Gonadotrophins versus clomiphene citrate with or without IUI in women with normogonadotropic anovulation and clomiphene failure: a cost-effectiveness analysis

Study Question: Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC? Summary Answer: Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC. What is Known Already: In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown. Study Design, Size, Duration: We performed an economic evaluation of ovulation induction with gonadotrophins compared with CC with or without IUI in a two-by-two factorial multicentre randomized controlled trial in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC. Between December 2008 and December 2015 women were allocated to six cycles with gonadotrophins plus IUI, six cycles with gonadotrophins plus intercourse, six cycles with CC plus IUI or six cycles with CC plus intercourse. The primary outcome was conception leading to a live birth achieved within 8 months of randomization. Participants/Materials, Setting, Methods: We performed a cost-effectiveness analysis on direct medical costs. We calculated the direct medical costs of ovulation induction with gonadotrophins versus CC and of IUI versus intercourse in six subsequent cycles. We included costs of medication, cycle monitoring, interventions, and pregnancy leading to live birth. Resource use was collected from the case report forms and unit costs were derived from various sources. We calculated incremental cost-effectiveness ratios (ICER) for gonadotrophins compared to CC and for IUI compared to intercourse. We used non-parametric bootstrap resampling to investigate the effect of uncertainty in our estimates. The analysis was performed according to the intention-to-treat principle. Main Results and the Role of Chance: We allocated 666 women in total to gonadotrophins and IUI (n = 166), gonadotrophins and intercourse (n = 165), CC and IUI (n = 163), or CC and intercourse (n = 172). Mean direct medical costs per woman receiving gonadotrophins or CC were €4495 versus €3006 (cost difference of €1475 (95% CI: €1457-€1493)). Live birth rates were 52% in women allocated to gonadotrophins and 41% in those allocated to CC (relative risk (RR) 1.24:95% CI: 1.05-1.46). The ICER was €15 258 (95% CI: €8721 to €63 654) per additional live birth with gonadotrophins. Mean direct medical costs per woman allocated to IUI or intercourse were €4497 versus €3005 (cost difference of €1510 (95% CI: €1492-€1529)). Live birth rates were 49% in women allocated to IUI and 43% in those allocated to intercourse (RR = 1.14:95% CI: 0.97-1.35). The ICER was €24 361 (95% CI: €-11 290 to €85 172) per additional live birth with IUI. Limitations, Reasons for Caution: We allowed participating hospitals to use their local protocols for ovulation induction and IUI, which may have led to variation in costs, but which increases generalizability. Indirect costs generated by transportation or productivity loss were not included. We did not evaluate letrozole, which is potentially more effective than CC. Wider Implications of the Findings: Gonadotrophins are more effective, but more expensive than CC, therefore, the use of gonadotrophins in women with normogonadotropic anovulation who have not conceived after six ovulatory CC cycles depends on society's willingness to pay for an additional child. In view of the uncertainty around the cost-effectiveness estimate of IUI, these data are not sufficient to make recommendations on the use of IUI in these women. In countries where ovulation induction regimens are reimbursed, policy makers and health care professionals may use our results in their guidelines.E.M. Bordewijk, N.S. Weiss, M.J. Nahuis, N. Bayram, M.H.A. van Hooff, D.E.S. Boks, D.A.M. Perquin, C.A.H. Janssen, R.J.T. van Golde, C.B. Lambalk, M. Goddijn, P.G. Hompes, F. van der Veen, B.W.J. Mol and M. van Wely, on behalf of the M-ovin study grou

[Foley catheter versus prostaglandin E2 gel for induction of labour at term: the PROBAAT study]

Objective To study the effectiveness and safety of induction of labour with a Foley catheter compared with vaginal prostaglandin E2 gel in full term pregnant women. Design Multicentre, randomised, open-label trial in 12 hospitals in the Netherlands between February 2009 and May 2010. Methods Women scheduled for induction of labour at full term singleton pregnancy in cephalic presentation, intact membranes, and an unripe cervix (Bishop score < 6) were enrolled by means of an on-line system. Participants were randomly allocated to induction of labour with a transcervical Foley catheter or vaginal prostaglandin E2 gel. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from induction to birth. Results A total of 824 women were allocated to induction of labour with a Foley catheter (n = 412) or prostaglandin E2 (n = 412). Caesarean section rates were comparable (23% versus 20%, RR 1.13, 95% CI 0.87 to 1.47). In the Foley catheter group fewer instrumental deliveries for foetal distress were performed (12% versus 18%, RR 0.68, 95% CI 0.49 to 0.95). Time to delivery (median hours (IQR)) was longer (29 (15-35) versus 18 (12-33)). Fewer mothers had suspected intrapartum infection (2% versus 4%, RR 0.41, 95% CI 0.17-0.98). Significantly fewer neonates were admitted toaneonatal ward after induction with a Foley catheter (12% versus 20%, RR 0.60, 95% CI 0.43 to 0.83). Conclusion In women with an unripe cervix at term, induction of labour with a Foley catheter does not reduce caesarean section rates, but there are fewer side-effects

[Foley catheter versus prostaglandin E2 gel for induction of labour at term: the PROBAAT study]

Item does not contain fulltextObjective To study the effectiveness and safety of induction of labour with a Foley catheter compared with vaginal prostaglandin E2 gel in full term pregnant women. Design Multicentre, randomised, open-label trial in 12 hospitals in the Netherlands between February 2009 and May 2010. Methods Women scheduled for induction of labour at full term singleton pregnancy in cephalic presentation, intact membranes, and an unripe cervix (Bishop score < 6) were enrolled by means of an on-line system. Participants were randomly allocated to induction of labour with a transcervical Foley catheter or vaginal prostaglandin E2 gel. The primary outcome was caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from induction to birth. Results A total of 824 women were allocated to induction of labour with a Foley catheter (n = 412) or prostaglandin E2 (n = 412). Caesarean section rates were comparable (23% versus 20%, RR 1.13, 95% CI 0.87 to 1.47). In the Foley catheter group fewer instrumental deliveries for foetal distress were performed (12% versus 18%, RR 0.68, 95% CI 0.49 to 0.95). Time to delivery (median hours (IQR)) was longer (29 (15-35) versus 18 (12-33)). Fewer mothers had suspected intrapartum infection (2% versus 4%, RR 0.41, 95% CI 0.17-0.98). Significantly fewer neonates were admitted toaneonatal ward after induction with a Foley catheter (12% versus 20%, RR 0.60, 95% CI 0.43 to 0.83). Conclusion In women with an unripe cervix at term, induction of labour with a Foley catheter does not reduce caesarean section rates, but there are fewer side-effects

Determinants of successful lifestyle change during a 6-month preconception lifestyle intervention in women with obesity and infertility

Purpose: To identify demographic, (bio)physical, behavioral, and psychological determinants of successful lifestyle change and program completion by performing a secondary analysis of the intervention arm of a randomized-controlled trial, investigating a preconception lifestyle intervention. Methods: The 6-month lifestyle intervention consisted of dietary counseling, physical activity, and behavioral modification, and was aimed at 5–10% weight loss. We operationalized successful lifestyle change as successful weight loss (≥ 5% weight/BMI ≤ 29 kg/m2), weight loss in kilograms, a reduction in energy intake, and an increase in physical activity during the intervention program. We performed logistic and mixed-effect regression analyses to identify baseline factors that were associated with successful change or program completion. Results: Women with higher external eating behavior scores had higher odds of successful weight loss (OR 1.10, 95% CI 1.05–1.16). Women with the previous dietetic support lost 0.94 kg less during the intervention period (95% CI 0.01–1.87 kg). Women with higher self-efficacy reduced energy intake more than women with lower self-efficacy (p < 0.01). Women with an older partner had an increased energy intake (6 kcal/year older, 95% CI 3–13). A high stage of change towards physical activity was associated with a higher number of daily steps (p = 0.03). A high stage of change towards weight loss was associated with completion of the intervention (p = 0.04). Conclusions: Determinants of lifestyle change and program completion were: higher external eating behavior, not having received previous dietetic support, high stage of change. This knowledge can be used to identify women likely to benefit from lifestyle interventions and develop new interventions for women requiring alternative support. Trial registration: The LIFEstyle study was registered at the Dutch trial registry (NTR 1530; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1530).</p