371 research outputs found

    Health of singletons born after frozen embryo transfer until early adulthood : a Finnish register study

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    STUDY QUESTION Is the health of singletons born after frozen embryo transfer (FET) comparable to that of singletons born after fresh embryo transfer (ET) until early adulthood? SUMMARY ANSWER The health of singletons born after FET does not differ from that of singletons born after fresh ET. WHAT IS KNOWN ALREADY The differences in perinatal outcomes of children born after FET and fresh ET are well known. FET is associated with an increased risk of large-for-gestational-age but diminished risks of preterm birth (PTB), small-for-gestational-age and decreased perinatal mortality compared to fresh ET. However, knowledge on the long-term health after FET is scarce. STUDY DESIGN, SIZE, DURATION This retrospective register-based cohort study compares singletons born after FET (n = 1825) between the years 1995 and 2006 to those born after fresh ET (n = 2933) and natural conception (NC, n = 31 136) with a mean follow-up time of 18-20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS Singletons born after FET were compared to those born after fresh ET and NC regarding the frequencies of diagnoses in the main ICD-10 chapters (International Statistical Classification of Diseases and Related Health Problems, 10th revision), the number of outpatient visits and hospital admissions, and mortality. Adjustments were made for PTB, maternal age, parity, socioeconomic status based on mother's occupation and offspring sex. The study combines data from the Finnish Medical Birth Register, the Finnish Care Register for Health Care (CRHC) and the Cause-of-Death Register at Statistics Finland. The Student's T-test was used for continuous variables, and the Chi-square test was used for categorical variables. Cox regression was used to estimate crude and adjusted hazard ratios (HRs and aHRs, respectively). A general linear model was used to compare the means of outpatient visits, hospital admissions and lengths of hospital stays per person. MAIN RESULTS AND THE ROLE OF CHANCE No significant differences between the FET and fresh ET groups were found in the frequency of diagnoses in any of the ICD-10 chapters or in the parameters describing the need for hospital care. However, compared to the NC group, higher proportions in the FET group had outpatient visits in the hospital (93.5% vs 92.2%, aHR 1.23, 95% CI 1.17, 1.30) or hospital admissions (48% vs 46.5%, aHR 1.28, 95% CI 1.19, 1.37). Compared to the NC group, the FET group had elevated adjusted risks of diagnoses of infectious and parasitic diseases (aHR 1.24; 95% CI 1.11, 1.38), neoplasms (aHR 1.68; 95% CI 1.48, 1.91), diseases of the eye and adnexa, the ear or mastoid process (aHR 1.11; 95% CI 1.01, 1.21), the respiratory system (aHR 1.15; 95% CI 1.06, 1.23), the digestive system (aHR 1.17; 95% CI 1.05, 1.32), the skin or subcutaneous tissue (aHR 1.28; 95% CI 1.14, 1.43) and the genitourinary system (aHR 1.27; 95% CI 1.11, 1.45), as well as congenital malformations or chromosomal abnormalities (aHR 1.31; 95% CI 1.14, 1.50) and symptoms, signs or abnormal clinical or laboratory findings (aHR 1.25, 95% CI 1.16, 1.34). LIMITATIONS, REASONS FOR CAUTION Only hospital-based inpatient and outpatient care is covered by the CRHC register, excluding milder cases diagnosed elsewhere. We were not able to study the effect of ART treatments and subfertility separately in our setting. In addition, although our cohort is reasonably sized, even larger cohorts would be needed to reliably study rare outcomes, such as cancer. WIDER IMPLICATIONS OF THE FINDINGS For many ICD-10 chapters, we present the first published data on the long-term outcome of singletons born after FET. The results on FET versus fresh ET are reassuring, whereas the results on FET versus NC warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S) Finnish government research funding was obtained for this study. Funding was also obtained from the Finnish Medical Society Duodecim, the Paivikki and Sakari Sohlberg Foundation, Orion Research Foundation, Finnish Society of Obstetrics and Gynaecology (research grants to A.M.T.) and Finnish government research funding. The funding sources were not involved in the planning or execution of the study. The authors have no competing interests to declare.Peer reviewe

    Mortality of midlife women with surgically verified endometriosis-a cohort study including 2.5 million person-years of observation

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    STUDY QUESTION Is all-cause and cause-specific mortality increased among women with surgically verified endometriosis? SUMMARY ANSWER The all-cause and cause-specific mortality in midlife was lower throughout the follow-up among women with surgically verified endometriosis compared to the reference cohort. WHAT IS KNOWN ALREADY Endometriosis has been associated with an increased risk of comorbidities such as certain cancers and cardiovascular diseases. These diseases are also common causes of death; however, little is known about the mortality of women with endometriosis. STUDY DESIGN, SIZE, DURATION A nationwide retrospective cohort study of women with surgically verified diagnosis of endometriosis was compared to the reference cohort in Finland (1987-2012). Follow-up ended at death or 31 December 2014. During the median follow-up of 17years, 2.5 million person-years accumulated. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-nine thousand nine hundred and fifty-six women with at least one record of surgically verified diagnosis of endometriosis in the Finnish Hospital Discharge Register between 1987 and 2012 were compared to a reference cohort of 98824 age- and municipality-matched women. The age (meanstandard deviation) of the endometriosis cohort was 36.49.0 and 53.612.1years at the beginning and at the end of the follow-up, respectively. By using the Poisson regression models the crude and adjusted all-cause and cause-specific mortality rate ratios (MRR) and 95% confidence intervals (CI) were assessed. Calendar time, age, time since the start of follow-up, educational level, and parity adjusted were considered in the multivariate analyses. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1656 and 4291 deaths occurred in the endometriosis and reference cohorts, respectively. A lower all-cause mortality was observed for the endometriosis cohort (adjusted MRR, 0.73 [95% CI 0.69 to 0.77])-there were four deaths less per 1000 women over 10years. A lower cause-specific mortality contributed to this: the adjusted MRR was 0.88 (95% CI 0.81 to 0.96) for any cancer and 0.55 (95% CI 0.47 to 0.65) for cardiovascular diseases, including 0.52 (95% CI 0.42 to 0.64) for ischemic heart disease and 0.60 (95% CI 0.47 to 0.76) for cerebrovascular disease. Mortality due to alcohol, accidents and violence, respiratory, and digestive disease-related causes was also decreased. LIMITATIONS, REASONS FOR CAUSATION These results are limited to women with endometriosis diagnosed by surgery. In addition, the study does not extend into the oldest age groups. The results might be explained by the characteristics and factors related to women's lifestyle, and/or increased medical attention and care received, rather than the disease itself. WIDER IMPLICATIONS OF THE FINDINGS These reassuring data are valuable to women with endometriosis and to their health care providers. Nonetheless, more studies are needed to address the causality. STUDY FUNDING/COMPETING INTEREST This research was funded by the Hospital District of Helsinki and Uusimaa and The Finnish Medical Foundation. None of the authors report any competing interest in relation to the present work; all the authors have completed the disclosure form.Peer reviewe

    Low anti-Müllerian hormone level is not a risk factor for early pregnancy loss in IVF/ICSI treatment

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    STUDY QUESTION: Is a low ( SUMMARY ANSWER: A low or moderately low serum AMH level does not associate with miscarriage, non-visualized pregnancy loss or overall early pregnancy loss rate in the IVF/ICSI treatment. WHAT IS KNOWN ALREADY: Low AMH predicts poor ovarian response and small oocyte yield in IVF/ICSI treatment, but its value in the evaluation of live birth rate (LBR) is modest Little is known about the risk of early pregnancy loss in ART among women with low AMH. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study on 1383 women undergoing their first oocyte retrieval for IVF/ICSI in Helsinki University Hospital in Helsinki, Finland, between 2012 and 2016, with all associated fresh (n = 1315) and frozen-thawed (n = 1418) ET cycles finished by August 2018. AMH was measured within 12 months before the IVF/ICSI stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of all the women, 235 (17.0%) had low (= 2.0 mu g/L) AMH. The primary outcomes were miscarriage, non-visualized pregnancy loss and early pregnancy loss (miscarriage and non-visualized pregnancy loss combined) after fresh or frozen-thawed ET. The impact of AMH on these outcomes was calculated in three populations: among all women who became pregnant, among women with AMH MAIN RESULTS AND THE ROLE OF CHANCE: Of 1123 pregnancies, 285 (25.4%) ended in non-visualized pregnancy loss and 143 (12.7%) in miscarriage. The LBR was 24.6% per ET (673/2733). Low or moderately low AMH, compared with normal AMH, did not associate with miscarriage or non-visualized pregnancy loss in analyses among all women who became pregnant (adjusted relative risk (RR) for miscarriage vs live birth, 0.70 and 95% CI 0.42-1.17 in low AMH and adjusted RR, 1.00 and 95% CI, 0.68-1.49 in moderately low AMH; adjusted RR for non-visualized pregnancy loss vs live birth, 0.90 and 95% CI, 0.65-1.23 in low AMH and adjusted RR, 1.09 and 95% CI 0.85-1.41 in moderately low AMH), nor did low or moderately low AMH associate with the overall early pregnancy loss rate (adjusted RR for early pregnancy loss vs live birth, 0.86 and 95% CI, 0.68-1.10 in low AMH and adjusted RR, 1.01 and 95% CI, 0.86-1.27 in moderately low AMH). Results remained similar after restricting the analysis to women with AMH LIMITATIONS, REASONS FOR CAUTION: The number of miscarriages in women with low AMH was moderately small, limiting the power of the study. The real-world clinical setting of the study restricted the ability to control for all factors causing selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The cLBR was higher among women with normal AMH than among women with low or moderately low AMH in their first IVF/ICSI treatment because these women had more oocytes and embryos. Women with low or moderately low AMH did not have an increased risk for early pregnancy loss. This information is reassuring for couples and useful in counseling. These results are also valuable when assessing the overall effectiveness of IVF/ICSI treatment.Peer reviewe

    Mortality in individuals with intellectual disabilities in Finland

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    Objectives: This study aimed at ascertaining the standardized mortality ratios (SMR) for those with an intellectual disability (ID) in Finland. Materials and Methods: We used the statistical database of the national insurance institution of Finland and Statistics Finland&#39;s mean population figures. We determined the number of individuals who received benefits (disability allowance, disability pension, or care allowance for pensioners) due to an ID diagnosis and the number of those whose benefit had been terminated due to death during the years 1996-2011. Results: SMR for females with a mild ID (IQ 50-69) was 2.8 (95% CI: 2.60-3.01) and for males 2.0 (95% CI: 1.88-2.14), and for females with a severe ID (IQ &lt; 50) 5.2 (95% CI: 4.99-5.50) and for males 2.6 (95% CI: 2.48-2.72). Conclusion: This significant difference in the SMR figures between males and females with ID warrants further research.</p

    The risk of psychiatric disorders among Finnish ART and spontaneously conceived children: Finnish population-based register study

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    Evidence regarding the psychiatric morbidity of children born after Assisted Reproductive Techniques (ART) is inconsistent and limited. While normal mental well-being for ART children is usually reported, concerns are still being raised. Previous studies examine only some psychiatric disorders, but not all of them, ignore the impact of multiplicity, and limit the follow-up time to childhood. We examined all psychiatric diagnoses for singletons until their young adulthood. The aim was to study whether the risk of psychiatric disorders differs between ART and spontaneously conceived (SC) singletons until young adulthood. This retrospective Finnish population-based register study includes all ART and SC live-born children born in Finland during 1990-2013 and their hospital care in 1990-2014 (n = 1,425,975 of which 1,385,956, 97.2% were singletons). After excluding multiples, the final population included 17,610 ART and 1,368,346 SC singletons in 1990-2013 from the Finnish Medical Birth Registry. These data were linked to the Finnish Hospital Discharge Registry with the child's and mother's encrypted IDs. ART singletons had fewer psychiatric diagnoses (ART 10.2%, n = 1796, SC 12.0%, n = 164,408), but they received their diagnoses earlier (mean 8.3 years old, SD 5.0) than SC singletons (mean 10.5 years old, SD 5.7). After adjusting for confounding factors, ART singletons had an increased likelihood of getting a psychiatric diagnosis until young adulthood and the results were similar for boys (adjusted hazard ratios [aHR] = 1.16, 95% confidence interval (CI) 1.10-1.24) and girls (aHR = 1.25, 95% CI 1.16-1.35). We conclude that ART children receive their psychiatric diagnoses earlier than SC children, in particular during childhood and early adolescence. After adjusting for confounding factors ART children a slightly increased likelihood of any psychiatric diagnosis compared to SC controls

    Puberty disorders among ART-conceived singletons : a Nordic register study from the CoNARTaS group

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    STUDY QUESTION Do ART-conceived children have an increased risk for puberty disorders? SUMMARY ANSWER Both ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys. WHAT IS KNOWN ALREADY Some physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited. STUDY DESIGN, SIZE, DURATION A register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994-2014), Finland (1990-2014), Norway (2002-2015) and Sweden (1985-2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE There were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29-1.64) and late puberty (aHR 1.47, 95% CI: 1.21-1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29-1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24-1.95). LIMITATIONS, REASONS FOR CAUTION Using reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers' own puberty characteristics and BMI, as well as children's BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility. WIDER IMPLICATIONS OF THE FINDINGS This large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg oresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway's Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium 'Family Formation in Flux-Causes, Consequences and Possible Futures', funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.Peer reviewe

    Predictive Values of Serum Chlamydia trachomatis TroA and HtrA IgG Antibodies as Markers of Persistent Infection in the Detection of Pelvic Adhesions and Tubal Occlusion

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    Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection

    Predictive Values of Serum Chlamydia trachomatis TroA and HtrA IgG Antibodies as Markers of Persistent Infection in the Detection of Pelvic Adhesions and Tubal Occlusion

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    Chlamydia trachomatis IgG antibody testing (CAT) has been used as a screening test for tubal factor infertility (TFI), but as the CAT is only a marker of a past exposure to C. trachomatis and not of late sequelae, the positive predictive value (PPV) of the test is low. The persistence of C. trachomatis in the upper genital tract has been suggested as one of the key mechanisms in the development of TFI. Serum antibodies against C. trachomatis TroA and HtrA, proteins expressed specifically during persistent infection, have been suggested as novel biomarkers for TFI diagnostics. We studied serum IgG antibody responses against C. trachomatis TroA, HtrA and MOMP in 79 subfertile women, of whom 28 had laparoscopically proven TFI. We confirmed that the accuracy of CAT in diagnosing TFI is low, whereas TroA IgG and HtrA IgG are more accurate tests in detecting tubal occlusion and pelvic adhesions. However, the sensitivity and negative predictive value (NPV) of TroA IgG and HtrA IgG are still too low to justify their use as a screening test in clinical practice. Individual immunogenetic profiles combined with TroA and HtrA antibody responses might identify women with the highest risk for developing late complications after C. trachomatis infection
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