Publicado em 09/01/2012 - Atualizado 26/07/2019

Atualizações científicas – 02 a 05 de janeiro de 2012


A comunidade científica publicou, na última semana, artigos sobre Infertilidade Masculina, Infertilidade Feminina e Reprodução Humana. Veja a seguir o resumo dos artigos publicados.

Reproductive consequences of developmental phytoestrogen exposure.

Publicado em 05 de Janeiro de 12 pela Human Reproduction, disponível no Oxfor Journal.


Phytoestrogens, estrogenic compounds derived from plants, are ubiquitous in human and animal diets. These chemicals are generally much less potent than estradiol but act via similar mechanisms. The most common source of phytoestrogen exposure to humans is soybean-derived foods that are rich in the isoflavones genistein and daidzein. These isoflavones are also found at relatively high levels in soy-based infant formulas. Phytoestrogens have been promoted as healthy alternatives to synthetic estrogens and are found in many dietary supplements. The aim of this review is to examine the evidence that phytoestrogen exposure, particularly in developmentally sensitive periods of life, has consequences for future reproductive health.

The possible role of genetic variants in autoimmune-related genes in the development of endometriosis.

Publicado em Dezembro de 2011 pela Hum. Immunol., disponível no Pub Med.


Numerous hypotheses have been put forward to explain the presence of ectopic endometrial tissue and stroma. The immune system participates in the homeostasis of the peritoneal cavity, and modifications in its functioning have been advanced to explain endometriosis and its consequences. Recently, the powerful anti-inflammatory effect of progesterone was recognized as a potential causal factor for endometriosis and could contribute to the autoimmune nature of endometriosis, as well as to more specific local and systemic changes. Autoimmune and inflammatory diseases are a diverse group of complex diseases characterized by loss of self-tolerance causing immune-mediated tissue destruction. Just as in autoimmune diseases, in endometriosis similar immunologic alterations occur, such as an increase in the number and cytotoxicity of macrophages, polyclonal increase in the activity of B lymphocytes, abnormalities in the functions and concentrations of B and T lymphocytes, and reduction in number or activity of natural killer cells. Furthermore, the presence of specific antiendometrial and antiovary antibodies was found both in endometriosis and infertility. Genetic factors play a role in the pathogenesis of endometriosis, and autoimmunity genes are therefore reasonable candidate genes for endometriosis and endometriosis-associated infertility. Single nucleotide polymorphisms are common in the human genome and affect the function of crucial components of the T-cell-antigen-receptor signaling pathways; they could have profound effects on the function of the immune system and thus on the development of autoimmune diseases. Here, we conducted a critical medical literature review about the possible role of genetic variants in autoimmune-related genes in the development of endometriosis.

Genomics and perinatal care.

Publicado em 05 de Janeiro de 12 pelo New England Journal of Medicine, disponível no Pub Med.


Advances in genomic technologies and methods of assisted reproduction have opened up new possibilities for testing and screening of prospective parents, their fertilized eggs, their fetuses, and their newborn babies.

The role of age, environmental and occupational factors on semen density.

Publicado Dezembro de 11pela Ann Agric Environ Med., disponível no Pub Med.


The problem of effect of the environment on human reproduction has been in the focus of researchers’ interest for many years.

OBJECTIVE: To examine the relationship between semen density in males with reproduction problems, and their age, living and working conditions.

MATERIAL AND METHOD: The study covered 224 males with reproduction problems. The study had a prospective character and was conducted in three stages – the first stage was carried out using the questionnaire devised by the authors; the second and the third stages consisted in the examination and evaluation of male semen density. Statistical analysis was used to search for the relationship between these groups and variables adopted in the study, i.e. age, occupation performed, place of residence, self-reported housing conditions and material standard, reporting by the males in the study of arduousness of work or health hazards perceived by the males examined, and duration of employment in such conditions.

RESULTS: The males in the study were divided into three groups according to their semen density. Group I (20 × 10(6) mln/ml or more) included 62 (27.7%) respondents, Group II (below 20 × 10(6) mln/ml) covered 121 males (54.0%),while Group III (only single spermatozoa or none) – 41 males (18.3%). Male semen density are significantly correlated with men’s ages and jobs as well as the general evaluations of the jobs held by the men (p<0.05). No significant relationship is observed between living conditions, arduous work conditions and occupational hazards as perceived by males, or duration of employment in such conditions, and male semen density (p>0.05).

CONCLUSIONS: The results obtained encourage continuation of the studies and cover a larger group of males with reproduction problems.

Occupational exposure to chemicals and fetal growth: the Generation R Study.

Publicado 02 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure to chemicals during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight.

METHODS: Associations between maternal occupational exposure to various chemicals and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002-2006),the Generation R Study. Mothers who filled out a questionnaire during mid-pregnancy (response: 77% of enrolment) were included if they conducted paid employment during pregnancy and had a spontaneously conceived singleton live born pregnancy (n = 4680). A job exposure matrix was used, linking job titles to expert judgement on exposure to chemicals in the workplace. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. Placental weight was obtained from medical records and hospital registries. Linear regression models for repeated measurements were used to study the associations between maternal occupational exposure to chemicals and intrauterine growth.

RESULTS: We observed that maternal occupational exposure to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds and pesticides adversely influenced several domains of fetal growth (fetal weight, fetal head circumference and fetal length). We found a significant association between pesticide and phthalate exposure with a decreased placental weight.

CONCLUSIONS: Our results suggest that maternal occupational exposure to several chemicals is associated with impaired fetal growth during pregnancy and a decreased placental weight. Further studies are needed to confirm these findings and to assess post-natal consequences.

Similarly increased congenital anomaly rates after intrauterine insemination and IVF technologies: a retrospective cohort study.

Publicado 02 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


While intrauterine insemination (IUI),a simple, inexpensive and non-invasive technique, is the most used assisted reproduction technology (ART) worldwide, the risk of major birth defects following IUI is paradoxically not well documented.

METHODS:Retrospective cohort study performed in Burgundy, France, over a 9-year period which consisted of the cross analysis of two prospective databases, the Burgundy perinatal network database and the database of the assisted conception units in Burgundy. A total of 1348 ART singletons [in vitro fertilization technologies (IVFT): n= 903; IUI: n= 445] matched with 4044 infants conceived naturally, 552 ART twins (IVFT: n= 362; IUI: n= 190) matched with 1656 twins who were conceived naturally. The major birth defects were categorized according to the European Surveillance of Congenital Anomalies classification EUROCAT.

RESULTS: Compared with naturally conceived singletons, singletons born after IUI and IVFT had a higher prevalence of major congenital malformations, with adjusted odd ratios (AOR) of 2.0 [95% confidence interval (CI) 1.0-3.8] and 2.0 (CI 1.3-3.1); 3.6 and 4.2% of infants born, respectively. All twins and unlike-sex twins born after IVFT but not IUI, have an increased prevalence of major birth defects compared with naturally conceived twins; AOR of 3.0 (CI 1.6-5.6) and 3.7 (CI 1.1-16.9),respectively. When comparing IUI with IVFT, no differences were observed for singletons (AOR 1.0; CI 0.4-2.2),all twins (AOR 0.4; CI 0.1-1.2) and unlike-sex twins (AOR 0.3; CI 0.1-4.5).

CONCLUSIONS:The risk of major birth defects in singletons conceived through IUI was increased over naturally conceived singletons. This risk was no different from that observed after IVFT.

Influence of prenatal organohalogen levels on infant male sexual development: sex hormone levels, testes volume and penile length.

Publicado 02 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


Prenatal exposure to endocrine disruptors, like organohalogen compounds (OHCs),might be responsible for the increased aberrations in human male sexual development (hypospadias, cryptorchidism, testicular cancer and fall in sperm count) observed over the past decades. This development is established during fetal life, and reflected in sex hormone levels, testes volume and penile length post-partum. The present study investigates the correlation between prenatal OHC levels and male sexual development outcomes.

METHODS AND RESULTS: Levels of eight neutral [2,2′-bis-(4-chlorophenyl)-1,1′-dichloroethene (4,4′-DDE),2,2′,4,4′,5,5′-hexachlorobiphenyl, 2,2′,4,4′-tetrabromodiphenyl ether (BDE)-47, -99, -100, -153, -154 and 1,2,5,6,9,10-hexabromocyclododecane, HBCDD] and four phenolic [(pentachlorophenol (PCP),4OH-CB-107 (4-hydroxy-2,3,3′,4′,5-pentachlorobiphenyl),-146 and -187)] OHCs were determined in 55 maternal serum samples taken at 35 weeks of pregnancy. Eight sex development-related hormones [testosterone, free testosterone, sex hormone-binding globulin (SHBG); LH, FSH, estradiol (E(2)),free E(2) (FE(2)) and inhibin B (InhB)] were determined in their sons at 3 months of age, and testes volume and penile length at 3 and 18 months of age. The following prenatal OHC levels correlated significantly with sex hormone levels: PCP with SHBG and InhB (ρ = 0.30 and -0.43, respectively),4OH-CB-107 with testosterone (ρ = 0.31) and BDE-154 with FE(2),E(2) and InhB (ρ = 0.49, 0.54 and 0.34, respectively). BDE-154 levels correlated positively with testes volume at 18 months of age (ρ = 0.34).

CONCLUSIONS: Prenatal OHC exposure is correlated with aspects of sexual development outcome in boys up to 18 months of age.

Mitochondrial haplotype does not influence sperm motility in a UK population of men.

Publicado 02 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


Sperm motility is regulated by mitochondrial enzymes that are partially encoded by mitochondrial DNA (mtDNA). MtDNA has therefore been suggested as a putative genetic marker of male fertility. However, recent studies in different populations have identified both significant and non-significant associations between mtDNA variation and sperm motility. Here, we tested whether mtDNA variation was associated with sperm motility in a large cohort of men from the UK, to test the robustness of previous studies and the reliability of mtDNA as a marker of poor sperm motility.

METHODS: A total of 463 men attending for semen analysis as part of infertility investigations were recruited from a UK laboratory. Sperm motility was measured using both computer-assisted sperm analysis and traditional manual measurements. MtDNA haplogroup and haplotype were determined in 357 and 298 men, respectively, using single nucleotide polymorphism (SNP) markers throughout the mtDNA genome, and compared with sperm motility data. The linkage between the SNP markers, and possible associations between individual SNPs and motility, were also investigated.

RESULTS: We found no statistical association between haplogroup or haplotype and sperm motility, regardless of how it was measured (P > 0.05 in all cases). Moreover, individual SNPs which were in linkage disequilibrium and dispersed across the mitochondrial genome, and therefore sensitive to mtDNA variation, were not predictive of sperm motility.

CONCLUSIONS: Mitochondrial haplotype is unlikely to be a reliable genetic marker of male factor infertility.

Expression pattern of osteopontin and αvβ3 integrin during the implantation window in infertile patients with early stages of endometriosis.

Publicado 02 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


To study endometrial receptivity in terms of osteopontin (OPN) and αvβ3 integrin expression and co-expression in infertile women with early stages of endometriosis.

METHODS: We investigated the immunohistochemical expression and co-expression of OPN and αvβ3 integrin in the endometrium of 20 infertile patients with Stage I or II endometriosis as the only detectable cause of infertility, 20 infertile patients with unexplained infertility and 20 fertile women undergoing tubal sterilization. Two endometrial biopsies were performed during a single menstrual cycle (postovulatory Day +7 to +8 and 4 days later) in each subject.

RESULTS:No statistically significant differences regarding OPN and αvβ3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvβ3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied.

CONCLUSIONS: Endometrial OPN and αvβ3 integrin expression or co-expression is not impaired during the window of implantation in patients with Stage I-II endometriosis. Further studies are needed to determine whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with these markers of implantation.

Individual serum levels of anti-Mullerian hormone in healthy girls persist through childhood and adolescence: a longitudinal cohort study.

Publicado 02 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


In adult women, the circulating level of anti-Müllerian hormone (AMH) is a novel marker of ovarian function, as it reflects the number of remaining ovarian follicles. Therefore, AMH has gained widespread attention in fertility clinics, and a low AMH is believed to predict impaired fertility and imminent menopause. However, the natural course of circulating AMH levels during female childhood and adolescence is not known.

METHODS: Serum levels of AMH and FSH were measured in girls participating in The COPENHAGEN Puberty Study. Longitudinal part: 85 healthy girls and adolescents were examined, and blood samples were drawn every 6 months for an average of 3 years: median (range) number of samples per girl was 6 (2-10),age at baseline was 9.2 (5.9-12.9) years. Cross-sectional part: 224 prepubertal girls (age 8.3, 5.6-11.7 years) were examined and each girl had one blood sample drawn.

RESULTS: The individual mean AMH levels in girls followed longitudinally ranged from 5 to 54 pmol/l (median 18 pmol/l). The mean intra-individual coefficient of variation of AMH was 22% (range 0-54%). Overall, each girl maintained her AMH level throughout childhood and adolescence although minor, but significant, changes occurred during pubertal transition. In prepubertal girls, AMH was negatively correlated with FSH (r = -0.31, P < 0.001). Twelve per cent (10/85) had mean AMH below a cut-off value of 8 pmol/l, indicating that the interpretation of low AMH as a marker of approaching menopause may not apply to pre- and peri-pubertal girls.

CONCLUSIONS: Circulating AMH exhibits only minor fluctuations during childhood and adolescence, and a random AMH measurement seems representative for a given girl. The negative AMH-FSH correlation in prepubertal girls supports the notion that AMH is a quantitative marker of ovarian follicles even in young girls.

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