Birth outcomes after spontaneous or assisted conception among infertile Australian women aged 28 to 36 years: A prospective, population-based study

Objective To examine the extent to which the odds of birth, pregnancy, or adverse birth outcomes are higher among women aged 28 to 36 years who use fertility treatment compared with untreated women. Design Prospective, population-based. Setting Not applicable. Patient(s) Participants in the ALSWH born in 1973 to 1978 who reported on their infertility and use of in vitro fertilization (IVF) or ovulation induction (OI). Intervention(s) Postal survey questionnaires administered as part of ALSWH. Main Outcome Measure(s) Among women treated with IVF or OI and untreated women, the odds of birth outcomes estimated by use of adjusted logistic regression modeling. Result(s) Among 7,280 women, 18.6% (n = 1,376) reported infertility. Half (53.0%) of the treated women gave birth compared with 43.8% of untreated women. Women with prior parity were less likely to use IVF compared with nulliparous women. Women using IVF or OI, respectively, were more likely to have given birth after treatment or be pregnant compared with untreated women. Women using IVF or OI were as likely to have ectopic pregnancies, stillbirths, or premature or low birthweight babies as untreated women. Conclusion(s) More than 40% of women aged 28–36 years reporting a history of infertility can achieve births without using treatment, indicating they are subfertile rather than infertile.

An algorithm to predict pregnancy in assisted conception

BACKGROUND: Male fertility potential cannot be measured by conventional parameters for assisted reproduction by intracytoplasmic sperm injection. This study determines the relationship between testicular and ejaculated sperm mitochondrial (mt) DNA deletions, nuclear (n) DNA fragmentation and fertilisation and pregnancy rates in ICSI. METHODS: Ejaculated sperm were obtained from 77 men and testicular sperm from 28 men with obstructive azoospermia undergoing ICSI. Testicular sperm were retrieved using a Trucut needle. MtDNA analysed using a long polymerase chain reaction. The alkaline Comet assay determined nDNA fragmentation. RESULTS: Of subjects who achieved a pregnancy (50%) using testicular sperm, only 26% had partners�??�?�¢?? sperm with wild type (WT) mtDNA. Of pregnant subjects (38%) using ejaculated sperm, only 8% had partner sperm with WT mtDNA.. In each, the successful group had less mtDNA deletions and less nDNA fragmentation. There were inverse relationships between pregnancy and mtDNA deletion numbers, size and nDNA fragmentation for both testicular and ejaculated sperm. No relationships were observed with fertilisation rates. An algorithm for the prediction of pregnancy is presented based on the quality of sperm nDNA and mtDNA. CONCLUSION: In both testicular and ejaculated sperm, mtDNA deletions and nDNA fragmentation are closely associated with pregnancy in ICSI.

Effects of vasectomy on spermatogenesis and fertility outcomes after assisted conception

Abstract BACKGROUND: Each year 40,000 men have a vasectomy in the UK whilst another 2400 request a reversal to begin a second family. Sperm can now be obtained by testicular biopsy and subsequently used in assisted conception with intracytoplasmic sperm injection (ICSI). The study aims were to compare sperm yields of men post-vasectomy or with obstructive azoospermia (OA) of unknown aetiology with fertile men and to assess any alteration in the clinical pregnancy rates after ICSI. METHODS: Testicular tissue was obtained by Trucut needle from men who had undergone a vasectomy >5yrs previously, had OA from other causes and from fertile men during vasectomy. Seminiferous tubules were milked to measure sperm yields. Numbers of Sertoli cells, spermatids and thickness of the seminiferous tubule walls were assessed using quantitative computerized analysis. RESULTS and CONCLUSIONS: Sperm yields/g testis were significantly decreased in men post-vasectomy and in men with OA, relative to fertile men. Significant reductions were also observed in early (40%) and mature (29%) spermatid numbers and an increase of 31% was seen in the seminiferous tubule wall (basal membrane and collagen thickness) of vasectomised men compared to fertile men. Clinical pregnancy rates in couples who had had a vasectomy were also significantly reduced.

The effects of cryopreservation on testicular sperm nuclear DNA fragmentation and its relationship with assisted conception outcome following intracytoplasmic sperm injection

M.E.M. Thompson-Cree, Neil McClure, Eilish T. Donnelly, Kristine E. Steele and Sheena E.M. Lewis

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Abstract Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes.
It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage
and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major
track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body
of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the
strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in
the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract,
the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials
addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency.

Listening to late discovery adoption and donor offspring stories : adoption, ethics and implications for contemporary donor insemination practices

For most of the 20th Century a ‘closed’ system of adoption was practised throughout Australia and other modern Western societies. This ‘closed’ system was characterised by sealed records; amended birth certificates to conceal the adoption, and prohibited contact with all biological family. Despite claims that these measures protected these children from the taint of illegitimacy the central motivations were far more complex, involving a desire to protect couples from the stigma of infertility and to provide a socially acceptable family structure (Triseliotis, Feast, & Kyle, 2005; Marshall & McDonald, 2001). From the 1960s significant evidence began to emerge that many adopted children and adults were experiencing higher incidences of psychological difficulties, characterised by problems with psychological adjustment, building self-esteem and forming a secure personal identity. These difficulties became grouped under the term ‘genealogical bewilderment’. As a result, new policies and practices were introduced to try to place the best interests of the child at the forefront. These changes reflected new understandings of adoption; as not only an individual process but also as a social and relational process that continues throughout life. Secrecy and the withholding of birth information are now prohibited in the overwhelming majority of all domestic adoptions processed in Australia (Marshall & McDonald, 2001). One little known consequence of this ‘closed’ system of adoption was the significant number of children who were never told of their adoptive status. As a consequence, some have discovered or had this information disclosed to them, as adults. The first study that looked at the late discovery of genetic origins experiences was conducted by the Post Adoption Resource Centre in New South Wales in 1999. This report found that the participants in their study expressed feelings of disbelief, confusion, anger, sorrow and loss. Further, the majority of participants continued to struggle with issues arising from this intentional concealment of their genetic origins (Perl & Markham, 1999). A second and more recent study (Passmore, Feeney & Foulstone, 2007) looked at the issue of secrecy in adoptive families as part of a broader study of 144 adult adoptees. This study found that secrecy and/or lies or misinformation on the part of adoptive parents had negative effects on both personal identity and relationships with others. The authors noted that those adoptees who found out about their adoption as adults were ‘especially likely to feel a sense of betrayal’ (p.4). Over recent years, stories of secrecy and late discovery have also started to emerge from sperm donor conceived adults (Spencer, 2007; Turner & Coyle, 2000). Current research evidence shows that although a majority of couples during the donor assisted conception process indicate that they intend to tell the offspring about their origins, as many as two-thirds or more of couples continue to withhold this information from their children (Akker, 2006; Gottlieb, A. McWhinnie, 2001; Salter-Ling, Hunter, & Glover, 2001). Why do they keep this secret? Infertility involves a range of complex factors that are often left unresolved or poorly understood by those choosing insemination by donor as a form of family building (Schaffer, J. A., & Diamond, R., 1993). These factors may only impact after the child is born, when resemblance talk becomes most pronounced. Resemblance talk is an accepted form of public discourse and a social convention that legitimises the child as part of the family and is part of the process of constructing the child’s identity within the family. Couples tend to become focused on resemblance as this is where they feel most vulnerable, and the lack of resemblance to the parenting father may trigger his sense of loss (Becker, Butler, & Nachtigall, 2005).

Identity and genetic origins : an ethical exploration of the late discovery of adoptive and donor-insemination offspring status

This thesis is an ethical and empirical exploration of the late discovery of genetic origins in two contexts, adoption and sperm donor-assisted conception. This exploration has two interlinked strands of concern. The first is the identification of ‘late discovery’ as a significant issue of concern, deserving of recognition and acknowledgment. The second concerns the ethical implications of late discovery experiences for the welfare of the child. The apparently simple act of recognition of a phenomenon is a precondition to any analysis and critique of it. This is especially important when the phenomenon arises out of social practices that arouse significant debate in ethical and legal contexts. As the new reproductive technologies and some adoption practices remain highly contested, an ethical exploration of this long neglected experience has the potential to offer new insights and perspectives in a range of contexts. It provides an opportunity to revisit developmental debate on the relative merit or otherwise of biological versus social influences, from the perspective of those who have lived this dichotomy in practise. Their experiences are the human face of the effects arising from decisions taken by others to intentionally separate their biological and social worlds, an action which has then been compounded by family and institutional secrecy from birth. This has been accompanied by a failure to ensure that normative standards and values are upheld for them. Following discovery, these factors can be exacerbated by a lack of recognition and acknowledgement of their concerns by family, friends, community and institutions. Late discovery experiences offer valuable insights to inform discussions on the ethical meanings of child welfare, best interests, parental responsibility, duty of care and child identity rights in this and other contexts. They can strengthen understandings of what factors are necessary for a child to be able to live a reasonably happy or worthwhile life.

Differences in mitochondrial and nuclear DNA status of high-density and low-density sperm fractions after density centrifugation preparation

Background: In order to isolate the â??bestâ?? sperm for assisted conception a discontinuous two-step density gradient centrifugation is usually employed. This technique is known to isolate a subpopulation with good motility, morphology and nuclear DNA (nDNA) integrity. As yet its ability to isolate sperm with unfragmented mitochondrial DNA (mtDNA) is unknown. Methods: Semen was obtained from men (n=28) attending our Regional Fertility Centre for infertility investigations. We employed a modified long polymerase chain reaction to study mtDNA and a modified alkaline Comet assay to determine nDNA fragmentation. Results: The high- density fraction displayed significantly more wild type mtDNA (75% of samples) than that of the low- density fraction (25% of samples). In the high-density fraction, there was a higher incidence of single, rather than double or multiple deletions and the deletions were predominantly small scale (0.1-4.0kb). There was a strong correlation between nDNA fragmentation, the number of mtDNA deletions (r=0.7, p

Fas and DNA double stranded breaks in human ejaculated sperm

Objective: to determine the incidence of Fas positivity and DNA double stranded breaks (DSB) as indicators of early and late stage apoptosis in ejaculated sperm. Design: Fas positivity was assessed by flow cytometry and DSB by neutral Comet assay Setting: Andrology Laboratory, Royal Maternity Hospita, Belfast Northern Ireland, UK. Patients: 45 infertile men undergoing infertility investigations and 10 fertile men undergoing vasectomies Main Outcome measures: Perecentage Fas positive cells, percentage DNA fragmentation, olive tail moments Results: The apoptotic marker Fas was detected in ejaculated sperm, with a higher incidence of Fas positivity in teratozoospermic and asthenozoospermic than in normozoospermic semen. No Fas positivity was observed in fertile mens’ sperm. DSB were greater in infertile than in fertile mens’ sperm and also greater in sperm in semen than in sperm prepared for assisted conception. There was an inverse relationship between DSB and both sperm concentration and motility. There was no relationship between Fas positivity and DNA damage. Conclusion: Fas was expressed in sperm of infertile men. In contrast, DNA fragmentation was observed in all sperm of fertile and infertile men and correlated with inadequate concentration and motility, which suggests that sperm DSB are ubiquitous and are not solely associated with apoptosis.

The Effects of Delta–9–Tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro.

Objective: to investigate the effects of tetrahydrocannabinol; THC on human sperm function in vitro. Design: laboratory analysis of sperm motility with and without exposure to THC using computer assisted semen analysis (CASA) and acrosome reaction by fluoroscein isothiocyanate labelled peanut agglutinin (FITC-PNA) staining. Setting: An ART unit in a tertiary medical centre. Patients: semen was obtained from 78 men attending the Regional Fertility Centre, Belfast. Interventions: Sperm were divided into 90% (the best fertilizing potential used in assisted conception) and 45% (the poorer subpopulation) fractions by density centrifugation and incubated with, or without (controls), tetrahydrocannabinol (THC) at concentrations equivalent to therapeutic (0.032�?�¯?�?�­M) and recreational (4.8 and 0.32�?�¯?�?�­M) plasma levels, at 37�?�¯?�?�°C for 3 hours. Main outcome measures: Sperm motility, spontaneous and induced acrosome reactions Results: There was a dose-dependent decrease in percentage progressive motility (-21% at 4.8�??�?�µM, p0.05) in the 90% fraction. The 45% fraction showed a greater decrease in percentage progressive motility (-56% at 4.8�??�?�µM, p=0.011; -23% at 0.32�??�?�µM, p= 0.039; and -28% at 0.032�??�?�µM, p=0.004). A decrease in the straight line velocity; VSL (-10%) and the average path velocity; VAP (-10%) were also observed in the 90% fraction. A significant inhibition (-15% at 4.8�??�?�µM, p=0.04) in spontaneous acrosome reaction was observed in the 90% fraction. The 45% fraction showed a more marked inhibition [-35% (p

Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro

Objective: to determine if sildenafil citrate; a cyclic monophosphate specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction. Design: laboratory analysis of sperm motility after exposure to sildenafil citrate using computer assisted semen analysis (CASA) and acrosome reaction by fluoroscein isothiocyanate labelled peanut agglutinin (FITC-PNA) staining. Setting: An ART unit Patients: 57 male patients Interventions: Sperm were divided into 90% (the best fertilizing potential used in assisted conception) and 45% (the poorer subpopulation) fractions by density centrifugation and incubated with sildenafil citrate ( 0.67uM) at 37ï?°C for up to 180 minutes. Main outcome measures: both the numbers and velocity of progressively motile sperm were significantly increased by sildenafil citrate between 15 and 135 minutes. Further, samples revealed that these effects were consistent in the 90% and 45% subpopulations of sperm. In both subpopulations, sildenafil also caused a significant increase in the proportion of acrosome reacted sperm - 22.1% compared with 11.8% in the control group of the good quality fraction (p