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      Paternal age and assisted reproductive outcomes in ICSI donor oocytes: is there an effect of older fathers?

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          Abstract

          STUDY QUESTION

          Does paternal age affect semen quality and reproductive outcomes in oocyte donor cycles with ICSI?

          SUMMARY ANSWER

          Paternal age is associated with a decrease in sperm quality, however it does not affect either pregnancy or live birth rates in reproductive treatments when the oocytes come from donors <36 years old and ICSI is used.

          WHAT IS KNOWN ALREADY

          The weight of evidence suggest that paternal age is associated with decreasing sperm quality, but uncertainty remains as to whether reproductive outcomes are affected. Although developed to treat severe sperm factor infertility, ICSI is gaining popularity and is often used even in the presence of mild male factor infertility.

          STUDY DESIGN, SIZE, DURATION

          A retrospective cohort study spanning the period between February 2007 and June 2010. A total of 4887 oocyte donation cycles were included.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          Fertilization was carried out by ICSI in all cycles included, and the semen sample used was from the male partner in all cases. The association of male age with semen parameters (volume, concentration, percentage of motile spermatozoa) was analyzed by multiple analysis of covariance. The association of male age with reproductive outcomes (biochemical pregnancy, miscarriage, ongoing pregnancy and live birth rate) was modeled by logistic regression, where the following covariates were introduced: donor age, recipient age, semen state (fresh versus frozen) and number of transferred embryos (3 and 2 versus 1).

          MAIN RESULTS AND THE ROLE OF CHANCE

          We identified a significant relationship between paternal age and all sperm parameters analyzed: for every 5 years of age, sperm volume decreases by 0.22 ml ( P < 0.001), concentration increases by 3.1 million sperm/ml ( P = 0.003) and percentage motile spermatozoa decreases by 1.2% ( P < 0.001). No differences were found in reproductive outcomes (biochemical pregnancy, miscarriage, clinical pregnancy, ongoing pregnancy and live birth) among different male age groups.

          LIMITATIONS, REASONS FOR CAUTION

          The use of donor oocytes, while extremely useful in highlighting the role of male age in reproductive outcomes, limits the generalization of our results to a population of young women with older male partners. No data were available on perinatal and obstetrical outcomes of these pregnancies. Most (75%) cycles used frozen/thawed sperm samples which might have introduced a bias owing to loss of viability after thawing. ICSI was performed in all cycles to control for fertilization method; this technique could mask the natural fertilization rate of poorer sperm samples. Furthermore, we did not use stringent ICSI indications; and our data are therefore not generalizable to cases where only severe male factor is considered. However, male patients were of different racial background, thus allowing generalizing our results to a wider patient base.

          WIDER IMPLICATIONS OF THE FINDINGS

          Our study suggests that paternal age does not affect reproductive outcomes when the oocyte donor is <36 years of age, indicating that ICSI and oocyte quality can jointly overcome the lower reproductive potential of older semen.

          STUDY FUNDING/COMPETING INTEREST(S)

          This study was supported in part by Fundació Privada EUGIN. The authors have no conflicts of interest to declare.

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          Most cited references39

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          Demographic and medical consequences of the postponement of parenthood.

          BACKGROUND Across the developed world couples are postponing parenthood. This review assesses the consequences of delayed family formation from a demographic and medical perspective. One main focus is on the quantitative importance of pregnancy postponement. METHODS Medical and social science databases were searched for publications on relevant subjects such as delayed parenthood, female and male age, fertility, infertility, time to pregnancy (TTP), fetal death, outcome of medically assisted reproduction (MAR) and mental well-being. RESULTS Postponement of parenthood is linked to a higher rate of involuntary childlessness and smaller families than desired due to increased infertility and fetal death with higher female and male age. For women, the increased risk of prolonged TTP, infertility, spontaneous abortions, ectopic pregnancies and trisomy 21 starts at around 30 years of age with a more pronounced effects >35 years, whereas the increasing risk of preterm births and stillbirths starts at around 35 years with a more pronounced effect >40 years. Advanced male age has an important but less pronounced effect on infertility and adverse outcomes. MAR treatment cannot overcome the age-related decline in fecundity. CONCLUSIONS In general, women have partners who are several years older than themselves and it is important to focus more on the combined effect of higher female and male age on infertility and reproductive outcome. Increasing public awareness of the impact of advanced female and male age on the reproductive outcome is essential for people to make well-informed decisions on when to start family formation.
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            Evidence for decreasing quality of semen during past 50 years.

            To investigate whether semen quality has changed during the past 50 years. Review of publications on semen quality in men without a history of infertility selected by means of Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). 14,947 men included in a total of 61 papers published between 1938 and 1991. Mean sperm density and mean seminal volume. Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.
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              Decline in semen quality among fertile men in Paris during the past 20 years.

              Several studies have suggested a population-wide decline in the quality of semen over the past 50 years, but clear evidence for decreasing semen quality in recent decades is lacking. From 1973 through 1992 we measured the volume of seminal fluid, the sperm concentration, and the percentages of motile and morphologically normal spermatozoa in 1351 healthy fertile men. The data on the semen samples were collected at one sperm bank in Paris. The data in each calendar year were analyzed as a function of the year of donation, the age of each patient, the year of birth, and the duration of sexual abstinence before semen collection. There was no change in semen volume during the study period. The mean concentration of sperm decreased by 2.1 percent per year, from 89 x 10(6) per milliliter in 1973 to 60 x 10(6) per milliliter in 1992 (P < 0.001). During the same period the percentages of motile and normal spermatozoa decreased by 0.6 percent and 0.5 percent per year, respectively (both P < 0.001). After adjustment in multiple regression analyses for age and the duration of sexual abstinence, each successive calendar year of birth accounted for 2.6 percent of the yearly decline in the sperm concentration and for 0.3 percent and 0.7 percent, respectively, of the yearly declines in the percentages of motile and normal spermatozoa (all P < 0.001). During the past 20 years, there has been a decline in the concentration and motility of sperm and in the percentage of morphologically normal spermatozoa in fertile men that is independent of the age of the men.
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                Author and article information

                Journal
                Hum Reprod
                Hum. Reprod
                humrep
                humrep
                Human Reproduction (Oxford, England)
                Oxford University Press
                0268-1161
                1460-2350
                10 October 2014
                28 July 2014
                28 July 2014
                : 29
                : 10
                : 2114-2122
                Affiliations
                [1 ]Clinica EUGIN, Barcelona 08029, Spain
                [2 ]Fundació Privada EUGIN, Barcelona 08029, Spain
                Author notes
                [* ]Correspondence address. Tel: +34-93-322-11-22; E-mail: rvassena@ 123456eugin.es
                Article
                deu189
                10.1093/humrep/deu189
                4164148
                25073975
                9a94459b-c8da-400e-ad4d-b73cca5487cb
                © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 23 January 2014
                : 3 June 2014
                : 1 July 2014
                Categories
                Original Articles
                Andrology

                Human biology
                male age,sperm,donor oocyte,icsi,pregnancy rate
                Human biology
                male age, sperm, donor oocyte, icsi, pregnancy rate

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