Age-related infertility and unexplained infertility: an intricate clinical dilemma

Abstract

A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed.

A systematic review and meta‐analysis of nonpharmacological adjuvant interventions for patients undergoing assisted reproductive technology treatment

“…As for the subgroup analyses by age, the pooled data indicated that, with respect to anxiety and pregnancy rate, nonpharmacological interventions are effective for the population younger than 35 years, whereas they are ineffective for those aged 35 years or older. This might be explained by differences in the reasons for infertility among the two populations and by the natural decline in human fertility by age . On the basis of the present results, nonpharmacological interventions are especially suitable for those younger than 35 years with better reproductive function.…”

Seminal Ferritin And Seminal Parameters In Patients Undergoing Chronic Hemodialysis

“…The similar age between the groups studied (p > 0.05) ensures greater reliability in the interpretation of the results and in the comparative statistical analysis of the impact of age on outcome variable [15].…”

Is early initiation of infertility treatment justified in women over the age of 35 years?

“…Indeed, both natural fecundity and the rate of success of Assisted Reproductive Techniques (ARTs) decrease at a similar rate after age 35 and definitely end at about age 45. Live births after this age are anecdotal (Leridon, 2004;Van Voorhis, 2007;Somigliana et al, 2016).…”

“…We argue that these recommendations actually generate a paradox with potential relevant public health consequences. In fact, it is recommended to anticipate clinical management in a population characterized by reduced fecundity, thus in a population that would conversely need a longer rather than a shorter duration of pregnancy seeking to reach a reliable diagnosis of infertility (Somigliana et al, 2016). This situation can engender over-diagnosis and over-treatment and the well-known associated wastage of resources and undue exposure to risks (Carroll, 2017;Korenstein et al, 2018).…”