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Newcastle upon Tyne, United Kingdom

Ghuman N.K.,Newcastle upon Tyne Hospitals NHS Foundation Trust | Mair E.,Newcastle Fertility Center | Pearce K.,Northumbria University | Choudhary M.,Newcastle upon Tyne Hospitals NHS Foundation Trust | Choudhary M.,Newcastle Fertility Center
Human Reproduction | Year: 2016

STUDY QUESTION Does age of the sperm donor have an effect on reproductive outcomes (live birth rate and miscarriage occurrence) of donor insemination or in vitro fertilization treatment using donated sperm? SUMMARY ANSWER Live birth and miscarriage occurrence in assisted reproduction treatment using donor sperms was not found to be affected by the age of sperm donors up to 45 years old. WHAT IS ALREADY KNOWN Literature on the effect of sperm donor age on outcome of medically assisted reproduction is scarce. Most researchers agree that semen parameters deteriorate with increasing paternal age. However, there is no substantial evidence to suggest that this deterioration adversely affects the reproductive outcomes in couples undergoing medically assisted reproduction. STUDY DESIGN, SIZE, DURATION This retrospective cohort study analysed 46 078 first donor insemination treatments and fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using donated sperm from 1991 to 2012. PARTICIPANTS/ DURATION/METHODS The first fresh donor insemination and IVF/ICSI treatment cycles (46 078 treatment cycles) using donated sperm from the long-term anonymized data registry from 1991 to 2012 of the HFEA, the UK regulator, were analysed by the binary logistic modelling technique for association between sperm donor age and reproductive outcomes (live birth occurrence and miscarriage occurrence). The statistical package SPSS (version 21) was used for analysis and results were considered to be statistically significant if the P-value was <0.05. MAIN RESULTS AND THE ROLE OF CHANCE Of 46 078 women, 84.6% (N = 38 974) underwent donor insemination treatment and the remainder, 15.4% (N = 7104), had IVF/ICSI treatment with donor sperm. The live birth occurrence decreased with increasing female age in both treatment groups; In the donor insemination treatment group, it was 11.1% in 18-34 year old women, 8.3% in 35-37 year old women and 4.7% in 38-50 year old women. The corresponding figures in the IVF/ICSI treatment group were 28.9, 22.0 and 12.9% respectively. In each of these subgroups, no evidence of declining likelihood of live birth with increasing sperm donor age was found (P > 0.05). The miscarriage occurrence (i.e. number of miscarriages per 100 women commencing treatment) was 1.3% in 18-34 year old women, 1.9% in 35-37 year old women and 1.9% in 38-50 year old women undergoing donor insemination treatment. In the sperm donation IVF/ICSI treatment group, these figures were 5.7, 8.4 and 6.8% respectively. The results were not suggestive of any unfavourable effect of advancing sperm donor age on the odds of miscarriage occurrence (P > 0.05). LIMITATIONS, REASONS FOR CAUTION As sperm donors are a select population based on good semen indices, the generalization of results to the paternal population at large may not be possible. Although the study subgroups were controlled for female age, treatment modality and effect of previous treatment cycles, adjustments for certain potential compounding factors, such as smoking status, BMI of women and stimulation protocol used in IVF/ICSI treatment cycles, were not possible. WIDER IMPLICATIONS OF THE FINDINGS Live birth and miscarriage occurrence following assisted reproduction weren't adversely affected by increasing sperm donor age up to 45 years. In view of the increasing demand for donor sperm, further studies may be required to ascertain the safe upper age limit for sperm donors. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. Source

Panagiotopoulou N.,Newcastle Fertility Center at Life | Panagiotopoulou N.,Newcastle Fertility Center | Karavolos S.,Aberdeen Center for Reproductive Medicine | Choudhary M.,Newcastle Fertility Center at Life
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2015

Endometrial injury to improve implantation for women undergoing assisted reproductive techniques has attracted a lot of attention recently and has rapidly become incorporated into clinical practice. The aim of this study is, thus, to assess the effectiveness and safety of endometrial injury performed in the cycle preceding assisted reproductive techniques in women with recurrent implantation failure. Electronic database searches, including MEDLINE, EMBASE, CENTRAL and grey literature, up to 30th May 2015 were conducted with no restrictions. Randomized controlled trials comparing endometrial injury versus placebo or no treatment in the cycle preceding assisted reproductive techniques in women with recurrent implantation failure were selected. The primary outcome was live birth rate. Secondary outcomes were clinical pregnancy, implantation, miscarriage and procedure-related complication rates. Of the 1115 publications identified, 4 met the inclusion criteria. Meta-analysis was not possible due to significant clinical heterogeneity among the included studies. Patients' characteristics differed, as did the intervention used with endometrial injury being performed at different phases of the preceding menstrual cycle. Moreover, the effect of endometrial injury on live birth and clinical pregnancy rates were inconsistent among the included studies. In summary, there is currently insufficient evidence to support the use of endometrial injury in women with recurrent implantation failure undergoing assisted reproductive techniques while the procedure-associated complication rate has not been assessed. Clinical implementation should, thus, be deferred until robust evidence becomes available. © 2015 Elsevier Ireland Ltd. All rights reserved. All rights reserved. Source

Herbert M.,Newcastle Fertility Center | Herbert M.,Northumbria University | Kalleas D.,Northumbria University | Cooney D.,Northumbria University | And 2 more authors.
Cold Spring Harbor Perspectives in Biology | Year: 2015

In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond ~35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is me-diated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromo-somes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved. Source

Richardson J.,Wellcome Trust Center for Mitochondrial Research | Richardson J.,Northumbria University | Irving L.,Wellcome Trust Center for Mitochondrial Research | Irving L.,Northumbria University | And 8 more authors.
Stem Cells | Year: 2015

While the fertilized egg inherits its nuclear DNA from both parents, the mitochondrial DNA is strictly maternally inherited. Cells contain multiple copies of mtDNA, each of which encodes 37 genes, which are essential for energy production by oxidative phosphorylation. Mutations can be present in all, or only in some copies of mtDNA. If present above a certain threshold, pathogenic mtDNA mutations can cause a range of debilitating and fatal diseases. Here, we provide an update of currently available options and new techniques under development to reduce the risk of transmitting mtDNA disease from mother to child. Preimplantation genetic diagnosis (PGD), a commonly used technique to detect mutations in nuclear DNA, is currently being offered to determine the mutation load of embryos produced by women who carry mtDNA mutations. The available evidence indicates that cells removed from an eight-cell embryo are predictive of the mutation load in the entire embryo, indicating that PGD provides an effective risk reduction strategy for women who produce embryos with low mutation loads. For those who do not, research is now focused on meiotic nuclear transplantation techniques to uncouple the inheritance of nuclear and mtDNA. These approaches include transplantation of any one of the products or female meiosis (meiosis II spindle, or either of the polar bodies) between oocytes, or the transplantation of pronuclei between fertilized eggs. In all cases, the transferred genetic material arises from a normal meiosis and should therefore, not be confused with cloning. The scientific progress and associated regulatory issues are discussed. Stem Cells 2015;33:639-645 © 2014 AlphaMed Press. Source

Karavolos S.,Newcastle Fertility Center | Reynolds M.,Northumbria University | Panagiotopoulou N.,Newcastle Fertility Center | McEleny K.,Newcastle Fertility Center | And 3 more authors.
Clinical Endocrinology | Year: 2015

Androgen- or anabolic steroid-induced hypogonadism (ASIH) is no longer confined to professional athletes; its prevalence amongst young men and teenagers using androgens and/or anabolic steroids (AASs) is rising fast, and those affected can experience significant symptoms. Clinicians are increasingly encountering demanding, well-informed men affected by ASIH, yet lacking authoritative information on the subject may struggle to project a credible message. In this article, we overview the methods and drugs that men use in an attempt to counteract ASIH (with a view to either preventing its onset, or reversing it once it has developed) and summarize the scientific evidence underpinning these. The main channel for obtaining these drugs is the Internet, where they can be readily sourced without a valid prescription. An Internet search using relevant terms revealed a huge number of websites providing advice on how to buy and use products to counteract ASIH. Drugs arising repeatedly in our search included human chorionic gonadotrophin (hCG), selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The quality and accuracy of the online information was variable, but review of medical literature also highlighted a lack of scientific data to guide clinical practice. It is important for clinicians to be aware of the AAS user's self-treatment strategies with regard to ASIH side-effect mitigation. By ensuring that they are well-informed, clinicians are more likely to retain the credibility and trust of AAS users, who will in turn likely be more open to engage with appropriate management. © 2014 John Wiley & Sons Ltd. Source

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