Progesterone concentrations on blastocyst transfer day in modified natural cycle frozen embryo transfer cycles.

RESEARCH QUESTION: Are serum progesterone concentrations on the day of modified natural cycle (mNC) frozen blastocyst transfer (FET) without luteal phase support (LPS) associated with clinical pregnancy rate (CPR)? DESIGN: Data were collected between January 2019 and October 2022 as a sub-study of an ongoing randomized controlled trial assessing pregnancy outcomes in mNC-FET. The sub-study included all women (n = 209) randomized to mNC-FET without LPS at the time of data extraction. Participants were aged 18-41 years, had regular menstrual cycles and underwent mNC-FET treatment with single-blastocyst transfer. Associations between the serum progesterone concentration on the day of blastocyst transfer and CPR, pregnancy rate and pregnancy loss rate (PLR) were examined between groups with low and higher progesterone concentrations using the 25th and 10th percentiles as cut-offs. Multivariate logistic regression analyses were performed to adjust for potential confounding factors. RESULTS: Progesterone concentrations on the day of blastocyst transfer in mNC-FET without LPS ranged from 4.9 to 91.8 nmol/l, with the 25th and 10th percentiles at 29.0 nmol/l and 22.5 nmol/l, respectively. Serum progesterone concentrations did not differ between women with or without a clinical pregnancy (mean [SD] 38.5 [14.0] versus 36.8 [12.4] nmol/l; P = 0.350). Furthermore, the CPR, pregancy rate and PLR were similar in women with low or high progesterone concentrations when using the 25th or the 10th progesterone percentile as cut-off. Multivariate regression analyses showed no association between progesterone concentrations and CPR. CONCLUSIONS: No association was found between progesterone concentration on the day of blastocyst transfer and pregnancy outcome in women undergoing mNC-FET without progesterone LPS.

Endometrial preparation methods prior to frozen embryo transfer: A retrospective cohort study comparing true natural cycle, modified natural cycle and artificial cycle.

PURPOSE: The aim of this study was to compare the outcomes of three endometrial preparation methods prior to frozen embryo transfer (FET): Natural cycle (NC), modified natural cycle (mNC), and programmed/artificial cycle (AC) protocols. Primary outcomes investigated were clinical pregnancy rate (CPR) and live birth rate (LBR). METHODS: A retrospective study on 2080 FET cycles including patients ≤ 35 years with a BMI ≤ 30 who underwent FET with a single autologous blastocyst stage embryo at Aarhus University Hospital or Horsens Regional Hospital in the period 2013-2019. Only blastocysts frozen by vitrification were included. No luteal phase support (LPS) was used in natural cycles. RESULTS: In NC, mNC and AC, CPRs were 34.9%, 40.6% and 32.0%, while LBRs were 32.3%, 36.3% and 26.6%, respectively. There were no significant differences in main outcomes when comparing AC with NC [LBR: OR = 0.9 (0.6; 1.2), p = 0.4]. Compared to NC, mNC-FET displayed significantly higher positive hCG, implantation rate, CPR and LBR [LBR: OR = 1.4 (1.0; 1.9), p = 0.03]. An analysis with mNC as reference group demonstrated significantly better outcomes in the mNC group compared to AC [LBR: OR 0.6 (0.5; 0.8), p = < 0.01]. CONCLUSION: The present study overall demonstrated better outcomes including LBR with mNC protocol as compared to NC and AC protocol, while comparison of AC and NC showed both protocols to be equally effective. A programmed cycle may be necessary for women with anovulatory cycles; however, normo-ovulating women may be offered a natural cycle protocol. TRIAL REGISTRATION NUMBER: 3-3013-3047/1 and 31-1522-44. Date of registration: June 24, 2019 and April 23, 2020.

Idiopathic early ovarian aging: is there a relation with premenopausal accelerated biological aging in young women with diminished response to ART?

PURPOSE: To evaluate whether young women with idiopathic early ovarian aging, as defined by producing fewer oocytes than expected for a given age over multiple in vitro fertilization (IVF) cycles, have changes in telomere length and epigenetic age indicating accelerated biological aging (i.e., increased risk of morbidity and mortality). METHODS: A prospective cohort study was conducted at two Danish public fertility clinics. A total of 55 young women (≤ 37 years) with at least two IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with follicle-stimulating hormone (FSH) were included in the early ovarian aging group. As controls, 52 young women (≤ 37 years) with normal ovarian function, defined by at least eight harvested oocytes, were included. Relative telomere length (rTL) and epigenetic age acceleration (AgeAccel) were measured in white blood cells as markers of premenopausal accelerated biological aging. RESULTS: rTL was comparable with a mean of 0.46 (± SD 0.12) in the early ovarian aging group and 0.47 (0.14) in the normal ovarian aging group. The AgeAccel of the early ovarian aging group was, insignificantly, 0.5 years older, but this difference disappeared when adjusting for chronological age. Sub-analysis using Anti-Müllerian hormone (AMH) as selection criterion for the two groups did not change the results. CONCLUSION: We did not find any indications of accelerated aging in whole blood from young women with idiopathic early ovarian aging. Further investigations in a similar cohort of premenopausal women or other tissues are needed to fully elucidate the potential relationship between premenopausal accelerated biological aging and early ovarian aging.

Preconceptional thyrotropin level in euthyroid women is inversely associated with the live birth rate in first in vitro fertilization cycle.

INTRODUCTION: Thyroid disorders have been associated with adverse reproductive outcome. Whether the preconceptional level of thyrotropin (TSH) in euthyroid women impacts on in vitro fertilization (IVF) outcome has been debated. This study reports the outcome of first IVF cycle in euthyroid women in relation to TSH level. MATERIAL AND METHODS: A retrospective study was conducted in women referred for fertility treatment in the period 1 January 2012 until 31 March 2014. Among the exclusion criteria were thyroid medication at referral and comorbidities. TSH was measured as part of the fertility workup, and women were followed until pregnancy loss or live birth. Outcome as well as patient characteristics were prospectively collected from a treatment database. RESULTS: A total of 623 euthyroid women underwent their first IVF cycle. The live birth rate was 27.0% (n = 168). Comparing women with a preconceptional TSH level above vs below 2.5 mIU/L, we found lower odds for clinical pregnancy (adjusted odds ratio [aOR] 0.52; 95% CI 0.29-0.95), and lower odds for live birth (aOR 0.53; 95% CI 0.29-0.99). CONCLUSIONS: A preconceptional TSH level >2.5 mIU/L was associated with lower odds for clinical pregnancy and live birth in euthyroid healthy women undergoing first IVF cycle.

Similar evolution of pain symptoms and quality of life in women with and without endometriosis undergoing assisted reproductive technology (ART).

INTRODUCTION: Altogether 10% of all women of fertile age suffer from endometriosis, and up to 25% of these women require assisted reproductive technology (ART) to conceive. During ART the process of controlled ovarian stimulation causes high levels of estrogen, which in theory increases the risk of the progression of symptoms related to this estrogen-dependent disorder. Because several case reports have described the worsening of endometriosis during ART we carried out this study to investigate whether controlled ovarian stimulation during ART aggravates symptoms in women with endometriosis in terms of pain and quality of life. MATERIAL AND METHODS: This prospective cohort study was based on questionnaires containing the Endometriosis Health Profile (EHP-30) and pain evaluated on the numerical rating scale (NRS). Women aged below 40 years were recruited and divided into three groups according to their endometriosis and ART status. Questionnaires were administered before and after controlled ovarian stimulation in one ART cycle. Change in EHP-30 and NRS scores from the 1st to 2nd questionnaire was analyzed. RESULTS: In total 52 women with endometriosis undergoing ART, 50 not undergoing ART, and 52 without endometriosis undergoing ART completed two questionnaires each. Both groups with endometriosis experienced a small increase in their quality of life, while women without endometriosis experienced a decrease. Pelvic pain worsened among women undergoing ART, but no greater worsening was detected among women with endometriosis compared with women without. CONCLUSIONS: This study showed no worsening in quality of life and a slight worsening in pelvic pain during ART regardless of endometriosis status.

Congenital Heart Disease and Fertility: A Danish Nationwide Cohort Study Including Both Men and Women.

Background Despite an increasing number of patients with congenital heart disease (CHD) reaching reproductive age, the fertility of these patients remains undescribed. Therefore, the aim of the study was to evaluate the fertility in men and women with CHD by estimating the risk of infertility and comparing the birth rates, proportions of individuals becoming parents or remaining childless, and the number of children per parent with unaffected individuals. Methods and Results The study population consisted of individuals born between 1977 and 2000. Information on CHD, infertility, and live born children were obtained from the Danish health registries. Hazard ratios for infertility were analyzed using a Cox regression model. Differences of proportions and birth rates were calculated and compared between groups. Among 1 385 895 individuals, a total of 8679 (0.6%) were diagnosed with CHD. Men and women with simple or moderate CHD had no increased risk of infertility when compared with the reference population. Estimates for complex CHD groups were too imprecise for evaluation. Individuals with CHD were more often childless with consequently lower birth rates compared with unaffected individuals. However, those becoming parents had the same number of children as the reference population. Conclusions Men and women with simple or moderate CHD had the same risk of infertility as the reference population. Despite patients with CHD more often being childless, those becoming parents had the same number of children as parents without CHD. The current findings increase the knowledge regarding fertility in the CHD population.

Congenital heart disease and the risk of impaired fertility: A Danish nationwide cohort study using time to pregnancy.

BACKGROUND: The number of women with congenital heart disease (CHD) becoming pregnant are increasing. Although menstrual irregularities appear to occur more often in these patients, knowledge on their fertility is limited. In this nationwide cohort study, we evaluated the risk of impaired fertility in women with CHD compared with unaffected women using time to pregnancy (TTP). METHODS: The Danish National Birth Cohort (DNBC) of pregnant women constituted the study population. Information on TTP and use of medically assisted reproduction (MAR) treatment was reported at a first trimester interview. Women with CHD were identified by linkage to the Danish National Patient Registry. TTP was divided into three categories; 0-5 months, 6-12 months (i.e. subfertile), and > 12 months or use of MAR treatment (i.e. infertile). Relative risk ratios (RRR) for subfertility and infertility with 95% confidence intervals were estimated using multinomial logistic regression. RESULTS: Among 93,832 pregnancies in 84,922 women, CHD was diagnosed in 333 women (0.4%), contributing with 360 pregnancies. The CHD was of simple complexity in 291 women (87.4%). No association was found between CHD and longer TTP (RRR of 1.02 (95% CI: 0.75-1.40) for subfertility, and RRR of 0.86 (95% CI: 0.61-1.20) for infertility). Similar was observed when comparing women with simple CHD and unaffected women. The number of women with complex CHD was too low for evaluation. CONCLUSIONS: Women with CHD had no increased risk of impaired fertility, assessed by TTP, when compared with unaffected women. Separate analysis of women with complex CHD was hampered by low numbers.

Timing of Pubertal Development in Boys and Girls With Congenital Heart Defects: A Nationwide Cohort Study.

Background Children with congenital heart defects (CHD) have an increased risk of developmental delay. It remains sparsely investigated if these patients also have a delayed pubertal development. In this nationwide cohort study, we evaluated if CHD was associated with timing of puberty using longitudinally collected data on pubertal milestones. Methods and Results We used data from the Danish nationwide Puberty Cohort. Information on CHD was obtained from the Danish National Patient Register. Information on pubertal development was obtained from 15 780 children through questionnaires answered half-yearly from 11 years until 18 years or full maturity. Using a multivariable regression model for censored time-to-event data, mean difference in age at attaining each pubertal milestone was estimated, including a combined pubertal marker. Compared with children without CHD, analyses were performed for both CHD overall and subdivided into simple and complex CHD. In a subanalysis, analyses were repeated in children born at term. In total, 137 children (62 boys and 75 girls) had a CHD diagnosis. Overall, no difference in age at pubertal timing was observed for children with CHD compared with unaffected children. The average differences were small for both boys (1.6 [95% CI, -2.6 to 5.7] months) and girls (1.0 [95% CI, -2.5 to 4.4] months). The same differences were observed when subdividing into simple or complex CHD and when restricting to children born at term. Conclusions We found no association between CHD and pubertal timing. For the group of children with complex CHD, we were unable to exclude a later pubertal timing.

Transcriptional expression of type-I interferon response genes and stability of housekeeping genes in the human endometrium and endometriosis.

Endometriosis is a painful chronic female disease defined by the presence of endometrial tissue implants in ectopic (Ec) locations. The pathogenesis is much debated, and type-I interferons (IFNs) could be involved. The expression of genes of the type-I IFN response were profiled by a specific PCR array of RNA obtained from Ec and eutopic (Eu) endometrium collected from nine endometriosis patients and nine healthy control women. Transcriptional expression levels of selected IFN-regulated and housekeeping genes (HKGs) were investigated by real-time quantitative reverse transcriptase PCR (qRT-PCR). Stably expressed HKGs for valid normalization of transcriptional studies of endometrium and endometriosis have not yet been published. Here, seven HKGs were evaluated for stability using the GeNorm and NormFinder software. A normalization factor based on HMBS, TBP and YWHAZ expression was suitable for normalization of qRT-PCR studies of Eu versus Ec endometrium. In the endometrial cell lines HEC1A, HEC1B, Ishikawa and RL95-2, HMBS and HPRT1 were the most stably expressed. The IFN-specific PCR array indicated significantly different expression of the genes BST2, COL16A1, HOXB2 and ISG20 between the endometrial tissue types. However, by correctly normalized qRT-PCR, levels of BST2, COL16A1 and the highly type-I IFN-stimulated genes ISG12A and 6-16 displayed insignificant variations. Conversely, HOXB2 and ISG20 transcriptions were significantly reduced in endometriosis lesions compared with endometrium from endometriosis patients and healthy controls. In conclusion, appropriate HKGs for normalization of qRT-PCR studies of endometrium and endometriosis have been identified here. Abolished expression of ISG20 and HOX genes could be important in endometriosis.

Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis.

Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score stage 1 (n= 1), 2 (n= 10), 3 (n= 11) or 4 (n= 1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1 and ESR1) were analyzed for promoter hypermethylation using methylation-specific melting curve analysis, and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel electrophoresis and direct sequencing. An oncogenic mutation in KRAS (c.34G > T; p.G12C) was detected in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order to identify the molecular basis of the susceptibility of endometriosis to malignant transformation.

Longitudinal measurement of cytokines in pre-eclamptic and normotensive pregnancies.

OBJECTIVE: To evaluate differences in plasma cytokine levels longitudinally in pre-eclamptic and normotensive pregnancies. An increased inflammatory response has long been associated with pre-eclampsia, both early and late in the pre-eclamptic pregnancy. DESIGN: Blood samples were collected longitudinally during pregnancy from a cohort of 1 631 pregnant women. Thirty-two women with pre-eclampsia and 67 normotensive pregnant women were identified from the cohort. SETTING: A Danish regional hospital. SAMPLES: Samples were collected from the 18th week of pregnancy until delivery and divided into the following four gestational intervals: <25th week, 26th-29th week, 30th-35th week and >36th week. METHODS: Simultaneous measurement of all nine cytokines was done using a capture bead system. MAIN OUTCOME MEASURES: Plasma levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α, interferon-γ and granulocyte macrophage colony-stimulating factor during pre-eclamptic and normotensive pregnancies. RESULTS: Pre-eclampsia was associated with increased tumor necrosis factor-α between the 26th and 29th week (p=0.0421) and increased IL-6 after the 36th week (p=0.0044). The other cytokines measured were comparable in the two groups. CONCLUSIONS: This large prospective collection of blood samples was undertaken to determine inflammatory status during pre-eclamptic and normotensive pregnancies. Our results support a tendency towards increased inflammation in pre-eclampsia, but the measured cytokines are not eligible for prediction, monitoring or diagnosing pre-eclampsia.

Low prevalence of DNA viruses in the human endometrium and endometriosis.

The chronic female disease endometriosis causes debilitating pain and lowered fertility. The aetiology is unknown, but indications of an infectious agent are present. This study investigates the possible involvement of a pathogenic virus in endometriosis patients and controls. DNA was purified from biopsies and subjected to highly sensitive PCR tests detecting human papillomavirus (HPV) types, the herpes family viruses HSV-1 and -2, CMV, and EBV, and the polyomaviruses SV40, JCV, BKV, KIV, WUV, and MCV. The prevalence of pathogenic DNA viruses in the human endometrium was generally low (0-10%). The virus prevalence was found to vary slightly when comparing the endometrium of healthy women and women with endometriosis. However, these were not significant differences, and no viruses were identified in endometriotic lesions. These results do not point towards any evidence that endometriosis is caused by these viruses.

Is urinary excretion of plasminogen associated with development of pre-eclampsia? An observational, explorative case-control study.

OBJECTIVES: Pre-eclampsia (PE) is characterised by renal glomerular endotheliosis and injury to the glomerular filtration barrier with proteinuria. Patients with PE display aberrant filtration of the plasma proenzyme plasminogen which is activated, in the tubular fluid, to plasmin. Plasmin may activate the epithelial sodium channel and cause impaired sodium excretion and contribute to hypertension. An explorative study was conducted to test the association between urinary total plasminogen/plasmin and the development of PE. A positive association was hypothesised. DESIGN: An observational, explorative, nested case-control study of healthy pregnant women. SETTINGS: A Danish County hospital. Samples were collected between 2001 and 2004. PARTICIPANTS: 1631 healthy pregnant women participated. Urine samples were collected longitudinally six times during pregnancy. 30 developed PE (cases) and were compared with 146 randomly selected healthy pregnant women (controls). PRIMARY OUTCOME: The association between total plasminogen/plasmin excreted in the urine and PE development is expressed by ORs. Total urinary excretion of plasminogen/plasmin was defined by the urine plasminogen-plasmin/creatinine ratio. SECONDARY OUTCOME: The association between urine (u)-albumin/creatinine ratio, u-aldosterone/creatinine ratio and PE development is expressed by ORs. The correlation between urinary (u-) plasmin and u-aldosterone concentration is expressed as a correlation coefficient. RESULTS: The development of PE in late pregnancy was associated with increased levels of the urine plasminogen-plasmin/creatinine ratio (OR=2.35; 95% CI: 1.12 to 4.93; p<0.05).U-aldosterone/creatinine ratio did not predict PE at any time. U-albumin/creatinine ratio was positively associated with the development of PE from gestational week 33 (OR=14.04; 95% CI: 2.56 to 76.97; p<0.01) and in week 33-35 (OR=14.15; 95% CI: 3.44 to 58.09; p<0.001) and after gestational week 36, respectively. CONCLUSION: Aberrant filtration of plasminogen may contribute to the pathophysiological features of impaired sodium excretion and hypertension associated with PE late in pregnancy. However, increased urinary albumin levels reveal stronger associations with PE development compared with urinary plasminogen levels.

Differential regulation of the interferon induced gene ISG12A by serum from healthy and preeclamptic pregnancies.

Endothelial-cell dysfunction is central in the preeclamptic pathogenesis. Several components present in the blood of the preeclamptic mother are capable of mediating this dysfunction. We analyzed the regulation of the ISG12A gene by serum from the third trimester, to elucidate the role of type 1 interferon ISGs late in both healthy and preeclamptic pregnancies. The ISG12A transcription was up-regulated by serum from healthy pregnant women, but not by preeclamptic serum in HeLa and human umbilical vein endothelial cells (HUVEC). However, the ISG12A up-regulation by healthy pregnancy serum was not due to a general type 1 interferon response, since 6-16 and OAS1 were not up-regulated similarly. Also, the up-regulation of ISG12A was independent of the interferon-alpha receptor 2, but dependent on STAT1. Stimulation with folic acid alone or in combination with preeclamptic serum up-regulated ISG12A and 6-16. We conclude that type 1 interferon is not increased in third trimester serum, neither from healthy nor preeclamptic pregnancies. However, since ISG12A mRNA is up-regulated in healthy pregnancies, the ISG12A protein might take part in maintaining endothelial stability, as this function is lacking in preeclamptic pregnancies. Folic acid may ameliorate endothelial cell stability in preeclampsia by up-regulating ISG12A.

Psychological aspects of endometriosis: differences between patients with or without pain on four psychological variables.

OBJECTIVE: Women with endometriosis often have pain symptoms that seemingly do not relate to the stage of disease. It has been suggested that psychological factors may contribute to this disproportion. The purpose of this study was to compare patients with and without pain symptoms to see whether they differed in profile on four psychological parameters. STUDY DESIGN: Sixty-three women with laparoscopically diagnosed endometriosis of whom 20 were symptom free, completed four psychometric tests assessing coping, emotional inhibition, depression, and anxiety. RESULTS: Significant positive correlations were found between coping and depression/anxiety, and between pain severity and subjective psychosocial impairment. There were no significant differences between the two groups on depression or anxiety and no correlations between pain severity and depression/anxiety. CONCLUSION: Coping appears to be of major importance to the psychological consequences of endometriosis. This may have implications for the treatment of endometriosis. The study could not confirm previous findings of pain related to endometriosis being associated with a higher prevalence of depression and anxiety.

Endometriosis, dysmenorrhea and diet--what is the evidence?

The objective of this study is to assess the literature concerning the effect of diet on endometriosis and dysmenorrhea and to elucidate evidential support, to give dietary recommendations to women suffering from these conditions. A systematic search in electronic databases on a relationship between diet and endometriosis/dysmenorrhea was performed. Data on diet and endometriosis were limited to four trials of which two were animal studies. The articles concerning human consumption found some relation between disease and low intake of vegetable and fruit and high intake of vegetarian polyunsaturated fat, ham, beef and other red meat. Results concerning fish intake were not consistent. Eight trials of different design, with a total of 1097 women, investigated the relationship between diet and dysmenorrhea. Intake of fish oil seemed to have a positive effect on pain symptoms. This study concludes that literature on diet and endometriosis is sparse, whereas eight studies have looked at diet and dysmenorrhea. No clear recommendations on what diet to eat or refrain from to reduce the symptoms of endometriosis can be given, while a few studies indicate that fish oil can reduce dysmenorrhea. Further research is recommended on both subjects.

A nine-nucleotide deletion and splice variation in the coding region of the interferon induced ISG12 gene.

Interferons (IFNs) are a family of cytokines with growth inhibitory, and antiviral functions. IFNs exert their biological actions through the expression of more than 1000 IFN stimulated genes, ISGs. ISG12 is an IFN type I induced gene encoding a protein of M(r) 12,000. We have identified a novel, IFN inducible splice variant of ISG12 lacking exon 2 leading to a putative truncated protein isoform of M(r) 7400, ISG12-S. In cells from blood and cervical cytobrush material from healthy women, the level of ISG12-S expression was higher than ISG12 expression, whereas the expression pattern was more evenly distributed between ISG12 and ISG12-S in breast carcinoma cells, in cancer cell lines and in cervical cytobrush material with neoplastic lesions. In addition, we have found a nine-nucleotide deletion situated in exon 4 of the ISG12 gene. This deletion leads to a three-amino-acid deletion (AMA) in the putative ISG12 gene products, ISG12Delta and ISG12-SDelta. We have determined the prevalence of the deletion ISG12Delta in normal and neoplastic cells. Homozygosity ISG12(0/0) and ISG12(Delta/Delta), and heterozygosity ISG12(0/Delta) were found, although the ISG12(Delta/Delta) genotype was rare. In heterozygous cells from cytobrush material with neoplastic lesions, we found a preference for expression of the ISG12(0) allele.

A single rapid point-of-care placental growth factor determination as an aid in the diagnosis of preeclampsia.

OBJECTIVES: To evaluate the clinical performance of a rapid point-of-care test, Triage PLGF (Alere, San Diego) in the diagnosis of preeclampsia. STUDY DESIGN: For the reference range 2212 plasma samples were collected from 595 subjects with normotensive pregnancies, between week 17 of gestation and delivery. In the case-control part, two cohorts of women with preeclampsia (80 women) were matched for maternal age, gestational age (GA) at sampling and parity with normotensive women who delivered at 37weeks or more. RESULTS: The areas under the receiver operating characteristic curves (GA<35weeks) were 1.0 and 0.994 (cohort 1 and 2, respectively). The clinical sensitivity of the Triage PLGF test for the pooled GA range of 21⩽GA<35, using a GA dependent cut-off, was 1.0 for both cohorts with specificities of 1.0 and 0.940. CONCLUSIONS: The Triage PLGF test distinguishes well between preterm pregnancies with and without preeclampsia.