Would you consider donating your left-over embryos to treat Parkinson's disease? Interviews with individuals that underwent IVF in Sweden.

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.

Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF.

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.

Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers.

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.

Comparing four ovarian reserve markers--associations with ovarian response and live births after assisted reproduction.

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.

Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction.

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.

Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries.

OBJECTIVE: To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. DESIGN: Prospective observational study. SETTING: University-affiliated private infertility center. PATIENT(S): 2,092 women undergoing 4,308 IVF-ICSI cycles. INTERVENTION(S): AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. MAIN OUTCOME MEASURE(S): Pregnancy rate, live-birth rate, and stimulation outcome parameters. RESULT(S): The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC ∼30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. CONCLUSION(S): Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity.

High basal LH levels in combination with low basal FSH levels are associated with high success rates at assisted reproduction.

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.

Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization.

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.

The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis.

A new orally active drug, laquinimod (ABR-215062), was shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (EAE). Furthermore, leukocyte infiltration into the central nervous system (CNS) was abolished in the laquinimod-treated animals. By direct comparison based on dose and total exposure, laquinimod was approximately 20 times more potent than the immunomodulator roquinimex. Laquinimod also had clear therapeutic effect when given after clinical onset in a chronic relapsing EAE model. It therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties for the treatment of the autoimmune disease multiple sclerosis.