Publicado em 14/02/2012 - Atualizado 26/07/2019

Atualizações Científicas – 06 a 10 de fevereiro de 2012


Aprenda um pouco mais sobre Reprodução Humana lendo os últimos artigos científicos publicados sobre o assunto.

Effect of cryopreservation and transplantation on the expression of kit ligand and anti-Mullerian hormone in human ovarian tissue

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Although cryopreservation and transplantation of ovarian tissue represent a promising alternative to safeguard fertility in cancer patients, low recovery rates of oocytes aspirated from antral follicles and a significant number of empty follicles have been observed in women with transplanted frozen-thawed ovarian tissue. In order to understand how freezing and/or grafting may affect follicular development, the follicular expression of kit ligand (KL) and anti-Müllerian hormone (AMH),two key factors activating and inhibiting follicle growth, were assessed after long-term grafting in severe combined immunodeficient (SCID) mice.

METHODS: Ovarian biopsies from eight patients were used for fresh and frozen-thawed tissue xenografting in 13 SCID mice for a period of 28 weeks, including 2 weeks of gonadotrophin stimulation. KL, AMH and proliferating cell nuclear antigen (PCNA) immunostaining were quantified before and after grafting in the two treatment groups (fresh and frozen-thawed grafted ovarian tissue).

RESULTS: Lower expression of KL was found in primordial and primary follicles after grafting of both fresh and frozen-thawed tissue. Consistent expression of AMH was found in most growing follicles at a similar rate in both graft types. In fresh and frozen-thawed grafts, 13-14% of primordial follicles were PCNA-positive, indicating a similar maintenance of quiescent follicles despite follicle activation.

CONCLUSIONS: Grafting and/or gonadotrophin stimulation appear to affect the follicular expression of KL, which may alter oocyte quality. AMH expression in growing follicles after ovarian tissue transplantation may be one of the factors contributing to the preservation of resting follicles in 28-week-old grafts.


Plasma level of calcitonin gene-related peptide in patients with polycystic ovary syndrome and its relationship to hormonal and metabolic parameters

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


The aim of the study was to evaluate the plasma level of calcitonin gene-related peptide (CGRP) in patients with polycystic ovary syndrome (PCOS) and its relationship to hormonal and metabolic parameters. We also observed the effect of CGRP on testosterone (T) and estradiol (E(2)) release in cultured human granulose cells. PCOS subjects (n=215) and matched healthy control women (n=103) at age of 22-38 years were enrolled in this study. We analyzed plasma CGRP concentrations, relationship of plasma CGRP with insulin resistance (IR),body mass index (BMI),luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio and T. The T and E(2) release levels of cultured human granulosa cells treated by CGRP were also measured. The results showed that plasma CGRP concentrations were significantly higher in women with PCOS than those of control subjects. In women with PCOS, there was a strong positive correlation between the plasma CGRP level with HOMA-IR, AUC-insulin, AUC-glucose, the ratio of LH/FSH and plasma T concentration. Human granulosa cells expressed CGRP receptor. Exogenous CGRP caused an elevation of T and E(2) released from the human granulosa cells. These findings suggest that CGRP may participate in the pathophysiological process of PCOS.

Human chorionic gonadotrophin stimulation test as a predictor of ovarian response and pregnancy in IVF cycles stimulated with GnRH agonist gonadotrophin treatment:a pilot study

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Recent evidence supports a specific and broad role of androgen produced by theca cells in reproductive physiology. This pilot study evaluated the usefulness of hCG theca stimulation test in predicting ovarian response and pregnancy.

METHODS: Prospective cohort study including 80 infertile women treated with IVF/ICSI. On Day 3 of the menstrual cycle preceding, the first IVF/ICSI cycle a blood sample was drawn to evaluate baseline FSH, estradiol (E(2)),17-hydroxy-progesterone, androstenedione and testosterone levels. All women then received 250 µg recombinant hCG s.c. and underwent a second blood sampling 24 h after hCG injection to measurement steroid serum levels.

RESULTS: Percentage increment of E(2) but not its precursors was significantly higher in normo-responders and pregnancy cycles than in poor responders and non-pregnancy cycles (P = 0.03 and P = 0.02, respectively) diagnostic accuracy being 67 and 75%, respectively. The percentage increase in E(2) thus still fails in as many as 33 and 25% of patients in predicting ovarian response and pregnancy, respectively. In addition, E(2) concentrations are poorly reproducible and a wide range of variation in all serum steroids investigated-including E(2)-after hCG injection was observed.

CONCLUSIONS: The predictive power of the hCG test is based on E(2) but not androgen response to hCG injection. This test cannot be recommended in routine clinical practice because it is too laborious for screening purposes, shows great variability in the response obtained and its overall accuracy is not better than that reported for other available markers of varian reserve. The use of the currently available markers, antral follicle count and anti-Müllerian hormone, is therefore recommended.

Human papillomavirus sperm infection and assisted reproduction: a dangerous hazard with a possible safe solution

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Human papillomavirus (HPV) infection has been demonstrated in the sperm of a large percentage of sexually active males and is associated with an impairment of sperm parameters, with a particular negative impact on sperm motility, suggesting a possible role in male infertility. Conventional sperm selection techniques have a low efficiency in removing HPV.

METHODS: Evaluation of sperm parameters, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling test to evaluate DNA fragmentation and fluorescence in situ hybridization or immunohistochemistry for HPV were performed on semen samples from infected patients (n= 22),control subjects (n= 13) and on pooled control sperm samples incubated with HPV16-L1 (HPV capsid),before and after direct swim-up and modified swim-up (with added Heparinase-III). Moreover, cytofluorimetry for HPV detection was performed in pooled sperm pre- and post-incubation with HPV 16-L1 before and after direct and modified swim-up. Statistical analysis was performed with a two-tailed Student’s t-test.

RESULTS: Direct swim-up reduces the number of HPV-infected sperm by ∼24% (P<0.01),while modified swim-up is able to remove completely HPV DNA both from naturally and artificially infected sperm. Enzymatic treatment with Heparinase-III tended to decrease sperm motility, viability and DNA integrity but the effects were not significant.

CONCLUSIONS: This study shows that Heparinase-III treatment seems not to affect spermatozoa in vitro and suggests that this treatment should be investigated further as a means of preparing sperm from patients who are infected with HPV in order to reduce the risk of HPV infection when using assisted reproduction techniques.

Understanding the perceptions of and emotional barriers to infertility treatment: a survey in four European countries

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Infertility can significantly impact women’s lives and personal relationships. Despite the negative impact of infertility, a significant number of women who are struggling to conceive do not consult a physician. This cross-sectional survey was conducted to determine the emotional impact of infertility on women to identify which aspects of fertility treatment contribute to the psychological stress experienced by so many patients and to identify barriers to seeking treatment.

METHODS: Women (n = 445; 18-44 years) who had received fertility treatment within the past 2 years or were having trouble conceiving but had not received treatment, completed a 15-min survey online.

RESULTS: Participants were from France (n = 108),Germany (n = 111),Italy (n = 112) and Spain (n = 114). Responses indicated that infertility causes a range of emotions and can strain relationships. Women who had received treatment were more likely to feel hopeful (26 versus 21%) and closer to their partner than women not in treatment (33 versus 19%, P < 0.05). Most women delayed starting treatment because of a desire to conceive naturally, and on the advice of physicians. Women aged ≥35 years took longer to seek help with their fertility issues. Injection-related anxiety was the second greatest barrier to treatment.

CONCLUSIONS:This study has provided insight into the physical and psychological challenges of infertility treatments and permitted a better understanding of the factors that impact patient lives. A treatment protocol with minimal injections and provision of additional information may lessen the emotional impact and challenges of infertility and contribute to patient satisfaction with fertility treatment protocols.

Tailored expectant management: a nationwide survey to quantify patients’ and professionals’ barriers and facilitators

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Prognostic models for natural conception help to identify subfertile couples with high chances of natural conception, who do not need fertility treatment yet. The use of such models and subsequent tailored expectant management (TEM) is not always practiced. Previous qualitative research has identified barriers and facilitators of TEM among patients and professionals. The aim of this study was to assess the prevalence of those barriers and facilitators and to evaluate which factors predict patients’ appreciation of TEM and professionals’ adherence to TEM.

METHODS: We performed a nationwide survey. Based on the previously identified barriers and facilitators two questionnaires were developed and sent to 195 couples and 167 professionals. Multivariate analysis was performed to evaluate which factors predicted patients’ appreciation of TEM and professional adherence to TEM.

RESULTS: In total, 118 (61%) couples and 117 (70%) professionals responded and 96 couples and 117 professionals were included  in the analysis. Patients’ mean appreciation of TEM was 5.7, on a 10-point Likert scale. Patients with a lower appreciation of TEM had a higher need for patient information (P = 0.047). The professionals reported a mean adherence to TEM of 63%. Adherence to TEM was higher when professionals were fertility doctors (P = 0.041). Facilitators in the clinical domain were associated with a higher adherence to TEM (P = 0.091). Barriers in the professional domain had a negative impact on adherence to TEM (P = 0.008).

CONCLUSIONS: The limited implementation of TEM is caused by both patient and professional-related factors. This study provides practical tools to improve the implementation of TEM.

Heated spermatozoa: effects on embryonic development and epigenetics

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Sperm chromatin is highly condensed and relatively resistant to chemical and physical treatments. The purpose of this study was to explore the highest temperature that sperm can tolerate and still produce live offspring.

METHODS: Mouse sperm were heated in a water bath at 50, 65, 80 or 95°C for 30 min before they were microinjected into mouse oocytes. Fertilization, embryo development and 1-cell embryo karyotypes were evaluated. Epigenetic reprogramming including DNA methylation and histone H3K4-trimethylation were evaluated by immunofluorescent staining.

RESULTS: The ability of mouse sperm to activate the egg after ICSI was heat sensitive; only 20% of eggs were activated by sperm that had been heated to 50°C and none was activated by sperm heated to 80°C. However, if eggs were activated artificially, mouse sperm subjected to 80°C for 30 min were able to produce live offspring, while 95°C treatment disabled sperm decondensation after ICSI. Once the heat-treated sperm nucleus had developed into a pronucleus, sperm chromatin was able to undergo normal active DNA demethylation and histone methylation. Aberrant chromosome rates increased from 16.3 to 100% when the temperature was raised from 50 to 95°C.

CONCLUSIONS: Heat treatment destroys integrity of sperm chromatin in a temperature-dependent manner. Eighty degree Celsius was the highest temperature that mouse sperm could withstand and still produce live offspring.

Glycodelin-A interferes with IL-2/IL-2R signalling to induce cell growth arrest, loss of effector functions and apoptosis in T-lymphocytes

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


The progesterone-regulated glycoprotein glycodelin-A (GdA),secreted by the decidualized endometrium at high concentrations in primates, inhibits the maternal immune response against fetal antigens and thereby contributes to the tolerance of the semi-allogenic fetus during a normal pregnancy. Our earlier studies demonstrated the ability of GdA to induce an intrinsic apoptotic cascade in CD4(+) T-lymphocytes and suppress the cytolytic effector function of CD8(+) T-lymphocytes. In this report, we investigated further into the mechanism of action of GdA controlling perforin and granzyme B expression in CD8(+) T-lymphocytes and the mechanism of action of GdA leading to lymphocyte death.

METHODS: Flow cytometry analysis was performed to check for the surface expression of interleukin-2 receptor α (IL-2Rα) and intracellular eomesodermin (Eomes) in activated T-lymphocytes, whereas quantitative RT-PCR analysis was used to find out their mRNA profile upon GdA treatment. Western analysis was carried out to confirm the protein level of Bax and Bcl-2.

RESULTS: GdA reduces the surface expression of the high-affinity IL-2R complex by down-regulating the synthesis of IL-2Rα (CD25). This disturbs the optimal IL-2 signalling and decreases the Eomes expression, which along with IL-2 directly regulates perforin and granzymes expression. Consequently, the CD8(+) T-lymphocytes undergo growth arrest and are unable to mature into competent cytotoxic T-lymphocytes. In the CD4(+) T-lymphocytes, growth factor IL-2 deprivation leads to proliferation inhibition, decreased Bcl-2/enhanced Bax expression, culminating in mitochondrial stress and cell death.

CONCLUSIONS: GdA spurs cell cycle arrest, loss of effector functions and apoptosis in different T-cell subsets by making T-lymphocytes unable to respond to IL-2.

Failure of a combined clinical- and hormonal-based strategy to detect early spermatogenesis and retrieve spermatogonial stem cells in 47,XXY boys by single testicular biopsy

Publicado em 07 de Fevereiro de 12 pela Human Reproduction, disponível no Pub Med.


Although germ cells in boys with Klinefelter syndrome (KS) are reduced in number as early as infancy, a severe germ cell loss occurs during mid-puberty. Therefore, we wanted to detect spermatogenesis at an early stage and investigate the strategy of preserving spermatozoa and/or testicular spermatogonial stem cells in adolescents with KS when signs of deteriorating spermatogenesis are observed.

METHODS: Tanner staging, testicular size, serum inhibin B and spermaturia  were assessed every 4 months before the attempt to procure gametogenic cells in seven non-mosaic 47,XXY adolescents, aged between 10 and 16 years.

RESULTS: Despite an increasing testis volume in the youngest and a Tanner staging of more than three in the oldest patients, no spermaturia was observed. In two patients serum inhibin B increased gradually, while in all others a rather rapid but variable decline was observed at different ages. No spermatozoa were observed after electroejaculation. No spermatocytes or spermatids were found at microscopic examination of single biopsies, while spermatogonia were identified in four subjects, three of whom had measurable serum inhibin B. Massive fibrosis and hyalinization were observed in all biopsies.

CONCLUSION: No spermatogenesis was documented in non-mosaic 47,XXY adolescents either by spermaturia, electroejaculation or testicular biopsy. Neither clinical nor hormonal parameters were of value in determining the timing for optimal spermatogonial stem cell retrieval. More data are needed to elucidate the potential role of testicular tissue cryopreservation in adolescents with KS. Therefore, at present, the cryopreservation of testes tissue for clinical reasons should not be recommended.

Correlations between Different Heavy Metals in Diverse Body Fluids: Studies of Human Semen Quality

Publicado em 24 de Janeiro de 12 pela Advances in Urology, disponível no Pub Med.


It has been hypothesized that exposure to heavy metals may impair male reproduction. To measure the effect produced by low doses of heavy metals on semen parameters, it is necessary to clarify in which body fluids those measurements must be performed. Sixty-one men attending infertility clinics participated in our study. Concentrations of lead, cadmium, and mercury were measured in whole blood, blood plasma, and seminal plasma using spectroanalytical and electrochemical methods. Semen analyses were performed according to World Health Organization criteria. For statistical analysis, Spearman’s rank correlations, mean comparison tests, and discriminant analysis were calculated. Significant correlations between the measured concentrations of the three heavy metals in the same biological fluids were observed. However, no similar relationship was seen when comparing the concentrations in different body fluids of the same metal. According to our results and previous publications, seminal plasma might be the best body fluid for assessing impairment of human semen parameters.

The use of androgens or androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis

Publicado em 03 de Fevereiro de 12 pela Human Reproduction Update, disponível no Pub Med.


The aim of this meta-analysis was to evaluate the role of androgens or androgen-modulating agents on the probability of pregnancy achievement in poor responders undergoing IVF.

METHODS: Medline, EMBASE, CENTRAL, Scopus and Web of Science databases were searched for the identification of randomized controlled trials evaluating the administration of testosterone, dehydroepiandrosterone (DHEA),aromatase inhibitors, recombinant luteinizing hormone (rLH) and recombinant human chorionic gonadotrophin (rhCG) before or during ovarian stimulation of poor responders.

RESULTS: In two trials involving 163 patients, pretreatment with transdermal testosterone was associated with an increase in clinical pregnancy [risk difference (RD): +15%, 95% confidence interval (CI): +3 to +26%] and live birth rates (RD: +11%, 95% CI: +0.3 to +22%) in poor responders undergoing ovarian stimulation for IVF. No significant differences in clinical pregnancy and live birth rates were observed between patients who received DHEA and those who did not. Similarly, (i) the use of aromatase inhibitors, (ii) addition of rLH and (iii) addition of rhCG in poor responders stimulated with rFSH for IVF were not associated with increased clinical pregnancy rates. In the only eligible study that provided data, live birth rate was increased in patients who received rLH when compared with those who did not (RD: +19%, 95% CI:+1 to +36%).

CONCLUSIONS: Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF.

Male fertility and reduction in semen parameters: a single tertiary-care center experience

Publicado em 26 de Janeiro de 12 pelo International Journal of Endocrinology, disponível no Pub Med.


Infertility is both a clinical and a public problem, affecting the life of the couple, the healthcare services, and social environment. Standard semen analysis is the surrogate measure of male fertility in clinical practice.

OBJECTIVE: To provide information about the relationship between semen parameters and spontaneous conception. Methods. We evaluated retrospectively 453 pregnancies that occurred among 2935 infertile couples evaluated at an infertility clinic of a tertiary-care university hospital, between 2004 and 2009.

RESULTS: Normal semen analysis was present only in 158 patients; 295 subfertile patients showed alterations in at least one seminal parameter. A reduction in all seminal parameters was observed in 41 patients. Etiological causes of male infertility were identified in 314 patients.

CONCLUSION: Our data highlights the possibility of a spontaneous conception with semen parameters below WHO reference values. Therefore, we support the importance of defining reference values on a population of fertile men. Finally, we analyzed the related ethical issues.

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