Clipping - Clínica Fecondare

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Relatório 23.07.2012 Fecondare Clipping Conteúdo publicado na web: Artigos científicos e
notícias sobre a Reprodução Humana e Andrologia
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Sumário
Artigos Científicos ..................................................................................................................................................... 5 1. Sacrococcygeal neurofibroma: rare cause for chronic pelvic pain…………………………...5 2. Implications of oocyte cryostorage for the practice of oocyte donation…………………..5 3. Dexamethasone Induces Germ Cell Apoptosis in the Human Fetal Ovary………………..6 4. Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women………………………………………………………………………………………………………………………..7 5. A randomized controlled dose-­‐response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization……………8 6. A reliable procedure for decontamination before thawing of human specimens cryostored in liquid nitrogen: three washes with sterile liquid nitrogen (SLN(2))………...10 7. Human somatic cell nuclear transfer and cloning………………………………………………...11 8. The influence of the type of embryo culture medium on neonatal birthweight after single embryo transfer in IVF……………………………………………………………………………………..11 9. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-­‐analysis……………………………………………………………………………………………………...13 10. Fetal-­‐Specific CD8+ Cytotoxic T Cell Responses Develop during Normal Human Pregnancy and Exhibit Broad Functional Capacity……………………………....14 11. Intravenous Immunoglobulin for Repeated IVF Failure and Unexplained Infertility……………………………………………………………………………………………….15 Notícias da Web: ..................................................................................................................................................... 16 12. Entire genome of human sperm sequenced for the first time…………………………….....16 13. Mothers who use fertility drugs may have shorter kids………………………………………..17 14. Vida na cidade grande pode piorar problemas de fertilidade..............................................19 Notícias da Clínica e Equipe Fecondare ....................................................................................................... 20 Clínica
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Clipagem - premissas
A clipagem médica tem o objetivo de fornecer aos profissionais da área da saúde atualizações científicas de sua especialidade. Essas atualizações possuem duas funções principais: 1.
Atualizar do corpo clínico, mantendo-­‐o informado das novidades da área; e 2.
Ser base para o desenvolvimento de artigos informativos, que poderão ser veiculados pelo site e mídias sociais da instituição. Para desenvolver o trabalho de clipagem, são feitas pesquisas em bancos de dados renomados no meio científico, bem como notícias sobre os temas definidos em veículos de grande circulação, sites de associações ou blogs, conforme especificado a seguir: Diretórios científicos: Sites temáticos: • Pubmed • Sociedades brasileiras • Portal do Ministério da Saúde • Blogs de profissionais referência na • Bireme -­‐ artigos brasileiros área • Scielo • Cochrane BVS o The Cochrane Library o Biblioteca Cochrane Plus • Resumos de Revisões Sistemáticas em Português Veículos de ampla circulação: Para as pesquisas, são utilizadas as seguintes palavras-­‐chave: • Jornal Estadão • Human reproduction • Jornal Folha de São Paulo • Andrologia • O Globo • Male infertility • Entre outros • Female infertility • Conception 4 Clínica
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Artigos Científicos
TEMA: Atualizações em Infertilidade Masculina, Infertilidade
Feminina e Reprodução Humana
1.
Sacrococcygeal neurofibroma: rare cause for chronic pelvic pain. Veículo: J Minim Invasive Gynecol Data: Julho de 2012 Fonte: PubMed Paul PG, Pravinkumar T, Sheetal B. Paul's Hospital, Centre For Advanced Endoscopy & Infertility Treatment, Cochin, Kerala, India. Resumo: Pelvic pain is a common gynecologic complaint. Retroperitoneal pelvic tumors are rarely a cause of pelvic pain. Neurofibroma is an uncommon pelvic retroperitoneal tumor, and only 17 cases are reported to date. A 38-­‐year-­‐old woman with chronic pelvic pain had a soft fixed mass that was the size of an orange in the right posterolateral fornix, with a normal uterus on pelvic examination, and a mass of 6.3 × 5.2 cm with mixed echotexture on the right side separate from both ovaries on transvaginal ultrasonography. A provisional diagnosis of retroperitoneal mass probably a retroperitoneal teratoma was made. Laparoscopy was performed; an ill-­‐defined retroperitoneal soft tissue mass of about 6 cm was seen on the right pararectal and presacral area, displacing the rectum toward the left side. The mass was soft and jellylike without a cyst wall. Histopathologic study and immunohistochemistry results were consistent with neurofibroma of the sacrococcygeal regions. To our knowledge this is the third case of sacrococcygeal neurofibroma treated by complete laparoscopic excision. Gynecologists should keep sacrococcygeal neurofibroma as a differential diagnosis of pelvic pain with atypical location of a pelvic mass. A high index of suspicion and an appropriate imaging technique are needed for accurate diagnosis. Laparoscopy seems to be a safe and effective method of managing retroperitoneal presacral neurofibromas. 2.
Implications of oocyte cryostorage for the practice of oocyte donation. Veículo: Hum Reprod. Data: 15 de julho de 2012 5 Clínica
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Fonte: OxforJournal Mertes H, Pennings G, Dondorp W, de Wert G. Bioethics Institute Ghent, Ghent University, Ghent, Belgium. Resumo: Artigo original na íntegra disponibilizado pela equipe E-­‐saúde encontra-­‐se no anexo. As the efficiency of oocyte cryopreservation has increased rapidly in recent years, oocytes are currently being stored either in the course of IVF treatments or as a fertility preservation measure. These practices may have an impact on the number of available donor oocytes due to two different dynamics: first, a certain percentage of women for whom oocytes were cryopreserved will eventually not use their oocytes and may decide to donate them to others; secondly, especially in the practice of social freezing, women may opt to donate a portion of the retrieved oocytes in 'freeze-­‐and-­‐share' schemes in order to reduce the costs. In this article, we aim to sketch the ethical implications of such developments in general and the issue of payment to oocyte donors in particular. 3.
Dexamethasone Induces Germ Cell Apoptosis in the Human Fetal Ovary. Veículo: J Clin Endocrinol Metab. Data: 16 de julho de 2012 Fonte: PubMed Poulain M, Frydman N, Duquenne C, N'tumba-­‐Byn T, Benachi A, Habert R, Rouiller-­‐Fabre V, Livera G. Commissariat à l'Energie Atomique (M.P., N.F., C.D., T.N'T.-­‐B., R.H., V.R.-­‐F., G.L.), Direction des sciences du vivant/Institut de radiobiologie cellulaire et moléculaire/Service cellules souches et radiation/ Laboratoire de Développement des Gonades (LDG), Unité Cellules Souches et Radiation; Université Paris-­‐Diderot (C.D., T.N'T.-­‐B., R.H., V.R.-­‐F., G.L.), Sorbonne Paris Cité, LDG, Unité Mixte de Recherche (UMR)-­‐967; Institut National de la Santé et de la Recherche Médicale Unité 967 (M.P., N.F., C.D., N.N'T.-­‐B., R.H., V.R.-­‐F., G.L.); and Université Paris-­‐Sud (M.P., N.F.), LDG, UMR-­‐967, F-­‐92265 Fontenay aux Roses, France; and Assistance Publique-­‐Hôpitaux de Paris, Unité de Biologie de la Reproduction(A.B., M.P., N.F.) and Service de Gynécologie-­‐Obstétrique et Médecine de la Reproduction (A.B.), Hôpital Antoine Béclère, and Université Paris-­‐Sud (A.B.), Clamart, F-­‐92140, France. Resumo: Artigo original na íntegra disponibilizado pela equipe E-­‐saúde encontra-­‐se no anexo. CONTEXT: The 21-­‐hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia. Pregnant women presenting a risk of genetic transmission may be treated with synthetic glucocorticoids such as dexamethasone (DEX) to prevent female fetus 6 Clínica
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virilization. OBJECTIVE: The aim of this study was to assess the potential deleterious effects of DEX exposure on fetal ovarian development.Settings:Human fetal ovaries, ranging from 8-­‐11 weeks after fertilization, were harvested from material available after legally induced abortions. They were cultured in the absence or presence of DEX (2, 10, or 50 μm) over 14 d, and histological analyses were performed. RESULTS: The glucocorticoid receptor NR3C1 was present and the signaling pathway active in the fetal ovary as demonstrated by the expression of NR3C1 target genes, such as PLZF and FKBP5, in response to DEX exposure. DEX decreased germ cell density at the 10 and 50 μm doses. Exposure to DEX, even at the highest dose, did not change oogonial proliferation as monitored by 5-­‐bromo-­‐2'-­‐deoxyuridine incorporation and significantly increased the apoptotic rate, detected with cleaved caspase 3 staining. Interestingly, the expression of the prosurvival gene KIT was significantly decreased in the presence of DEX during the course of the culture. CONCLUSION: We have demonstrated for the first time that in vitro exposure to high doses of DEX impairs human fetal oogenesis through an increase in apoptosis. These data are of high importance, and additional epidemiological studies are required to investigate the female fertility of those women who have been exposed to DEX during fetal life. 4.
Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women. Veículo: Hum Reprod. Data: 14 de julho de 2012 Fonte: OxforJournal Zhu L, Li Y, Xu A. Department of Reproductive Medicine, Xiangya Hospital, Central-­‐south University, Changsha City, Hunan Province, P.R. China. Resumo: Artigo original na íntegra disponibilizado pela equipe E-­‐saúde encontra-­‐se no anexo. STUDY QUESTION Is there a difference in the characteristics of uterine peristalsis in natural and controlled ovarian hyperstimulation (COH) cycles? SUMMARY ANSWER COH significantly changed the uterine peristaltic pattern.WHAT IS KNOWN ALREADYIn natural menstrual cycles, the periodic changes of uterine peristalsis are closely related to the reproductive process. STUDY DESIGN, SIZE, DURATION This is a prospective cohort study with a total of 64 subjects involved. The study was performed between May 2011 and August 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS Sixty-­‐four infertile women with regular, 7 Clínica
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ovulatory menstrual cycles underwent follicular tracking in one natural cycle and after ovarian stimulation (GnRH-­‐agonist down-­‐regulation) in the subsequent cycle (COH). Three time points were studied in both cycles: at LH surge/HCG plus 1 day, ovulation/oocyte retrieval and 2 days after ovulation/retrieval. The study was performed in an IVF center of the university-­‐affiliated Xiangya hospital. MAIN RESULTS AND THE ROLE OF CHANCE Uterine peristaltic wave frequency was 1.31 times higher in the COH than in the natural cycle (P< 0.01). At all three time points in the COH cycle, waves moving from the cervix to fundus dominated, comprising 80-­‐90% of the wave types observed, while 'no activity' was more frequently observed in the natural cycle. The wave frequency was positively correlated with the level of serum estradiol (E(2)) (r= 0.30; P< 0.01) and negatively correlated with the progesterone level (r= -­‐0.48; P< 0.01) for the physiological range of steroid levels. No correlation was found between the wave frequency and supraphysiological concentrations of E(2) or progesterone. LIMITATIONS, REASONS FOR CAUTIONThe two observers were not independent and this was a limitation of the study. Quantitative measurements of wave amplitude in the different cycles should be compared in future research. WIDER IMPLICATIONS OF THE FINDINGS Uterine peristalsis was much higher in the COH cycle than in the natural cycle. The endometrial movements did not weaken to the natural level before embryo transfer, even with high levels of progesterone. The wave frequency was positively correlated with serum E(2) level and negatively correlated with that of progesterone within the physiological range. No correlation was found between the wave frequency and supraphysiological concentrations of E(2) and progesterone.STUDY FUNDING/COMPETING INTEREST(S)The authors declare that they have no study funding or competing interests in this study. 5.
A randomized controlled dose-­‐response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization. Veículo: Hum Reprod. Data: 12 de julho de 2012 Fonte: OxforJournal Thuesen LL, Loft A, Egeberg AN, Smitz J, Petersen JH, Nyboe Andersen A. The Fertility Clinic, Section 4071, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Resumo: STUDY QUESTION Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? 8 Clínica
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SUMMARY ANSWER Supplementation with hCG from the first day of stimulation may increase the number of top-­‐quality embryos per patient. Daily doses of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-­‐response was seen for pre-­‐ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Prospective multicentre studies have indicated increased live birth rates and increased number of top-­‐quality embryos when low doses of hCG were associated with FSH. We analysed the clinical, embryological and endocrine aspects of adding increasing doses of hCG to rFSH from the first day of stimulation for IVF. DESIGN A prospective randomized, controlled, open-­‐label dose-­‐response pilot study was conducted between February 2009 and June 2010 at Copenhagen University Hospital, Rigshospitalet, Denmark. Adequate allocation concealment was assured from sequentially numbered, opaque, sealed envelopes prepared from a computer-­‐generated list. Scoring of the embryos was done in an assessor-­‐blinded way. PARTICIPANTS AND SETTING Endocrinologically normal IVF patients aged 25-­‐37 years, BMI 18-­‐30 kg/m(2), regular cycles and FSH <12 IU/l, were treated with a fixed dose of rFSH 150 IU/day and randomized to daily hCG dose of 0, 50, 100 or 150 IU from Day 1 of stimulation. Primary end-­‐point was the total number of top-­‐quality embryos on Day 3. DATA ANALYSIS METHOD Data were analysed by analysis of variance, Kruskal-­‐Wallis test, chi-­‐squared test or Poisson distribution count. MAIN FINDINGS A total of 62 patients were randomized into four hCG dose groups: Dose 0 (D0; n= 16), Dose 50 (D50; n= 15), Dose 100 (D100; n= 16) and Dose 150 (D150; n= 15). Two patients in D150 were withdrawn after randomization because of major (10-­‐ to 30-­‐
fold) hCG dosing errors, leaving 13 patients in this group. Thus, the results are based on the per protocol population. The mean numbers of top-­‐quality embryos per patient were D0: 0.8 ± 1.2, D50: 0.5 ± 0.7, D100: 1.2 ± 1.7 and D150: 1.5 ± 1.7 (P= 0.04). All pregnancies were singleton gestations, and the live birth rates per started cycle were D0: 25%, D50: 27%, D100: 25% and D150: 31% (P= 0.98). Steady state level of serum (s)-­‐hCG was reached on Day 6 of stimulation. S-­‐hCG levels (IU/l) on the day of hCG administration were D0: <0.1, D50: 3.1 (2.6-­‐3.6), D100: 5.5 (4.1-­‐7.4) and D150: 11.0 (8.9-­‐13.6) (P< 0.01). The patients receiving hCG supplementation were stratified by 33 and 66% percentiles into three groups according to the concentration of s-­‐hCG on Day 6 of stimulation: 0.5-­‐3.5 IU/l (n= 16), 3.5-­‐8.0 IU/l (n= 14) and 8.0-­‐21.1 IU/l (n= 14). The mean numbers of top-­‐quality embryos in the three groups were 0.5 ± 0.9, 1.1 ± 1.8 and 1.5 ± 1.5, respectively (P= 0.03). The progesterone increments from stimulation Day 1 to the day of hCG triggering were D0 = 49%, D50 = 79%, D100 = 110% and D150 = 160% (P= 0.02). S-­‐androstenedione level was highest in D150 (P< 0.01). S-­‐E(2) was 2-­‐fold higher in the D100 and D 150 compared with D0 (P= 0.09). BIAS, LIMITATION, GENERALISABILITYOur study has a limited sample size. Supplementation with daily hCG dose up to 150 IU throughout stimulation has never been 9 Clínica
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used before. Hence, this had to be tested in a small study before conducting a larger trial. STUDY FUNDING/COMPETING INTERESTS Ferring Pharmaceuticals, Research and Development, provided funds for the endocrine measurements. CLINICALTRIAL.GOV REGISTRATIONNCT00844311. 6.
A reliable procedure for decontamination before thawing of human specimens cryostored in liquid nitrogen: three washes with sterile liquid nitrogen (SLN(2)). Veículo: Fertil Steril Data: 13 de julho de 2012 Fonte: PubMed Parmegiani L, Accorsi A, Bernardi S, Arnone A, Cognigni GE, Filicori M. Reproductive Medicine Unit, GynePro Medical Centers, Bologna, Italy. Resumo: OBJECTIVE: To report a washing procedure, to be performed as frozen specimens are taken out of cryobanks, to minimize the risk of hypothetical culture contamination during thawing. DESIGN: Basic research. SETTING: Private assisted reproduction center. INTERVENTION(S): Two batches of liquid nitrogen (LN(2)) were experimentally contaminated, one with bacteria (Pseudomonas aeruginosa, Escherichia coli, Stenotrophomonas maltophilia) and the other with fungi (Aspergillus niger). Two hundred thirty-­‐two of the most common humangamete/embryo vitrification carriers (Cryotop, Cryoleaf, Cryopette) were immersed in the contaminated LN(2) (117 in the bacteria and 25 in the fungi-­‐contaminated LN(2)). The carriers were tested microbiologically, one group without washing (control) and the other after three subsequent washings in certified ultraviolet sterile liquid nitrogen (SLN(2)). The carriers were randomly allocated to the "three-­‐wash procedure" (three-­‐wash group, 142 carriers) or "no-­‐wash" (control group, 90 carriers) using a specific software tool. MEAN OUTCOME MEASURE(S): Assessment of microorganism growth. RESULT(S): In the no-­‐wash control group, 78.6% of the carriers were contaminated by the bacteria and 100% by the fungi. No carriers were found to be contaminated, either by bacteria or fungi, after the three-­‐wash procedure. CONCLUSION(S): The three-­‐wash procedure with SLN(2) produced an efficient decontamination of carriers in extreme experimental conditions. For this reason, this procedure could be routinely performed in IVF laboratories for safe thawing 10 Clínica
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of human specimens that are cryostored in nonhermetical cryocontainers, particularly in the case of open or single-­‐straw closed vitrification systems. 7.
Human somatic cell nuclear transfer and cloning. Veículo: Fertil Steril. Data: 12 de julho de 2012 Fonte: OxforJournal The Ethics Committee of the American Society for Reproductive Medicine. American Society for Reproductive Medicine, Birmingham, Alabama. Resumo: Artigo original na íntegra disponibilizado pela equipe E-­‐saúde encontra-­‐se no anexo. This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-­‐6 8.
The influence of the type of embryo culture medium on neonatal birthweight after single embryo transfer in IVF. Veículo: Hum Reprod Data: 12 de julho de 2012 Fonte: OxforJournal Vergouw CG, Hanna Kostelijk E, Doejaaren E, Hompes PG, Lambalk CB, Schats R. IVF Center, Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam, PO Box 7057, 1007 MB, The Netherlands. Resumo: STUDY QUESTION Does the type of medium used to culture fresh and frozen-­‐thawed embryos influence neonatal birthweight after single embryo transfer (SET) in IVF? SUMMARY ANSWER A comparison of two commercially available culture media showed no significant influence on mean birthweight and mean birthweight adjusted for gestational age, gender and parity (z-­‐scores) of singletons born after a fresh or frozen-­‐
thawed SET. Furthermore, we show that embryo freezing and thawing cycles may lead to 11 Clínica
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a significantly higher mean birthweight. WHAT IS KNOWN AND WHAT THIS PAPER ADDS Animal studies have shown that culture media constituents are responsible for changes in birthweight of offspring. In human IVF, there is still little knowledge of the effect of medium type on birthweight. Until now, only a small number of commercially available culture media have been investigated (Vitrolife, Cook(®) Medical and IVF online medium). Our study adds new information: it has a larger population of singleton births compared with the previously published studies, it includes outcomes of other media types (HTF and Sage(®)), not previously analysed, and it includes data on frozen-­‐thawed SETs. DESIGN This study was a retrospective analysis of birthweights of singleton newborns after fresh (Day 3) or frozen-­‐thawed (Day 5) SET cycles, using embryos cultured in either of two different types of commercially available culture media, between 2008 and 2011. PARTICIPANTS AND SETTING Before January 2009, a single-­‐step culture medium was used: human tubal fluid (HTF) with 4 mg/ml humanserum albumin. From January 2009 onwards, a commercially available sequential medium was introduced: Sage(®), Quinn's advantage protein plus medium. Singletons born after a fresh SET (99 embryos cultured in HTF and 259 in Sage(®)) and singletons born after a frozen-­‐thawed SET (32 embryos cultured in HTF only, 41 in HTF and Sage(®) and 86 in Sage(®) only) were analysed. Only patients using autologous gametes without the use of a gestational carrier were considered. Also excluded were (vanishing) twins, triplets, babies with congenital or chromosomal abnormalities and babies born before 22 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Analysis of 358 singletons born after a fresh SET and 159 singletons born after a frozen-­‐thawed SET showed no significant difference between the HTF and Sage(®) groups in terms of birthweight. Gestational age, parity and gender of the baby were significantly related to birthweight in multiple linear regression analyses, and other possible confounding factors included maternal age, BMI and smoking, the number of blastomeres in the transferred embryo and the type of culture medium. Maternal age, BMI and smoking, gestational age at birth, gender of the baby and the percentage of firstborns did not differ significantly between the HTF and Sage(®) groups; however, among the fresh embryos, those cultured in Sage(®) had significantly more blastomeres at the time of embryo transfer compared with the embryos cultured in HTF. Birthweights adjusted for gestational age and gender or gestational age and parity (z-­‐
scores) were not significantly different between the HTF and Sage(®) groups for fresh or frozen-­‐thawed SETs. Mean birthweight, as well as the mean birthweight among firstborns and the mean birthweights adjusted for gestational age and gender or parity (z-­‐scores) were significantly higher in the cryopreservation group compared with the fresh embryo transfer group. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION Our study is limited by its retrospective design and only two commercially available types of culture media were tested. More research is necessary to investigate the potential influence of culture media on gene expression. GENERALIZABILITY TO OTHER POPULATIONS Although our data do not indicate the major influences of the HTF and Sage(®) culture media on birthweight, our results cannot be 12 Clínica
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extrapolated to other culture media types. Furthermore, there remains a potential influence of embryo culture environment on epigenetic variation not represented by birthweight differences but by more subtle features. STUDY FUNDING/COMPETING INTEREST(S)No external funding was obtained for this study. 9.
The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-­‐analysis. Veículo: Hum Reprod. Data: 12 de julho de 2012 Fonte: OxforJournal Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, Kirkman-­‐Brown J, Coomarasamy A. Centre for Human Reproductive Science, Birmingham Women's Hospital, Mindelsohn Drive, Edgbaston, Birmingham B15 2TG, UK. Resumo: STUDY QUESTION s there an association between high levels of sperm DNA damage and miscarriage? SUMMARY ANSWER Miscarriage rates are positively correlated with sperm DNA damage levels. WHAT IS KNOWN ALREADY Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-­‐strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates. STUDY DESIGN, SIZE, DURATION A systematic review and meta-­‐analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS We used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-­‐Ottawa Scale. Meta-­‐analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of 13 Clínica
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which were prospective. Eight studies used acridine orange-­‐based assays, six the TUNEL assay and two the COMET assay. Meta-­‐analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P < 0.00001). LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss. WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy. STUDY FUNDING/COMPETING INTEREST(S)None. 10.
Fetal-­‐Specific CD8+ Cytotoxic T Cell Responses Develop during Normal Human Pregnancy and Exhibit Broad Functional Capacity. Veículo: J Immunol. Data: 15 de julho de 2012 Fonte: PubMed Lissauer D, Piper K, Goodyear O, Kilby MD, Moss PA. Reproduction, Genes and Development Theme, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom. Resumo: Tolerance of the semiallogeneic fetus presents a significant challenge to the maternal immune system during human pregnancy. T cells with specificity for fetal epitopes have been detected in women with a history of previous pregnancy, but it has been thought that such fetal-­‐specific cells were generally deleted during pregnancy as a mechanism to maintain maternal tolerance of the fetus. We used MHC-­‐peptide dextramer multimers containing an immunodominant peptide derived from HY to identify fetal-­‐specific T cells in women who were pregnant with a male fetus. Fetal-­‐specific CD8(+) T lymphocytes were observed in half of all pregnancies and often became detectable from the first trimester. The fetal-­‐specific immune response increased during pregnancy and persisted in the postnatal period. Fetal-­‐specific cells demonstrated an effector memory phenotype and were broadly functional. They retained their ability to proliferate, secrete IFN-­‐γ, and lyse target cells following recognition of naturally processed peptide on male cells. These data show that the development of a fetal-­‐specific adaptive cellular immune response is a 14 Clínica
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normal consequence ofhuman pregnancy and that unlike reports from some murine models, fetal-­‐specific T cells are not deleted during human pregnancy. This has broad implications for study of the natural physiology of pregnancy and for the understanding of pregnancy-­‐related complications. 11.
Intravenous Immunoglobulin for Repeated IVF Failure and Unexplained Infertility. Veículo: Am J Reprod Immunol. Data: 17 de julho de 2012 Fonte: PubMed Virro MR, Winger EE, Reed JL. Markham Fertility Centre, Markham, ON, Canada. Resumo: PROBLEM: We set out to determine whether intravenous immunoglobulin (IVIG) improves in vitro fertilization (IVF) success rates in women with a difficult history of multiple (≥2) prior IVF failures and /or 'unexplained' infertility. METHOD OF STUDY: A total of 229 women with multiple IVF failures (3.3 ± 2.1) and/or unexplained infertility (3.8 ± 2.7 years) were given IVIG on the day of egg retrieval, and the subsequent IVF success rates were compared with published success rates from the Canadian database (CARTR). RESULTS: The pregnancy rate per IVIG-­‐treated cycle was 60.3% (138/229), and the live birth rate per IVIG-­‐treated cycle was 40.2% (92/229). This is a significantly higher success rate compared to the Canadian average (30% live birth rate; CARTR statistics from 2010; P = 0.0012). In cases where a single embryo was transferred, pregnancy rate using IVIG was almost twofold the CARTR pregnancy rate [(61%(20/33) to 34.9% (428/1225)]. In cases where two high quality (≥Grade 3) day 5 blastocysts were transferred, nearly a 100% pregnancy rate was achieved using IVIG (30/31). CONCLUSION: IVIG may be a useful treatment option for patients with previous IVF failure and/ or unexplained infertility. The data confirm previously published studies at other centers. 15 Clínica
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Notícias da Web:
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Entire genome of human sperm sequenced for the first time. Veículo: foxnews Data: 19 de julho de 2012 Fonte: http://www.foxnews.com/health/2012/07/19/entire-­‐genome-­‐human-­‐sperm-­‐
sequenced-­‐for-­‐first-­‐time/ Researchers at Stanford University have sequenced the entire genomes of 91 human sperm from a single man – providing insight into the genetic variation that naturally occurs in a single individual. The project marks the first time the whole-­‐genome of a human gamete has been sequenced. Published in the journal Cell, the study offers more detailed knowledge about the process of genetic recombination – the method in which DNA from both a mother and a father blend together in the children they produce. Recombination facilitates both the breaking apart and rejoining of chromosomes during reproduction. “We learned some really interesting details about how the body mixes together the genomes from parents to create new genomes for their potential children,” said Steve Quake, professor of bioengineering and applied physics at Stanford University as well as the study’s lead author. “That’s why every sperm cell has a different genome. Your body mixes to create unique genomes so your offspring have different genetic diversity.” Providing greater detail Quake and his colleagues isolated and sequenced nearly 100 sperm cells from a 40-­‐year-­‐old man with healthy children. They compared the sperm sequences with the man’s whole-­‐
genome sequence, ultimately allowing them to identify where and when recombination took place. Until this sequencing project, scientists could only rely on genetic studies of population to estimate how often recombination occurred in sperm and egg cells as well as the amount of genetic mixing the process needed. The Stanford study essentially confirmed what these previous studies theorized: Each sperm in the sample underwent 23 recombination events, or mixing events. However, the study also showed that the degree of genetic mixing varied greatly between individual sperm, as well as the frequency and severity of spontaneous genetic mutations. According to the researchers, the sequencing technique used in their study can provide a better guide as to what exactly happens during a sperm’s development. “[Before this study], we have no way to catalogue the mutations and the recombination events of an individual,” co-­‐author Barry Behr, professor of obstetrics and gynecology and director of Stanford’s in vitro fertilization laboratory, told FoxNews.com. “Once we get our understanding of these, we can map them and see how they change as a man ages. We could map these in healthy versus unhealthy people. We could map these in fertile and infertile people, and really get a better understanding as to what the fundamental makeup 16 Clínica
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of a good sperm versus a bad sperm is.” Understanding infertility The majority of cells in the human body carry two copies of each of 23 chromosomes. Recombination occurs during meiosis – a type of cell division necessary for reproduction in which one copy of each chromosome is separated into a sperm (for men) or an egg (for women). This ensures that when a sperm fertilizes an egg, the resulting embryo has a full set of matching DNA. However, when the pairs of chromosomes align during recombination, sometimes portions of matching chromosomes are randomly swapped out – what is known as genetic mixing. This process allows for much more genetic variation in potential children. According to Behr and Quake’s research, the degree and frequency of this genetic mixing was unique for each sperm and egg cell. The sequencing technique revealed that spontaneous genetic mutations – variability in sperm that happens randomly – varied greatly in between individual cells as well. “We discovered that measuring the rate at which new mutations form in sperm is somewhat higher than we expected,” Quake said. “It presents a nifty puzzle for us to solve…. We’re now in position to use this technique to work out what is the truth between new mutation rates in between individuals.” While genetic mutations can also be responsible for genetic variation in offspring , if they occur at particular points in the genome, adverse effects can occur. According to Behr, this insight into mutation rates could potentially be used to get a better understanding of male infertility in the future. “I would put money on the fact that we or others will be able to demonstrate using our approaches that infertile men have higher mutation rates or have different types of mutation rates than those men who have normal fertility rates,” Behr said. “That in and of itself will be a huge contribution to understanding fertility, but specifically male fertility, which is really a decade or two behind studying female fertility.” Behr also noted that each individual cell is destroyed by the sequencing process, so the sperm they studied could not go on to fertilize eggs. However, Behr said that having such intricate knowledge of just a few sperm from a sample could provide a good snapshot of a man’s overall sperm trends. “I anticipate as technology proceeds, we may be able to find information out about individual sperm cells and then use them,” Behr said. “But currently what we’re able to do, which I think is valid, is that we can look at maybe a subset of the whole sperm population and make a very accurate determination on the compliment or the characteristics of that sample.” 13.
Mothers who use fertility drugs may have shorter kids Veículo: foxnews Data: 16 de julho de 2012 17 Clínica
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Fonte: http://www.foxnews.com/health/2012/07/16/mothers-­‐who-­‐use-­‐fertility-­‐drugs-­‐may-­‐
have-­‐shorter-­‐kids/ Children conceived through use of fertility drugs may not grow quite as tall as other kids, a new study from Australia suggests. In the study, boys whose mothers used fertility drugs were on average 1 inch (3 centimeters) shorter at ages 3 to 10, compared with boys of mothers who did not use the drugs. While girls whose mothers who used fertility drugs also tended to be shorter than other kids, the findings were not as strong and could have been due to chance. It's possible it wasn't the drugs, but something related to the parent's fertility problems that influenced the children's height, but the researchers found this was not the case. Children whose parents who used fertility drugs were shorter than children whose parents who had trouble having kids, but eventually conceived without taking fertility drugs. The results were unexpected, the researchers said. Previous studies have found that children conceived using in vitro fertilization, which also uses fertility drugs, are taller than naturally-­‐
conceived children. Because they study was small, further research is needed to confirm the findings. Additional studies are also needed to see whether the height difference persists into adulthood, the researchers said. Other experts are not convinced by the findings. Dr. Avner Hershlag, chief of the Center For Human Reproduction at the North Shore Long Island Jewish Health System in Manhasset, N.Y., urged women considering fertility treatment not to resist treatment because of this study's results. "There is not solid evidence right now" of the link between fertility drug use and short stature in children, Hershlag said. Effects of fertility drugs While several studies have examined the effects of fertility treatments such as in vitro fertilization on children, few studies have examined the effects of fertility drug use alone. In the new study, Wayne Cutfield, of the University of Auckland, and colleagues analyzed information from 84 children whose mothers underwent ovarian stimulation with fertility drugs. They compared this group with 214 children whose parents were fertile and conceived naturally, and 54 children whose parents took more than 12 months to conceive, but eventually did so without treatments. The average age of children in the study was 7.5. The link between a shorter stature in children and use of fertility drugs held even after the researchers took into account factors that affect the height of children, such as the height and weight of the parents. It's possible that ovarian stimulation with fertility drugs leads to alterations in certain genes in the embryo that result in developmental changes, the researchers said. Complex trait However, height is a very complex trait, and is influenced by many factors, including the environment a child grows up in, and the food he or she eats, Hershlag said. "To me, that would be much more important than a drug given before conception," Hershlag said. The researchers tried to account for family factors that could influence height by limiting their study to children of European descent, from families living in high socioeconomic 18 Clínica
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communities. But Hershlag pointed out even siblings from the same family have different heights. In addition, mothers in the study received different fertility treatments — some received the oral drug clomiphene, other received injections of follicle-­‐stimulating hormone, and some received both treatments at once. This "hodgepodge" of treatments makes it hard to draw firm conclusions from the study, Hershlag said. The study was published online July 9 in the journal Human Reproduction. Pass it on: In a new study from Australia, boys whose mothers used fertility drugs were about one inch shorter than boys whose mothers did not use fertility drugs. 14.
Vida na cidade grande pode piorar problemas de fertilidade Veículo: terraonline Data: 16 de julho de 2012 Fonte: http://vidaeestilo.terra.com.br/fertilidade/noticias/0,,OI5896265-­‐EI20142,00-­‐
Vida+na+cidade+grande+pode+piorar+problemas+de+fertilidade.html A vida nas cidades grandes pode ter suas vantagens, mas traz também muitos efeitos negativos. Em alguns casos, a poluição, o estresse e a agitação podem, inclusive, diminuir as chances de engravidar. Os efeitos da poluição do ar são mais conhecidos entre os estudiosos da fertilidade. Essas substâncias podem comprometer a qualidade do espermatozoide. Uma das causas é o desencadeamento de reação imunológica em que o organismo reconhece o gameta como uma célula alterada que precisa ser atacada. Outro poluente prejudicial à fertilidade seria o ozônio, que é tóxico quando respirado. "Ele é um radical livre de oxigênio. A relação entre radicais livres e a piora da qualidade seminal é algo bem conhecido. Por analogia, dá para considerar também que o ozônio afeta a fertilidade", afirma Edward Carilho, especialista em reprodução humana da clínica Engravida, de São Paulo. O ozônio se concentra em áreas abertas próximas a locais poluídos, como nos parques das grandes cidades. Estresse Trânsito, filas, correria, poluição sonora, violência... Há muitas condições típicas das cidades grandes que levam ao aumento do estresse. Embora não haja estudos conclusivos sobre o assunto, a hipótese de que o estresse pode afetar a fertilidade é bastante conhecida. O estresse pode causar alterações hormonais que levam a variações no ciclo menstrual, o que atrapalha o período fértil. Diferenças pessoais O quanto a vida nas grandes cidades vai afetar a fertilidade depende do indivíduo. "Cada 19 Clínica
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pessoa lida com o estresse de uma maneira diferente. Tem gente que lida muito bem com o trânsito. Outras que são superativas e fazem exercício físico, o que diminui o estresse", explica Edward. Além disso, não são apenas os efeitos da cidade que vão levar a um comprometimento da fertilidade. "Para um homem que tenha meio bilhão de espermatozoides, ficar num ambiente poluído não vai causar problema. Agora, para aquele homem que tem uma fertilidade baixa, ele pode ser prejudicado", analisa o especialista. Mas o fato de a procura por processos de reprodução assistida ser maior nas grandes cidades tem mais relação com a idade com que as mulheres passam a tentar engravidar, explica Edward. "A cidade grande muda o comportamento das pessoas, inclusive na decisão de quando ter filhos. A variação da idade é mais importante do que os fatores ambientais", afirma. Mudança de hábito Uma maneira de diminuir o impacto da vida urbana na fertilidade é a prática de atividades físicas. "A pessoa que mora nas cidades geralmente tem uma alimentação pior. Ela já não tem hábitos saudáveis. Ter uma alimentação melhor ou buscar uma atividade física para diminuir o estresse são saídas. Tudo que diminui o estresse é favorável", diz o médico. O uso de vitaminas, como a E ou o zinco, sob orientação médica, também são uma opção, segundo ele. Isso não significa, no entanto, que a pessoa está imune aos efeitos da cidade. "Não adianta também tapar o sol com a peneira e falar que fazer exercício vai resolver o problema de quem fica quatro horas no trânsito. Até porque para essa pessoa é difícil encaixar a atividade na rotina", afirma. Notícias da Clínica e Equipe Fecondare
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