Circulating fibroblast growth factor 21 as a potential biomarker for missed abortion in humans.

OBJECTIVE: To investigate whether serum levels of fibroblast growth factor 21 (FGF21) and fatty acid-binding protein-4 (FABP4) are associated with missed abortion (MA) in humans. DESIGN: Cross-sectional study. SETTING: University-affiliated hospital. PATIENT(S): Patients with MA at 8-12 weeks of gestation. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Serum levels of FGF21 and FABP4 were tested by enzyme-linked immunosorbent assay. Placental samples were collected during dilation and curettage surgery, and the expression of FGF21 and its related genes were measured using quantitative polymerase chain reaction. RESULT(S): In the discovery cohort, 78 patients with MA and 79 healthy pregnant women matched for maternal age and body mass index were nested from a prospective cohort. Circulating levels of FGF21 and FABP4 were significantly and independently elevated in patients with MA relative to the levels in the healthy controls. A single measurement of FGF21 serum level effectively discriminated MA with an area under the receiver operating characteristics curve of 0.80 (95% confidence interval: 0.73-0.87). Importantly, in our external validation cohort that comprised subjects with MA (n = 34) or induced abortion (n = 27), the FGF21 serum levels achieved an area under the receiver operating characteristics curve of 0.85 (95% confidence interval: 0.75-0.96) when identifying those with MA. Nevertheless, expression of FGF21 in the placenta was not associated with its serum concentration. Placental tissues from patients with MA exhibited impaired FGF21 signaling. CONCLUSION(S): Our results suggested that serum levels of FGF21 and FABP4 were associated with MA. Circulating FGF21 may serve as a potential biomarker for the recognition of MA.

Platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in missed abortion

Abstract Objective Missed abortion occurs in ~ 15% of all clinical pregnancies. The pathogenesis is not clearly known. However, defective placentation resulting in maternal systemic inflammatory response is considered responsible for missed abortion. Platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) are increasingly cited parameters of inflammation in the literature. However, no study evaluated the PLR and NLR rates in missed abortions so far. The aim of the present study is to investigate whether complete blood count (CBC) inflammatory parameters such as NLR and PLR are increased in patients with missed abortion. Methods Medical records of 40 pregnant women whose gestation ended in missed abortion at between 6 and14 weeks of gestation and of 40 healthy pregnant women were collected and compared retrospectively. The groups were compared regarding hemoglobin, hematocrit, platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), PLR and NLR. Results Platelet distribution width, NLR and PLR values were higher in the missed abortion group compared with the healthy pregnant women group (rates are p = 0.043; p = 0.038; and p = 0.010, respectively). Hematocrit, MPV, and lymphocyte values were found to be lower in the missed abortion group compared with the healthy pregnant women group (p = 0.027, p = 0.044 and p = 0.025, respectively). Conclusion The PDW, NLR and PLR values of the missed abortion group were reported high; and MPV values were reported low in the present study. These findings may help to speculate a defective placentation in the pathogenesis of missed abortion.

Serum progesterone levels could predict diagnosis, completion and complications of miscarriage.

BACKGROUND: Low serum progesterone levels were strongly correlated with miscarriages in several publications and with completion of miscarriage in one paper. This study evaluated several parameters, predominantly serum progesterone, as predictors for miscarriages, their swift non-surgical completion and their complications. BASIC PROCEDURES: Suspected or confirmed non-viable pregnancies with available concomitant serum progesterone measurements were retrospectively reviewed. The performance of serum progesterone, either alone or combined with other parameters, to predict viability, surgical removal and delay of non-surgical evacuation of non-viable pregnancy and complications, was analysed by logistic regression combined with Akaike and Bayesian information criteria, likelihood, receiver operated characteristic (ROC) curves, Mann-Whitney test and Fisher's exact test. MAIN FINDINGS: From 151 included pregnancies, 104 (68.9 %) were non-viable with 91 completions of miscarriage without surgery. The probability of viability was correlated linearly and curvilinearly with serum progesterone (p < 0.001). The probability of surgical removal, and the delay before non-surgical evacuation, showed a linear relationship with progesterone. No complication occurred when progesterone levels remained below 10 µg/L, while its rates were 9.5 % of non-viable pregnancies with progesterone levels between 10 and 20 µg/L and 26.7 % of cases with progesterone levels above 20 µg/L. Combined with progesterone, either "parity" or "history of miscarriage" improved the prediction of viability, "history of supra-isthmic uterine surgery" improved the prediction of surgery and "history of miscarriage" improved the prediction of delayed non-surgical evacuations. CONCLUSION: Serum progesterone can probably predict the odds of miscarriages, surgical removal, delayed non-surgical evacuation and complications, with potential improvements when different predictors are combined.

Biochemical clinical factors associated with missed abortion independent of maternal age: A retrospective study of 795 cases with missed abortion and 694 cases with normal pregnancy.

The incidence of fertile women with missed abortion dramatically increased in recent years, while very few serum indices have been identified for the diagnosis of missed abortion. The aim of this study was to identify related factors for missed abortion through a retrospective study of serum indices.A total of 795 cases of women with missed abortion and 694 cases of women with normal pregnancy between March 2014 and March 2017 were included in the present study. The diagnosis of missed abortion was based on clinical history, clinical examination, and transvaginal ultrasound findings. The final diagnosis of missed abortion was based on assessment of pregnancy structures (i.e., a gestational sac without fetal heart rate) via transvaginal ultrasound. We evaluated the clinical values of 4 serum indices and their relationship to missed abortion: gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), adenosine deaminase (ADA), and fibrinogen (FIB).The serum levels of GGT, ADA, and FIB showed statistically significant differences comparing women who experienced missed abortion with women who had normal pregnancies (controls). Among women with missed abortion, the levels of GGT and ADA were dramatically increased (GGT: P < .0001; ADA: P = .0459), while FIB levels were slightly lower (P = .0084) compared to controls. The LDH levels exhibited a non-significant trend toward lower levels in the missed abortion group (P = .3951). Interestingly, the observed significant increase in serum GTT levels among women with missed abortion was not affected by maternal age.This study found that GTT may be a useful marker which was associated with missed abortion, indicating its potential clinical roles in missed abortion.

The decreased expression of TIPE2 protein in the decidua of patients with missed abortion and possible significance.

BACKGROUND: Missed abortion is a common occurrence for otherwise healthy women. Immunological factor is one of the most important reasons. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) is a novel negative immune regulator related to several human diseases. However, the expression level and clinical significance of TIPE2 in missed abortion remain unclear. METHODS: The expression of TIPE2 mRNA and protein in decidua and chorion from 36 missed abortion patients and 36 healthy controls was detected using quantitative real-time PCR, western blot and immunohistochemistry. In addition, serum TNF-ɑ and IL-10 levels were measured using flow cytometry. Serum estradiol and progesterone levels were measured by radioimmunoassay test. The correlations of TIPE2 protein levels with TNF-ɑ, IL-10, estradiol and progesterone were further analyzed. RESULTS: TIPE2 protein levels were significantly lower in decidual tissues of missed abortion patients than those in healthy controls. The patients with missed abortion had significantly higher levels of serum TNF-ɑ, and lower levels of serum IL-10, estradiol and progesterone compared with healthy controls. The TIPE2 protein levels were positively related to serum IL-10 levels. CONCLUSION: Our data indicate TIPE2 could play important roles in maintaining the maternal-fetal tolerance and decreased TIPE2 expression in the decidua may be related to the development of missed abortion.

Utility of ßhCG monitoring in the follow-up of medical management of miscarriage.

OBJECTIVE: To evaluate the percentage change in total ßeta-unit human chorionic gonadotropin (ßhCG) levels (%ΔßhCG) in the prediction of treatment outcomes following intravaginal misoprostol for missed miscarriage before 13 weeks. METHODS: A secondary analysis of a randomised controlled study of medical management of miscarriage was performed. Total ßhCG levels were collected before misoprostol (baseline) and after a planned seven day interval (follow-up), when a transvaginal ultrasound (TVUS) reported a gestational sac as present or not. If no sac at TVUS, surgery was indicated on clinical criteria. %ΔßhCG ((baseline ßhCG - follow-up ßhCG)/baseline ßhCG × 100) was evaluated in the prediction of a sac at TVUS and surgery on clinical criteria. RESULTS: %ΔßhCG was calculated for cases with ßhCG levels within two days of misoprostol and TVUS; calculation interval determined case number. The median %ΔßhCG for 24 cases with a persistent sac (6-9 day interval) was significantly lower than for 145 with no sac (58.75% (interquartile range (IQR): 37.59-76.69; maximum 86.54) vs 97.65% (IQR: 95.44-98.43); P < 0.0001). The median %ΔßhCG for eight cases needing surgery on clinical criteria (5-9 day interval) was significantly lower than for 140 cases with no sac not needing surgery (79.68% (IQR: 64.63-91.15; maximum 94.06) vs 97.68% (IQR: 95.61-98.50); P < 0.0001). The area under the receiver-operator curve was 0.975 for prediction of a persistent sac and 0.944 for prediction of surgery on clinical criteria, respectively. %ΔßhCG > 87% predicted no sac at TVUS. %ΔßhCG > 94.5% predicted no surgery on clinical criteria. CONCLUSION: %ΔßhCG calculation over one week reliably predicted treatment outcomes after medical management of missed miscarriage.

Maternal serum markers in predicting successful outcome in expectant management of missed miscarriage.

The aim of this study was to evaluate the use of biological serum markers, available routinely in most hospital clinical laboratories, in predicting successful outcomes of expectant management in women presenting with a missed miscarriage. This is a single centre observational prospective study over a 16-month period. Among the 490 women who consented to the study protocol, 83 presented with missed miscarriage during the first trimester of pregnancy and opted for expectant management. The mean gestation sac diameter and volume of the gestation sac were recorded during ultrasound examination. Maternal serum samples were obtained in each case and assayed for human chorionic gonadotrophin, progesterone, pregnancy associated plasma protein A (PAPP-A) and high-sensitivity C-reactive protein using commercial assays. When examined individually, maternal age (P = 0.01), progesterone (P = 0.03) and PAPP-A (P = 0.02) were all significantly associated with successful expectant management. Increased maternal age was associated with an increased chance of success with the odds of success increased by around 75% for a 5-year increase in age. Higher values of progesterone and PAPP-A were associated with a reduced chance of successful management. Low maternal serum progesterone concentration was the strongest parameter associated with a successful spontaneous completion of miscarriage.

Placental growth factor, soluble fms-like tyrosine kinase 1 and progesterone as diagnostic biomarkers for ectopic pregnancy and missed abortion.

OBJECTIVE: The aim of this study is to investigate if progesterone, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) serum levels are useful markers to differentiate between ectopic pregnancy (EP), missed abortion (MA) and viable intrauterine implantation pregnancy (IUP). METHODS: We designed a retrospective case-control study which included 100 pregnant women (50 EP and 50 MA) at 6-8 weeks of gestation with ßhCG serum levels between 800 and 3500 UI/L and a viable IUP group. Progesterone, PlGF and sFlt-1 levels were measured with an electrochemiluminescence assay (Roche Diagnostics, Manheim, Alemania). A non parametric test was used to compare the markers in the different groups and we used receiver operating characteristic (ROC) curve analysis to calculate the area under the curve (AUC). RESULTS: When we compared the EP group with the MA group, we didn't find significant differences for PlGF (15.1[13.2-17.4]/16.7[12.8-18.7] pg/mL) (p=0.275). We only obtained significant differences for progesterone (9.1[3.1-16.8]/2.6[1.3-6.1] ng/mL) (p<0.001) and sFlt-1 (84[65-96]/126[94-256] pg/mL) (p<0.001). The AUC for progesterone was 0.756 and the cutoff point with better sensitivity and lower false positive rate was 6 ng/mL (sensitivity=60%, specificity=72.7%). The AUC for sFlt-1 was 0.842 and the cutoff point was 93 pg/mL (sensitivity=84.5%, specificity=86.3%). The combination of both markers allowed us to increase the AUC to 0.910. CONCLUSIONS: In conclusion, the present study suggests that sFlt-1 could be a useful marker to differentiate between an EP or a MA when ßhCG levels are similar in both groups. The combination of sFlt-1 with progesterone helps to increase the diagnostic performance.

The association between serum progesterone and outcome of medical management of early fetal demise: a pilot study.

The study objective was to determine the relationship between serum progesterone level and the outcome of mifepristone-misoprostol regimen for medical management of missed miscarriage up to 12 weeks. A blood sample was collected just before mifepristone administration for serum progesterone assay. After 48 h, misoprostol 800 µg was administered vaginally; further 400 µg was administered 4 h later if necessary. Treatment was classed as a success if retained tissues were expelled within 72 h (Group 1), and a failure if this did not occur (Group 2). Of 52 analysed cases, complete medical evacuation occurred within 72 h in 40 (76.9%) women (serum progesterone ranged 13-90 nmol/l). Serum progesterone between the two groups were statistically significant (p < 0.001), by Mann-Whitney test. Of the 12 patients who did not respond, nine (75%) women had serum progesterone < 10 nmol/l. We found mifepristone-misoprostol regimen is less effective in missed miscarriage when serum progesterone is < 10 nmol/l.

Angiopoietin-1 and angiopoietin-2 as serum biomarkers for ectopic pregnancy and missed abortion: a case-control study.

BACKGROUND: A case-control study to evaluate whether a single serum measurement of angiopoietin-1 (ANG-1) and angiopoietin-2 (ANG-2) at 6-8 weeks gestation can differentiate failed pregnancies, whether ectopic pregnancies (EP) or missed abortions (MA), from healthy intrauterine pregnancies (IUP). INTERVENTION(S): Serum and tissue mRNA determination of ANG-1 and ANG-2 levels by ELISA and RTPCR, from 60 (30 EP and 30 MA) patients with failed early pregnancy and 33 IUPs. RESULTS: ANG-1 and ANG-2 concentrations and their ratio are lower in EP (median, 689 and 302 pg/ml, respectively) and MA cases (median, 810 and 402 pg/ml, respectively) compared to IUP (median, 963 and 1477 pg/ml, respectively) (p<0.05, for all). Unlike ANG-2, serum ANG-1 discriminates an EP from a MA (p=0.011). Trophoblastic ANG-1 mRNA expression levels are lower in EP compared to MA and IUP (p<0.05), while ANG-2 mRNA is higher in EP and MA than in IUP (p<0.05). CONCLUSIONS: A single measurement of serum ANG-1 and ANG-2 at 6-8 weeks of gestation designate the outcome of a pregnancy, as their levels are significantly decreased in failed than normal pregnancies. Serum ANG-1 showed potential to discriminate MA from EP.

[Expression and significance of estrogen receptor alpha gene polymorphisms in blood and villi of missed abortion].

OBJECTIVE: To explore the differences of estrogen receptor α (ERα) gene polymorphism in patients with missed abortion and normal pregnancy and examine the relationship between ERα gene polymorphism and missed abortion. METHODS: A total of 100 cases of missed abortion patients and 102 cases of normal pregnant women were selected as the experimental and control groups. And 2ml blood samples and chorionic villus specimens were collected. The method of polymerase chain reaction restriction fragment length polymorphism was employed for ERα gene PvuII and XbaI polymorphism. And the data was analyzed to explore the relationship between ERα gene polymorphism and missed abortion. RESULTS: There was statistic significance in the frequency of ERα gene PvuII enzyme cleavage allele P and p from blood and villi samples between two groups, blood (χ(2) = 5.542, P < 0.05) OR: 1.742, villi (χ(2) = 7.559, P < 0.01), OR: 1.948. Statistic significances existed in the difference of frequency for ERα gene XbαI enzyme cleavage allele X and x from blood and villi samples between two groups, blood (χ(2) = 15.205, P < 0.01), OR:2.519; villi (χ(2) = 13.750, P < 0.01), OR: 2.499. There was a positive correlation of the frequency in ERα gene PvuII and XbαI genotype from blood and villi samples in the experimental group. CONCLUSIONS: It suggests that ERα gene polymorphism is correlated with the pathogenesis of missed abortion. Alleles P and X may be susceptibility genes.

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.

Soluble FMS-like tyrosine kinase-1 (sFlt-1) and serum placental growth factor (PlGF) as biomarkers for ectopic pregnancy and missed abortion.

CONTEXT: Diagnosis of early pregnancy failure is hampered by the lack of reliable serological markers. OBJECTIVE: We assessed whether a single serum measurement of placental growth factor (PlGF) and the soluble Flt-1 (sFlt-1) receptor of vascular endothelial growth factor at 6-8 wk gestation could differentiate failed pregnancies, whether ectopic pregnancies (EP) or missed abortions (MA), from healthy intrauterine pregnancies (IUP). DESIGN AND SETTING: We conducted a prospective clinical study at a tertiary university hospital between January 2009 and February 2011. PATIENTS: A total of 78 consecutive patients (38 EP, 40 MA) with failed early pregnancy and 50 IUP (control group) participated in the study. INTERVENTION(S): Determination of serum PlGF and sFlt-1 has been carried out by ELISA. Gene expression of PlGF and Flt-1 in trophoblasts was performed by RT-PCR. MAIN OUTCOME MEASURE(S): We investigated whether a single, combined serum measurement of the above markers could contribute to the differential diagnosis. RESULTS: PlGF and sFlt-1 concentration was lower in both EP (mean, 14.60 ± 3.42/178.16 ± 76.03 pg/ml) and MA (mean, 16.25 ± 4.73/399.42 ± 337.54 pg/ml) compared to IUP (mean, 21.64 ± 5.68/1390.32 ± 655.37 pg/ml). sFlt-1 (P = 0.033) and sFlt-1/PlGF ratio (P = 0.029) but not PlGF had the ability to discriminate MA from EP. Compared to women with viable IUP, mRNA gene expression levels of PlGF and Flt-1 were considerably lower in women with MA and in women with EP. CONCLUSIONS: Combined measurement of sFlt-1 and PlGF levels can differentiate normal from failed pregnancies, whereas sFlt-1 as well as sFlt-1/PlGF ratio can also discriminate EP from MA. PlGF and Flt-1 gene expression in trophoblasts from women with EP and MA appears impaired.

Early pregnancy failure: factors affecting successful medical treatment.

BACKGROUND: The results of medical treatment for early pregnancy failure are conflicting. OBJECTIVES: To determine whether gestational sac volume measurement as well as other variables can predict the success rate of medical treatment for early pregnancy failure. METHODS: The study group comprised 81 women diagnosed with missed abortion or anembryonic pregnancy who consented to medical treatment. Demographic data were collected and beta-human chorionic gonadotropin level was documented. Crown-rump length and the sac volume were measured using transvaginal ultrasound. TVU was performed 12-24 hours after intravaginal administration of 800 micro g misoprostol. If the thickness of the uterine cavity was less than 30 mm, the women were discharged. If the sac was still intact or the thickness of the uterine cavity exceeded 30 mm, they were offered an additional dosage of intravaginal misoprostol or surgical uterine evacuation. RESULTS: Medical treatment successfully terminated 32 pregnancies (39.5%), 30 after one dose of misoprostol and 2 after two doses (group A); 49 underwent surgical evacuation (group B), 47 following one dose of misoprostol and 2 following two doses. There were no significant differences between the groups in age and gestational week. Gestational sac volume did not differ between groups A and B (10.03 and 11.98 ml respectively, P = 0.283). Parity (0.87 and 1.43, P = 0.015), previous pregnancies (2.38 and 2.88, P = 0.037), and betahCG concentration (6961 and 28,748 mlU, P = 0.013) differed significantly between the groups. CONCLUSIONS: Gestational sac volume is not a predictor of successful medical treatment for early pregnancy failure. Previous pregnancies and deliveries and higher betahCG concentration negatively affect the success rate of medical treatment.

First trimester aneuploidy screening in the presence of a vanishing twin: implications for maternal serum markers.

OBJECTIVE: To assess the impact of a vanishing twin on the levels of the biochemical markers used in the first trimester aneuploidy screening. METHODS: A retrospective analysis of free beta-hCG and PAPP-A levels in 270 women with a normal singleton fetus with ultrasound evidence of a vanishing twin pregnancy. Marker levels (as MoM) were compared in three groups-76 women with a second empty gestational sac, 194 women with a second gestational sac containing a dead fetus with a measurable crown rump length (CRL), and 1360 matched singleton pregnancies. RESULTS: In women with a second empty gestational sac, the median free beta-hCG and PAPP-A MoMs (0.968 and 1.040, respectively) were not significantly different from the 1.0 MoM in singleton pregnancies. In the group with a vanished twin with a measurable-CRL-there was a significantly increased median PAPP-A MoM (1.317) but the median free beta-hCG MoM was not changed (1.024). Modelling this bias in PAPP-A MoM the detection rate for trisomy 21 would fall from 85 to 75%. CONCLUSION: First trimester screening in the presence of a vanishing twin may lead to errors in risk estimation. In such circumstances it may be advisable to restrict screening to the use of nuchal translucency (NT) alone.

T-helper 2-cytokine levels in women with threatened abortion.

OBJECTIVE: Considering that successful embryo development has been immunologically attributed to a T-helper 2 phenomenon and that threatened abortion is a very frequent but pathogenetically not well-defined clinical entity, our purpose was to investigate serum levels of the main T-helper 2-type cytokines during the evolution of this condition. STUDY DESIGN: Three T-helper 2-type cytokines (interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-13 (IL-13)) were measured by an enzyme-linked immunosorbent assay (ELISA) in serum of 12 women with threatened abortion both at hospital admission and discharge time. Fourteen women with missed abortion, 14 normal pregnant women and 14 normal non-pregnant women represent study control groups. RESULTS: Serum concentrations of the selected T-helper 2-type cytokines showed no significant differences in women with threatened abortion with those of normal pregnant and non-pregnant women, whereas showed significantly lower values in women with missed abortion. CONCLUSION: Our data (a) confirm the concept that first-trimester normal pregnancy is a T-helper 2 phenomenon, (b) show that threatened abortion, when T-helper 2-biased, may tend to a positive evolution of the condition, (c) display that interleukin-10, particularly, may represent a useful diagnostic and prognostic marker for predicting the normal continuance of the pregnancy in threatened abortion, (d) confirm the existence of a T-helper 2-type pattern deficiency in missed abortion, and finally (e) may open the way to new T-helper 2-biased immune therapies in case of difficult first-trimester pregnancies.

Circulating levels of inhibin A, activin A and follistatin in missed and recurrent miscarriages.

BACKGROUND: The aim of this study was to investigate the changes in circulating levels and the clinical use of inhibin A, activin A and follistatin as endocrine markers of early pregnancy loss. METHODS: Blood samples were collected from women presenting with a sporadic missed miscarriage (n = 10), and controls having pregnancy termination at 8-12 weeks (n = 15) and from women with a history of unexplained recurrent miscarriages (n = 12) at 6-12 weeks gestation. All samples were assayed for inhibin A, inhibin B, activin A, follistatin, hCG, estradiol and progesterone. RESULTS: Serum inhibin A, hCG, estradiol and progesterone levels were significantly ( approximately 2-3 fold) decreased in sporadic miscarriages compared with controls. In the recurrent miscarriage group, time dependent changes in plasma inhibin A and hCG levels were significantly (P < 0.05) altered in the group that had a subsequent miscarriage compared with those who had a live birth. At 6-7 weeks gestation, plasma inhibin A ( approximately 4 fold, P < 0.01), hCG ( approximately 4 fold, P < 0.01) and estradiol ( approximately 2 fold, P < 0.001) levels were significantly lower in women who went on to have another miscarriage than those with a live birth. Inhibin B levels were near the detection limit of the assay. CONCLUSIONS: Our findings suggest that inhibin A is a specific marker of early pregnancy loss before the onset of the clinical symptoms of recurrent miscarriage. There is a high degree of association between levels of inhibin A and hCG in cases of miscarriage, indicating that these two proteins could be used in combination to predict future pregnancy outcome.

Management of missed abortion in a patient with congenital cervical atresia.

OBJECTIVE: To describe a patient with congenital cervical atresia who became pregnant through IVF and thawed transmyometrial ET and then experienced a missed abortion. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A patient with congenital cervical atresia who underwent reconstructive surgery at 23 years of age and underwent IVF twice at 28 and 30 years of age. INTERVENTION(S): Abortion management. MAIN OUTCOME MEASURE(S): Medical follow-up of IVF-ET, resultant pregnancy, and abortion. RESULT(S): After the second cycle of IVF with frozen-thawed transmyometrial ET, the patient became pregnant but then experienced a missed abortion. Serum beta-hCG levels decreased, the two gestational sacs disappeared, and genital bleeding without signs of infection occurred 14 weeks after diagnosis of the abortion. The abortion was managed conservatively. CONCLUSION(S): When assisted reproductive techniques are used in patients with congenital cervical atresia, the risks (including those relating to the management of an abortion) should be explained in detail to the couple and sufficient informed consent should be obtained before starting IVF-ET procedures.

[Clinical features of missed abortion]. / Objawy poronienia zatrzymanego.

RATIONALE: There is no general agreement concerning the definition of missed abortion which remains one of the most commonly encountered pregnancy complication of an extremely variable clinical picture. AIM OF THIS STUDY: The analysis of the clinical symptoms of missed abortion. SETTING: Academic Medical Center. MATERIALS AND METHODS: Consecutive 50 women with non-viable pregnancy from 7 to 22 weeks, diagnosed by clinical examination, ultrasonography and serum beta-HCG evaluation were studied. RESULTS: In 92% of the missed abortion cases a vaginal spotting was observed before the diagnosis was established. The average period of the estimated retention of the products of conception was 2.8 weeks. In only one patients this period exceeded 8 weeks. The reverse correlation was established between the gravidity of a patient and the period of asymptomatic retention of the non-viable conception products in uterus. The obtained results confirm that the onset of vaginal bleeding does not reflect the moment of embryonal/fetal death.

Elevated day 3 serum follicle stimulating hormone and/or estradiol may predict fetal aneuploidy.

OBJECTIVE: To determine whether baseline serum FSH and/or E2 concentrations can predict the risk for fetal chromosomal abnormalities. DESIGN: Case control study. SETTING: Reproductive technology program at a university hospital. PATIENT(S): Patients who underwent dilation and curettage (D + C), and whose products of conception were karyotyped. INTERVENTION(S): Patients underwent natural conception or controlled ovarian hyperstimulation followed by intrauterine insemination, in vitro fertilization and embryo transfer, gamete intrafallopian transfer, or zygote intrafallopian transfer. MAIN OUTCOME MEASURE(S): Baseline serum FSH and E2 concentrations and fetal karyotype. RESULT(S): Genetic evaluation of 78 D + C specimens revealed 34 normal and 44 abnormal fetal karyotypes. A significantly greater proportion of women with abnormal fetal karyotype had elevated baseline serum FSH (> or =15 mIU/mL [RIA] or 10 mIU/mL [Immulite]) and/or E2 > or = 50 pg/mL [Immulite]) compared with women of normal fetal karyotype. Among karyotypically abnormal abortuses, autosomal trisomy was the most common abnormality noted (79.5%), followed by mosaicism (6.8%), triploidy (6.8%), monosomy XO (4.5%), and balanced translocation (2.3%). CONCLUSION(S): Baseline serum FSH and/or E2 concentrations may be valuable as predictors of fetal aneuploidy.