American Journal of Epidemiology Advance Access published online on April 11, 2008
American Journal of Epidemiology, doi:10.1093/aje/kwn076
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Original Contribution |
Parental Subfecundity and Risk of Decreased Semen Quality in the Male Offspring: A Follow-up Study
1 Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark
2 Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA
Correspondence to Dr. Cecilia Høst Ramlau-Hansen, Department of Occupational Medicine, Aarhus University Hospital, Norrebrogade 44, Building 2C, DK-8000 Aarhus C, Denmark (e-mail: craha{at}as.aaa.dk).
Received for publication January 4, 2008. Accepted for publication March 11, 2008.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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A few studies have found poor semen quality in sons whose mothers have received fertility treatment, but it is unknown whether the poor semen quality is related to the infertility treatment or to infertility per se, for example, whether it is caused by hereditable factors. Using data from a population-based, Danish follow-up study conducted in 2005–2006, the authors of the present study examined whether sons of subfertile couples who had not received fertility treatment had poorer semen quality than sons of fertile couples. Among the 311 participants, an inverse association between parental waiting time to pregnancy and both semen volume and total sperm count was observed (p trend = 0.04 and p trend = 0.046, respectively). Semen volume in sons of subfertile parents (pregnant after
1 years) was 19% lower in comparison with that in sons of parents whose waiting time to pregnancy was 0–6 months (p = 0.02). Additionally, sperm concentration and percentage of morphologically normal sperm were, respectively, 22% (p = 0.15) and 23% (p = 0.13) lower in sons of subfertile parents. Results suggest a small-to-moderate effect of parental subfecundity on semen quality in sons, comparable with the hypothesis that low fecundity has at least partly hereditable causes.
fertility; gonadal steroid hormones; heredity; prenatal exposure delayed effects; semen; sperm count
Abbreviations: TTP, waiting time to pregnancy
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Genetic factors are of importance for spermatogenesis, and, in a twin study, heritability was estimated to account for 20 percent of the variation in sperm concentration; even higher heritability estimates were found for percentages of morphologically normal sperm cells (41 percent) and inhibin B (76 percent), a hormone reflecting Sertoli cell function (1). The twin method may, however, overestimate the heritable factor if testis function is partly programmed by intrauterine conditions during fetal life. Increased frequency of reproductive health problems, including poor semen quality, has been found among fathers of boys with hypospadias, suggesting that fathers and sons share causes for reproductive dysfunction such as, for example, susceptibility genes (2).
The quantity of couples seeking infertility treatment is increasing in a number of countries (3), and approximately 7 percent of all Danish children born in the last few years have been conceived after assisted reproduction (4). This trend is of concern if sons of infertile parents inherit infertility and pass on the problem of infertility to future generations.
Jensen et al. (5) observed that men whose mothers had received infertility treatment, including hormones, had poor semen quality, and this finding was later supported by one of our studies (6). It is, however, unknown whether the poor semen quality is related to the infertility treatment or is caused by parental infertility, that is, through maternal or paternal hereditable factors.
To our knowledge, no one has investigated the association between parental waiting time to pregnancy (TTP) and semen quality in adult sons. In this paper, we examine whether sons of subfertile couples who had not received infertility treatment had poorer semen quality than sons of fertile couples. If subfecundity rather than infertility treatment is responsible for the present finding, we expect sons of parents with a long TTP to have poorer semen quality than sons of parents with a shorter TTP.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Population
The study participants were sons of mothers recruited to the Healthy Habits for Two cohort during their pregnancy from April 1984 to April 1987 (7). The Healthy Habits for Two study took place in two Danish municipalities (Aalborg and Odense), and 11,980 women with singleton pregnancies (more than 80 percent of all those invited, regardless of parity) participated. They provided information on TTP, lifestyle factors during pregnancy, and health-related characteristics by filling out a self-administered questionnaire distributed by the midwives around the 36th week of gestation and returned in sealed envelopes to Aarhus University's research department within a couple of weeks. Data on prepregnant heights and weights were entered in the women's antenatal records by their general practitioners at the first routine antenatal care visit and were later extracted from medical files together with birth data. Sons who were alive and living in Denmark by December 2004 were identified in the Danish Civil Registration System (N = 5,109).
Because the study was designed primarily to examine the association between prenatal smoking exposure and adult semen quality (8), the participants were selected according to levels of maternal smoking during pregnancy and without knowing anything about their sons' semen quality. Letters of invitation were sent consecutively, the oldest and those living close to either Aalborg (north of Jutland) or Odense (Funen) having priority, starting at the city centers and as far as approximately 30 km from the centers. Having a limited number of men heavily exposed to tobacco prenatally resulted in use of an expanded geographic area for this group. Additionally, men whose mothers had reported information on health-related issues from childhood to adolescence by means of a self-administered questionnaire when the sons were 16–19 years of age were given priority. A total of 716 men were invited to take part in the study, and 347 (48.5 percent) gave consent and participated. Of 100 men who declined participation by mail or telephone, 82 provided some information on their health. Information on parental TTP was available for 342 (98.6 percent) sons; after exclusion of 31 sons whose mothers reported ever having been examined or treated for childlessness, 311 (89.6 percent) young men remained available for this study.
The selected participants were 18–21 years of age and received an economic incentive (about US $85) for taking part in the study. Men with severe handicaps or congenital syndromes, such as spastic paraplegia or Down's syndrome, as well as men with metabolic diseases or psychiatric disorders, were not invited. The study was approved by the regional ethics committee (registration number 20040174), and participation was conditional on written informed consent.
Determinants
The question on TTP asked of the pregnant women was phrased as follows: How long a time did it take before you became pregnant, that is, how long did it take for you to become pregnant counting from when you and your husband/partner discontinued use of birth control? (translated from Danish). The following response categories were given: Became pregnant in spite of use of birth control, 0–6 months, 7–12 months, and 1 year or more. We combined the two most fertile groups—couples who became pregnant in spite of use of birth control (n = 20) and couples with a TTP of 0–6 months (n = 224)—into one reference group, hereafter referred to as parents with a TTP of 0–6 months.
Endpoints
Data were collected from February 2005 through January 2006. The participants were instructed to provide the semen sample by masturbating into a plastic container at home after at least 48 hours of sexual abstinence. The container was then to be kept close to the body during transportation to the mobile laboratory to avoid cooling, and a trained medical laboratory technician performed the initial semen analysis. Blood samples were taken between 7:25 a.m. and 7:15 p.m. (median time, 1:05 p.m.). The participants completed questionnaires on their reproductive experience, medical and lifestyle factors, time and date of the preceding ejaculation, and spillage during sample collection.
Semen analysis
Semen analyses were performed blinded to any prenatal conditions. Semen volume was estimated by its weight (1 g = 1 ml). Sperm motility and sperm concentration were assessed as described in the World Health Organization's WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction (9). Examination of 82.0 percent of the samples was initiated within the first hour, when it has been shown that motility is stable (10), and examination of 99.7 percent of the samples was initiated within 2 hours. Sperm morphology was determined by using the strict criteria of Kruger et al. (11). The laboratory took part in the European Society for Human Reproduction and Embryology Nordic external quality control program, and all control tests were within the limits set by this organization.
Serum sample analysis
After centrifugation, serum was stored at –80°C for a maximum of 16 months until analysis. Serum samples for testosterone and follicle-stimulating hormone were analyzed by Avida Centaur (Bayer Healthcare, Leverkusen, Germany). Inhibin B was measured by a commercially available enzyme-linked immunosorbent assay (Oxford Bio-Innovation Ltd., Oxford, United Kingdom) according to the manufacturer's instructions. The blood samples were analyzed blinded to parental TTP and as single measurements in random order over a short period of time. The detection limits and total (intraassay and interassay) coefficients of variation for the immunoassays were as follows: testosterone: 0.35–52.1 nmol/liter, <7.7 percent; follicle-stimulating hormone: 0.3–200 IU/liter, <4.0 percent; and inhibin B: 15.0–1,000 pg/ml, <7 percent. In one sample, the concentration of inhibin B was below the detection limit for the specific assay (15.0 pg/ml); therefore, the concentration was arbitrarily set to 14.0 pg/ml before statistical analyses were performed.
The inhibin B samples were analyzed at the Laboratory of Reproductive Biology, University Hospital of Copenhagen, Denmark. Testosterone and follicle-stimulating hormone were analyzed at the Department of Clinical Chemistry, Aarhus University Hospital, Denmark.
Statistical analysis
Crude median, 25th, and 75th percentiles were calculated for all outcome variables. For each of the outcome variables, we performed multiple linear regression with parental TTP as the main determinant by considering sons of parents with a TTP of 0–6 months as the reference category. When we tested for trend, TTP group was entered as a continuous explanatory variable (x levels), using sons of parents with a TTP of 0–6 months as a starting point.
Data on all outcome variables, with the exception of percentages of motile sperm and inhibin B, were cubic-root transformed to obtain an approximate normal distribution of residuals. Data on percentage of motile sperm were logit transformed. In this paper, back-transformed means are presented with 95 percent confidence intervals and were adjusted for season (summer/winter), history of diseases of the reproductive organs (present, not present), smoking (yes/no), and maternal smoking during pregnancy (yes/no). The semen outcome variables were additionally adjusted for abstinence time (
48 hours, 49 hours–5 days, >5 days) and spillage during collection of the sample (yes, no). Data on participants who reported spillage during masturbation (n = 76) were, however, excluded from all statistical analysis on semen volume and total sperm count. The results on motility were also adjusted for time from ejaculation to analysis (continuous, in minutes). The blood sample outcome variables were, in addition to season, diseases of the reproductive organs and own and maternal smoking, also adjusted for time of day of blood sampling (6:00 a.m. to 8.59 a.m., 9:00 a.m. to 12:00 noon, after 12:00 noon).
All statistics were performed by using Intercooled Stata 8.2 software (Stata Corporation, College Station, Texas). A two-tailed p value of less than 0.05 was considered statistically significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Of the 311 participants, 244 (78 percent) were sons of couples whose TTP was 0–6 months (including sons of parents who became pregnant in spite of using birth control), 33 (11 percent) were sons of parents whose TTP was 7–12 months, and 34 (11 percent) were sons of parents whose TTP was 1 year or more. Characteristics of the participants according to parental TTP are given in table 1. Spillage at semen sampling and blood collection in the morning tended to be, respectively, more and less frequent among sons of parents whose TTP was 7–12 months in comparison with the reference groups of sons of parents who became pregnant after 0–6 months (p = 0.10 and p = 0.08), but the groups were otherwise quite similar.
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The adjusted mean semen volume of sons of parents who became pregnant after 1 year was 19 percent lower in comparison with sons of parents whose TTP was 0–6 months (p = 0.02) (table 2). When we tested for trend across parental TTP strata, an inverse association between parental TTP and semen volume of the sons was observed (p trend = 0.04). Additionally, total sperm count decreased with increasing parental TTP (p trend = 0.046).
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The adjusted sperm concentration and the percentage of morphologically normal sperm were, respectively, 22 percent and 23 percent lower in sons of parents whose TTP was 1 year or more compared with sons of parents whose TTP was 0–6 months, but the differences were not statistically significant (p = 0.15 and p = 0.13, correspondingly). In addition, the trend tests for sperm concentration and percentage of morphologically normal sperm were not statistically significant (p trend = 0.07 and p trend = 0.22, respectively) (table 2).
With regard to the remaining outcome variables—percentage of motile sperm and serum levels of testosterone, follicle-stimulating hormone, and inhibin B—no differences between TTP groups or trends were observed (table 2).
We repeated the analyzes by additionally adjusting for the young men's body mass index (<18.50 kg/m2, 18.50–24.99 kg/m2, >25.00 kg/m2) and maternal prepregnant body mass index (<18.50 kg/m2, 18.50–24.99 kg/m2, >25.00 kg/m2), and the magnitude of the effect of parental TTP on the outcome variables was essentially unchanged by the adjustment (data not shown). We also separated the group of sons of parents whose TTP was 0–6 months into the original two groups (pregnant in spite of use of birth control (n = 20) and pregnant after 0–6 months (n = 224)) and repeated the analyses, but doing so did not change the results either (data not shown). Finally, we analyzed data on sperm concentration, semen volume, and total sperm count without adjusting for cryptorchidism or hypospadias because these diseases may be in the causal pathway, but that also did not change the results (data not shown).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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This study indicates an association of parental TTP with semen quality and level of reproductive hormones in the male offspring. Only semen volume and total sperm count were statistically significantly inversely related to TTP, but the study had limited power to identify moderate associations, as indicated by the confidence limits. If the associations reflect causal mechanisms, they could be related to inherited genetic factors or environmental factors that are stable over at least two generations.
The association between parental TTP and semen quality in the offspring has, to the best of our knowledge, never been studied before, but it has been shown that sons of parents who had infertility treatment have reduced semen quality, the sperm concentration being approximately 40–46 percent lower (5, 6). In the present study, sperm concentration was 22 percent (p = 0.15) lower in sons of the most subfertile parents (TTP of 1 year or more), indicating that parental subfecundity or its causes may be at least partly responsible for the observed association between parental infertility treatment and poor semen quality.
Treated or untreated parental subfecundity has previously been found to be associated with adverse pregnancy outcomes such as preterm birth and low birth weight (12–14). A large Danish study found that singletons born of infertile couples, conceived either naturally or after fertility treatment, had a higher prevalence of congenital malformations in comparison with singletons of fertile couples (15). Comparing singletons born to infertile couples (conceived naturally vs. after infertility treatment) showed that hormonal treatment for infertility might be related to increased risk of malformations of the genital organs, but, for other malformations, the prevalence was not different between the two groups. In the same cohort, an increased risk of children being born small for gestational age was observed for infertile couples with or without infertility treatment, suggesting that infertility may be a risk factor for intrauterine growth restriction and that the treatment may have little effect on fetal growth (16). A Dutch study found, however, that poor perinatal outcomes such as preterm birth and low birth weight after assisted reproduction could not be explained by subfertility (17).
The concern about passing infertility on to future generations is justified. Genes responsible for impaired sperm production would normally be eliminated by evolution, but assisted reproduction technology interferes with this force of selection, and the long-term consequences are not known. Microdeletions in the Y chromosome have been associated with impaired sperm production (18), and microdeletions in infertile men have been found to be transmitted to the male offspring via intracytoplasmic sperm injection (19, 20). Usually, Y chromosome microdeletions are not transmitted to sons unless intracytoplasmic sperm injection or in vitro fertilization are performed. Boys conceived by intracytoplasmic sperm injection because of male infertility have lower serum testosterone levels at 3 months of age in comparison with naturally conceived boys, suggesting a possible inherited impairment in Leydig cell function (21).
An increasing prevalence of subfecundity genes is also expected to follow widely access to inexpensive contraception and family planning methods. Relatively fewer children will therefore be born of highly fertile parents, and population fecundity is expected to decrease over time (22, 23).
Strengths of our study include use of data on TTP reported by the mother, when she was pregnant with the son we studied, and recall of TTP should be good. Any misclassification of TTP is probably not related to the sons' semen quality, and, if random misclassification is also nondifferential, the bias will usually be toward the null.
Our study's participation rate (48.5 percent) was high for semen quality studies but not high enough to prohibit selection bias. To cause bias, selection has to be related to both semen quality and parental TTP. The source population was young, most had no reproductive experience, and they were not aware of the hypothesis evaluated, but we cannot exclude the possibility that the participants, despite their age and lack of reproductive experience, may have been able to self-select themselves for the study in a way that caused selection bias. If so, the participation rate of men with both poor semen quality and parents with a long TTP must be higher. One study showed that men with reduced fertility are more willing than other men to participate in semen-quality studies (24), but these men were older than the participants in our study, and it is unlikely that the sons know their mothers' TTP. We compared participants and nonparticipants who completed the small questionnaire on health (n = 82) and found no difference in the proportion of men with diseases of the reproductive organs (including cryptorchidism and hypospadias). Comparing the sperm concentration of participants who responded to the first invitation letter (fast responders, 61 percent) with that of participants who responded to the reminder (slow responders, 39 percent) showed a tendency toward a lower sperm concentration among slow responders. This tendency was strongest for sons of parents whose TTP was 0–6 months but was statistically nonsignificant both before and after transformation and adjustment. If nonresponders are more similar to the slow responders than to the fast responders in terms of semen quality, the direction of this bias, if it exists, would be away from the null.
Both parental TTP and birth weight were not related to participation when we compared the 347 participants and 369 nonparticipants: The percentages of men whose parental TTP was 0–6 months were, respectively, 76 percent and 74 percent among participants and nonparticipants, and the corresponding mean birth weights were 3,489 g and 3,461 g. Seventy-eight percent of the parents had a TTP of less than or equal to 6 months, which is in accordance with earlier reports for comparable populations (25, 26).
The participants in our study were restricted to those whose mothers were still pregnant in late pregnancy (approximately gestational week 36). This restriction may have resulted in a study population that includes more fertile couples than the background population, since preterm birth is associated with low fecundity. The consequence of this possible selection of fecund couples is a smaller exposure contrast and thereby a smaller chance of finding an association between parental TTP and semen quality.
In our analysis, we controlled for abstinence time, diseases of the reproductive organs, and a number of other potential confounders, but confounding by other unknown factors cannot be ruled out. We controlled for the men's own and maternal body mass index because these variables might be risk factors for decreased semen quality (27, 28), but doing so did not change the estimates. We also separated the reference group into "pregnant in spite of use of birth control" and "pregnant after 0–6 months" because the first-mentioned group may differ from the other groups. We found results similar to those presented here.
In conclusion, the results of this study suggest a small-to-moderate effect of parental subfecundity on semen quality in sons, but the study had limited power and should be repeated. We encourage others who have the necessary data to follow up on this important hypothesis.
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ACKNOWLEDGMENTS |
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The study was supported by the Danish Medical Research Council (grant 271-07-0051).
Conflict of interest: none declared.
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References |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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- Storgaard L, Bonde JP, Ernst E, et al. Genetic and environmental correlates of semen quality: a twin study. Epidemiology (2006) 17:674–81.[CrossRef][Web of Science][Medline]
- Asklund C, Jorgensen N, Skakkebaek NE, et al. Increased frequency of reproductive health problems among fathers of boys with hypospadias. Hum Reprod (2007) 22:2639–46.
[Abstract/Free Full Text] - Olsen J, Basso O, Spinelli A, et al. Correlates of care seeking for infertility treatment in Europe. Implications for health services and research. Eur J Public Health (1998) 8:15–28.
[Abstract/Free Full Text] - Nyboe AA, Erb K. Register data on Assisted Reproductive Technology (ART) in Europe including a detailed description of ART in Denmark. Int J Androl (2006) 29:12–16.[CrossRef][Web of Science][Medline]
- Jensen TK, Jorgensen N, Asklund C, et al. Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population. Am J Epidemiol (2007) 165:583–90.
[Abstract/Free Full Text] - Ramlau-Hansen CH, Thulstrup AM, Bonde JP, et al. Parental infertility and semen quality in male offspring: a follow-up study. Am J Epidemiol (2007) 166:568–70.
[Abstract/Free Full Text] - Olsen J, Frische G, Poulsen AO, et al. Changing smoking, drinking, and eating behaviour among pregnant women in Denmark. Evaluation of a health campaign in a local region. Scand J Soc Med (1989) 17:277–80.[Web of Science][Medline]
- Ramlau-Hansen CH, Thulstrup AM, Storgaard L, et al. Is prenatal exposure to tobacco smoking a cause of poor semen quality? A follow-up study. Am J Epidemiol (2007) 165:1372–9.
[Abstract/Free Full Text] - World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4th ed. Cambridge. (1999) United Kingdom: Cambridge University Press.
- Makler A, Zaidise I, Paldi E, et al. Factors affecting sperm motility. I. In vitro change in motility with time after ejaculation. Fertil Steril (1979) 31:147–54.[Web of Science][Medline]
- Kruger TF, Acosta AA, Simmons KF, et al. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril (1988) 49:112–17.[Web of Science][Medline]
- Henriksen TB, Baird DD, Olsen J, et al. Time to pregnancy and preterm delivery. Obstet Gynecol (1997) 89:594–9.[CrossRef][Web of Science][Medline]
- Basso O, Baird DD. Infertility and preterm delivery, birthweight, and Caesarean section: a study within the Danish National Birth Cohort. Hum Reprod (2003) 18:2478–84.
[Abstract/Free Full Text] - Schieve LA, Rasmussen SA, Buck GM, et al. Are children born after assisted reproductive technology at increased risk for adverse health outcomes? Obstet Gynecol (2004) 103:1154–63.[CrossRef][Web of Science][Medline]
- Zhu JL, Basso O, Obel C, et al. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ (2006) 333:679.
[Abstract/Free Full Text] - Zhu JL, Obel C, Hammer BB, et al. Infertility, infertility treatment, and fetal growth restriction. Obstet Gynecol (2007) 110:1326–34.[CrossRef][Web of Science][Medline]
- Kapiteijn K, de Bruijn CS, de Boer E, et al. Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation? Hum Reprod (2006) 21:3228–34.
[Abstract/Free Full Text] - Silber SJ, Alagappan R, Brown LG, et al. Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction. Hum Reprod (1998) 13:3332–7.
[Abstract/Free Full Text] - Page DC, Silber S, Brown LG. Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection, but are likely to transmit the deletion and infertility. Hum Reprod (1999) 14:1722–6.
[Abstract/Free Full Text] - Cram DS, Ma K, Bhasin S, et al. Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: vertical transmission of deletions and rarity of de novo deletions. Fertil Steril (2000) 74:909–15.[CrossRef][Web of Science][Medline]
- Mau KC, Main KM, Andersen AN, et al. Reduced serum testosterone levels in infant boys conceived by intracytoplasmic sperm injection. J Clin Endocrinol Metab (2007) 92:2598–603.
[Abstract/Free Full Text] - Czeizel AE, Rothman KJ. Does relaxed reproductive selection explain the decline in male reproductive health? A new hypothesis. Epidemiology (2002) 13:113–14.[Web of Science][Medline]
- Hjollund H, Storgaard L, Bonde JP, et al. Can a negative time trend of sperm density be explained by changes in reproductive pattern? Epidemiology (2002) 13:746–8.[CrossRef][Web of Science][Medline]
- Bonde JP, Giwercman A, Ernst E. Identifying environmental risk to male reproductive function by occupational sperm studies: logistics and design options. Occup Environ Med (1996) 53:511–19.
[Abstract/Free Full Text] - Jensen TK, Slama R, Ducot B, et al. Regional differences in waiting time to pregnancy among fertile couples from four European cities. Hum Reprod (2001) 16:2697–704.
[Abstract/Free Full Text] - Bonde JP, Ernst E, Jensen TK, et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet (1998) 352:1172–7.[CrossRef][Web of Science][Medline]
- Jensen TK, Andersson AM, Jorgensen N, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril (2004) 82:863–70.[CrossRef][Web of Science][Medline]
- Ramlau-Hansen CH, Nohr EA, Thulstrup AM, et al. Is maternal obesity related to semen quality in the male offspring? A pilot study. Hum Reprod (2007) 22:2758–62.
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