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Reliable methods of contraception were introduced in the1960s and enabled women to postpone childbearing and to prevent the birth of not-yet-wanted children. This allowed women to delay the start of their family. However, with increasing female age (>30 years and especially >35 years), there is increased risk of aneuploidy and either miscarriage or a deformed baby. The availability of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) methods allows embryo selection prior to implantation in these women and birth of healthy babies. This allows older women to delay their first pregnancy and plan to have more than 1 child. As a result, the mean age of women at first childbirth increased by 4 to 5 years since the 1970s in most European countries, and the proportion who have their first child at older than 30 years has increased from about 8% to 40%. Both the treatment-independent and treatment-dependent (IVF/ICSI) chances of pregnancy decline with female age. Research on the age-dependent effects has focused on the chance of a first pregnancy and not on having more than 1 child. This study was designed to estimate at what age couples can wait to start a family without compromising their chances of realizing the desired number of children (a 1-, 2-, or 3-child family). The investigators used an established computer simulation model of fertility to simulate a cohort of 10,000 couples in order to assess the chances of realizing a 1-, 2-, or 3-child family. The model used treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI updated with recent IVF success rates. Three levels of importance a couple attaches to achieving a desired family size were singled out: (i) The extremely important level is aimed for at least a 90% success chance; (ii) important (but not at all costs) is aimed at a 75% success chance; and (iii) good to have children (parenthood is not essential) is aimed at a 50% success chance. Based on the computer model, couples who wish to have at least a 90% chance to realize a 1-child family, the age for the female partner to start trying to conceive using IVF should be 35 years or younger. For those desiring 2 children using IVF, the latest starting age should be 31 years, and for 3 children, 28 years. Without IVF, couples who desire a 90% chance should start no later than age 32 years for a 1-child family, at 27 years for a 2-child family, and at 23 years for 3 children. If a 75% or lower chance is acceptable for couples attempting to conceive naturally, they can start 4 to 11 years later for a 1-, 2-, or 3-child family (at 37, 34, and 31 years of age, respectively). Use of IVF has the greatest impact on the starting age for the couples wishing a 90% chance of conceiving. For a 50% or 75% chance at older ages of realizing a 2- or 3-child family, there was little improvement for couples using IVF. The data appeared to be robust for plausible changes in model assumptions. The latest female age at which a couple should start trying to become pregnant is strongly dependent on the importance they attach to achieving a desired family size and on whether IVF is an acceptable option if no natural pregnancy occurs. In the absence of large-scale prospective studies (which would provide more conclusive data), this evidence-based simulation study is the next best option. With continuing improvements in IVF technology, the assumptions on success chances with IVF run the risk of becoming outdated. Therefore, simulations should be updated every 5 to 10 years with new evidence. These findings are important for prospective parents in family planning and for preconception counseling. This information is also useful for inclusion in educational courses in human biology and for increasing public awareness on possibilities and limitations of human reproduction.

Background: We will assess to what extent in vitro fertilization (IVF) is effective in ncreasing 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. Key words: in vitro fertilization / assisted reproduction / total fertility rate / multiple pregnancies / IVF policy

Background: Obesity is increasing rapidly among women all over the world. Obesity is a known risk factor for subfertility due to anovulation, but it is unknown whether obesity also affects spontaneous pregnancy chances in subfertile, ovulatory women. Methods: We evaluated whether obesity affected the chance of a spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive subfertile couples. Women had to be ovulatory and had to have at least one patent tube, whereas men had to have a normal semen analysis. Time to spontaneous ongoing pregnancy within 12 months was the primary endpoint. Results: The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m(2). Corrected for possible related factors, women with a high BMI had a 4% lower pregnancy rate per kg/m(2) increase [hazard ratio: 0.96 (95% CI 0.91-0.99)]. Conclusions: These results indicate that obesity is associated with lower pregnancy rates in subfertile ovulatory women.

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics.Sixteen prognostic groups are defined, according to the presence or absence of: age30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000.The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively.The conventional treatment protocol is efficient for women aged30 years with normal androgen levels. For women30 years old with elevated androgen levels, FSH may be skipped.

BACKGROUND: Intrauterine insemination (IUI) can be performed with or without controlled ovarian hyperstimulation (COH). Studies in which the additional benefit of COH on IUI for cervical factor subfertility is assessed are lacking. We assessed whether COH in IUI improved pregnancy rates in cervical factor subfertility. METHODS: We performed a historical cohort study among couples with cervical factor subfertility, treated with IUI. A cervical factor was diagnosed by a well-timed, non-progressive post-coital test with normal semen parameters. We compared ongoing pregnancy rate per cycle in groups treated with IUI with or without COH. We tabulated ongoing pregnancy rates per cycle number and compared the effectiveness of COH by stratified univariable analysis. RESULTS: We included 181 couples who underwent 330 cycles without COH and 417 cycles with COH. Ongoing pregnancy rates in IUI cycles without and with COH were 9.7% and 12.7%, respectively (odds ratio 1.4; 95% confidence interval 0.85-2.2). The pregnancy rates in IUI without COH in cycles 1, 2, 3 and 4 were 14%, 11%, 6% and 15%, respectively. For IUI with COH, these rates were 17%, 15%, 14% and 16%, respectively. CONCLUSIONS: Although our data indicate that COH improves the pregnancy rate over IUI without COH, IUI without COH generates acceptable pregnancy rates in couples with cervical factor subfertility. Since IUI without COH bears no increased risk for multiple pregnancy, this treatment should be seriously considered in couples with cervical factor subfertility.

BACKGROUND: Medical induction of ovulation using clomiphene citrate (CC) as first line and exogenous gonadotrophins as second line forms the classical treatment algorithm in normogonadotrophic anovulatory infertility. Because the chances of success following classical ovulation induction are not well established, a shift in first-line therapy can be observed towards alternative treatment. The study aim was to: (i) reliably assess the probability of singleton live birth following classical induction of ovulation; and (ii) construct a prediction model, based on individual patient characteristics assessed upon standardized initial screening, to help identify patients with poor chances of success. METHODS: A total of 240 consecutive women visiting a specialist academic fertility unit with a history of infertility, oligomenorrhoea or amenorrhoea, and normal FSH and estradiol serum concentrations (WHO group 2) was prospectively followed. The women had not been previously treated with ovulation-inducing agents. All patients commenced with CC. Patients who did not ovulate within three treatment cycles of incremental daily doses up to 150 mg for 5 consecutive days or ovulatory CC patients who did not conceive within six cycles, subsequently underwent gonadotrophin induction of ovulation applying a step-down dose regimen. The main outcome measure was pregnancy resulting in singleton live birth. Cox regression was used to construct a multivariable prediction model. RESULTS: Overall, there were 134 pregnancies ending in a singleton live birth (56% of women). The cumulative pregnancy rate after 12 and 24 months of follow-up was 50% and 71% respectively. Polycystic ovary syndrome (PCOS) patients (49%), clearly non-PCOS patients (13%) and the in-between group did not differ in prognosis (P = 0.9). The multivariable Cox regression model contained the woman's age, the insulin:glucose ratio and duration of infertility. With a cut-off value of 30% for low chance, the model predicted probabilities at 12 months lower than this cut-off for 25 out of 240 patients (10.4%). CONCLUSIONS: Classical ovulation induction produces very good results in normogonadotrophic anovulatory infertility. Alternative treatment options may not be indicated as first-line therapy in these patients, except for subgroups with poor prognosis. These women can be identified by older age, longer duration of infertility and higher insulin:glucose ratio.

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.