Second-trimester Miscarriage Research Articles

Use of misoprostol for second-trimester termination in a woman with four previous caesarean sections – a case report

Induction of labour for women with second-trimester spontaneous abortion who have a uterine scar present is a contentious issue due to the potential risk of uterine scar rupture which is...

The pattern of pregnancy loss in women with congenital uterine anomalies and recurrent miscarriage

Congenital uterine anomalies (CUA) are a known cause of recurrent miscarriage (RM), but the pattern of pregnancy loss that different CUA produce remains unknown. This study included 665 women with RM who were screened for CUA using a combined two-dimensional ultrasound (2D-US) and hysterosalpingography (HSG) approach. All suspected CUA were definitively diagnosed and classified via a combined hysteroscopy/laparoscopy procedure. Pregnancy outcomes were evaluated and compared for each type of CUA versus a control group of women with no identifiable cause of RM (unexplained RM). Fifty-six women with CUA and 107 women with unexplained RM were identified. In total, 881 pregnancies were analysed. Analysis showed that women with a septate or bicornuate uterus suffered from significantly increased second-trimester miscarriages compared with controls (13.2% and 13.8% versus 1.0%; P<0.001 and P<0.05, respectively). Women with an arcuate, septate or bicornuate uterus showed significantly reduced rates of biochemical pregnancy losses compared with controls (9.5%, 11.1% and 11.1% versus 30.4%; P<0.01, P<0.01 and P<0.05, respectively). Pregnancies of women with RM and CUA are not associated with early implantation failure and are compromised at a more advanced gestational age.

Fetal Pathology in Second-Trimester Miscarriages

Objective: We aimed to analyze, based upon autopsy, the main characteristics of miscarriages in the second trimester. Methods: We have processed the results of fetopathological investigations of 544 aborted fetuses resulting from 486 second-trimester miscarriages. Results: Malformation could be identified in 13.05% of all cases. In almost one third of the patients there was a positive history. In the cases having a malformation, expressed dominance of male fetuses could be observed. Among the fetopathologically identified malformations, 49 were isolated. The most common was the single umbilical artery (22.4%). In 1.3% of the cases a chromosome aberration was verified. Conclusion: Miscarriage in pregnancies complicated by a malformation occurs approximately 3 weeks earlier than in cases without a confirmed malformation. There is practically no difference between affected and unaffected miscarriages as far as the cumulative ratio of positive history is concerned. A single umbilical artery alone predisposes to miscarriage, while in association with other malformations it may result from chromosome aberration.

Recurrent pregnancy loss and inherited thrombophilia: who should be tested?

Successful outcome of pregnancy is dependent on the development of adequate placental circulation. Abnormalities of placental vasculature may result in a number of gestational pathologies, including first- and second-trimester miscarriages,...

Réduction embryonnaire : indications, techniques, impact psychologique

High-order multiple pregnancies (triplets and above) are associated with high pediatric mortality and morbidity, mainly due to their premature delivery. Maternal morbidity is also substantially higher than for singleton gestations. The main goal of multifetal pregnancy reduction (MFPR) is to decrease the rate of severe prematurity and its consequences, including neurodevelopmental handicaps. It may also reduce the risk of maternal complications. Transabdominal needle-guided procedures, performed at 10-12 weeks, are the most common technique for MFPR. Transvaginal needle aspiration can be used successfully earlier in gestation (7-8 weeks). Transcervical aspiration is no longer used. There is generally no medical indication for MFPR in twins. MFPR does not reduce the risk of loss of the entire pregnancy before 24 weeks and may increase the risk of a second-trimester miscarriage by 1-2%. MFPR substantially decreases premature delivery rates, cutting the risk of delivery at 29-32 menstrual weeks in triplet pregnancies in half for reductions to twins and by five for reduction to singletons. The positive effect of MFPR on perinatal outcome is incontrovertible for quadruplets and higher-order pregnancies. Advances in perinatal medicine have substantially reduced mortality in premature triplet deliveries, however, and this should be taken into account when considering the potential benefit of MFPR. MFPR is a distressing experience for parents, but seems not to have long-term adverse effects on women's psychological well-being. Maternal distress related to MFPR tends to fade with time. The negative psychological impact of MFPR should be weighed against that related to raising the children from high-order pregnancies. Prevention of high-order multifetal pregnancies is essential and requires careful monitoring of infertility therapies.

OC56: Miscarriage after a normal scan at 12–14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening

The aim was to estimate the risk of second-trimester miscarriage in women with a low risk of carrying a fetus with chromosomal abnormality according to nuchal translucency (NT) screening, and to determine if NT thickness or other factors affect the risk. The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1 : 250 at NT scan, and in whom no fetal karyotyping was performed at < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. The median risk of Down syndrome was 1 : 3138 (range, 1 : 9651–1 : 251) and median NT was 1.7 (range, 0.4–3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4–0.6%). After controlling for maternal age we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48 (95% CI, 1.22–1.80), P < 0.0001; OR for each previous miscarriage 1.34 (95% CI, 1.07–1.68), P = 0.01. Excluding women with any previous miscarriage and adjusting for parity we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). In singleton pregnancies with an estimated risk of Down syndrome < 1 : 250 according to NT screening at 12–14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women.

Miscarriage after a normal scan at 12–14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening

To estimate the risk of second-trimester miscarriage in women with low risk of carrying a fetus with chromosomal abnormality, according to nuchal translucency (NT) screening, and to determine whether NT thickness or other factors affect the risk. The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1:250 at NT scan, and where no fetal karyotyping was performed < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. The median risk of Down syndrome was 1 : 3138 (range 1 : 9651-1 : 251) and median NT was 1.7 (range 0.4-3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4-0.6). After having controlled for maternal age, we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48, 95% CI 1.22-1.94, P < 0.0001; OR for each previous miscarriage 1.34, 95% CI 1.07-1.68, P = 0.01. Excluding women with any previous miscarriage and adjusting for parity, we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). In singleton pregnancies with estimated risk of Down syndrome < 1:250 according to NT screening at 12-14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women.

Noninvasive Cerclage for the Management of Cervical Incompetence: A Prospective Study

Surgical cerclage is a traditional treatment for cervical incompetence, but randomized, controlled trials of its effectiveness have yielded conflicting results. This method does not convincingly lower the rate of spontaneous preterm birth. The investigators evaluated a noninvasive cerclage pessary in a prospective cohort study of 32 pregnant women treated for cervical incompetence during the years 2001-2004. All of them had a history of second-trimester miscarriage, delivery before 34 weeks gestation, cervical conization, or multiple pregnancy. Starting at 17-19 weeks gestation, cervical ultrasound studies were done at 2- to 3-week intervals. A cerclage pessary was offered to women with progressive cervical shortening before 30 weeks gestation when cervical length was 25 mm or less. After a sterile vaginal speculum examination and taking cervical swabs, the pessary was inserted into the vagina and fitted around the cervix as high as possible. Women received two 12-mg doses of betamethasone intramuscularly 24 hours apart at the time the pessary was placed or at 23-24 weeks gestation. The pessary was removed at 34-36 weeks gestation or earlier in the event of membrane rupture, uterine contractions, vaginal bleeding, or significant discomfort. Nearly half of the 32 women in the study had two or more risk factors for preterm delivery, and eight had positive vaginal swab cultures. The mean gestational age when placing cerclage was 23 weeks, and cervical length averaged 17 mm. Excluding three indicated preterm births, the mean interval between cerclage placement and delivery was 10.4 weeks. The mean gestational age at delivery was 34 weeks. Nearly half the women (45%) delivered before 34 weeks gestation. Birth weight averaged 2255 g. The cerclage-to-delivery interval was only 7.4 weeks in women having multiple gestations, and they delivered 5 weeks earlier on average than those with singleton pregnancies. Nearly one fourth of women had cesarean section. There were four intrapartum fetal deaths. Two women had the pessary removed prematurely because of constipation and discomfort. The only other significant complication was increased vaginal discharge. It proved easy to insert and remove the pessary. Placement of a cerclage pessary may prove helpful in women with cervical incompetence, but further studies are needed to be sure that this is a viable noninvasive alternative to surgical cerclage.

Association Between Low Day 16 hCG and Miscarriage After Proven Cardiac Activity

To investigate an association between low human chorionic gonadotrophin (hCG) levels at the end of the first week of implantation and later clinical miscarriage occurring after ultrasound confirmation of a live pregnancy. This was an observational retrospective study of 1,054 women who underwent in vitro fertilization and achieved an ultrasound-confirmed live singleton pregnancy with cardiac activity. The incidence of miscarriage diagnosed at 8-19 weeks +6 days of gestation was estimated in these 3 subgroups according to their hCG concentrations at day 16 after conception: less than the 25th, 25th-75th, and more than the 75th percentiles. The overall incidence of miscarriage was 11.1% (117/1,054), and the median gestational age at diagnosis was 10 weeks and 4 days. The median (95% confidence interval) day 16 hCG level in the miscarriage group was 182 mIU/mL (157-211), significantly lower than the median level in those who had an ongoing pregnancy (223 mIU/mL [213-233], P < .003). There was an increasing risk of miscarriage associated with decreased hCG levels (8.0% at > 75th percentile; 9.9% at 25th-75th percentiles; 16.7% at < 25th percentile; P = .003). Low hCG levels in very early pregnancy are associated with an increased risk of miscarriage occurring after the clinical recognition of pregnancy. The mechanisms underlying late first-trimester and second-trimester miscarriages may have begun as early as the first week of implantation. III.

Role of three-dimensional ultrasound in diagnosis of uterine anomalies

AbstractCongenital uterine anomalies are commonly associated with repeated pregnancy failure, in particular an increased risk of first- and second-trimester miscarriages and preterm delivery. Recent reports on three-dimensional ultrasound (3D US) and saline contrast hysterosonography appear promising for diagnosis and classification of uterine anomalies. The ability to visualize both the uterine cavity and the fundal uterine contour on a 3D US scan facilitates the diagnosis of uterine anomalies and enables differentiation between septate and bicornuate uterus. Color Doppler ultrasound allows visualization of intra-septal vascularity and may help in distinguishing avascular from vascularized septa. Less connective tissue in the septum may result in poor decidualization and placentation, while an increased amount of muscle tissue in the septum can cause miscarriage by the production of local uncoordinated muscular contractility. Hysteroscopic septum excision is an effective procedure which significantly imp...

The protein C system in placental massive perivillous fibrin deposition.

Massive perivillous fibrin deposition (MPFD) is associated with intrauterine growth retardation and first-trimester and second-trimester spontaneous abortion. Histologically, villi near the maternal interface are completely surrounded by fibrinoid material. This work compared the expression of thrombomodulin (TM) and endothelial protein C receptor (EPCR) in early miscarriage specimens with and without MPFD. Ten specimens with a gestational age of 7-12 weeks (mean 10 weeks) and 10 age-matched miscarriage specimens lacking MPFD were sampled. Formalin-fixed paraffin-embedded sections were stained with monoclonal antibodies against TM and EPCR using an immunoperoxidase method. The slides were independently reviewed by two pathologists using a semiquantitative grading system. Among unaffected villi, there was no difference in staining for TM or EPCR in cases of massive perivillous fibrin deposition compared with the control group. In the MPFD cases, loss of membrane positivity was noted for both TM and EPCR at the junction between normal villous epithelium and villous epithelium with deposition of fibrin. This could imply an underlying defect of trophoblastic protein C activation. Alternatively, it may represent a degenerative change secondary to impedence of oxygen and nutrient supply to the trophoblastic epithelium.

Dilation and evacuation at ≥20 weeks: comparison of operative techniques

Objective The objective of this study is to compare the relative safety of 2 techniques for surgical abortion late in the second trimester. Study design Retrospective review of patients who underwent surgical abortion at ≥20 weeks' gestation at our hospital from June 1996 through June 2003. Records were reviewed to determine whether the technique used was dilation and evacuation or intact dilation and extraction. Subsequent pregnancies at our hospital were identified, and obstetric outcomes were recorded. Categorical data were compared with Fisher exact test and χ 2 analysis. Continuous data were compared with Mann-Whitney U test. Results Three hundred eighty-three patients met inclusion criteria. Intact dilation and extraction was performed in 120 cases, and dilation and evacuation was used in 263. Intact dilation and extraction was associated with higher parity, later gestational age, and more preoperative cervical dilation. There was no difference in procedure time or estimated blood loss in the 2 groups. Complications occurred in 19 cases (5.0%), and occurred with similar frequency in the 2 groups. We identified 62 subsequent pregnancies. There were no second-trimester miscarriages. Spontaneous preterm birth occurred in 2 of 17 (11.8%) pregnancies in the intact dilation and extraction group, compared with 2 of 45 (4.4%) in the dilation and evacuation group ( P = .30). Conclusion Outcomes appear similar between patients undergoing dilation and evacuation and intact dilation and extraction after 20 weeks' gestation. Subsequent obstetric outcomes are similar between the 2 groups. The technique for surgical abortion should be determined by the physician on the basis of intraoperative factors.

Laparoscopic Transabdominal Cervicoisthmic Cerclage during Pregnancy

Study Objective To evaluate and describe our experience in the management of recurrent second-trimester miscarriage and preterm delivery by laparoscopic transabdominal cervicoisthmic cerclage (LTCC), after failure of transvaginal cervical cerclage. Design Retrospective review (Canadian Task Force classification III). Setting Tertiary care teaching hospital. Patients Twenty women in whom it was not technically possible to perform transvaginal cerclage. Intervention LTCC. Measurements and Main Results Mean operating time was 55 minutes (range 40–75 min). There were no operative or immediate postoperative complications. Mean gestational age at the time of cerclage placement was 12.1weeks (range 11–14wks). Nineteen women successfully delivered 21 live babies (2 sets of twins; live birth rate 95%). One loss occurred after rupture of membrane at 19 weeks' after cerclage. Conclusion LTCC during pregnancy can be safe and effective treatment for well-selected patients with cervical incompetence, and eliminates the need for open laparotomy.

Risk Factors for Spontaneous Preterm Birth: A Northern Italian Multicenter Case-Control Study

Preterm birth remains one of the most serious problems facing obstetricians. The aim of this study was to investigate the risk factors for spontaneous preterm birth in northern Italy. Nine different collaborating institutions participated in this multicenter case-control study. Cases were defined as women who were spontaneously delivered of a live singleton newborn between 20 and 37 weeks of gestation. One control was matched to each case by delivery date, maternal age and parity. Seven hundred and fifty-four cases and 754 controls were available for data analysis. Demographic and clinical characteristics were obtained using a standardized questionnaire. At the time of hospital admission, urine and cervico-vaginal samples were collected and tested for bacterial infections and bacterial vaginosis, respectively. Variables found to be statistically significant in the univariate analysis were entered in a multivariate model to examine their independent effects. In order of decreasing odds ratios (ORs), the factors that showed a significant association with preterm delivery were: previous preterm birth (OR 5.7, confidence interval (CI) 2.5–12.9); second-trimester miscarriages (OR 4.4, CI 1.3–15.3); genital bleeding before 24 weeks of gestation (OR 2.5, CI 1.6–3.8); bacterial vaginosis (OR 2.0, CI 1.3–3.1), and previous genital infections (OR 1.6, CI 1.1–2.5). This study confirms that infections play a role in the etiology of preterm birth and that reproductive history is still the most important factor in identifying women at increased risk.

Leiomyomata uteri, genetic amniocentesis, and the risk of second-trimester spontaneous abortion

Objective: The purpose of this study was to determine the impact of leiomyomata uteri on the risk of second-trimester spontaneous abortion and to determine whether genetic amniocentesis further increases this risk. Study Design: We retrospectively identified pregnant women with leiomyomata uteri who underwent genetic amniocentesis (cases) at the University of Rochester and the Johns Hopkins Hospital between April 1994 and June 2000. Two control groups were also identified: (1) pregnant women without leiomyomata who had undergone genetic amniocentesis (amnio only) and (2) pregnant women at similar gestational ages with leiomyomata who had not undergone amniocentesis (myoma only). Cases and controls were matched for maternal age and parity. All subjects were then followed up to ascertain pregnancy outcomes. Results: One hundred twenty-eight women with leiomyomata uteri who underwent genetic amniocentesis were identified and matched with 128 amnio-only controls and 128 myoma-only controls. The incidence of spontaneous abortion was 6.3% among the cases, 0.8% in the amnio-only controls, and 7.0% in the myoma-only controls. The relative risk (95% CI) for spontaneous abortion was 8.0 (1.02-63.04) for cases versus amnio only but was not significantly different from 1.0 for cases versus myoma-only controls. Conclusions: Women with leiomyomata are at an increased risk for second-trimester spontaneous abortion. Midtrimester amniocentesis does not appear to further increase this risk.(Am J Obstet Gynecol 2002;186: 913-5.)

Clinical implications of sonographic detection of uterine anomalies for reproductive outcome

The purpose of this review article was to analyze the literature on the prevalence, diagnosis and treatment of the congenital uterine anomalies and to discuss current dilemmas on their influence on reproductive outcome. Congenital uterine anomalies are commonly associated with repeated pregnancy failure, in particular an increased risk of first- and second-trimester miscarriages and preterm delivery. Recent reports on two-dimensional and three-dimensional transvaginal ultrasound and saline contrast sonohysterography appear promising for diagnosis and classification of congenital uterine anomalies. The ability to visualize both the uterine cavity and the fundal uterine contour on a three-dimensional scan facilitates the diagnosis of uterine anomalies and enables differentiation between septate and bicornuate uteri. Color Doppler ultrasound allows visualization of intraseptal vascularity and may help in distinguishing the avascular from the vascular septum. Less connective tissue in the septum may result in poor decidualization and placentation, while an increased amount of muscle tissue in the septum can cause miscarriage by the production of local uncoordinated myometrial contractility. Hysteroscopic septum excision is an effective procedure which improves live-birth rates. Because of its simplicity, minimal invasiveness, low morbidity and low cost, a more liberal approach to the treatment of uterine anomalies is being advocated.

Laparoscopic removal of a transabdominal cervical cerclage

Cervical incompetence has been acknowledged as a significant entity predisposing patients to second-trimester miscarriage. Various surgical techniques and approaches have been used in an attempt to prolong pregnancy and improve perinatal outcome. These include transvaginal and transabdominal cervical cerclage. Some patients require the placement of a transabdominal cervicoisthmic cerclage. Should the cerclage fail or the patient have preterm premature rupture of membranes, removal of the cerclage may be necessary. As a result the application of laparoscopy for the management of cervicoisthmic cerclage removal has been advocated in an effort to limit surgical complications. We report a case of laparoscopic removal of a transabdominally placed cervical cerclage in a 32-year-old woman at 16 weeks’ gestation with preterm premature rupture of membranes and inevitable miscarriage. Laparoscopy appeared to be a safe and effective means of managing the removal of this transabdominally placed cervicoisthmic cerclage. (Am J Obstet Gynecol 2000;182:1086-8.)

Thrombophilia and Adverse Pregnancy Outcome

The hemostatic system plays an important role in three crucial stages of pregnancy: ovulation, implantation, and placentation. A thrombophilic defect is an abnormality in the coagulation pathways that predisposes an individual to thrombosis. Pregnancy is a hypercoaguable state and interest has focused on the potential role that thrombophilic defects may play in the etiology not only of recurrent miscarriage but also of late pregnancy complications. Maternal intervillous blood flow does not develop to any significant extent before 8 weeks of gestation and thrombophilic defects are therefore unlikely to contribute to pregnancy loss before this time. Retrospective studies have reported a similar prevalence of genetic thrombophilic defects among women with recurrent first-trimester miscarriage and controls but an increased prevalence among those with second-trimester miscarriage and later pregnancy complications. There is a paucity of data documenting the prospective outcome of untreated pregnancies among women with thrombophilic defects and of the placental histology in these pregnancies. Until these issues have been addressed, routine thromboprophylaxis during pregnancy cannot be recommended for women with thrombophilic abnormalities.

Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy.

Factor V (FV) Leiden and thermolabile methylenetetrahydrofolate reductase (MTHFR) are 2 common polymorphisms that have been implicated in vascular thrombosis. We determined whether these mutations predicted an adverse outcome in pregnancy. Second, we looked for an interaction between these 2 mutations in patients with recurrent fetal loss or thrombosis in pregnancy. Primigravid subjects at their booking visit to the National Maternity Hospital (Holles Street, Dublin, Ireland) were screened for the polymorphisms. Thermolabile MTHFR and FV Leiden genotypes were detected by either restriction fragment length polymorphism or heteroduplex capillary chromatography. The carrier frequency of FV Leiden in the screened primigravid population was 2.7% (allele frequency 1.36%), all being heterozygous for the mutation. This value was lower than expected from previous studies in European populations. Forty-nine percent of the screened population (289 of 584) were heterozygous for thermolabile MTHFR, and 10.6% were homozygous (62 of 584). The frequency of the 2 polymorphisms was no higher in those who subsequently developed preeclampsia (n=12) or intrauterine growth retardation (n=9), and none of the screened population developed thrombosis. However, the frequency of FV Leiden was higher in patients who subsequently miscarried after the first trimester of pregnancy (allele frequency of 5.5%, P=0.0356). Among those positive for FV Leiden, 3 of 27 miscarried, compared with 24 of 572 of FV Leiden-negative patients (11% versus 4.2%). No interaction was found between the 2 mutations in the control or patient populations. In patients with a prior history of venous thrombosis, the carrier rate of FV Leiden was increased (4 of 33, allele frequency of 7.6%, P=0. 0115). In contrast, the carrier frequency for thermolabile MTHFR was no higher, and there was no interaction between the 2 mutations. Neither mutation occurred at a significantly higher frequency in patients with a prior history of recurrent fetal loss. In conclusion, FV Leiden is a risk factor for thrombosis in pregnancy and possibly for second-trimester miscarriage independent of thermolabile MTHFR. However, prospective analysis suggests that the risk conferred by FV Leiden is low in a primigravid population. The thermolabile MTHFR genotype was not implicated in any adverse outcome.

Pregnancy outcome after treatment with etoposide (VP-16) for low-risk gestational trophoblastic tumor.

The aim of this study was to evaluate subsequent fertility and pregnancy in patients treated for persistent trophoblastic tumors with single-agent VP-16. Records of all patients treated for persistent trophoblastic tumors at the Chiba University Hospital between January 1, 1986 and December 31, 1997 were reviewed. Of these, 85 patients were initially treated with single-agent VP-16. Subsequent pregnancy outcome of these patients was investigated. After remission with VP-16, 36 patients (92.3%) of those who wished for a pregnancy (45.9% of all patients studied) conceived, and 91.7% had at least one live birth. A total of 56 conceptions resulted in 42 (75.0%) term live births, seven (12.5%) first-trimester spontaneous abortions, one (1.8%) second-trimester spontaneous abortion, four (7.1%) therapeutic abortions, and two (3.6%) repeated moles. There were no congenital anomalies, no stillbirths, and the neonates' physical growth was comparable to that of the standard population in Japan. Single VP-16 regimen for patients with low-risk gestational trophoblastic tumor appears to have no adverse effects on fertility potential and pregnancy outcome.