Semen quality in young men has been clearly declining over the past 15 years

First study to examine a very large population of sperm donors within the same laboratory over a long observation period

January 2017 Study Abstract

Objective
To provide information of semen quality among young Chinese men in the past 15 years.

Design
Retrospective cross-sectional study.

Setting
Sperm bank.

Patient(s)
A total of 30,636 young adult men who applied to be sperm donors at the Hunan Province Human Sperm Bank of China in 2001–2015 were included in the study.

Decline in semen quality among 30,636 young Chinese men from 2001 to 2015, Fertility and Sterility: dx.doi.org/10.1016/j.fertnstert.2016.09.035, January 2017 (Volume 107, Issue 1), Pages 83–88.e2.

The Sperm Bike credit bikecitizens.

Intervention(s)
Physical examination and analysis of blood and semen samples.

Main Outcome Measure(s)
Semen parameters, such as semen volume, sperm concentration, total sperm count, progressively motile sperm count, sperm progressive motility, sperm morphology, and round cells.

Result(s)
Many of the semen parameters showed a decreasing trend over the 15-year observation period. The sperm concentration and percentage of sperm with normal morphology decreased from 68 × 106/mL to 47 × 106/mL and from 31.8% to 10.8%, respectively. Although sperm progressive motility showed irregular variation, the progressively motile sperm count decreased from 34 × 106 to 21 × 106 over the 15-year period. Furthermore, the rate of qualified donors fell from 55.78% in 2001 to 17.80% in 2015, and the rate for 2015 was approximately threefold lower than the corresponding rates in 2001.

Conclusion(s)
This is the first study to investigate the semen quality of a large population within the same laboratory in China over a long observation period. Our data clearly illustrate that the semen quality among young Chinese men has declined over a period of 15 years, especially in terms of sperm concentration, total sperm count, sperm progressive motility, and normal morphology. Moreover, the percentage of qualified donors also showed a decreasing trend during this time period. Although bulk semen parameters (reflected by 95% confidence intervals) overlap substantially throughout the study period, overall, these findings are a serious reproductive health warning, and further studies are warranted to confirm the findings of this study in China and to determine the factors causing this phenomenon.

Low Testosterone

Illness inflation – How everyday conditions become medical disorders

Millions may have ‘low testosterone. But critics say it is just about getting older and fatter.

Independent experts say the new definition is an example of ‘medicalization’ – turning common evolution into medical conditions that call for treatment.

Preconception exposures to phthalates effect in fathers on reproductive success via embryo quality

Dad’s exposure to phthalates in plastics may affect embryonic development

Abstract

STUDY QUESTION
Are preconception urinary concentrations of phthalates and phthalate alternatives associated with diminished early stage embryo quality in couples undergoing IVF?

SUMMARY ANSWER
Male, but not female, urinary concentrations of select metabolites of phthalates and phthalate alternatives are associated with diminished blastocyst quality.

WHAT IS KNOWN ALREADY
Although phthalates are endocrine disrupting compounds associated with adverse reproductive health, they are in widespread use across the world. Male and female preconception exposures to select phthalates have been previously associated with adverse reproductive outcomes in both the general population and in those undergoing IVF.

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment, Oxford Journals, Medicine & Health, Human Reproduction, Advance Access10.1093/humrep/dew301, October 28, 2016.

“Odd ducks Bob, Squish, and Slim. The Boon company seems very proud that their ducks are “BpA-free, Phthalate-free, and PVC-free” I bet they are also Gluten-free, Fat-free, and Sugar-free. So go ahead and eat one!” said Jamie – Image © all rights reserved.

STUDY DESIGN, SIZE, DURATION
This prospective cohort included 50 subfertile couples undergoing IVF in western Massachusetts.

PARTICIPANTS/MATERIALS, SETTING, METHODS
This study includes the first 50 couples recruited from the Baystate Medical Center’s Fertility Center in Springfield, MA, as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Relevant data from both partners, including embryo quality at the cleavage (Day 3) and blastocyst (Day 5) stages, were collected by clinic personnel during the normal course of an IVF cycle. A spot urine sample was collected from both male and female partners on the same day as semen sample procurement and oocyte retrieval. Concentrations of 17 urinary metabolite were quantified by liquid chromatography mass spectrometry and normalized via specific gravity. Generalized estimating equations were used to estimate odds ratios (OR) and 95% CI, with urinary phthalates and phthalate alternatives fitted as continuous variables and embryo quality as a binary variable.

MAIN RESULTS AND THE ROLE OF CHANCE
The 50 couples contributed 761 oocytes, of which 423 progressed to the cleavage stage, 261 were high-quality cleavage stage embryos, 137 were transferrable quality blastocysts and 47 were high-quality blastocysts. At the cleavage stage, male urinary monoethyl phthalate concentrations were positively associated with high-quality cleavage stage embryos (OR = 1.20, 95% CI 1.01–1.43, P = 0.04); no other significant associations were observed at this stage. At the blastocyst stage, male urinary concentrations of monobenzyl phthalate (OR = 0.55, 95% CI 0.36–0.84, P = 0.01), mono-3-hydroxybutyl phthalate (OR = 0.37, 95% CI 0.18–0.76, P = 0.01), mono-n-butyl phthalate (OR = 0.55, 95% CI 0.42–0.73, P < 0.01) and monomethyl phthalate (OR = 0.39, 95% CI 0.26–0.60, P < 0.01) were inversely associated with high-quality blastocysts. A borderline statistically significant relationship was observed for male concentrations of mono(2-ethylhexyl) phthalate (OR = 0.52, 95% CI 0.27–1.00, P = 0.05) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (OR = 0.21, 95% CI 0.04–1.03, P = 0.05) at the blastocyst stage. Similar inverse associations were observed between male urinary phthalate metabolite concentrations and likelihood of transferrable quality blastocysts. For female partners, select metabolites were positively associated with odds of high or transferrable blastocyst quality, but the observed associations were not consistent across blastocyst quality measures or between sex-specific and couples-level models. All models were adjusted for age of both partners, urinary metabolite concentrations of female partners and male infertility status, while models of blastocysts were additionally adjusted for embryo quality at cleavage stage.

LIMITATIONS, REASONS FOR CAUTION
Our modest sample included only 50 couples contributing one cycle each. In addition, non-differential misclassification of exposure remains a concern given the single-spot urine collection and the short half-life of phthalates.

WIDER IMPLICATIONS OF THE FINDINGS
Our results suggest an inverse association between male preconception concentrations of select phthalate metabolites and blastocyst quality, likely occurring after genomic activation. If corroborated with other studies, such findings will have public health and clinical significance for both the general population and those undergoing IVF.

STUDY FUNDING/COMPETING INTERESTS
This work was generously supported by grant K22-ES023085 from the National Institute of Environmental Health Sciences. The authors declare no competing interests.

Testosterone treatment and risk of venous thromboembolism

Population based case-control study, The BMJ, November 2016

Abstract

Objective
To determine the risk of venous thromboembolism associated with use of testosterone treatment in men, focusing particularly on the timing of the risk.

Design
Population based case-control study

Setting
370 general practices in UK primary care with linked hospital discharge diagnoses and in-hospital procedures and information on all cause mortality.

Testosterone treatment and risk of venous thromboembolism: population based case-control study, The BMJ 2016;355:i5968, 30 November 2016.

Participants
19 215 patients with confirmed venous thromboembolism (comprising deep venous thrombosis and pulmonary embolism) and 909 530 age matched controls from source population including more than 2.22 million men between January 2001 and May 2013.

Exposure of interest
Three mutually exclusive testosterone exposure groups were identified: current treatment, recent (but not current) treatment, and no treatment in the previous two years. Current treatment was subdivided into duration of more or less than six months.

Main outcome measure
Rate ratios of venous thromboembolism in association with current testosterone treatment compared with no treatment were estimated using conditional logistic regression and adjusted for comorbidities and all matching factors.

Results
The adjusted rate ratio of venous thromboembolism was 1.25 (95% confidence interval 0.94 to 1.66) for current versus no testosterone treatment. In the first six months of testosterone treatment, the rate ratio of venous thromboembolism was 1.63 (1.12 to 2.37), corresponding to 10.0 (1.9 to 21.6) additional venous thromboembolisms above the base rate of 15.8 per 10 000 person years. The rate ratio after more than six months’ treatment was 1.00 (0.68 to 1.47), and after treatment cessation it was 0.68 (0.43 to 1.07). Increased rate ratios within the first six months of treatment were observed in all strata: the rate ratio was 1.52 (0.94 to 2.46) for patients with pathological hypogonadism and 1.88 (1.02 to 3.45) for those without it, and 1.41 (0.82 to 2.41) for those with a known risk factor for venous thromboembolism and 1.91 (1.13 to 3.23) for those without one.

Conclusions
Starting testosterone treatment was associated with an increased risk of venous thromboembolism, which peaked within six months and declined thereafter.

Morphologic and molecular changes in the placenta: what we can learn from environmental exposures

Environmental exposures: pregnancy, placenta, and miscarriage

Abstract

In mammals, the extraembryonic tissues, which include the placenta, are crucial for embryonic development and growth.

Because the placenta is no longer needed for postnatal life, however, it has been relatively understudied as a tissue of interest in biomedical research.

Recently, increased efforts have been placed on understanding the placenta and how it may play a key role in human health and disease.

Morphologic and molecular changes in the placenta: what we can learn from environmental exposures, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 930–940, September 15, 2016.

Pregnancy image: kulden.

In this review, we discuss two very different types of environmental exposures: assisted reproductive technologies and in utero exposure to endocrine-disrupting chemicals.

We summarize the current literature on their effects on placental development in both rodent and human, and comment on the potential use of placental biomarkers as predictors of offspring health outcomes.

Environmental influences on reproductive health: the importance of chemical exposures

Environmental exposures: pregnancy, placenta, and miscarriage

Abstract

Chemical exposures during pregnancy can have a profound and life-long impact on human health.

Because of the omnipresence of chemicals in our daily life, there is continuous contact with chemicals in food, water, air, and consumer products.

Consequently, human biomonitoring studies show that pregnant women around the globe are exposed to a variety of chemicals.

In this review we provide a summary of current data on maternal and fetal exposure, as well as health consequences from these exposures.

Environmental influences on reproductive health: the importance of chemical exposures, Fertility and Sterility, Volume 106, Issue 4, Pages 905–929, September 15, 2016.

Pregnancy image: Stefan Pasch.

We review several chemical classes, including polychlorinated biphenyls, perfluoroalkyl substances, polybrominated diphenyl ethers, phenols, phthalates, pesticides, and metals.

Additionally, we discuss environmental disparities and vulnerable populations, and future research directions.

We conclude by providing some recommendations for prevention of chemical exposure and its adverse reproductive health consequences.

Very clear evidence that testosterone does not help men’s health

Treatment of Men for “Low Testosterone”: No Benefits…

A group of researchers have announced that they have established testosterone treatments benefits: none.

Abstract

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition.

We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables.

Treatment of Men for “Low Testosterone”: A Systematic Review, PLOS one, September 21, 2016.

*Testosterone, Baby! marshallsegal.

Testosterone supplementation did not show consistent benefit for cardiovascular risk, sexual function, mood and behavior, or cognition. Studies that examined clinical cardiovascular endpoints have not favored testosterone therapy over placebo. Testosterone is ineffective in treating erectile dysfunction and controlled trials did not show a consistent effect on libido. Testosterone supplementation consistently increased muscle strength but did not have beneficial effects on physical function. Most studies on mood-related endpoints found no beneficial effect of testosterone treatment on personality, psychological well-being, or mood.

Researchers say there are no benefits of testosterone treatments for men, the guardian, 21 September 2016.

The prescription of testosterone supplementation for low-T for cardiovascular health, sexual function, physical function, mood, or cognitive function is without support from randomized clinical trials.

Outdoor air pollution and human infertility

Outdoor air pollution and reproduction, 2016

Abstract

Air pollution is a current research priority because of its adverse effects on human health, including on fertility.

However, the mechanisms through which air pollution impairs fertility remain unclear.

In this article, we perform a systematic review to evaluate currently available evidence on the impact of air pollution on fertility in humans.

Several studies have assessed the impact of air pollutants on the general population, and have found reduced fertility rates and increased risk of miscarriage.

Outdoor air pollution and human infertility: a systematic review, Fertility and Sterility, Volume 106, Issue 4, Pages 897–904, September 15, 2016.

Image: Environmental Research Group, King’s College London, London Air Quality Network.

In subfertile patients, women exposed to higher concentrations of air pollutants while undergoing IVF showed lower live birth rates and higher rates of miscarriage.

After exposure to similar levels of air pollutants, comparable results have been found regardless of the mode of conception (IVF versus spontaneous conception), suggesting that infertile women are not more susceptible to the effects of pollutants than the general population.

In addition, previous studies have not observed impaired embryo quality after exposure to air pollution, although evidence for this question is sparse.

Outdoor air pollution and sperm quality

Outdoor air pollution and reproduction, 2016

Abstract

Exposure to air pollution has been clearly associated with a range of adverse health effects, including reproductive toxicity, but its effects on male semen quality are still unclear.

We performed a systematic review (up to June 2016) to assess the impact of air pollutants on sperm quality. We included 17 semi-ecological, panel, and cohort studies, assessing outdoor air pollutants, such as PM2.5, PM10, NOx, SO2, and O3, and their effects on DNA fragmentation, sperm count, sperm motility, and sperm morphology.

Outdoor air pollution and sperm quality, Fertility and Sterility, Volume 106, Issue 4, Pages 880–896, September 15, 2016.

London Air Pollution View from Hackney, zongo.

Thirteen studies assessed air pollution exposure measured environmentally, and six used biomarkers of air pollution exposure (two did both).

We rated the studies using the Newcastle-Ottawa Scale and assessed with the exposure method. Taking into account these factors and the number of studies finding significant results (positive or negative), the evidence supporting an effect of air pollution on DNA fragmentation is weak but suggestive, on sperm motility is limited and probably inexistent, on lower sperm count is inconclusive, and on sperm morphology is very suggestive. Because of the diversity of air pollutants and sperm parameters, and the studies’ designs, we were unable to perform a meta-analysis.

In summary, most studies concluded that outdoor air pollution affects at least one of the four semen quality parameters included in the review. However, results lack consistency, and furthermore, studies were not comparable. Studies using standardized air pollution and semen measures are required to obtain more reliable conclusions.

Endocrine disrupters, microRNAs, and primordial germ cells: a dangerous cocktail

Endocrine disrupting chemicals: female and male reproduction

Abstract

Endocrine-disrupting chemicals (EDCs) are environmental pollutants that may change the homeostasis of the endocrine system, altering the differentiation of germ cells with consequences for reproduction.

In mammals, germ cell differentiation begins with primordial germ cells (PGCs) during embryogenesis.

Primordial germ cell development and gametogenesis are genetically regulated processes, in which the posttranscriptional gene regulation could be mediated by small noncoding RNAs (sncRNAs) such as microRNAs (miRNAs).

Endocrine disrupters, microRNAs, and primordial germ cells: a dangerous cocktail, Fertility and Sterility, Volume 106, Issue 4, Pages 871–879, September 15, 2016.

An Early Fall, light_seeker.

Here, we review the deleterious effects of exposure during fetal life to EDCs mediated by deregulation of ncRNAs, and specifically miRNAs on PGC differentiation.

Moreover, the environmental stress induced by exposure to some EDCs during the embryonic window of development could trigger reproductive dysfunctions transgenerationally transmitted by epigenetic mechanisms with the involvement of miRNAs expressed in germ line cells.