Is human fecundity declining?

Skakkebæk, Niels E.; Jørgensen, Niels; Main, Katharina M.; Meyts, Ewa Rajpert‐De; Leffers, Henrik; Andersson, Anna‐Maria; Juul, Anders; Carlsen, Elisabeth; Mortensen, G.K.; Jensen, Tina Kold; Toppari, Jorma

doi:10.1111/j.1365-2605.2005.00573.x

Cited by 265 publications

(163 citation statements)

References 93 publications

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“…With increasing concern about the impact of endocrine disrupting chemicals on male fecundity, particularly in light of a large fraction of male infertility attributed to such exposure (Hauser et al ., 2015), coupled with evolving biomarkers of male fecundity (Isobe, 2012; Kovac et al ., 2013), environment‐wide association study (EWAS) approaches offer options for identifying predictors of male fecundity and fertility. Novel approaches are needed if we are to understand the relatively high prevalence of male infertility in some populations (Louis et al ., 2013), reported declines in sperm morphology (Rolland et al ., 2013) and more generalized concerns about declining human fecundity (Skakkebaek et al ., 2006; te Velde et al ., 2010). …”

Section: Discussionmentioning

confidence: 99%

A data‐driven search for semen‐related phenotypes in conception delay

2016

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SummarySperm count, morphology, and motility have been reported to be predictive of pregnancy, although with equivocal basis prompting some authors to question the prognostic value of semen analysis. To assess the utility of including semen quality data in predicting conception delay or requiring >6 cycles to become pregnant (referred to as conception delay), we utilized novel data‐driven analytic techniques in a pre‐conception cohort of couples prospectively followed up for time‐to‐pregnancy. The study cohort comprised 402 (80%) male partners who provided semen samples and had time‐to‐pregnancy information. Female partners used home pregnancy tests and recorded results in daily journals. Odds ratios (OR), false discovery rates, and 95% confidence intervals (CIs) for conception delay (time‐to‐pregnancy > 6 cycles) were estimated for 40 semen quality phenotypes comprising 35 semen quality endpoints and 5 closely related fecundity determinants (body mass index, time of contraception, lipids, cotinine and seminal white blood cells). Both traditional and strict sperm phenotype measures were associated with lower odds of conception delay. Specifically, for an increase in percent morphologically normal spermatozoa using traditional methods, we observed a 40% decrease in conception delay (OR = 0.6, 95% CI = 0.50, 0.81; p = 0.0003). Similarly, for an increase in strict criteria, we observed a 30% decrease in odds for conception delay (OR = 0.7, 95% CI = 0.52, 0.83; p = 0.001). On the other hand, an increase in percent coiled tail spermatozoa was associated with a 40% increase in the odds for conception delay (OR = 1.4, 95% CI = 1.12, 1.75; p = 0.003). However, our findings suggest that semen phenotypes have little predictive value of conception delay (area under the curve of 73%). In a multivariate model containing significant semen factors and traditional risk factors (i.e. age, body mass index, cotinine and ever having fathered a pregnancy), there was a modest improvement in prediction of conception delay (16% increase in area under the curve, p < 0.0002).

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Section: Discussionmentioning

confidence: 99%

A data‐driven search for semen‐related phenotypes in conception delay

2016

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“…diethylhexyl phthalate, dibutyl phthalate, and butyl benzyl phthalate) results in many changes in the male reproductive tract, such as decreased anogenital distance, hypospadias, cryptorchidism, disturbed development of prostate, epididymis, vas deferens, and seminal vesicles, retained nipples, and decreased sperm production (Mylchreest et al, 1998(Mylchreest et al, , 1999(Mylchreest et al, , 2000(Mylchreest et al, , 2002Gray et al, 2000;Kavlock et al, 2002a,b,c,d,e;Lottrup et al, 2006;Skakkebaek et al, 2006;Weisbach et al, 2006). The critical window for all of these effects is the latter half of gestation (days 12-21), which is the time during which male sexual differentiation occurs (Mylchreest et al, 1999).…”

Section: ) Phthalatesmentioning

confidence: 99%

“…45X/46XY and androgen insensitivity) also have high risk of testicular cancer, often combined with cryptorchidism and hypospadias (Savage & Lowe, 1990). It has been proposed that all these human disorders (testicular germ cell cancer, cryptorchidism, hypospadias, and low sperm counts) have common origins in fetal life, and thus they all represent different symptoms of the same underlying entity called testicular dysgenesis syndrome (Aarskog, 1970;Scully, 1981;Sharpe & Skakkebaek, 1993;Skakkebaek et al, 2001Skakkebaek et al, , 2006Sharpe, 2003;Asklund et al, 2004). Since the testicular and other changes in dibutyl phthalate-exposed rats have also been reported in human testicular dysgenesis syndrome, it has been proposed that in utero exposure of the rat to dibutyl phthalate is a possible model for studying human testicular dysgenesis syndrome (Fisher et al, 2003).…”

Section: ) Phthalatesmentioning

confidence: 99%

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Liu

Xia

Guo

et al. 2012

J Expo Sci Environ Epidemiol

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The urinary metabolites of phthalates are well-accepted exposure biomarkers for adults and children older than 6 years but are not commonly used for infants owing to non-convenient sampling. In the light of this situation, a novel sampling method based on monitoring the urine expressed from the gel diaper was developed. The urine was expressed from the gel absorbent after mixing the absorbent with CaCl2 and then collected by a laboratory-made device; the urinary phthalate metabolites were extracted and cleaned using a solid-phase extraction (SPE) column and analyzed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate the method's feasibility, the following factors were investigated: the proportion of CaCl2 to gel absorbent, the urination volume variation and the target compounds' deposition bias in the diaper, the matrix blank of the different diaper brands, the storage stabilities and the recoveries of creatinine and phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the urine can be expressed from the diaper, and the expressed spiking recoveries and the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50 ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper samples from 15 infants, and the pilot data suggests the infants are commonly exposed to phthalates. In summary, the method for monitoring of infant exposure to phthalates is sound and validated, and the potential health effects from the vulnerable infants' exposure to phthalates should be concerned.39th Scientific Research Foundation for the Returned Overseas Chinese Scholars (SRF for ROCS); Hundred Talent Program of Chinese Academy of Sciences (CAS); CAS/SAFEA International Partnership Program for Creative Research Teams [KZCX2-YW-T08

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“…Infertility is a worldwide reproductive health problem that affects about 15 % of couples [1], and the marked decrease in fertility rates in many industrialized countries demand further scientific attention [2]. Half of infertility cases are due to male factors, and 75 % of such cases are idiopathic [3].…”

Section: Introductionmentioning

confidence: 99%

Calcium- and integrin-binding protein-1 is down-regulated in the sperm of patients with oligoasthenozoospermia

Sun

Guan

Wen

et al. 2014

J Assist Reprod Genet

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Purpose The aim of this study was to determine whether altered expression and distribution of calcium-and integrinbinding protein-1 (CIB1) is involved in the pathogenesis of patients with oligoasthenozoospermia. Methods Sperm samples were obtained from 25 infertile Chinese men who had failed to achieve conception after a period of 1-2 y and had been referred to the Reproductive Laboratory of the second hospital affiliated to the Shandong University of Traditional Chinese Medicine. Participants were divided into two groups: oligoasthenozoospermia (n=13) and asthenozoospermia (n=12); as a third group, fertile men (n=19) were included as controls. The expression levels of mRNA and protein levels of CIB1 and cyclin-dependent kinase 1 (CDK1) were measured using qRT-PCR and western blotting. Results mRNA and protein expression levels of CIB1 were decreased in the oligoasthenozoospermia patients. Interestingly mRNA and protein expression levels of CDK1 were increased in the oligoasthenozoospermia patients. Conclusion The results of the present study indicate that that CIB1 may be involved in the pathogenesis of oligoasthenozoospermia by the CDK1 signaling pathway.

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Is human fecundity declining?

Cited by 265 publications

References 93 publications

A data‐driven search for semen‐related phenotypes in conception delay

A data‐driven search for semen‐related phenotypes in conception delay

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Calcium- and integrin-binding protein-1 is down-regulated in the sperm of patients with oligoasthenozoospermia

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