Atualizações científicas – 09 a 13 de janeiro de 2012

Publicado em: 17 de Janeiro de 2012

Novos artigos sobre reprodução humana foram publicados na última semana. Saiba mais com a leitura do resumo dos principais artigos a seguir:

Patient-focused Internet interventions in reproductive medicine: a scoping review

Publicado em 22 de Novembro de 11 pela Human Reproduction Update, disponível no Oxfor Journal.


The Internet has revolutionized fertility care since it became a popular source of information and support for infertile patients in the last decade. The aim of this scoping review is to map (i) the main categories of patient-focused Internet interventions within fertility care, (ii) the detailed composition of the interventions and (iii) how these interventions were evaluated.

METHODS: A literature search used various ‘Internet’ and ‘Infertility’ search terms to identify relevant studies published up to 1 September 2011. The selected studies had to include patients facing infertility and using an infertility-related Internet intervention. We charted data regarding categories of interventions, components of interventions and evaluation methodology. We categorized the stages of research using the UK’s Medical Research Council framework for evaluating complex interventions.

RESULTS: We included 20 studies and identified 3 educational interventions, 2 self-help interventions, 1 human-supported therapeutic intervention, 9 online support groups and 2 counselling services. Information provision, support and mental health promotion were common aims. Few interactive online components were present in the online programmes. Three studies were in the pilot phase and 17 were in the evaluation phase.

CONCLUSIONS: Several categories of patient-focused Internet-based interventions in fertility care are primarily applied to provide support and education and promote mental health. The interventions could be improved by using more interactive and dynamic elements as their key components. Finally, more emphasis on methodological standards for complex interventions is needed to produce more rigorous evaluations. This review shows where further development or research into patient-focused Internet interventions in fertility-care practice may be warranted.


Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis

Publicado em 22 de Novembro de 11 pela Human Reproduction Update, disponível no Oxfor Journal.


Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with cardiovascular disease (CVD) risk factors and metabolic disturbances. This systematic review and meta-analysis was conducted to determine whether carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is higher in women with PCOS compared with women without PCOS.

METHODS: Primary articles reporting the mean CIMT in women with PCOS and controls were identified using Ovid MEDLINE, EMBASE and PUBMED. We performed a random-effects meta-analysis and created forest plots of the mean difference in CIMT and conducted tests for heterogeneity and publication bias. Studies were grouped by quality, defined by reporting reproducibility of CIMT and averaging both common carotid arteries versus one side for CIMT.

RESULTS: From the 36 eligible full-text studies, 8 studies were included in the systematic review and 19 studies were included in the meta- analysis (total n 1⁄4 1123 women with PCOS, n 1⁄4 923 controls). The summary mean difference in CIMT among women with PCOS compared with controls was 0.072 mm [95% confidence interval (CI) 0.040, 0.105, P , 0.0001] for highest quality studies, 0.084 mm (95% CI 0.042,0.126, P 1⁄4 0.0001) for good quality studies, 0.041 (95% CI 20.038, 0.120, P 1⁄4 0.310) for fair-quality studies and 0.045 (95% CI 20.020, 0.111, P 1⁄4 0.173) for lower quality studies.

CONCLUSIONS: Larger studies with a well-defined PCOS population using rigorous methodology may be required to draw a more robust conclusion. However, these results suggest women with PCOS are at a greater risk of premature atherosclerosis, which emphasizes the importance of screening and monitoring CVD risk factors in women with PCOS.

Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society

Publicado em 06 de Novembro de 11 pela Human Reproduction Update, disponível no Oxfor Journal.


Hirsutism, defined by the presence of excessive terminal hair in androgen-sensitive areas of the female body, is one of the most common disorders in women during reproductive age.

METHODS: We conducted a systematic review and critical assessment of the available evidence pertaining to the epidemiology, patho- physiology, diagnosis and management of hirsutism.

RESULTS: The prevalence of hirsutism is 10% in most populations, with the important exception of Far-East Asian women who present hirsutism less frequently. Although usually caused by relatively benign functional conditions, with the polycystic ovary syndrome leading the list of the most frequent etiologies, hirsutism may be the presenting symptom of a life-threatening tumor requiring immediate intervention.

CONCLUSIONS: Following evidence-based diagnostic and treatment strategies that address not only the amelioration of hirsutism but also the treatment of the underlying etiology is essential for the proper management of affected women, especially considering that hirsutism is, in most cases, a chronic disorder needing long-term follow-up. Accordingly, we provide evidence-based guidelines for the etiological diagnosis and for the management of this frequent medical complaint.

Patient preferences for characteristics differentiating ovarian stimulation treatments.

Publicado em 12 de janeiro de 12 pela Human Reproduction, disponível no Pub Med.


Little is known concerning patient preferences for IVF treatments. The objective of this study was to elicit patient preferences for characteristics differentiating ovarian stimulation treatments.METHODSWomen undergoing IVF were recruited from six clinics in Sweden between May 2010 and December 2010. Included patients completed a study questionnaire consisting of one contingent valuation (CV) question (with six different bids) and 16 conjoint analysis (CA) questions formulated as discrete choices between two hypothetical ovarian stimulation treatments (defined in terms of manufacturing method, method of administration, time required for administration, dose variability and hypothetical price). Patient preferences were derived using multinomial logit modelling.

RESULTS: The final study population consisted of 294 women (mean age of 35). Respondents were willing to pay €360 [95% confidence interval (CI): €340-€390] to receive FSH derived from DNA technology instead of highly purified extract from urine from post-menopausal women, €300 (95% CI: €280-€320) to administer the FSH using a prefilled injection pen instead of a conventional syringe, €30 (95% CI: €20-€40) per saved minute required for administration and €530 (95% CI: €500-€570) to reduce the dose variability from 10-20% to 1-2% (P< 0.001 for all estimates). The result from the CV was similar to the CA.

CONCLUSIONS: Women undergoing IVF place significant value on characteristics differentiating ovarian stimulation treatments. Product-specific aspects should be taken into account by decision-makers when discriminating between commercial gonadotrophins in clinical practice to align health-care decision-making with patient preferences and potentially improve the effectiveness of IVF interventions through enhanced patient satisfaction and treatment compliance. Preferences for treatment characteristics should also be considered in evaluations of ovarian stimulation products to capture their true value from a patient perspective.

Global gene analysis of oocytes from early stages in human folliculogenesis shows high expression of novel genes in reproduction

Publicado em Dezembro de 11 pela Mol Hum Reprod., disponível no Pub Med.


The pool of primordial follicles in humans are laid down during embryonic development and follicles can remain dormant for prolonged intervals, often decades, until individual follicles resume growth. The mechanisms that induce growth and maturation of primordial follicles are poorly understood but follicles once activated either continue growth or undergo atresia. We have isolated pure populations of oocytes from human primordial, intermediate and primary follicles using laser capture micro-dissection microscopy and evaluated the global gene expression profiles by whole genome microarray analysis. The array data was confirmed by qPCR for selected genes.A total of 6,301 unique genes were identified as significantly expressed representing enriched specific functional categories such as ‘RNA binding’, ‘translation initiation’ and ‘structural molecule activity’. Several genes, some not previously known to be associated with early oocyte development, were identified with exceptionally high expression levels, such as the anti-proliferative transmembrane protein with an EGF-like and two follistatin-like domains (TMEFF2), the Rho-GTPase activating protein oligophrenin 1 (OPHN1) and the mitochondrial encoded ATPase6 (ATP6). Thus, the present study provides not only a technique to capture and perform transcriptome analysis of the sparse material of human oocytes from the earliest follicle stages but further includes a comprehensive basis for our understanding of the regulatory factors and pathways present during early human folliculogenesis.

Array comparative genomic hybridization in male infertility

Publicado em 11 de Janeiro de 12 pela Human Reproduction disponível no Pub Med.


Male infertility caused by a maturation arrest of spermatogenesis is a condition with an abrupt stop in spermatogenesis, mostly at the level of primary spermatocytes. The etiology remains largely unknown.

METHODS: We focused on patients with a complete arrest at the spermatocyte level (n = 9) and used array comparative genomic hybridization to screen for deletions or duplications that might be associated with maturation arrest. Interesting copy number variations (CNVs) were further examined by using quantitative PCR. Where appropriate, the expression pattern was analyzed in multiple human tissues including the testis.

RESULTS:A total of 227 CNVs were detected in the patient group. After the elimination of CNVs that were also present in the control group or that were not likely to be involved in male infertility, the remaining 11 regions were investigated more in detail. We first determined the expression pattern of seven genes, for which expression had not been reported to be investigated in testicular tissue, after which one region could be eliminated. Next, all 10 promising candidate regions were analyzed by quantitative PCR in a control population.

CONCLUSIONS:Eight deletions/duplications were absent in our control group, and therefore might be linked with the male infertility in our patients. One of these alterations, however, has been detected in a proven fertile father group. Further research is necessary to determine the relationship between the observed genomic alterations and maturation arrest of spermatogenesis. Furthermore, several of the above genes have not been studied at the functional level and consequently, more research is required to determine their role in spermatogenesis.

Robotic treatment of colorectal endometriosis: technique, feasibility and short-term results

Publicado em 11 de Janeiro de 12 pela Human Reproduction disponível no Pub Med.


Deep infiltrating endometriosis (DIE) is a complex disease that impairs the quality of life and the fertility of women. Since a medical approach is often insufficient, a minimally invasive approach is considered the gold standard for complete disease excision. Robotic-assisted surgery is a revolutionary approach, with several advantages compared with traditional laparoscopic surgery.

METHODS: From March 2010 to May 2011, we performed 22 consecutive robotic-assisted complete laparoscopic excisions of DIE endometriosis with colorectal involvement. All clinical data were collected by our team and all patients were interviewed preoperatively and 3 and 6 months post-operatively and yearly thereafter regarding endometriosis-related symptoms. Dysmenorrhoea, dyschezia, dyspareunia and dysuria were evaluated with a 10-point analog rating scale.

RESULTS: There were 12 patients, with a median larger endometriotic nodule of 35 mm, who underwent segmental resection, and 10 patients, with a median larger endometriotic nodule of 30 mm, who underwent complete nodule debulking by colorectal wall-shaving technique. No laparotomic conversions were performed, nor was any blood transfusion necessary. No intra-operative complications were observed and, in particular, there were no inadvertent rectal perforations in any of the cases treated by the shaving technique. None of the patients had ileostomy or colostomy. No major post-operative complications were observed, except one small bowel occlusion 14 days post-surgery that was resolved in 3 days with medical treatment. Post-operatively, a statistically significant improvement of patient symptoms was shown for all the investigated parameters.

CONCLUSIONS: To our knowledge, this is the first study reporting the feasibility and short-term results and complications of laparoscopic robotic-assisted treatment of DIE with colorectal involvement. We demonstrate that this approach is feasible and safe, without conversion to laparotomy.

Anti-Mullerian hormone: clairvoyance or crystal clear?

Publicado em 11 de Janeiro de 12 pela Human Reproduction disponível no Pub Med.


The clinical use of anti-Müllerian hormone (AMH) has increased exponentially due to its unique relationship with the ovarian reserve and ability to predict ovarian response, facilitate pretreatment counselling and individualize treatment strategies to minimize the risk of ovarian hyperstimulation syndrome. There is now a rapidly increasing literature examining additional possibilities for AMH, all of which suggest that its reach extends far beyond the assisted conception clinic. The recognition that it is a significantly more accurate and reliable measure of ovarian reserve than the antral follicle count or FSH has led to its adoption by physicians to counsel women on their reproductive lifespan, the impact of gonadotoxic chemotherapy, radiotherapy and surgery on the ovarian reserve and allow polycystic ovarian syndrome to be diagnosed by primary care physicians. We propose that there is an adequate literature base to embrace this technology while continuing to develop and refine how AMH can optimize patient care.

The effect of the swim-up and hyaluronan-binding methods on the frequency of abnormal spermatozoa detected by FISH and SCSA in carriers of balanced chromosomal translocations

Publicado em Dezembro de 11 pela Human Reproduction disponível no Pub Med.


The swim-up and hyaluronan (HA)-binding methods are used for the selection of good quality spermatozoa to improve pregnancy rates and embryo quality and to reduce the number of miscarriages after IVF. We evaluated whether the processing of sperm by these methods reduces the frequency of spermatozoa with abnormal karyotypes and altered chromatin quality in balanced translocation carriers.

METHODS: Semen samples of 12 carriers of balanced chromosomal translocations were analysed for the frequency of spermatozoa, which are chromosomally unbalanced due to the segregation of balanced translocations, aneuploidies for chromosomes 7, 8, 13, 18, 21, X or Y, diploid sperm or sperm with fragmented DNA and poorly condensed chromatin. Results obtained by fluorescence in situ hybridization (FISH) and sperm chromatin structure assay were compared between ejaculated (n = 12), swim-up (n = 12) and HA-binding processed (n = 6) semen samples of the translocation carriers and with the control group (n = 10).RESULTSThe mean frequencies of unbalanced segregation products were 17.5 and 16.5% in neat and swim-up processed samples from Robertsonian translocation carriers, and 55.4, 54.5 and 50.9% in neat, swim-up and HA-bound sperm samples from reciprocal translocation carriers. Significant decreases in the frequency of sperm showing chromosome 18 and XY disomy and of diploidy, and in the rates of high-density staining sperm were observed in the motile swim-up fractions. There were significantly more sperm showing fragmented chromatin in the group of translocation carriers than in the control group, but no differences in the aneuploidy and diploidy rates were observed.

CONCLUSIONS: The swim-up method is suitable for selection of sperm with condensed chromatin and a lower frequency of some aneuploidies and of diploidy. The frequency of spermatozoa chromosomally unbalanced due to the segregation of reciprocal (but not Robertsonian) translocations is significantly lower in HA-bound sperm. However, the advantages of either method for selecting normal sperm are limited.

The use of power Doppler colour scoring to predict successful expectant management in women with an incomplete miscarriage

Publicado em 9 de Janeiro de 12 pela Human Reproduction disponível no Pub Med.


OBJECTIVE:To evaluate whether the use of power Doppler to confirm the presence or absence of blood flow within retained products of conception (RPC) in women with  an incomplete miscarriage can predict subsequent successful expectant management.METHODSProspective observational study in the Acute Gynaecology and

Early Pregnancy Unit (AGEPU) at Nepean Hospital from November 2006 to February 2009. Incomplete miscarriage was defined by the presence of a measurable focus of hyperechoeic material, in three planes, within the endometrial cavity using two-dimensional greyscale transvaginal ultrasound (TVS). Subjective qualitative power Doppler colour scoring (PDCS) of the RPC was performed. The vascularization of the RPC was scored using the colour scoring system of the International Ovarian Tumour Analysis (IOTA) group. PDCS 1 meant absence of vascularity, PCDS 2 represented minimal vascularity, PDCS 3 rather strong vascularity and PDCS 4 very strong vascularity. The correlation between the PDCS and successful expectant management of miscarriage was analysed. The volume of RPC was calculated using the ellipsoid formula and then compared with both the PDCS and the outcome of expectant management. Successful expectant management was defined as the resolution of symptoms and the absence of RPC on follow-up TVS.

RESULTS: A total of 1395 consecutive pregnant women underwent TVS. Of them, 198 women were diagnosed with an incomplete miscarriage; 172 were managed expectantly. Complete data were available on 158 cases. In total 84.8% (134/158) were managed successfully whilst 15.2% (24/158) failed expectant management. Of the total, 89% (121/136) of women with a PDCS 1 had successful expectant management compared with 57.1 (8/14) with PDCS 2 and 62.5% (5/8) with PDCS 3. Comparing absence of flow (PDCS 1) to presence of flow (PDCS 2 or more), the rate of success was significantly higher in the first group (89 versus 60.9%, Fisher’s exact test P= 0.00136). In the prediction of success, the absence of flow showed a sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of 90.3, 37.5, 89, 40.9% and 1.445 (95% confidence interval: 1.055-1.979), respectively. There was no correlation between the volume of RPC and the PDCS; and there was no relationship between the volume of RPC and the success of expectant management.

CONCLUSIONS: PDCS can predict the likelihood of successful expectant management of incomplete miscarriage. The absence of flow on power Doppler is associated with a significant improvement in the rate of successful expectant management. This new approach may be helpful in quantifying the chances of successful expectant management in those women with an incomplete miscarriagee at the primary scan.

Conteúdo atualizado em: 17 de Abril de 2014

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