Treatment and preservation at the extremes of reproductive age: a case report outlining the ethical dilemmas.

PURPOSE: The purpose of the study was to report a livebirth from a cryopreserved embryo created from autologous oocytes collected at 47 years and 9 months that outlines the ethical difficulties of decision-making at the extreme of reproductive age. METHODS: The method used was IVF and embryo cryopreservation within an assisted conception unit prior to adjuvant cancer treatment in a nulliparous patient diagnosed with breast carcinoma (47 years and 9 months at oocyte collection). RESULTS: A 47-year-old nulliparous woman was diagnosed with breast malignancy during work-up for fertility treatment. Ovarian stimulation yielded one embryo from four oocytes that was cryopreserved to allow completion of adjuvant treatment. Subsequent embryo transfer cycle led to a live birth of a healthy baby girl at term, weighing 3.37 kg. CONCLUSION: This paper demonstrates the oldest reported age of autologous oocyte collection to have achieved a livebirth. In women where most would consider treatment futile, we highlight the difficulties in decision-making in this group of patients.

What can we learn from a decade of promoting safe embryo transfer practices? A comparative analysis of policies and outcomes in the UK and Australia, 2001-2010.

STUDY QUESTION: Given similar socio-demographic profiles and costs of healthcare, why has Australia been significantly more successful than the UK in reducing the assisted reproductive technology (ART) multiple birth rate? SUMMARY ANSWER: The Australian model of supportive public ART funding, permissive clinical guidelines and an absence of published clinic league tables has enabled Australian fertility specialists to act collectively to achieve rapid and widespread adoption of single embryo transfer (SET). WHAT IS KNOWN ALREADY: There are striking differences in ART utilization and clinical practice between Australia and the UK. The ART multiple birth rate in Australia is <8% compared with slightly <20% in the UK. The role played by public funding, clinical guidelines, league tables and educational campaigns deserves further evaluation. STUDY DESIGN, SIZE, DURATION: Parallel time-series analysis was performed on ART treatment and outcome data sourced from the Human Fertilisation and Embryology Authority (HFEA) ART Registry and the Australian and New Zealand Assisted Reproduction Database (ANZARD). Funding arrangements, clinical practice guidelines and key professional and public education campaigns were mapped to trends in clinical practice and ART treatment outcomes between 2001 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 425 360 and 422 003 autologous treatment cycles undertaken between 2001 and 2010 in the UK and Australia were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: From 2001 to 2010, the most striking difference in clinical practice was the increase in SET cycles in Australia from 21 to 70% of cycles, compared with an increase from 8.4 to 31% in the UK. In 2004-2005, both countries introduced clinical guidelines encouraging safe embryo practices, however, Australia has a history of supportive funding for ART, while the National Health Service has a more restrictive and fragmented approach. While clinical guidelines and education campaigns have an important role to play, funding remains a key element in the promotion of SET. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive population study and therefore quantifying the independent effect of differential levels of public funding was not possible. WIDER IMPLICATIONS OF THE FINDINGS: With demand for ART continuing to increase worldwide, it is imperative that we remove barriers that impede safe embryo transfer practices. This analysis highlights the importance of supportive public funding in achieving this goal.

Prognostic value of first IVF cycle on success of a subsequent cycle.

OBJECTIVE: To determine whether a live birth or miscarriage in a previous IVF cycle is predictive of success in a subsequent cycle. DESIGN: Retrospective study SETTING: Private IVF unit PATIENTS: 1141 couples having a second IVF cycle. INTERVENTION: 3 groups; Group I: women who had a live birth in the first cycle, Group II those who had a miscarriage, Group III, women who had a negative pregnancy test in their first cycle. OUTCOME MEASURES: Pregnancy (PR), Live birth (LBR) & miscarriage rates in the second cycle. RESULTS: For women < than 40: PR was 46.4% (368/793), miscarriage rate was 29.9% and the LBR was 32.5% (258/793). Women in groups I & II had a statistically higher PR than those in group III 63.3% v 55.2% v 41.9% respectively. LBR was higher 45% v 37.8 v 29.6% respectively. Miscarriage rate was similar. For women 40 years and older: The PR was 21.0% (73/348), miscarriage rate was 52.1% (38/73) and the LBR was 10.1% (35/348).There was no significant difference in PR among women in groups I, II & III. The LBR and miscarriage rates were similar in all groups. CONCLUSION: Young women who had a live birth and those who experienced an early miscarriage after IVF have a greater likelihood of achieving a live birth in a second cycle. Outcome of first IVF cycle however does not predict subsequent IVF success in older women.

Is meaningful reporting of national IVF outcome data possible?

The traditional use of live birth per IVF cycle started as the sole indicator of success can be potentially misleading. Different policies regarding reporting IVF cycles started, variations in the number of embryos transferred and associated multiple births have a profound effect on success, such that results from clinics or countries with similar expertise may appear significantly different. To account for these differences, we recommend the use of live birth per embryo-calculated as the number live birth events per 100 embryos transferred-as an outcome measure. This method of reporting can correct for under reported cycles started, adjust for differences in embryo transfer policies and provides an objective and reproducible international benchmark. Combining live birth outcomes from fresh and frozen cycles in the same reporting period per oocyte collection is also recommended. These data should be published as a range related to the national average without a mean or central point. Furthermore, for proper interpretation of results, it would be helpful if the policies regarding patient inclusion and cycle cancellation at all clinics are published.

Are US results for assisted reproduction better than the rest? Is it a question of competence or policies?

A comparison of nationally published 2006 data from the USA, UK and Australia and New Zealand (ANZ) was performed. Although live births/cycle was higher in USA, live birth/embryo transferred was significantly higher in ANZ (18.2%) compared with both USA and UK (13.8%) (P<0.001). The multiple rates were significantly lower in ANZ (12.0%) compared with USA (30.7%) and UK (25.2%) (P<0.001). The incidence of oocyte donation was significantly higher in the USA (11.1%) than in ANZ (2.8%) and UK (3.9%) (P<0.001). There was significantly higher cycle cancellation in USA (11.5%) compared with the UK (6.8%) and ANZ (9.5%) (P<0.001). The incidence of frozen embryo transfer cycles was significantly higher in ANZ (59%) compared with both UK (24%) and USA (22%) (P<0.001). The total live birth rate from fresh and frozen cycles for the same year was significantly higher in ANZ at 32.0% compared with the UK at 28.8% (P<0.001) with half the multiple rate. It is argued that the USA's higher success rates are explained by policy (transferring higher number of embryos) and selection issues (cancelling or avoiding poor responders) rather than being a matter of clinical competence.

Association of Sleep Apnea with Mortality in Patients with Advanced Kidney Disease.

BACKGROUND AND OBJECTIVES: In the general population, sleep disorders are associated with mortality. However, such evidence in patients with CKD and ESKD is limited and shows conflicting results. Our aim was to examine the association of sleep apnea with mortality among patients with CKD and ESKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this prospective cohort study, 180 patients (88 with CKD stage 4 or 5, 92 with ESKD) underwent in-home polysomnography, and sleep apnea measures such as apnea hypopnea index (AHI) and nocturnal hypoxemia were obtained. Mortality data were obtained from the National Death Index. Cox proportional hazard models were used for survival analysis. RESULTS: Among the 180 patients (mean age 54 years, 37% women, 39% with diabetes, 49% CKD with mean eGFR 18±7 ml/min per 1.73 m2), 71% had sleep apnea (AHI>5) and 23% had severe sleep apnea (AHI>30). Median AHI was 13 (range, 4-29) and was not significantly different in patients with advanced CKD or ESKD. Over a median follow-up of 9 years, there were 84 (47%) deaths. AHI was not significantly associated with mortality after adjusting for age, sex, race, diabetes, body mass index, CKD/ESKD status, and kidney transplant status (AHI>30: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 0.6 to 4.0; AHI >15 to 30: HR, 2.3; 95% CI, 0.9 to 5.9; AHI >5 to 15: HR, 2.1; 95% CI, 0.8 to 5.4, compared with AHI≤5). Higher proportion of sleep time with oxygen saturation <90% and lower mean oxygen saturation were significantly associated with higher mortality in adjusted analysis (HR, 1.4; 95% CI, 1.1 to 1.7; P=0.007 for every 15% higher proportion, and HR, 1.6; 95% CI, 1.2 to 2.1; P=0.003 for every 2% lower saturation, respectively). Sleep duration, sleep efficiency, or periodic limb movement index were not associated with mortality. CONCLUSIONS: Hypoxemia-based measures of sleep apnea are significantly associated with increased risk of death among advanced CKD and ESKD.

A systematic review investigating psychosocial aspects of egg sharing in the United Kingdom and their potential effects on egg donation numbers.

This review aims to provide an up-to-date knowledge of the psychosocial aspects of egg donation from the perspectives of the egg share donor and their recipient. It explores the motives, experiences and attitudes of egg sharers and their views towards donor anonymity and disclosure. Conclusions are made on how these findings can guide clinical practice and improve egg sharing numbers. A systematic search of peer-reviewed journals of four computerized databases was undertaken. Eleven studies were included in the review. Psychosocial aspects towards donation were positive from the egg share donor and recipient. Concerns raised were whether participating in the egg sharing scheme would impact on their success rates, as well as frustration expressed by a minority regarding the lack of knowledge of egg sharing outside of fertility clinics. The 2005 legislative changes in the UK have not caused the anticipated dramatic decrease in egg donation; however, oocyte donation still falls short of demand. Egg sharing provides a practical option for more patients to access IVF, whilst also providing more donor oocytes. Improved information provision will result in greater awareness of egg sharing, with the potential to recruit more donors and meet the needs of recipients currently on long waiting lists.

Metabolomics as a tool to identify biomarkers to predict and improve outcomes in reproductive medicine: a systematic review.

BACKGROUND: Infertility is a complex disorder with significant medical, psychological and financial consequences for patients. With live-birth rates per cycle below 30% and a drive from the Human Fertilisation and Embryology Authority (HFEA) to encourage single embryo transfer, there is significant research in different areas aiming to improve success rates of fertility treatments. One such area is investigating the causes of infertility at a molecular level, and metabolomics techniques provide a platform for studying relevant biofluids in the reproductive tract. OBJECTIVE AND RATIONALE: The aim of this systematic review is to examine the recent findings for the potential application of metabolomics to female reproduction, specifically to the metabolomics of follicular fluid (FF), embryo culture medium (ECM) and endometrial fluid. To our knowledge no other systematic review has investigated this topic. SEARCH METHODS: English peer-reviewed journals on PubMed, Science Direct, SciFinder, were systematically searched for studies investigating metabolomics and the female reproductive tract with no time restriction set for publications. Studies were assessed for quality using the risk of bias assessment and ROBIN-I. OUTCOMES: There were 21 studies that met the inclusion criteria and were included in the systematic review. Metabolomic studies have been employed for the compositional analysis of various biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid and endometrial fluid. There is some weak evidence that metabolomics technologies studying ECM might be able to predict the viability of individual embryos and implantation rate better than standard embryo morphology, However these data were not supported by randomized the controlled trials (RCTs) which showed no evidence that using metabolomics is able to improve the most important reproductive outcomes, such as clinical pregnancy and live-birth rates. This systematic review provides guidance for future metabolomic studies on biofluids of the female reproductive tract, with a summary of the current findings, promise and pitfalls in metabolomic techniques. The approaches discussed can be adapted by other metabolomic studies. WIDER IMPLICATIONS: A range of sophisticated modern metabolomic techniques are now more widely available and have been applied to the analysis of the female reproductive tract. However, this review has revealed the paucity of metabolomic studies in the field of fertility and the inconsistencies of findings between different studies, as well as a lack of research examining the metabolic effects of various gynecological diseases. By incorporating metabolomic technology into an increased number of well designed studies, a much greater understanding of infertility at a molecular level could be achieved. However, there is currently no evidence for the use of metabolomics in clinical practice to improve fertility outcomes.

Investigating psychosocial attitudes, motivations and experiences of oocyte donors, recipients and egg sharers: a systematic review.

INTRODUCTION: The donation of oocytes has been made feasible as a result of in vitro fertilization (IVF). This treatment offers an answer for infertile women with ovarian conditions, such as primary ovarian insufficiency. Demand for oocyte donors has been on the rise globally, with infertile couples, as well as gay men, increasingly using it as a means to found their families. With an acute shortage of oocyte donors globally, the psychosocial aspects behind oocyte donation are important for fertility clinics to understand. This paper aims primarily to provide an up-to-date systematic review of the psychosocial aspects of oocyte donation from the point of view of oocyte donors and recipients and egg sharers. Its secondary aims are to explore the motives and experiences of donors as well as attitudes towards donor anonymity and disclosure. An emphasis has been placed on the analysis of donors in the UK. No review has analysed together the aforementioned donor groups along with recipient group. METHODS: A systematic search of English peer-reviewed journals of four computerized databases was undertaken, with no time restriction set for publications. RESULTS: There were 62 studies which met the inclusion criteria and were included in the systematic review. Attitudes towards donation were positive from both a donor oocyte and recipient point of view, with medical procedures being well tolerated and excellent post-donation satisfaction among all donor groups. There were distinct differences between the different donor groups and recipients in motivation for oocyte donation and decisions for disclosure. Attitudes towards anonymity issues were reassuring with a significant proportion of donors of all types willing to donate as identifiable donors. However, there were methodological limitations identified in the studies reviewed. CONCLUSION: This review successfully explored the important psychosocial aspects of oocyte donation. In general terms the attitudes and feeling of patients involved from all sides of the donation process were extremely positive. A number of key and consistent issues emerged which demonstrated differences and similarities between the different donor groups, as well as a greater understanding of the recipient. With regard to psychosocial well-being, the results were reassuring throughout all donor groups, especially the egg share donors. Although it seems the 2005 legislative changes in the UK have not caused the anticipated dramatic decrease in gamete donation, oocyte donation still falls far short of demand. The UK has an increasing population of patients from different ethnic backgrounds and same sex relationships seeking oocyte donation, with very few studies including these groups of patients. An increased number of well-designed studies looking into the psychological issues surrounding gamete donation of different patient groups, could allow more directed assessment and counselling of oocyte donors and recipients, with a resulting increase in donor recruitment.

Rheumatoid Arthritis as a Therapeutic Challenge in a Patient with Lynch Syndrome.

BACKGROUND: Lynch syndrome (LS) is an inherited colorectal cancer (CRC) syndrome accounting for about 3-5% of all cases and involves significantly higher risk of subsequent malignancies, colonic as well as extra-colonic. Increased risk of malignancies, especially lymphoid malignancies, have been described in patients with autoimmune diseases like rheumatoid arthritis (RA), systemic lupus erythematosus, and Sjögren's syndrome. Epidemiological studies demonstrated that hematopoietic, lung, skin, and prostate cancers are increased in RA, while breast and colon cancers are decreased, with an overall slight increase in all cancers. CASE REPORT: Our case demonstrates the development of CRC, endometrial cancer, and breast cancer as a presentation of LS in a patient with RA and presents a therapeutic challenge for RA treatment. CONCLUSIONS: We describe a patient with LS and RA presenting a therapeutic challenge because biologic agents commonly used to treat severe RA need to be used cautiously in patients with history of malignancy.

Malignant Hypertension and Thrombotic Thrombocytopenic Purpura: False Friends.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic disorder resulting in hemolysis of red blood cells, consumption of platelets, and occlusion of microvasculature. Malignant hypertension is the clinical syndrome of severe elevations in blood pressure and funduscopic hypertensive retinopathy, including bilateral flame-shaped hemorrhage and papilledema. CASE REPORT: We describe the case of a 63-year-old man who presented with features of TTP and malignant hypertension treated with plasma exchange and developing end-stage renal disease. CONCLUSIONS: Given the diagnostic uncertainty at presentation, clinicians should quickly intervene to control hypertension and institute plasma exchange as needed.

Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies contained groups that were comparable in age, although the criteria of reporting age varied. Taking all studies into account, the incidence of uterine cancer was 0.14% (150 of 103,758) in the fertility treatment group and 2.22% (14,918 of 672,466) in the non-fertility treatment group. Using the random-effect model to analyze uterine cancer incidence, this difference was not found to be of statistical significance: OR 0.78 (95% CI, 0.39-1.57). The degree of heterogeneity was high (I(2)=68%). The risk for the development of uterine and in particular endometrial cancer posed by infertility and an unopposed oestrogen state is widely recognized. The present analysis aimed to perceive whether standard fertility drugs were also a risk to future uterine cancer development. The treatment does increase the concentrations of unopposed oestrogen for a short periods of time but if successful leads to fertility. This meta-analysis points to a non-deleterious effect of fertility drugs towards the development of uterine cancer, a conclusion strongly supported by our sub-group analysis.

Parenting infants conceived by gamete donation.

In recent years, concerns have been raised regarding the potentially negative consequences of gamete donation for parent-child relationships. Findings are presented of a study of families with an infant conceived by gamete donation. Fifty donor insemination families and 51 egg donation families were compared with 80 natural conception families on standardized interview and questionnaire measures of the psychological well-being of the parents, the quality of parent-child relationships, and infant temperament. The differences that were identified indicated more positive parent-child relationships among the gamete donation than the natural conception parents, accompanied by greater emotional involvement with the child. Comparisons were also carried out between the donor insemination and the egg donation parents on their experiences of gamete donation. In contrast to the findings of earlier investigations, the donor insemination and egg donation parents appeared to be more open toward disclosing the donor conception to the child. It was concluded that infants conceived by egg or sperm donation did not appear to be at risk for parenting difficulties.

Poor response cycles: when should we cancel? Comparison of outcome between egg collection, intrauterine insemination conversion, and follow-up cycles after abandonment.

OBJECTIVE: To determine optimal management with one or two mature follicles after stimulation. DESIGN: Retrospective analysis. SETTING: Lister fertility clinic. PATIENT(S): A total of 1,350 IVF/intracytoplasmic sperm injection cycles (7.3% of total) during 1998-2009 were found to have one or two mature follicles. INTERVENTION(S): Group 1 (n = 807) comprised those who proceeded to vaginal egg collection (VEC) (59.8%; outcome per egg collection), group 2 (n=248) those who converted to IUI (18.4%; outcome per insemination) and group 3 (n=259) those who abandoned the current cycle (21.9%; outcome per abandoned cycle in first subsequent cycle). MAIN OUTCOME MEASURE(S): Live birth rate, clinical pregnancy rate, and biochemical pregnancy rate. RESULT(S): Biochemical pregnancy rates of 13.1%, 4.9%, and 9.7%, clinical pregnancy rates of 8.1%, 3.6%, and 7.2%, and ongoing pregnancy rates of 6.8%, 2.0%, and 5.5% were achieved in groups 1, 2, and 3, respectively. All pregnancy outcomes were significantly higher after VEC (group 1) than for those converted to IUI (group 2), and all pregnancy outcomes were higher with borderline significance in group 3 vs. group 2. There was no significant difference in outcome between groups 1 and 3. CONCLUSION(S): Our data suggest that for such poor responders, proceeding to VEC may represent their best chance of successful outcome. Conversion to IUI offers the poorest outcome, and despite the potential for improvements in cycle protocol, abandoning and a further attempt does not improve outcome (using abandoned cycle as the denominator).

The effect of duration of coasting and estradiol drop on the outcome of assisted reproduction: 13 years of experience in 1,068 coasted cycles to prevent ovarian hyperstimulation.

OBJECTIVE: To determine the effect of duration of coasting (Cd), estradiol levels at trigger (E(2)), and level of estradiol drop (E(2)d) on live birth rate (LBR) in cycle outcome. DESIGN: Retrospective analysis. SETTING: Hospital-based fertility clinic. PATIENT(S): A total of 1,068 coasted cycles (5.7% of total) of IVF/ICSI from 1996 to 2008. INTERVENTION(S): Coasting in IVF/ICSI cycles. MAIN OUTCOME MEASURE(S): Live birth rate and secondary cycle outcomes. RESULT(S): Mean Cd, E(2), and E(2)d were 4.7 days, 11,567 pmol/L, and 9,760 pmol/L, respectively. Maternal age, duration of subfertility, and serum FSH were significantly lower, and AMH (39.7 vs. 15.1 pmol/L) and prevalence of polycystic ovary syndrome (31.8% vs. 17.8%) significantly higher, in coasted cycles. Fertilization rate, clinical pregnancy rate, and LBR per cycle and implantation rate of 64.4%, 40.7%, 35.7%, and 24.7%, respectively, were demonstrated, with no significant difference in LBR in cycles coasted for up to 8 days or when divided according to E(2) or E(2)d. Lack of predictive capability on LBR was confirmed by receiver operator curve analysis which demonstrated areas under the curve of 0.51, 0.53, and 0.54 for E(2), Cd, and E(2)d, respectively. CONCLUSION(S): Although cycle numbers beyond 6 days are limited, coasting for up to 8 days does not affect LBR, and E(2) and E(2)d levels do not significantly affect cycle outcome.

Dichorionic triamniotic triplet pregnancy with monozygotic twins discordant for trisomy 13 after preimplantation genetic screening: case report.

OBJECTIVE: To report the first dichorionic triamniotic triplet pregnancy discordant for trisomy 13 after in vitro fertilization (IVF) treatment with preimplantation genetic screening (PGS). DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 40-year-old para 1+6 woman. INTERVENTION(S): IVF combined with PGS for chromosomes 13, 16, 18, 21, and 22, resulting in the transfer of two embryos. MAIN OUTCOME MEASURE(S): Prenatal fetal ultrasonography revealed a dichorionic triamniotic triplet pregnancy. An amniocentesis, performed at 15-weeks' gestation, confirmed that the singleton and one monozygotic twin were normal but the other monozygotic twin was trisomy 13. RESULT(S): After diagnosis and counseling, selective termination of the trisomy 13 monozygotic twin was performed at 16 weeks and 4 days. At 18 weeks and 4 days the co-twin died. A healthy boy was delivered by elective caesarean section at 36-weeks' gestation. CONCLUSION(S): Assisted reproductive techniques that breach the embryo's zona pellucida such as assisted hatching and PGS embryo biopsy increase the incidence of monozygotic twins. Due to high levels of mosaicism in human preimplantation embryos, PGS cannot ensure that embryos diagnosed as normal and selected for transfer do not contain abnormal cells. Hence, further reports of discordant monozygotic twins following PGS are expected, emphasizing the need for appropriate counseling of patients wishing to embark on an IVF/PGS treatment cycle.

Relationship between women's age and basal follicle-stimulating hormone levels with aneuploidy risk in in vitro fertilization treatment.

OBJECTIVE: To assess the relationship of age and basal FSH level to the genetic quality of the embryo and the association with IVF treatment outcome. DESIGN: Prospective observation study. SETTING: A major inner London fertility clinic in the United Kingdom. PATIENT(S): One hundred fifty-one women who underwent IVF treatment cycles in conjunction with preimplantation genetic diagnosis for aneuploidy screening before fresh embryo transfer, between July 2003 and July 2005. INTERVENTION(S): Basal FSH levels (days 2-4) were determined at an earlier cycle, and women were divided into two groups: high basal FSH (>or=10 IU/L) and low basal FSH (<10 IU/L). Chromosome analysis was performed on a single blastomere by using fluorescence in situ hybridization. MAIN OUTCOME MEASURE(S): Percentage of aneuploid embryos. RESULT(S): The percentage of aneuploid embryos was not statistically significantly different between the high- (50.0%, n = 32) and low- (50.2%, n = 119) basal FSH groups. However, the percentage of aneuploid embryos was statistically significantly higher (56.2%, n = 109) for women aged >or=38 years, as compared with women <38 years of age (37.5%, n = 42), independent of basal FSH levels. CONCLUSION(S): Elevated basal FSH levels reflect lower ovarian reserve but have no association with genetic quality of embryos. The percentage of aneuploid embryos is increased with advanced maternal age.

Prednisolone suppresses NK cell cytotoxicity in vitro in women with a history of infertility and elevated NK cell cytotoxicity.

PROBLEM: To evaluate the effect of prednisolone on NK cell cytotoxicity in vitro environment and also to compare the effect of prednisolone versus immunoglobulin-G (IVIG) on NK cell cytotoxicity using in vitro co-culture with K562 cells. METHOD OF STUDY: The following is a prospective observational study, between August 2006 and February 2007, was carried out on blood samples from 110 patients with a history of recurrent miscarriage or recurrent failed implantation. Peripheral blood mononuclear cells containing NK cells were isolated and co-cultured with target cell K562 in three different effector-to-target (E:T) ratios of 50:1, 25:1 and 12.5:1. Prednisolone or IVIG was then added to the tube with E:T ratio of 50:1 to assess suppressive effect. The percentage killing was recorded and statistical analysis performed using Student's t-test. RESULTS: In the experiments with an E:T ratio of 50:1 without prednisolone or IVIG in the co-culture, the mean target cell killing percentage was 26.4%. In cultures using the same E:T ratio, this killing percentage was significantly reduced in the presence of IVIG (9.9%) or prednisolone (13.6%), (P<0.001 in both analyses). On comparing the reduction in killing percentage of target cells by prednisolone versus IVIG, a slightly lower reduction in the prednisolone co-culture was noted but this was not statistically significant (P>0.05). CONCLUSION: The results of this study show that prednisolone is able to suppress the cytolytic activity of the NK cell. Prednisolone and IVIG are almost equally effective in suppressing in vitro NK cell cytolytic activity.

The relationship of systemic TNF-alpha and IFN-gamma with IVF treatment outcome and peripheral blood NK cells.

BACKGROUND: To evaluate the association of serum tumour necrotic factor (TNF)-alpha and interferon (IFN)-gamma levels with IVF treatment outcome and peripheral blood NK cells. METHODS: Prospective observational study of 126 randomly selected women who underwent IVF treatment. The serum levels of TNF-alpha and IFN-gamma were determined by multiplex suspension beads array system. RESULTS: There were no significant differences with regard to the systemic TNF-alpha and IFN-gamma levels between the pregnant (n = 51, TNF-alpha: 53.5 pg/mL; IFN-gamma: 4.6 pg/mL) and not pregnant (n = 75, TNF-alpha: 63.0; IFN-gamma: 7.5) women after IVF treatment. For those women with a positive pregnancy after IVF treatment, the systemic TNF-alpha and IFN-gamma levels were higher in those women who miscarried (n = 13, TNF-alpha: 67.4; IFN-gamma: 9.1) when compared with those who had a live birth (n = 38, TNF-alpha: 48.7; IFN-gamma: 1.4), however this difference was not statistically significant. Interestingly, the systemic TNF-alpha and IFN-gamma levels were significantly higher in women who had a higher level of activated (CD69(+)) NK cells (n = 39, TNF-alpha: 86.8; IFN-gamma: 4.7) when compared with women who had a low level of activated NK cells (n = 87, TNF-alpha: 46.9; IFN-gamma: 1.7 P = 0.028 and 0.045 respectively). CONCLUSION: The systemic levels of TNF-alpha and IFN-gamma have no association with implantation rate or miscarriage rate in women undergoing IVF treatment. However, high levels of TNF-alpha and IFN-gamma are associated with elevated levels of activated NK cells and this may subsequently exert a negative impact on reproduction.