Risk factors for spontaneous abortion: a case-control study in France.

A case-control study was conducted in seven maternity hospitals in the Paris area in 1988 to evaluate the role of several risk factors in spontaneous abortion. A total of 279 cases and 279 controls were compared for socio-demographic characteristics, reproductive history and for conditions of conception. Prior fetal losses [odds ratio (OR) = 2.30 for n greater than or equal to 2; 95% confidence interval (CI) = 1.17-4.61] and maternal age at pregnancy (greater than 30 years) appeared to be major and independent risk factors of spontaneous abortion. Other factors associated with an increased risk of fetal loss were: geographical or ethnic origin (OR = 2.85 for North African women; 95% CI = 1.58-5.10); psychological problems at the time of conception, either related to the outcome of the pregnancy (OR = 3.08; 95% CI = 0.92-10.25) or unrelated to this outcome (OR = 3.35; 95% CI = 1.41-8.00). The following factors were not associated with spontaneous abortion: gravidity, parity, prior induced abortion, prior sexually transmitted diseases and Chlamydia trachomatis serology, menstrual cycle abnormalities, induced conception cycle and in-vitro fertilization, cigarette smoking, current or past use of combined oestrogen/progestagen pill or intrauterine device. These findings confirm the importance of two risk factors for fetal loss: maternal age and number of prior spontaneous abortions. Two risk factors, ethnic origin and psychological problems at the time of conception are also identified, which require further study.     

Does caffeine and alcohol intake before pregnancy predict the occurrence of spontaneous abortion?

BACKGROUND: Consumption of caffeine and alcohol is suspected to affect pregnancy outcome. Use of both stimulants is widespread and even minor effects on fetal viability are of public health interest. METHODS: We performed a nested case-control study using prospective data from a population-based cohort comprising 11088 women aged 20-29 years. From this cohort, women who experienced either a spontaneous abortion (n = 303) or who gave birth (n = 1381) during follow-up [mean time: 2.1 years (range: 1.6-3.4)] were selected. Associations between self-reported exposures to caffeine and/or alcohol at enrolment and spontaneous abortion were analysed by means of logistic regression. RESULTS: Compared with women with a pre-pregnancy intake of <75 mg caffeine per day, the adjusted odds ratio (95% confidence interval) for spontaneous abortion was 1.26 (0.77-2.06), 1.45 (0.87-2.41), 1.44 (0.87-2.37) and 1.72 (1.00-2.96) for a pre-pregnancy intake on 75-300, 301-500, 501-900 and >900 mg caffeine per day respectively (P = 0.05 for trend). A pre-pregnancy intake of alcohol was not a predictor for spontaneous abortion. CONCLUSIONS: A high intake of caffeine prior to pregnancy seems to be associated with an increased risk of spontaneous abortion, whereas a low-to-moderate alcohol intake does not influence the risk.     

Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment.

BACKGROUND: A high proportion of infertile patients have polycystic ovarian syndrome (PCOS) with a reportedly greater risk of spontaneous abortion. Because of the close link between PCOS and obesity and the independent association of obesity with poor pregnancy outcomes, it is important to distinguish the possible confounding effect of body mass index (BMI) or other variables from that of PCOS. This study aims to determine the effect of PCOS status on the risk of spontaneous abortion with adjustment for body mass and several other confounding factors in a large cohort of pregnant infertile women. METHODS: The patients (n = 1018) were treated in a tertiary infertility centre. Their PCOS status was determined by standard criteria and their BMI had been taken less than 1 year before the pregnancy. Patients whose PCOS status or BMI measurements were not assessed were excluded. Student's t-test or chi2 test were used to test the difference between the PCOS and non-PCOS groups while a multivariate logistical regression model was used to assess the effect of PCOS, BMI and other confounding factors. RESULTS: Overall, the incidence of PCOS was 37% in this cohort. The overall incidence of spontaneous abortion in the study population was 21%. Univariate analysis showed that women with PCOS had a significantly greater risk of spontaneous abortion compared with non-PCOS women (25 versus 18%, P < 0.01). However, using multivariate logistic regression analysis this effect was reduced to a non-significant level [odds ratio (OR) = 1.10, 95% confidence interval (CI) 0.85-1.36] after adjusting for obesity and patients/treatment combination factor, and to nil after adjusting for all confounding factors considered in this study (OR = 0.98, 95% CI 0.75-1.28). CONCLUSION: The results of this study suggest that the higher risk of spontaneous abortion observed in women with PCOS is likely to be due to their high prevalence of obesity and the type of treatment they receive.     

Endocrine abnormalities during the follicular phase in women with recurrent spontaneous abortion.

The frequency of endocrine abnormalities during the follicular phase in non-pregnant women with a history of recurrent abortion was investigated in a case-control study. A total of 42 consecutive women with recurrent spontaneous abortion (three or more consecutive abortions, mean +/- SD: 3.9 +/- 1.1 range 3-8) with no parental chromosome rearrangement or uterine abnormality were studied during the early follicular phase under standardized conditions. Serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, androstenedione, testosterone, dehydroepiandro-stenedione, 17-OH-progesterone, oestradiol, progesterone and thyroid stimulating hormone (TSH) were measured by commercially available radioimmunoassays. Controls were 42 nulligravid females with tubal or male factor infertility without miscarriage. Mean (SD) concentrations of prolactin and androstenedione were 14.2 +/- 6.7 ng/ml versus 10.5 +/- 3.5 ng/ml (95% CI 0.8-6.1) and 2.3 +/- 0.9 ng/ml versus 1.7 +/- 0.6 ng/ml (95% CI 0.2-0.9) in the study and control groups respectively. The other endocrine parameters were comparable in both groups. Obesity [BMI weight (kg)/height (m2) > or = 25] was more prevalent (23 versus 5 women, P = 0.0001) in the study than the control group. Recurrent spontaneous abortion is associated with abnormalities in prolactin and androgen secretion during the follicular phase, suggesting an endocrine aetiology in this disorder. Reduction of body weight and correction of hyperprolactinaemia and of hyperandrogenism may reduce the rate of miscarriage in a subsequent pregnancy in these women.     

Pregnancy: The roles of oligomenorrhoea and fetal chromosomal abnormalities in spontaneous abortions

The pathogenesis of spontaneous abortions, other than fetalchromosomal abnormalities, is not fully understood. We examinedthe incidence of oligomenorrhoea in relation to fetal chromosomalanalyses and ultrasonographic examination in women who abortedspontaneously. The data demonstrated that the incidence of oligomenorrhoeawas higher in women with normal fetal karyotyped abortions,especially normal karyotyped anembryonic pregnancies, than inthose with abnormal karyotyped abortions (34.0 versus 12.5%,<italic>P</italic> <0.01). Furthermore, the incidenceof oligomenorrhoea was inversely correlated with fetal sizeexclusively in abortions with normal fetal karyotypes. It issuggested that oligomenorrhoea, i.e. delayed ovulation, itselfmay be closely associated with sporadic spontaneous abortion.     

Pregnancy: Bereavement, grieving and psychological morbidity after first trimester spontaneous abortion: comparing expectant management with surgical evacuation

Early pregnancy loss is a profound adverse life event for manywomen, and increased psychiatric morbidity has been shown tooccur after spontaneous abortion. Dilatation and curettage (D&C)has been the cornerstone in the treatment of first trimesterspontaneous abortion over the last few decades. During recentyears the possibility of conservative management has, however,been increasingly discussed. In a prospective randomized trial,we compared psychological reactions and morbidity, after eitherexpect ant management or D&C, for miscarriages of <13weeks gestation In which a transvaginal ultrasound examinationshowed Intrauterine tissue and/or blood clots with an antero-posteriordiameter of between 15 and 50 mm. Of the 86 patients included,58 were randomized to expectant management and 28 to primaryD&C. In patients randomized to expectant management, pregnancyproducts shown by transvaginal ultrasound disappeared within3 days in 43 cases (74%), whereas 15 patients (26%) underwentD&C owing to retained products of conception after 3 days.At 2 weeks after indusion, all patients answered self-administeredquestionnaires, induding visual analogue scales, concerningtheir experience of the pregnancy loss, the present situationand concerns about the future. A brief anxiety status inventorywas included. This study showed no increase in anxiety or depressivereactions 2 weeks after a first trimester spontaneous abortionwhen these patients were compared with non-pregnant healthyworking females 19–39 years of age. Moreover, there wereno significant differences in psychological reactions betweenpatients managed either expectantly or by D&C.     

Q fever and spontaneous abortion

Q fever, caused by Coxiella burnetii, may result in abortions in infected animals and pregnant women. However, the role that Q fever plays in spontaneous abortions is still unknown. This study examined the association between Q fever serology and abortion in a region where Q fever is endemic. A case–control population-based study was conducted in General Yagüe Hospital (Burgos area, Spain) between June 2009 and July 2010. A total of 801 samples from 500 pregnant women were tested, of whom 273 had a spontaneous abortion and 227 gave birth. IgG and IgM antibody titres against Q fever were determined in their two phases (I and II) by immunofluorescence assay. Seropositivity (phase I IgG ≥1:16 or phase II IgG ≥1:80) was detected in 88/273 (32.2%) cases and 53/227 (23.3%) controls; p <0.01, OR 1.5, 95% CI 1.0–2.3. Seropositivity for both phases of IgG, compatible with recent or persistent infection, was detected in 55 (20.1%) vs 22 (9.7%); p <0.001, OR 2.3, 95% CI 1.3–3.9. High phase II IgG antibodies compatible with active or recent infection (titres ≥1:160) were detected in 27 (9.6%) vs 7 (3.1%); p <0.002, OR 3.4, 95% CI 1.4–8.0, respectively. Q fever was diagnosed in 14 (5.1%) cases. The risk of abortion associated with serological markers of active or recent Q fever in pregnant women was measurable and noticeable in this population, and accounted for 12% (95% CI 4–21%).     

Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study

The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo.     

Epidemiology of recurrent spontaneous abortion.

With recent scientific advances leading to better understanding of the immunobiology of recurrent spontaneous abortion (RSA), interest has now focused upon the epidemiology of RSA. A cohort of 214 couples with a history of two or more consecutive abortions were studied for the prevalence of etiologic factors and association with other reproductive failures. The prevalence of causes of RSA in this cohort was compared with etiologic factors among 179 couples with a history of three or more consecutive abortions. The obstetrical histories of 214 women with RSA were analyzed for the total number of pregnancies, live births, stillbirths, spontaneous abortions, ectopic pregnancies, and hydatidiform moles. These numbers were compared with the expected frequency of each in the general population. The prevalence of etiologies among 214 with RSA were as follows: chromosomal-6%, anatomic-1%, hormonal-5%, immunologic-65%, and unexplained-23%. No differences in the prevalence of etiologic factors exist when couples with a history of two or more abortions are compared with three or more abortions. When the number of ectopic pregnancies, molar pregnancies, and stillbirths among 214 women with RSA were compared with the expected numbers, the odds ratios were 2.2 for ectopic pregnancies, 6.0 for molar pregnancies, and 2.3 for stillbirths. These data indicate that no difference in the prevalence of etiologies of RSA exist when couples with two or more abortions are compared with three or more and a comorbidity between RSA and other types of reproductive failure exists.     

The transcobalamin codon 259 polymorphism influences the risk of human spontaneous abortion

BACKGROUND: The remethylation cycle of methionine is folate and vitamin B(12) (cobalamin) dependent and appears to be crucial for embryonic development, probably through effects on synthesis of DNA, proteins and polyamines. Transcobalamin (TC) transports vitamin B(12) to the tissues. The objective of the present investigation was to explore the putative association between the major TC genetic polymorphism (Pro259Arg) and human spontaneous abortion. METHODS: The prevalence of the TC Pro259Arg polymorphism was determined in DNA samples from embryos that had been spontaneously aborted between the 6th and 20th week after conception, and adult controls using solid-phase minisequencing technique. RESULTS: The 259-Pro allele was significantly less frequent in the spontaneous abortion group than in the control group (42.2 and 57.0% respectively; P = 0.005), while the frequency of 259-Arg was significantly increased. There was a lower prevalence of 259-Pro homozygotes in the spontaneous abortion group compared with the control group (9.1 and 32.2% respectively; P < 0.001). CONCLUSIONS: The 259-Pro allele seems to have beneficial influences during embryogenesis, conceivably through its positive effect on vitamin B(12) intracellular bioavailability. Our results warrant additional investigations addressing the question if vitamin B(12) supplementation in addition to folic acid supplementation may prevent spontaneous abortion in women planning a pregnancy.     

Infectious diseases: Further evidence that infection is an infrequent cause of first trimester spontaneous abortion

A previous cohort study found no clinical evidence that infectionoccurred more often in subjects experiencing pregnancy losscompared with those experiencing success ful pregnancy [Simpsonet al (1996) Hum. Reprod., 11, 668—672]. Given these surprisingfindings, we conducted a similar analysis on another cohortalso followed prospectively. Using couples practising naturalfamily planning for conception or contraception, Informationon clinical evidence of infection was gathered beginning withweek 5 of gestation. Information on fever and signs of overtinfection was specilically sought by interview and physicalexamination. Frequencies of urinary, vaginal and other Infectionsin subjects experiencing pregnancy loss were 11.1, 9.5 and 8.7%respectively, not significantly different from rates in subjectshaving liveborns (10.1, 10.2 and 10.3% respectively). Thus,no association between clinical infection and early pregnancyloss (16 weeks) was observed. Cohort studies utilizing biologicallybased assays are awaited because extant data do not provideevidence that clinically evident infections play major rolesin first trimester pregnancy losses.     

Ultrasonographic detection of a live fetus in recurrent spontaneous abortion during the first trimester

To examine whether recurrent spontaneous abortion (RSA) canbe distinguished from repeated sporadic spontaneous abortion,the clinical course of 38 cases with three or more consecutiveand unexplained first trimester RSAs were retrospectively investigatedin this study. For comparison with controls, the clinical coursewas examined of 38 fertile females, who had had sporadic abortions.In 19 (50%) RSAs and 6 (16%) controls, fetal cardiac activitywas demonstrated by ultrasound during the course of pregnancy.The rate of detection of live fetus during pregnancy or at 8weeks ± 7 days gestation, was significantly greater inthe RSA group compared to the control. The rate of vaginal bleedingbefore spontaneous abortion was significantly less in the RSAgroup than in the control group. There was no difference betweenthe two groups in age or gestational age at spontaneous abortion.The patients with RSA were all examined for antiphospholipidantibodies in their sera and these were detected in eight ofthem. However, there was no difference in the rate of positivefetal cardiac activity between the RSA patients who tested positiveor negative for antibody. These results reveal that the clinicalcourse of RSA is very different from the course of sporadicabortion. Although sporadic abortion is a common complicationof pregnancy, RSA is not a random repeated abortion, but rathera separate disease from sporadic abortion in normal fertilefemales.     

Maternal KIR repertoire is not associated with recurrent spontaneous abortion

BACKGROUND: In view of evidence suggesting an immunological cause of recurrent spontaneous abortions (RSA) and the large number of maternal natural killer (NK) cells present in the pregnant uterus, we investigated the genetic polymorphism of the killer cell immunoglobulin-like receptors (KIR) in women with RSA. METHODS: KIR gene repertoire and KIR2DL4 (a receptor for HLA-G) genotyping were determined by SSP and SSCP respectively, in women experiencing RSA and controls. RESULTS: The KIR repertoire did not differ between RSA patients and controls in terms of: (i) the number of inhibitory receptors; (ii) the number of activating receptors; (iii) the ratio of inhibitory to activating receptors. KIR2DL4, a receptor for HLA-G, has different transmembrane alleles, which produce functionally different phenotypes. The frequency of KIR2DL4 transmembrane genotypes differed significantly between RSA patients and controls (P=0.03). However, although homozygosity for a membrane-bound receptor was more frequent in patients (25%) than controls (10%), other genotypes that would produce the same phenotype were not more frequent in patients than controls. CONCLUSIONS: The data provide little evidence that KIR polymorphism plays a role in predisposition to RSA.     

Immunology: Influence of histocompatibility antigens in recurrent spontaneous abortion and its relevance to leukocyte immunotherapy

A total of 108 couples with recurrent spontaneous abortion (RSA)were studied to investigate the possible influence of histocompatibilityantigens (HLA) on their condition and its management. HLA-B18was shown to be at a higher frequency in RSA women, but notsignificantly so after statistical correction. Just over halfthe RSA women shared two or more HLA-A, B or DR antigens withtheir partners (P < 0.01), but this group did not differfrom the others in clinical or laboratory features, nor in subsequentpregnancy success rate. Leukocyte immunotherapy in which thedonor shared at least one HLA-DR antigen with his partner wasnot associated with a significant improvement in subsequentpregnancy outcome compared with HLA-DR mismatched immunotherapy.HLA antibody production following leukocyte immunotherapy wasinfluenced by both inoculum size and degree of HLA incompatibility,but had no effect on birthweight. Tissue-typing investigationsare not indicated for individual RSA patients seeking adviceor treatment.     

Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology

BACKGROUND: There has been increasing number of pregnancies following assisted reproductive technology treatment and their survival is understandably a matter of interest. The relative risk of spontaneous abortion in these pregnancies remains unclear. The objectives of this study were to quantify the relative risk in assisted reproductive technology pregnancies in relation to two cohorts of naturally conceived pregnancies and to assess the possible risk factors for spontaneous abortion among assisted reproductive technology pregnancies. METHODS: Three cohorts of pregnancies, 1945 pregnancies conceived following assisted reproductive technology treatment in a tertiary infertility clinic, 549 natural pregnancies in a prospective study of lifestyle and pregnancy (the Ford cohort), and 4265 pregnancies from another cohort (the Treloar cohort), were used in the study. RESULTS: After adjusting for age, the relative risk of spontaneous abortion was 1.20 (95% CI 1.03-1.46) in the assisted reproductive technology cohort in comparison with the Ford cohort. Within the assisted reproductive technology cohort, a history of spontaneous abortion predicted increased risk, while a low level of ovarian stimulation seemed to be related to a reduced risk. CONCLUSIONS: The study showed that the risk of spontaneous abortion was slightly increased in the assisted reproductive technology pregnancies after adjusting for maternal age and previous spontaneous abortion. Within the assisted reproductive technology cohort, several variables, including the level of stimulation, appeared to be linked with the risk of spontaneous abortion.     

The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion.

Thrombosis of placental vessels can be a major cause of recurrent spontaneous abortion (RSA). The factor V Leiden (FVL) mutation, a single point mutation in the factor V gene, is the most common genetic predisposition to thrombosis in European countries and the United States. However, even among Caucasian populations, the association between the FVL mutation and RSA is still controversial. The objectives of the present study were to investigate the prevalence of the FVL mutation in Japanese women who have experienced RSA and to clarify the contribution of the FVL mutation to recurrent miscarriages. A total of 52 Japanese women with a history of three or more consecutive idiopathic first trimester miscarriages and 41 of their male partners were studied. The control group consisted of 55 parous women without obstetric complications. Peripheral blood cell DNA was examined for the presence of the FVL alleles by polymerase chain reaction with Mnl I restriction fragment length polymorphisms. None of the 52 women with RSA and the 41 partners carried the mutation. We also found no subject carrying the FVL alleles in the control group. These results suggest that the FVL alleles are not concentrated in women with RSA at least to clinically significant levels and that there is no apparent association between the FVL mutation and RSA in our Japanese population.     

A prospective study of 63 couples with a history of recurrent spontaneous abortion: contributing factors and outcome of subsequent pregnancies

To evaluate the possible causes of recurrent spontaneous abortion(RSA) and to elucidate the prognosis for subsequent pregnancies63 RSA patients were studied. Parental karyo-typing revealedchromosomal aberrations in six of the 63 couples (4.8%). Therate of increased concentrations of antibodies against cardiolipinwas comparable in the patients (10.0%) and in 30 parous controls(6.7%), as was also the occurrence of other autoantibodies (43.3and 36.7%, respectively). Hysteroscopy revealed uterine cavityabnormalities in 11 of the 55 patients studied (20.0%). Altogether,for 35 RSA women (55.4%) investigations resulted in entirelynormal findings; abnormal findings were more frequently encounteredin primary aborters (56.8%) than in secondary aborters (26.9%,P < 0.05). During the follow-up period of 24.1 ± 15.4months, 48 patients became pregnant a total of 65 times, andthe cumulative live birth rate was 62.5%. A living fetus wasseen in ultrasound examination in 46 pregnancies (70.7%), whereasa blighted ovum was diagnosed in nine pregnancies (13.8%). Anadditional nine pregnancies aborted so suddenly that no ultrasoundexamination was performed, and one ectopic pregnancy was treatedlaparoscopically. Of the initially viable pregnancies, 13 (28.3%)ended in miscarriage and two were terminated due to fetal anomalies.Normal findings in the investigations were associated with asmaller risk for abortion (40.0%) than were abnormal findings(65.5%, P < 0.05). Of the 30 babies, six (20.0%, with babiesfrom one twin pregnancy excluded) were growth-retarded, 9.7%were born before 37 weeks of gestation, and 22.8% of the mothershad impaired glucose tolerance during pregnancy. Thus pregnanciesin RSA women were accompanied by increased risk for fetal growthretardation, preterm delivery and impaired glucose toleranceand needed, therefore, to be followed carefully.     

Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis

BACKGROUND: Misoprostol and expectant care have been shown to be acceptable alternatives to routine surgical evacuation for treatment of spontaneous abortion in the first trimester of pregnancy. The objective of this study was to analyse the cost of expectant care, misoprostol therapy and surgical evacuation. METHODS: A decision tree was designed to simulate the clinical outcome and health care resource utilization of surgical evacuation, misoprostol and expectant care for patients presenting with uncomplicated spontaneous abortion in the first trimester of pregnancy. Clinical inputs were estimated from literature and the cost analysis was conducted from the perspective of a public health care provider in Hong Kong. RESULTS: The base-case analysis showed that the misoprostol group (1000 US dollars per patient) was the least costly alternative, followed by the expectant care (1172 US dollars per patient) and surgical evacuation (2007 US dollars per patient). Rates of complete abortion using misoprostol and expectant care were identified as influential factors. Monte Carlo simulation (10000 cohorts) showed that the misoprostol and the expectant care groups were less costly than the surgical evacuation group 100 and 88% of the time. The misoprostol group was less costly than the expectant group 100% of the time. CONCLUSIONS: Misoprostol therapy appears to be the least costly approach for treatment of uncomplicated spontaneous abortion.     

基因多态性与复发性自然流产的相关性研究

复发性自然流产（recurrent spontaneous abortions,RSA）是指连续发生2次或2次以上流产者。RSA的病因复杂,包括胚胎染色体异常、免疫功能异常、黄体功能不足、感染、生殖道异常等。但目前仍有部分RSA患者病因及发病机制尚不清楚,遗传背景等因素的改变可能使部分人群易发生RSA[1]。近年来从免疫遗传角度提出了一些新的观点,认为RSA的发生与遗传有关。寻找RSA的易感基因或致病基因,从根本上阐明RSA的发病机理,是RSA治疗和预防的重要途径。     

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.