| 1. |
- Ternby, Ellen, 1987-
(författare)
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Information prior to prenatal diagnosis : Knowledge, informational needs and decision-making
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to explore different aspects of information relevant to decision-making regarding prenatal diagnosis (PND) for chromosomal anomalies (CA). In Papers I–II, women and partners undergoing combined ultrasound and biochemistry (CUB) tests, invasive tests or declining PND for CAs answered a questionnaire. Overall, expectant parents had varying to low levels of knowledge about Down syndrome (DS), with few differences between women and partners, or between those accepting or declining PND. Thus, knowledge at these levels does not seem to influence the decision to accept or decline PND. Some seem to regard CUB as a routine test.Paper III explored midwives' perspectives with a questionnaire. The majority believed they had not received sufficient education about PND, and few felt knowledgeable enough to provide information about DS. Most midwives desired more education regarding tests and DS. Actual knowledge levels concerning DS varied, and in some cases, were low.Paper IV explored the factors influencing decisions concerning PND through interviews with pregnant women. The decision-making process is affected by individual factors (i.e. attitude towards anomalies, worry and need for reassurance, and self-perceived risk) and external factors (i.e. test characteristics and influence from others). The quality of life for an affected individual and the impact on the family is important for some women when making decisions about PND. Healthcare professionals can influence women’s decisions through their attitudes, how they present the tests, and the woman’s individual probability of CAs.Paper V used Q methodology to explore women’s views on what is important when receiving information about PND. Some women prefer receiving information gradually, while others prefer comprehensive information early in pregnancy. Some value information about the conditions tested for early in the process. The extent to which women wanted to involve their partner in the decision-making process varied. None preferred group information sessions.In conclusion, providing information and pre-test counselling to pregnant women is a complex task. There is room for improvement in the information provided to expectant parents, and in the education provided to midwives related to PND and DS. Women’s decisions regarding PND are influenced by both individual and external factors. Information about test characteristics and conditions tested for could be helpful for pregnant women when they make decisions. Healthcare professionals’ approach can influence women’s decisions. Women have varying informational needs, making individual and non-directive pre-test counselling with a competent healthcare professional essential to facilitate informed decision-making.
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| 2. |
- Berggrund, Malin, 1989-
(författare)
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Identification and clinical implementation of biomarkers for cervical cancer
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction of organised screening programs and prophylactic vaccination against human papilloma virus (HPV) have successfully reduced the incidence of cervical cancer globally. In Sweden, the incidence has been reduced by about 50 % since the introduction of the national screening programme in the late 1960’s. Despite these efforts, cervical cancer is still a major cause of cancer deaths globally.In order to reduce cervical cancer, the screening program should have a high participation rate and be based on a sensitive and specific screening test. About 20 % of women in Sweden do not participate in the organised screening program, and during the last years we have also seen a rise in cervical cancer cases in Sweden among women who participate in the screening program. Thus, there is a need to develop improved screening strategies that result in a higher participation rate, and are based on tests that more precisely identify women with high risk of developing cervical cancer. This includes searching for novel biological markers (biomarkers) that can be used to more accurately identify women with a high risk of developing cervical cancer.By offering women self-sampling for HPV analysis through direct mailing of sample kits with a chemically treated paper card, the FTA card, we were able to increase the participation rate in the screening program. We also found that the use of repeated self-sampling for women that were HPV positive in the primary screening sample increased the number of women detected with higher risk of cervical cancer (Paper II). Self-sampling was shown to be non-inferior to assisted sampling by midwife (Paper III). Using this sample collection device, we further investigated the association between increased risk of cervical cancer and HPV viral load (Paper V) as well as the vaginal microbiota (Paper VI). We also showed that proteins in the vaginal fluid can be studied using self-sampling and the FTA card (Paper I). Lastly, we identified plasma proteins that are associated with cervical cancer and could represent future biomarkers (Paper IV).This thesis has provided novel aspects on the present screening strategy, explored opportunities to increase the participation rate as well as examined possible future biomarkers for screening of cervical cancer.
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| 3. |
- Björk, Emma, 1977-
(författare)
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Immunosuppressive mechanisms in endometriosis : a focus on the role of exosomes
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endometriosis is defined as the presence of endometrial-like tissue outside the uterine cavity. It has been suggested that the aberrant immunological mechanisms that cause dysfunction of immune cells and mediators are involved in the pathogenesis of endometriosis. There is substantial evidence of downregulated NK cell cytotoxicity and changes in inflammatory mediators such as cytokines in endometriosis. This research aimed to elucidate the immunosuppressive mechanisms in endometriosis, focusing on NK cells, the role of cytokines, and exosomes derived from endometriotic tissue.Cytokines are small peptides/proteins used for intercellular communication, and regulate immune-effector functions in health and disease. In Paper I, real-time RT-qPCR and a set of primers and probes for 11 cytokines were used defining cytotoxic Th1, humoral Th2, regulatory Tr1/Th3, and inflammatory cytokine profiles. Cytokine mRNA expression in endometriotic tissue was compared with endometrium, and systemically with peripheral blood mononuclear cells (PBMC) from women with endometriosis and healthy controls. In addition, immunohistochemical staining with monoclonal antibodies was performed to investigate T-regulatory cells in endometriotic lesions. A downregulation of mRNA for cytokines that mediate cytotoxicity and antibody response was found in the endometriotic lesions. At the same time, there was an upregulation of inflammatory and T-regulatory cytokines in the endometriotic lesions, suggesting enhanced local inflammation and priming of an adaptive regulatory response. Consistent with these findings, T-regulatory cells were abundant in the endometriotic lesions. These findings suggest that the ectopic implantation seen in endometriosis may be a consequence of increased inflammation and priming of adaptive T regulatory cells, resulting in impaired cytotoxicity and enhanced immune suppression. Exosomes are nanometer-sized extracellular vesicles of endosomal origin; they are produced by most cells in the body, convey intercellular communication and participate in both normal and pathological processes. Paper II show that endometriotic lesions produce high amounts of exosomes. The exosomes expressed on their surfaces the NKG2D ligands MICA/B and ULBP1-3 and the proapoptotic molecules FasL and TRAIL. These molecules are known as immunosuppressive signatures. Functional experiments were performed to show that these exosomes can downregulate the main activating NK receptor NKG2D on CTL and NK cells, reduce the killing ability of PBMC from healthy donors, and induce apoptosis of activated lymphocytes through the FasL/Fas pathway. The production and secretion of exosomes from the endometriotic tissue may be further enhanced by the vigorous local inflammation at ectopic sites. The results show that endometriotic lesions secrete immunosuppressive exosomes that inhibit cytotoxicity and promote apoptosis of activated immune cells. The exosomes form a “protective shield” around the endometriotic tissue thus promoting their survival.NK cells are cytotoxic cells of the innate immune system. Human NK cells can be divided into two subsets: CD56+bright and CD56+dim. The CD56+dim subset is more naturally cytotoxic, whereas the CD56+bright subset produces more cytokines, but has low natural cytotoxicity. The majority (>90%) of circulating NK cells are CD56+dim, whereas very few (0-10 %) are CD56+bright. In Paper III a higher amount of CD56+bright cells in serum was observed in one third of endometriosis patients compared to healthy controls. The amount of these cells was normalized after treatment with surgery, with or without medical treatment. Untreated patients had a lower expression of NKG2D receptors on their NK cells and CTLs compared to treated patients and healthy controls, which could be due to endometriotic exosomes carrying the NKG2D ligands that downregulate the receptor. Thus, surgery might have a beneficial effect on cytotoxic NK-cell function in endometriosis.Endometriosis is considered a benign disease; however it has many features in common with tumors, and shares multiple microenvironmental hallmarks with cancer, including angiogenesis, immune dysregulation, inflammation, invasion, and metastasis. Paper II shows that endometriotic tissue secretes immunosuppressive exosomes. In Paper IV, exosomes in the peripheral blood of epithelial ovarian cancer (EOC) patients, and the impairment of the NKG2D receptor-ligand system in vivo before and after surgery, were studied. The serum exosomes isolated from the EOC patients carried the NKG2D ligands MICA/B and ULBP1-3. In functional experiments, the EOC exosomes downregulated the expression of the NKG2D receptor, and subdued NKG2D-mediated cytotoxicity in NK cells from healthy donors in a similar manner to the endometriotic exosomes studied in Paper II. In Paper IV, surgery of the primary EOC tumor had a beneficial effect, alleviating the exosome-mediated suppression of NKG2D-mediated cytotoxicity. Thus, exosome-mediated immunosuppression is revealed as a common mechanism of action for immune escape in endometriosis and cancer. The results presented in this thesis provide novel and important insights into the function of the immune system in endometriosis, and give new explanations for why ectopic endometrial tissue persists and proliferates outside the uterine cavity. Furthermore, the immunosuppression in the microenvironment of endometriosis, which has many similarities with the local tumor microenvironment (TME), was investigated with a focus on the role of endometriotic exosomes. Taken together, this thesis contributes to understanding of the pathogenesis of endometriosis, and might be useful in identifying biomarkers for endometriosis and developing new immunomodulatory therapies.
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| 4. |
- Helmestam, Malin
(författare)
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Effects of Endocrine Disrupting Chemicals on Human Endometrial Endothelial Cells In Vitro
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Evidence from an abundant number of studies suggests that human female reproductive functions have become impaired over the past half century and that there might be a relationship between endocrine disrupting chemicals (EDCs) and reduced fertility. It is, however, not known by what mechanisms EDCs affect different reproductive functions such as endometrial receptivity, embryo implantation and placentation.The endometrium is continuously changing its morphological and functional properties, responding to cyclic changes of oestrogen and progesterone levels during the menstrual cycle. These changes include monthly preparation for embryo implantation through changed endometrial angiogenic activity and consequent changes in endometrial vasculature.Use of primary human endometrial endothelial cells (HEECs) in this work was evaluated as a possible screening tool for effects caused by EDCs on human endometrial vasculature and subsequently on various endometrial functions.In this study HEEC and endometrial stromal cells were isolated. HEECs were grown in monocultures, and together with stromal cells in co-cultures, and exposed to endocrine active substances. These were cadmium, which has oestrogenic properties, tamoxifen, with anti-oestrogenic effects, mifepristone, which is an anti-progestin, and bisphenol A, with oestrogenic properties. The effects were evaluated by using proliferation and viability assays, migration and tube formation assays, quantitative PCR (qPCR), immunohistochemistry and western blot.Cadmium affected the expression of angiogenesis-related genes, and caused different effects in HEECs cultured alone vs. HEECs co-cultured with stromal cells. Tamoxifen altered the expression of angiogenesis-related genes and reduced HEEC migration, thus having an anti-angiogenic effect. Mifepristone caused reduced formation of tubular structures in tube-formation assays involving HEECs co-cultured with stromal cells. Bisphenol A promoted tube formation in co-cultured HEECs which was related to changes in the expression of several angiogenesis-related genes as well as up-regulated expression of VEGF-D protein.In conclusion, we showed that EDCs have the ability to induce changes in endometrial angiogenic activity in vitro and may thus disturb normal endometrial functions related to fertility and pregnancy. HEECs grown in vitro may provide valuable information on the effects of EDCs on human endometrial functions. However, this model is not suitable as a large-scale screening tool.
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| 5. |
- Junus, Katja, 1982-
(författare)
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Preeclampsia – Studies on the Placenta and B-type Natriuretic Peptide
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia has several pathophysiological pathways, but the placenta has a central role. The pathophysiology appears to differ between the two subtypes – early- and late-onset preeclampsia. In clinically evident preeclampsia, maternal circulatory levels of the cardiac peptide B-type natriuretic peptide (BNP) and its cleavage fragment NT-proBNP are elevated, but whether or not the peptides are involved in the pathophysiology of preeclampsia is unknown. The overall aim of the current work was to expand knowledge of preeclampsia pathophysiology, with a main focus on the relationship between BNP and NT-proBNP, and early- and late-onset preeclampsia.In Paper I, the placental transcriptional profiles of early- and late-onset preeclampsia were compared by using microarrays and bioinformatics. A total of 196 transcripts were differently regulated in the two groups. Using qRT-PCR, mRNA levels of the two angiogenesis-related transcripts ACVRL1 and EGFL7 were confirmed to be lower in early-onset preeclampsia than in both late-onset preeclampsia and early controls.In Paper II, the circulatory levels of NT-proBNP were higher in both early- and late-onset preeclampsia than in gestational age-matched controls. BNP mRNA and protein were detected by qRT-PCR and immunohistochemistry in placentas from both women with preeclampsia and controls.In Paper III, circulatory levels of NT-proBNP were measured in the early second-trimester in women who later developed early-onset preeclampsia and in women who continued to have normal pregnancies. No differences were found between the two groups of women.In Paper IV, the secretion of NT-proBNP, and the mRNA levels of BNP and BNP receptors were investigated in cultured primary trophoblasts. Low levels of NT-proBNP were found in the supernatants of term but not first-trimester trophoblasts. BNP and BNP-receptor mRNA were detected in term trophoblasts.The results of this work strengthen the concept of the two subtypes of preeclampsia (early- and late-onset) having partly different pathophysiological pathways. The results also indicate that the placenta releases BNP and that BNP may have receptor-mediated effects on the placenta.
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| 6. |
- Kempe, Per
(författare)
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Multiple Sclerosis in relation to sex steroid exposure
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is a potentially severe chronic inflammatory disease of the central nervous system (CNS) and is usually diagnosed between 20 and 40 years of age. The incidence of MS is two to three times higher among women and the type and course of the disease often differ between the sexes. Sex steroids, especially estrogens, have been shown to influence the immunopathology involved in MS and the mouse model experimental allergic encephalomyelitis (EAE), as well as radiological and clinical signs of the disease. The ovarian cycle and hormonal contraception result in fluctuations in sex steroid concentrations that could possibly affect MS. The incidence of MS in women is highest at an age when a reliable contraceptive method is an important matter but the effects of estrogen-containing combined hormonal contraceptives (CHC) on MS have not been thoroughly studied. The general aim of the research for this thesis was to investigate how fluctuations in sex steroid exposure during the menstrual cycle and use of CHC affect MS in a clinical context.Paper I is based on female MS patients with or without hormonal contraception. Symptoms were reported prospectively in an MS-symptom diary. In contrast with results from previous retrospective studies, 16 women without hormonal contraception reported fewer complaints regarding one out of 13 symptoms during the low estrogen/progesterone phase of the menstrual cycle. Seven women who used CHC experienced three of the symptoms significantly more strongly during the low estrogen/progestogen, pill-free period. In paper II 22 women with MS who used CHC reported higher scores for four out of 10 symptoms during the “pill-free” week, i.e. during the low-estrogen/progestogen phase using a modified symptom diary. Women with MS who did not use hormonal contraception reported no differences in symptom scores between high and low estrogen/progesterone phases. Paper III included 770 women who answered a questionnaire that was designed to investigate whether longer periods of high estrogen concentration such as CHC-use and pregnancies delay the onset of MS. The mean age at MS onset was significantly higher among women who had been using COC before their first MS symptom (26 vs 19 years, p<0.001) and the longer the women had been using COC the higher the mean age at MS onset. The number of children born before the first symptom of MS was positively correlated with age at MS onset (r=0.6; p<0.001). Paper IV aimed to investigate if peripheral blood levels of cytokines, chemokines, and transcription factors for different T helper (Th) cell subsets change in relation to high and low estrogen/progestogen states in women with MS and healthy controls with and without CHC using multiplex bead technology and qPCR. Expression of the B cell-associated chemokine CXCL13 was generally higher in high the estrogen/progestogen phase than in the low estrogen/progestogen phase and the expression of the transcription factors showed a general activation of peripheral blood T cells during high estrogen and progestogen phases in women with MS as well as in healthy women.The clinical implication of these and other studies is that there is probably no reason for avoiding CHC as a contraceptive method in women with MS. It is also probably beneficial for women with MS to use CHC regimens with longer estrogen periods and fewer pill-free intervals. Future studies should investigate the outcomes of such regimens on relapse rate, MRI lesions, disease activity related cytokines and chemokines in CSF and peripheral blood and the women’s experiences of their symptoms.
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| 7. |
- Moberg, Christian, 1972-
(författare)
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The Human Endometrium : Studies on Angiogenesis and Endometriosis
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiogenesis is thought to play a pivotal role in the cycling endometrium. Coordinated by oestrogen and progesterone, endometrial blood vessel development is primarily mediated by vascular endothelial growth factor-A (VEGF-A), which promotes endothelial cell (EC) proliferation and protects ECs from induced apoptosis. Studying changes at transcript level in human endometrial endothelial cells (HEECs) in response to mitogenic and inhibitory stimuli is one way towards understanding the regulation of physiological endometrial angiogenesis.Endometriosis, the presence of endometrial-like tissue outside the uterine cavity, is a common gynaecological disorder in women of reproductive age, often causing pelvic pain and reduced fertility. Chronic inflammation in the peritoneal environment and defective endometrial protein expression are some of the contributors to the complex pathophysiology of endometriosis. The aim of this work was to study the changes in the transcriptome induced by VEGF-A and partial serum deprivation in primary HEECs, and to investigate biochemical factors associated with subfertility and chronic pelvic pain in endometriosis patients.Exposing primary HEECs to VEGF-A, and serum withdrawal was found to regulate transcripts associated with survival, migration, apoptosis and progression through the cell cycle, when assessed using microarray technology and bioinformatic tools. A subset of 88 transcripts was reciprocally regulated under the two experimental conditions; thus probably important in HEEC biology.Higher endometrial epithelial staining scores of oestrogen receptor-α and reduced staining of progesterone receptors were seen in subfertile endometriosis patients. Lower levels of the receptivity biomarker leukaemia inhibitory factor (LIF) and its receptor, as well as signs of dysregulated αB-crystallin expression and increased peritoneal fluid concentrations of interleukin (IL)-1α and IL-6 were associated with reduced pregnancy rates.Endometriosis patients with chronic pelvic pain had higher levels of vasoactive intestinal peptide (VIP) in eutopic endometria and in endometriotic lesions compared with patients without chronic pain. The presence of chronic pelvic pain was also associated with increased concentrations of VIP and IL-6 in peritoneal fluid.The present results may constitute a basis for further investigation of regulatory pathways in endometrial angiogenesis as well as for studies of endometrial receptivity and pain in women with endometriosis.
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| 8. |
- Bergengren, Lovisa, 1972-
(författare)
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Cervical screening with primary HPV : from research to clinical effectiveness
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organized cervical screening has greatly reduced the incidence of cervical cancer where implemented. Human papilloma virus (HPV) is the cause of cervical cancer, and in later years, convincing evidence has led to cervical screening with HPV as the primary method being implemented around the world. The overall aim of this thesis is to improve cervical screening, with focus on HPV screening.Papers I–III were performed with focus on postmenopausal women. Women aged, 55–59 years, excluded from the screening with a normal cytology cervical sample were found to have a high-risk HPV (hrHPV) prevalence of 5.5% in paper II. In a follow-up sample, 56% (71/126) had a persistent infection with the same genotype. Nineteen per cent of the women had dysplasia, where the majority of the high-grade squamous intraepithelial lesions (HSILs) were associated with HPV types other than HPV 16/18.Women 55-59 has a lower attendance rate in the study region, and since self-sample has been proven to increase attendance, paper I was performed to compare self-sample and professionally collected samples in these postmenopausal women. The concordance between the sampling methods was 83%, and both tests detected all histological HSILs. When including a study with older women (aged 70 years) in paper III, 23% of histological HSILs were found in hrHPV-positive women.Paper IV is a scientific evaluation of an implemented HPV-based screening programme, comparing clinical effectiveness and cost with cytology screening. More HSIL+ were detected in the new programme but at a higher cost than the old cytology-based programme. The screening visits for sampling accounted for two thirds of the costs.Altogether, the results indicate the importance of having a negative HPVtest before exiting screening. Data also present the necessity to find biomarkers that are more specific than cytology and HPV 16/18 for triaging women with hrHPV to further follow-up, both among postmenopausal women and other age groups when screening with HPV, since many women without HSIL are coming for clinical follow-up and treatment. Extending the screening interval between hrHPV-negative tests as well as implementing selfsampling to a greater extent can be important changes, since two thirds of the costs in the programme come from screening visits for sampling.
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| 9. |
- Brodin, Thomas, 1963-
(författare)
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Ovarian Reserve and Assisted Reproduction
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treatment success in IVF-ICSI is mainly limited by female age, but differences in ovarian reserve (OR; the remaining pool of oocytes and their quality) between individuals modify treatment prerequisites among women of similar age. OR may be assessed by OR tests (ORTs). The main aims of this work were to study menstrual cycle length (MCL), basal levels of circulating gonadotrophins, antral follicle count (AFC) and serum Anti-Müllerian hormone (AMH) levels and their associations with and prognostic capacities regarding IVF-ICSI outcome in large cohorts of unselected women.Age-adjusted MCL was positively and linearly associated with pregnancy rates (PRs), live-birth rates (LBRs) and ovarian response to controlled ovarian hyperstimulation. An MCL of >34 days almost doubled the LBR compared with an MCL of <26 days.The grouped variable ‘combined FSH and LH levels’ was superior to both individual gonadotrophin levels and the LH:FSH ratio. The highest mean PR was seen in connection with a combination of FSH <6.7 U/l with LH >4.9 U/l; PRs were lowest when FSH-LH levels were opposite to this (high-low) and intermediate when FSH-LH levels were low-low or high-high. Associations with LBR and ovarian response were similar as those for PR.AFCs and serum AMH levels were positively and log-linearly associated with PR, LBR and ovarian response. Success rates levelled out above AFC 30 or AMH 5 ng/ml. Treatment outcome was superior among women with polycystic ovaries.Among the studied ORTs, logAFC and logAMH concentration correlated most strongly. After multivariate testing, entering all studied ORTs, AMH and female age remained independently associated with LBR. AMH + AFC + age predicted both poor and excessive ovarian responses with high accuracy.Adjusting for age and oocyte yield, all ORTs remained significant for LBR, implying that ORTs also capture information on oocyte quality.In conclusion, measures of OR are strongly associated with PR, LBR and ovarian response in a log-linear fashion, and partly reflect oocyte quality. The OR spectrum is continuous, from small ‘oligofollicular’ ovaries (the low extreme) to polycystic ovaries (the high extreme). Among the studied ORTs, AMH together with age provide the most powerful basal estimate for IVF/ICSI outcome.
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| 10. |
- Sohlberg, Sara, 1977-
(författare)
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Placental Function : An Epidemiological and Magnetic Resonance Study
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Placental function is central for normal pregnancy and in many of the major pregnancy disorders. We used magnetic resonance imaging techniques to investigate placental function in normal pregnancy, in early and late preeclampsia and in intrauterine growth restriction. We also investigated maternal body mass index and height, as risk factors for preeclampsia.A high body mass index and a short maternal stature increase the risk of preeclampsia, of all severities. The association seems especially strong between short stature and early preeclampsia, and a high body mass index and late preeclampsia. (Study I)Using diffusion-weighted magnetic resonance imaging, we found that the placental perfusion fraction decreases with increasing gestational age in normal pregnancy. Also, the placental perfusion fraction is smaller in early preeclampsia, and larger in late preeclampsia, compared with normal pregnancies. That these differences are in opposite directions, suggests that there are differences in the underlying pathophysiology of early and late preeclampsia. (Study II)Using magnetic resonance spectroscopy, we found that the phosphodiester spectral intensity fraction and the phosphodiester/phosphomonoester spectral intensity ratio increases with increasing gestational age. Also, we found that the phosphodiester spectral intensity fraction and the phosphodiester/phosphomonoester spectral intensity ratio are higher in early preeclampsia, compared with early normal pregnancy. These findings indicate increased apoptosis with increasing gestational age in normal pregnancy, and increased apoptosis in early preeclampsia. (Study III)The placental perfusion fraction is smaller in intrauterine growth restriction than in normal pregnancy. Fetal growth, Doppler blood flow in maternal and fetal vessels, infant birth weight and plasma markers of placental function are all correlated to the placental perfusion fraction. The placental perfusion fraction examination seems therefore to offer a fast, direct estimate of the degree of placental dysfunction. (Study IV)In conclusion: Our findings in studies I-III all support the hypothesis of partly different pathophysiology between early and late preeclampsia, and suggest a strong link between early preeclampsia and placental dysfunction. Study IV shows that the placental perfusion fraction has potential to contribute to the clinical assessment of placental dysfunction.
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