Women with female infertility seeking medically assisted reproduction are not at increased risk of developing multiple sclerosis.

STUDY QUESTION: Is female infertility among women seeking medically assisted reproduction (MAR) associated with prevalent as well as incident multiple sclerosis (MS)? SUMMARY ANSWER: Women with a record of female infertility did not have an increased risk of developing MS compared with apparent fertile women; however, the prevalence of MS was slightly higher among women undergoing MAR compared with women who had a child without MAR, but this was not related to origin of infertility (i.e. male versus female factor infertility). WHAT IS KNOWN ALREADY: Women with MS have fewer children compared with women without MS. Persons with MS more often have other coexisting autoimmune disorders including hypothyroidism compared with the general population. Thyroid dysfunction is associated with ovarian cause of infertility, miscarriage and ovarian failure. Conversely, women with endometriosis, that is highly associated with infertility, also more often have other coexisting autoimmune diseases including MS and hypothyroidism compared with the general population. However, whether the low fertility rate among women with MS is due to a genetically predisposition to other autoimmune and endocrine disorders that leads to reduced fertility, or an active choice of the woman, disease-related pathology or treatment-specific effect on endocrine and/or ovarian function, is not completely understood. STUDY DESIGN, SIZE, DURATION: A register-based cohort study of a total of 310 357 women from 1996 to 2018. A cross-sectional design was used for analysing prevalence of MS, whereas a cohort design with up to 24 years of follow-up was used for analysing incidence of MS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three cohorts were included in the study (i) 55 404 women with a female infertility diagnosis registered in the Danish IVF register; (ii) 25 096 women with only male factor infertility recorded in the IVF register and thus no female infertility diagnosis and (iii) 229 857 age- and calendar-matched women with a record of first child birth in the Danish Medical Birth Register (DMBR) and no record ever in the IVF register. The prevalence and incidence of MS in the female infertility cohort were compared with the two control cohorts of apparent fertile women using log-binomial regression and Cox proportional hazard regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: The crude prevalence of having MS per 1000 persons was 3.2 for women who had undergone MAR treatment regardless of origin of infertility (i.e. male versus female factor infertility) and 2.3 for fertile DMBR controls. The age, calendar and educational level adjusted prevalence ratio of having a diagnosis of MS at the first MAR treatment was 1.27 (95% CI 1.07-1.52) for infertile women compared with fertile DMBR controls, and 1.00 (95% CI 0.77-1.31) for comparison to women with a male partner with infertility who had also undergone MAR treatment. We found no association between incident MS and female infertility compared with either of the control groups of fertile women. LIMITATIONS, REASON FOR CAUTION: The cohort of infertile women is highly selected on the basis of their choice of having fertility treatment and thus does not include women with unestablished infertility or women who, for some reason, have chosen not to have MAR treatment. Additionally, due to the nature of the observational study design, we cannot exclude the possibility of unmeasured and/or residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that women with MS may undergo MAR treatment more often than women without MS due to more awareness about the possibility of MAR treatments, sexual dysfunction related to MS disease, but also need for timing of the pregnancy to avoid an unnecessary long time period without disease modifying therapy-especially of high efficacy-and hence a wish to conceive quickly. These findings are important for clinicians dealing with women with MS of childbearing age. STUDY FUNDING/COMPETING INTEREST(S): The authors received no financial support for the study. T.I.K. has served on a scientific advisory board for Novartis and has received support for congress participation from Biogen. M.M. has served on scientific advisory boards for Biogen, Sanofi, Roche, Novartis, Merck, Abbvie and Alexion. She has received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi and Genzyme and has received research support and support for congress participation from Biogen, Genzyme, Roche, Merck and Novartis. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Assisted reproductive technology treatment and risk of breast cancer: a population-based cohort study.

STUDY QUESTION: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation? SUMMARY ANSWER: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years. WHAT IS KNOWN ALREADY: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment. STUDY DESIGN, SIZE, DURATION: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08). LIMITATIONS, REASONS FOR CAUTION: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation. WIDER IMPLICATIONS OF THE FINDINGS: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Serial endometrial thickness and risk of non-endometrial hormone-dependent cancers in postmenopausal women in UK Collaborative Trial of Ovarian Cancer Screening.

OBJECTIVE: Estrogen is a well-established risk factor for various cancers. It causes endometrial proliferation, which is assessed routinely as endometrial thickness (ET) using transvaginal ultrasound (TVS). Only one previous study, restricted to endometrial and breast cancer, has considered ET and the risk of non-endometrial cancer. The aim of this study was to explore the association between baseline and serial ET measurements and nine non-endometrial hormone-sensitive cancers, in postmenopausal women, using contemporary statistical methodology that attempts to minimize the biases typical of endogenous serial data. METHODS: This was a cohort study nested within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). In the ultrasound arm of UKCTOCS, 50639 postmenopausal women, aged 50-74, underwent annual TVS examination, of whom 38 105 had a valid ET measurement, no prior hysterectomy and complete covariate data, and were included in this study. All women were followed up through linkage to national cancer registries. The effect of ET on the risk of six estrogen-dependent cancers (breast, ovarian, colorectal, bladder, lung and pancreatic) was assessed using joint models for longitudinal biomarker and time-to-event data, and Cox models were used to assess the association between baseline ET measurement and these six cancers in addition to liver cancer, gastric cancer and non-Hodgkin's lymphoma (NHL). All models were adjusted for current hormone-replacement therapy (HRT) use, body mass index, age at last menstrual period, parity and oral contraceptive pill use. RESULTS: The 38 105 included women had a combined total of 267 567 (median, 8; interquartile range, 5-9) valid ET measurements. During a combined total of 407 838 (median, 10.9) years of follow-up, 1398 breast, 351 endometrial, 381 lung, 495 colorectal, 222 ovarian, 94 pancreatic, 79 bladder, 62 gastric, 38 liver cancers and 52 NHLs were registered. Using joint models, a doubling of ET increased significantly the risk of breast (hazard ratio (HR), 1.21; 95% CI, 1.09-1.36; P = 0.001), ovarian (HR, 1.39; 95% CI, 1.06-1.82; P = 0.018) and lung (HR, 1.25; 95% CI, 1.02-1.54; P = 0.036) cancers. There were no statistically significant associations between ET and the remaining six cancers. CONCLUSION: Postmenopausal women with high/increasing ET on TVS are at increased risk of breast, ovarian and lung cancer. It is important that clinicians are aware of these risks, as TVS is a common investigation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Assisted reproductive technology treatment and risk of ovarian cancer-a nationwide population-based cohort study.

STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

Prevalence and predictors of complementary and alternative medicine/non-pharmacological interventions use for menopausal symptoms within the UK Collaborative Trial of Ovarian Cancer Screening.

OBJECTIVES: The negative publicity about menopausal hormone therapy (MHT) has led to increased use of complementary and alternative medicines (CAM) and non-pharmacological interventions (NPI) for menopausal symptom relief. We report on the prevalence and predictors of CAM/NPI among UK postmenopausal women. METHOD: Postmenopausal women aged 50-74 years were invited to participate in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). A total of 202 638 women were recruited and completed a baseline questionnaire. Of these, 136 020 were sent a postal follow-up-questionnaire between September 2006 and May 2009 which included ever-use of CAM/NPI for menopausal symptom relief. Both questionnaires included MHT use. RESULTS: A total of 88 430 (65.0%) women returned a completed follow-up-questionnaire; 22 206 (25.1%) reported ever-use of one or more CAM/NPI. Highest use was reported for herbal therapies (43.8%; 9725/22 206), vitamins (42.6%; 9458/22 206), lifestyle approaches (32.1%; 7137/22 206) and phytoestrogens (21.6%; 4802/22 206). Older women reported less ever-use of herbal therapies, vitamins and phytoestrogens. Lifestyle approaches, aromatherapy/reflexology/acupuncture and homeopathy were similar across age groups. Higher education, Black ethnicity, MHT or previous oral contraceptive pill use were associated with higher CAM/NPI use. Women assessed as being less hopeful about their future were less likely to use CAM/NPI. CONCLUSION: One in four postmenopausal women reported ever-use of CAM therapies/NPI for menopausal symptom relief, with lower use reported by older women. Higher levels of education and previous MHT use were positive predictors of CAM/NPI use. UKCTOCS Trial registration: ISRCTN22488978.

Acute eosinophilic pneumonia in AIDS.

A 39-year-old man with AIDS presented with acute respiratory distress and diffuse bilateral infiltrates seen on a chest radiograph. Acute eosinophilic pneumonia (AEP) was diagnosed by thoracoscopic lung biopsy. There was no evidence of an infectious etiology, and the patient rapidly improved with corticosteroid therapy. Several of the idiopathic interstitial pneumonias have been reported in adult patients with AIDS. To our knowledge, this case represents the first tissue-confirmed case of AEP associated with adult AIDS.

Radiographic appearance of interstitial lung disease.

Interstitial lung disease has many forms, and its appearance can vary widely under radiographic imaging. This article reviews the anatomy and physiology of the lung, then describes the most common radiographic characteristics of ILD-the ground glass effect, consolidation, cysts, honey-combing, pulmonary nodules and interstitial thickening. Also included is a discussion of the advantages of using high-resolution computed tomography to image ILD.