Egbert R. te Velde

Effects of varicocele treatment in adolescents: a randomized study

OBJECTIVE To study the effects of varicocele treatment on testicular function in adolescents. DESIGN A prospective controlled study in 88 randomly selected adolescents. SETTING All participants were referred to the fertility outpatient clinic of our university hospital. PARTICIPANTS All participants with a varicocele were randomly assigned into two groups. Group 1 (n = 33) was not treated, whereas group 2 (n = 34) was treated. A similar group of healthy volunteers without a varicocele served as a control group (group 3, n = 21). INTERVENTIONS Testes volumes were measured at intake and during follow-up using an orchiometer. Semen analysis was performed according to standard procedures both at intake and after 1 year of follow-up. Serum hormone levels were determined at intake using a radioimmunoassay. Treatment was performed by means of transcatheter embolization of the left testicular vein. MAIN OUTCOME MEASURES Testes volumes and semen quality at intake and after 1 year of follow-up were compared within and between the three groups. Hormonal parameters were determined at intake only. RESULTS Before treatment, the mean left testis volume in groups 1 (n = 26) and 2 (n = 27) (20.0 mL; 95% confidence interval [CI]: 18.2 to 21.8 and 21.6 mL; 95% CI: 19.4 to 23.8, respectively) were significantly smaller than those in the control group (n = 19) (24.5 mL; 95% CI: 22.7 to 26.4). During follow-up, left testis volumes of the treated group were comparable with those in the control group (24.2 mL; 95% CI: 22.2 to 26.1 and 24.8 mL; 95% CI: 23.0 to 26.7 respectively) and significantly (P < 0.001) different from the untreated group (20.3 mL; 95% CI: 18.8 to 21.8). A significant increase in left (P < 0.01) as well as right (P < 0.05) testis volume was observed after treatment. Semen parameters before treatment were not significantly different between the three groups. Sperm concentration increased significantly (P < 0.01) from 47.4 x 10(6)/mL (95% CI: 42.5 to 53.3) to 68.9 x 10(6)/mL (95% CI: 50.6 to 87.2) in the treated group, whereas semen quality in the untreated and control groups did not change. Although both testes volumes and sperm concentration improved in the treated group, these phenomena were not consistently correlated to each other. CONCLUSIONS Although not apparent in all adolescents, varicocele correction resulted in an increase in left testis volume and sperm concentration. At this moment, it is not clear if early preventive treatment of varicocele in adolescents, in time, will have a positive effect on testicular function.

The prediction of the chance to conceive in subfertile couples

OBJECTIVE To develop a model that can predict the chance to conceive spontaneously in subfertile couples. DESIGN In a cohort study, a consecutive series of patients consulting infertility was followed up. We related information from previous history, physical examination, postcoital tests (PCT), semen analyses, and sperm penetration meter tests with the occurrence of a spontaneous pregnancy. SETTING Fertility center in a university hospital. PATIENTS Nine hundred ninety-six couples consulting for infertility due to cervical hostility, male subfertility, or unexplained infertility. INTERVENTIONS None. MAIN OUTCOME MEASURE(S) Time between intake and occurrence of the first spontaneous pregnancy. RESULTS Information from the previous history (duration of infertility, primary or secondary female infertility, age of the woman, fertility problems in males family), the percentage motile sperm in the first semen analysis, and the result of the first PCT are sufficient to predict the chance to conceive. A pocket chart is presented for easy use of the model. CONCLUSIONS With a limited amount of diagnostic information, the chance to conceive spontaneously can be predicted.

Age-dependent decrease in embryo implantation rate after in vitro fertilization

OBJECTIVE To investigate the relation between the implantation rate per embryo after replacement in IVF-ET in relation to female age. DESIGN Retrospective study using linear and biphasic models in a multivariate analysis. SETTING Academic tertiary care institution. INTERVENTION(S) In vitro fertilization-ET and determination of gestational sacs at 6 to 7 weeks of pregnancy buy ultrasound. MAIN OUTCOME MEASURE(S) Implantation rate as defined by the number of gestational sacs per embryo replaced. RESULT(S) Womans age and embryo morphology were strongly related to the implantation rate, indication for IVF-ET and cycle rank number also were related significantly but less strongly. A linear model was built describing the decrease in implantation rate with age, resulting in a decrease of approximately 7%. A biphasic model was tested also and performed significantly better, resulting in a yearly decrease of > 20% after 37 years of age. CONCLUSION(S) The most important independent factors related to the ability of embryos to implant are female age and embryo morphology. The best way to describe the relation with female age is biphasic model with a discontinuity at approximately 37 years of age.

The effect of in vitro fertilization on birth rates in western countries

BACKGROUND We will assess to what extent in vitro fertilization (IVF) is effective in increasing the number of births overall and whether earlier application of IVF will increase this number. METHODS We simulate 100 000 women trying for their first and second child. Natural and IVF pregnancy rates and infertility rates are age-dependent and based on published data. The age at which women start trying for their first child is based on the Netherlands 2002 data. Three cycles of IVF are given during a 12-month period after 1 or 3 years of trying to conceive unsuccessfully. Main outcome measures are live born deliveries and children, both naturally conceived or after IVF, as well as numbers of singletons, twins and triplets, the total fertility rate (TFR) and the number of IVF cycles performed. RESULTS Full access to IVF after 3 years increases the TFR by 0.08 children. Applying IVF after 1 year leads to an additional TFR increase of 0.04, with double the number of IVF cycles and twin and triplet children, and a shift from naturally conceived children to IVF children. CONCLUSIONS Full access to IVF after 3 years is important. It does increase the TFR. Early availability of IVF would further increase the TFR, but with side-effects and high costs.

Is human fecundity declining in Western countries

Since Carlsen and co-workers reported in 1992 that sperm counts have decreased during the second half of the last century in Western societies, there has been widespread anxiety about the adverse effects of environmental pollutants on human fecundity. The Carlsen report was followed by several re-analyses of their data set and by many studies on time trends in sperm quality and on secular trends in fecundity. However, the results of these studies were diverse, complex, difficult to interpret and, therefore, less straightforward than the Carlsen report suggested. The claims that population fecundity is declining and that environmental pollutants are involved, can neither be confirmed nor rejected, in our opinion. However, it is of great importance to find out because the possible influence of widespread environmental pollution, which would adversely affect human reproduction, should be a matter of great concern triggering large-scale studies into its causes and possibilities for prevention. The fundamental reason we still do not know whether population fecundity is declining is the lack of an appropriate surveillance system. Is such a system possible? In our opinion, determining total sperm counts (as a measure of male reproductive health) in combination with time to pregnancy (as a measure of couple fecundity) in carefully selected populations is a feasible option for such a monitoring system. If we want to find out whether or not population fecundity will be declining within the following 20-30 years, we must start monitoring now.

Advanced maternal age, short interpregnancy interval, and perinatal outcome

OBJECTIVE The purpose of this study was to evaluate whether the association between short interpregnancy intervals and perinatal outcome varies with maternal age. STUDY DESIGN We performed a retrospective cohort study among 263,142 Dutch women with second deliveries that occurred between 2000 and 2007. Outcome variables were preterm delivery (<37 weeks of gestation), low birthweight in term deliveries (<2500 g) and small-for-gestational age (<10th percentile for gestational age on the basis of sex- and parity-specific Dutch standards). RESULTS Short interpregnancy intervals (<6 months) was associated positively with preterm delivery and low birthweight, but not with being small for gestational age. The association of short interpregnancy interval with the risk of preterm delivery was weaker among older than younger women. There was no clear interaction between short interpregnancy interval and maternal age in relation to low birthweight or small for gestational age. CONCLUSION The results of this study indicate that the association of short interpregnancy interval with preterm delivery attenuates with increasing maternal age.

Predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation : population based study of linked cycle data from 113 873 women

Objective To develop a prediction model to estimate the chances of a live birth over multiple complete cycles of in vitro fertilisation (IVF) based on a couple’s specific characteristics and treatment information. Design Population based cohort study. Setting All licensed IVF clinics in the UK. National data from the Human Fertilisation and Embryology Authority register. Participants All 253 417 women who started IVF (including intracytoplasmic sperm injection) treatment in the UK from 1999 to 2008 using their own eggs and partner’s sperm. Main outcome measure Two clinical prediction models were developed to estimate the individualised cumulative chance of a first live birth over a maximum of six complete cycles of IVF—one model using information available before starting treatment and the other based on additional information collected during the first IVF attempt. A complete cycle is defined as all fresh and frozen-thawed embryo transfers arising from one episode of ovarian stimulation. Results After exclusions, 113 873 women with 184 269 complete cycles were included, of whom 33 154 (29.1%) had a live birth after their first complete cycle and 48 925 (43.0%) after six complete cycles. Key pretreatment predictors of live birth were the woman’s age (31 v 37 years; adjusted odds ratio 1.66, 95% confidence interval 1.62 to 1.71) and duration of infertility (3 v 6 years; 1.09, 1.08 to 1.10). Post-treatment predictors included number of eggs collected (13 v 5 eggs; 1.29, 1.27 to 1.32), cryopreservation of embryos (1.91, 1.86 to 1.96), the woman’s age (1.53, 1.49 to 1.58), and stage of embryos transferred (eg, double blastocyst v double cleavage; 1.79, 1.67 to 1.91). Pretreatment, a 30 year old woman with two years of unexplained primary infertility has a 46% chance of having a live birth from the first complete cycle of IVF and a 79% chance over three complete cycles. If she then has five eggs collected in her first complete cycle followed by a single cleavage stage embryo transfer (with no embryos left for freezing) her chances change to 28% and 56%, respectively. Conclusions This study provides an individualised estimate of a couple’s cumulative chances of having a baby over a complete package of IVF both before treatment and after the first fresh embryo transfer. This novel resource may help couples plan their treatment and prepare emotionally and financially for their IVF journey.

Can assisted reproductive technologies help to offset population ageing

In conclusion, we think that IVF is the most important treatment for couples who have no or little chance of conceiving naturally and that all these couples should have the opportunity to have IVF. However, early IVF is only indicated in the minority of couples: those who have a clearly identifiable cause of their infertility. Many couples need more time for realizing a natural pregnancy. Hoorens et al. grossly overestimate the impact of IVF as a policy measure to boost birth rates. If governments would follow their recommendations, this would have serious health consequences for mothers and children.

Is there a carryover effect of mild ovarian hyperstimulation with gonadotropins on the subsequent cycle

OBJECTIVE To investigate the effect of mild ovarian hyperstimulation on hormonal and sonographic variables of the subsequent natural cycle. DESIGN Prospective study of three consecutive cycles. SETTING University Hospital, Department of Reproductive Medicine, Division of Obstetrics and Gynecology. PATIENTS Twelve couples with subnormal semen as the only identifiable cause of subfertility. INTERVENTIONS Subjects were offered IUI for three cycles. In the second cycle, mild ovarian hyperstimulation with 75 IU IM hMG was applied daily and ovulation was induced with 5,000 IU hCG. In the first and third both natural cycles, serum samples were obtained for hormone measurements and ultrasound (US) scanning of the ovaries was performed. MAIN OUTCOME MEASURE To determine whether there was a carryover effect of mild ovarian hyperstimulation as applied in the second cycle, hormone levels and US scans of cycle 3 were compared with those of cycle 1. RESULTS None of the variables of cycle 3 were significantly different from those of cycle 1. CONCLUSION Because hormonal and sonographic variables in the subsequent natural cycle remain unchanged, a carryover effect of mild ovarian hyperstimulation with gonadotropins seems unlikely.

An improvement in the method used to assess discriminatory ability when predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation

Our paper presents two clinical prediction models that estimate the chance of having a baby over multiple complete cycles of in vitro fertilisation (IVF)—that is, cumulative live birth.1 The pretreatment model predicts the chance of cumulative live birth before treatment starts, and the post-treatment model predicts the chance of cumulative live birth just after the first embryo transfer. Through a collaboration with researchers from the University of Utrecht, who have externally validated these models, we have decided to revise the method used to assess the discriminatory ability of our models in the original study. In time to event models, such as ours, discrimination indicates the proportion of all pairs of women who can be ordered such that the woman with the lower predicted chance of live birth is the one who either did not have a live birth or had more complete cycles of IVF to have a live …