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| Evaluating the necessity for universal screening ... | Human Reproduction | |
BACKGROUND To minimize the potential for harmful inheritable conditions, donors are rigorously screened according to standard guidelines, yet such guidelines may not be sufficient to exclude egg donors with certain known inheritable conditions. We compared universal screening of oocyte donors with Tay-Sachs, Fragile X, karyotype and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) versus standard American Society of Reproductive Medicine (ASRM) guidelines that do not include such testing. METHODS In this 12 year retrospective cohort study, results of enhanced universal screening of all anonymous oocyte donor candidates from 1997 to 2008 at a university hospital oocyte donation program were reviewed. Primary outcomes were the frequency of oocyte donor candidates excluded as a result of enhanced universal screening (Tay-Sachs, Fragile X, karyotypic analysis and MMPI-2) versus basic screening according to ASRM guidelines. RESULTS Of 1303 candidates who underwent on-site evaluation, 47% passed the screening process, 23% were lost to follow-up and 31% were excluded. Genetic and psychological factors accounted for the most common reasons for candidate exclusion. Enhanced genetic screening excluded an additional 25 candidates (19% of all genetic exclusions) and enhanced psychological screening excluded an additional 15 candidates (12% of all psychological exclusions). Altogether enhanced screening accounted for 40 candidates (10%) of the total pool of excluded candidates. CONCLUSIONS Although our study is limited by its retrospective nature and center-specific conclusions, we show that enhanced comprehensive screening can exclude a significant number of candidates from an oocyte donor program and should be encouraged to assure optimal short-term and long-term outcomes for pregnancies achieved through oocyte donation. |
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| Secular trends in gestational age and birthweight... | Human Reproduction | |
BACKGROUND In recent decades, the overall rate of preterm births has increased. The aim of the present study was to examine whether this trend is also seen for multiple gestations. More specifically, we examined if there has been a decrease in gestational age for live born monozygotic (MZ) and dizygotic (DZ) twins and if there has been a simultaneous change in birthweight. The contributions of fertility treatments and Caesarean sections were taken into consideration. All analyses were carried out in two large European twin cohorts. METHODS Cross-sectional study of 6310 live born twin pairs, born between 1964–2007, from the Belgian East Flanders Prospective Twin Survey and 14 712 twin pairs, born between 1990–2006, from the Netherlands Twin Register. Multiple regression analyses were performed with gestational age as outcome variable, and multilevel analysis with birthweight as outcome variable. All analyses were performed with and without adjustment for zygosity, parity, maternal age, mode of conception and delivery and, for the analyses of birthweight, gestational age. RESULTS Gestational age decreased in a linear fashion from 1964 to 2007 with a decrease of 0.25 days per year in a similar way for MZ and DZ twins. Changes in birthweight depended on gestational age: up to 32 weeks, birthweight decreased and after 32 weeks birthweight increased. The frequency of infertility treatment and Caesarean sections, primiparity and advanced maternal age increased over the years, but none of these factors influenced the secular trends in gestational age and birthweight. CONCLUSIONS The decrease in gestational age and change in birthweight in twins are sources of concern, especially for very preterm twins, for whom birthweight decreased. For twins born after 32 weeks, an increase in birthweight was observed and this is very likely the explanation for the decrease in gestational age. |
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| Fertility is not altered in young adults born sma... | Human Reproduction | |
BACKGROUND The intrauterine environment may have a lifelong impact on individuals' health. However, results on the relationship between birth size and gonadal function are conflicting, and it remains unknown whether reproductive function is altered in adults born small for gestational age (SGA). The aim of the present study was to compare the fertility of young adults from the general population, born either SGA or appropriate for gestational age (AGA). METHODS There were 579 adults born SGA (birthweight under the 10th percentile) who were compared with 703 subjects of the same age (age 29.4 ± 4.1 years) born AGA (birthweight between 25th and 75th percentiles). They fulfilled a questionnaire focusing on the first attempt to give birth, to have a measure of the time to pregnancy and an estimation of the fecundability (the monthly pregnancy probability), two relevant indicators of fertility at the couple level. Ratios of fecundability between AGA and SGA subjects were adjusted for known fertility factors (age, smoking, reproductive history) and for socioeconomic status. RESULTS Time to pregnancy was comparable in the two groups: 5.7 ± 8.0 versus 6.6 ± 10.5 months in AGA and SGA, respectively (P = 0.31), in women and 5.1 ± 7 versus 6.0 ± 9 months in AGA and SGA, respectively, in men (P = 0.53). The adjusted ratios of fecundability comparing SGA to AGA subjects were not significant: HR = 0.91 [0.68;1.21] (P = 0.5) in women and HR = 0.95 [0.67;1.74] (P = 0.82) in men. CONCLUSION When studied in young adults from the general population, fertility is not reduced in those born SGA. |
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| Prospective cohort study in high responder oocyte... | Human Reproduction | |
BACKGROUND Ovarian stimulation regimens for in vitro fertilization seem to have a deleterious effect on oocyte quality and embryo aneuploidy in a dose-dependent manner. This study aims to test the influence of gonadotrophin doses on embryo aneuploidy rates. METHODS A total of 32 young oocyte donors with a high response to ovarian stimulation, were included in the study. Two subsequent stimulation treatments were performed in each donor: first, a standard dose cycle using a 225 IU starting dose of recombinant FSH (r-FSH) and secondly, a reduced dose cycle with a starting dose of 150 IU r-FSH. In both cycles, GnRH agonist co-treatment was used for down-regulation. Ovarian response, embryo development and aneuploidy for chromosomes 13, 15, 16, 17, 18, 21, 22, X and Y were the main outcomes of the study. RESULTS A total of 22 donors completed both treatments with different gonadotrophin doses. In the remaining 10 donors, the reduced dose cycle was cancelled due to low ovarian response. In those donors who completed both regimens, significant increases in rates of fertilization and chromosomally normal blastocysts were observed in the reduced dose cycle. No differences were observed in pregnancy and implantation rates in recipients who received oocytes from standard and reduced doses cycles. CONCLUSIONS Despite the limited numbers in our study, we can conclude that in high responder donors, a decrease in the gonadotrophin dose could improve fertilization rates and embryo quality. However, due to the reduced oocyte numbers with lower doses, a similar reproductive outcome in terms of live births would be expected. Clinical Trial.gov Identifier: nCT 00802295. |
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| Metabolism and karyotype analysis of oocytes from... | Human Reproduction | |
BACKGROUND Polycystic ovary syndrome (PCOS) is associated with metabolic disturbances which include impaired insulin signalling and glucose metabolism in ovarian follicles. The oocyte is metabolically dependent upon its follicle environment during development, but it is unclear whether PCOS or polycystic ovarian (PCO) morphology alone affect oocyte metabolism and energy-demanding processes such as meiosis. METHODS Immature human oocytes were donated by PCOS (n = 14), PCO (n = 14) and control (n = 46) patients attending the assisted conception programme at Leeds Teaching Hospitals NHS Trust. Oocytes were cultured individually and carbohydrate metabolism was assessed during overnight in vitro maturation (IVM). Meiotic status was assessed and oocyte intracellular nicotinamide adenine dinucleotide phosphate (NAD(P)H) content and mitochondria activity were measured prior to karyotype analysis by multifluor in situ hybridization. RESULTS Patient aetiology had no significant effect on oocyte maturation potential or incidence of numerical chromosome abnormalities (44%), although PCOS and PCO oocytes were more likely to suffer predivision. Group G chromosomes were most likely to be involved in non-disjunction and predivision. PCOS was associated with increased glucose consumption (2.06 ± 0.43 and 0.54 ± 0.12 pmol/h for PCOS and control oocytes, respectively) and increased pyruvate consumption (18.4 ± 1.2 and 13.9 ± 0.9 pmol/h for PCOS and control oocytes, respectively) during IVM. Prior prescription of metformin significantly attenuated pyruvate consumption by maturing oocytes (8.5 ± 1.8 pmol/h) from PCOS patients. Oocytes from PCO patients had intermediate metabolism profiles. Higher pyruvate turnover was associated with abnormal oocyte karyotypes (13.4 ± 1.9 and 19.9 ± 2.1 pmol/h for normal versus abnormal oocytes, respectively). Similarly, oocyte NAD(P)H content was 1.35-fold higher in abnormal oocytes. CONCLUSIONS The chromosomal constitution of in vitro matured oocytes from PCOS is similar to that of controls, but aspects of oocyte metabolism are perturbed by PCOS. Elevated pyruvate consumption was associated with abnormal oocyte karyotype. |
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| Maternal alcohol consumption during pregnancy and... | Human Reproduction | |
BACKGROUND Concurrent alcohol exposure has been associated with reduced fecundity, but no studies have estimated the effect of prenatal alcohol exposure on male fecundity. The aim of this study was to investigate the association between maternal alcohol consumption during pregnancy, semen quality and levels of reproductive hormones in young, adult men. METHODS From a Danish pregnancy cohort established in 1984–1987, 347 sons were selected for a follow-up study conducted in 2005–2006. Semen and blood samples were analyzed for conventional semen characteristics and reproductive hormones, respectively, and results were related to prospectively self-reported information on maternal alcohol consumption during pregnancy. RESULTS The sperm concentration decreased with increasing prenatal alcohol exposure. The adjusted mean sperm concentration among sons of mothers drinking ≥4.5 drinks per week during pregnancy was 40 (95% CI: 25–60) millions/ml. This concentration was ~32% lower compared with men exposed to <1.0 drink per week, who had a sperm concentration of 59 (95% CI: 44–77) millions/ml. The semen volume and the total sperm count were also associated with prenatal alcohol exposure; sons prenatally exposed to 1.0–1.5 drinks per week had the highest values. No associations were found for sperm motility, sperm morphology or any of the reproductive hormones, including testosterone. CONCLUSIONS These results indicate that prenatal exposure to alcohol may have a persisting adverse effect on Sertoli cells, and thereby sperm concentration. If these associations are causal they could explain some of the reported differences between populations and long-term changes in semen quality. |
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| Dynamics of cohesin proteins REC8, STAG3, SMC1{be... | Human Reproduction | |
BACKGROUND Sister chromatid cohesion is essential for ordered chromosome segregation at mitosis and meiosis. This is carried out by cohesin complexes, comprising four proteins, which seem to form a ring-like complex. Data from animal models suggest that loss of sister chromatid cohesion may be involved in age-related non-disjunction in human oocytes. Here, we describe the distribution of cohesins throughout meiosis in human oocytes. METHODS We used immunofluorescence in human oocytes at different meiotic stages to detect cohesin subunits REC8, STAG3, SMC1β and SMC3, [also synaptonemal complex (SC) protein 3 and shugoshin 1]. Samples from euploid fetuses and adult women were collected, and 51 metaphase I (MI) and 113 metaphase II (MII) oocytes analyzed. SMC1β transcript levels were quantified in 85 maturing germinal vesicle (GV) oocytes from 34 women aged 19–43 years by real-time PCR. RESULTS At prophase I, cohesin subunits REC8, STAG3, SMC1β and SMC3 overlapped with the lateral element of the SC. Short cohesin fibers are observed in the oocyte nucleus during dictyate arrest. All four subunits are observed at centromeres and along chromosomal arms, except at chiasmata, at MI and are present at centromeric domains from anaphase I to MII. SMC1β transcripts were detected (with high inter-sample variability) in GV oocytes but no correlation between SMC1β mRNA levels and age was found. CONCLUSIONS The dynamics of cohesins REC8, STAG3, SMC1β and SMC3 suggest their participation in sister chromatid cohesion throughout the whole meiotic process in human oocytes. Our data do not support the view that decreased levels of SMC1β gene expression in older women are involved in age-related non-disjunction. |
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| Estrogen and progesterone exposure is reduced in ... | Human Reproduction | |
BACKGROUND Alterations in circulating steroids are believed to be important mediators of the impact that diet and exercise have on breast cancer risk and changes in bone density. This study aimed to test the hypothesis that moderate exercise training combined with caloric restriction would produce significant menstrual disturbances and alterations in ovarian steroids in premenopausal women. METHODS Sedentary premenopausal women (25–40 years; body mass index: 23.6 ± 0.6 kg/m2) assigned to either a light conditioning (LC, n = 9) or an exercise combined with caloric restriction group (EX + CR, n = 24) were studied for one screening, one baseline and four intervention periods equivalent to the length of subjects’ menstrual cycles. Exercise consisted of supervised training sessions, i.e. two LC or four EX + CR times per week, 30–60 min at a moderate intensity. The EX + CR group was prescribed a diet representing a caloric restriction of 20–35% below baseline energy requirements, whereas the LC group remained eucaloric. Ovarian steroid exposure was determined with daily urinary estrone-1- and pregnanediol glucuronides (E1G and PdG, respectively) and mid-cycle urinary LH measures. Fitness, body composition, and serum sex hormone binding globulin (SHBG) and serum estradiol (E2) were assessed repeatedly. RESULTS The intervention produced significant increases in VO2 max and decreases in both body weight (–3.7 ± 0.5 kg; ranged from –8.8 to +1.8 kg) and percent body fat (–4.5 ± 0.7%; ranged from –12 to +0.3%), which were attributable primarily to changes in the EX + CR subjects (time x group; P < 0.05). Serum E2 and urinary E1G and PdG concentrations declined significantly across the intervention period (time; P < 0.05), whereas SHBG increased transiently (time; P < 0.05) in the EX + CR subjects, with no significant changes observed in the LC group. The decrease in E1G area under the curve was significantly related to the daily energy deficit (R =0.61; P = 0.003), not the amount of weight lost. There was no significant impact of the intervention on menstrual cyclicity or the incidence of menstrual disturbances in either group. CONCLUSIONS A moderate aerobic exercise training program combined with modest weight loss in accordance with recommended guidelines produces significant reductions in ovarian steroid exposure without disrupting menstrual cyclicity in premenopausal women aged 25–40 years. Exposure to a daily energy deficit is a stronger predictor of the decline in estrogen exposure than decreases in body weight. |
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