Bakgrund: I Sverige definieras begreppet upprepade missfall som att en kvinna har fått tre eller flera missfall i följd och det uppskattas drabba ca en procent av världens alla par i fertil ålder. Då detta är en liten grupp kvinnor kan det vara svårt för den drabbade kvinnan att veta var hon kan vända sig med sina funderingar och vad hon har rätt till för vidare hjälp. Vid flera upprepade missfall växer behovet av att få svar på vad som sker och varför samtidigt som behovet av stöd och förståelse från sina närstående blir större. Tillgången till utredning och behandling ser olika ut men med hjälp från barnmorskans och vårdens sida kan lämplig planering utifrån kvinnan situation utvecklas. Syfte: Syftet med denna studie är att undersöka kvinnans upplevelse av upprepade missfall och belysa hennes behov under och tiden efter missfallet. Metod: Metoden för denna uppsats var en kvalitativ metasyntes med metaetnografisk analysmetod. Totalt kvalitetsgranskades 29 artiklar varav 16 gick igenom kvalitetsgranskningen och sammanställdes till ett resultat. Resultat: Sju kategorier med nyckelbegrepp bildades. Kategorierna som identifierades var missfallsprocessen, utrymme för sorg, undvikande beteende, partnerrollen, socialt stöd, förväntningar på vården och att bli gravid igen. Slutsats: Då alla kvinnor är olika varierar upplevelsen och behoven vid en missfallsprocess. Genom att ha kunskap om vad kvinnan går igenom både fysiskt- och psykiskt vid upprepade missfall bidrar det till en ökad förståelse för vad kvinnan behöver, både från sin omgivning men även från vårdens sida. Klinisk tillämpbarhet: Studien skulle kunna bidra till att utforska möjligheten att ändra på kriterierna för utredning vid upprepade missfall. Studien skulle även kunna leda till en förbättring av kunskapsläget både för individen, samhället och vården gällande hur bemötandet av denna grupp av kvinnor ser ut. Barnmorskor kan som yrkesgrupp stödja och hjälpa denna grupp kvinnor genom uppföljning i samband med att de kommer i kontakt med barnmorskemottagningen för att meddela att graviditeten har slutat i ännu ett missfall. Vidare kan etableringen av stödgrupper inom vården vara ett bra stöd för kvinnor som är med om upprepade missfall och dessa grupper skulle potentiellt ledas och samordnas av en barnmorska som innehar kompetens inom området upprepade missfall. / Background: In Sweden, the concept of recurrent miscarriage is defined as a woman having three or more miscarriages in succession and it is estimated to affect about one percent of all couples of childbearing age worldwide. Since this is a small group of women, it can be difficult for the effected woman to know where she can turn with her thoughts and what she is entitled to regarding further help. After enduring multiple recurrent miscarriages, the need to get some answers and at the same time the need to receive support and understanding from their close surroundings increases. The access to further investigation and treatment is different depending on where you are but with some help from a midwife and other healthcare providers, an appropriate plan based on the woman's situation can be developed. Purpose: The aim of this essay was to investigate the experiences of women who have endured recurrent miscarriages and their further needs that occurred during and the time after the miscarriage. Methods: The method used in this essay was a qualitative metasynthesis with metaethnographic analysis method. In total, 29 articles were collected of which 16 of them went through the quality review and were compiled to a result. Results: seven categories containing of key concepts were formed. The categories identified were the process of miscarrying, room for griefing, avoiding behavior, the partners role, social support, expectations of the healthcare and becoming pregnant again. Conclusion: Due to the fact that all women are different, the experiences and needs during a miscarrying process varies. By having the knowledge of what the woman goes through both physically and mentally during recurrent miscarriages, it contributes to a greater understanding of what the woman needs, both from her surroundings but also from the healthcare. Clinical applicability: This essay could help to explore the possibilities of modifying the criteria for an investigation of recurrent miscarriages. The essay could also lead to improvement of the knowledge situation for the individual, the society and the care providers regarding how this group of women wants to be treated. Midwives as a profession could help to support this group of women by initiating contact with the women when or after she has contacted the midwife clinic to announce another pregnancy loss. Furthermore, the establishment of support groups for women with recurrent miscarriages could be helpful and supportive for these women. The support groups could potentially be coordinated by a midwife with specific knowledge about recurrent miscarriage.

Hypothyroidism is a common endocrine disorder affecting women of reproductive age. On a global level, iodine deficiency is still the most common cause of hypothyroidism. Also genetic variations, in particular SNP rs4704397 in the PDE8B gene, are responsible for a significant proportion of TSH variations.  Untreated hypothyroidism has significant adverse effects on pregnancy and fetal outcome. Most international guidelines suggest targeted thyroid testing in pregnant women with risk factors for thyroid disturbances. In a case-control study, an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage was found. The explanation for this association is unknown. In a nationwide survey, all guidelines for thyroid testing and management of hypothyroidism during pregnancy in Sweden were collected and compared with international guidelines. The local guidelines were variable and poorly compliant with the international guidelines. In a follow-up in one district, 5,254 pregnant women were included for subsequent review of their medical reports. We found a targeted thyroid testing rate of 20.1% in clinical practice, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More disturbingly, half of the women who were on levothyroxine treatment at the time of conception had an elevated TSH level at thyroid testing. In a subsequent cohort study of the 5,254 women, we found the prevalence of trimester-specific elevated TSH and overt hypothyroidism to be equal in targeted thyroid tested and untested women. In a cross-sectional study, a median urinary iodine concentration (UIC) of 98 μg/l was found in the study population. According to WHO/UNICEF/IGN criteria, the population-based median UIC during pregnancy should be 150-249 μg/l. In conclusion, genetic variations may contribute to adverse pregnancy outcomes. In clinical practice, thyroid testing and the management of hypothyroidism during pregnancy is unsatisfactory, regarding the whole chain from development of local guidelines to their implementation and to targeted thyroid testing. Moreover, our results indicate insufficient iodine status in the pregnant population of Sweden.

Uterine NK (uNK) cells are a distinct subset of NK cells in the decidua of humans and rodents during pregnancy, which are essential for remodelling of the spiral arteries supplying the feto-placental unit. Similarly to peripheral NK cells, uNK cells express Natural Killer receptors (NKRs) that engage MHC class I molecules. Evidence from human genetic association studies suggests that, in the presence of allogeneic cognate paternal MHC class I ligands, inhibitory uterine NKRs are associated with disorders of pregnancy arising from impaired decidual vascular remodelling. Conversely, enhancement of human uNK cell activity through activating NKRs is associated with high birth weight. Evidence from mouse models corroborates that uNK cell activity is modulated by interactions between NKRs and MHC class I, but has largely focussed on the effect of paternal MHC. In this study, the contribution of maternal immunogenetic regulation of NK cell function to reproductive outcome was assessed independently of parental MHC disparity in mice. To evaluate the role of NKR genes in isolation, I used congenic B6.BALB-TC1 (TC1) mice that differ from C57BL/6 (B6) mice only within the region of chromosome six encoding NKRs that recognise MHC class I. Absence of a major inhibitory NKR for self-MHC, Ly49I, in TC1 mice causes a compensatory shift in the NKR repertoire expressed and preserves a majority subpopulation of educated NK cells. B6 and TC1 splenic and uterine NK cells are similarly functionally reactive and mature, and no significant differences could be detected in spiral arterial remodelling or fetal growth between these strains in MHC-syngeneic matings. This supports data from human immunogenetic studies showing that maternal uterine NKRs are not associated with differences in pregnancy outcome in the absence of novel paternal MHC class I ligands, and highlights the importance of maternal and paternal co-regulation of uNK cell activity during pregnancy. No mouse models of uNK cell activation are currently available with which to corroborate human immunogenetic associations between activating uterine NKRs and high birth weight. Male m157-transgenic (m157-Tg) mice, which ubiquitously express viral m157 glycoprotein ligands for the activating NKR Ly49H, were mated with B6 females. Exclusive expression of m157 glycoprotein by trophoblast improved placental efficiency, but did not enhance fetal growth. Some fertility clinics surmise that uNK cell activation initiates the pathogenesis of spontaneous abortion. It has been suggested that this may occur due to reduced expression by human uNK cells of miR-483-3p, which stimulates endogenous insulin-like growth factor (IGF)-1 production and uNK cell cytotoxicity in vitro. It is demonstrated here that neither miR-483-3p nor IGF-1 regulate murine NK cell development, maturation or function. No discernible reproductive phenotype is evident in miR-483 deficient females. It can be inferred that post-transcriptional control by miR-483 is not biologically relevant to murine NK cell function. Although m157-Tg mice may provide an interesting model to further study uNK cell-mediated placental adaptations, it remains important to identify a murine model of enhanced uNK cell function to corroborate human immunogenetic associations with high birth weight and to challenge the supposition that uNK cell activation is harmful to pregnancy.

Infertility affects 15% of reproductive-aged couples. The milieu surrounding the growing embryo is of outmost importance, and should be optimised during in vitro fertilisation (IVF). Many biological processes, such as angiogenesis, coagulation, and immune processes need to be well regulated for a pregnancy to occur and progress normally. Histidine-rich glycoprotein (HRG) is a plasma protein that regulates components of these systems by building complexes with various ligands. A single nucleotide polymorphism (SNP) in HRG, denoted HRG C633T, seem to be of importance for IVF treatment outcomes. The aim of this thesis was to further investigate the proposed human fertility effects of the HRG C633T SNP. According to the findings of this thesis, the HRG C633T genotype is associated with primary recurrent miscarriage. Male HRG C633T genotype is associated with semen characteristics in infertile men, and pregnancy rates following IVF. However, the distribution of the HRG C633T SNP does not differ between infertile and fertile couples. We further examined the role of the region surrounding the HRG C633T SNP for regulation of endometrial angiogenesis and human embryo development. The region affects primary endometrial endothelial cell migration, proliferation and tube-formation in vitro but does not appear to affect human embryo development. No effect of the HRG peptide was noted on the secretome of human embryos. However, early embryos secrete proteins into the surrounding culture media and the level of secretion of VEGF-A, IL-6, EMMPRIN and PlGF is greater in embryos of higher developmental stages. In conclusion, the HRG C633T genotype appears to play a role only if infertility is established. The region surrounding HRG C633T SNP is of relevance in vitro for regulation of human endometrial endothelial cell angiogenesis. To predict which embryos to transfer in IVF, we have highlighted a number of proteins of interest for further investigation.