To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART) and provide recommendations for their management, and to review investigations in the assessment of ovarian aging.
This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility.
The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility.
Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (ovarian aging, ovarian reserve, advanced maternal age, advanced paternal age, ART). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010.
The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table).
Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for assisted reproductive technology.
1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. (II-2A) 2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive. (III-B) 3. Ovarian reserve testing may be considered for women = 35 years of age or for women 40 years of age. Women > 40 years should consider IVF if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation. (II-2B) 6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman's own eggs. (II-2B) 7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established. (II-2A) 8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40. (III-B) 9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small. (II-2C).
Evolutionary theory of senescence emphasizes the importance of intense selection on early reproduction owing to the declining force of natural selection with age that constrains lifespan. In humans, recent studies have, however, suggested that late-life mortality might be more closely related to late rather than early reproduction, although the role of late reproduction on fitness remains unclear. We examined the association between early and late reproduction with longevity in historical post-reproductive Sami women. We also estimated the strength of natural selection on early and late reproduction using path analysis, and the effect of reproductive timing on offspring survival to adulthood and maternal risk of dying at childbirth. We found that natural selection favoured both earlier start and later cessation of reproduction, and higher total fecundity. Maternal age at childbirth was not related to offspring or maternal survival. Interestingly, females who produced their last offspring at advanced age also lived longest, while age at first reproduction and total fecundity were unrelated to female longevity. Our results thus suggest that reproductive and somatic senescence may have been coupled in these human populations, and that selection could have favoured late reproduction. We discuss alternative hypotheses for the mechanisms which might have promoted the association between late reproduction and longevity.
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Centre for Reproductive Biology in Uppsala, PO Box 7023, SE-750 07 Uppsala, Sweden. email@example.com
The incidence of normal and atypical progesterone profiles in Swedish dairy cows was studied. Data were collected from an experimental herd over 15 yr, and included 1,049 postpartum periods from 183 Swedish Holstein and 326 Swedish Red and White dairy cows. Milk progesterone samples were taken twice weekly until initiation of cyclical ovarian activity and less frequently thereafter. Progesterone profiles were 1) normal profile: first rise in milk progesterone above the threshold value before d 56 postpartum, followed by regular cyclical ovarian activity (70.4%); 2) delayed onset of cyclical ovarian activity: low milk progesterone the first 56 d postpartum (15.6%); 3) cessation of cyclical ovarian activity: ovarian activity resumed within 56 d postpartum, but ceased for a period of 14 d or more (6.6%); and 4) prolonged luteal phase: ovarian activity resumed within 56 d postpartum, but milk progesterone remained elevated in the nonpregnant cow for a period of 20 d or more (7.3%). Swedish Holsteins had 1.5 times higher risk of atypical profile than Swedish Red and Whites. Risk of atypical profiles was 0.5 and 0.7 times lower for older cows compared with first-parity cows; 2.3 times higher for cows in tie-stalls compared with those in loose housing; 2.6 times higher for cows calving during winter compared with summer; 0.5 times lower for cows in earlier (1994-1999) calving-year groups compared with the most recent (2000-2002); 2.5 times higher for cows with planned extended calving interval compared with conventional calving interval; and 2.2 times higher for an atypical profile in previous lactation compared with a normal profile. Cows with atypical profiles had a 15-d increase in interval from calving to first artificial insemination and an 18-d increase in interval from calving to conception. Progesterone samples taken within the first 60 d postpartum were used to calculate the percentage of samples above the threshold value of luteal activity. This measure had a significantly different mean in profiles and can be used to separate delayed onset of cyclical ovarian activity profiles and prolonged luteal phase profiles from normal. Thereby, it may be a more effective tool than measurements based only on the onset of ovarian cyclical activity in genetic evaluation of early postpartum fertility in dairy cows.
A survey of blood selenium (Se) concentrations in Norwegian Red heifers and dry period cows was conducted to reveal possible association to management, feeding, health and fertility. Selenium contents were determined in 254 herd blood samples consisting of pooled samples from individual non-lactating animals from herds in 5 counties. The Se concentrations showed a normal distribution with mean 0.09 microg Se/g blood, with a standard deviation (SD) of 0.05, and ranged from 0.02 to 0.23 microg/g, with 50 % of the samples being between 0.06 and 0.11 microg/g. The herds with Se concentrations below 0.06 microg/g were smaller (21.4 +/- 8.7 cow-years) than those with Se levels above 0.11 microg/g (27.5 +/- 14.1 cow-years) (P
In most societies, women at age 39 with higher levels of education have fewer children. To understand this association, we investigated the effects of childbearing on educational attainment and the effects of education on fertility in the 1964 birth cohort of Norwegian women. Using detailed annual data from ages 17 to 39, we estimated the probabilities of an additional birth, a change in educational level, and enrollment in the coming year, conditional on fertility history, educational level, and enrollment history at the beginning of each year. A simple model reproduced a declining gradient of children ever born with increasing educational level at age 39. When a counterfactual simulation assumed no effects of childbearing on educational progression or enrollment (without changing the estimated effects of education on childbearing), the simulated number of children ever born decreased very little with increasing completed educational level, contrary to data. However, when another counterfactual simulation assumed no effects of current educational level and enrollment on childbearing (without changing the estimated effects of childbearing on education), the simulated number of children ever born decreased with increasing completed educational level nearly as much as the decrease in the data. In summary, in these Norwegian data, childbearing impeded education much more than education impeded childbearing. These results suggest that women with advanced degrees have lower completed fertility on the average principally because women who have one or more children early are more likely to leave or not enter long educational tracks and never attain a high educational level.
In highly seasonal environments, offspring production by vertebrates is timed to coincide with the annual peak of resource availability. For herbivores, this resource peak is represented by the annual onset and progression of the plant growth season. As plant phenology advances in response to climatic warming, there is potential for development of a mismatch between the peak of resource demands by reproducing herbivores and the peak of resource availability. For migratory herbivores, such as caribou, development of a trophic mismatch is particularly likely because the timing of their seasonal migration to summer ranges, where calves are born, is cued by changes in day length, while onset of the plant-growing season on the same ranges is cued by local temperatures. Using data collected since 1993 on timing of calving by caribou and timing of plant growth in West Greenland, we document the consequences for reproductive success of a developing trophic mismatch between caribou and their forage plants. As mean spring temperatures at our study site have risen by more than 4 degrees C, caribou have not kept pace with advancement of the plant-growing season on their calving range. As a consequence, offspring mortality has risen and offspring production has dropped fourfold.
Prior investigations suggest that women living with HIV (WLWH) experience higher rates of anxiety compared to the general population. This study investigates correlates of anxiety among 361 WLWH of reproductive age in Ontario, Canada who completed a series of self-reported measures. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS-A). Thirty-seven percent of the sample had high anxiety (HADS-A = 11). HIV-related stigma, reproductive health-related worries, having experienced judgment from family and friends for trying to become pregnant and use of antiretrovirals were associated with high anxiety. Being in a romantic/sexual relationship, older age, and undetectable viral load were associated with low anxiety. Findings highlight the importance of HIV-related stigma and having experienced judgment from family and friends for trying to become pregnant as important predictors of anxiety among WLWH of reproductive age. There is a need for appropriate management of anxiety and stigma for WLWH of childbearing age.
To examine the costs to the public health care system of couples in medically assisted reproduction.
Longitudinal cohort study of infertile couples initiating medically assisted reproduction treatment.
Specialized public fertility clinics in Denmark.
Seven hundred and thirty-nine couples having no child at study entry and with data on kind of treatment and live birth (yes/no) for each treatment attempt at the specialized public fertility clinic.
Treatment data for medically assisted reproduction attempts conducted at the public fertility clinics were abstracted from medical records. Flow diagrams were drawn for different standard treatment cycles and direct costs at each stage in the flow charts were measured and valued by a bottom-up procedure. Indirect costs were distributed to each treatment cycle on the basis of number of visits as basis. Costs were adjusted to 2012 prices using a constructed medical price index.
Live birth, costs.
Total costs per live birth in 2012 prices were estimated to 10,755€. Costs per treated couple - irrespective of whether the treatment was terminated by a live birth or not - were estimated at 6607€. Costs per live birth of women
In studies of the fertility of migrants in which the data are confined to the migrants only, estimation bias will normally appear in comparisons of childbearing before and after migration. The same issue arises in studies of union formation before and after first birth, marriage formation before and after home purchase, and in any other comparison of behaviour before and after an index event if one confines the study only to those who have experienced the index event. It is normally better to avoid analysis of behaviour before the index event because such analysis actually conditions on the later arrival of the index event. In this paper, we provide graphical and mathematical representations of this problem and show how one can get a meaningful (unconditional) comparison of behaviour before and after the index event provided the data contain enough information for both sub-periods. Otherwise, the analyst should refrain from making a comparison of this nature.