Rethinking mechanisms, diagnosis and management of endometriosis

To assess the impact of endometriosis on health-related quality of life (HRQoL) and work productivity. Multicenter cross-sectional study with prospective recruitment. Sixteen clinical centers in ten countries. A total of 1,418 premenopausal women, aged 18-45 years, without a previous surgical diagnosis of endometriosis, having laparoscopy to investigate symptoms or to be sterilized. None. Diagnostic delay, HRQoL, and work productivity. There was a delay of 6.7 years, principally in primary care, between onset of symptoms and a surgical diagnosis of endometriosis, which was longer in centers where women received predominantly state-funded health care (8.3 vs. 5.5 years). Delay was positively associated with the number of pelvic symptoms (chronic pelvic pain, dysmenorrhoea, dyspareunia, and heavy periods) and a higher body mass index. Physical HRQoL was significantly reduced in affected women compared with those with similar symptoms and no endometriosis. Each affected woman lost on average 10.8 hours (SD 12.2) of work weekly, mainly owing to reduced effectiveness while working. Loss of work productivity translated into significant costs per woman/week, from US$4 in Nigeria to US$456 in Italy. Endometriosis impairs HRQoL and work productivity across countries and ethnicities, yet women continue to experience diagnostic delays in primary care. A higher index of suspicion is needed to expedite specialist assessment of symptomatic women. Future research should seek to clarify pain mechanisms in relation to endometriosis severity. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitment and renders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Here we review the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. We discuss how disorders that subvert the programming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure.

Earlier reviews have suggested that IVF/ICSI pregnancies are associated with higher risks. However, there have been recent advances in the way IVF/ICSI is done, leading to some controversy as to whether IVF/ICSI singletons are associated with higher perinatal risks. The objective of this systematic review was to provide an up-to-date comparison of obstetric and perinatal outcomes of the singletons born after IVF/ICSI and compare them with those of spontaneous conceptions. Extensive searches were done by two authors. The protocol was agreed a priori. PRISMA guidance was followed. The data were extracted in 2 × 2 tables. Risk ratio and risk difference were calculated on pooled data using Rev Man 5.1. Quality assessment of studies was performed using Critical Appraisal Skills programme. Sensitivity analysis was performed when the heterogeneity was high (I(2) > 50%). There were 20 matched cohort studies and 10 unmatched cohort studies included in this review. IVF/ICSI singleton pregnancies were associated with a higher risk (95% confidence interval) of ante-partum haemorrhage (2.49, 2.30-2.69), congenital anomalies (1.67, 1.33-2.09), hypertensive disorders of pregnancy (1.49, 1.39-1.59), preterm rupture of membranes (1.16, 1.07-1.26), Caesarean section (1.56, 1.51-1.60), low birthweight (1.65, 1.56-1.75), perinatal mortality (1.87, 1.48-2.37), preterm delivery (1.54, 1.47-1.62), gestational diabetes (1.48, 1.33-1.66), induction of labour (1.18, 1.10-1.28) and small for gestational age (1.39, 1.27-1.53). Singletons pregnancies after IVF/ICSI are associated with higher risks of obstetric and perinatal complications when compared with spontaneous conception. Further research is needed to determine which aspect of assisted reproduction technology poses most risk and how this risk can be minimized.