STUDY QUESTION What changes have occurred in the incidence of miscarriage, its treatment options, and the profile of the women having miscarriages in Finland between 1998 and 2016? SUMMARY ANSWER The annual incidence of registry-identified miscarriage has declined significantly between 1998 and 2016, and non-surgical management has become the dominant treatment. WHAT IS KNOWN ALREADY Miscarriage occurs in 8–15% of clinically recognized pregnancies and in ~30% of all pregnancies. Increasing maternal age is associated with an increasing risk of miscarriage. The treatment of miscarriage has evolved significantly in recent years: previously, surgical evacuation of the uterus was the standard of care, but nowadays medical and expectant management are increasingly used. STUDY DESIGN, SIZE, DURATION We conducted a nationwide retrospective cohort study of 128 381 women that had experienced a miscarriage that was managed in public healthcare between 1998 and 2016 in Finland. PARTICIPANTS/MATERIALS, SETTING, METHODS We used the National Hospital Discharge Registry for the data. Women aged 15–49 years that had experienced their first miscarriage during the follow-up period and had miscarriage-related diagnoses during their admission to public hospital were included in the study. Miscarriages were defined by the 10th Revision of the International Statistical Classification of Diseases and related Medical Problems (ICD-10) diagnostic codes O02*, O03* and O08*. Women with ectopic, molar and continuing pregnancies and induced abortions were excluded. Treatment was divided into surgical and non-surgical treatment using the surgical procedure codes. MAIN RESULTS AND THE ROLE OF CHANCE The annual incidence of registry-identified miscarriage has declined from 6.8/1000 15–49-year-old women in 1998 to 5.0/1000 in 2016 (P < 0.001). Also, the incidence rate of registry-identified miscarriage (i.e. the proportion of miscarriages of registry-identified pregnancies [i.e. deliveries, induced abortions, and miscarriages]) has declined from 112/1000 15–49-year-old pregnant women in 1998 to 83/1000 in 2016 (P < 0.001). The largest decrease in this proportion occurred among women over 40 years of age, among whom 26.5% of registry-identified pregnancies in 1998 ended in miscarriage compared to that of 16.4% in 2016. The proportion of missed abortion has increased (30.3 to 38.8%, P < 0.001) whereas that of blighted ovum has decreased (25.4 to 12.8%, P < 0.001). The proportion of registry-identified miscarriages seen among nulliparous women has increased from 43.7 to 49.6% (P < 0.001). Mean age at the time of miscarriage remained at 31 years throughout the study. Altogether, 29% of all miscarriages were treated surgically and 71% underwent medical or expectant management. The proportion of surgical management has decreased from 38.0 to 1.6% for spontaneous abortion, from 60.7 to 9.4% for blighted ovum and 70.9 to 11.2% for missed abortion between 1998 and 2016. LIMITATIONS, REASONS FOR CAUTION This study includes only women with registry-identified pregnancies, i.e. women who were treated in public hospitals. However, the number of women treated elsewhere is presumed to be small. Neither can this study estimate the number of women having spontaneous miscarriage with no hospital contact. WIDER IMPLICATIONS OF THE FINDINGS Both the annual incidence and incidence rate of miscarriage of all registry-identified pregnancies has decreased, and non-surgical management has become the standard of care. These findings are of value when planning allocation of healthcare resources and at individual level considering fertility and miscarriage questions. We speculate that improving ultrasound diagnostics explains the increasing proportion of missed abortion relative to other types of miscarriage. More investigation is needed to examine potential risk factors, complications and morbidity associated with miscarriages. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the research funds of the Helsinki and Uusimaa hospital system, by a personal grant from Viipurin Tuberkuloosisäätiö to R.L. and by a personal grant from The Finnish Cultural Foundation to N.H. The authors have no conflicts of interest to declare.
BackgroundTrophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs).MethodsThis study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89).ResultsMMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies.ConclusionsHuman placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.
National Institute for Health and Welfare and the Academy of Finland. No competing interests.
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