Psychiatric comorbidity among women with endometriosis: nationwide cohort study in Sweden.

BACKGROUND: Endometriosis is a common gynecologic condition affecting women of reproductive age. It has been linked with greater rates of depression and anxiety in small, cross-sectional, and clinical studies. Other studies have reported that women with endometriosis have increased risk of bipolar disorder. These reports suggest that psychiatric disorders might be more common among women with endometriosis, contributing to increased burden of mental ill-health in this population of women. However, this hypothesis has not been adequately studied. OBJECTIVES: In this population-based study, we investigated the overall psychiatric comorbidity among women with endometriosis, and the role of familial liability. STUDY DESIGN: Several Swedish national registers were linked and used to follow all women born in Sweden in 1973-1990 for diagnosed psychiatric disorders and endometriosis from age 14 years until year 2016. Sibling comparison analyses were performed in a subsample of 173,650 families. RESULTS: After adjustment for birth characteristics and education, women with endometriosis had an increased risk of being later diagnosed with depressive-, anxiety and stress-related disorders, alcohol/drug dependence, and attention-deficit hyperactivity disorder compared with the general population and with their sisters without endometriosis. The adjusted hazard ratios ranged from 1.56 (95% confidence interval, 1.29-1.88) for depressive disorders to 1.98 (95% confidence interval, 1.34-2.93) for attention-deficit hyperactivity disorder in the sibling analysis. Also, women with previous affective psychotic disorders, depressive-, anxiety and stress-related disorders, eating disorders, personality disorders, and attention-deficit hyperactivity disorder were more likely to be later diagnosed with endometriosis. The adjusted hazard ratios ranged from 1.51 (95% confidence interval, 1.30-1.76) for depressive disorders to 1.93 (95% confidence interval, 1.47-2.52) for personality disorders. CONCLUSION: These findings reveal a high degree of comorbidity between endometriosis and many psychiatric disorders that was not entirely explained by shared familial confounding. Clinical practice may consider psychosocial support to women with endometriosis and treating them from a multidisciplinary perspective.

Treatment efficacy for idiopathic recurrent pregnancy loss - a systematic review and meta-analyses.

INTRODUCTION: Medical treatment of women with idiopathic recurrent pregnancy loss is controversial. The objective was to assess the effects of different treatments on live birth rates and complications in women with unexplained recurrent pregnancy loss. MATERIAL AND METHODS: We searched MEDLINE, Embase and the Cochrane Library, and identified 1415 publications. This systematic review included 21 randomized controlled trials regarding acetylsalicylic acid, low-molecular-weight heparin, progesterone, intravenous immunoglobulin or leukocyte immune therapy in women with three or more consecutive miscarriages of unknown cause. The study quality was assessed and data was extracted independently by at least two authors. RESULTS: No significant difference in live birth rate was found when acetylsalicylic acid was compared with low-molecular-weight heparin or with placebo. Meta-analyses of low-molecular-weight heparin vs. control found no significant differences in live birth rate [risk ratio (RR) 1.47, 95% CI 0.83-2.61]. Treatment with progesterone starting in the luteal phase seemed effective in increasing live birth rate (RR 1.18, 95% CI 1.09-1.27) but not when started after conception. Intravenous immunoglobulin showed no effect on live birth rate compared with placebo (RR 1.07, 95% CI 0.91-1.26). Paternal immunization compared with autologous immunization showed a significant difference in outcome (RR 1.8, 95% CI 1.34-2.41), although the studies were small and at high risk of bias. CONCLUSION: The literature does not allow advice on any specific treatment for idiopathic recurrent pregnancy loss, with the exception of progesterone starting from ovulation. We suggest that any treatment for recurrent pregnancy loss should be used within the context of a randomized controlled trial.

Compartmentalized gene expression profiling of receptive endometrium reveals progesterone regulated ENPP3 is differentially expressed and secreted in glycosylated form.

The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation. Interestingly, there was high expression of ENPP3 mRNA in stroma but not protein. Presence of N-glycosylated ENPP3 in receptive phase uterine fluid in women confirms its regulation by progesterone and makes it possible to use in a non-invasive test of endometrial receptivity.

Uterine fibroids.

Uterine fibroids (also known as leiomyomas or myomas) are common clonal neoplasms of the uterus. Fibroids have both smooth muscle and fibroblast components, in addition to a substantial amount of fibrous extracellular matrix, which all contribute to the pathogenetic process. Fibroids are extremely heterogeneous in their pathophysiology, size, location and clinical symptomatology. They are also a part of a range of disease in which some variants have facets of malignant behaviour but overall are benign. Risk for fibroids is associated with race; black women have a higher risk of developing fibroids earlier in life than their white counterparts and also develop more-severe forms of the disease. Clinically, fibroids account for one-third to half of all hysterectomies and are associated with substantial morbidity and health care costs for women of reproductive age. Indeed, current treatments are primarily surgical and interventional; approximately three-quarters of all fibroid treatments are hysterectomies. However, clinical innovations are emerging in the use of progesterone receptor modulators as a medical therapy. New information is rapidly accumulating about the genetic subgroups that lead to fibroid formation, which might aid further understanding of the clinical heterogeneity of this disease and lead to individualized treatments. This information is a crucial development given the current lack of high-quality evidence on which to base therapeutic decisions.

Recent advances in understanding endometrial receptivity: molecular basis and clinical applications.

Advancement in the field of ART has lead to the possibility of achieving good quality embryos. However, the success rate in ART needs further improvement. This is largely dependent on identifying the receptive endometrium for the successful implantation of embryos as well as modulating the endometrium to the receptive stage. In the last half-a-decade, focus has been shifting toward identifying the receptive endometrium. Here, we summarize different tools explored to identify receptive endometrium from the literature, mainly focusing on the past decade, with the help of PubMed. The quest to identify endometrial receptivity markers has lead to the exploration of morphological features at micro and macro scale levels. A large number of studies at molecular levels have focused on genomic, proteomic and lipidomic targets. Recent development of endometrial receptivity array is a promising diagnostic instrument. However, a noninvasive possibility for the diagnosis of endometrial receptivity would be an ideal tool, which could be used in the clinic to improve the success rate of ART. Improved knowledge on endometrial receptivity will not only help to improve the diagnosis and treatment of infertility but will also give possibilities to develop new contraceptive methods targeting the endometrium.

Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT.

OBJECTIVE: To study the effect of polyethylene glycated leukemia inhibitory factor (LIF) antagonist (PEGLA) in the human blastocyst viability and implantation process. DESIGN: In vitro study. SETTING: University hospital and research laboratory. PATIENT(S): Endometrial biopsy samples from fertile donors (n = 20), and surplus, frozen, good-quality human embryos obtained from an in vitro fertilization (IVF) clinic that survived thawing (n = 51). INTERVENTION(S): Timed human endometrial biopsy on the day of luteinizing hormone peak + 4 days (LH + 4). MAIN OUTCOME MEASURE(S): Human embryo attachment rate, embryo quality, and expression of AKT and caspase-3. RESULT(S): PEGLA significantly reduced the embryo attachment rate to the endometrial construct. It decreased both mRNA and protein for LIF in the endometrial construct. Inhibition of embryonic LIF triggered apoptosis. Analysis of these blastocysts by immunofluorescence and real-time polymerase chain reaction showed a down-regulation in AKT activation and an increase in caspase-3 activation compared with the control group of blastocysts. CONCLUSION(S): The LIF inhibitor PEGLA could be a potential nonsteroidal fertility-regulating agent in humans. It acts on endometrial epithelial cells by down-regulating endometrial epithelial LIF. Inhibition of blastocyst LIF decreased its cell survival factor p-AKT and increased apoptosis (cleaved caspase-3). This highlights that embryonic LIF is vital for human embryo implantation.

Endometrial receptivity and human embryo implantation.

PROBLEM: The pre-requisite of successful implantation involves an intricate cascade of molecular interactions which plays a crucial role in preparing receptive endometrium and implanting blastocyst. METHOD OF STUDY: Data are hereby presented for a better understanding of endometrial receptivity in women, hoping to provide a comprehensive picture of the process and identify new areas of basic and translational research in the biology of blastocyst implantation. RESULTS: Timely regulation of the expression of a number of complex molecules like hormones, cytokines and growth factors, and their crosstalk from embryonic and maternal endometrial side play a major role in determining the fate of the embryo. The molecular basis of endometrial receptivity and the mechanisms by which the blastocyst first adheres to the luminal epithelium and then penetrates into the stroma are only just beginning to be resolved. CONCLUSION: Advances in the development of implantation models and 'omics' technologies, particularly proteomics and metabolomics, are set to have a major impact on the development of this field.

Second trimester medical abortion with mifepristone-misoprostol and misoprostol alone: a review of methods and management.

Second trimester abortions constitute 10-15% of all induced abortions worldwide but are responsible for two-thirds of major abortion-related complications. During the last decade, medical methods for second trimester induced abortion have been considerably improved and become safe and more accessible. Today, in most cases, safe and efficient medical abortion services can be offered or improved by minor changes in existing health care facilities. Second trimester medical abortion can be provided by a nurse-midwife with the back-up of a gynaecologist. Because of the potential for heavy vaginal bleeding and serious complications, it is advisable that second trimester terminations take place in a health care facility where blood transfusion and emergency surgery (including laparotomy) are available. This article provides basic information on regimens recommended for second trimester medical abortion. The combination of mifepristone and misoprostol is now an established and highly effective method for second trimester abortion. Where mifepristone is not available or affordable, misoprostol alone has also been shown to be effective, although a higher total dose is needed and efficacy is lower than for the combined regimen. Therefore, whenever possible, the combined regimen should be used. Efforts should be made to reduce unnecessary surgical evacuation of the uterus after expulsion of the fetus. Future studies should focus on improving pain management, the treatment of women with failed medical abortion after 24 hours, and the safety of medical abortion regimens in women with a previous caesarean section or uterine scar.