A. Pexsters

Limitations of current definitions of miscarriage using mean gestational sac diameter and crown–rump length measurements: a multicenter observational study

There is significant variation in cut‐off values for mean gestational sac diameter (MSD) and embryo crown–rump length (CRL) used to define miscarriage, values suggested in the literature ranging from 13 to 25 mm for MSD and from 3 to 8 mm for CRL. We aimed to define the false‐positive rate (FPR) for the diagnosis of miscarriage associated with different CRL and MSD measurements with or without a yolk sac in a large study population of patients attending early pregnancy clinics. We also aimed to define cut‐off values for CRL and MSD that, on the basis of a single measurement, can definitively diagnose a miscarriage and so exclude possible inadvertent termination of pregnancy.

Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?

Endometriosis is more frequently diagnosed in patients with infertility than in a normal population. The goal of this paper is to give an overview of the clinical and fundamental evidence for a possible link between endometriosis and (recurrent) miscarriage or implantation failure after treatment with assisted reproductive technology. According to the literature, there is insufficient evidence for an association between endometriosis and (recurrent) miscarriage, but there is, however, epidemiological evidence to support the link between endometriosis and recurrent implantation failure after assisted reproduction. This can possibly be explained by alterations in humoral and cell-mediated immunity in women with endometriosis. Humoral immunological changes include increased formation of antibodies against endometrial antigens, anti-laminin-1 auto-antibodies and other auto-immune antibodies (e.g. antiphospholipid). Cell-mediated immunological changes include alterations in peritoneal and follicular fluid immune cells and cytokines. The possible negative effect of these immunological changes on folliculogenesis, ovulation, oocyte quality, early embryonic development and implantation in women with endometriosis suggests that infertility in endometriosis patients may be related to alterations within the follicle or oocyte, resulting in embryos with decreased ability to implant.

Ovarian hyperstimulation syndrome and complications of ART

This article reviews serious clinical complications related to assisted reproductive technology (ART) procedures (ovarian stimulation and oocyte aspiration), including ovarian hyperstimulation syndrome (OHSS), bleeding and infection. These complications are rare, but can be severe and even life-threatening. It is important that general practitioners and gynaecologists are aware of these complications, because they will often be the first to be contacted by patients. Similarly, patients should be counselled before starting ART procedures that iatrogenic complications can be associated with ovarian stimulation and/or oocyte aspiration.

Clinical implications of intra- and interobserver reproducibility of transvaginal sonographic measurement of gestational sac and crown-rump length at 6-9 weeks' gestation

To assess intra‐ and interobserver agreement of routinely performed measurements—crown–rump length (CRL) and mean gestational sac diameter (MSD)—for assessing the likelihood of miscarriage in the first trimester of pregnancy using transvaginal sonography.

Standardized approach for imaging and measuring Cesarean section scars using ultrasonography

Incomplete healing of the scar is a recognized sequel of Cesarean section (CS) and may be associated with complications in later pregnancies. These complications can include scar pregnancy, a morbidly adherent placenta, scar dehiscence or rupture. To date there is uncertainty relating to the factors that lead to poor scar healing and how to recognize it. In recent years, there has been an increase in studies using ultrasound that describe scars as deficient, or poorly, incompletely or inadequately healed with few data to associate the morphology of the scar with the functional integrity of the lower segment of the uterus. There have been multiple attempts to describe CS scars using ultrasonography. Different terminology, methods and results have been reported, yet there is still no consensus regarding the prevalence, clinical significance or most appropriate method to describe the appearances of these scars. Developing a test that can predict the likelihood of women having problems associated with a CS scar is becoming increasingly important. On the other hand, understanding whether the ultrasound appearances of the scar can tell us anything about its integrity is not well supported by the research evidence. In this article we present an overview of ultrasound‐based definitions and methods used to describe CS scars. We also present information relating to the performance of alternative techniques used to evaluate CS scars. Having examined the current evidence we suggest a standardized approach to describe CS scars using ultrasound so that future studies can be meaningfully compared. Copyright

Assessing first trimester growth: the influence of ethnic background and maternal age

BACKGROUND First trimester growth restriction may predict miscarriage or adverse outcome later in the pregnancy, but determinants of early growth are not well described. Our objective was to examine factors influencing fetal and gestational sac size in the first trimester. METHODS Prospective observational study of 1828 singleton pregnancies before 12 weeks gestation. Maternal characteristics (ethnicity, maternal age, obstetric history, abdominal pain and vaginal bleeding), crown rump length (CRL) and mean gestational sac diameter (MSD) were recorded. A stepwise linear mixed effects analysis was performed to determine factors influencing rate of change in CRL and MSD. RESULTS 1063 scans, in 464 women, were included. Rate of increase in CRL was higher in women of black ethnic origin (P = 0.0261) compared with white, and increased with advancing maternal age (P = 0.0046). Maternal age also influenced MSD: older women had gestational sacs which were 0.118 mm larger for each one year increase in maternal age (P = 0.0073). Bleeding, pain and prior obstetric history did not influence CRL or MSD. CONCLUSIONS Rate of increase in CRL was greater in fetuses of black versus white women and increased with advancing maternal age. As CRL is used to date pregnancies, and this influences further growth assessment, consideration should be given to the use of individualized growth charts which take account of maternal factors found to influence first trimester growth.

PGD for a complex chromosomal rearrangement by array comparative genomic hybridization

Patients carrying a chromosomal rearrangement (CR) have an increased risk for chromosomally unbalanced conceptions. Preimplantation genetic diagnosis (PGD) may avoid the transfer of embryos carrying unbalanced rearrangements, therefore increasing the chance of pregnancy. Only 7-12 loci can be screened by fluorescence in situ hybridization whereas microarray technology can detect genome-wide imbalances at the single cell level. We performed PGD for a CR carrier with karyotype 46,XY,ins(3;2)(p23;q23q14.2),t(6;14)(p12.2;q13) using array comparative genomic hybridization. Selection of embryos for transfer was only based on copy number status of the chromosomes involved in both rearrangements. In two ICSI-PGD cycles, nine and seven embryos were analysed by array, leaving three and one embryo(s) suitable for transfer, respectively. The sensitivity and specificity of single cell arrays was 100 and 88.8%, respectively. In both cycles a single embryo was transferred, resulting in pregnancy following the second cycle. The embryo giving rise to the pregnancy was normal/balanced for the insertion and translocation but carried a trisomy 8 and nullisomy 9 in one of the two biopsied blastomeres. After 7 weeks of pregnancy the couple miscarried. Genetic analysis following hystero-embryoscopy showed a diploid (90%)/tetraploid (10%) mosaic chorion, while the gestational sac was empty. No chromosome 8 aneuploidy was detected in the chorion, while 8% of the cells carried a monosomy for chromosome 9. In summary, we demonstrate the feasibility and determine the accuracy of single cell array technology to test against transmission of the unbalanced meiotic products that can derive from CRs. Our findings also demonstrate that the genomic constitution of extra-embryonic tissue cannot necessarily be predicted from the copy number status of a single blastomere.

Gestational sac and embryonic growth are not useful as criteria to define miscarriage: a multicenter observational study

We studied changes in mean gestational sac diameter (MSD) and embryonic crown–rump length (CRL) in intrauterine pregnancies of uncertain viability (IPUVs). We aimed to establish cut‐off values for MSD and CRL growth that could be definitively associated with either viability or miscarriage, and to establish the relationship between growth in MSD and appearance of embryonic structures in the gestational sac.

Cytogenetic and morphological analysis of early products of conception following hystero-embryoscopy from couples with recurrent pregnancy loss

Our knowledge about miscarriages mainly concerns pregnancies of at least 8 weeks’ gestation. Information about the morphology and the genetic determinants of early aborted embryos remains limited. In addition, it is known that aneuploidies account for less than half of recurrent spontaneous abortions. We hypothesized that (recurrent) early pregnancy losses might have other genetic causes.

Functional linear discriminant analysis: a new longitudinal approach to the assessment of embryonic growth

BACKGROUND Functional linear discriminant analysis (FLDA) is a new growth assessment technique using serial measurements to discriminate between normal and abnormal fetal growth. We used FLDA to assess and compare growth in live pregnancies destined to miscarry with those remaining viable. METHODS This was a prospective cohort study of women with ultrasound scans on at least two separate occasions showing live pregnancies. Serial crown-rump length (CRL), mean gestational sac diameter and mean yolk sac diameter measurements were recorded. The ability of FLDA to predict subsequent miscarriage was compared with that of a single CRL measurement. RESULTS Of 521 included pregnancies, 493 (94.6%) remained viable at 14 weeks and 28 (5.4%) miscarried. The CRL growth rate was significantly lower in those that miscarried (one-sample t-test, P = 2.638E-22). The sensitivity of FLDA in predicting miscarriage from serial CRL measurements was 60.7% and specificity was 93.1% [positive predictive value (PPV) 33.3%, negative predictive value (NPV) 97.7%]. This was significantly better for predicting miscarriage than a single CRL observation of more than 2SD below that expected (sensitivity 53.6%, specificity 72.2%, PPV 9.9%, NPV 96.5%). CONCLUSIONS FLDA discriminates between normal and abnormal growth to predict miscarriage with high specificity. FLDA predicts miscarriage better than a single observation of a small CRL.