title: 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.
authors.affiliation: Obstet-Gynecol Dept, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy dadosomigliana@yahoo.it.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Somigliana
authors.affiliation: Obstet-Gynecol Dept, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Paffoni
authors.affiliation: Obstet-Gynecol Dept, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy Università degli Studi di Milano, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Busnelli
authors.affiliation: Obstet-Gynecol Dept, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Filippi
authors.affiliation: Obstet-Gynecol Dept, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pagliardini
authors.affiliation: Obstet-Gynecol Dept, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vigano
authors.affiliation: Obstet-Gynecol Dept, Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy Università degli Studi di Milano, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vercellini
mesh_terms: D000328:Adult; D000367:Age Factors; D003937:Diagnosis, Differential; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007247:Infertility, Female / Q000175:diagnosis* / Q000628:therapy; D008423:Maternal Age; D008954:Models, Biological; D027724:Reproductive Techniques, Assisted / Q000191:economics
keywords: ART; IVF; age; economic; risk; unexplained infertility