortions before 14weeks of pregnancy. Eighty-one cases were recruited from four hospitals, with the same number of controls matched on hospital, maternal age (+/-8years), gravidity (1 or >1), and gestational age (+/-30days). Two maternal measures of PAH exposures were obtained based on benzo[a]pyrene (BaP) DNA adducts in 1) aborted tissues and 2) maternal blood (for a subset of subjects). In addition, proxy measures for PAH exposures from different sources were derived from maternal interviews. RESULTS: In conditional logistic regression analyses, we estimated more than 4-fold increase in risk of having experienced a missed abortion in women with above the median levels of blood BaP-DNA adducts (adjusted OR=4.27; 95% CI, 1.41-12.99); but no increase with adduct levels in aborted tissues (adjusted OR=0.76; 95% CI, 0.37-1.54). BaP-DNA adduct levels in maternal blood and aborted tissues were poorly correlated (r=-0.12; n=102). Missed abortion risk also was higher among women reporting traffic congestion near the residence, commuting by walking, and performing regular cooking activities during pregnancy. CONCLUSION: High levels of maternal PAH exposures may contribute to an increased risk of experiencing a missed abortion during early pregnancy.

Factors influencing the duration of pregnancy termination with vaginal misoprostol for fetal abnormality.

OBJECTIVE: Evaluation of factors influencing the duration of second-trimester pregnancy interruption with vaginal misoprostol for fetal abnormality. METHODS: All medical terminations >or=13 weeks of gestation 1/1997 to 12/2007 were prospectively identified. Cases receiving vaginal misoprostol 400 microg 6-hourly were extracted from the database and outcomes reviewed. RESULTS: This consecutive case series comprised 1066 women. Median maternal age was 31 years [interquartile range (IQR) 26, 36] and 15.4% had at least one prior cesarean delivery. Principal indications for termination were aneuploidy (37.6%), neural tube defects (15.9%) and cardiac anomalies (9.4%). Median gestation at termination was 19.5 weeks (IQR 17.9, 21). Median abortion interval was 16.1 h (IQR 12, 23.5). Lower maternal age (median duration 17.6 vs 15.2 vs 13.6 h, age < 30 vs 30-39 vs > 40 years, p < 0.001), nulliparity (median duration 19 vs 14.3 h, nulliparous vs parous, p < 0.001) and increasing gestation (median duration 13 vs 17.8 h, <16 vs >20 weeks, p < 0.001) were associated with abortion prolongation. Controlling for gestation, age and parity, apart from musculoskeletal abnormalities (associated with abortion prolongation, p = 0.03), the specific fetal anomaly did not influence duration. CONCLUSIONS: Three factors: nulliparity, younger maternal age and increasing gestation, were associated with abortion prolongation. Apart from musculoskeletal abnormalities, the fetal anomaly had no impact on abortion duration.