Abstract Aims Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known. Purpose We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF. Method A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) <50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR<2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD. Results Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p<0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p<0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2). Conclusion CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.

Abstract Background Parkinson’s disease (PD) has been considered to be one of the most promising target diseases for forthcoming cell-based therapy. The aim of this study is to explore the views of individuals with cryopreserved embryos on using human embryonic stem cells for treating PD. Methods The study was performed as a qualitative, semi-structured interview study in June–October 2020. Participants were recruited at a private fertility clinic located in one of the larger Swedish cities. The clinic provides both publicly financed and privately financed IVF-treatments. All interviews were performed by telephone and analyzed using thematic content analysis. Five main categories emerged from 27 sub-categories. Results In total, 18 interviews were performed with 22 individuals, as either a couple (n = 16) or separately (n = 6). Participants had different views on what a cryopreserved embryo is. Some participants addressed cryopreserved embryos as ‘a lump of cells’, and some in terms of their ‘unborn child’. Conditions for donation of cryopreserved embryos for cell-based treatment in PD were: not losing control of what is happening to the embryo, that donating must be voluntary and based on informed consent with time for reflection, that reimbursement, equality and transparency. Conclusions Using cryopreserved embryos to treat PD is associated with fundamental ethical and practical issues. This study shows that IVF couples with left-over embryos may be supportive but there is a need for future research to assess people’s views on using cryopreserved embryos for cell-based treatment in PD on a more aggregated level.

Abstract Background Coronary microvascular disease (CMD) is prevalent in patients with heart failure with preserved ejection fraction (HFpEF). CMD can be assessed by coronary flow reserve (CFR) using transthoracic echocardiography (TTE). We hypothesised that the coronary Doppler flow profile in LAD at rest could reveal information about the downstream resistance in the vessel, where increased resistance is a sign of CMD. Purpose We aimed to measure features of the acceleration and deceleration of the LAD Doppler flow profile to investigate association with coronary and cardiac function. Methods CFR was assessed in 202 patients by TTE in the PROMIS-HFpEF-study. Detailed flow profile measurements were possible in 169 patients (84%) who constituted the study population. The coronary Doppler flow profiles were analysed with respect to acceleration time (corAT) and slope (corAS) and deceleration pressure half time (corPHT) (figure 1). Results The average age was 75±9 years and 55% were female. Atrial fibrillation (AF) was present in 53% and 62% were current or previous smokers. There was no significant difference in gender, age, BMI, blood pressure or heart rate in the CMD vs non-CMD group, but AF as well as a history of smoking was more prevalent in the CMD group, p=0.022 and 0.003 respectively. Further, there were no significant differences in neither corAT nor corAS between the two groups. However, patients with CMD had shorter corPHT of 268±64 ms compared to 298±67 ms, p=0.01. A longer corPHT was associated with increased TAPSE (R=0.205, p=0.007) and higher CFR (R=0.231, p=0.002). In a multivariable analysis adjusted for age, sex, BMI, SBP, reactive hyperemia index, HR, AF, diabetes, CVD, smoking, LVM and study site*, corPHT independently predicted CFR (table 1, p=0.016). Conclusion Short pressure half time, indicating a steep deceleration of the coronary Doppler signal at rest, may provide useful information for prediction of CFR determined by transthoracic ultrasound by reflecting the increased resistance in the coronary microvasculature associated with CMD. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Sahlgrenska University Hospital, Sponsor AstraZeneca

Are we looking under the lamp although we know the lost key is somewhere else? : Or is it just about the egg?

Research question: Elective single-embryo transfer (eSET) at blastocyst stage is widely used to reduce the frequency of multiple pregnancies after IVF. There are, however, concerns about increased risks for the offspring with prolonged embryo culture. Is it possible to select embryos for transfer at the early cleavage stage and still achieve low twin rates at preserved high live birth rates? Design: A prediction model (PM) was developed to optimize eSET based on variables known 2 days after oocyte retrieval (fresh day 2 embryo transfers; double-embryo transfers 1999-2002 (n=2846) and SET 1999-2003 (n=945); n total=3791). Seventy-five variables were analysed for association with pregnancy chance and twin risk and combined for PM construction. This PM was validated in 2004-2016 including frozen-thawed transfers (FET), to compare cumulative live birth rate (CLBR) and twin rate before (1999-2002 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2007, n=3495) and after (2004-2011 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2016, n=11195) implementing the model. Results: The PM was constructed from four independent variables: female age, embryo score, ovarian sensitivity and treatment history. The calibration, i.e. the fit of observed versus predicted results, was excellent both at construction and at validation. Without compromising CLBR, twin rate was reduced from 25.2% to 3.8%, accompanied by profound improvements in perinatal outcome. Conclusion: The results provide the first successful construction, validation and impact analysis of a day 2 transfer PM to reduce multiple pregnancies.

Objective: To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture.Design: Prospective observational cohort study.Setting: University-affiliated private infertility center.Patient(s): SET in 8,451 IVF/ICSI treatments in 5,699 unselected consecutive couples during 1999-2014.Intervention(s): A total of 100 basal patient characteristics and treatment data were analyzed for associations with live birth after IVF/ICSI (adjusted for repeated treatments) and subsequently combined for prediction model construction.Main Outcome Measure(s): Live birth rate (LBR) and performance of live birth prediction model.Result(s): Embryo score, treatment history, ovarian sensitivity index (OSI; number of oocytes/total dose of FSH administered), female age, infertility cause, endometrial thickness, and female height were all independent predictors of live birth. A prediction model (training data set; n = 5,722) based on these variables showed moderate discrimination, but predicted LBR with high accuracy in subgroups of patients, with LBR estimates ranging from <10% to >40%. Outcomes were similar in an internal validation data set (n = 2,460).Conclusion(s): Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI. (C)2016 by American Society for Reproductive Medicine.

INTRODUCTION:We compared the ability of four different ovarian reserve tests (ORTs) to predict live births per started in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycle, and poor and excessive response to controlled ovarian hyperstimulation.MATERIAL AND METHODS:This was a cohort study in a private infertility center in collaboration with Uppsala University, comprising 1230 IVF-ICSI cycles in 892 consecutive women between April 2008 and June 2011. Anti-Müllerian hormone (AMH) levels, antral follicle counts (AFC), combinations of basal levels of follicle-stimulating hormone and luteinizing hormone, and menstrual cycle lengths were analyzed for correlation and treatment outcome prediction in age-adjusted statistical models. Stepwise multivariable generalized estimating equation analyses were carried out in a sub-group with complete data on all four ORTs (620 cycles in 443 women). Odds ratios and c-statistics were calculated in the largest available set of data for each significant variable. Primary outcomes were live birth rate per started cycle and poor and excessive ovarian response to controlled ovarian hyper-stimulation (defined by the ovarian sensitivity index).RESULTS:All ORTs correlated significantly with each other, with the strongest correlation between AFC and AMH (r = 0.71, p < 0.0001). Univariately, AMH and age equivalently predicted live birth (c-statistic 0.61), and together they provided a significantly better model (c-statistic 0.64). For prediction of poor and excessive response the best model included AMH, AFC and age (c-statistic 0.89).CONCLUSIONS:AMH improves the ability to estimate live birth rates after assisted reproduction compared with female age alone. AMH, AFC and age together constituted the best model for prediction of ovarian response.

We compared the ability of four different ovarian reserve tests (ORTs) to predict live births per started in vitro fertilization–intracytoplasmic sperm injection (IVF-ICSI) cycle, and poor and excessive response to controlled ovarian hyperstimulation. This was a cohort study in a private infertility center in collaboration with Uppsala University, comprising 1230 IVF-ICSI cycles in 892 consecutive women between April 2008 and June 2011. Anti-Müllerian hormone (AMH) levels, antral follicle counts (AFC), combinations of basal levels of follicle-stimulating hormone and luteinizing hormone, and menstrual cycle lengths were analyzed for correlation and treatment outcome prediction in age-adjusted statistical models. Stepwise multivariable generalized estimating equation analyses were carried out in a sub-group with complete data on all four ORTs (620 cycles in 443 women). Odds ratios and c -statistics were calculated in the largest available set of data for each significant variable. Primary outcomes were live birth rate per started cycle and poor and excessive ovarian response to controlled ovarian hyper-stimulation (defined by the ovarian sensitivity index). All ORTs correlated significantly with each other, with the strongest correlation between AFC and AMH ( r  = 0.71, p  < 0.0001). Univariately, AMH and age equivalently predicted live birth ( c -statistic 0.61), and together they provided a significantly better model ( c -statistic 0.64). For prediction of poor and excessive response the best model included AMH, AFC and age ( c -statistic 0.89). AMH improves the ability to estimate live birth rates after assisted reproduction compared with female age alone. AMH, AFC and age together constituted the best model for prediction of ovarian response.

Treatment success in IVF-ICSI is mainly limited by female age, but differences in ovarian reserve (OR; the remaining pool of oocytes and their quality) between individuals modify treatment prerequi ...

CONTEXT Previous studies have suggested that antimüllerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. OBJECTIVE The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. DESIGN The study was a prospective cohort study between April 2008 and June 2011. SETTING The study was done at a university-affiliated private infertility center. PATIENTS The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. INTERVENTION(S) AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. MAIN OUTCOME MEASURES Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. RESULTS AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), Ptrend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. CONCLUSIONS AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

Keywords:: anti-müllerian hormonehigh ovarian response IVFovarian hyperstimulationovarian reserve controlledpolycystic ovary syndrome

A comparison of four different ovarian reserve tests (ORT) for predicting the ovarian response and chance of live birth after IVF-ICSI treatment

Antimullerian hormone predicts pregnancy and live-birth rates after assisted reproduction and reflect oocyte quality besides oocyte quantity

Studies investigating the possibility that measures of ovarian reserve may be predictive for assisted reproductive outcomes have had conflicting results. It remains unclear whether there is an association between ovarian reserve and assisted reproductive outcome. It is also unclear whether estimates of ovarian reserve can provide information on oocyte quality in addition to oocyte quantity. Women with polycystic ovaries have the greatest number of antral follicles and comprise a large proportion of the assisted reproductive technology populations, but are usually excluded from ovarian reserve studies. This prospective observational study used antral follicle count (AFC) as a measure of ovarian reserve to test the hypothesis that ovarian reserve was associated with pregnancy and live birth rates in a large unselected assisted reproduction population covering the entire range of AFC. A secondary aim of the study was to determine whether AFC is just a quantitative measure of ovarian reserve or also provides information on oocyte quality. The study population was comprised 2092 women undergoing 4308 in vitro fertilization/intracytoplasmic sperm injection treatment cycles at a university-affiliated private infertility center between 1999 and 2009. The primary study outcome measures were pregnancy rate and live birth per started stimulation. There was a clear log-linear relationship between treatment outcome and AFC; pregnancy rate and life-birth rate increased relative to log-transformed AFC and leveled out (with no further increase) above an AFC of about 30. Women with polycystic ovaries had higher pregnancy rates and live birth rates (both P < 0.0001), independent of ovulatory status. These results remained significant after adjustment for age and number of oocytes retrieved. These findings show a strong log-linear association between AFC as a measure of ovarian reserve and assisted reproduction outcomes of pregnancy and live birth rate. The data suggest that women with polycystic ovaries, with the best outcome and highest ovarian reserve, are at the one extreme in the spectrum of AFC, with poor treatment outcome and the lowest reserve at the other extreme. The results also suggest that AFC provides information on oocyte quality as well as quality.

BACKGROUND The objective of this study was to evaluate the associations of basal gonadotrophins with pregnancy and delivery rates at IVF/ICSI. METHODS A prospective observational study was conducted at a university-affiliated private infertility centre. Patients were 745 women, who underwent 1328 IVF/ICSI treatment cycles. Basal FSH, basal LH and combinations of FSH and LH versus treatment data and pregnancy and delivery rates were measured. RESULTS Combinations of FSH and LH gave significantly better information than the LH:FSH ratio, or each gonadotrophin alone: highest mean pregnancy rate (39%) was achieved in women with low FSH (<6.7 U/l) and with high LH levels (>4.9 U/l), whereas pregnancy rate was lowest (22%) in women with high FSH and low LH levels. Pregnancy rates were intermediate (27-28%) if FSH and LH were either both low or both high (P for trend = 0.0004). Associations to delivery rates and measures of ovarian response and embryo quality followed the same pattern. CONCLUSIONS Basal LH modifies and improves the information given by basal FSH alone. Low FSH level combined with high LH probably reflects a well-preserved ovarian reserve and is associated with the highest success rates at IVF/ICSI.

OBJECTIVE:To investigate whether menstrual cycle length correlates with success rates at IVF/intracytoplasmic sperm injection (ICSI) and could be used as a marker of ovarian reserve. DESIGN:Prospective observational study. SETTING:Private infertility centre. PATIENT(S):A total of 6271 IVF/ICSI treatment cycles. INTERVENTION(S):Self-reported mean number of menstrual days during the last year was recorded before initiation of IVF/ICSI treatment. MAIN OUTCOME MEASURE(S):Relations between menstrual cycle length and pregnancy and delivery rates. RESULT(S):Increasing age was associated with a subtle shortening of mean menstrual cycle length. Menstrual cycle length correlated linearly with pregnancy and delivery rates, even after age adjustment. The chance of delivery after IVF/ICSI was almost doubled for women with a menstrual cycle length >34 days compared with women with a menstrual cycle length <26 days. Menstrual cycle length was also significantly associated with ovarian response to FSH/hMG stimulation and embryo quality. CONCLUSION(S):Mean menstrual cycle length is highly related to success rates in assisted reproduction, independently of age. A precise menstrual cycle history could be used as a simple marker of ovarian reserve.