Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success

Objective: To evaluate sperm DNA fragmentation and semen parameters to diagnose male factor infertility and predict pregnancy after IVF.
Design: Prospective study.
Setting: Academic research laboratory.
Patient(s): Seventy-five couples undergoing IVF and 28 fertile donors.
Intervention(s): Sperm DNA fragmentation was measured by the alkaline Comet assay in semen and sperm after density gradient centrifugation (DGC). Binary logistic regression was used to analyze odds ratios (OR) and relative risks (RR) for IVF outcomes.
Main Outcome Measure(s): Semen parameters and sperm DNA fragmentation in semen and DGC sperm compared with fertilization rates, embryo quality, and pregnancy.
Result(s): Men with sperm DNA fragmentation at more than a diagnostic threshold of 25% had a high risk of infertility (OR: 117.33, 95% confidence interval [CI]: 12.72–2,731.84, RR: 8.75). Fertilization rates and embryo quality decreased as sperm DNA fragmentation increased in semen and DGC sperm. The risk of failure to achieve a pregnancy increased when sperm DNA fragmentation exceeded a prognostic threshold value of 52% for semen (OR: 76.00, CI: 8.69–1,714.44, RR: 4.75) and 42% for DGC sperm (OR: 24.18, CI: 2.89–522.34, RR: 2.16).
Conclusion(s): Sperm DNA testing by the alkaline Comet assay is useful for both diagnosis of male factor infertility and prediction of IVF outcome.

Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes

The exchange of histones with protamines in sperm DNA results in sperm chromatin compaction and protection. Variations in sperm protamine expression are associated with male infertility. The aim of this study was to investigate relationships between DNA fragmentation, sperm protamines and assisted reproduction treatment. Semen and spermatozoa prepared by density-gradient centrifugation (DGC) from 73 men undergoing IVF and 24 men undergoing intracytoplasmic sperm injection (ICSI) were included in the study. Nuclear DNA fragmentation was assessed using the alkaline Comet assay and protamines were separated by acid-urea polyacrylamide gels. Sperm DNA fragmentation and protamine content (P1-DNA, P2-DNA, P1 + P2-DNA) decreased in spermatozoa after DGC. Abnormally high and low P1/P2 ratios were associated with increased sperm DNA fragmentation. Couples with idiopathic infertility had abnormally high P1/P2 ratios. Fertilization rates and embryo quality decreased as sperm DNA fragmentation or protamines increased. Sperm DNA fragmentation was lower in couples achieving pregnancies after IVF, but not after ICSI. There was no correlation between protamine content (P1-DNA, P2-DNA, P1 + P2-DNA) or P1/P2 ratios and IVF or ICSI pregnancies. Increased sperm DNA fragmentation was associated with abnormal protamination and resulted in lower fertilization rates, poorer embryo quality and reduced pregnancy rates. During late spermatogenesis, around 85% of the histones in the sperm nucleus are replaced with protamines. This process results in sperm chromatin compaction and also transcription silencing. In the human, protamines are comprised of two types: protamine-1 (P1) and protamine-2 (P2). Variations in sperm protamine expression are associated with male infertility. Similarly, sperm DNA integrity is important for male fertility. The aim of this study was to investigate relationships between DNA fragmentation, sperm protamines and assisted reproduction treatment. Semen and spermatozoa prepared by density-gradient centrifugation (DGC) from 73 men undergoing IVF and 24 men undergoing intracytoplasmic sperm injection (ICSI) were included in the study. Nuclear DNA fragmentation was assessed using the alkaline Comet assay and protamines were separated by acid-urea polyacrylamide gels. Sperm DNA fragmentation and protamine content decreased in spermatozoa after DGC. Abnormally high and low P1/P2 ratios were associated with increased sperm DNA fragmentation. Couples with idiopathic infertility had abnormally high P1/P2 ratios. Fertilization rates and embryo quality decreased as sperm DNA fragmentation or protamines increased. Sperm DNA fragmentation was lower in couples achieving pregnancies after IVF, but not after ICSI. There was no correlation between protamine content or P1/P2 ratios and IVF or ICSI pregnancies. Increased sperm DNA fragmentation was associated with abnormal protamination and resulted in lower fertilization rates, poorer embryo quality and reduced pregnancy rates.

Leisure goods, education attainment and fertility choice

This paper proposes a novel mechanism for the fertility decline that occurred across the world since the late nineteenth century. It suggests that the rise in the cost of children relative to leisure goods in the process of development contributed to the decline in fertility. The paper develops a unified growth model in which children are substitutes for leisure goods in the parental utility function. The theory suggests that the rise in income, the decline in the relative price of leisure goods and the increase in educational attainment in the process of development speed up the demographic transition from high to low fertility and contributed to the transition from stagnation to growth.

Do fertility transitions influence infant mortality declines? Evidence from early modern Germany

The timing and sequencing of fertility transitions and early-life mortality declines in historical Western societies indicate that reductions in sibship (number of siblings) may have contributed to improvements in infant health. Surprisingly, however, this demographic relationship has received little attention in empirical research. We outline the difficulties associated with establishing the effect of sibship on infant mortality and discuss the inherent bias associated with conventional empirical approaches. We offer a solution that permits an empirical test of this relationship while accounting for reverse causality and potential omitted variable bias. Our approach is illustrated by evaluating the causal impact of family size on infant mortality using genealogical data from 13 German parishes spanning the sixteenth, seventeenth, eighteenth, and nineteenth centuries. Overall, our findings do not support the hypothesis that declining fertility led to increased infant survival probabilities in historical populations.

Wanted and Unwanted Fertility in Bolivia:Does Ethnicity Matter?

CONTEXT: In Bolivia, the total fertility rate (TFR) among indigenous populations is higher than that among the nonindigenous population. It is important to investigate whether this difference is attributable to ethnic differences in wanted or unwanted fertility.
METHODS: Data from the 2003 Bolivian Demographic and Health Survey were used to estimate women's wanted and unwanted TFRs. Logistic regression analyses were conducted to examine whether women's, men's and couples' characteristics were associated with use of any contraceptive method and modern methods.
RESULTS: The TFRs for indigenous and nonindigenous women were 1.5 and 1.7, [corrected] respectively. The wanted fertility rate for indigenous women was nearly the same as that for nonindigenous women (2.8 and 1.4, [corrected] respectively); virtually all of the ethnic difference in the TFRs was attributable to the ethnic difference in unwanted fertility. The proportion of women in need of contraception was greater among indigenous women than among nonindigenous women (26% vs. 19%). In logistic regression analyses, male fertility preferences explained only a small part of the ethnic difference in contraceptive use.
CONCLUSION: Women's, men's and couples' preferences contribute only marginally to unwanted fertility, suggesting that structural factors act as obstacles to preventing unwanted fertility.

Desire for fertility and associated factors among people living with HIV/AIDS (PLWHA) in selected antiretroviral therapy (ART) clinics of Horro Guduru Wollega Zone, North West Oromia, Ethiopia- A cross sectional study

Background: Most recently fertility issues in HIV positive men and women are becoming increasingly important. Because of ART access and its good life effect, it is expected that the need and desire to get married, to have children and to have sexual partners for PLWHA would change with the regard to reproductive health. In Ethiopia HIV positive individuals may or may not have desire to have children. And the extent of this desire and how it varies by individual, health and demographic characteristics is not well known.

Objective: the aim of the study was to assess desire for fertility and associated factors among PLWHA in selected ART clinics of Horro Guduru Wollega Zone, Oromia National Regional State, Ethiopia.

Methods: A cross-sectional, institutional-based study that employed quantitative and qualitative in-depth interviews was conducted. Three hundred twenty one study subjects were selected using systematic random sampling technique and the data was collected using interviewer administered structured questionnaire. Data entry and analysis were performed using EPI Info version 3.5.1 and SPSS version 16. P-value <0.05 was taken as statistically significant and logistic regression was used to control potential confounding factors.

Results: Seventy three (57.9%) of the males and seventy six (39%) of the females desired to have children, giving a total of 149(46.4%) of all study participants. PLWHA who desired children were younger (AOR:3.3, 95%CI: 1.3-8.9), married (AOR: 5.8, 95%CI: 2.7-12.8), had no children (AOR: 75, 95%CI: 20.1-273.3) and males (AOR; 1.9, 95%CI: 1.02-3.62) compared with their counter parts. The major reason for those people who did not desire children were having desired number of children 80 (46.5%) followed by fear of HIV transmission to child reported by 42 (24.4%) of them.

Conclusion: A considerable number of PLWHA wants to have a child currently or in the near future. Many variables like socio demography, partner related, number of alive children and HIV related disease condition were significantly associated with fertility desire.

KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility

Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

Inbreeding uncovers fundamental differences in the genetic load affecting male and female fertility in a butterfly

Inbreeding depression is most pronounced for traits closely associated with fitness. The traditional explanation is that natural selection eliminates deleterious mutations with additive or dominant effects more effectively than recessive mutations, leading to directional dominance for traits subject to strong directional selection. Here we report the unexpected finding that, in the butterfly Bicyclus anynana, male sterility contributes disproportionately to inbreeding depression for fitness (complete sterility in about half the sons from brother-sister matings), while female fertility is insensitive to inbreeding. The contrast between the sexes for functionally equivalent traits is inconsistent with standard selection arguments, and suggests that trait-specific developmental properties and cryptic selection play crucial roles in shaping genetic architecture. There is evidence that spermatogenesis is less developmentally stable than oogenesis, though the unusually high male fertility load in B. anynana additionally suggests the operation of complex selection maintaining male sterility recessives. Analysis of the precise causes of inbreeding depression will be needed to generate a model that reliably explains variation in directional dominance and reconciles the gap between observed and expected genetic loads carried by populations. This challenging evolutionary puzzle should stimulate work on the occurrence and causes of sex differences in fertility load.