Publicado em 06/02/2012 - Atualizado 26/07/2019

Atualizações científicas – 30 de janeiro a 3 de fevereiro de 2012


Na última semana de janeiro, a comunidade científica publicou artigos sobre Reprodução Humana. Confira a seguir o resumo dos principais artigos publicados

Intrauterine exposure to mild analgesics during pregnancy and the occurrence ofcryptorchidism and hypospadia in the offspring: the Generation R Study

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


Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring.

METHODS: Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002-2006),the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14-22 weeks of gestation and 20-32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia.

RESULTS: The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14-22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17-3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01-3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys.

CONCLUSIONS: Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism.

Selection against small males in utero: a test of the Wells hypothesis

Publicado em Dezembro de 11 pela Human Reproduction, disponível no Oxfor Journal.


The argument that women in stressful environments spontaneously abort their least fit fetuses enjoys wide dissemination despite the fact that several of its most intuitive predictions remain untested. The literature includes no tests, for example, of the hypothesis that these mechanisms select against small for gestational age (SGA) males.

METHODS:We apply time-series modeling to 4.9 million California male term births to test the hypothesis that the rate of SGA infants in 1096 weekly birth cohorts varies inversely with labor market contraction, a known stressor of contemporary populations.

RESULTS: We find support  for the hypothesis that small size becomes less frequent among term male infants when the labor market contracts.CONCLUSIONSOur findings contribute to the evidence supporting selection in utero. They also suggest that research into the association between maternal stress and adverse birth outcomes should acknowledge the possibility that fetal loss may affect findings and their interpretation. Strengths of our analyses include the large number and size of our birth cohorts and our control for autocorrelation. Weaknesses include that we, like nearly all researchers in the field, have no direct measure of fetal loss.

A short exposure to polychlorinated biphenyls deregulates cellular autophagy in mammalian blastocyst in vitro

Publicado em 01 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Polychlorinated biphenyls (PCBs) are common environmental contaminants that represent an important risk factor of reproductive disorders in chronically exposed human populations. However, it is not known whether a short accidental exposure of embryos to PCBs before implantation might influence their further development and whether the effect might be reversible.

METHODS AND RESULTS: To this aim, in vitro-matured sheep blastocysts were incubated with 2 or 4 µg/ml Aroclor 1254 (A1254),a mixture of 60 PCB congeners for 48h after which blastocyst proliferation and ability for outgrowth in vitro were assessed. Blastocysts exposed to A1254 showed: (i) reduced proliferation and cell number (particularly in the inner cell mass compartment); (ii) accumulation of vacuoles and lipid droplets, diffused mitochondrial damage and up-regulation of autophagy markers (ATG6 and LC3),all signs indicative of deregulated autophagy, and (iii) massive cell death. Although exposed embryos resumed growth following A1254 removal, their subsequent development remained severely perturbed.

CONCLUSIONS: These findings indicate that short exposure of blastocysts to PCBs leads to its damage characterized by deregulated autophagy and subsequent cell death.

Molecular characterization of the porcine MTPAP gene associated with meat quality traits: chromosome localization, expression distribution, and transcriptional regulation

Publicado em 02 de Fevereiro de 12 pela Molecular and Cellular Biochemistry, disponível no Pub Med.


MTPAP (mitochondrial poly(A) polymerase) gene plays a role in stabilizing the level of mitochondrial mRNAs and controlling the poly(A) length of human mitochondrial mRNAs. In this study, 2,296 bp partial cDNA sequences of the porcine MTPAP gene were obtained, which contained 1,746 bp full-length coding regions flanked by a 500 bp partial 3′-UTR. The porcine MTPAP gene was assigned to SSC10q14-q16 using the radiation hybrid (IMpRH) panel and chromosome electric location methods. Q-PCR analysis showed that MTPAP was expressed in all analyzed tissues, and has higher expression in heart, liver, skeletal muscles, and fat. One single nucleotide polymorphism g.2421T>A in intron5 of MTPAP gene was identified and detected by DdeI PCR-RFLP. Association of the genotypes with economic traits showed that different genotypes were significantly associated with juiciness, individuals with genotype AT displayed a significantly higher juiciness compared to genotype TT. The C/EBPβ transcription factors was up-regulation the expression of MTPAP by analyzing a series of MTPAP promoter reporter constructs using the dual-luciferase assay system, it indicated that MTPAP gene maybe play a critical role in fat deposition regulation which is regulated by C/EBPβ transcription factor. These findings provide an important basis for further understanding of porcine MTPAP regulation and function in swine.

Glutathione peroxidase activity in seminal plasma and its relationship with classical sperm parameters and in vitro fertilization-intracytoplasmic sperm injection outcome

Publicado em 31 de Janeiro de 12pela Fertil Steril, disponível no Pub Med.


OBJECTIVE: To relate the glutathione peroxidase (GPX) activity level in human seminal plasma with standard semen parameters and spermatozoa fertilization potential in terms of fertilization and pregnancy rates in an IVF program.

DESIGN: Prospective study.

SETTING: Human Reproduction Unit at Cruces Hospital (Vizcaya, Spain).

PATIENT(S): Three hundred consecutive males from infertile couples participating in the IVF program.



MEASURE(S): Analysis of GPX activity in seminal plasma by spectrophotometry.

RESULT(S): GPX activity in seminal plasma was significantly lower in patients with abnormal sperm as assessed by 1999 and 2010 World Health Organization (WHO) criteria, compared with normozoospermic individuals. There was a more significant decrease in those samples with severe sperm pathologies. GPX values were significantly lower in samples with severe asthenozoospermia, oligozoospermia, and teratozoospermia compared with normal samples. However, there was no correlation between GPX activity in seminal plasma in IVF patients and fertilization rates or pregnancy outcome.

CONCLUSION(S): Although seminal plasma GPX activity was related to semen quality according to WHO parameters, such an association was not found with IVF-intracytoplasmic sperm injection (ICSI) outcome, presumably because of the well-known ability of IVF-ICSI procedures to overcome sperm deficiencies in the fertilization process.

Seasonal variability in the fertilization rate of women undergoing assisted reproduction treatments

Publicado em 01 de Fevereiro de 12pela Gynecological Endocrinology, disponível no Pub Med.


The objective of this study was to evaluate whether seasonality affects human-assisted reproduction treatment outcomes. For this, 1932 patients undergoing intracytoplasmic sperm injection (ICSI) were assigned to a season group according to the day of oocyte retrieval: winter (n = 435),spring (n = 444),summer (n = 469) or autumn (n = 584). Analysis of variance was used to compare the ICSI outcomes. The fertilization rate was increased during the spring (winter: 67.9%, spring: 73.5%, summer: 68.7% and autumn: 69.0%; p < 0.01). In fact, a nearly 50% increase in the fertilization rate during the spring was observed (odds ratio 1.45, confidence interval 1.20-1.75; p < 0.01). The oestradiol concentration per number of oocytes was significantly higher during the spring (winter: 235.8 pg/mL, spring: 282.1 pg/mL, summer: 226.1 pg/mL and autumn: 228.7 pg/mL; p = 0.030). This study demonstrates a seasonal variability in fertilization after ICSI, where fertilization is higher during the spring than at any other time.

In vitro exposure of Acer negundo pollen to atmospheric levels of SO2 and NO2: Effects on allergenicity and germination

Publicado em 01 de Fevereiro de 12 pela Environmental Science & Technology, disponível no Pub Med.


In the last years, a rising trend of pollen allergies in urban areas has been attributed to atmospheric pollution. In this work, we investigated the effects of SO2 and NO2 on the protein content, allergenicity and germination rate of Acer negundo pollen. A novel environmental chamber was assembled to exposure pollen samples with SO2 or NO2 at two different levels: just below and two times the atmospheric hour-limit value acceptable for human health protection in Europe. Results showed that protein content was lower in SO2-exposed pollen samples and slightly higher in NO2-exposed pollen compared to control sample. No different polypeptide profiles were revealed by SDS-PAGE between exposed and non-exposed pollen, but the immunodetection assays indicated higher IgE recognition by all sera of polysensitized patients to Acer negundo pollen extracts in all exposed samples in comparison to non-exposed. It was verified a decrease in the germination rate of exposed in contrast to non-exposed pollen, which was more pronounced for NO2-exposed samples. Our results indicated that, in urban areas, concentrations of SO2 and NO2, below the limits established for human protection can indirectly aggravate pollen allergy on predisposed individuals and affect plant reproduction.

Australian perspectives on surrogacy: the influence of cognitions, psychological and demographic characteristics

Publicado em 30 de Janeiro de 12pela Human Reproduction, disponível no Pub Med.


The aim of the present study was to explore current Australian support levels for surrogacy treatments and also whether this support differed between traditional surrogacy and gestational surrogacy. The focus was also on understanding the underlying influences on surrogacy attitudes. It was hypothesized that cognitions, psychological and demographic characteristics would all predict attitudes to surrogacy and that cognitive concerns about surrogacy would be the strongest predictor.METHODSParticipants (N = 195: 79 male, 116 female; age range 18-76 years) were first-year psychology undergraduates (47%) and friends and associates of the authors (53%). They completed a survey pack which assessed attitudes and knowledge about surrogacy, as well as empathy and other personality characteristics.RESULTSThe results indicated that there has been a marked increase in support for surrogacy treatment in recent years, with nearly 80% of participants supporting surrogacy, and that support for gestational surrogacy was greater than that for traditional surrogacy (P< 0.001). As anticipated, cognitive concerns about surrogacy were the strongest predictors of surrogacy attitudes (R(2)= 0.393).CONCLUSIONSA limitation of the present study was the use of a non-representative, self-selected sample that tended to be well educated and perhaps liberal minded. Despite this, given the high levels of support, it could be concluded that the recent, more permissive legislative changes, which were finalized in 2010, are reflective of the values of Australian society.

The limits for detection of activated caspases of spermatozoa by western blot in human semen

Publicado em 01 de Fevereiro de 12pela Andrologia, disponível no Pub Med.


Detection of activated caspases of spermatozoa could be helpful to evaluate male infertility. Although western blot is validated as a highly specific method to detect the proteins extracted from cells, the ability of this technique to detect activated sperm caspases in human semen may be limited. Indeed, round cells, which potentially contain some activated caspases, may be present in semen and interfere with the detection of activated sperm caspases. Moreover, it is necessary to evaluate the minimum amount of spermatozoa necessary to optimise the detection of activated caspases in semen samples. Our results showed that interference due to round cells contained in semen with activated caspase-3 requires separation of spermatozoa by density migration. This sperm preparation selects a mature sperm population that does not reflect the whole sperm population, and in infertile men with oligoasthenoteratozoospermia, the amount of spermatozoa thus selected is usually low. Moreover, the western blot technique’s low detection sensitivity and the low level of caspase enzyme activity in human spermatozoa for activated caspase-3, -8 and -9 mean that large quantities of spermatozoa are needed to detect the expression of the activated caspases. These limitations prevent this method being used for routine analysis in clinical practice.

An introduction to infertility counseling: a guide for mental health and medical professionals

Publicado em 31 de Janeiro de 12pelo Journal of Assisted Reproduction and Genetics, disponível no Pub Med.


The practice of infertility counseling delivered by mental health and medical professionals has become more sophisticated and widespread over the past decade.  This paper summarizes information presented at the second campus workshop of the  Special Interest Group of Psychology and Counseling of the European Society of Human Reproduction and Embryology (ESHRE). This group is dedicated to improving infertility services by creating meaningful connections between mental health and medical professionals. The paper identifies key issues that infertility counselors must consider in their work with couples experiencing infertility. The use of supportive psychosocial interventions and treatments are highlighted. The paper also details the process for choosing the most appropriate type of infertility counseling, and the use of assessment tools that assist in understanding infertility related symptoms. Infertility counselors should also consider gender differences, the impact of infertility on a couple’s sexual relationship, and the unique challenges couples face regarding third-party conception. Finally, the paper addresses specific recommendations for infertility counselors in mental health and medical settings.

Endometrial stem cells and reproduction

Publicado em Janeiro de 12pela Obstetrics and Gynecology International, disponível no Pub Med.


Abnormal endometrial function remains a significant cause of implantation failure, recurrent pregnancy loss, and other pathologies responsible for female infertility. The development of novel therapies to treat infertility due to endometrial dysfunction requires an understanding of the latest advancements in endometrial cell biology, such as the role of endometrial stem cells. The remarkable regenerative capacity of the human endometrium is absolutely essential for successful reproduction and likely requires a population of stem cells in the endometrium. The purpose of this review is to provide an introduction to some of the newest concepts in endometrial stem cell biology.

Premature birth and low birthweight are associated with a lower rate of reproduction in adulthood: a Swedish population-based registry study

Publicado em 26 Janeiro de 12pela Human Reproduction, disponível no Pub Med.


The aim of this study was to investigate if individuals born with sub-optimal birth characteristics have reduced probability of reproducing in adulthood.METHODSUsing population-based registries, the authors included 522 216 males and 494 692 females born between 1973 and 1983 and examined their reproductive status as of 2006. Outcome measure was the hazard ratio (HR) of reproducing. Adjustments were made for socio-economic factors.

RESULTS: Males and females born very premature displayed a reduced probability of reproducing [HR = 0.78, 95% confidence interval (CI): 0.70-0.86 for males; HR = 0.81, CI: 0.75-0.88 for females]. Likewise for very low birthweight (HR = 0.83, CI: 0.71-0.95 for males; HR = 0.80, 95% CI: 0.72-0.89 for females). Individuals born large for gestational age (LGA) displayed no significant changes. Males born small for gestational age (SGA) had a 9% lower reproductive rate (CI: 0.89-0.94) and that reduction increased as the individuals aged. Women born SGA tended to start reproducing at an earlier age.

CONCLUSION: The results suggest that being born with low birthweight, premature or SGA (for males) is associated with a reduced probability of reproducing as an adult. LGA shows no statistically significant relationship with future reproduction.

A novel application of cell-free seminal mRNA: non-invasive identification of the presence of germ cells or complete obstruction in men with azoospermia

Publicado em 26 Janeiro de 12pela Human Reproduction, disponível no Pub Med.


Cell-free seminal mRNA (cfs-mRNA) exists in human ejaculate at high concentrations and with high stability, and contains many tissue-specific transcripts secreted from the male reproductive system. Owing to the sensitivity of RNA technology, cfs-mRNAs are ideal candidates for non-invasive biomarkers of physiopathological conditions. This study applied cfs-mRNA in identifying the presence of either germ cells or complete obstruction in men with azoospermia.

METHODS: RT-PCR was performed to amplify the germ cell-specific (DDX4),seminal vesicle-specific (SEMG1) and prostate-specific (TGM4) mRNAs from cfs-mRNAs, which were isolated from the seminal plasma of men with non-obstructive azoospermia (NOA) or obstructive azoospermia (OA). The 39 patients with NOA, diagnosed by testicular biopsy, included 8 men with maturation arrest (MA),3 men with incomplete sertoli cell only (iSCO) syndrome and 28 men with complete SCO (cSCO). The 29 patients with OA, confirmed by the presence of sperm in the testis or epididymis, included 8 men with congenital bilateral absence of the vas deferens (CBAVD) and 21 men with non-CBAVD. Healthy individuals and vasectomized men were enrolled as controls.

RESULTS: TGM4 was detected in all participants. Consistent with their diagnosis, DDX4 was detected  in all patients with MA or iSCO but was absent in most cases of cSCO (n = 21, 75.0%) or non-CBAVD (n = 18, 85.7%),and in all men with vasectomy or CBAVD. The presence of DDX4 in the other seven men with cSCO and three patients with non-CBAVD suggests the presence of germ cells in the testis, and incomplete obstruction, respectively. SEMG1 was undetectable in three patients with CBAVD with bilateral absence of the seminal vesicles, and in two non-CBAVD cases with low ejaculate volume.

CONCLUSIONS: These results suggest that, with high sensitivity and representativity, cfs-mRNA could be non-invasive biomarkers for identifying the presence of germ cells or complete obstruction in azoospermia.

In vitro effect of unacylated ghrelin and obestatin on human luteal cell function

Publicado em 26 Janeiro de 12pela Human Reproduction, disponível no Pub Med.


OBJECTIVE: To evaluate whether unacylated ghrelin and obestatin were able to influence human luteal cell function. The effect of these two ghrelin-relate peptides on progesterone (P4),prostaglandin (PG) F(2α),PGE(2),and vascular endothelial growth factor (VEGF) release and on VEGF expression in isolated human steroidogenic cells has been investigated. DESIGN: Prospective laboratory study.

SETTING: University hospital.

PATIENT(S): Corpora lutea were obtained from 23 normally menstruating patients in the midluteal phase of the menstrual cycle.

INTERVENTION(S): Human luteal cells were isolated from corpora lutea, and primary cultures were established.

MAIN OUTCOME MEASURE(S): P4 and PGs release was assayed by enzyme immunoassay, VEGF secretion by ELISA, and VEGF mRNA expression  by real-time polymerase chain reaction.

RESULT(S): P4 and VEGF release were significantly reduced by both unacylated ghrelin and obestatin. Moreover, the highest concentration of obestatin was able to reduce the release of PGE(2) and PGF(2α). VEGF mRNA expression was not affected by the incubation with any of these ghrelin-related peptides. As expected, CoCl(2) was able to induce VEGF release and mRNA expression in luteal cells.

CONCLUSION(S): Our results suggest that, similar to ghrelin, both unacylated ghrelin and obestatin might play a role in regulating the luteal cell function that affects both luteal steroidogenesis and luteotrophic/luteolytic imbalance. These results further underline the pivotal correlation between the ghrelin system and reproduction.

Does exogenous LH in ovarian stimulation improve assisted reproduction success? an appraisal of the literature

Publicado em 26 Janeiro de 12pela Reproductive BioMedicine Online, disponível no Pub Med.


A review of the scientific literature on the use of exogenous LH in assisted reproductive technology was performed by searching the MEDLINE, PubMed and Cochrane online databases. Scientific evidence was reviewed comparing recombinant FSH-only protocols to protocols supplemented with exogenous LH activity: human menopausal gonadotrophin (HMG),recombinant LH and mid-follicular human chorionic gonadotrophin (HCG). Studies were further compared based on pituitary suppression with gonadotrophin-releasing hormone (GnRH) antagonist and agonist protocols. Primary focus was given to randomized controlled trials and meta-analyses. Data from hypogonadotrophic hypogonadal patients demonstrated the importance of LH activity for success of assisted reproduction treatment. However, the majority of normogonadotrophic patients had adequate endogenous LH to successfully drive ovarian steroidogenesis and oocyte maturation. Exogenous LH supplementation was consistently associated with higher peak oestradiol concentrations. The use of HMG in long GnRH agonist cycles was associated with a 3-4% increase in live birth rate. There was insufficient evidence to make definitive conclusions on the need for exogenous LH activity in GnRH antagonist cycles or the benefit of recombinant LH and HCG protocols. Poor responders and patients 35years of age and older may benefit from exogenous LH. LH is essential in natural human reproduction. In many infertile patients treated with assisted reproductive technology, LH concentrations are naturally sufficient to allow for successful conception. The need for the physician to supplement the patient with additional LH as a medication has been a matter of medical controversy. This article reviews the scientific evidence available on the importance of LH in assisted reproduction treatment. Using a form of LH combined with FSH derived from humans (human menopausal gonadotrophin) results in a 3-4% higher live birth rate. Insufficient scientific evidence exists to recommend other forms of LH and more research is needed to clarify this question. Patients who are over the age of 35 or who are poor responders to ovarian stimulation may also benefit from the addition of LH to their ovarian stimulation protocol.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Publicado em 25 Janeiro de 12pela Medical Hypotheses, disponível no Pub Med.


Infertility represents one of the main long-term consequences of the chemotherapy used for the adjuvant treatment of breast cancer. Approximately 60-65% of breast  cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ breast cancer with respect to recurrence-free survival and overall survival. It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+tumours) if they want to preserve their reproductive function. The evaluation of ovarian reserve tests: follicle stimulating hormone (FSH),anti-Mullerian hormone (AMH),inhibin B, antral follicle count (AFC) and ovarian volume 6months, and 1year after the end of therapy with GnRHa/tamoxifen must be realised. The recurrence-free survival and overall survival should be analysed. The major implication of this hypothesis will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases and subsequent pregnancy a real possibility.

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