EDCs : evidence that co-exposures should be considered when evaluating the risk of a single chemical

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

2017 Study Abstract

BACKGROUND
Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.

OBJECTIVES
Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.

METHODS
We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.

RESULTS
We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.

CONCLUSIONS
Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.

Discussion

Concerns that the traditional focus of chemical risk assessment on single chemical exposures might underestimate the risks associated with adverse effects of multiple chemicals have been expressed earlier (Kortenkamp 2014), but the impact on risk estimates has been proven difficult to define. This is partly due to incomplete information about the complexity of combined human exposures and to a lack of clarity about the approaches and methods that should be used for mixture risk assessment. Our study provides important advances in improving the scientific basis for human mixture risk assessment. To our knowledge, we demonstrate for the first time that the mixture assessment concept of dose addition is applicable to human tissues. This not only enabled us to avoid certain uncertainties associated with animal-to-human extrapolations, but also enabled us to use a predictive approach. Rather than studying every conceivable combination of chemicals within a mixture, the joint effects of anti-androgenic chemicals in the FEGA can now be approximated on the basis of the effects of each single component by using dose addition as the default assumption.

To utilize the FEGA in multi-component mixture studies required making a leap from qualitative studies to quantitative dose–response analyses. Due to the inhomogeneity of the material and the variations inevitably introduced through the age differences of the fetal testes, the assay outcome (fetal testosterone production) shows high variability, which we had to deal with by rigorously controlling experimental conditions. We achieved good reproducibility, which was essential for realizing our goal of analyzing whether the combined effects of multiple chemicals can be predicted accurately on the basis of the effects of individual mixture components and of assessing the impact of co-exposures on the dose–response curves of single chemicals.

A difficulty in using the FEGA as a screening method for the identification of chemicals with endocrine disruptive properties is the limited availability of human fetal tissue. An additional challenge is in the requirement of collecting tissues of comparable age.

Our study provides direct evidence that co-exposures should be considered when evaluating the risk of a single chemical. We show that effects of a single chemical are underestimated when co-exposure to related chemicals are not considered, and that this underestimation is driven by the number, type, and potency of co-occurring chemicals. In this study, overlooking co-exposures to only seven chemicals led to an underestimation of the potency of BPA by a factor of 10. A corollary of the principles of dose addition is that co-exposure to a larger number of chemicals will drive up the extent of such underestimations if these chemicals are present at levels equipotent with the components we used in our experiments. Alternatively, replacement of some components with larger numbers of other chemicals, but at lower levels, may lead to similar underestimations. More studies using the FEGA are needed to establish these assumptions.

Based on our findings, we suggest that the impact of mixture effects on male sexual differentiation during the first trimester of pregnancy may be considerable. However, although in this study the selection of chemicals was empirically based on the results obtained in our dose–response study, analysis of individual chemicals, assessment of the extent of adverse effects in human fetuses will require more knowledge about the spectrum of chemicals capable of suppressing testosterone synthesis. Future FEGA studies will help close this knowledge gap, especially if based on companion studies that identify all of the exogenous chemicals found in maternal and fetal tissues.

Full Study
  • Featured image : predicted and observed testosterone secretion in human fetal testis by four chemical mixtures. Experimental data are shown as mean ± SEM (blue) of at least four independent experiments. Testosterone production is represented as relative to the first day of culture (D0) production and the control level, see text for more details. The mixture effects were predicted according to dose addition (DA) (thick red curve), with dashed curves the respective 95% confidence intervals (CIs) (dotted orange lines) credit ehp.
  • Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants, Environmental Health Perspectives, DOI:10.1289/EHP1014, AUGUST 2017 | VOLUME 125 | ISSUE 8. Full PDF.
Endocrine Disruptors

Do we need to choose between improved sperm selection or efficacy ?

The latest attempt to improve the sperm’s path

Our goal in the in vitro fertilization laboratory is to maximize the ratio between the number of oocytes retrieved and the production of highly viable embryos. We receive the raw material from our patients (oocytes and sperm cells) and, with our knowledge and the available technologies; we try to improve our success rates day by day. One of our endpoints should be the objective application of validated, repeatable, and non-biased therapies and technologies. Few options remain available for oocytes as all the oocytes will be treated to achieve fertilization. In the case of sperm, millions of cells are available to us, but only a few of them will be used. Is there room to improve the sperm’s path? We must move away from the classical methods of sperm selection (swim up or gradients) and pursue any kind of technology that may take into consideration their molecular characteristics, which are related to successful fertilization, embryo development, and live birth.”…

…continue reading What else can we do? The latest attempt to improve the sperm’s path on Fertility and Sterility, Volume 108, Issue 3, Pages 444–445, September 2017.

Multiple generations of chemical exposure may lead to absolute infertility in males

Science : Are we in a male fertility death spiral ?

Written by Pete Myers, Environmental Health Sciences, July 26, 2017.

Margaret Atwood’s 1985 book, The Handmaid’s Tale, played out in a world with declining human births because pollution and sexually transmitted disease were causing sterility.

Does fiction anticipate reality? Two new research papers add scientific weight to the possibility that pollution, especially endocrine disrupting chemicals (EDCs), are undermining male fertility.

“The study is a wakeup that we are in a death spiral of infertility in men”

Frederick vom Saal, Curators’ Distinguished Professor Emeritus of Biological Sciences at the University of Missouri and expert on endocrine disruption.

The first, published Tuesday, is the strongest confirmation yet obtained that human sperm concentration and count are in a long-term decline: more than 50 percent from 1973 to 2013, with no sign that the decline is slowing.

“The study provides a mechanistic explanation for a progressive decrease in sperm count over generations.”

Frederick vom Saal.

The second, published last week by different authors, offers a possible explanation. It found that early life exposure of male mouse pups to a model environmental estrogen, ethinyl estradiol, causes mistakes in development in the reproductive tract that will lead to lower sperm counts.

But there is much more to this study, led by Washington State University doctoral student Tegan Horan and published in the journal PLoS Genet. The senior author on the paper, Washington State University’s Distinguished Professor of Molecular Biosciences, Patricia Hunt, is one of the world’s leading authorities on how endocrine disrupting chemicals harm the development of sperm and eggs.

What makes this study unique is that it examined what happened when three successive generations of males were exposed—instead of just looking only at the first. Hunt, in an email, said

“we asked a simple question with real-world relevance that had simply never been addressed.”

Successive, constant exposure

More than a dozen papers have now been published on “trans-generational epigenetic inheritance,” where exposure in a great-grandmother causes adverse effects in great-grandson—without further exposures and without changes in DNA sequence.

But crucially these experiments typically only expose one generation—the first—rather induce ongoing exposures across generations, which is the reality of human experience.

In the real world, since World War II, successive generations of people have been exposed to a growing number and quantity of environmental estrogens—chemicals that behave like the human hormone estrogen. Thousands of papers published in the scientific literature (reviewed here) tie these to a wide array of adverse consequences, including infertility and sperm count decline.

This phenomenon—exposure of multiple generations of mammals to endocrine disrupting compounds—had never been studied experimentally, even though that’s how humans have experienced EDC exposures for at least the last 70 years. That’s almost three generations of human males. Men moving into the age of fatherhood are ground zero for this serial exposure.

So Horan, Hunt and their colleagues at WSU set out to mimic, for the first time, this real-world reality. They discovered that the effects are amplified in successive generations.

They observed adverse effects starting in the first generation of mouse lineages where each generation was exposed for a brief period shortly after birth. The impacts worsened in the second generation compared to the first, and by the third generation the scientists were finding animals that could not produce sperm at all. This latter condition was not seen in the first two generations exposed. Details of the experimental results actually suggested that multiple generations of exposure may have increased male sensitivity to the chemical.

Laura Vandenberg, an expert on endocrine disruption effects at the University of Massachusetts, Amherst and who did not participate in either study called Horan and Hunt’s work

“an elegantly designed study that looks at several really important issues in environmental health.” “As the authors rightly point out, over the past several decades, exposures to environmental chemicals—and estrogens in particular—have continued to rise.” Exposure today, is life-long, not episodic. “Remarkably, the damage that is seen in any one generation gets worse and worse as more generations are exposed,” “I have never seen a study examine these different generations so beautifully – this is a tremendous amount of work!”

Vandenberg said.

Long-term decline

The first paper, published Tuesday in the journal Human Reproduction, analyzes data from all studies on the topic researchers could find published in the scientific literature between 1981 and 2013.  Researchers, including Hagai Levine of the Hebrew University of Jerusalem and Shanna Swan of the Icahn School of Medicine in New York found 185 studies that sampled a total of 42,000 men across four  decades beginning in 1973.

“20 percent of Danish men do not father children.”

Niels Skakkebæk, University of Copenhagen

Declines in sperm concentration and total sperm count were “highly significant” for samples from North America, Europe, Australia and New Zealand. Those from South America, Asia and Africa were not significant, possibly a result of a much smaller sample size.

Hunt sees considerable linkage between the two studies.

“Our data are showing that things get progressively worse as subsequent generations are exposed,” “These large changes in human sperm count and concentration reveal that we are already well down the road.”

she said.

Niels Skakkebæk, a Danish pediatrician and researcher whose 1992 paper with Elisabeth Carlsen reporting large long-term declines in human sperm count kicked off over 20 years of debate, added:

“These two new papers add significantly to existing literature on adverse trends in male reproductive health problems. Importantly, the data are in line with data on testicular cancer which is increasing worldwide.” “Here in Denmark, there is an epidemic of infertility,” “More than 20 percent of Danish men do not father children.” “Most worryingly [in Denmark] is that semen quality is in general so poor that an average young Danish man has much fewer sperm than men had a couple of generations ago, and more than 90 percent of their sperm are abnormal.”

Skakkebæk did not participate in either study.

Skakkebæk’s concerns about younger men are reinforced by some of the details of the new sperm study because it reports that men in a subgroup of the total sample whose partners are not yet pregnant nor do they have children (i.e., they are not confirmed fertile men) have experienced a drop in average sperm count of almost 50 percent over four decades, to 47 million sperm per milliliter. That puts counts close to what the World Health Organization considers impairment in ability fertilize an egg—40 million sperm per milliliter.

Indicator of male health?

Poor sperm count is associated with overall morbidity and mortality.

That’s the average reduction. Every average has a distribution: Some with more reduction, some less. And those who fall in the “more” category may wind up below the level where WHO considers fertilization unlikely—15 million sperm per milliliter. The new study specifically notes that a high proportion of men from Western countries have concentrations below 40 million per milliliter.

The sperm count study raises a larger issue, beyond reductions in the ability to fertilize an egg.

“Poor sperm count is associated with overall morbidity and mortality,” “A decline in sperm count might be considered as a ‘canary in the coal mine’ for male health across the lifespan. Our report of a continuing and robust decline should, therefore, trigger research into its causes, aiming for prevention.”

the authors wrote.

Are we, as suggested by Dr. vom Saal, in a “death spiral” of male infertility? And if so, what are the larger implications? Perhaps the most far-reaching, if this is true, would be what this means there will be changes in age distributions in populations in nations suffering from this spiral.

A core assumption driving economic policies around the world is that growth is essential. Populations that are declining because of infertility face big problems because economic activity depends upon have a large number of working people compared to those that are retired. Expectations for economic growth diminish.

Would further declines in male fertility undermine the assumptions that fuel faith in economic growth, as the age distribution shifts to one with more retired people and fewer working? These are vital questions that traditional demographers have largely chosen to ignore.

Pete Myers,
Founder and chief science officer of Environmental Health News, publisher of EHN.org and DailyClimate.org.

Featured image credit womenshealth.gov.

Age and body mass index v. Triclosan exposure, and diminished ovarian reserve

Urinary triclosan concentrations and diminished ovarian reserve among women undergoing treatment in a fertility clinic

2017 Study Abstract

Objective
To investigate the association between urinary triclosan concentrations and antral follicle count (AFC), a well-accepted marker of ovarian reserve, among women from a fertility center.

Design
Prospective cohort study.

Setting
Hospital fertility center.

Patient(s)
A total of 109 women.

Intervention(s)
Urinary triclosan concentrations quantified by online solid phase extraction-high performance liquid chromatography-isotope dilution tandem mass spectrometry.

Main Outcome Measure(s)
AFC through transvaginal ultrasonography on the third day of an unstimulated menstrual cycle or on the third day of a progesterone withdrawal bleed.

Result(s)
The geometric mean of the specific gravity–adjusted urinary triclosan concentrations for the 225 samples provided by the 109 women was 13.0 μg/L (95% confidence interval [CI], 8.9, 19.1). Women had median (with interquartile range) AFC of 13 (8, 18). The specific gravity–adjusted urinary triclosan concentrations were inversely associated with AFC (−4%; 95% CI, −7%, −1%). Women with triclosan concentrations above the median had lower AFC compared with those whose triclosan concentrations were equal to or below the median, with an adjusted difference of −3.2 (95% CI, −3.9, −1.6) among those with a body mass index <25 kg/m2 and −1.8 (95% CI, −3.2, −0.3) among those who were <35 years old.

Conclusion(s)
Specific gravity–adjusted urinary triclosan concentrations were inversely associated with AFC in women seeking care at a fertility center. This association was modified by age and body mass index, with the younger and leaner women showing larger decreases in AFC.

  • Urinary triclosan concentrations and diminished ovarian reserve among women undergoing treatment in a fertility clinic, American Society for Reproductive Medicine, Volume 108, Issue 2, Pages 312–319, August 2017.
  • Antibacterial Soap Triclosan image credit Mike Mozart.

Sperm concentration has declined more than 50% in less than 40 years

Temporal trends in sperm count : a systematic review and meta-regression analysis

New Meta-analysis finds that among men from North America, Europe and Australia, sperm concentration has declined more than 50% in less than 40 years and points toward importance of further investigation into environmental factors.

Temporal trends in sperm count: a systematic review and meta-regression analysis, by the Hebrew University of Jerusalem, points to an alarming decline in male reproductive health, and suggests worrying implications for male fertility and reproduction. Based on data collected on men from North America, Europe, Australia and New Zealand from 1973 to 2011, the study performed the first ever systematic review and meta-analysis on sperm counts and found a decline of more than 59%, with no sign of levelling off over time. The findings are significant considering that low sperm levels have also been linked with higher risks of hospitalization and death.

2017 Study Abstract

BACKGROUND
Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality.

OBJECTIVE AND RATIONALE
To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group.

SEARCH METHODS
PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981–2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973–2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group (‘Unselected by fertility’ versus ‘Fertile’), geographic group (‘Western’, including North America, Europe Australia and New Zealand versus ‘Other’, including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models.

OUTCOMES
SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models −0.70 million/ml/year; 95% CI: −0.72 to −0.69; P < 0.001; slope in adjusted meta-regression models = −0.64; −1.06 to −0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (−1.38; −2.02 to −0.74; P < 0.001) and among Fertile Western (−0.68; −1.31 to −0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (−5.33 million/year, −7.56 to −3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (−2.06 million/ml, −3.38 to −0.74; P = 0.004 and −8.12 million, −13.73 to −2.51, P = 0.006, respectively).

WIDER IMPLICATIONS
This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50–60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

Sources and Press Releases
  • Temporal trends in sperm count: a systematic review and meta-regression analysis, Hum Reprod Update, doi.org/10.1093/humupd/dmx022, 25 July 2017.
  • New Meta-analysis finds that among men from North America, Europe and Australia, sperm concentration has declined more than 50% in less than 40 years, Health & Environment, 26 July 2017.
  • Featured image credit freemalaysiatoday.

Psychological and emotional concomitants of infertility diagnosis in women with diminished ovarian reserve or anatomical cause of infertility

Fertility and Sterility, Mental health, Volume 108, Issue 1, July 2017

2017 Study Abstract

Objective
To examine the magnitude and predictors of emotional reactions to an infertility diagnosis in two groups of women: those with diminished ovarian reserve (DOR), and those clinically diagnosed with an anatomical cause of infertility (ACI).

Design
Cross-sectional study.

Setting
Academic and private fertility clinics.

Patient(s)
Women diagnosed with DOR (n = 51) and women diagnosed with ACI (n = 51).

Main Outcome Measure(s)

Psychological and emotional concomitants of infertility diagnosis in women with diminished ovarian reserve or anatomical cause of infertility, Fertility and Sterility, Mental health, Volume 108, Issue 1, dx.doi.org/10.1016/j.fertnstert.2017.05.008, July 2017.

Image credit Petras Gagilas.

Fertility Problem Inventory (infertility distress), Rosenberg Self-Esteem Scale, Health Orientation Scale (emotional reactions to receiving a diagnosis).

Result(s)
Women with DOR had statistically significantly higher infertility distress scores than women with ACI and higher scores on subscales assessing distress from social concerns, sexual concerns, and a need for parenthood. In both groups, higher self-esteem was associated with lower infertility distress. Hierarchical multiple regression analyses revealed that for women with DOR and those with ACI lower infertility distress but not self-esteem predicted a more positive emotional reaction toward receiving a fertility diagnosis.

Conclusion(s)
Women diagnosed with DOR have greater infertility distress but similar self-esteem and emotional reactions to their diagnosis compared with women who have an anatomical cause of infertility. These results suggest that for both groups distress surrounding infertility itself may influence the way women respond to learning the cause of their infertility.

Can non-daytime shifts and physically demanding jobs decrease women’s fertility?

Indeed : heavy lifting, shift work could affect women’s fertility

Women who lift heavy loads at work may experience decreased fertility, and the effect appears stronger among overweight or obese women and older women, according to a new study from Harvard T.H. Chan School of Public Health.

Working non-daytime work schedules may also decrease fertility, the researchers found. 

2017 Study Abstract

Objectives
To explore whether work schedules and physically demanding work were associated with markers of ovarian reserve and response.

Methods
This analysis included women (n=473 and n=313 for ovarian reserve and ovarian response analysis, respectively) enrolled in a prospective cohort study of couples presenting to an academic fertility centre (2004–2015). Information on occupational factors was collected on a take-home questionnaire, and reproductive outcomes were abstracted from electronic medical records. Generalised linear models and generalised linear mixed models were used to evaluate the associations.

Occupational factors and markers of ovarian reserve and response among women at a fertility centre, BMJ, dx.doi.org/10.1136/oemed-2016-103953, 6 February 2017.

Results
Women who reported lifting or moving heavy objects at work had 1.0 fewer total oocytes (p=0.08), 1.4 fewer mature oocytes (p=0.007) and 0.7 fewer antral follicles (p=0.06) compared with women who reported never lifting or moving heavy objects at work. The inverse association between heavy lifting and oocyte yield was stronger in women >37 years and with a Body Mass Index ≥25 kg/m2. Women who worked evening/night/rotating shifts had 2.3 (p<0.001) fewer mature oocytes, on average, compared with women who worked day-only shifts. None of the occupational exposures were associated with day 3 follicle-stimulating hormone or peak oestradiol levels.

Conclusions
Women working non-daytime shifts and those with physically demanding jobs had fewer mature oocytes retrieved after controlled ovarian hyperstimulation. Our results provide insight into possible mechanisms linking these occupational exposures with decreased fecundity.

Perturbateurs endocriniens : tous intoxiqués?

Les nouveaux poisons de notre quotidien

Enquête de santé, Allo Docteurs France 5, 01/02/2017.

Un documentaire / débat diffusé le 31 janvier 2017 sur France 5.

Documentaire

Débat

Les perturbateurs endocriniens, substances chimiques, sont présentes dans de nombreux objets de consommation courante : plastiques, résidus de pesticides sur les fruits et légumes, OGM, cosmétiques, lunettes, semelles de chaussures… Ils interagissent avec le système hormonal et seraient responsables de l’augmentation de certains cancers, selon des associations impliquées dans les problèmes de santé liés à l’environnement.

Sur le même sujet

Le Distilbène, Perturbateur Endocrinien

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.

Normal vs. T-shaped Uterus

Utero-salpingography showing Diethylstilboestrol exposure in-utero uterus

Diethylstilboestrol (DES) exposure in-utero has been shown to have a potentially negative impact on pregnancy. Negative effects include an increased risk of early pregnancy loss, ectopic gestation and infertility.

These women may also present reproductive tract abnormalities leading to pregnancy complications. The most common anomalies include uterine defects such as T-shaped uterus or hypoplastic uterine cavity.

Image Sources

More DES DiEthylStilbestrol Resources