World Health Organization reference values for human semen characteristics

Centre of Reproductive Medicine and Andrology of the University, Domagkstrasse 11, Münster, Germany.
Human Reproduction Update (Impact Factor: 10.17). 11/2009; 16(3):231-45. DOI: 10.1093/humupd/dmp048
Source: PubMed


Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated.
Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population.
The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men.
The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

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Available from: Trine B Haugen, Apr 21, 2014
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    • "Patients were selected for IVF according to clinical indications and semen quality: e.g. normal sperm concentration and motility (Cooper et al., 2010) and 1 × 10 6 progressively motile cells post-preparation. "
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    ABSTRACT: Study question: Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? Summary answer: Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. What is known already: In human spermatozoa, Ca(2+) influx induced by progesterone is mediated by CatSper, a sperm-specific Ca(2+) channel. A suboptimal Ca(2+) influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca(2+)]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. Study design, size, duration: Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. Participants/materials, setting, methods: Samples were primarily screened using the Ca(2+) influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca(2+) response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca(2+) response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis. Main results and the role of chance: A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca(2+) response. The mean (±SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca(2+) response. Three men were initially identified with a defective Ca(2+) influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF. Limitations, reasons for caution: A key limitation relates to working with a specific functional parameter (Ca(2+) influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼22% of IVF patients) could not be screened. As such the incidence of significant Ca(2+) abnormalities induced by progesterone may be higher than the ∼1% observed here. Additionally, we used a strict definition of a defective Ca(2+) influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca(2+) influx. Wider implications of the findings: These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception. Study funding/competing interests: Initial funding was from NHS Tayside, Infertility Research Trust, TENOVUS, Chief Scientist Office NRS Fellowship, the Wellcome Trust, University of Abertay. The majority of the data were obtained using funding from a MRC project grant (# 4190). The authors declare that there is no conflict of interest. Trial registration number: Not applicable.
    Human Reproduction 10/2015; DOI:10.1093/humrep/dev243 · 4.57 Impact Factor
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    • "We use the joint model detailed in Section 2 to connect the woman-specific MCL distribution with the couple's fecundity , as measured by the probability of pregnancy in a menstrual cycle. In the fecundity model, we adjust for male and female active smoking status determined by baseline cotinine level ≥100 ng/mL (see Wall et al., 1988), average of male and female age, difference between male and female age, and four WHO semen quality parameters; semen volume (in ml), sperm concentration (10 6 /ml), total sperm count (concentration × volume), and morphology (strict criteria) as discussed in Cooper et al. (2010). These authors define cut-points to categorize semen quality, we use the continuous measurements . "
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    ABSTRACT: Menstrual cycle length (MCL) has been shown to play an important role in couple fecundity, which is the biologic capacity for reproduction irrespective of pregnancy intentions. However, a comprehensive assessment of its role requires a fecundity model that accounts for male and female attributes and the couple's intercourse pattern relative to the ovulation day. To this end, we employ a Bayesian joint model for MCL and pregnancy. MCLs follow a scale multiplied (accelerated) mixture model with Gaussian and Gumbel components; the pregnancy model includes MCL as a covariate and computes the cycle-specific probability of pregnancy in a menstrual cycle conditional on the pattern of intercourse and no previous fertilization. Day-specific fertilization probability is modeled using natural, cubic splines. We analyze data from the Longitudinal Investigation of Fertility and the Environment Study (the LIFE Study), a couple based prospective pregnancy study, and find a statistically significant quadratic relation between fecundity and menstrual cycle length, after adjustment for intercourse pattern and other attributes, including male semen quality, both partner's age, and active smoking status (determined by baseline cotinine level 100 ng/mL). We compare results to those produced by a more basic model and show the advantages of a more comprehensive approach. © 2015, The International Biometric Society.
    Biometrics 08/2015; DOI:10.1111/biom.12379 · 1.57 Impact Factor
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    • "Semen samples from five individuals with normal sperm parameters according to WHO values (Cooper et al., 2010) were incubated with an equal volume of T. munbyanus dilutions of essential oil or thymol. Solutions of T. munbyanus essential oil were prepared in 5% dimethyl sulfoxide (DMSO) at concentrations of 100, 250, 500, 750 and 1000 µg/ml; control samples were incubated with 5% DMSO. "
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    ABSTRACT: Traditional medicine has been used worldwide for centuries to cure or prevent disease and for male or female contraception. Only a few studies have directly investigated the effects of herbal compounds on spermatozoa. In this study, essential oil from Thymus munbyanus was extracted and its effect on human spermatozoa in vitro was analysed. Gas chromatography and Gas chromatography-mass spectrometry analyses identified 64 components, accounting for 98.9% of the composition of the oil. The principal components were thymol (52.0%), γ-terpinene (11.0%), ρ-cymene (8.5%) and carvacrol (5.2%). Freshly ejaculated spermatozoa was exposed from control individuals to various doses of the essential oil for different time periods, and recorded the vitality, the mean motility, the movement characteristics (computer-aided sperm analysis), the morphology and the ability to undergo protein hyperphosphorylation and acrosomal reaction, which constitute two markers of sperm capacitation and fertilizing ability. In vitro, both the essential oil extracted from T. munbyanus and thymol, the principal compound present in this oil, impaired human sperm motility and its capacity to undergo hyperphosphorylation and acrosome reaction. These compounds may, therefore, be of interest in the field of reproductive biology, as potential anti-spermatic agents. Copyright © 2015. Published by Elsevier Ltd.
    Reproductive biomedicine online 06/2015; 31(3). DOI:10.1016/j.rbmo.2015.06.011 · 3.02 Impact Factor
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