Atualizações Científicas – 13 a 17 de fevereiro de 2012

Publicado em: 23 de Fevereiro de 2012

Na última semana a comunidade científica publicou novos artigos sobre Reprodução Humana e Andrologia. Conheça mais sobre o assunto:

Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE

Publicado em 17 de Fevereiro de 12 pela Human Reproduction, disponível no Oxfor Journal.


This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007.

METHODS: From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner’s (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI- D (+7.2%).

RESULTS: In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6 million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged , 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women , 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%.

CONCLUSIONS: In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.

Prevalence of functional disorders of androgen excess in unselected premenopausal women: a study in blood donors

Publicado em 17 de Fevereiro de 12 pela Human Reproduction, disponível no Oxfor Journal.


The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. On the contrary, the prevalences of other disorders of androgen excess such as idiopathic hyperandrogenism and idiopathic hirsutism remain unknown. We aimed to obtain an unbiased estimate of the prevalence in premenopausal women of (i) signs of androgen excess and (ii) PCOS, idiopathic hyperandrogenism and idiopathic hirsutism.

METHODS: A multicenter prevalence survey included 592 consecutive premenopausal women (393 from Madrid, Spain and 199 from Bologna, Italy) reporting spontaneously for blood donation. Immediately before donation, we conducted clinical and biochemical phenotyping for androgen excess disorders. We determined the prevalence of (i) hirsutism, acne and alopecia as clinical signs of androgen excess and (ii) functional disorders of androgen excess, including PCOS, defined by the National Institute of Child Health and Human Development/National Institute of Health criteria, idiopathic hyperandrogenism and idiopathic hirsutism.

RESULTS: Regarding clinical signs of hyperandrogenism, hirsutism and acne were equally frequent [12.2% prevalence; 95% confidence interval (CI): 9.5–14.8%], whereas alopecia was uncommon (1.7% prevalence, 95% CI: 0.7–2.7%). Regarding functional disorders of androgen excess, PCOS and idiopathic hirsutism were equally frequent (5.4% prevalence, 95% CI: 3.6–7.2) followed by idiopathic hyperandrogenism (3.9% prevalence, 95% CI: 2.3–5.4).

CONCLUSIONS: Clinical signs of hyperandrogenism and functional disorders of androgen excess show a high prevalence in premenopau- sal women. The prevalences of idiopathic hyperandrogenism and idiopathic hirsutism are similar to that of PCOS, highlighting the need for further research on the pathophysiology, consequences for health and clinical implications of these functional forms of androgen excess.

Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen

Publicado em 17 de Fevereiro de 12 pela Human Reproduction, disponível no Oxfor Journal.


Premature ovarian failure (POF) is currently managed by non-physiological sex steroid regimens which are inadequate at optimizing uterine characteristics. Previous short-term studies have demonstrated some benefits of a sex steroid replacement (SSR) regimen devised to replicate the physiological cycle. This study aimed to directly compare the effects of longer-term administration of physiological SSR (pSSR) and standard SSR (sSSR) regimens on the uterine volume, blood flow and endometrial thickness (ET) in women with POF.

METHODS: In a controlled crossover trial, 34 women with POF were randomized to receive 12 months of 4-week cycles of transdermal estradiol and vaginal progesterone (pSSR) followed by 12 months of 4-week cycles of oral ethinylestradiol and norethisterone (sSSR), or vice versa. Each treatment period was preceded by a 2-month washout period. At 0, 3, 6 and 12 months of each treatment period, transvaginal ultrasound examined the uterine volume and ET, as primary end-points, and uterine artery resistance (UARI) and pulsatility indices (UAPI), as secondary end-points. Serum estradiol, progesterone and gonadotrophins were also measured.

RESULTS: Of the 29 women eligible for the uterine analysis, 17 completed the entire study protocol, but 25 women contributed data to statistical analysis of treatment effect. There was a greater estimated mean ET with the use of pSSR (4.8 mm) compared to that with standard therapy (3.0 mm), with an estimated difference of 1.8 mm [95% confidence interval (CI), 0.7 to 2.8, P 1⁄4 0.002]. The estimated mean uterine volume was also greater during physiological treatment (24.8 cm3) than during standard treatment (20.6 cm3), but the estimated difference of 4.2 cm3 (95% CI 20.4 to 8.7) was not statitsically significant, P 1⁄4 0.070. The small differences between the two treatments in the mean UARI and mean UAPI were not statistically significant. The estimated treatment differences were fairly constant across the treatment periods, suggesting that prolonged treatment does not increase response.

CONCLUSIONS: pSSR has a greater beneficial effect upon ET in women with POF in comparison with standard therapy. A similar trend was seen for uterine volume. Further studies are required to optimize treatment and to assess pregnancy rate and outcome.

Differential RNAs in the sperm cells of asthenozoospermic patients

Publicado em 17 de Fevereiro de 12 pela Human Reproduction, disponível no Oxfor Journal.


Alterations in RNAs present in sperm have been identified using microarrays in teratozoospermic patients and in other types of infertile patients. However, so far, there have been no reports on using microarrays to determine the RNA content of sperm from asthenozoospermic patients.

METHODS: We started the present project with the goal of characterizing the RNA abundance in the sperm cells of asthenozoospermic patients when compared with controls. To reach this objective, we initially selected four normal fertile donors and four asthenozoospermic infertile patients. Equal amounts of RNA were extracted from the sperm samples, subjected to different quality controls and hybridized to the Affymetrix U133 Plus version 2 arrays.

RESULTS: Several transcripts were identified that were present in different abundance in patients compared with controls. Subsequently, we validated the differential expression of three of the detected transcripts (ANXA2, BRD2 and OAZ3), using real-time PCR in a larger set of samples. A positive correlation between the expression of these transcripts and progressive motility was observed.

CONCLUSIONS: The sperm cells of asthenozoospermic patients contain an altered amount of some RNAs as detected using microarray analysis and subsequently validated using real-time PCR. These results open up the possibility to investigate the implication of these genes in the pathogenic mechanisms in asthenozoospermia and to consider their potential utility as infertility biomarkers.

Is there an optimal pH for culture media used in clinical IVF?

Publicado em 06 de Fevereiro de 12 pela Human Reproduction Update, disponível no Oxfor Journal.


Reducing environmental stress imposed upon gametes and embryos in the IVF laboratory is crucial in optimizing culture conditions and development. One environmental parameter of particular importance is external pH (pHe) of culture media. An optimal pHe has not been identified.

METHODS: Electronic searches were performed using keywords focused on pH and the embryo using PUBMED through August 2011, with no limits placed on a beginning time. Examples of keywords include CO2, bicarbonate and hydrogen ion. Relevant papers were then examined to obtain additional publications.

RESULTS: Determining optimal pHe is problematic due to difficulty in isolating pHe from other variables, such as CO2 and bicarbonate. Various commercial media companies recommend differing pHe ranges, most within the range of 7.2–7.4, with some companies recom- mending altering pHe based on the gamete or stage of the embryo. However, changing pHe during culture has not been experimentally shown to improve outcomes. Further complicating attempts to define an optimal pHe is that media components can impact intracellular pH (pHi). As a result, media with different concentrations of substances, such as lactate or amino acids, may have different pHi, despite being in the same pHe.

CONCLUSIONS: Due to the plasticity of embryos, a range of pHe’s can support development, and defining an optimal pHe is difficult. It is unclear whether there is any benefit in changing pHe at various steps during IVF. The ideal pHe will likely vary from media to media and, until comparative studies have been performed isolating pHe, adherence to manufacturer recommendations and maintenance of a small accept- able pHe range are advisable.

The ESHRE PGD Consortium: 10 years of data collection

Publicado em 16 de Fevereiro de 12 pela Human Reproduction Update, disponível no Oxfor Journal.


Since it was established in 1997, the ESHRE PGD Consortium has been collecting data from international preimplanta-tion genetic diagnosis (PGD) centres. Ten papers have been published, including data from January 1997 to December 2007.

METHODS: The data collection originally used a hard-copy format, then an excel database and finally a FileMaker Pro database. The indications are divided into five categories: PGD for chromosome abnormalities, sexing for X-linked disease, PGD for single gene defects, pre-implantation genetic screening (PGS) and PGD for social sexing. The main end-points are pregnancy outcome and follow-up of deliveries.

RESULTS: In data collection I, 16 centres contributed data, which increased to 57 centres by data X (average of 39 centres per data col- lection). These centres contributed data on over 27 000 cycles that reached oocyte retrieval. Of these cycles, 61% were for aneuploidy screening, 17% for single gene disorders, 16% for chromosomal abnormalities, 4% for sexing of X-linked disease and 2% for social sexing. Cumulatively, 5187 clinical pregnancies gave rise to 4140 deliveries and 5135 newborns (singletons: 3182, twins: 921, triplets: 37).

CONCLUSIONS: In this paper, we present an overview of the first 10 years of PGD data, highlighting trends. These include the intro- duction of laser-assisted biopsy, an increase in polar body and trophectoderm biopsy, new strategies, methodologies and technologies for diagnosis, including recently arrays, and the more frequent use of freezing biopsied embryos. The Consortium data reports represent a valuable resource for information about the practice of PGD.

Challenging cell phone impact on reproduction: A Review

Publicado em 16 de Fevereiro de 12 pelo Journal of Assisted Reproduction and Genetics, disponível no Pub Med.


PURPOSE: The radiofrequency electromagnetic radiation (RF-EMR) produced by cell phones can enhance the excitability of the brain and has recently been classified as carcinogenic. The suggested use of hands-free kits lowers the exposure to the brain, but it might theoretically increase exposure to the reproductive organs. This report summarizes the potential effects of RF-EMR on reproductive potentials in both males and females.

METHODS: A critical review of the literature pertaining to the impact of cell phone RF-EMR on reproduction in male and female animals and humans was performed, with a focus on gonad metabolism, apoptosis of reproductive cells, fertility status, and serum reproductive hormones.

RESULTS: While some animal and human studies revealed alterations in reproductive physiology in both males and females, others did not report any association. The in vitro and in vivo studies to date are highly diverse, very inconsistent in conduct and, in many cases, report different primary outcomes.

CONCLUSION: The increasing use of cell phone warrants well-designed studies to ascertain the effect of their RF-EMR on reproduction.

Genetic selection of embryos that later develop the metabolic syndrome

Publicado em 18 de Fevereiro de 12 pela Medical Hypothesesand Genetics, disponível no Pub Med.


THE BARKER HYPOTHESIS: Is an excellent explanation of the process where human and animal foetuses exposed to malnutrition, either by maternal malnutrition or placental insufficiency, are metabolically programmed, with selective stunting of cell differentiation and organ growth. With the postnatal excess of nutrition observed in developed countries, this irreversible programming causes metabolic syndrome, including obesity, type 2 diabetes, and hypertension. Metabolic programming involves epigenetic changes including imprinting which might be transmitted through more than one generation rather than being completely re-set or erased during reproduction. The Barker hypothesis was supported by epidemiological data that recognised no excess fetal or postnatal mortality when pregnant women were starved during the Dutch famine in World War II. This argued against the “thrifty genotype” theory introduced in 1962, which proposed that starvation selected against members of the population with less “thrifty” genes, but the survivors who had “thrifty” genes developed metabolic syndrome if they were subsequently over-nourished. EMBRYONIC/FETAL SELECTION: Embryos or early foetuses could be selected very early in pregnancy on the basis of their genotype, by maternal malnutrition, hypertension, obesity or other causes of placental insufficiency. The genotype that allows embryos, or cells within them, to survive a less hospitable environment in the decidua after implantation might contribute to the later development of metabolic syndrome. This article hypothesises that an adverse intrauterine environment, caused by maternal malnutrition or placental insufficiency, kills a proportion of embryos and selects a surviving population of early embryos whose growth in utero is retarded by their genotype, their environment or a combination of both. The metabolic syndrome follows if the offspring is over-nourished later in life. The embryonic selection hypothesis presented here could be tested by using single nucleotide polymorphism (SNP) microarrays to study adults who had a history of intrauterine growth retardation (IUGR) and subsequent metabolic syndrome. Their SNP array could be compared with their parents and unaffected unrelated or related controls. If there were no selection based on a “thrifty genotype”, all parental sequences would be expected to appear in their surviving children, whether or not they had IUGR or developed metabolic syndrome. SNP sequences present in parents or controls but missing from adult offspring with metabolic syndrome who had IUGR, could be associated with or linked to genes that influence susceptibility to metabolic syndrome. This hypothesis proposes that missing genotypes would be lost if the embryos that inherited them died very early in pregnancy.

Seminal vesicles ultrasound features in a cohort of infertility patients

Publicado em 16 de Fevereiro de 12 pela Human reproduction, disponível no Oxfor Journal.


OBJECTIVES: Previous studies concerning ultrasound evaluation of the seminal vesicles (SV) were performed on a limited series of subjects, and considered few parameters, often only before ejaculation and without assessing the patients’ sexual abstinence. The aim of this study was to evaluate the volume and the emptying characteristics of the SV and their possible correlations with scrotal and transrectal ultrasound features.

METHODS: The SV of 368 men seeking medical care for couple infertility were evaluated by ultrasound. All patients underwent, during the same ultrasound session, scrotal and transrectal evaluation, before and after ejaculation, and the ejaculate was subjected to semen analysis. A new parameter, SV ejection fraction, calculated as: [(SV volume before ejaculation –  SV volume after ejaculation)/SV volume before ejaculation] × 100, was evaluated.

RESULTS: After adjusting for sexual abstinence and age, both pre-ejaculatory SV volume and SV ejection fraction were positively associated with ejaculate volume. As assessed by receiver operating characteristic curve, a cut-off for SV ejection fraction of 21.6% discriminates subjects with normal ejaculate volume (≥1.5 ml) and pH (≥7.2 ml) with both sensitivity and specificity equal to 75%. Subjects with SV ejection fraction of <21.6% more often had a higher post-ejaculatory SV volume and ejaculatory duct abnormalities. Furthermore, a higher post-ejaculatory SV volume was associated with a higher prostate volume and SV abnormalities. Higher epididymal and deferential diameters were also detected in subjects with a higher post-ejaculatory SV volume or reduced SV ejection fraction. No association between SV and testis ultrasound features or sperm parameters was observed. Associations with SV ejection fraction were confirmed in nested 1:1 case-control analysis.

CONCLUSIONS: The SV contribute significantly to the ejaculate volume. A new parameter, SV ejection fraction, could be useful in assessing SV emptying. A SV ejection fraction of <21.6% was associated with prostate-vesicular and epididymal ultrasound abnormalities.

Conteúdo atualizado em: 17 de Abril de 2014

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