The effect of insemination/injection time on the results of IVF and ICSI.

BACKGROUND: The aim of this study was to investigate whether a pre-incubation time between oocyte retrieval and insemination or injection had any effect on the success rate of IVF or intracytoplasmic sperm injection (ICSI). Based on previously published data, many laboratories retain a time interval of several hours between oocyte retrieval and insemination/injection. In our setting, insemination and injection times are dependent only on the laboratory workload. METHODS: Totals of 881 IVF and 432 ICSI cycles performed between 1997 and 1999 were analysed retrospectively. Oocyte retrieval occurred 36 h after human chorionic gonadotrophin administration, and insemination or injection took place 1--7 or 0.5--8 h after oocyte retrieval respectively. RESULTS: No statistically significant differences were found between these time periods and outcome of IVF and ICSI with respect to fertilization rate, embryo quality, implantation rate, abortion and ongoing pregnancy rates, except for the abortion rate after IVF. As this finding may be due to chance and no differences were found in the ongoing pregnancy rates, this finding was considered to be of less importance. CONCLUSIONS: If laboratory control and efficiency demands early insemination or injection, it could be performed without reservation.

External validation of the templeton model for predicting success after IVF.

This study aimed to externally validate the prognostic model presented by Templeton in 1996 for live births resulting from IVF treatment. Data were used from the University Hospital, Nijmegen, The Netherlands, from March 1991 to January 1999. The predictive capacity of the model in our population discriminated between those women with a low probability of success and those with a relatively high probability. Despite these encouraging findings, our data show that implementation of the model in clinical decision-making remains difficult. The Templeton model is not applicable or usable in daily clinical practice, because the model did not give more information about the prognosis for the vast majority of the patients. Therefore, the search for better prognostic factors resulting in better predictive models should continue.

Cumulative probability of achieving an ongoing pregnancy after in-vitro fertilization and intracytoplasmic sperm injection according to a woman's age, subfertility diagnosis and primary or secondary subfertility.

The aim of this study was to estimate reliable cumulative probabilities of achieving an ongoing pregnancy after successive in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles, according to a woman's age, subfertility diagnosis and primary or secondary subfertility. Therefore reasons for quitting treatment without achieving an ongoing pregnancy were taken into account. Moreover, we studied whether there were trends in cumulative probabilities after adjustment for potential confounding effects of the other two characteristics, duration of subfertility, year of first treatment and reason for quitting treatment. In total, 2984 IVF/ICSI cycles were performed in 1315 couples at the University Hospital Nijmegen, The Netherlands, between 1991 and 1998. The 'realistic' cumulative probability of achieving an ongoing pregnancy was 54.5% after five consecutive IVF/ICSI cycles, which was about 10% lower (absolute value) than the optimistic probability calculated by life-table analysis and about 10% higher (absolute value) than the most pessimistic estimate. Women of 35 years or younger had a higher probability of achieving an ongoing pregnancy than the older women. As ICSI is now an option, there were no obvious differences between the subfertility diagnosis subgroups. The cumulative probability after the first two IVF/ICSI cycles was higher in women with secondary subfertility than in those with primary subfertility; this advantage disappeared after further treatment. These trends remained valid after adjustment for confounding factors.

Studying seasonality by using sine and cosine functions in regression analysis.

STUDY OBJECTIVE: A statistical test that allows for adjustment of confounding can be helpful for the study of seasonal patterns. The aim of this article is to supply a detailed description of such a method. An example of its application is given. DESIGN: A statistical test is presented that retains the information on the connection of time periods by describing the seasonal pattern as one sine and one cosine function. Such functions can be included into a regression model. The resulting form of the seasonal pattern follows a cosine function with variable amplitude and shift. MAIN RESULTS: The test is shown to be applicable to test for seasonality. Not only one cosine function per time period, but also a mixture of cosine functions can be used to describe the seasonal pattern. Adjustment for confounding effects is possible. CONCLUSIONS: This method for studying seasonal patterns can be applied easily in a regression model. Adjusted prevalences and odds ratios can be calculated.

External validation of prognostic models for ongoing pregnancy after in-vitro fertilization.

This study aimed to validate prognostic models for predicting ongoing pregnancy after the first and second in-vitro fertilization cycles. Models were developed using data from the University Hospital, Nijmegen, 1991-1994 and tested using more recent data from the same centre and data from two other centres. Although the variables included in the models seemed plausible, the predictions of the models were unsatisfactory. The models did not discriminate between women who had achieved pregnancy and women who did not achieve pregnancy; neither could they indicate which women had a (very) low probability of ongoing pregnancy. Taking into account the success rate of a specific clinic or the success rate during a specific period did not show any advantage. The predictions were even inaccurate in the same hospital during another period. It is obvious that these prognostic models should not be used. This study shows the importance of validating prognostic models before their implementation in clinical practice.

Seasonal variation in the prevalence of Down syndrome at birth: a review.

STUDY OBJECTIVE: Many studies on seasonality in Down syndrome (DS) have been performed and have come to different conclusions. It is suggested that seasonal variation in hormone production by the hypothalamus-pituitary-ovarian axis just before ovulation leads to seasonality in conception rates of DS. This study aimed to determine whether there is seasonal variation in the prevalence of DS at birth as a proxy for seasonality in DS at conception. DESIGN: All the English and Dutch articles on this topic were reviewed. Articles published between 1966 and January 1996 were traced by Medline, and by the reference lists. MAIN RESULTS: Twenty articles met the criteria for inclusion. Although seven of these studies reported seasonality in DS prevalence, no consistent seasonal pattern was found in DS at birth in these studies, or in the remaining studies. A seasonal pattern could not have been masked by the effects of maternal age, induced abortions, shortened gestation, or misclassification of DS. CONCLUSION: Seasonality in the prevalence of DS at birth does not exist. Evidence did not support the suggestion that DS occurrence is related to seasonality in hormone production.

The impact of the woman's age on the success of standard and donor in vitro fertilization.

OBJECTIVE: To study the effect of the age of the woman who provides the oocytes or who receives the embryos on results of IVF-ET. DESIGN: Historical cohort study. Multivariate regression analysis was used to study the age effect continuously and after adjustment for confounding. SETTING: Patients of the University of Southern California, Los Angeles, California. PATIENT(S): Couples who underwent standard (n = 277) or donor IVF-ET (n = 294) between January 1991 and July 1995. INTERVENTION(S): One cycle of standard or donor IVF-ET. MAIN OUTCOME MEASURE(S): Successive IVF outcomes from number of oocytes to ongoing pregnancy and several measures of pregnancy loss. RESULT(S): The number of oocytes decreased with aging of the oocyte provider. More women who received oocytes from donors aged 20 to 23 years had at least one good embryo transferred than women who received oocytes from older donors. The age of the woman who received the embryos had no effect on IVF outcomes. In women > 40 years who underwent standard IVF, the probability of pregnancy decreased. No such relationships were observed for donor IVF, but all the oocyte donors were younger. CONCLUSION(S): An age effect for ongoing pregnancy was only found in women > 40 years who underwent standard IVF independent of the lower number of oocytes and suggests decreasing oocyte quality.

Seasonal variation in the time to pregnancy: a secondary analysis of three Danish databases.

Three Danish databases were reanalysed to investigate seasonal variation in the time to pregnancy. Information was available on cohorts of women selected on the basis of union membership or residence in a given area: textile workers in Denmark (with 1,053 first and 1,771 second pregnancies), pharmacy assistants in Denmark (with 734 first and 725 second pregnancies) and pregnant women in the 36th week of pregnancy in two Danish cities (with 3,657 first and 3,526 second pregnancies). The influence of the season was of primary interest, because it is presumed to cause impaired ovarian function and hence a prolonged time to pregnancy. Furthermore, we studied whether the waiting time was prolonged in other situations with possibility of decreased ovarian function: in young and older women. In genera, seasonality in the time to pregnancy based on the time of conception was found with a higher chance of a prolonged waiting time before conceiving in February-April and a lower chance of a prolonged waiting time before conceiving in August-October. This association was not distorted by the age of the women or diabetes mellitus. A prolonged time to pregnancy was found in women of 30 years or older. Women of 20 years or younger did not have a prolonged waiting time, but most of them were well beyond the age of menarche and thus beyond the period of impaired ovarian function. On a population level, there was evidence for seasonality in the time to pregnancy, which is compatible with seasonal variation in pregnancy planning as well as with biological influences.

Prognostic models for the probability of achieving an ongoing pregnancy after in-vitro fertilization and the importance of testing their predictive value.

The aim of this study was to create reliable models to predict the probability of achieving an ongoing pregnancy during in-vitro fertilization (IVF) treatment: model A, at the start of the first treatment, model B at the time of embryo transfer, and model C, during the second treatment at the end of the first IVF treatment. Prognostic models were created using data from the University Hospital Nijmegen (n = 757) and applied to the data from the Catharina Hospital Eindhoven (n = 432), The Netherlands, to test their predictive performance. The predictions of model B (made at time of embryo transfer) were fairly good (c = 0.672 in the test population). For instance, 93% of the patients who had a predicted probability of achieving an ongoing pregnancy of < 10% did not achieve an ongoing pregnancy. However, the predictions of the other two models (A and C) for Eindhoven were less reliable. The predictive value of model C was fairly high in Nijmegen (c = 0.673). Its poor performance in the test population may be explained partly by differences in effectiveness of the ovulation stimulation protocols and the decision about when to discontinue the cycle. Thus, before using prognostic models at an IVF centre, their reliability at that specific centre should be tested.

Is there seasonality in human ovulation?

To study seasonality in human ovulation in a direct way, we measured the occurrence of ovulation in infertile patients with spontaneous menstrual cycles (< 6 weeks) who visited the fertility clinic at the University Hospital Nijmegen in the Netherlands for the first time in 1991 or 1992 (n = 407). Ovulation was detected using serial transvaginal ultrasound and midluteal progesterone measurement and was performed during one screening cycle. The frequency of ovulatory cycles per month varied from 73% to 93% (not statistically significant). No seasonal pattern in ovulation was found in subfecund Dutch women with spontaneous menstrual cycles. This finding was not confounded by the effects of age of the women, body mass index, or disorders that could influence ovulation.

Seasonal variation in the time to pregnancy: avoiding bias by using the date of onset.

To study seasonality in human fecundability, measured indirectly by time to the first pregnancy, we used data from 18,970 French-Canadian women who married for the first time during the 17th or 18th century. The time to pregnancy was approximated by the interval between marriage and first birth minus 38 weeks. We used the week of marriage and the week of conception as references to study seasonality. We found a minor seasonal pattern in time to pregnancy when using the week of marriage as a reference. The proportions of women with a short time to pregnancy were highest during December-January and June-July, indicating that these may be the most fecund periods. In contrast, we found an obvious seasonal pattern when using the date of conception as a reference. This pattern can be largely explained by a strong seasonal pattern in pregnancy planning (in this case, in marriages). When studying seasonal variation in the time to pregnancy, the date of onset of the time to pregnancy should be used as reference, not the date of conception. Otherwise, results will be biased owing to seasonality in pregnancy planning. The same is true for studies on seasonally bound exposures in relation to time to pregnancy.

A more realistic approach to the cumulative pregnancy rate after in-vitro fertilization.

As most studies overestimate the cumulative pregnancy rate, a method is proposed to estimate a more realistic cumulative pregnancy rate by taking into account the reasons for an early cessation of treatment with in-vitro fertilization (IVF). Three methods for calculating cumulative pregnancy rates were compared. The first method assumed that those who stopped treatment had no chance at all of pregnancy. The second method, the one used most often, assumed the same probability of pregnancy for those who stopped as for those who continued. The third method assumed that only those who stopped treatment, because of a medical indication, had no chance at all of pregnancy and that the others who stopped had the same probability of pregnancy as those who continued treatment. Data were used from 616 women treated at the University Hospital Nijmegen, Nijmegen, The Netherlands. The cumulative pregnancy rates after five initiated IVF cycles for the three calculation methods were in the ranges 37-51% for the positive pregnancy test result, 33-55% for a clinical pregnancy and 30-56% for an ongoing pregnancy. As expected, the first method underestimated the cumulative pregnancy rate and the second overestimated it. The third method produced the most realistic cumulative pregnancy rates.

Comparison of parameters to study seasonality in reproductive outcome.

This report compares validity, precision and convenience of three frequently used parameters used to describe seasonality in reproductive outcome: prevalence, index and ratio observed versus expected. Each has its advantages and disadvantages; the choice of the parameter depends on the aim of the study. It is advisable to report the number of cases and referents per month, because all three parameters can be derived from this information.

Seasonality in the results of in-vitro fertilization.

Seasonal variation has been found in various reproductive outcomes. As known causes for reducing the rate of success of in-vitro fertilization (IVF) cannot explain all the variation in IVF results, we studied whether the season had any additional explanatory power. The study population consisted of 1126 women who were treated for the first time with IVF at the University Hospital in Nijmegen, The Netherlands, between 1987 and 1993. Only first IVF cycles were analysed. After adjusting for confounding by the age of the woman, type of infertility, indication for IVF and year of aspiration, some seasonal variation was observed in the fertilization rate, embryo quality, pregnancy rate and birth rate.

Effect of a monounsaturated diet vs. a polyunsaturated fatty acid-enriched diet on blood pressure in normotensive women and men.

The effect on blood pressure of monounsaturated and (n-6)polyunsaturated fatty acids was studied under strict dietary control in normotensive subjects. For 17 days 31 women and 27 men received a control diet providing 19.3% of energy as saturated fat. Then subjects were randomized over two test diets: one diet provided 15.1% of energy from monounsaturated and 7.9% from polyunsaturated fatty acids ('mono diet'), and the other diet provided 10.8% from monounsaturated and 12.7% from polyunsaturated fatty acids ('poly diet'). Saturated fat intake was now 12.8% on both diets. Mean blood pressure at the end of the control period was 116/69 mmHg for the mono group and 117/73 mmHg for the poly group. After 5 weeks on the test diet, blood pressure was 115/67 mmHg for the mono group and 117/72 mmHg for the poly group (difference in changes between the two diet groups was not significant). These findings suggest that at a high fat intake, linoleic acid, when providing more than 7.9% of energy intake, does not influence blood pressure relative to oleic acid in normotensive women and men.