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Paternal Age Affects Fertility and Progeny Outcome in the Brown Norway Rat
MALE INFERTILITY
MALE INFERTILITY Paternal Age Affects Fertility and Progeny Outcome in the Brown Norway Rat
V. SERRE AND B. ROBAIRE, Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada Fertil. Steril., 7 0 625-631, 1998 Objective: To investigate the effects of paternal age on fertility and progeny outcome using the Brown Norway rat model. Design: Controlled prospective study. Setting: McIntyre Animal Centre, McGill University, Montreal, Quebec, Canada. Intervention(s): Brown Norway male rats of increasing age were mated to young Sprague-Dawley females. Main Outcome Measurek): Pregnancy outcome was assessed by counting the numbers of corpora lutea, resorptions, and live fetuses on day 20 of gestation. To evaluate progeny outcome, pups were examined for external malformations and weighed daily for 2 months. Result(s): There were no significant changes in the numbers of resorptions, offspring, or in the incidence of external malformations. However, there was an increase in preimplantation loss (corpora lutea minus implantation sites) in litters fathered by older males. Furthermore, a significant decrease in the average fetal weight was found with increasing paternal age. A significant increase in neonatal deaths for progeny fathered by older males also was found. Conclusion(s): These results indicate that the quality of spermatozoa decreases as males age. Editorial Comment: The relationship between maternal age and adverse effects on progeny has been well documented and, consequently, genetic counseling is routinely offered to older women attempting conception. In contrast, the effect of paternal age on progeny is not as well defined. It has been thought that age has less effect on male germ cells since sperm are constantly renewed through spermatogenesis, whereas oocytes are fixed in number and arrested in meiosis at birth. This study suggests that paternal age has a tremendous adverse effect on progeny, including preimplantation loss, reduced fetal weight and an increase in neonatal death rate. This study was performed using a Brown Norway rat animal model for male reproductive aging and it is not yet clear whether these findings are applicable to man. However, their Brown Norway rat model does replicate many other processes observed -in man, which lends credence to this model and suggests that further study of this issue is warranted. Jonathan P. Jarow, M.D. Outcome of Pregnancies After Intracytoplasmic Sperm Injection and the Effect of Sperm Origin and Quality on This Outcome
A. AYTOZ,M. Cmus, H. TOURNAYE, M. BONDUELLE, A. VAN STEIRTECHEM AND P. DEVROEY, Centers for Reproductive Medicine and Medical Genetics, Brussels Free University, Brussels, Belgium Fertil. Steril., 7 0 500-505, 1998 Objective: To describe the outcome of pregnancies obtained after intracytoplasmic sperm injection (ICSI) and the impact of the origin and quality of sperm used on this outcome. Design: Retrospective analysis. Setting: A tertiary referral center for assisted reproduction. Patient(s): Pregnant patients conceived after microinjection of ejaculated sperm (n = 1,4271, epididymal sperm (n = 79), and testicular sperm ( n = 93). Interventioncs): ICSI, epididymal sperm aspiration, and testicular biopsy. Main Outcome Measure(s): Stillbirth, prematurity, and early perinatal mortality. Result(s): The delivery rate of multiple births was 31.49, and the preterm delivery rate was 25.69. The prematurity rates in singletons, twins, and triplets were 9.9%, 56.79, and 96.6’X1respectively. The early perinatal mortality rate of the entire population was 26.1%. In the ejaculated-sperm group, when the sperm was severely defective (group l),14 intrauterine deaths occurred (3.1%).In the second and third groups, in which sperm was moderately defective, there were 2 deaths and 1 death (0.6%and 0.4%),respectively. The difference between the number of deaths in group 1vs. groups 213 was statistically significant. Conclusion(s):The rates of multiple pregnancies, preterm deliveries, low birth weight, and early pennatal mortality were higher after ICSI than after natural conception. In the ejaculated-sperm group, the rate of intrauterine death was higher in the severely defective sperm group than in the better-quality sperm groups. Editorial Comment: This retrospective review of intracytoplasmic sperm iqjection pregnancies confirms the findings of most other in vitro fertilization studies that document an adverse effect on early and late obstetric outcomes, The mqjority of these effects can be explained by the much higher multiple gestation rates that are associated with in vitro fertilization, ranging h m 30 to 400/0. Yet examination of singleton in vitro fertilization pregnancies alone s t i l l reveals
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MALE INFERTILITY Paternal Age Affects Fertility and Progeny Outcome in the Brown Norway Rat
V. SERRE AND B. ROBAIRE, Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada Fertil. Steril., 7 0 625-631, 1998 Objective: To investigate the effects of paternal age on fertility and progeny outcome using the Brown Norway rat model. Design: Controlled prospective study. Setting: McIntyre Animal Centre, McGill University, Montreal, Quebec, Canada. Intervention(s): Brown Norway male rats of increasing age were mated to young Sprague-Dawley females. Main Outcome Measurek): Pregnancy outcome was assessed by counting the numbers of corpora lutea, resorptions, and live fetuses on day 20 of gestation. To evaluate progeny outcome, pups were examined for external malformations and weighed daily for 2 months. Result(s): There were no significant changes in the numbers of resorptions, offspring, or in the incidence of external malformations. However, there was an increase in preimplantation loss (corpora lutea minus implantation sites) in litters fathered by older males. Furthermore, a significant decrease in the average fetal weight was found with increasing paternal age. A significant increase in neonatal deaths for progeny fathered by older males also was found. Conclusion(s): These results indicate that the quality of spermatozoa decreases as males age. Editorial Comment: The relationship between maternal age and adverse effects on progeny has been well documented and, consequently, genetic counseling is routinely offered to older women attempting conception. In contrast, the effect of paternal age on progeny is not as well defined. It has been thought that age has less effect on male germ cells since sperm are constantly renewed through spermatogenesis, whereas oocytes are fixed in number and arrested in meiosis at birth. This study suggests that paternal age has a tremendous adverse effect on progeny, including preimplantation loss, reduced fetal weight and an increase in neonatal death rate. This study was performed using a Brown Norway rat animal model for male reproductive aging and it is not yet clear whether these findings are applicable to man. However, their Brown Norway rat model does replicate many other processes observed -in man, which lends credence to this model and suggests that further study of this issue is warranted. Jonathan P. Jarow, M.D. Outcome of Pregnancies After Intracytoplasmic Sperm Injection and the Effect of Sperm Origin and Quality on This Outcome
A. AYTOZ,M. Cmus, H. TOURNAYE, M. BONDUELLE, A. VAN STEIRTECHEM AND P. DEVROEY, Centers for Reproductive Medicine and Medical Genetics, Brussels Free University, Brussels, Belgium Fertil. Steril., 7 0 500-505, 1998 Objective: To describe the outcome of pregnancies obtained after intracytoplasmic sperm injection (ICSI) and the impact of the origin and quality of sperm used on this outcome. Design: Retrospective analysis. Setting: A tertiary referral center for assisted reproduction. Patient(s): Pregnant patients conceived after microinjection of ejaculated sperm (n = 1,4271, epididymal sperm (n = 79), and testicular sperm ( n = 93). Interventioncs): ICSI, epididymal sperm aspiration, and testicular biopsy. Main Outcome Measure(s): Stillbirth, prematurity, and early perinatal mortality. Result(s): The delivery rate of multiple births was 31.49, and the preterm delivery rate was 25.69. The prematurity rates in singletons, twins, and triplets were 9.9%, 56.79, and 96.6’X1respectively. The early perinatal mortality rate of the entire population was 26.1%. In the ejaculated-sperm group, when the sperm was severely defective (group l),14 intrauterine deaths occurred (3.1%).In the second and third groups, in which sperm was moderately defective, there were 2 deaths and 1 death (0.6%and 0.4%),respectively. The difference between the number of deaths in group 1vs. groups 213 was statistically significant. Conclusion(s):The rates of multiple pregnancies, preterm deliveries, low birth weight, and early pennatal mortality were higher after ICSI than after natural conception. In the ejaculated-sperm group, the rate of intrauterine death was higher in the severely defective sperm group than in the better-quality sperm groups. Editorial Comment: This retrospective review of intracytoplasmic sperm iqjection pregnancies confirms the findings of most other in vitro fertilization studies that document an adverse effect on early and late obstetric outcomes, The mqjority of these effects can be explained by the much higher multiple gestation rates that are associated with in vitro fertilization, ranging h m 30 to 400/0. Yet examination of singleton in vitro fertilization pregnancies alone s t i l l reveals
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