NMR studies of preimplantation embryo metabolism in human assisted reproductive techniques: a new biomarker for assessment of embryo implantation potential

There has been growing interest in understanding energy metabolism in human embryos generated using assisted reproductive techniques (ART) for improving the overall success rate of the method. Using NMR spectroscopy as a noninvasive tool, we studied human embryo metabolism to identify specific biomarkers to assess the quality of embryos for their implantation potential. The study was based on estimation of pyruvate, lactate and alanine levels in the growth medium, ISM1, used in the culture of embryos. An NMR study involving 127 embryos from 48 couples revealed that embryos transferred on Day 3 (after 72 h in vitro culture) with successful implantation (pregnancy) exhibited significantly (p < 10(-5)) lower pyruvate/alanine ratios compared to those that failed to implant. Lactate levels in media were similar for all embryos. This implies that in addition to lactate production, successfully implanted embryos use pyruvate to produce alanine and other cellular functions. While pyruvate and alanine individually have been used as biomarkers, the present study highlights the potential of combining them to provide a single parameter that correlates strongly with implantation potential. Copyright (C) 2012 John Wiley & Sons, Ltd.

The effect of anxiety and depression scores of couples who underwent assisted reproductive techniques on the pregnancy outcomes.

Objective: The aim of this study was to determine the effect of anxiety and depression scores of couples who underwent Assisted Reproductive Techniques (ART) on pregnancy outcomes. Method: This study was conducted as a prospective and comparative study with 217 couples. The study data was collected by using a semi-structured questionnaire and the Turkish version of the State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). The questionnaire, STAI and BDI were applied to couples who initiated ART treatment. Couples’ state anxiety scores were re-evaluated after embryo transfer (ET). Results: A significant relationship was found between the depression score of women and pregnancy outcome (p < 0.05). It was determined that anxiety scores for both men and women were higher before the ART procedure, but their anxiety scores decreased after ET (p < 0.05). Spouses of women with a negative pregnancy outcome had higher trait and state anxiety mean scores (p > 0.05) and lower depression scores (p <0.05) than spouses of women with a positive pregnancy outcome. Conclusion: Study results indicated that the anxiety and depression scores of couples who had achieved a positive pregnancy result were lower than for couples with a negative result. The results of this study will contribute to the health professionals especially to the nurses who spend the most time with couples in providing consulting services and supporting psychological status of couples during ART process in Turkey.

Assisted reproductive technology success rates /

Vol. for 1995 in 3 pts.: v. 1 Eastern United States ; v. 2 Central United States ; v. 3 Western United States.

EULAR Recommendations for Women's Health and the Management of Family Planning, Assisted Reproduction, Pregnancy and Menopause in Patients with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Public goods and procreation.

Procreation is the ultimate public goods problem. Each new child affects the welfare of many other people, and some (but not all) children produce uncompensated value that future people will enjoy. This essay addresses challenges that arise if we think of procreation and parenting as public goods. These include whether individual choices are likely to lead to a socially desirable outcome, and whether changes in laws, social norms, or access to genetic engineering and embryo selection might improve the aggregate outcome of our reproductive choices.

Acurácia da histerossonografia versus ultrassonografia transvaginal em mulheres inférteis candidatas às técnicas de reprodução assistida

PURPOSE: To compare the diagnostic accuracy of sonohysterography (HSN) and conventional transvaginal ultrasound (USG) in assessing the uterine cavity of infertile women candidate to assisted reproduction techniques (ART). METHODS: Comparative cross-sectional study with 120 infertile women candidate to ART, assisted at Centro de Reprodução Assistida (CRA) of Hospital Regional da Asa Sul (HRAS), Brasília-DF, from August 2009 to November 2010. Sonohysterography was performed with saline solution infusion in a close system. The sonohysterography finding was compared to previous USG results. The uterine cavity was considered abnormal whenthe endometrium was found to be thicker than expectedduring the menstrual cycle and whenan endometrial polyp, a submucous myoma and an abnormal shape of the uterine cavity were observed. The statistical analysis was doneusing absolute frequencies, percentage values and the χ 2, with the level of significance set at5%. RESULTS:HSN revealed that 92 (76.7%) infertile women candidate to ARThad anormal uterine cavity, while 28 (23.3%) had the following abnormalities: 15 polyps (12.5%).

Acupuntura: Um auxílio efetivo em procedimentos de fertilização in vitro?

The purpose of the present study was to evaluate the impact of acupuncture on in vitro fertilization outcomes of patients undergoing acupuncture during embryo transfer. A retrospective study was realized with records of 30 patients undergoing acupuncture and 108 patients not undergoing acupuncture during embryo transfer. The data was compared to verify the differences onto fertilization, embryo cleavage, pregnancy and abortion rate. To the statistical evaluation the X2 Test was performed, set as significant p<0.05. There was no statistical significance difference in any feature analyzed among the groups, although the acupuncture group presented higher pregnancy rate and lower abortion rate. Acupuncture did not presented positive or negative statistical relevant effects into the outcomes of in vitro fertilization procedures. Regardless this result, the present study did not exclude the possibility of acupuncture administration as a tool to pain relief during other procedures, as the transvaginal ultrasound-guided oocyte retrieval. © Todos os direitos reservados a.

Assisted reproductive technology – IVF treatment in Ireland: A study of couples with successful outcomes

Human Fertility 17(3):165-9 This article describes the experiences of twelve Irish couples who had successful IVF treatment in Ireland. Irish Medical guidelines specify that IVF may only be used when no other treatment is likely to be effective. This article is based on data drawn from a longitudinal research study by Cotter (2009) which tells the stories of 34 couples who sought fertility treatment. Initially, the women assumed that they would become pregnant when they stopped using contraception. As a couple, it was the ‘right time’ for them to have a child - they were ready, socially and financially. For several months they were patient, hoping it would happen naturally. With envy and some despair they watched as their friends had babies. Infertility came as a shock to most of them. They were reluctant to talk about it to anyone, and over time their anxieties were accompanied by feelings of regret, stigma and social exclusion. They finally sought medical treatment. The latter involved a series of diagnostic treatments, which eventually culminated in IVF which offered them a final chance of having a ‘child of their own’. While IVF can be clinically assessed in terms of cycle success rates, their stories showed treatment as a series of discoveries, as an extensive range of diagnostic tests and procedures helped to reveal to them where their problems might lie. They described their treatments as a series of sequential ‘hurdles’ that they had to overcome, which further strengthened their resolve to try IVF. Much more knowledgeable at that stage, they embraced IVF as a final challenge with single minded dedication while drawing on all their psychological and biological resources to promote a successful outcome. Of the 34 couples who took part in the study, twelve got pregnant. Unfortunately, two children died shortly after birth but eighteen babies survived (see Table I). The findings suggest that health policy should raise awareness of infertility, and advise women to become aware of it just as in the past, when health policy addressed contraception. Increased public knowledge would reduce the stigma attached to the inability to have a baby. In the Irish case, infertility diagnosis should be reviewed with a view to giving eligible couples earlier access to IVF.  

Regulating IVF and pre-implantation tissue-typing for the creation of "saviour siblings" : a harm analysis

Scientific discoveries, developments in medicine and health issues are the constant focus of media attention and the principles surrounding the creation of so called ‘saviour siblings’ are of no exception. The development in the field of reproductive techniques has provided the ability to genetically analyse embryos created in the laboratory to enable parents to implant selected embryos to create a tissue-matched child who may be able to cure an existing sick child. The research undertaken in this thesis examines the regulatory frameworks overseeing the delivery of assisted reproductive technologies (ART) in Australia and the United Kingdom and considers how those frameworks impact on the accessibility of in vitro fertilisation (IVF) procedures for the creation of ‘saviour siblings’. In some jurisdictions, the accessibility of such techniques is limited by statutory requirements. The limitations and restrictions imposed by the state in relation to the technology are analysed in order to establish whether such restrictions are justified. The analysis is conducted on the basis of a harm framework. The framework seeks to establish whether those affected by the use of the technology (including the child who will be created) are harmed. In order to undertake such evaluation, the concept of harm is considered under the scope of John Stuart Mill’s liberal theory and the Harm Principle is used as a normative tool to judge whether the level of harm that may result, justifies state intervention or restriction with the reproductive decision-making of parents in this context. The harm analysis conducted in this thesis seeks to determine an appropriate regulatory response in relation to the use of pre-implantation tissue-typing for the creation of ‘saviour siblings’. The proposals outlined in the last part of this thesis seek to address the concern that harm may result from the practice of pre-implantation tissue-typing. The current regulatory frameworks in place are also analysed on the basis of the harm framework established in this thesis. The material referred to in this thesis reflects the law and policy in place in Australia and the UK at the time the thesis was submitted for examination (December 2009).

Using UHF proximity loggers to quantify male–female interactions: A scoping study of estrous activity in cattle

Reproductive efficiency is an important determinant of profitable cattle breeding systems and the success of assisted reproductive techniques (ART) in wildlife conservation programs. Methods of estrous detection used in intensive beef and dairy cattle systems lack accuracy and remain the single biggest issue for improvement of reproductive rates and such methods are not practical for either large-scale extensive beef cattle enterprises or free-living mammalian species. Recent developments in UHF (ultra high frequency) proximity logger telemetry devices have been used to provide a continuous pair-wise measure of associations between individual animals for both livestock and wildlife. The objective of this study was to explore the potential of using UHF telemetry to identify the reproductive cycle phenotype in terms of intensity and duration of estrus. The study was conducted using Belmont Red (interbred Africander Brahman Hereford–Shorthorn) cattle grazing irrigated pasture on Belmont Research Station, northeastern Australia. The cow-bull associations from three groups of cows each with one bull were recorded over a 7-week breeding season and the stage of estrus was identified using ultrasonography. Telemetry data from bull and cows, collected over 4 8-day logger deployments, were log transformed and analyzed by ANOVA. Both the number and duration of bull-cow affiliations were significantly (P < 0.001) greater in estrous cows compared to anestrus cows. These results support the development of the UHF technology as a hands-off and noninvasive means of gathering socio-sexual information on both wildlife and livestock for reproductive management.

Reprodução assistida: a organização da atenção às infertilidades e o acesso às técnicas reprodutivas em dois serviços público-universitários no Estado do Rio de Janeiro.

Nesta tese foram analisadas iniciativas e ações individuais e coletivas de gestores e profissionais de dois Hospitais Público-Universitários de Saúde, que mantêm serviços de referência no atendimento às infertilidades, no Estado do Rio de Janeiro. É visada a implementação de tecnologias de reprodução assistida (RA) pelo SUS, no Estado. O estudo constou de entrevistas com profissionais de saúde destes serviços e especialistas na área que ali atuam, leitura de prontuários e pesquisa documental no Departamento de Serviço Social de um dos serviços, além de atualização bibliográfica no campo estudado. Os resultados obtidos de material primário e documental evidenciam a não priorização da reprodução assistida em políticas públicas de saúde no Brasil. No entanto, foi possível encontrar importantes iniciativas dos próprios profissionais de saúde para a ampliação da atenção em infertilidade e do acesso às tecnologias reprodutivas no Rio de Janeiro. Em geral, foram mobilizações individuais, que dependeram do empenho direto dos médicos responsáveis dos serviços. As motivações para estas ações incluíam aspectos acadêmicos, assistenciais, de direitos reprodutivos, além de interesses público-privados. A única mobilização interinstitucional, organizada inicialmente pelo Serviço Social, não conseguiu garantir o acesso à assistência integral em reprodução assistida no Rio de Janeiro. No caso da reprodução assistida, há uma forte desigualdade de base socioeconômica, já que mulheres e casais pobres são excluídos, ou quase, do acesso à IIU, Fiv e ICSI, pois não têm condições econômicas para tentar um tratamento particular, onde se encontram concentradas mais de 90% da assistência no país. Este segmento populacional não encontra recursos, nem tecnológicos, nem humanos, nos serviços públicos de saúde. Este quadro aumenta sua vulnerabilidade e reduz sua autonomia reprodutiva pela falta de acesso.

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.