Subsequent pregnancy outcomes after second trimester miscarriage or termination for medical/fetal reason: A systematic review and meta-analysis of observational studies.

INTRODUCTION: Women with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about the impact of a second trimester pregnancy loss on subsequent pregnancy outcome. This review investigated if second trimester miscarriage or termination for medical reason or fetal anomaly (TFMR/TOPFA) is associated with future adverse pregnancy outcomes. MATERIAL AND METHODS: A systematic review of observational studies was conducted. Eligible studies included women with a history of a second trimester miscarriage or termination for medical reasons and their pregnancy outcomes in the subsequent pregnancy. Where comparative studies were identified, studies which compared subsequent pregnancy outcomes for women with and without a history of second trimester loss or TFMR/TOPFA were included. The primary outcome was livebirth, and secondary outcomes included: miscarriage (first and second trimester), termination of pregnancy, fetal growth restriction, cesarean section, preterm birth, pre-eclampsia, antepartum hemorrhage, stillbirth and neonatal death. Studies were excluded if exposure was nonmedical termination or if related to twins or higher multiple pregnancies. Electronic searches were conducted using the online databases (MEDLINE, Embase, PubMed and The Cochrane Library) and searches were last updated on June 16, 2023. Risk of bias was assessed using the Newcastle-Ottawa scale. Where possible, meta-analysis was undertaken. PROSPERO registration: CRD42023375033. RESULTS: Ten studies were included, reporting on 12 004 subsequent pregnancies after a second trimester pregnancy miscarriage. No studies were found on outcomes after second trimester TFMR/TOPFA. Overall, available data were of "very low quality" using GRADE assessment. Meta-analysis of cohort studies generated estimated outcome frequencies for women with a previous second trimester loss as follows: live birth 81% (95% CI: 64-94), miscarriage 15% (95% CI: 4-30, preterm birth 13% [95% CI: 6-23]).The pooled odds ratio for preterm birth in subsequent pregnancy after second trimester loss in case-control studies was OR 4.52 (95% CI: 3.03-6.74). CONCLUSIONS: Very low certainty evidence suggests there may be an increased risk of preterm birth in a subsequent pregnancy after a late miscarriage. However, evidence is limited. Larger, higher quality cohort studies are needed to investigate this potential association.

Clinical presentation, investigation, underlying causes, and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage.

AIM: To evaluate the causes of miscarriage and subsequent pregnancy outcomes among different phenotypes of second trimester miscarriage. METHODS: Retrospective analysis of 170 consecutive second trimester miscarriages between 14 + 0 and 23 + 6 weeks recorded in the Clinical Data Analysis and Reporting System from 2012 to 2021. Cases were excluded if miscarriages occurred before 14 + 0 weeks of gestation, data were incomplete, or passage of the fetus happened before the clinical assessment. Cases were classified with a stepwise approach into three phenotypic groups including silent miscarriages (ST-SM), rupture of membranes (ST-ROM), and inevitable miscarriages (ST-IM) depending on the fetal heart pulsation and leakage of liquor at presentation. Clinical investigation of the underlying causes and the outcome of the subsequent pregnancy was then reviewed. RESULTS: There were 97 cases of ST-SM, 21 cases of ST-ROM, and 52 cases of ST-IM. Placental histology and karyotype examination were more likely to yield significant results in the cases of ST-ROM and ST-SM (p < 0.05). The phenotypic examination identified different underlying causes including fetal anomaly, suspected cervical insufficiency, diabetes mellitus, and unknown causes (p < 0.001). Sixty-four cases achieved a subsequent pregnancy. Although women with history of ST-ROM and ST-IM received more cervical length monitoring and cervical cerclage than those with ST-SM (66.7% vs. 44.4% vs. 7.5%, p = 0.0002; and 16.7% vs. 22.2% vs. 2.5%, p = 0.031, respectively), the risk of recurrent second trimester miscarriage was higher in ST-ROM and ST-IM than in ST-SM (16.7% vs. 0%, p = 0.018). CONCLUSION: The classification can differentiate different second trimester miscarriage phenotypes, which offers essential information to guide investigation panels of the underlying cause of miscarriages, and the prognosis and management of subsequent pregnancy. Future researches focused on second trimester miscarriage should report their findings according to different phenotypes.

The association between vaginal bacterial composition and miscarriage: a nested case-control study.

OBJECTIVE: To characterise vaginal bacterial composition in early pregnancy and investigate its relationship with first and second trimester miscarriages. DESIGN: Nested case-control study. SETTING: Queen Charlotte's and Chelsea Hospital, Imperial College Healthcare NHS Trust, London. POPULATION: 161 pregnancies: 64 resulting in first trimester miscarriage, 14 in second trimester miscarriage and 83 term pregnancies. METHODS: Prospective profiling and comparison of vaginal bacteria composition using 16S rRNA gene-based metataxonomics from 5 weeks' gestation in pregnancies ending in miscarriage or uncomplicated term deliveries matched for age, gestation and body mass index. MAIN OUTCOME MEASURES: Relative vaginal bacteria abundance, diversity and richness. Pregnancy outcomes defined as first or second trimester miscarriage, or uncomplicated term delivery. RESULTS: First trimester miscarriage associated with reduced prevalence of Lactobacillus spp.-dominated vaginal microbiota classified using hierarchical clustering analysis (65.6 versus 87.7%; P = 0.005), higher alpha diversity (mean Inverse Simpson Index 2.5 [95% confidence interval 1.8-3.0] versus 1.5 [1.3-1.7], P = 0.003) and higher richness 25.1 (18.5-31.7) versus 16.7 (13.4-20), P = 0.017), compared with viable pregnancies. This was independent of vaginal bleeding and observable before first trimester miscarriage diagnosis (P = 0.015). Incomplete/complete miscarriage associated with higher proportions of Lactobacillus spp.-depleted communities compared with missed miscarriage. Early pregnancy vaginal bacterial stability was similar between miscarriage and term pregnancies. CONCLUSIONS: These findings associate the bacterial component of vaginal microbiota with first trimester miscarriage and indicate suboptimal community composition is established in early pregnancy. While further studies are required to elucidate the mechanism, vaginal bacterial composition may represent a modifiable risk factor for first trimester miscarriage. TWEETABLE ABSTRACT: Vaginal bacterial composition in first trimester miscarriage is associated with reduced Lactobacillus spp. abundance and is independent of vaginal bleeding.

Recurrence of second trimester miscarriage and extreme preterm delivery at 16-27 weeks of gestation with a focus on cervical insufficiency and prophylactic cerclage.

INTRODUCTION: The objective of this study was to describe recurrence rates of second trimester miscarriage and extreme preterm delivery by phenotype and use of prophylactic cerclage in a register-based cohort. MATERIAL AND METHODS: We included women with a first second trimester miscarriage or extreme preterm delivery (16+0 to 27+6 gestational weeks) in Denmark in 1997-2012 (n = 9602) by combined use of the Danish Medical Birth Register and the Danish National Patient Register. Eight phenotypes were identified by ICD-10 codes in a hierarchy with the following sequence: major fetal anomaly, multiple gestation, uterine anomaly, placental insufficiency, antepartum bleeding, cervical insufficiency, preterm premature rupture of membranes, and intrauterine fetal death. Recurrence rate after a second trimester miscarriage/spontaneous delivery in the period was calculated based on the register data. In cervical insufficiency outcome was stratified by prophylactic cerclage applied <16 weeks of gestation. RESULTS: Overall recurrence rate was 7.3% (n = 452), a rate that differed by phenotype from <5% (fetal anomaly, multiple gestations, intrauterine fetal death) to 21% (cervical insufficiency). In women with cervical insufficiency the recurrence rate was 28% without cerclage; vaginal cerclage was associated with a significant reduction [adjusted odds ratio (OR) 0.47; 95% CI 0.29-0.76] and abdominal cerclage with an even greater reduction (adjusted OR 0.14; 95% CI 0.03-0.61). CONCLUSIONS: The overall recurrence rate of second trimester miscarriage or extreme preterm delivery was 7%, but it differed significantly by phenotype. The highest rate, 28%, was found in cervical insufficiency, and prophylactic cerclage was associated with a significant reduction in recurrence.

Cerclage suture type to prevent pregnancy loss in women requiring a vaginal cervical cerclage: the C-STICH RCT.

Background: Second trimester miscarriage and preterm birth is a significant global problem. Surgical cervical cerclage is performed to prevent pregnancy loss and preterm birth. It utilises either a monofilament or braided suture. It is hypothesised that a braided material becomes colonised with pathogenic bacteria that causes vaginal dysbiosis, infection and cerclage failure. Objectives: The primary objective of the study was to examine the effectiveness of using a monofilament suture material as opposed to a braided suture material on pregnancy loss in women requiring a vaginal cervical cerclage. Design: Superiority open randomised controlled trial. Setting: Seventy-five maternity sites across the UK. Participants: Women experiencing a singleton pregnancy requiring a cervical cerclage. Interventions: Monofilament suture or braided suture. Main outcome measures: The primary outcome was pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life). Secondary outcomes included the core outcome set for preterm birth. Methods: Women were randomised on a 1 : 1 basis to monofilament or braided cerclage utilising a bespoke randomisation service with minimisation dependent on the site, indication for cerclage, intention to use progesterone and planned surgical technique. The inclusion criteria were three or more previous mid-trimester losses or preterm births, insertion of a cerclage in a previous pregnancy, a history of a mid-trimester loss or preterm birth with a shortened cervical length in the current pregnancy or in women who clinicians deemed at risk of preterm birth. The exclusion criteria were an emergency or rescue cerclage, age of < 18 years, being unable to give informed consent or the cerclage having to be placed abdominally. The original sample size was calculated based on a relative risk reduction of 41% from a pregnancy loss rate of 19% in the braided group to 11% in the monofilament group with 90% power and alpha at p = 0.05. The independent data monitoring committee noted a lower-than-anticipated pooled event rate within the trial and recommended an increase in sample size to 2050. The outcome data were collected using clinical record forms from the maternal and neonatal medical records and reported to Birmingham Clinical Trials Unit. Results: A total of 2049 women were randomised, after withdrawals and loss to follow-up, data on 1005 women in the monofilament group and 993 women in the braided group were included. The baseline demographics between the groups were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups (80/1003 vs. 75/993; adjusted risk ratio: 1.05, 95% confidence interval: 0.79 to 1.40; adjusted risk difference: 0.002, 95% confidence interval: -0.02 to 0.03). Limitations: The trial did not collect long-term paediatric outcomes. There were no safety concerns. Conclusions: There was no evidence of a difference in pregnancy loss between a monofilament suture and a braided suture. Future work: Long-term follow-up of neonates born within the C-STICH (cerclage suture type for an insufficient cervix and its effects on health outcomes) trial. Trial registration: This trial is registered as ISRCTN15373349. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/04/107) and is published in full in Health Technology Assessment; Vol. 28, No. 40. See the NIHR Funding and Awards website for further award information.

Cervical cerclage is an operation performed in pregnancy to prevent miscarriage and preterm birth. A cervical cerclage is sometimes recommended in women who have had babies born prematurely before or who have had previous cervical surgery. A cerclage operation involves a stitch being inserted around the neck of the womb (cervix) to keep it closed during pregnancy and to prevent it opening prematurely. When performing the operation, the doctor can use different types of threads made of different materials. The threads used to perform the operation are called sutures. One suture type is a single strand or monofilament thread, and the other is a multifilament braided thread with lots of thin strands woven together. Some evidence has suggested that using a monofilament suture thread prevented pregnancy loss by preventing infection. Therefore, we performed a randomised controlled trial of the use of monofilament suture thread versus braided suture thread, aiming to reduce pregnancy loss in women who were having a cerclage as part of their routine care. The women consented to take part in the study and were randomly allocated to their cerclage performed with either a monofilament or braided suture thread; there was no other change to their planned pregnancy care. What happened in their pregnancy was recorded from their medical records and analysed. A total of 2049 women agreed to take part in the study and consented to the analysis of their pregnancy and neonatal outcomes. Cerclage suture type for an insufficient cervix and its effects on health outcomes showed that there was no difference in pregnancy loss between the two suture threads. There was decreased maternal sepsis and decreased chorioamnionitis (which is an infection inside the womb during labour) in the women who received a monofilament suture, which needs further investigation. Although more women who had a cerclage using the monofilament thread needed a small operation and an anaesthetic, often between 36 and 37 weeks, to remove the monofilament suture prior to a vaginal birth, there were no differences in the outcomes for their babies.

Differences in the incidence of obstetric complications depending on the extent and location of adenomyosis lesions.

OBJECTIVES: Although adenomyosis is reportedly associated with adverse pregnancy outcomes, clinical factors related to the high risk of obstetric complications are unclear. This study aimed to elucidate the characteristics of adenomyosis lesions associated with the increased incidence of obstetric complications based on imaging findings. METHODS: This was a retrospective, observational cohort study conducted in a tertiary perinatal care center. Eighty-eight singleton pregnant women with adenomyosis were included in the study. Based on magnetic resonance imaging or ultrasonography before and/or during pregnancy, patients were classified according to three types of image characteristics: the extent of adenomyosis lesion (focal type or diffuse type), location of the lesion (extrinsic type, intrinsic type, or indeterminate type), the positional relationship between the lesion and the placenta (placenta distant from adenomyosis or placenta over adenomyosis), and the incidence of obstetric complications were examined. RESULTS: Patients with diffuse type adenomyosis are significantly more likely to have spontaneous second-trimester miscarriage (diffuse type vs. focal type: 16.7 vs. 0%, p < .01), preterm premature rupture of membranes (19.4 vs. 1.9%, p < .01), and preeclampsia (25.0 vs. 7.7%, p = .02), as compared to those with focal type adenomyosis. In a comparison of the three location types, the incidence of placental malposition was higher in patients with the extrinsic type adenomyosis (extrinsic type vs. intrinsic type vs. indeterminate type: 20.0 vs. 6.7 vs. 2.3%, p = .03). Comparisons between the types of the placenta over or distant from adenomyosis lesion displayed no significant differences in the frequencies of obstetric complications. CONCLUSIONS: We demonstrated that the frequency of obstetric complications related to adenomyosis varies depending on the extent and location of the lesion; patients with diffuse type adenomyosis have an increased risk of spontaneous second-trimester miscarriage, preterm premature rupture of membranes, and preeclampsia, while patients with extrinsic type adenomyosis have an increased risk of placental malposition. Imaging evaluation of adenomyosis prior to conception or early in pregnancy may be useful for the obstetrical risk assessment among patients with adenomyosis.

Second-trimester miscarriage: a review of postnatal investigations and subsequent pregnancy outcomes.

BACKGROUND: Second-trimester loss is pregnancy loss after the 12th and before the 24th completed weeks of pregnancy. This study aims to review cases of second-trimester miscarriage who attended a large maternity hospital and to examine pregnancy outcomes in this group of women. METHODS: This study is a review of cases of second-trimester miscarriage using descriptive, exploratory design, involving a retrospective chart review. RESULTS: In this study, 106 cases of second-trimester miscarriage were reviewed. The cause of the miscarriage was found in 42.5% (n = 45) of cases. The majority of women, 84.5% (n = 82) had a normal pelvic ultrasound scan and 18.3% (n = 17) of cases were diagnosed with antiphospholipid syndrome. In women who became pregnant again, 60.9% (n = 39) had a live birth. CONCLUSIONS: Establishing the cause of second-trimester miscarriage can be challenging, despite completing all recommended investigations. Outcomes in subsequent pregnancies are reassuring. This review highlights the need to undertake all recommended investigations to elicit the cause of second-trimester miscarriage and underpins the need for further research in this area.

Association of late second trimester miscarriages with placental histology and autopsy findings.

OBJECTIVES: To describe the placental histology and autopsy findings in pregnancies where fetal demise occurred before a gestational age of 22 weeks. STUDY DESIGN: This study was a subset of a larger study where the effect of alcohol exposure during pregnancy on stillbirths was studied. In a prospective cohort, 7,010 singleton pregnancies were followed from the first antenatal visit until infant one year of age visit. Gestational age was assessed by ultrasound, preferably at the first antenatal visit. All pregnancy losses were identified and when the fetuses delivered at or after a gestation of 20 weeks, the mother or parents were approached for consent for autopsy. This study describes the placental pathology and findings at autopsy in losses before 22 weeks gestation (late second trimester miscarriages). RESULTS: Fourteen cases were identified in which 13 had an autopsy and 12 had a histological examination of the placenta. The most prevalent histological abnormality was placental abruption which was seen in 6 miscarriages, occasionally on its own, or in combination with maternal vascular malperfusion or acute chorioamnionitis. The second most frequent finding was maternal vascular malperfusion, as found in five placentas, alone or in combination with other pathology. The third most frequent pathology was acute chorioamnionitis, found in four placentas, in combination or alone. Other causes were diffuse chronic villitis due to cytomegalovirus infection and early amnion rupture with anhydramnios and cord obstruction. CONCLUSIONS: Causes of fetal demise at the end of the second trimester differ little from causes of stillbirth. There is value in using placental histology in late second trimester miscarriages to try to identify the cause of demise.

Subsequent pregnancy outcomes following second trimester miscarriage-A prospective cohort study.

OBJECTIVES: Pregnancy after second-trimester miscarriage represents as clinical challenge. This study sought to determine the rates of recurrence, preterm birth and live births in a cohort of 185 women with previous second-trimester miscarriage. We hypothesized that there would be a higher rate of second-trimester miscarriage and preterm birth in subsequent pregnancy after second trimester miscarriage. The primary objectives of this study were to establish rates of second-trimester miscarriage, preterm birth and live births in this cohort. Secondary objectives were to examine medical and surgical interventions, in addition to other pregnancy outcomes and complications. STUDY DESIGN: This was a prospective cohort study carried out in a tertiary referral center in southern Ireland with over 8000 deliveries per year. 175 women were followed up. Inclusion criteria were an ultrasound confirmed second-trimester miscarriage between June 2009 and June 2013 and subsequently having a pregnancy between July 2009 and January 2016. Fifty-five women did not become pregnant during the study period and were excluded. Ten women were excluded for missing data. RESULTS: Between July 2009 and January 2016, 110 women became pregnant following a previous second-trimester miscarriage. In total, 81 babies were born to 77 mothers. The recurrence rate of second-trimester miscarriage was 6.3% (7/110) and the preterm birth rate was also 6.3% (7/110). The cesarean section rate was 45%. Including those who experienced first or second trimester miscarriage, 47% (78/155) of those who were followed up did not go on to have a live infant. CONCLUSIONS: Women experiencing second-trimester miscarriage are at increased risk in subsequent pregnancies of recurrence. Second-trimester miscarriage needs to be highlighted as a risk factor for adverse pregnancy outcomes. Greater research into its pathophysiology is required to advance preventative measures.

Are 3D ultrasound and office hysteroscopy useful for the assessment of uterine cavity after late foetal loss?

OBJECTIVE: To assess the efficacy of office hysteroscopy and 3D ultrasound for the diagnostic of uterine anomalies after late foetal loss. METHOD: This retrospective observational study took place in the gynaecologic unit of a teaching hospital from 2009 to 2014. Women with late foetal loss (<22 weeks of gestation) had an office hysteroscopy and 3D ultrasound within three months after delivery. The results of the ultrasound and hysteroscopy were recorded and compared. RESULTS: Eighty women were included with a mean age of 29.8 years (28.2-31.4). Forty-seven women had both hysteroscopy and 3D ultrasound, and a uterine cavity's anomaly (bicornuate uterus, T-Shape uterus and septate uterus) was found in ten women (21%) at 3D sonography and in 13 women (28%) at office hysteroscopy. Concordance between the two exams was very good with a kappa at 0.83. In three cases, a uterine cavity's anomaly was found at hysteroscopy whereas sonography was normal. Anomalies at ultrasound (uterine cavity's anomaly, myometrium anomaly or ovarian anomaly) were found in 27.6% of cases. CONCLUSIONS: Both 3D ultrasound and office hysteroscopy are useful for assessment of the uterine cavity after late foetal loss. The application of these two exams is important, as hysteroscopy is generally used for assessment of the uterine cavity and endometrium, while 3D ultrasound is generally used to identify the precise type of uterine malformation and for the examination of the myometrium and annexes.

[Use of pessaries to prevent preterm birth: Are we going back to mechanical devices in obstetrics?]. / La prévention de l'accouchement prématuré par le pessaire: retour des outils mécaniques en obstétrique ?

AIM: To review the available data in the literature on the use of pessaries in preventing preterm birth. MATERIALS AND METHODS: We searched PubMed and the Cochrane library with pessary preterm birth. RESULTS: Fifty-eight papers were identified, most of them with little scientific value. A randomized study, including 385 singleton pregnancies with a transvaginal ultrasound cervical length less than 25 mm between 18 and 22 WG, shows a reduction of spontaneous prematurity before 34 WG in the pessary group, with an OR of 0.18 (95%CI: 0.08-0.37). Another study on multiple pregnancies randomized between 12 and 20 WG, with a cervix measured by ultrasound between 16 and 22 WG, showed a reduction of neonatal morbidity in the pessary group (RR: 0.42; 95%CI: 0.19-0.91) in a sub-group with a cervical length<38 mm. CONCLUSIONS: These first results from randomized controlled study are encouraging. Other studies on singleton and twin pregnancies are ongoing or about to start.