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Effect of Male Age on Fertility: Evidence for the Decline in Male Fertility with Increasing Age
Abstract
To evaluate the effect of men's age on time to pregnancy (TTP) using age at the onset of pregnancy attempts, adjusting for the confounding effects of women's age, coital frequency, and life-style characteristics.
Observational study.
Teaching hospital in Hull, United Kingdom.
Two thousand one hundred twelve consecutive pregnant women.
A questionnaire inquiring about TTP, contraceptive use, pregnancy planning, previous subfertility, previous pregnancies, age, and individual life-style characteristics of both partners.
Time to pregnancy, conception rates, and relative risk of subfecundity for men and women's age groups.
As with women's age, increasing men's age was associated with significantly rising TTP and declining conception rates. A fivefold increase in TTP occurred with men's age >45 years. Relative to men <25 years old, those >45 years were 4.6-fold and 12.5-fold more likely to have had TTP of >1 or >2 years. Restricting the analysis to partners of young women revealed similar effects of increasing men's age. Women >35 years were 2.2-fold more likely to be subfertile than women <25 years. The results were comparable, whether age at conception or at the onset of pregnancy attempts was analyzed, and they remained unchanged after adjustment for the confounding factors.
Evidence for and quantification of the decline in men's fertility with increasing age is provided.
... Johnson et al. pointed to a trade-off between aging in males and early offspring fitness, suggesting a potential influence on fertilization [113]. Hassan & Killick argued that standard sperm evaluations might not fully capture the fertilizing capacity in the context of aging [114]. Meanwhile, Wu et al. reported no significant impact of paternal age on fertilization rates. ...
As global demographics shift toward increasing paternal age, the realm of assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), faces new challenges and opportunities. This study provides a comprehensive exploration of the implications of advanced paternal age on ART outcomes. Background research highlights the social, cultural, and economic factors driving men toward later fatherhood, with a focus on the impact of delayed paternity on reproductive outcomes. Methods involve a thorough review of existing literature, centering on changes in testicular function, semen quality, and genetic and epigenetic shifts associated with advancing age. Study results point to intricate associations between the father's age and ART outcomes, with older age being linked to diminished semen quality, potential genetic risks, and varied impacts on embryo quality, implantation rates, and birth outcomes. The conclusions drawn from the current study suggest that while advanced paternal age presents certain risks and challenges, understanding and mitigating these through strategies such as sperm cryopreservation, lifestyle modifications, and preimplantation genetic testing can optimize ART outcomes. Future research directions are identified to further comprehend the epigenetic mechanisms and long-term effects of the older father on offspring health. This study underscores the need for a comprehensive approach in navigating the intricacies of delayed fatherhood within the context of ART, aiming for the best possible outcomes for couples and their children.
... In couples with male partners over 40 years of age, all these possible mechanisms underlying age-related alterations in seminal quality may also result in poorer couple fertility outcomes [3] and increased risk of miscarriage [37]. In a study by Hassa and Killick [38], involving 2,112 couples, advancing men's age was associated with significantly rising time to pregnancy (TTP) and declining conception rates, especially above the age of 45 years, even when analysis was restricted to partners of young women. In autologous oocyte cycles, a paternal age threshold of 40 years appears to be associated with significantly lower pregnancy and live birth rates [39]. ...
Purpose
We aimed to evaluate whether and to what extent an association exists between male aging and worsening of semen parameters and to determine whether a threshold age can be identified above which the decline in semen quality becomes statistically significant.
Methods
2612 men (age: 16–56 years) attending an andrology outpatient clinic for semen analysis and clinical evaluation were studied. Semen analyses were performed according to the ongoing WHO-recommended procedures. Total motile count (TMC) and total progressive motile count (TPMC) were calculated by multiplying total sperm number by total motility and progressive motility, respectively.
Results
Significant negative correlations were found between age and total motility (r = − 0.131, p < 0.0001), progressive motility (r = − 0.112, p < 0.0001), TPMC (r = − 0.042, p = 0.037), and normal sperm morphology (r = − 0.053, p = 0.007). All these associations persisted in multivariate regression models adjusted for abstinence time, smoking, history of male accessory gland infections, varicocele and the year in which semen analysis was performed. When comparisons were performed among quartiles of increasing age, the fourth quartile, corresponding to the age group > 40 years, was associated with a significant decrease in total and progressive motility. An earlier decline in the TPMC and percentage of normal forms was also observed.
Conclusion
Advancing male age exhibits an independent association with a decrease in the percentage of motile and morphologically normal spermatozoa, with greater evidence from the age of > 40 years. Further studies are warranted to elucidate the mechanisms and clinical reflections of these associations.
... The Centers for Disease Control and Prevention (CDC) report that most men experience a significant age-related fertility decline after they reach the age of 40. Other studies show that the decline begins around age 35 (2). In one study that evaluated the relationship between age and semen parameters, they concluded that male fertility peaks between 30 and 35 and its decline begins at 35 (3). ...
... This delayed parenthood is attributed to secular and socioeconomic factors (Waldenström, 2016 ), reproductive technological advancement (Bray et al., 2006 ), and higher levels of post-graduate education (Mills et al., 2011 ). Emerging evidence suggests that higher male age contributes to poor pregnancy outcomes (Hassan & Killick, 2003 ), lower odds of live birth (Horta et al., 2019 ), and adverse health of offspring in later life (Montgomery et al., 2004 ;Puleo et al., 2012 ;Saha et al., 2009 ), including increased susceptibility to early development of cancer (Contreras et al., 2017 ), as well as neurodevelopmental, and psychiatric disorders such as schizophrenia (Gratten et al., 2016 ) and autism (Reichenberg et al., 2006 ). In experiments with mice it was demonstrated that higher male age is associated with reduced life span in offspring (Xie et al., 2018 ). ...
Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at the time of conception. Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. Animal experiments also demonstrate that epigenetic transfer of maladaptive information of advanced age fathers is associated with reduced offspring health including reduced life span. The mechanism(s) linking paternal age with epigenetic changes in sperm remain unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB is regulated by the balance of two mTOR complexes in Sertoli cells. We hypothesized that this balance is also responsible for age-dependent changes in the sperm epigenome. Experiments with transgenic mice demonstrate that the shift of the balance in favor of mTOR complex two rejuvenates sperm DNA-methylome while the shift in favor of mTOR complex one accelerates aging of the sperm DNA-methylome and results in a reproductive phenotype concordant with older age. These results demonstrate for the first time that the balance of mTOR complexes in Sertoli cells regulates the rate of sperm epigenetic aging. Thus, mTOR pathway in Sertoli cells may be used as novel target of therapeutic interventions to rejuvenate the sperm epigenome in advanced-age fathers.
... This delayed parenthood is attributed to secular and socioeconomic factors (Waldenström, 2016 ), reproductive technological advancement (Bray et al., 2006 ), and higher levels of post-graduate education (Mills et al., 2011 ). Emerging evidence suggests that higher male age contributes to poor pregnancy outcomes (Hassan & Killick, 2003 ), lower odds of live birth (Horta et al., 2019 ), and adverse health of offspring in later life (Montgomery et al., 2004 ;Puleo et al., 2012 ;Saha et al., 2009 ), including increased susceptibility to early development of cancer (Contreras et al., 2017 ), as well as neurodevelopmental, and psychiatric disorders such as schizophrenia (Gratten et al., 2016 ) and autism (Reichenberg et al., 2006 ). In experiments with mice it was demonstrated that higher male age is associated with reduced life span in offspring (Xie et al., 2018 ). ...
Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at the time of conception. Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. Animal experiments also demonstrate that epigenetic transfer of maladaptive information of advanced age fathers is associated with reduced offspring health including reduced life span. The mechanism(s) linking paternal age with epigenetic changes in sperm remain unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB is regulated by the balance of two mTOR complexes in Sertoli cells. We hypothesized that this balance is also responsible for age-dependent changes in the sperm epigenome. Experiments with transgenic mice demonstrate that the shift of the balance in favor of mTOR complex two rejuvenates sperm DNA-methylome while the shift in favor of mTOR complex one accelerates aging of the sperm DNA-methylome and results in a reproductive phenotype concordant with older age. These results demonstrate for the first time that the balance of mTOR complexes in Sertoli cells regulates the rate of sperm epigenetic aging. Thus, mTOR pathway in Sertoli cells may be used as novel target of therapeutic interventions to rejuvenate the sperm epigenome in advanced-age fathers.
... TTP is defined as the time to success to conceive under unprotected intercourse and is generally a well recalled sensitive measure of fecundity in both women and men (Zielhuis et al., 1992;Joffe et al., 1995). Age is the single most important factor for fecundity in both women (Steiner and Jukic, 2016;Wesselink et al., 2017) and men Hassan and Killick, 2003;Martins da Silva and Anderson, 2022). Environmental factors (including lifestyle factors) explain around 70% of impaired fecundity (defined as a TTP > 10 months) in women and 95% in men, leaving 30 and 5%, respectively, for genetic factors (Ahrenfeldt et al., 2020). ...
STUDY QUESTION
Is fecundity, measured as time to pregnancy (TTP), associated with mortality in parents?
SUMMARY ANSWER
Prolonged TTP is associated with increased mortality in both mothers and fathers in a dose–response manner.
WHAT IS KNOWN ALREADY
Several studies have linked both male and female fecundity to mortality. In women, infertility has been linked to several diseases, but studies suggest that the underlying conditions, rather than infertility, increase mortality.
STUDY DESIGN, SIZE, DURATION
A prospective cohort study was carried out on 18 796 pregnant couples, in which the pregnant women attended prophylactic antenatal care between 1973 and 1987 at a primary and tertiary care unit. The couples were followed in Danish mortality registers from their child’s birth date until death or until 2018. The follow-up period was up to 47 years, and there was complete follow-up until death, emigration or end of study.
PARTICIPANTS/MATERIALS, SETTING, METHODS
At the first antenatal visit, the pregnant women were asked to report the time to the current pregnancy. Inclusion was restricted to the first pregnancy, and TTP was categorised into <12 months, ≥12 months, not planned, and not available. In sub-analyses, TTP ≥12 was further categorized into 12–35, 36–60, and >60 months. Information for parents was linked to several Danish nationwide health registries. Survival analysis was used to estimate the hazard ratios (HRs) with a 95% CI for survival and adjusted for age at the first attempt to become pregnant, year of birth, socioeconomic status, mother’s smoking during pregnancy, and mother’s BMI.
MAIN RESULTS AND THE ROLE OF CHANCE
Mothers and fathers with TTP >60 months survived, respectively, 3.5 (95% CI: 2.6–4.3) and 2.7 (95% CI: 1.8–3.7) years shorter than parents with a TTP <12 months. The mortality was higher for fathers (HR: 1.21, 95% CI: 1.09–1.34) and mothers (HR: 1.29, 95% CI: 1.12–1.49) with TTP ≥12 months compared to parents with TTP <12 months. The risk of all-cause mortality during the study period increased in a dose–response manner with the highest adjusted HR of 1.98 (95% CI: 1.62–2.41) for fathers and 2.03 (95% CI: 1.56–2.63) for mothers with TTP >60 months. Prolonged TTP was associated with several different causes of death in both fathers and mothers, indicating that the underlying causes of the relation between fecundity and survival may be multi-factorial.
LIMITATIONS, REASONS FOR CAUTION
A limitation is that fecundity is measured using a pregnancy-based approach. Thus, the cohort is conditioned on fertility success and excludes sterile couples, unsuccessful attempts and spontaneous abortions. The question used to measure TTP when the pregnant woman was interviewed at her first attended prophylactic antenatal care: ‘From the time you wanted a pregnancy until it occurred, how much time passed?’ could potentially have led to serious misclassification if the woman did not answer on time starting unprotected intercourse but on the start of wishing to have a child.
WIDER IMPLICATIONS OF THE FINDINGS
We found that TTP is a strong marker of survival, contributing to the still-emerging evidence that fecundity in men and women reflects their health and survival potential.
STUDY FUNDING/COMPETING INTEREST(S)
The authors acknowledge an unrestricted grant from Ferring. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. M.L.E. is an advisor to Ro, VSeat, Doveras, and Next.
TRIAL REGISTRATION NUMBER
N/A.
... It is worth noting that critical points of the U-shaped function (50.02) and the metaregression based on the whole sample (49.92) are both greater than peak reproductive years around 20-30 (Hassan & Killick, 2003;Sartorius & Nieschlag, 2010). Thus, fertility-mortalitybased predictions alone are not sufficient to account for the results. ...
A long-running debate about the developmental trajectory of delay discounting has received growing attention since 1994. Relevant theories, ranging from developmental psychology and evolutionary biology to behavioral economics, yield contradictory predictions. Encompassing a wide age range from 6.7 to 83.1 years, we evaluated these theories based on meta-analyses of 178 effect sizes from 105 articles that examined age-dependent delay discounting, providing up-to-date the most comprehensive review of the topic. Delay discounting decreased with advancing age (Fisher’s z = -.059). However, meta-regression suggested that this linear trend masked a U-shaped function, as implied by some theoretical models. We developed a derivative-based method and recovered this nonlinear function based on 58 effects. Both the meta-regression based on all 178 effect sizes and the derivative-based method convergently demonstrated that delay discounting was the lowest for middle-aged people around 50, depending on the magnitude of the reward. The U-shaped function was steeper for people with shorter life expectancies; the turning point comes at a younger age for medium-to-large rewards, and delay discounting models explained heterogeneity across studies. We expanded the current theoretical frameworks by synthesizing the life-history theory and the antagonistic pleiotropy hypothesis. Built upon the mortality-fertility tradeoff model of Sozou and Seymour (2003), we postulated the role of parental investment in postponing the increase of delay discounting in late adulthood, suggesting a three-way mortality-fertility-parenting tradeoff. Possible proximate mechanisms were also discussed. Overall, when allocating assets over temporal intervals, a higher delay discount rate accompanies a lower future reproductive opportunity.
... 22,23 This decline is believed to be a progressive event as the exact age of this decline is yet to be determined. [22][23][24] Semen concentration and total sperm number are directly related to time to pregnancy, and pregnancy rates. Normal sperm concentration usually ranges from 15 to 200 million. ...
... 22,23 This decline is believed to be a progressive event as the exact age of this decline is yet to be determined. [22][23][24] Semen concentration and total sperm number are directly related to time to pregnancy, and pregnancy rates. Normal sperm concentration usually ranges from 15 to 200 million. ...
Background: Male infertility contributes 40 % of couple infertility. The prevalence of abnormal semen parameters has been on the increase. Age among other factors affects the fertility potential of males. This study analysed the pattern of seminal fluid parameters of males, seeking fertility treatment in hospitals and the relationship between age, volume and liquefaction time on these other semen parameters.
Methods: This is a multicentre retrospective cohort study conducted in eight secondary and tertiary hospitals in Nigeria. The case notes of couples that sort fertility care at the Gynaecology and Urology clinics of these hospitals from January 1st 2022 to December 31st 2022 were retrieved after receiving ethical approval. A purposeddesigned proforma based on the WHO manual for the examination of human semen was used for data collection. Outcome measures were time of semen collection and examination, volume of semen, sperm number, sperm concentration, PH, agglutination, liquefaction, motility,morphology, vitality, and white blood cell count. Data was analysed using SPSS version 23. Data were presented as means and proportions. P-value of < 0.05 was used as the level of significance.
Results: Overall, 1063 couples attended gynaecology and urology clinics with fertility-related concerns within the study period with a retrieval rate of 98.3%. The mean age of participants was 38.24 ± 8 years, while the mean semen volume and sperm concentrations were 2.62 ± 1.6 mls and 34.32 ± 7.4 million respectively. The age of participants significantly affected motility, volume and morphology (p-values of 0.001, 0.001 and 0.004 respectively). The total motility and sperm concentration have an inverse relationship with the age of the participants.
Conclusion: This study shows that sperm motility decreases with the age of participants. It was also observed that the most common combined abnormality was oligoasthenozoospermia.
Keywords: Male infertility; Nigeria; Seminal fluid abnormalities.
... 22,23 This decline is believed to be a progressive event as the exact age of this decline is yet to be determined. [22][23][24] Semen concentration and total sperm number are directly related to time to pregnancy, and pregnancy rates. Normal sperm concentration usually ranges from 15 to 200 million. ...
Background:
Male infertility contributes 40 % of couple infertility. The prevalence of abnormal semen parameters has been on the increase. Age among other factors affects the fertility potential of males. This study analysed the pattern of seminal fluid parameters of males, seeking fertility treatment in hospitals and the relationship between age, volume and liquefaction time on these other semen parameters.
Methods:
This is a multicentre retrospective cohort study conducted in eight secondary and tertiary hospitals in Nigeria. The case notes of couples that sort fertility care at the Gynaecology and Urology clinics of these hospitals from January 1st 2022 to December 31st 2022 were retrieved after receiving ethical approval. A purposeddesigned proforma based on the WHO manual for the examination of human semen was used for data collection. Outcome measures were time of semen collection and examination, volume of semen, sperm number, sperm concentration, PH, agglutination, liquefaction, motility,morphology, vitality, and white blood cell count. Data was analysed using SPSS version 23. Data were presented as means and proportions. P-value of < 0.05 was used as the level of significance.
Results:
Overall, 1063 couples attended gynaecology and urology clinics with fertility-related concerns within the study period with a retrieval rate of 98.3%. The mean age of participants was 38.24 ± 8 years, while the mean semen volume and sperm concentrations were 2.62 ± 1.6 mls and 34.32 ± 7.4 million respectively. The age of participants significantly affected motility, volume and morphology (p-values of 0.001, 0.001 and 0.004 respectively). The total motility and sperm concentration have an inverse relationship with the age of the participants.
Conclusion:
This study shows that sperm motility decreases with the age of participants. It was also observed that the most common combined abnormality was oligoasthenozoospermia.
... It has been reported that men's spouses >45 years, are at risk of delay in time to achieve pregnancy. 21 Following the later, majority of the participants were within the reproductive active stage. ...
Background: The objective was to study the extent of infertility knowledge, attitude and care seeking behavioral
pattern of infertile men in Lagos.
Methods: A cross sectional study was carried out using questionnaire between 2009 and 2014. Adult males who were
clinically infertile, visiting the clinics for the first time and consented were studied. Descriptive statistics were used
for the analysis.
Results: Only 226 men, mean age 38±5.8 years participated. Up to 20.8% had sired a child for between >1 but <2,
20.4% for 2-5 and 58.8% for ≥6 years. Couples had coitus for once and >3 times (mean coitus 2.3±0.9 times) weekly.
Only 11.1% knew about male-female factor infertility. Up to 42.9% knew about fertility and the sign of female
ovulation and 38.1% correctly defined clinical infertility. Up to 40.3% switched treatment for competency of the new
places and exorbitant price by 22.1%. Sixty-six (29.2%) made the first visit to a proper care place within a period >1
but <2 years, 45.1% within 2-3 years and 25.7% waited for >3 years. Majority (50 %) sought to know the causes of
infertility, 14.6% how to improve fertility and 6.6% the reality of male infertility.
Conclusions: Majority of the participants sought inappropriate help and delayed in seeking appropriate care. Poor
collaboration and referral system observed. There is need for edification of both care providers and seekers to be
ethical in their actions. Infertility care cost intervention is needed.
Keywords: Male infertility, Nigeria, Seeking for care and lagos
... Decreased sperm motility, instead of other abnormal semen parameters, significantly affects assisted reproductive technology outcomes in elderly infertile men [45,46]. Sperm-fertilizing capacity can be compromised with age as evidenced by the negative effects of paternal age on time to conceive or assisted reproductive technology outcomes using donor eggs [47,48]. These observational studies provide substantial evidence of the susceptibility of the epididymis to aging, which impairs the process of sperm maturation. ...
Background
Morphological and functional alterations in aging reproductive organs result in decreased male fertility. The epididymis functions as the transition region for post-testicular sperm maturation. And we have previously demonstrated that the epididymal initial segment (IS), a region of the reproductive tract essential for sperm maturation and capacitation, undergoes considerable histological changes and chronic immune activation in mice during aging. However, the local aging-associated cellular and molecular changes in the aged epididymal IS are poorly understood.
Results
We conducted single-cell RNA sequencing analysis on the epididymal IS of young (3-month-old) and old (21-month-old) mice. In total, 10,027 cells from the epididymal IS tissues of young and old mice were obtained and annotated. The cell composition, including the expansion of a principal cell subtype and Ms4a4bHiMs4a6bHi T cells, changed with age. Aged principal cells displayed multiple functional gene expression changes associated with acrosome reaction and sperm maturation, suggesting an asynchronous process of sperm activation and maturation during epididymal transit. Meanwhile, aging-related altered pathways in immune cells, especially the “cell chemotaxis” in Cx3cr1Hi epididymal dendritic cells (eDCs), were identified. The monocyte-specific expression of chemokine Ccl8 increased with age in eDCs. And the aged epididymal IS showed increased inflammatory cell infiltration and cytokine secretion. Furthermore, cell–cell communication analysis indicated that age increased inflammatory signaling in the epididymal IS.
Conclusion
Contrary to the general pattern of lower immune responses in the male proximal genital tract, we revealed an inflammaging status in mouse epididymal initial segment. These findings will allow future studies to enable the delay of male reproductive aging via immune regulation.
... However for reasons beyond personal adequate knowledge of preventable factors that impair them from achieving this (Karin et al., 2013). Increasing maternal and paternal age has been shown to negatively affect fertility and obstetric outcomes (Chapman et al., 2006(Chapman et al., 2012De Graaff et al., 2011;Fretts 2001;Hassan et al., 2003;Jolly et al., 2000). Worldwide, there has been an increased in age of childbearing in last decade Li et al., 2011;Schmidt et al., 2012 It has been argued that fertility is a variable which an et al., 1987). ...
Background: infertility after some time faces considerable emotional, physical and psych Aim: To explore knowledge of effect of age, obesity, smoking, timing of intercourse, previous STIs and environmental pollutants on fertility among University students. Methods: University of Technology (LAUTECH), Ogbomoso. They were interviewed through self-administered pre inferential statistics using SPSS 20 statistical package. Results: of the respondents were single at the time of interview. A (third 33 10years, the age at which fertility starts to decline in women. Only one in four participants correctly identified that female fertility start to decline before 35years. Every one in five participants believed that fertile period in women's menstrual cycle. Majority of male (60.8%) and female (70.1%) respondents believed that smoking has "a lot," of effects on male and female fertility believed to have no effect on fertility by females compared with the males (31% vs. 15% P< 0.001).Higher proportion of males than females agreed that alcohol has no effect on fertility (10.3% vs. 3.8% P< 0.001). Obesity was believ females respectively. With use of modern contraception, 64.5% the participants believed that it has "a lot," of effect on female fertility, while more male than female said it has "no effect" on female fertility (13.5% vs. 3.3% P< 0.001). Conclusions: influence fertility. Students with prior knowledge of impact of the modifiable factors on fertility potential of both men and women. Copyright © 2015 Kola M Owonikoko et al. This is an open access article distributed under the unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
... However for reasons beyond personal adequate knowledge of preventable factors that impair them from achieving this (Karin et al., 2013). Increasing maternal and paternal age has been shown to negatively affect fertility and obstetric outcomes (Chapman et al., 2006(Chapman et al., 2012De Graaff et al., 2011;Fretts 2001;Hassan et al., 2003;Jolly et al., 2000). Worldwide, there has been an increased in age of childbearing in last decade Li et al., 2011;Schmidt et al., 2012 It has been argued that fertility is a variable which an et al., 1987). ...
... However, the effects of male aging on fertility remains uncertain and the review of the literature shows inconsistent results [17]. Previous studies showed that male aging was associated with a decline in fertility, as reflected by decreased pregnancy rates and increased time to pregnancy and frequency of subfecundity [18,19]. Demir et al. [20] found that men's age was a critical factor for intrauterine insemination (IUI) success, even if they had normal semen parameters. ...
Background
Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since its discovery in December 2019. Research published since the COVID-19 outbreak has focused on whether semen quality and reproductive hormone levels are affected by COVID-19. However, there is limited evidence on semen quality of uninfected men. This study aimed to compare semen parameters among uninfected Chinese sperm donors before and after the COVID-19 pandemic to determine the impact of the COVID-19 pandemic-related stress and lifestyle changes on uninfected men.
Results
All semen parameters were non-significant except semen volume. The average age of sperm donors was higher after the COVID-19 (all P < 0.05). The average age of qualified sperm donors increased from 25.9 (SD: 5.3) to 27.6 (SD: 6.0) years. Before the COVID-19, 45.0% qualified sperm donors were students, but after the COVID-19, 52.9% were physical laborers ( P < 0.05). The proportion of qualified sperm donors with a college education dropped from 80.8 to 64.4% after the COVID-19 ( P < 0.05).
Conclusion
Although the sociodemographic characteristics of sperm donors changed after the COVID-19 pandemic, no decline in semen quality was found. There is no concern about the quality of cryopreserved semen in human sperm banks after the COVID-19 pandemic.
... Fertility is strongly related to age, for both male and female partners, which can be seen in the differences in the conception groups in this study (Hassan and Killick, 2003; American Society for Reproductive Medicine, 2014). The increased birth defect risk in the OI/IUI, non-ART siblings, and ART autologous-fresh and thawed groups suggests an association with underlying parental subfertility, while the increased risk in the donor-thawed versus the donor-fresh group may be associated with the process of cryopreservation. ...
As the proportion of births conceived with assisted reproductive technology (ART) continues to increase, a growing body of literature continues to examine the risks involved such as the higher risk of birth defects. Recently, several studies have suggested that ART-conceived children may have a greater risk of childhood cancer.
This population-based cohort study aimed to evaluate the risk of childhood cancer as a function of birth defect status and method of conception. Data were obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, birth certificates (2004–2013), birth defect registries, and cancer registries in 4 states. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System contains comprehensive information on ART procedures from 86% of all clinics and more than 92% of all ART cycles in the United States. Assisted reproductive technology cycles reported from January 2004 to December 2017 that resulted in live births were included in this study. For each ART-conceived delivery, the subsequent 10 deliveries were selected as the non-ART comparison group, and siblings of each ART birth were selected as the ART sibling group. The ART group was divided into 4 subgroups based on the combination of oocyte source (autologous or donor) and embryo state (fresh or thawed). A host of independent variables with established associations on birth defects, cancer, and/or ART were selected a priori for inclusion in statistical models.
The total study population included 165,125 ART-conceived children, 31,524 non-ART siblings, 12,451 children born as a result of infertility treatment without ART (ovulation induction/intrauterine insemination [OI/IUI]), and 1,353,440 naturally conceived children. A total of 29,571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect. Compared with naturally conceived children, risks for defects were increased for all other groups for nonchromosomal (adjusted odds ratios [AORs] ranged from 1.20 to 1.24, except for donor-fresh), blastogenesis (AORs, 1.22–1.74), cardiovascular (AORs, 1.04–1.26), gastrointestinal (AORs, 1.28–2.01), musculoskeletal (AORs, 1.10–1.48), and genitourinary among male children (AORs, 1.15–1.40, except for donor-fresh). Orofacial defects were increased in the OI/IUI and autologous-fresh and autologous-thawed groups (AORs, 1.26–1.42). The risk of any cancer was increased among ART autologous-fresh and non-ART siblings (hazard ratios [HRs], 1.31 and 1.34, respectively). A total of 127 children had both birth defects and cancer, with 53 (42%) of these children having leukemia. A Cox proportional hazards regression model identified 2 components for the risk of cancer: method of conception and type and number of birth defects. The presence of chromosomal defects was strongly associated with cancer risk (HRs, 8.70 for all cancers and 21.90 for leukemia), and this was further increased in the presence of both chromosomal and nonchromosomal defects (HRs, 21.29 for all cancers, 64.83 for leukemia, and 4.71 for embryonal tumors).
The results of this study demonstrate that compared with naturally conceived children a significantly increased risk of nonchromosomal birth defects was found among children conceived with infertility treatment and that the risk of cancer was increased by greater than 30% among non-ART siblings and ART children born from autologous-fresh cycles. Among both naturally conceived and ART-conceived children, the presence of birth defects was associated with a greater risk of cancer.
... We recruited American participants from Amazon Mechanical Turk (MTurk). Following Sng et al. (2017), we sought participants no more than 40 years old since fertility begins to decline significantly after 40 years old (e.g., Eijkemans et al., 2014;Hassan & Killick, 2003), and reproductive decisions would typically already be made. In addition, the number of planned children could be significantly affected by whether people already have children. ...
Many important family decisions, such as when to have offspring, essentially manifest different life history strategies, ranging from slow to fast ones. The current research examined how one critical societal factor, social mobility (i.e., the shift of socioeconomic status in a society), may contribute to such slow (vs. fast) life history strategies. With four multi-method studies, including archival data at the national level, a large-sample survey (N = 6787), and experimental studies (N = 497), we found that a high level of social mobility predicted and resulted in delayed reproduction. Specifically, a high level of social mobility, indexed by both objective reality and subjective perception, predicted individuals’ positive future expectations. This further leads them to focus on long-term goals and foster a slow life history strategy, i.e., preferring delayed reproduction. Theoretical implications are discussed.
... Although only one sperm is necessary for conception, a decline in sperm concentration does affect fertility. The time to conceive for fathers over the age of 45 is approximately 5-fold longer than that for young fathers (27). The deterioration of sperm production during aging can be attributed to the impairment of testicular histological architecture, presented as thinning of the seminiferous epithelium, reduced vascularization of the testes and narrowing of the tubules (28). ...
In recent years, the postponement of childbearing has become a critical social issue. Male fertility is negatively associated with age because of testis aging. Spermatogenesis is impaired with age, but the molecular mechanism remains unknown. The dynamic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc), which is a type of monosaccharide modification, has been shown to drive the process of aging in various systems, but it has not yet been investigated in the testis and male reproductive aging. Thus, this study aims to investigate the alteration of O-GlcNAc with aging and explore the role of O-GlcNAc in spermatogenesis. Here, we demonstrate that the decline in spermatogenesis in aged mice is associated with elevation of O-GlcNAc. O-GlcNAc is specifically localized in differentiating spermatogonia and spermatocytes, indicating its crucial role in meiotic initiation and progression. Mimicking the age-related elevation of O-GlcNAc in young mice by disabling O-GlcNAcase (OGA) using the chemical inhibitor Thiamet-G can recapitulate the impairment of spermatogenesis in aged mice. Mechanistically, the elevation of O-GlcNAc in the testis leads to meiotic pachytene arrest due to defects in synapsis and recombination. Furthermore, decreasing O-GlcNAc in aged testes using an O-GlcNAc transferase (OGT) inhibitor can partially rescue the age-related impairment of spermatogenesis. Our results highlight that O-GlcNAc, as a novel posttranslational modification, participates in meiotic progression and drives the impairment of spermatogenesis during aging.
... followed by those between 18 and 30 years' age bracket. This is outside the norm as it is usually known that old men are the ones who usually require the intake of aphrodisiacs (5,9). This drift could be because of an increase in sexual promiscuity among the youth and the recreational use of aphrodisiacs (10). ...
Sexuality is an important part of an individual’s quality of life. Reduced sexual function is common and can be treated. People search all heights and depths for substances they could use to stimulate and increase sexual desire in themselves and others. The non-prescription procurement and use of medicines have become a major challenge in Ghana. However, it is unknown how serious this situation is with regards to aphrodisiacs. This study therefore assessed the purchase and consumption of aphrodisiacs within the Kumasi metropolis. Retail pharmacies were involved in this study. Quota sampling was used to determine the number of pharmacies to be selected from each sub-metro while stratified sampling was then used to select participating pharmacies for the study. Males between the ages of 31 and 45 years purchased aphrodisiacs from pharmacies the most (56, 38.5%) and the rate of purchase of aphrodisiacs from retail outlets (104, 70.3%) is high. Aphrodisiacs were consumed to prolong erection as well as enhance pleasure. However, this practice is seen by many as inappropriate and reported by many to be associated with very serious adverse effects, with headaches being the most dominant adverse effect reported.
... Compared to men < 25y, adjusted odds ratios for conception within 12 months was 0.62 (95% CI 0.40, 0.98) for men aged 30 to 34 years, 0.50 (95% CI 0.31, 0.81) for men aged 35 to 39 years and 0.51 (95% CI 0.31, 0.86) for men ≥ 40 years [68]. Time to pregnancy (TTP) was also noted to be significantly affected by increase in male age in an observational study of 2112 pregnant women, with a 5-fold increase in TTP for men > 45 years [69]. Similarly, epidemiological studies have reported a significant influence of paternal age on natural conception, with impaired fertility in men older than 35 to 40 years [70]. ...
Compared to women, increasing male age is not accompanied by such marked changes in reproductive function but changes certainly do happen. These include alterations to the hypothalamo-pituitary-testicular axis, with resultant implications for testosterone production and bioavailability as well as spermatogenesis. There is a decline in sexual function as men age, with a dramatic increase in the prevalence of erectile dysfunction after the age of 40, which is a marker for both clinically evident as well as covert coronary artery disease. Despite a quantitative decline in spermatogenesis and reduced fecundability, the male potential for fertility persists throughout adult life, however there are also increasingly recognised alterations in sperm quality and function with significant implications for offspring health. These changes are relevant to both natural and medically assisted conception.
Approximately one in twenty men have sperm counts low enough to impair fertility but little progress has been made in answering fundamental questions in andrology or in developing new diagnostic tools or management strategies in infertile men. Many of these problems increase with age, leading to a growing population of men seeking help. To address this, there is a strong movement towards integrating male reproductive and sexual healthcare involving clinicians such as andrologists, urologists, endocrinologists and counselors. This book will emphasize this integrated approach to male reproductive and sexual health throughout the lifespan. Practical advice on how to perform both clinical and laboratory evaluations of infertile men is given, as well as a variety of methods for medically and surgically managing common issues. This text ties together the three major pillars of clinical andrology: clinical care, the andrology laboratory, and translational research.
The process of aging refers to physiological changes that occur to an organism as time progresses and involves changes to DNA, proteins, metabolism, cells, and organs. Like the rest of the cells in the body, gametes age, and it is well established that there is a decline in reproductive capabilities in females and males with aging. One of the major pathways known to be involved in aging is epigenetic changes. The epigenome is the multitude of chemical modifications performed on DNA and chromatin that affect the ability of chromatin to be transcribed. In this review, we explore the effects of aging on female and male gametes with a focus on the epigenetic changes that occur in gametes throughout aging. Quality decline in oocytes occurs at a relatively early age. Epigenetic changes constitute an important part of oocyte aging. DNA methylation is reduced with age, along with reduced expression of DNA methyltransferases (DNMTs). Histone deacetylases (HDAC) expression is also reduced, and a loss of heterochromatin marks occurs with age. As a consequence of heterochromatin loss, retrotransposon expression is elevated, and aged oocytes suffer from DNA damage. In sperm, aging affects sperm number, motility and fecundity, and epigenetic changes may constitute a part of this process. 5 methyl‐cytosine (5mC) methylation is elevated in sperm from aged men, but methylation on Long interspersed nuclear elements (LINE) elements is reduced. Di and trimethylation of histone 3 lysine 9 (H3K9me2/3) is reduced in sperm from aged men and trimethylation of histone 3 lysine 27 (H3K27me3) is elevated. The protamine makeup of sperm from aged men is also changed, with reduced protamine expression and a misbalanced ratio between protamine proteins protamine P1 and protamine P2. The study of epigenetic reproductive aging is recently gaining interest. The current status of the field suggests that many aspects of gamete epigenetic aging are still open for investigation. The clinical applications of these investigations have far‐reaching consequences for fertility and sociological human behavior.
Thanks to increasing life expectancy with its concomitant number of aging men, medicine is forced to focus more strongly on the endocrine situation of this age group. In men, although there is no climacteric, there is a gradual decline in testosterone, and levels may well remain within the normal range of younger men. In some men, however, levels fall below normal. When this occurs in conjunction with characteristic symptoms, it may be genuine late-onset hypogonadism (LOH) or functional hypogonadism. In these cases, testosterone substitution may be considered and must be closely monitored.
Objective:
To study the effect of methotrexate on male fertility and subsequent effects on their children, for which data are scarce and contradictory.
Design:
Nationwide multiregister cohort study.
Setting:
Not applicable.
Patient(s):
All children born alive in Sweden between 2006 and 2014 and their fathers. Three cohorts were defined: children to fathers with periconceptional methotrexate exposure (exposed cohort), children whose fathers stopped methotrexate intake ≥2 years before conception (previously exposed cohort), and children to fathers with no methotrexate exposure (control cohort).
Intervention(s):
The father having at least one dispensed methotrexate prescription from pharmacies 0-3 months before conception, along with at least one more dispensed methotrexate prescription 0-12 months before conception (periconceptional exposure). Previously exposed cohort: the father having no dispensed methotrexate prescriptions in the 2 years before conception, but having at least two dispensed prescriptions before that.
Main outcome measures:
Congenital anomalies (major and any; primary outcomes), preterm birth (PTB) and being small for gestational age (SGA; secondary outcomes), as well as need of intracytoplasmic sperm injection (ICSI) to achieve pregnancy (primary outcome in exposed cohort vs. controls, exploratory outcome in previously exposed cohort vs. controls). Outcomes were analyzed using logistic regression.
Results:
A total of 223 children to fathers with periconceptional methotrexate exposure were identified, along with 356 children whose fathers stopped methotrexate intake ≥2 years before conception and 809,706 not methotrexate-treated controls. In children with fathers periconceptionally exposed to methotrexate, the adjusted and unadjusted odds ratios (95% confidence intervals) for major congenital anomalies were 1.1 (0.4-2.6) and 1.1 (0.4-2.4), any congenital anomalies 1.3 (0.7-2.4) and 1.4 (0.7-2.3), PTB 1.0 (0.5-1.8) and 1.0 (0.5-1.8), SGA 1.1 (0.4-2.6) and 1.0 (0.4-2.2), and conception by use of ICSI 3.9 (2.2-7.1) and 4.6 (2.5-7.7). Use of ICSI was not increased among fathers who stopped methotrexate intake ≥2 years before conception, having adjusted and unadjusted odds ratios 0.9 (0.4-1.9) and 1.5 (0.6-2.9).
Conclusion:
This study suggests that paternal periconceptional methotrexate use does not increase risk of congenital anomalies, PTB, or SGA in the offspring but may temporarily reduce fertility.
Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. The mechanism(s) linking paternal age with epigenetic changes in sperm remains unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB is regulated by the balance of two mTOR complexes in Sertoli cells. We hypothesized that this balance is also responsible for age-dependent changes in the sperm epigenome. Experiments with transgenic mice demonstrate that the shift of the balance in favor of mTOR complex two rejuvenates sperm DNA-methylome while the shift in favor of mTOR complex one accelerates aging of the sperm DNA-methylome and results in a reproductive phenotype concordant with older age.
One-Sentence Summary
The balance between mTOR complexes in Sertoli cells regulates sperm methylome aging.
Infertility is a common experience among individuals and couples worldwide, but few studies focus on men's reports of infertility or perceived chance of conceiving, particularly in high-fertility, pronatalist contexts where infertility is highly stigmatized. Using data from the fourth wave of the Umoyo wa Thanzi (UTHA) cohort study in rural Central Malawi (2017-2018), we examine the relationship between self-reported infertility, the perceived chance of conceiving within one year, and sociodemographic characteristics among men (N = 484). While 13% of men reported that they had experienced infertility, just 4% of men perceived that they were unlikely or there was no chance they would conceive with their partner within one year of having sex without contraception. In multivariable logistic regression models, older age was associated with experienced infertility (AOR: 1.06, p < 0.05) and higher parity was associated with lower odds of reporting that conception was unlikely or there was no chance of conception (AOR: 0.08; p < 0.05). We argue that additional research on infertility focusing on men is critical in gaining a more holistic and gender-equitable understanding of infertility. Including men in infertility research may also contribute to destigmatizing infertility among both women and men by acknowledging men's roles in infertility.
Advanced paternal age is associated with increased risks for reproductive and offspring medical problems. Accumulating evidence suggests age-related changes in the sperm epigenome as one underlying mechanism. Using reduced representation bisulfite sequencing on 73 sperm samples of males attending a fertility center, we identified 1,162 (74%) regions which were significantly (FDR-adjusted) hypomethylated and 403 regions (26%) being hypermethylated with age. There were no significant correlations with paternal BMI, semen quality, or ART outcome. The majority (1,152 of 1,565; 74%) of age-related differentially methylated regions (ageDMRs) were located within genic regions, including 1,002 genes with symbols. Hypomethylated ageDMRs were closer to transcription start sites than hypermethylated DMRs, half of which reside in gene-distal regions. In this and conceptually related genome-wide studies, so far 2,355 genes have been reported with significant sperm ageDMRs, however most (90%) of them in only one study. The 241 genes which have been replicated at least once showed significant functional enrichments in 41 biological processes associated with development and the nervous system and in 10 cellular components associated with synapses and neurons. This supports the hypothesis that paternal age effects on the sperm methylome affect offspring behaviour and neurodevelopment. It is interesting to note that sperm ageDMRs were not randomly distributed throughout the human genome; chromosome 19 showed a highly significant twofold enrichment with sperm ageDMRs. Although the high gene density and CpG content have been conserved, the orthologous marmoset chromosome 22 did not appear to exhibit an increased regulatory potential by age-related DNA methylation changes.
Die Dank der steigenden Lebenserwartung zunehmende Zahl alternder Männer rückt die endokrine Situation dieser Altersgruppe mehr und mehr in den Fokus der Medizin. Bei Männern gibt es zwar kein Klimakterium, aber einen allmählichen Abfall des Testosterons, wobei die Werte durchaus im Normbereich jüngerer Männer bleiben können. Bei einigen Männern fallen die Werte jedoch unter die Normalgrenze. Wenn dies in Verbindung mit charakteristischen Symptomen auftritt, kann es sich um einen genuinen Altershypogondismus (LOH = late onset hypogonadism) oder um einen funktionellen Hypogonadismus handeln. In diesen Fällen kann eine Testosteronsubstitution erwogen werden, die streng überwacht werden muss.
Background:
The increase in paternal age and the percentage of births after assisted reproductive technologies (ART) may have consequences on offspring and society's position regarding access to ART must be questioned. Most countries recommend limiting ART to men under 60 years. What is the rationale for this threshold?
Objective:
This systematic review assesses scientific arguments to establish links between paternal age, male fertility, and offspring health.
Material and methods:
Using the PRISMA guidelines, this systematic review of the literature analyzed 111 articles selected after screening PubMed, ScienceDirect, and Web of Science for articles published between January 1st , 1995, and December 31, 2021.
Results:
A strong correlation was highlighted between advanced paternal age and a decrease of some sperm parameters (semen volume and sperm motility) and infant morbidity (exponentially increased incidence of achondroplasia and Apert syndrome, and more moderately increased incidence of autism and schizophrenia). The impact of paternal age on pregnancy and fetal aneuploidy rates is more controversial. No association was found with spontaneous abortion rates.
Discussion and conclusion:
The scientific parameters should be explained to older parents undergoing ART. And for countries that discuss a limit on paternal age for access to ART, the debate requires consideration of social and ethical arguments. This article is protected by copyright. All rights reserved.
Background:
Despite growing evidence suggesting age-related molecular changes in gametes, the impact of paternal age on clinical outcomes during infertility treatments has not been adequately assessed.
Objectives:
This study aims to assess the correlation of paternal age to clinical pregnancy and live birth rates in egg donation cycles undergoing intracytoplasmic sperm injection.
Materials and methods:
This retrospective cohort study includes 4930 fresh oocyte donation cycles from 3995 couples between April 2005 and February 2020 in a private IVF hospital. Clinical pregnancy and live birth rates were the primary outcome measures. The results were also assessed according to the paternal age groups, donor characteristics, semen parameters, fertilization rate and quality of the transferred embryos.
Results:
The age and BMI of the donors, oocyte maturation, fertilization rates and the mean number of transferred embryo quality were comparable on day-3 but not on day-5 embryo transfers between paternal age groups (p>0.05). Paternal age was found to be negatively correlated to the number of oocytes utilized, normal semen parameters, fertilization, clinical pregnancy, and live birth rates (p<0.05). In day-5 embryo transfer cycles, only the rate of cycles with normal sperm, number of allocated oocytes, and pregnancy were found to be statistically significant.
Discussion and conclusion:
Paternal age may influence reproductive outcomes and should be considered during infertility evaluations in ICSI donor cycles. Further research is needed to confirm these findings. This article is protected by copyright. All rights reserved.
This user-friendly second edition provides a practical introduction to gynaecological ultrasound. It describes and explains background anatomy and physiology, instrumentation and how to make the best use of equipment. Emphasis is placed on how to maximise image quality, and how to recognise normal and pathological features. The volume also assesses other relevant diagnostic techniques and various management strategies, and evaluates the role of ultrasound as part of patient management. It includes chapters on pathology of the uterus, ovaries and adnexae, paediatric and trauma cases, together with management of infertility and other gynaecological perspectives of patient management. Illustrated throughout with numerous high-quality ultrasound images and line drawings, many of them new for this latest edition, this is essential reading for practitioners in training, including radiologists, gynaecologists and sonographers.
What is happening to the human male?Something strange is happening to the human male. The incidence of testicular cancer is increasing dramatically in all the advanced economies on Earth, male infertility has reached epidemic proportions, sperm counts are declining at an alarming rate and paternal impacts on offspring health are becoming increasingly apparent. Notably, the incidence of testicular cancer shows a strong correlation with socio-economic development such that, globally, it has become the major cancer afflicting young males. In parallel with the increased incidence of testicular cancer, sperm counts have been falling across the globe. The reason for this decline in semen quality is uncertain at the present time but it may be an indirect reflection of falling testosterone levels, possibly fuelled by oestogenic factors in the environments we inhabit, the food we eat, the water we drink, the drugs we take, the lifestyles we adopt and the metabolic patterns we experience in affluent society. The resultant oestrogenic load may impact male reproductive health at any point in sexual development from fetal life to adulthood. Controlling the exposures responsible for these impacts on male reproduction is essential because, if current trends continue unabated, it will have as major impact on the future of our species.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
Historically, sperm have been seen as simply a mechanism of transferring a haploid set of chromosomes to the oocyte. However, data from assisted reproduction therapies (ART) have demonstrated that in many couples the sperm appears to be responsible for abnormal embryogenesis. Recent advances in genetic and epigenetic techniques have identified key mechanisms by which the sperm, and the DNA carried by the sperm, can affect early embryonic development. Paternal Influences on Human Reproductive Success examines the genetic and epigenetic influences on embryogenesis, as well as practical clinical factors related to the male contribution to reproductive success. It also provides 'cutting edge' data and analysis of recent evaluations of the role of advanced paternal age, environmental influences and lifestyle factors on male reproductive fitness, making this an invaluable text for physicians treating patients for infertility, recurrent pregnancy loss, and developmental anomalies, as well as basic scientists studying embryogenesis and spermatogenesis.
The objective of this study was examine geographical variation in couple fecundity in Europe. The study was based upon all
recently pregnant (or still pregnant) women within well-defined geographical areas in Europe (Denmark, Germany, Italy, Sweden
and France) at a given time period in 1992. Altogether, 4035 women responded to a highly structured questionnaire. Highest
fecundity was found in Southern Italy and Northern Sweden; lowest fecundity was seen in data from the East German centre.
Approximately 16% of the study population had a waiting time of more than 12 months to become pregnant. Most of the pregnancies
were planned (64%) and approximately 14% were the result of contraceptive failures. The study shows that smoking, body mass
index, age and parity did not explain the differences in fecundity found between the centres. Regional differences in fecundity
exist and the causes may be genetic or due to variations in behavioural and environmental exposures.
To study the age of the start of the fall (critical age) in fecundity; the probability of a pregnancy leading to a healthy baby taking into account the age of the woman; and, combining these results, to determine the age dependent probability of getting a healthy baby.
Cohort study of all women who had entered a donor insemination programme.
Two fertility clinics serving a large part of The Netherlands.
Of 1637 women attending for artificial insemination 751 fulfilled the selection criteria, being married to an azoospermic husband and nulliparous and never having received donor insemination before.
The number of cycles before pregnancy (a positive pregnancy test result) or stopping treatment; and result of the pregnancy (successful outcome).
Of the 751 women, 555 became pregnant and 461 had healthy babies. The fall in fecundity was estimated to start at around 31 years (critical age); after 12 cycles the probability of pregnancy in a woman aged greater than 31 was 0.54 compared with 0.74 in a woman aged 20.31. After 24 cycles this difference had decreased (probability of conception 0.75 in women greater than 31 and 0.85 in women 20.31). The probability of having a healthy baby also decreased--by 3.5% a year after the age of 30. Combining both these age effects, the chance of a woman aged 35 having a healthy baby was about half that of a woman aged 25.
After the age of 31 the probability of conception falls rapidly, but this can be partly compensated for by continuing insemination for more cycles. In addition, the probability of an adverse pregnancy outcome starts to increase at about the same age.
Specialist infertility practice was studied in a group of 708 couples within a population of residents of a single health district in England. They represented an annual incidence of 1.2 couples for every 1000 of the population. At least one in six couples needed specialist help at some time in their lives because of an average of infertility of 21/2 years, 71% of whom were trying for their first baby. Those attending gynaecology clinics made up 10% of new and 22% of all attendances. Failure of ovulation (amenorrhoea or oligomenorrhoea) occurred in 21% of cases and was successfully treated (two year conception rates of 96% and 78%). Tubal damage (14%) had a poor outlook (19%) despite surgery. Endometriosis accounted for infertility in 6%, although seldom because of tubal damage, cervical mucus defects or dysfunction in 3%, and coital failure in up to 6%. Sperm defects or dysfunction were the commonest defined cause of infertility (24%) and led to a poor chance of pregnancy (0-27%) without donor insemination. Obstructive azoospermia or primary spermatogenic failure was uncommon (2%) and hormonal causes of male infertility rare. Infertility was unexplained in 28% and the chance of pregnancy (overall 72%) was mainly determined by duration of infertility. In vitro fertilisation could benefit 80% of cases of tubal damage and 25% of unexplained infertility--that is, 18% of all cases, representing up to 216 new cases each year per million of the total population.
To study the effect of body fat distribution in women of reproductive age on fecundity.
Prospective cohort study of all women who had entered a donor insemination programme.
One fertility clinic serving a large part of the midwest of the Netherlands.
Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study.
Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment.
A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity.
Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.
The purpose of this study was to investigate any influence of maternal and/or paternal age on gamete characteristics and pregnancy outcomes in intracytoplasmic sperm injection (ICSI) cycles. In all, 821 consecutive ICSI cases were analysed retrospectively. While a significant linear decline in semen volume was detected, no significant differences in the concentration, motility or morphology of the spermatozoa were found with paternal ageing. A significant decline in the number of oocytes retrieved and the number of mature oocytes obtained was found with advancing maternal age. An increase in the occurrence of digyny was noted with parental ageing, while no difference in single or bipronuclear fertilization was found. Older women had a decreased incidence of single pronucleus formation and an increase in digyny, but no significant difference in the percentage of oocytes that underwent two-pronuclear fertilization was detected with regard to maternal ageing. Pregnancy outcomes were not influenced by the age of the male partner, while a strong negative correlation was found with maternal ageing. To better analyse male partner ageing as a factor affecting pregnancy outcome, we analysed a subgroup of patients with a female partner aged <35 years who underwent ICSI. No paternal influence on ICSI pregnancy outcome was found in this subgroup of patients. We conclude that the influence on pregnancy outcome after ICSI is related mostly to maternal and not paternal age.
Our purpose was to determine the influence of age on the outcome of assisted reproduction, with particular interest in women aged 40 years or older.
A retrospective review of the 779 patients enrolled in the Royal Hospital for Women Fertility Group fertility program between 1987 and 1994 was performed. The results for women aged 40 years or older were compared with those for women between 36 and 39 years and those younger than 36 years. The main outcome measures were pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response.
Compared with those in younger women, pregnancy rate, pregnancy outcome, fertilization rate, and ovarian response to controlled ovarian stimulation were significantly worse in women aged 40 years or older.
The outcome of assisted reproduction in women of 40 years of age or older was extremely poor. Compared with those in younger women, pregnancy outcome and ovarian response to controlled ovarian stimulation were significantly worse in women of 40 years or more.
To investigate the association between the level of social deprivation in electoral wards and various life events. Life events include mortality, self reported long term illness, and for women: still-birth, underweight birth, birth while a teenager, and sole registered birth. Associations with area deprivation are tested before and after allowing for levels of personal deprivation.
Prospective census follow up using the Office for National Statistics Longitudinal Study.
England and Wales.
A random sample of more than 300,000 people enumerated at the 1981 census, and aged 10 to 64 in 1981. Some analyses are necessarily restricted to certain age/sex groups.
Several outcomes in the decade 1981-1992 are investigated: risk of premature death (before age 70, all cause), risk of long term limiting illness in 1991, and risk of inauspicious fertility outcomes in women.
Without adjusting for personal circumstances all outcomes, except risk of stillbirth, show a clear, significant, and approximately linear association with social deprivation of ward of residence in 1981. Associations are much stronger for outcomes where a greater "social" component can be constructed (teenage birth, sole registered birth) than for outcomes that are probably more physiologically determined (mortality, stillbirth, low birth weight). When adjustment is made for personal disadvantage the simple associations with local area deprivation are all attenuated, especially for those living in the more deprived areas.
A variety of adverse or "inauspicious" life events show association with residence in more deprived areas. These are particularly strong for teenage birth and sole registered birth, but are also stronger for long term illness than mortality. These associations seem to be largely because residence in more deprived areas is associated with personal disadvantage, which is more damaging to life chances than area of residence. For some outcomes there is evidence that the personally disadvantaged fare less well if living in relatively advantaged areas, than if living in more homogenously deprived areas.
Of 17 032 women taking part in the Oxford Family Planning Association contraceptive study, 4104 stopped using a birth control method to plan a pregnancy on a total of 6199 occasions. The influence of various factors on fertility in these women was assessed by measuring the time taken to give birth to a child. An appreciable inverse relation was observed between age at stopping contraception and fertility both in nulliparous and parous women, but the effect was much greater in the nulliparous women. The most important finding was a consistent and highly significant trend of decreasing fertility with increasing numbers of cigarettes smoked per day; it was estimated that five years after stopping contraception 10.7% of smokers smoking more than 20 cigarettes a day, but only 5.4% of non-smokers, remained undelivered. Some relation was found between fertility and social class, age at marriage, and a history of gynaecological disease, but weight, height, and Quetelet's index were without noticeable effect.
Developed countries have experienced both some population growth and unprecedented declines in fertility rates during the
last half of the twentieth century. Couples now have fewer than two children on average in most European countries and they
tend to postpone these births until a later age. A decline in male fertility has been suggested by some studies of semen quality,
but there is contrasting evidence of shorter times to pregnancy for couples trying to conceive. An important economic factor
is the income of young men relative to their parents' incomes, which determines how they rate the ability of their own earnings
to support a family. Lower relative income in the 1970s was associated with a lower fertility rate. The decline in fertility
in the USA may have been attenuated by the sharp rise in female income during the late 1960s and early 1970s, allowing women
to take advantage of purchased child care, thus maintaining the relative family income. The level of demand for children does
not appear to be set by known psychological factors, although explanations for the desire to reproduce have been sought in
biological, psychoanalytical and socio-cultural research. Recent studies indicate that adults with secure attachment relationships
are more interested in being parents. Possible epidemiological factors include age at first marriage, but in Eastern Europe,
where age at first marriage is as low as 22 years, fecundity rates do not exceed 1.5. When mothers' age cohorts are analysed,
the mean fecundity rate has been falling since the 1920s. Health factors affecting population trends include the change in
contraceptive prevalence over the last 40 years. The prevalence of sub-fertility remains close to 10%, and studies from a
number of countries indicate that ~50% of infertile couples make use of infertility services including IVF and intracytoplasmic
sperm injection which are available in 45 countries covering 78% of the world's population. It is estimated that the level
of service is sufficient for less than one-third of the need.
Many studies have found decreased fecundability, that is, the ability to conceive in a menstrual cycle, with increasing female age. To evaluate the effect of maternal age on waiting time to pregnancy, the authors reviewed hospital charts of all pregnant women attending prophylactic antenatal care at Odense University Hospital, Denmark, during 1972-1987. Only the first pregnancy of each woman and only planned pregnancies were included (n = 14,754). The fecundability odds ratio (FR) was calculated as the odds of a conception in a menstrual cycle among the older women divided by the odds among women aged 15-24 years. The FR for women aged 25-29 years was 1.12 (95% confidence interval (Cl): 1.04, 1.20), for women aged 30-34 years it was 1.15 (95% Cl: 1.01, 1.30), and for women above 34 years the FR was 2.44 (95% Cl: 1.84, 3.22) after adjustment for confounders. The increased fecundability with age is contrary to previous studies and may be explained by selection bias, as sterile women were not included. In addition, some very fertile young women who became pregnant by accident before efficient birth control methods were available and therefore were excluded from time to pregnancy studies may now use oral contraceptives until they plan a pregnancy later in life and are included.
The retrospective study based on pregnancy samples is the most commonly used method for studying time to pregnancy. Using a simple Monte Carlo simulation, this note focuses on a particular selection bias problem associated with this design: even if each woman's fecundity decreases with age, estimation of the effect of age may show the opposite trend. We recommend exercising increased caution in interpreting findings from pregnancy-based time-to-pregnancy studies.
Objective To determine the likely risk factors, such as smoking and drinking habits, and occupational groups, for infertility in a group of infertile men with no known cause, compared with a group of fertile men; and to examine the effects of the semen parameters, such as volume, density, motility, viability and normal morphology, on fertility.
Design A case-control study.
Setting The department of obstetric and gynaecology of a tertiary general hospital.
Participants Six hundred and forty consecutive male partners of couples trying to conceive were recruited from an infertility clinic. Of these, the cases comprised 218 men who had no known cause for their infertility. Two hundred and forty men whose wives were pregnant at the time of the study were recruited as controls.
Results The semen parameters (e.g. density, total sperm counts, motility, viability and normal morphology) of all cases were significantly poorer than that of the controls. The risk of infertility is associated with smoking (crude OR 2.82, 95% CI 1.93–4.13; adjusted OR 2.96; 95% CI 1.98–4.42). Technicians (adjusted OR 2.81; 95% CI 1.51–4.24) and professional, senior officials and managers were also at a greater risk of infertility (adjusted OR 2.36; 95% CI 1.26–4.40), compared with service and clerical workers. The significant factors predicting infertility were smoking, density of sperm, and viability of sperm. Smoking increased the odds of being infertile. Higher sperm counts and larger percentage of viable sperm decrease the odds of infertility. Based on the multiple logistic regression model, the odds ratio for infertility = 94.70 × 2.88smoking× 0.29logdensity× 0.95viability.
Conclusion Smoking, density of sperm and the viability of sperm are significant predictors for infertility among men.
The impact of male age on fecundity remains controversial. Here, a large population study was used to investigate the effect
of paternal age on time to conception. All couples in the Avon Health district expecting a baby between 1 April 1991 and 31
December 1992 were eligible. Questionnaires completed by both the man and the woman at 18 weeks gestation covered specific
fertility factors, e.g. parity, paternity, cohabitation and oral contraception; and non-specific factors, e.g. educational
achievement, housing, cigarette smoking, alcohol consumption, obesity. Logistic regression was used to identify factors independently
related to conception in ≤6 or ≤12 months. Of 8515 planned pregnancies, 74% were conceived in ≤6 months, 14% in the second
6 months and 12% after more than a year. Nine variables, including the age of the woman, were independently related to time
to conception. After adjustment for these, the likelihood of conception within 6 or 12 months was lower in older men. Compared
to men <25 years old, the adjusted odds ratios (95% confidence interval) for conception in ≤12 months were 0.62 (0.40, 0.98),
0.50 (0.31, 0.81) and 0.51 (0.31, 0.86) in men aged 30–34, 35–39 and ≥40 years respectively.
A new method for the estimation of the mean and variance of fecundability is described. The data input required for this procedure is the distribution of the interval from marriage to first birth, or from the resumption of the conception risk after contraction to the subsequent birth. The estimates of the mean and variance of fecundability are obtained by fitting a model to the observed interval distribution. To test the method, it is applied to data from five historical populations. The fecundability means in these populations ranged from 0.18 to 0.31 while the co-efficients of variation all had values near 0.56. A short method for the estimation of the mean of fecundability based on the same model, but not requiring a computer, is also presented.
To examine possible mechanisms for the association between cigarette smoking and reduced fertility, we have measured the concentration of the nicotine metabolite cotinine in ovarian follicular fluid collected at the time of oocyte recovery during treatment for in-vitro fertilisation. In a group of women in whom follicular fluid cotinine could not be detected (limit of accurate measurement 20 ng/ml) 116 oocytes were collected, of which 84 became fertilised (72%), whereas among women with cotinine concentration greater than 20 ng/ml 20/45 (44%) oocytes did so (p < 0.01). The median fertilisation rates for individuals (range 1-8 eggs each) in the high and low cotinine groups were 57% and 75%, respectively (p < 0.05). These findings suggest that infertile women should be advised to stop or reduce smoking generally, and especially before treatment by in-vitro fertilisation.
The effectiveness of infertility treatments is still questioned, particularly the assisted conception methods because of their complexity and cost. Furthermore, pregnancies often occur independent of treatment but many treatments have not been properly evaluated. The most basic audit of outcome with or without treatment requires pregnancy and preferably birth rates to be calculated in a cycle-specific and/or time-specific way; cumulative rates are the preferable method of calculation, in order to account for the usual tendency for fecundity to fall progressively. The choice of treatment usually depends on a balance of the chances of conceiving with or without treatment, and with more or less complicated treatments, and on other factors such as duration of infertility and the woman's age. This review aims to address those choices by assessing the actual and comparative effectiveness of treatments insofar as there are well defined and strictly comparable time-specific or cycle-specific published data available. Cumulative rates are described wherever possible and presented graphically for easy reference.
A questionnaire-based study of infertility has been carried out in two age cohorts of women in a defined geographical region. Women were aged 36-40 years or 46-50 years at the time of the survey. The prevalence of infertility (no conception after 2 years of trying) was approximately 14% in both age cohorts. However, a significantly higher proportion of younger women had sought medical help. In both age cohorts there was a higher incidence of spontaneous abortion among infertile women. These findings suggest no significant increase in the prevalence of infertility over a decade but a considerable increase in the use of medical services.
To determine the relationship between age and female fecundity, 210 women were studied prospectively. The subjects had negative infertility evaluations and were receiving therapeutic donor insemination. Life-table analysis was performed on 751 donor insemination cycles. For comparison, patients were divided into five separate age groups and into two separate groups, ages 19-34 and 35-45. Monthly fecundity and cumulative conception rates were calculated for each group. A significant difference was found when all age groups were compared (P = .05) and when those at or above age 35 and those below age 35 were compared (P less than .05). Frozen semen was used in 92% of all cycles. The average monthly fecundity of all patients treated with frozen semen was 16%. This study confirms a progressive decline in fecundity with age in a completely evaluated group of women undergoing therapeutic donor insemination and demonstrates that frozen semen can yield acceptable fecundity provided sufficient numbers of motile sperm are used for each procedure.
Recreational drug (marijuana, lysergic acid diethylamide or LSD, speed, cocaine, and "other") exposures of women with primary infertility were compared with those of a matched control group of women with proven fertility. Women who reported smoking marijuana had a slightly elevated risk for infertility due to an ovulatory abnormality (RR = 1.7, 95% CI = 1.0 to 3.0). The risk was greatest among women who had used marijuana within one year of trying to become pregnant (RR = 2.1, 95% CI = 1.1 to 4.0). No consistent frequency or duration of use effects could be demonstrated, and the risk was confined to low-frequency users. Risks associated with the use of other drugs were not elevated. The risk of infertility from a tubal abnormality associated with cocaine use was greatly increased (RR = 11.1, 95% CI = 1.7 to 70.8). Our results are consistent with animal studies suggesting that smoking marijuana may cause a transient disruption of ovulatory function. The possibility that cocaine exposure influences the development of tubal infertility needs further investigation.
Time to pregnancy according to the age of the father and the mother has been studied among 10,886 couples from Odense and Aalborg. Late in their pregnancy (36th week) all woman in the two cities were given a questionnaire on time to pregnancy as well as a number of other items. Eighty-six percent responded to this questionnaire, and data concerning previous pregnancies, the outcome of the pregnancy in question, etc., were later collected from medical files. The study showed a strong correlation between mother's age and subfecundity, even after adjustment for a number of potential confounders. The association between subfecundity and the age of the father was much weaker and did not reach statistical significance. Interpretations and implications of these findings are discussed in the paper.
To study the prevalence of infertility, both primary and secondary, outcome of pregnancy, occupation, and uptake of medical services in a total population of women from a geographically defined area.
A postal questionnaire survey of an age cohort of women who had completed their fertility, and who were randomly selected from the Grampian Health Board's primary care register.
Aberdeen city district.
1024 Women in the age group 46-50, of whom 130 had to be excluded. Of the remaining 894 women, 766 (86%) responded to the questionnaire.
Response to questionnaire on pregnancy history, the length of time taken to become pregnant each time, and whether medical advice had been sought.
Among the 766 women contacted, 602 (79%) reported no difficulties in having children, 56 (7%) had chosen not to have children, and the remaining 108 (14%) had experienced infertility, defined as having difficulty in becoming pregnant for more than two years. In total 68 (9%) women had primary infertility, of whom 41 (5%) eventually conceived. Of the 40 (5%) with secondary infertility, 23 (3%) conceived. Overall, 52 (7%) of the population were left with an unresolved problem of infertility. Only 67 (62%) infertile women had made use of hospital services, and a further 8 (7%) had consulted their general practitioners. Among those who conceived there was no difference in the proportion who sought advice compared with those who did not.
The overall prevalence of infertility was 14%, although half of these women eventually conceived. Primary infertility was more common than secondary infertility. Only 62% of infertile women attended a hospital clinic for treatment of their infertility.
The effect of husband's age on the probability of conception is evaluated from World Fertility Survey data in five developing countries: the Ivory Coast, Ghana Kenya, the Sudan, and Syria. Proportional hazards models, which include wife's age, husband's age, marriage duration, union type, and post-partum exposure as covariates, are used to describe the monthly conception rate for second and higher-order birth intervals in which no contraception was used. With the exception of Syria, the resulting models indicate that the effects of male age are generally small in relation to the influences of marital duration and the age of the woman.
A study was initiated to compare the spermiograms according to age in 570 consecutive men with a history of infertility. The semen was evaluated by computer-assisted semen analysis (CSA) and by the hyposmotic swelling test (HOS). A statistical difference was seen between men over 50 years of age compared with younger men, but only for the HOS scores and velocity. No statistical differences were found on any of the other parameters. Since most semen parameters were similar even in the men over age 50, a definite decline in fertility potential with increasing age could not be determined by this study.
The objectives of this study were two-fold: firstly to determine whether female age exerts an influence on the fertility outcome of couples attending an infertility clinic, independent of demographic and clinical details; and secondly to examine the relationship between the length of involuntary infertility prior to investigation and the subsequent chance of conception. Seven-hundred-and-thirty-one subjects whose partner did not have azoospermia were recruited to the study. Female age ranged from 20 to 46 (mean = 31.1). The range of involuntary infertility prior to investigation was 12-216 (mean = 62) months. One-hundred-and-twenty-four women conceived. The following variables achieved the 5% level of significance when a stepwise analysis was performed on all cases; the concentration of spermatozoa exhibiting slow or sluggish linear or non-linear motility (chi 2(1) = 17.57, P less than 0.0001, RR = 1.67 per 50 x 10(6)), female age (chi 2(1) = 12.44, P = 0.0004, RR = 0.92 per annum), tubal status (chi 2(1) = 12.22, P = 0.0005, RR = 2.15), length of infertility before investigation (chi 2(1) = 11.22, P = 0.0008, RR = 0.87 per annum) and past paternity (chi 2(1) = 8.43, P = 0.0037, RR = 1.81). Female age was found to be positively correlated with the incidence and severity of ovulatory dysfunction, tubal occlusive disease, pelvic adhesions and endometriosis. Where the female partner was 'normal' on investigation, all conceptions were independent of treatment to either partner.(ABSTRACT TRUNCATED AT 250 WORDS)
892 infertile couples were studied retrospectively over a 4 year and 7 month period for their chance of spontaneous conception after first attendance at the clinic. The Kaplan-Meier method was used for all calculations. Most of the spontaneous conceptions took place within two years. As the age of the female patient increased, beginning at age 30, the cumulative spontaneous conception rate decreased. The same was true for the duration of infertility beginning at 4.5 years. The influence of the latter was more important. The cumulative conception rate was not influenced by whether the infertility was primary or secondary. Patients referred by a general physician had a better chance of achieving spontaneous conception than patients referred by a gynaecologist. It is concluded that time plays a significant role in the achievement of pregnancies in our clinic, but should no longer be relied upon two years after entering the clinic.
Direct evidence on age patterns of infecundity and sterility cannot be obtained from contemporary populations because such large fractions of couples use contraception or have been sterilized. Instead, historical data are exploited to yield upper bounds applicable to contemporary populations on the proportions sterile at each age. Examination of recent changes in sexual behavior that may increase infecundity indicates that sexually transmitted infections, the prime candidate for hypothesized rises in infertility, are unlikely to have added to infecundity to any great extent. These results imply that a woman in a monogamous union faces only moderate increases in the probability of becoming sterile (or infecund) until her late thirties. Nevertheless, it appears that recent changes in reproductive behavior were guaranteed to result in the perception that infecundity is on the rise.
Sperm morphology and motility are believed to be important prognostic factors for fertility. Results of a group of 67 men investigated for primary infertility who had mean sperm concentrations greater than 5 million per ml and who later produced pregnancies, were compared with those of 67 matched controls who remained infertile. All female partners were potentially fertile. The groups were matched for other known prognostic factors for fertility, namely, wife's age, the duration of infertility, sperm concentration and varicocele size. There were no significant differences between the two groups overall in the (mean +/- SEM)% of sperm with normal morphology (58.3 +/- 2.1; 58.5 +/- 2.2), or motility (40.6 +/- 1.8; 37.0 +/- 2.0). However, among oligospermic men from the two groups, sperm motility was significantly higher (P less than 0.05) in the subsequently fertile group (43.1 +/- 2.6%) than in the persistently infertile group (33.3 +/- 3.7). These results indicate that sperm morphology as currently assessed may not be important in predicting fertility in subfertile men with a mean sperm concentration over 5 million/ml and the % sperm motility may only be a relevant predictor in oligospermic men.
Of 17 032 women taking part in the Oxford Family Planning Association contraceptive study, 4104 stopped using a birth control method to plan a pregnancy on a total of 6199 occasions. The influence of various factors on fertility in these women was assessed by measuring the time taken to give birth to a child. An appreciable inverse relation was observed between age at stopping contraception and fertility both in nulliparous and parous women, but the effect was much greater in the nulliparous women. The most important finding was a consistent and highly significant trend of decreasing fertility with increasing numbers of cigarettes smoked per day; it was estimated that five years after stopping contraception 10.7% of smokers smoking more than 20 cigarettes a day, but only 5.4% of non-smokers, remained undelivered. Some relation was found between fertility and social class, age at marriage, and a history of gynaecological disease, but weight, height, and Quetelet's index were without noticeable effect.
A wide variety of disorders, medications, physical factors, and trauma can alter testicular function and reproductive function in men as they age. There are no precise age limits for 'aging men', but most studies consider 50-80-yr-old subjects. Assuming we have healthy individuals, there are still changes that occur with aging. There is progressive testicular failure as evidenced by gradually increasing levels of both gonadotropins with aging. Although basal levels of male hormone remain reasonably normal in healthy older men, the ability of the Leydig cells to respond to acute stimulation with LH is reduced. There are changes in the penis, prostate, and seminal vesicle which occur with aging. Potency tends to be reduced with age. Sperm production per testis falls off with aging. The amount of capsular tissue increases in the testis with advancing years. There is very limited data about men in extreme old age (80 yr and older). Of older men who produce spermatozoa in their ejaculates, sperm motility, a manifestation of viability and fertilizing capacity, tends to be reduced. The ability of men to impregnate their wives gradually reduces from age 25 onward. Using the zona pellucida-free hamster egg, penetration by spermatozoa from aged healthy men appears to be as good as that from younger fathers. This test cannot guarantee equal fertility, but it is the best test available and correlated reasonably well with fertility. Thus, if an older man can get an erection, can ejaculate, and can produce an ejaculate with a reasonable number of motile sperm, the likelihood is that he is fertile.
Current epidemiological evidence suggests that 15% of couples will experience infertility and in half this number the problem will remain unresolved. Background prevalence rates now appear to be reasonably stable, but there is evidence of an increase in the rate of referrals for medical help. Rates of secondary infertility are higher in the population than represented by clinic referrals. The distribution of the main diagnostic groups is as follows: Male 25%; Ovulation 25%; Tubal 20%; Unexplained 25%; and Endometriosis 5%. Effective management in the male includes donor insemination and assisted reproduction (including intra-cytoplasmic sperm injection). Drugs are ineffective for idiopathic oligozoospermia, while the role of varicocele ligation is uncertain, but marginal at best. Ovulation problems can be treated with a high degree of success, except in cases of clomiphene resistant polycystic ovarian disease. However there are continuing concerns over multiple pregnancy rates and future research is needed to clarify the additional risks, if any, of ovarian carcinoma. Surgical correction of tubal abnormalities should be left to specialised units, where audit indicates that the results can match those achieved by assisted reproduction. There is no evidence that the medical (drug) management of endometriosis improves fertility, although surgery for moderate and severe disease can still be considered. However the results should be compared with those achieved by assisted reproduction. Superovulation and intra-uterine insemination appears to be an effective treatment for certain cases of mild male factor infertility, mild endometriosis and unexplained infertility and can be considered, where the duration of infertility is more than four years. A pregnancy rate of around 10% per cycle can be anticipated, but there is a significant risk of multiple pregnancy. The evidence is that IVF (and GIFT) has achieved significantly improved results in recent years, with fecundity rates of 20% per cycle being a reasonable target in women under 40 years.
To determine the effects of age on reproductive performance of women using oocyte donation as an in vivo model.
Oocyte donation and IVF programs at the Instituto Valenciano de Infertilidad.
Seventy-six women undergoing 90 cycles of ovum donation, who were recipients of 36 donors undergoing IVF, and 9 fertile women.
Prospective longitudinal study: [1] recipients underwent an artificial cycle to demonstrate adequate response of the endometrium to exogenous steroids; [2] oocytes from the same cohort of follicles were distributed randomly into recipients younger and older than 40 years; and [3] pregnancies were followed during the first trimester.
Endometrial histology, fertilization, embryo quality, pregnancy, implantation, and abortion rates in both groups of recipients. Serum E2, P and beta-hCG levels during initial pregnancy.
Similar implantation rates but significantly higher abortion rates were detected in women > 40 years despite an appropriate action of P on the endometrium and the transfer of embryos in similar number and quality. The secretion of E2 and P by the placenta started earlier in pregnancies included in the group < 40 years.
Age increases pregnancy losses in ovum donation patients after implantation is completed. This is accompanied by a retardation of steroid synthesis and suggests that the mechanism(s) responsible for placenta formation and functioning in the uterus is affected by age. Thus, uterine aging also is a factor influencing the poor reproductive performance of women with advancing age.
To establish the degree of validity of data on time to pregnancy, derived retrospectively using a short questionnaire.
Information from the questionnaire was compared with data that had been collected concurrently from the same individuals.
Questionnaires were mailed to 1647 women who continue to be followed up by the Oxford Family Planning Association contraceptive study, and a further 424 were approached for personal interview. Response rates were 91% and 79% respectively.
Matching was successful in 91% of pregnancies. Median recall time was 14 years (interquartile range, 11-16 years). At the group level, remarkably good agreement was found between the two sources of information, presented as cumulative percentage distributions of live births. The findings were at least as good with longer recall (> 14 years) as with shorter recall. Digit performance was present to a limited degree. At the individual level, some misclassification was evident, which has implications for statistical power. For detection of clinical infertility (no conception within 12 months), the sensitivity was in the range 67%-91%, and the specificity was 92%-96%. Variations with format, duration of recall, age at delivery, year of birth, parity, social class, smoking habit, last contraceptive method, and outcome (live birth or not) were generally small, and were not statistically significant.
Time to pregnancy is a sensitive way of assessing reproductive function in either sex. Valid data at a group level can be derived retrospectively, with a long duration of recall, using a short questionnaire.
To investigate changes in menstrual cycle hormones and endometrial maturation that may contribute to the decline in fertility with aging.
Prospective controlled clinical study.
Normal human volunteers in an academic research institution.
Women with regular menstrual cycles.
Thirty-two women, aged 20 to 30 or 40 to 50 years, had daily blood drawing starting on cycle day 6 to 10 and continuing until 2 days after the onset of next menses. In addition, 60 women, aged 20 to 30 or 40 to 50 years, had a total of 93 endometrial biopsies performed on day 7 to 9 after the LH surge.
Serum LH, FSH, E2, inhibin, P, and placental protein 14 (PP14) levels and histologic maturation of the endometrium.
Serum FSH levels were increased whereas inhibin concentrations were reduced in the luteal-follicular transition of women > 40 years. No other hormonal changes were seen in this population, including P and PP14 secretion. Disruption of endometrial maturation occurred at a similar frequency in both age groups.
Follicular recruitment, but not luteal function or endometrial maturation, is disturbed in cycling women > 40 years and may contribute to the decline in fertility with aging.
In distinction to the course of reproductive ageing in women, men do not experience a rapid decline of Leydig cell function or irreversible arrest of reproductive capacity in old age. Hence, strictu sensu, the andropause does not exist. Nevertheless, both spermatogenesis and fertility as well as Leydig cell function do decline with age, as shown by a decrease of +/- 35% of total and of 50% of free testosterone levels between the age of 20 and 80 years. The origin of this decline of Leydig cell function resides on the one hand in the testes, and is essentially characterized by a decreased number of Leydig (and Sertoli) cells and on the other hand in the hypothalamo-pituitary complex characterized by a decreased luteinzing hormone (LH) pulse amplitude, LH pulse frequency being maintained. As the responsiveness of the gonadotrophs to gonadotropin-releasing hormone (GnRH) remains unimpaired, one may assume that the amount of GnRH released at each pulse is also reduced, possibly as the consequence of a reduction of the cellular mass of GnRH neurones. Plasma levels of testosterone below the lower normal limit occur, however, only in a minority of elderly men from 7% in the age group 40-60, to 20% in the age group 60-80 and 35% in the age group over 80 years old. Factors influencing testosterone levels in elderly men are multiple: hereditary, environmental (obesity, stress), psychosocial (depression, smoking, drugs) or socioeconomical (diet, hygiene). Whether these elderly men should be substituted with androgens remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)
Onset of capacity for childbearing in women is dated biologically by menarche, although actual onset may be delayed. The end of childbearing is less understood but recent demographic and biological research on fertility at older ages is clarifying the end of fertility.
The demographic view of declining fertility with age is based on age-specific fertility in natural fertility populations, artificial insemination and pregnancy rates by age and World Fertility Survey data. New data from the Demographic and Health Surveys on exposure to the risk of pregnancy shows that whereas older women biologically need longer exposure to pregnancy, exposure declines on behavioural grounds such as duration of marriage. Actual fecundity is obscured by factors of fecundability. Recent research on medically assisted conception is adding to the understanding of declining fecundity with age, especially the relative contributions of endometrial and ovarian ageing.
This paper reviews the available information on declining fertility with age and discusses the implications of the extension of fertility through new medical technologies.
Fertility is affected by the age of the female partner, but not that of the male partner, in the age ranges within which most attempts at conception occur. However, the literature on the effect of the smoking status of each partner is inconclusive. As part of a longitudinal study representative of all people born in Britain in 1958, 11,407 people were interviewed in 1991, of whom 3,132 female and 2,576 male cohort members had had or fathered at least one pregnancy. The outcome measure was the time to pregnancy of the first pregnancy (live births only), and the antecedent variables were the cohort member's age at that time and both partner's smoking habits and educational levels. Unadjusted analysis demonstrated that both the time to pregnancy and clinical subfertility were associated with higher maternal but not paternal age and with the smoking habits and educational levels of both parents. Multivariate analysis showed that paternal smoking failed to enter the model if the educational variables were also included. Findings were similar in the two separate analyses on male and female cohort members. This study confirms previous findings on the relative importance of maternal and paternal age in this age range. Maternal smoking affects fertility, but earlier reports of an apparent effect of paternal smoking may be due to confounding with socioeconomic status.
Objective - Delineation of change in male hormone and gonadotropin levels from age 21 to 85. Subjects - Healthy married volunteers with one or more children. Methods - A 5-mL venous blood sample, serum separated within one hour; testosterone measured by direct RIA, FSH and LH by immunoradiometric assay and magnetic separation. Results - FSH significantly higher from 6th decade, LH from 7th decade; testosterone lower from 6th decade. Conclusions - Apparently, a rise in FSH and reduction in testosterone precede a rise in LH concentration.
When couples elect to defer child bearing, the effects of age on reproductive potential must be considered. The impact of advancing age on female reproductive potential has been well documented. Relatively less attention, however, has been directed toward the effect of age on male reproductive function. Although less pronounced than its effect on female fertility, advancing age does have an impact on male reproduction. Among men, increasing age is associated with a decrease in sexual function as well as changes in testicular histology and a decline in basic fertility parameters. Additionally, there is an identifiable association between advanced paternal age and subsequent birth defects. These issues should be borne in mind when men are counseled regarding the age at which they elect to establish families.
There is approximately a 50% decrease in the fertility rate of unselected women attempting pregnancy at age 40 or older compared with younger women and a two to three fold increased rate of spontaneous abortion. Approximately 45% of older women achieve a term outcome, however.
Proper counseling of the older patient should include a realistic view of the following risks: a 30% to 50% reduced pregnancy potential, effect of pregnancy on other maternal illnesses, an increased risk of pre-eclampsia, hypertension, and diabetes,¹ and an increased risk of chromosomal abnormalities, abortion, and stillbirth. Knowing these risks, additional testing for ovarian reserve may help to identify women with favorable indices in whom IVF, other forms of assisted reproduction, or surgery to restore fertility are most appropriate. Women with decreased ovarian reserve could be offered oocyte donation as an alternative to surgical correction for infertility, because pregnancy rates are excellent when donor oocytes are transferred to the uteri of women older than the age of 40. In short, age alone should no longer be a deterrent in the treatment of infertility.
To evaluate the fertilizing capacity of spermatozoa from elderly men, ejaculates from 29 older fathers (mean age 503 years)
were compared with those from 35 younger fathers (mean age 32.2 years). In addition to conventional semen parameters, sperm
functions were studied that have been reported to be positively correlated with the fertilization rate: progressive motility,
acrosin activity, inducible acrosome reaction, and chromosome condensation. Sperm concentration and follicle stimulating hormone
concentration differed significantly in both groups. With regard to sperm functions there were no differences between older
men and younger men, except for decreased sperm motility in the older group which, however, reached nearly normal values according
to World Health Organization criteria. Decreased fertility of older couples is obviously more dependent on the age of the
female partner. The significance of genetic risks remains to be clarified, especially when methods of assisted reproduction
are applied.
To determine the effect of age on sperm fecundability using oocyte donation as an in vivo model.
Oocyte donation and IVF programs at the Instituto Valenciano de Infertilidad.
Retrospective study in which four groups of oocyte donation cycles were established according to age of the male providing the semen sample: group 1 (n = 31) < 30 years; group 2 (n = 195) 31 to 40 years; group 3 (n = 98) 41 to 50 years; group 4 (n = 21) > 51 years, the oldest being 64 years. All donated oocytes were obtained from patients < 35 years old.
Male age, sperm characteristics (volume, concentration, motility, morphology), fertilization, embryo quality, pregnancy, implantation, and abortion rates among recipients.
Similar sperm characteristics in fresh as well as after preparation for IVF were observed among males of different ages. Fertilization, embryo quality, pregnancy, and implantation were similar among the established groups. The mean age of the females included in each group significantly increased from group 1 to group 4.
Age (up to 64 years) does not affect sperm characteristics or its ability to fertilize human eggs. Similarly, embryo development in vitro as well as implantation in recipient uteri are not affected by age of the male providing the semen sample.
In order to evaluate possible age-dependent influences on male infertility, semen parameters, sex hormone levels and pregnancy rates were compared retrospectively in three groups of men attending our fertility clinic: group A: 39 patients > 50 years. Group B (39 patients < 30 years) was established as the 'standard infertile patient' seen in our Institute. These patients were matched with patients of group A according to the year of their first visit to the clinic. Group C: 39 young patients (< 30 years) who were selected on the basis of their wives' advanced age. The frequency of sexual intercourse in group A was significantly lower compared to group C. The period of sexual abstinence was longer in group A than in group B. Ejaculate volume and sperm motility in group A were lower compared to groups B and C. The differences in other semen parameters were only minor. The differences in serum levels of testosterone and FSH were significant between group A and groups B and C. Pregnancies were reported in 6 of 26 couples from group A (duration of infertility: mean 79 months, range 16-187), in 17 of 28 couples from group B (duration of infertility; mean 54 months, range 16-104) and in nine of 30 couples from group C (duration of infertility; mean 66 months, range 25-125). Since the infertility pattern of the older patients desiring offspring was not significantly different from that of younger patients, it is concluded that the age of the female partner, rather than the age of the husband, is most important in determining the fertility chances of couples presenting with infertility.
Oestradiol and progesterone profiles from naturally occurring conception and exposed non-conception cycles were compared to assess the impact of natural variation in concentrations of ovarian steroid hormones on female fecundity. In a prospective, longitudinal study, 24 women collected saliva samples twice daily and recorded intercourse for up to 1 year or until a pregnancy was clinically confirmed. Oestradiol and progesterone concentrations were measured by a salivary radioimmunoassay. Average mid-follicular oestradiol concentrations were significantly higher in conception than in non-conception cycles (12.6 +/- 1.7 versus 8.5 +/- 0.6 pmol/l, P < 0.01). A separate analysis, including only cycles from those women who contributed both conception and non-conception cycles, demonstrated an even more pronounced difference in mid-follicular oestradiol concentrations, not just for conception and non-conception cycles as groups (14.5 +/- 2.3 versus 6.5 +/- 0.7 pmol/l, P < 0.001), but also between the conception and average non-conception concentrations of individual women. Among these women, relative mid-follicular oestradiol concentration was highly correlated with the probability of successful conception. In addition, relative body weight was significantly positively correlated with mid-follicular oestradiol concentration. These findings indicate that variation in follicular development, reflected in variation in follicular oestradiol concentrations, is an important indicator of fecundity.
This study analyses the influence of female and male patient age and human menopausal gonadotrophin (HMG) requirements on
clinical pregnancy rates and live birth rates with ovulation stimulation using HMG in combination with intrauterine insemination
(IUI). In this study, 363 consecutive HMG/IUI treatment cycles in 184 patients carried out at a university fertility centre
were analysed in a retrospective fashion. The main outcomes measured were clinical pregnancy rates and live birth rates. Increased
female partner age (> or = 35) and male partner age (> or = 40) were found to negatively influence pregnancy rates with HMG/
IUI therapy. In addition, this study demonstrated a critical threshold of HMG requirements beyond which pregnancy did not
occur. No pregnancies occurred in treatment cycles requiring > 25 ampoules (1875 IU) of menotrophins to achieve follicular
maturity, irrespective of patient age. In conclusion, female partner age, male partner age, and HMG requirements all significantly
influence pregnancy rates with HMG/IUI therapy.
Introduction:
Growing evidence of reproductive effects associated with occupational and environmental agents has created the need for research with sensitive and well validated methods. There is a complex relation between manifest effects and underlying pathogenic processes. Conceptions will on average tend to be delayed in a population exposed to an agent that causes embryonic damage, an increase in germ cell mutations, or decreased fertility.
Studying time to pregnancy:
Time to pregnancy can be used to measure the degree of delay in conceiving, across the whole continuum of biological fertility, in either men or women. The distribution of time to pregnancy largely reflects a sorting process, as the more fertile couples become progressively less well represented with the passage of time. The basic research strategy is comparison of the time to pregnancy within groups defined by their exposures, allowing for potential confounding factors relating not only to the study subject but also to his or her partner.
Measurement and validity:
Prospective and retrospective methods are available, and each has strengths and weaknesses. Prospective studies have some theoretical advantages, but have unrepresentative populations and problems of feasibility and cost. Retrospective assessment of time to pregnancy is feasible with a short questionnaire, without intruding into sensitive areas of respondents' lives, with good validity at the group level, and without the necessity of large populations. Potential biases have been identified that can be minimised by careful design and analysis; the principal remaining problem is difficulty in obtaining exposure data retrospectively.
To determine whether the age-related decline in fertility is due to degenerative oocytes or to aneuploidy.
Retrospective.
Fertility center of a public and tertiary institution.
One hundred fifty-one women (ages 24 to 44 years) undergoing 158 cycles of conventional IVF or IVF with intracytoplasmic sperm injection (ICSI) between January 1993 and December 1995 were divided into three age groups (group 1, < or = 34 years; group 2, between 35 and 39 years; and group 3, > or = 40 years). They were selected on the basis of available oocytes that remained unfertilized after IVF and that had analyzable chromosomes.
Standard pituitary down-regulation and ovarian stimulation with FSH and hMG were done for both IVF and ICSI patients. In addition, all patients were given luteal phase support with P, administered orally, via pessaries, or by IM injections from the day of transfer.
Fertilization rates and pregnancy rates (PRs), and cytogenetic analyses of unfertilized oocytes.
Although fertilization rates were not different among women in groups 1, 2, and 3 (50.9%, 49.3%, and 37.9%, respectively), PRs were significantly lower between groups 1 and 3 (43.2% versus 14.3%). A total of 383 oocytes were examined, of which 287 (75%) could be karyotyped. Of these, 201 oocytes showed a normal 23,X karyotype (70%), 40 (13.9%) were aneuploid, 24 (8.4%) were diploid, 12 (4.2%) had structural aberrations, and 13 (4.5%) had single chromatids only. No increase in the aneuploidy rate was detected between groups 1 and 2 (14.8% versus 12.4%). However, highly significant differences in the rate of oocyte chromosome degeneration, characterized by chromosomes splitting into unassociated chromatids, were observed with increasing age (group 1, 23.7%; group 2, 52.0%; and group 3, 95.8%).
It seems that the age-related decline in fertility may be due more to degenerative oocytes than to aneuploidy. A decline in the number of oocytes retrieved with age may be of less importance than the decline in oocyte quality. Women in the older age group have a higher chance of achieving pregnancy from ovum-donation programs than by persisting in using their own aged oocytes, which have a very poor prognosis for success.
Variations of the male partner fertility according to his age are difficult to study, because of bias represented by some decrease of both sexual activity and fecundity of the female partner beyond 35 years old. The few studies which are available show that sperm concentration as percentage of normal forms, are stable with age. The percentage of motility is the only parameter which decreases systematically with age according to all studies. Nevertheless, sperm fertilizing capacity does not seem to be decreased. FIVNAT data allow to analyse almost 30,000 IVF cycles for tubal sterility; they confirm the absence of an important alteration of semen characteristics with age. Despite a significant decrease--even moderate--of the mean fertilization rates, the pregnancy rates remain roughly constant for a given range of maternal age.