Environmental factors in declining human fertility

Skakkebæk, Niels E.; Lindahl-Jacobsen, Rune; Levine, Hagai; Andersson, Anna‐Maria; Jørgensen, Niels; Main, Katharina M.; Lidegaard, Øjvind; Priskorn, Lærke; Holmboe, Sarah; Bräuner, Elvira Vaclavik; Almstrup, Kristian; França, Luiz R.; Znaor, Ariana; Kortenkamp, Andreas; Hart, Roger; Juul, Anders

doi:10.1038/s41574-021-00598-8

Cited by 193 publications

(103 citation statements)

References 211 publications

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“…Assisted reproductive techniques (ARTs) represent an important treatment option for infertile couples and its utilization has constantly increased with growth rates between 2.4% and 18.3% per annum in Europe, USA, Australia, and New Zealand in the years from 2012 to 2016 [1], resulting in about 1.3 million ART cycles in 2016 in these areas. Such an increase may be caused by several factors, including socio-economic [2] and environmental factors [3]. This is also paralleled with the observation of the temporal decline of human fertility in many countries [4].…”

Section: Introductionmentioning

confidence: 81%

Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment

et al. 2022

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Oxidative stress (OS) due to an imbalance between reactive oxygen species (ROS) and antioxidants has been established as an important factor that can negatively affect the outcomes of assisted reproductive techniques (ARTs). Excess ROS exert their pathological effects through damage to cellular lipids, organelles, and DNA, alteration of enzymatic function, and apoptosis. ROS can be produced intracellularly, from immature sperm, oocytes, and embryos. Additionally, several external factors may induce high ROS production in the ART setup, including atmospheric oxygen, CO2 incubators, consumables, visible light, temperature, humidity, volatile organic compounds, and culture media additives. Pathological amounts of ROS can also be generated during the cryopreservation-thawing process of gametes or embryos. Generally, these factors can act at any stage during ART, from gamete preparation to embryo development, till the blastocyst stage. In this review, we discuss the in vitro conditions and environmental factors responsible for the induction of OS in an ART setting. In addition, we describe the effects of OS on gametes and embryos. Furthermore, we highlight strategies to ameliorate the impact of OS during the whole human embryo culture period, from gametes to blastocyst stage.

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Section: Introductionmentioning

confidence: 81%

Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment

et al. 2022

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“…The study population consisted of a total of 393 men recruited to an either fertile or infertile study group as described elsewhere 14,15 . In brief, all men were recruited at Rigshospitalet (University Hospital in Copenhagen, Denmark), and inclusion criteria in both groups were age between 20 and 45 years, and that the man and his mother were born and raised in Denmark, as testicular function is hypothesized to be partly determined prenatally and depending on the environment in which the mother lived 16,17 . Thus, the included men were mainly Caucasian.…”

Section: Methodsmentioning

confidence: 99%

Anogenital distance, male factor infertility and time to pregnancy

et al. 2022

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Background: Anogenital distance (AGD), the distance between the anus and genitals, is in rodents a well-established marker of early androgen action and has been suggested to be so in humans as well. Thus, a link between human AGD and semen quality and potentially fecundity may exist. Objective:The aim of this study was to assess the association between AGD and male factor infertility and among proven fertile men also time to pregnancy (TTP).Material and methods: All included men were recruited from and examined at Copenhagen University Hospital -Rigshospitalet, Denmark (N = 388). Men with impaired semen quality were included from infertile couples (N = 128), and men with naturally conceived pregnant partners were invited to participate when their partners had their routine second trimester examination (N = 260). All men underwent a physical examination, completed a questionnaire (including TTP for the fertile men), delivered a semen sample and had a blood sample drawn. The primary exposure was AGD AS measured from the centre of the anus to the posterior base of the scrotum. Associations between AGD and fertility status as well as between AGD and TTP among the fertile men were calculated using multiple logistic regression adjusted for covariates.Results: AGD did not show a statistically significant association with fertility status.In adjusted logistic regression models, the odds of infertility per 1 cm increase in AGD AS were 1.02 (95% confidence interval [CI]: 0.88; 1.19). Among fertile men, a 1cm increase in AGD AS was associated with an 8% non-statistically significantly reduced odds of having a longer (>3months) TTP (adjusted odds ratio (OR) = 0.92, 95% CI: 0.76-1.11). Conclusion:Our study showed that the clinical application of AGD as a predictor of fertility and fecundity seems to be limited as no associations were observed between AGD and fertility status, nor was the decreased risk of experiencing a longer TTP with longer AGD AS statistically significant.

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“…Incidence,15-44 years old present one preventive opportunity that could additionally serve to prevent subfertility. 33 The identification of exposures remains a difficult task, given a huge number of potential EDC and their mixtures produced and used in different countries, including commonly used pharmaceuticals (over-the-counter analgesics), which can disrupt foetal testis development and have been associated with increased risk of cryptorchidism. 34,35 A protracted time window between the exposure undergone by the mother and diagnosis of the disease in the male descendant is an additional hurdle.…”

Section: No Data Not Applicablementioning

confidence: 99%

Global patterns in testicular cancer incidence and mortality in 2020

Znaor

Skakkebæk

Meyts

et al. 2022

Intl Journal of Cancer

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With 74 500 new cases worldwide in 2020, testicular cancer ranks as the 20th leading cancer type, but is the most common cancer in young men of European ancestry. While testicular cancer incidence has been rising in many populations, mortality trends, at least those in high-income settings, have been in decline since the 1970s following the introduction of platinum-based chemotherapy. To examine current incidence and mortality patterns, we extracted the new cases of, and deaths from cancers of the testis from the GLOBOCAN 2020 database. In 2020, testicular cancer was the most common cancer in men aged 15 to 44 in 62 countries worldwide. Incidence rates were highest in West-, North-and South-Europe and Oceania (age-standardised rate, ASR ≥7/100 000), followed by North America (5.6/100 000 and lowest (<2/100 000) in Asia and Africa.The mortality rates were highest in Central and South America (0.84 and 0.54 per 100 000, respectively), followed by Eastern and Southern Europe, and Western and Southern Africa. The lowest mortality rates were in Northern Europe, Northern Africa and Eastern Asia (0.16, 0.14, 0.9 per 100 000, respectively). At the country level, incidence rates varied over 100-fold, from 10/100 000 in Norway, Slovenia, Denmark and Germany to ≤0.10/100 000 in Gambia, Guinea, Liberia, Lesotho. Mortality rates were highest in Fiji, Argentina and Mexico. Our results indicate a higher mortality burden in countries undergoing economic transitions and reinforce the need for more equitable access to testicular cancer diagnosis and treatment globally.

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Environmental factors in declining human fertility

Cited by 193 publications

References 211 publications

Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment

Oxidative Stress and Assisted Reproduction: A Comprehensive Review of Its Pathophysiological Role and Strategies for Optimizing Embryo Culture Environment

Anogenital distance, male factor infertility and time to pregnancy

Global patterns in testicular cancer incidence and mortality in 2020

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