Postponing pregnancy seeking and anticipating infertility treatments: an unwise combination

Study question: Is the current recommendation to anticipate the infertility work-up after only 6 months of pregnancy seeking in older women justified? Summary answer: Anticipating clinical management in older women seeking pregnancy is clinically and economically questionable and can unwisely boost over-diagnosis and over-treatment. What is known already: Postponing motherhood exposes women to the risk of childlessness. Natural fecundity decreases with age and, unfortunately, Assisted Reproductive Techniques (ARTs) do not overcome the detrimental effects of aging. For this reason, in women older than 35 years, it is recommended to initiate the infertility work-up after only 6 months of attempts rather than after the usual one year period. In fact, it is paradoxically claimed to anticipate clinical management in a population of reduced fecundity, thus in a population who would conversely need a longer rather than a shorter duration of pregnancy seeking to reach a reliable diagnosis of infertility. Study design, size, duration: The aim of this theoretical model was to explore the effects of starting the infertility work-up after 6 months of pregnancy seeking rather than the usual 12 months’ period in women older than 35 years.We aimed at determining whether the detrimental impact of a 6 months’ delay on the chances of success of ARTs could justify this position. The model was based on cost-beneficial considerations. The perspective was the one of the health provider. Participants/materials, setting, methods: The assumptions of the model were: 1) infertile women >35 years are straightly treated with IVF for up to three cycles; 2) IVF success rate at first cycle linearly declines with age from 30% at 35 years to 0% at 45 years, 3) the drop-out rate after the 1st and 2nd cycle is 18% and 25%, respectively, 4) the relative reduction of the success rate at 2nd and 3rd cycle is 16% and 26%, respectively. Main results and the role of chance:The increase in the success of the IVF program associated to an anticipation of 6 months changed with age, increasing from 2.0% at age 35 to 3.0% at age 43. The corresponding Number of women Needed to be Treated (NNTs) decreased from 49 at age 35 to 34 at age 43. Sensitivity analyses modifying the gradient of pregnancy loss per year (decline from 40% to 0% from age 35 to age 45, corresponding to an annual loss of 4%) did not markedly change the results (the increase in success remains <4% at all ages). In order to shed light on the incremental cost-beneficial ratio of the anticipation of treatment we also calculated the incremental success rate per cycle. In the basal situation (live birth rate at 35 years of 30%), it decreased from 1.4% to 1.3% from age 35 to age 43. When setting the live birth rate at 35 years at 40%, the incremental success rate per cycle decreased from 1.9% to 1.8% from age 35 to age 43. In all the scenarios, the estimated impact is wellbelow the thresholds of 4-10% of success used to define IVF as cost-beneficial (ESHRE CapriWorkshop Group, 2015). Limitations,reasons for caution:Themodel is theoretical and based on the still debated ideas that IVF cannot overcome the detrimental effects of age and that the available tests for the diagnosis of infertility are inaccurate (duration of infertility still plays a crucial role for a definite diagnosis). Wider implications of the findings:The position of stakeholders and major International Societies should be less trenchant. More consideration should be given to the consistent risks of overdiagnosis and overtreatment associated to an anticipation of the infertility work-up. Trial registration number:NA