EFICÁCIA ADAPTATIVA DE MULHERES, COM HISTÓRIA DE ABORTAMENTO, PACIENTES DE UM AMBULATÓRIO DE REPRODUÇÃO HUMANA

O objetivo principal desta pesquisa foi investigar eficácia adaptativa de mulheres que vivenciaram abortamento e freqüentam um Ambulatório de Reprodução Humana. Os objetivos específicos foram: avaliar a eficácia adaptativa; identificar as repercussões psicológicas destes abortamentos. O instrumento utilizado foi a entrevista clínica preventiva- EDAO (Escala Diagnóstica Adaptativa Operacionalizada). Participaram do estudo 10 mulheres que freqüentavam um Ambulatório especializado em Reprodução Assistida. Os resultados deste trabalho revelaram que o abortamento teve uma repercussão importante no mundo interno e externo das mulheres que participaram desta pesquisa. Os abortamentos provocados e espontâneos são relatados com intensa angústia, tristeza, culpa e sentimentos de inferioridade. No caso do abortamento espontâneo predomina o medo de perder novamente, e no caso de aborto provocado, predominam sentimentos de culpa. As pacientes, de forma geral, apresentam intensa angústia e expectativa em relação ao tratamento; porém a experiência do tratamento para engravidar, somado à experiência anterior de abortamento, intensificou as angústias dessas mulheres. A psicoterapia breve operacionalizada pode auxiliar a paciente a lidar de forma mais adequada com os conflitos vividos no tratamento. E no caso específico deste estudo, auxiliar também a elaboração das perdas anteriores. Este estudo trouxe questionamentos relevantes sobre a vivência emocional de mulheres que buscam tratamento para engravidar e já sofreram abortamento espontâneo ou provocado. A realização de outros estudos é fundamental para maior compreensão do tema.(AU)

EFICÁCIA ADAPTATIVA DE MULHERES, COM HISTÓRIA DE ABORTAMENTO, PACIENTES DE UM AMBULATÓRIO DE REPRODUÇÃO HUMANA

O objetivo principal desta pesquisa foi investigar eficácia adaptativa de mulheres que vivenciaram abortamento e freqüentam um Ambulatório de Reprodução Humana. Os objetivos específicos foram: avaliar a eficácia adaptativa; identificar as repercussões psicológicas destes abortamentos. O instrumento utilizado foi a entrevista clínica preventiva- EDAO (Escala Diagnóstica Adaptativa Operacionalizada). Participaram do estudo 10 mulheres que freqüentavam um Ambulatório especializado em Reprodução Assistida. Os resultados deste trabalho revelaram que o abortamento teve uma repercussão importante no mundo interno e externo das mulheres que participaram desta pesquisa. Os abortamentos provocados e espontâneos são relatados com intensa angústia, tristeza, culpa e sentimentos de inferioridade. No caso do abortamento espontâneo predomina o medo de perder novamente, e no caso de aborto provocado, predominam sentimentos de culpa. As pacientes, de forma geral, apresentam intensa angústia e expectativa em relação ao tratamento; porém a experiência do tratamento para engravidar, somado à experiência anterior de abortamento, intensificou as angústias dessas mulheres. A psicoterapia breve operacionalizada pode auxiliar a paciente a lidar de forma mais adequada com os conflitos vividos no tratamento. E no caso específico deste estudo, auxiliar também a elaboração das perdas anteriores. Este estudo trouxe questionamentos relevantes sobre a vivência emocional de mulheres que buscam tratamento para engravidar e já sofreram abortamento espontâneo ou provocado. A realização de outros estudos é fundamental para maior compreensão do tema.(AU)

EFICÁCIA ADAPTATIVA DE MULHERES, COM HISTÓRIA DE ABORTAMENTO, PACIENTES DE UM AMBULATÓRIO DE REPRODUÇÃO HUMANA

O objetivo principal desta pesquisa foi investigar eficácia adaptativa de mulheres que vivenciaram abortamento e freqüentam um Ambulatório de Reprodução Humana. Os objetivos específicos foram: avaliar a eficácia adaptativa; identificar as repercussões psicológicas destes abortamentos. O instrumento utilizado foi a entrevista clínica preventiva- EDAO (Escala Diagnóstica Adaptativa Operacionalizada). Participaram do estudo 10 mulheres que freqüentavam um Ambulatório especializado em Reprodução Assistida. Os resultados deste trabalho revelaram que o abortamento teve uma repercussão importante no mundo interno e externo das mulheres que participaram desta pesquisa. Os abortamentos provocados e espontâneos são relatados com intensa angústia, tristeza, culpa e sentimentos de inferioridade. No caso do abortamento espontâneo predomina o medo de perder novamente, e no caso de aborto provocado, predominam sentimentos de culpa. As pacientes, de forma geral, apresentam intensa angústia e expectativa em relação ao tratamento; porém a experiência do tratamento para engravidar, somado à experiência anterior de abortamento, intensificou as angústias dessas mulheres. A psicoterapia breve operacionalizada pode auxiliar a paciente a lidar de forma mais adequada com os conflitos vividos no tratamento. E no caso específico deste estudo, auxiliar também a elaboração das perdas anteriores. Este estudo trouxe questionamentos relevantes sobre a vivência emocional de mulheres que buscam tratamento para engravidar e já sofreram abortamento espontâneo ou provocado. A realização de outros estudos é fundamental para maior compreensão do tema.(AU)

Report of The Commission on Assisted Human Reproduction

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Role of fibroblast growth factor (FGF) signaling in the neuroendocrine control of human reproduction.

Fibroblast growth factor (FGF) signaling is critical for a broad range of developmental processes. In 2003, Fibroblast growth factor receptor 1 (FGFR1) was discovered as a novel locus causing both forms of isolate GnRH Deficiency, Kallmann syndrome [KS with anosmia] and normosmic idiopathic hypogonadotropic hypogonadism [nIHH] eventually accounting for approximately 10% of gonadotropin-releasing hormone (GnRH) deficiency cases. Such cases are characterized by a broad spectrum of reproductive phenotypes from severe congenital forms of GnRH deficiency to reversal of HH. Additionally, the variable expressivity of both reproductive and non-reproductive phenotypes among patients and family members harboring the identical FGFR1 mutations has pointed to a more complex, oligogenic model for GnRH deficiency. Further, reversal of HH in patients carrying FGFR1 mutations suggests potential gene-environment interactions in human GnRH deficiency disorders.

An ancient founder mutation in PROKR2 impairs human reproduction.

Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ~123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.

The role of the prokineticin 2 pathway in human reproduction: evidence from the study of human and murine gene mutations.

A widely dispersed network of hypothalamic GnRH neurons controls the reproductive axis in mammals. Genetic investigation of the human disease model of isolated GnRH deficiency has revealed several key genes crucial for GnRH neuronal ontogeny and GnRH secretion. Among these genes, prokineticin 2 (PROK2), and PROK2 receptor (PROKR2) have recently emerged as critical regulators of reproduction in both mice and humans. Both prok2- and prokr2-deficient mice recapitulate the human Kallmann syndrome phenotype. Additionally, PROK2 and PROKR2 mutations are seen in humans with Kallmann syndrome, thus implicating this pathway in GnRH neuronal migration. However, PROK2/PROKR2 mutations are also seen in normosmic GnRH deficiency, suggesting a role for the prokineticin signaling system in GnRH biology that is beyond neuronal migration. This observation is particularly surprising because mature GnRH neurons do not express PROKR2. Moreover, mutations in both PROK2 and PROKR2 are predominantly detected in the heterozygous state with incomplete penetrance or variable expressivity frequently seen within and across pedigrees. In some of these pedigrees, a "second hit" or oligogenicity has been documented. Besides reproduction, a pleiotropic physiological role for PROK2 is now recognized, including regulation of pain perception, circadian rhythms, hematopoiesis, and immune response. Therefore, further detailed clinical studies of patients with PROK2/PROKR2 mutations will help to map the broader biological role of the PROK2/PROKR2 pathway and identify other interacting genes/proteins that mediate its molecular effects in humans.

The puzzles of the prokineticin 2 pathway in human reproduction.

Prokineticin, 1 (PROK1) and prokineticin 2 (PROK2), are two closely related proteins that were identified as the mammalian homologs of their two amphibian homologs, mamba intestinal toxin (MIT-1) and Bv8. MIT-1 was initially identified as a non-toxic constituent in the venom of the black mamba snake (Dendroaspis polylepis) (Joubert and Strydom, 1980) while Bv8 was identified in the skin secretion of the toad, Bombina variegate (Mollay et al., 1999). All three homologs stimulate gastrointestinal motility thus accounting for their family name "prokineticins" (Schweitz et al., 1990, 1999). However, since its initial description, both PROK1 and PROK2 have been found to regulate a dazzling array of biological functions throughout the body. In particular, PROK1 acts as a potent angiogenic mitogen on endocrine vascular epithelium, thus earning its other name, Endocrine gland-vascular endothelial factor (EG-VEGF) (LeCouter et al., 2002). In contrast, the PROK2 signaling pathway is a critical regulator of olfactory bulb morphogenesis and sexual maturation in mammals and this function is the focus of this review.

Microbes central to human reproduction

As studies uncover the breadth of microbes associated with human life, opportunities will emerge to manipulate and augment their functions in ways that improve health and longevity. From involvement in the complexities of reproduction and fetal/infant development, to delaying the onset of disease, and indeed countering many maladies, microbes offer hope for human well-being. Evidence is emerging to suggest that microbes may play a beneficial role in body sites traditionally viewed as being sterile. Although further evidence is required, we propose that much of medical dogma is about to change significantly through recognition and understanding of these hitherto unrecognized microbe–host interactions. A meeting of the International Scientific Association for Probiotics and Prebiotics held in Aberdeen, Scotland (June 2014), presented new views and challenged established concepts on the role of microbes in reproduction and health of the mother and infant. This article summarizes some of the main aspects of these discussions.

An ancient founder mutation in PROKR2 impairs human reproduction

Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutations age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same approximate to 123 kb haplotype whose population frequency is 10. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction.

Physiological changes in plasma proteins characteristic of human reproduction; cross-sectional and longitudinal electrophoretic data for women during and following uncomplicated and complicated pregnancies,

Includes bibliographies.

Factor V Leiden and factor II G20210A mutations in patients with recurrent abortion

Recurrent abortion (RA) represents an intriguing problem in obstetric practice in which genetic and acquired factors may play a role. In the present investigation we sought to assess the possibility that inherited thrombophilia might determine the risk of RA. We therefore investigated the prevalence of two genetic abnormalities frequently associated with venous thrombosis [factor V Leiden (FVL) and factor II G20210A] in 56 patients with primary or secondary abortion and in 384 healthy control women. Polymerase chain reaction amplification followed by digestion with the restriction enzymes MnlI and HindIII was used to define the FVL and FII G20210A genotypes respectively. FVL was found in 4/56 patients (7.1%) and in 6/384 controls (1.6%), yielding an odds ratio (OR) for RA related to FVL of 4.9 [95% confidence interval (CI): 1.3-17.8]. FII G20210A was detected in 2/56 (3.6%) patients and in 4/384 (1%) controls (OR for RA: 3.5, CI: 0.6-19.7). In conclusion, FVL and FII G20210A mutations in patients with RA were more prevalent in comparison with controls. These data support a role for both mutations as determinants of the risk of RA and strengthen the notion that thrombophilia plays a role in this clinical entity.

Ethinylestradiol and estradiol have different effects on oxidative stress and nitric oxide synthesis in human endothelial cell cultures

Study objective: To compare the effects of ethinylestradiol (EE) and 17 beta-estradiol (E(2)) on nitric oxide (NO) production and protection against oxidative stress in human endothelial cell cultures. Design: Experimental study. Settings: Research laboratory. Material: Human ECV304 endothelial cell cultures. Intervention(s): The NO synthesis was determined by flow cytometry, and oxidative stress was determined by a cell viability assay, after exposure to hydrogen peroxide (H(2)O(2)) and stimulation of endothelial cells with EE at concentrations similar to those of a contraceptive containing 30 mu g EE. Main Outcome Measure(s): The effects of EE were compared with those of E(2) at concentrations similar to those occurring during the follicular phase. Result(s): Ethinylestradiol did not increase NO synthesis and did not protect cells against oxidative stress. The viability of the cells incubated with E(2) in combination with H(2)O(2) was greater than the viability obtained with H(2)O(2) only or with H(2)O(2) in combination with EE. The cells stimulated with E(2) presented a significant increase in NO production compared with control. Conclusion(s): In contrast to the effects of E(2), EE did not protect human ECV304 endothelial cells against oxidative stress and did not increase their production of NO. (Fertil Steril (R) 2010; 94: 1578-82. (C) 2010 by American Society for Reproductive Medicine.)