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Hamdan M.,University of Southampton | Hamdan M.,University of Malaya | Hamdan M.,Maastricht University | Hamdan M.,Complete Fertility Center | And 9 more authors.
Obstetrics and Gynecology | Year: 2015

OBJECTIVE: To investigate the association of endometriosis on assisted reproductive technology (ART) outcomes and to review if surgical treatment of endometriosis before ART affects the outcomes. DATA SOURCES: We searched studies published between 1980 and 2014 on endometriosis and ART outcome. We searched MEDLINE, PubMed, ClinicalTrials.gov, and Cochrane databases and performed a manual search. METHODS OF STUDY SELECTION: A total of 1,346 articles were identified, and 36 studies were eligible to be included for data synthesis. We included published cohort studies and randomized controlled trials. TABULATION, INTEGRATION, AND RESULTS: Compared with women without endometriosis, women with endometriosis undertaking in vitro fertilization and intracytoplasmic sperm injection have a similar live birth rate per woman (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.84-1.06, 13 studies, 12,682 patients, I2=35%), a lower clinical pregnancy rate per woman (OR 0.78, 95% CI 0.65-0.94), 24 studies, 20,757 patients, I2=66%), a lower mean number of oocyte retrieved per cycle (mean difference 21.98, 95% CI 22.87 to 21.09, 17 studies, 17,593 cycles, I297%), and a similar miscarriage rate per woman (OR 1.26, 95% CI (0.92-1.70, nine studies, 1,259 patients, I2=0%). Women with more severe disease (American Society for Reproductive Medicine III-IV) have a lower live birth rate, clinical pregnancy rate, and mean number of oocytes retrieved when compared with women with no endometriosis. CONCLUSION: Women with and without endometriosis have comparable ART outcomes in terms of live births, whereas those with severe endometriosis have inferior outcomes. There is insufficient evidence to recommend surgery routinely before undergoing ART. © 2014 by The American College of Obstetricians and Gynecologists. Source

Vassard D.,Copenhagen University | Lallemant C.,Complete Fertility Center | Nyboe Andersen A.,Copenhagen University | Macklon N.,Complete Fertility Center | Schmidt L.,Copenhagen University
Upsala Journal of Medical Sciences | Year: 2016

Background: Across several European countries family formation is increasingly postponed. The aims of the study were to investigate the desire for family building and fertility awareness in the UK and Denmark. Methods: A population-based internet survey was used among women (n = 1,000) and men (n = 237) from the UK (40%) and Denmark (60%). Data covered socio-demographics, family formation, and awareness of female age-related fertility. Data analysis used descriptive statistics and logistic regression analysis for studying associations between low fertility awareness and desired family formation. Results: The majority of all participants desired two or three children. Two-thirds of the childless participants desired a first child at 30+ years, and one-fifth of the women and one-third of the men desired a last child at age 40. Overall, 83% of women and 73% of men were aware that female fertility starts to decline around 25–30 years. Men had significantly lower fertility awareness. Women who underestimated the impact of age on female fertility were significantly more likely to have a desire or attempted their first child at a higher age. Conclusion: Even though the majority were aware of the age-related decrease in female fertility, most desired having children at an age when female fertility has declined. Women who were not sufficiently aware of the impact of advanced age were significantly more likely to have their first child at a higher age. There is a need for developing educational programs for women and men in order to increase the population’s knowledge of fertility and risk factors for infertility. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Source

Kermack A.J.,University of Southampton | Kermack A.J.,Complete Fertility Center | Kermack A.J.,National Health Research Institute | MacKlon N.S.,University of Southampton | And 2 more authors.
Reproduction, Fertility and Development | Year: 2015

Approximately one in six couples suffer from subfertility, and many seek treatment with artificial reproductive technologies (ART). Despite improvements in laboratory techniques and ovarian stimulation, ongoing pregnancy rates per cycle remain at ∼25%. Couples wanting to improve their chances may turn to adjuvant therapies, such as nutritional supplements. There is growing evidence that periconceptional nutritional status is a key determinant of fertility and long-term health of the offspring, and a lucrative market has developed to meet the demand based on these benefits. However, the practice of routine dietary supplementation before and during IVF treatment has not been subject to well-powered prospective randomised trials. In this article, the potential roles of specific nutritional supplements in the context of improving IVF outcomes are reviewed and an assessment is made of the evidence base supporting their clinical use in this context. Finally, current research needs in the field are outlined. © CSIRO 2015. Source

Alasmari W.,University of Dundee | Alasmari W.,University of Umm Al - Qura | Barratt C.L.R.,University of Dundee | Barratt C.L.R.,Assisted Conception Unit | And 8 more authors.
Human Reproduction | Year: 2013

STUDY QUESTION: What is the prevalence of defects in the Ca 2+-signalling pathways mediating hyperactivation (calcium influx and store mobilization) among donors and sub-fertile patients and are they functionally significant, i.e. related to fertilization success at IVF?SUMMARY ANSWERThis study identifies, for the first time, the prevalence of Ca 2+ store defects in sperm from research donors, IVF and ICSI patients. It highlights the biological role and importance of Ca2+ signalling (Ca2+ store mobilization) for fertilization at IVF.WHAT IS KNOWN ALREADYSperm motility and hyperactivation (HA) are important for fertility, mice with sperm incapable of HA are sterile. Recently, there has been significant progress in our knowledge of the factors controlling these events, in particular the generation and regulation of calcium signals. Both pH-regulated membrane Ca2+ channels (CatSper) and Ca2+ stores (potentially activating store-operated Ca2+ channels) have been implicated in controlling HA.STUDY DESIGN, SIZE, AND DURATIONThis was a prospective study examining a panel of 68 donors and 181 sub-fertile patients attending the Assisted Conception Unit, Ninewells Hospital Dundee for IVF and ICSI. Twenty-five of the donors gave a second sample (∼4 weeks later) to confirm consistency/reliability of the recorded responses. Ca2+ signalling was manipulated using three agonists, NH4Cl (activates CatSper via pH), progesterone (direct activation of CatSper channels, potentially enhancing mobilization of stored Ca2+ by CICR) and 4-aminopyridine (4-AP) (effect on pH equivalent to NH4Cl and mobilizes stored Ca2+). The broad-spectrum phosphodiesterase inhibitor 3-isobutyl-1-methyxanthine (IBMX), a potent activator of HA was also used for comparison. For patient samples, an aliquot surplus to requirements for IVF/ICSI treatment was examined, allowing direct comparison of Ca2+ signalling and motility data with functional competence of the sperm.MATERIALS, SETTING, METHODSThe donors and sub-fertile patients were screened for HA (using CASA) and changes in intracellular Ca2+ were assessed by loading with Fura-2 and measuring fluorescence using a plate reader (FluoStar). MAIN RESULTS AND THE ROLE OF CHANCE: The relative efficacy of the stimuli in inducing HA was 4-AP >> IBMX > progesterone. NH4Cl increased [Ca 2+]i similarly to 4-AP and progesterone but did not induce a significant increase in HA. Failure of samples to generate HA (no significant increase in response to stimulation with 4-AP) was seen in just 2% of research donors but occurred in 10% of IVF patients (P = 0.025). All donor samples generated a significant [Ca2+]i increase when stimulated with 4-AP but 3.3% of IVF and 28.6% of ICSI patients failed to respond. Amplitudes of HA and [Ca2+]i responses to 4-AP were correlated with fertilization rate at IVF (P= 0.029; P = 0.031, respectively). Progesterone reliably induced [Ca2+]i responses (97% of donors, 100% of IVF patients) but was significantly less effective than 4-AP in inducing HA. Twenty seven per cent of ICSI patients failed to generate a [Ca2+]i response to progesterone (P= 0.035). Progesterone-induced [Ca2+]i responses were correlated with fertilization rate at IVF (P= 0.037) but induction of HA was not. In donor samples examined on more than one occasion consistent responses for 4-AP-induced [Ca2+]i (R2 = 0.97) and HA (R2 = 0.579) were obtained. In summary, the data indicate that defects in Ca 2+ signalling leading to poor HA do occur and that ability to undergo Ca2+ -induced HA affects IVF fertilizing capacity. The data also confirm that release of stored Ca2+ is the crucial component of Ca2+ signals leading to HA and that Ca2+ store defects may therefore underlie HA failure. LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study of sperm function. While the repeatability of the [Ca 2+]i and HA responses in samples from the same donor were confirmed, data for patients were from 1 assessment and thus the robustness of the failed responses in patients' needs to be established. The focus of this study was on using 4AP, which mobilizes stored Ca2+ and is a potent inducer of HA. The n values for other agonists, especially calcium assessments, are smaller. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies have shown a significant relationship between basal levels of HA, calcium responses to progesterone and IVF fertilization rates. Here, we have systematically investigated the ability/failure of human sperm to generate Ca2+ signals and HA in response to targeted pharmacological challenge and, related defects in these responses to IVF success. [Ca2+]i signalling is fundamental for sperm motility and data from this study will lead to assessment of the nature of these defects using techniques such as single-cell imaging and patch clamping. STUDY FUNDING/COMPETING INTEREST(S): Resources from a Wellcome Trust Project Grant (#086470, Publicover and Barratt PI) primarily funded the study. The authors have no competing interests. © 2013 The Author. Source

Shreeve N.,University of Southampton | Cagampang F.,University of Southampton | Sadek K.,University of Southampton | Tolhurst M.,University of Southampton | And 7 more authors.
Human Reproduction | Year: 2013

study question: Are daily cycles in urinary melatonin and oxidative stress marker levels (8-hydroxydeoxyguanosine) altered in PCOS, and is this associated with changes in sleep quality? summary answer: There is an association between elevated nighttime melatonin and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and poor sleep quality in our PCOS study group. what is known already: Women with PCOS are known to have poorer sleep. However, there have been few studies examining the possible association between melatonin levels and sleep quality in women with polycystic ovarian syndrome (PCOS). study design, size, duration: This is a case-control study of PCOS (n = 26) and non-PCOS control (n = 26) subjects recruited from a tertiary gynaecological centre. participants/ materials, setting, methods: The participants were requested to complete sleep questionnaires for a month. In a subgroup from these cohorts (PCOS, n = 15; controls, n = 18), urine samples were also collected at various time points over a 24-h period. In addition, their sleep patterns and lighting environment were monitored for 3 consecutive days and nights using a wrist-mounted Actiwatch device. main results and the role of chance: PCOS women had significantly elevated night-time urinary levels of the melatonin metabolite 6-sulfatoxymelatonin (aMT6s) and of 8-OHdG (both at P , 0.05), as well as significantly reduced sleep quality (P , 0.05), compared with the controls. limitations, reasons for caution: Due to the small sample size of the study, further studies will be required to confirm our findings. wider implications of the findings: Our preliminary work provides a possible new insight into the interactions between melatonin, increased oxidative stress and sleep in women with PCOS. study funding/competing interest(s): The study was funded by the Faculty of Medicine, University of Southampton. © 2013 The Author. Source

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