Advertisement
Article| Volume 40, ISSUE 3, P393-398, March 2020

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

Published:December 17, 2019DOI:https://doi.org/10.1016/j.rbmo.2019.12.006

      Abstract

      Research question

      Natural fecundity and the success of IVF and intracytoplasmic sperm injection (ICSI) rate both decrease with age. For this reason, in women older than 35 years, it is generally recommended to start the infertility work-up after only 6 months. This assumption, however, may expose couples to over-diagnosis and over-treatment.

      Design

      A theoretical model aimed at assessing the effects of starting the infertility work-up after 6 rather than 12 months of trying to conceive naturally was developed. The assumptions of the model were as follows: infertile women are treated with IVF/ICSI for up to three cycles; IVF/ICSI success rate at first cycle linearly declines with age (3% per year between the ages of 35 and 45 years); the drop-out rate after the first and second cycle is 18% and 25%, respectively; the relative reduction of the success rate at second and third cycle is 16% and 26%, respectively.

      Results

      Early initiation of treatment moderately improved the cumulative chances of live birth resulting from a full IVF/ICSI programme. This improvement is dependent on age. Specifically, it increased from 2.0% at age 35 years to 3.0% at age 43 years. Conversely, the incremental success rate per single IVF cycle was mainly stable, varying only from 1.4% at age 35 years to 1.3% at age 43 years.

      Conclusions

      In women older than 35 years, early initiation of the infertility work-up is associated with only a modest increase in the rate of success of IVF/ICSI. In most scenarios, this advantage may compare unfavourably with the chances of natural conception during the 6-month period.

      KEYWORDS

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; Practice Committee of the American Society for Reproductive Medicine
        Female age-related fertility decline. Committee Opinion No. 589.
        Obstet. Gynecol. 2014; 123: 719-721
        • Carroll A.E.
        The High Costs of Unnecessary Care.
        JAMA. 2017; 318: 1748-1749
        • Crawford N.M.
        • Steiner A.Z.
        Age-related infertility.
        Obstet. Gynecol. Clin. North Am. 2015; 42: 15-25
        • Devesa M.
        • Tur R.
        • Rodríguez I.
        • Coroleu B.
        • Martínez F.
        • Polyzos N.P.
        Cumulative live birth rates and number of oocytes retrieved in women of advanced age. A single centre analysis including 4500 women ≥38 years old.
        Hum. Reprod. 2018; 33: 2010-2017
        • Eijkemans M.J.C.
        • Kersten F.A.M.
        • Lintsen A.M.E.
        • Hunault C.C.
        • Bouwmans C.A.M.
        • Roijen L.H.
        • Habbema J.D.F.
        • Braat D.D.M.
        Cost-effectiveness of 'immediate IVF' versus 'delayed IVF': a prospective study.
        Hum. Reprod. 2017; 32: 999-1008
        • ESHRE Capri Workshop Group
        Economic aspects of infertility care: a challenge for researchers and clinicians.
        Hum. Reprod. 2015; 30: 2243-2248
        • ESHRE Capri Workshop Group
        A prognosis-based approach to infertility: understanding the role of time.
        Hum. Reprod. 2017; 32: 1556-1559
        • Evers J.L.
        Female subfertility.
        Lancet. 2002; 360: 151-159
        • Gameiro S.
        • Verhaak C.M.
        • Kremer J.A.
        • Boivin J.
        Why we should talk about compliance with assisted reproductive technologies (ART): a systematic review and meta-analysis of ART compliance rates.
        Hum. Reprod Update. 2013; 19: 124-135
        • Goldman M.B.
        • Thornton K.L.
        • Ryley D.
        • Alper M.M.
        • Fung J.L.
        • Hornstein M.D.
        • Reindollar R.H.
        A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T).
        Fertil. Steril. 2014; 101: 1574-1581
        • Guzick D.S.
        • Overstreet J.W.
        • Factor-Litvak P.
        • Brazil C.K.
        • Nakajima S.T.
        • Coutifaris C.
        • Carson S.A.
        • Cisneros P.
        • Steinkampf M.P.
        • Hill J.A.
        • Xu D.
        • Vogel D.L.
        • National Cooperative Reproductive Medicine Network
        Sperm morphology, motility, and concentration in fertile and infertile men.
        N. Engl. J. Med. 2001; 345: 1388-1393
        • Igarashi H.
        • Takahashi T.
        • Nagase S.
        Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies.
        Reprod. Med. Biol. 2015; 14: 159-169
        • Korenstein D.
        • Chimonas S.
        • Barrow B.
        • Keyhani S.
        • Troy A.
        • Lipitz-Snyderman A.
        Development of a Conceptual Map of Negative Consequences for Patients of Overuse of Medical Tests and Treatments.
        JAMA Intern. Med. 2018; 178: 1401-1407
        • Leone Roberti Maggiore U.
        • Scala C.
        • Venturini P.L.
        • Remorgida V.
        • Ferrero S.
        Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation.
        Hum. Reprod. 2015; 30: 299-307
        • Leone Roberti Maggiore U.
        • Scala C.
        • Tafi E.
        • Racca A.
        • Biscaldi E.
        • Vellone V.G.
        • Venturini P.L.
        • Ferrero S.
        Spontaneous fertility after expectant or surgical management of rectovaginal endometriosis in women with or without ovarian endometrioma: a retrospective analysis.
        Fertil. Steril. 2017; 107: 969-976
        • Leridon H.
        Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment.
        Hum. Reprod. 2004; 19: 1548-1553
        • McLernon D.J.
        • Maheshwari A.
        • Lee A.J.
        • Bhattacharya S.
        Cumulative live birth rates after one or more complete cycles of IVF: a population-based study of linked cycle data from 178,898 women.
        Hum. Reprod. 2016; 31: 572-581
        • Mills M.
        • Rindfuss R.R.
        • McDonald P.
        • te Velde E.
        • ESHRE Reproduction and Society Task Force
        Why do people postpone parenthood? Reasons and social policy incentives.
        Hum. Reprod. Update. 2011; 17: 848-860
        • NICE - National Institute for Health and Clinical Excellence. National Collaborating Centre for Women's and Children's Health
        Fertility: assessment and treatment for people with fertility problems.
        2013 Feb.: 63 (London (UK)(Clinical guideline; no. 156))
        • Schmidt L.
        • Sobotka T.
        • Bentzen J.G.
        • Nyboe Andersen A.
        • ESHRE Reproduction and Society Task Force
        Demographic and medical consequences of the postponement of parenthood.
        Hum. Reprod. Update. 2012; 18: 29-43
        • Somigliana E.
        • Paffoni A.
        • Busnelli A.
        • Filippi F.
        • Pagliardini L.
        • Vigano P.
        • Vercellini P.
        Age-related infertility and unexplained infertility: an intricate clinical dilemma.
        Hum. Reprod. 2016; 31: 1390-1396
        • Sunderam S.
        • Kissin D.M.
        • Crawford S.B.
        • Folger S.G.
        • Boulet S.L.
        • Warner L.
        • Barfield W.D.
        Assisted Reproductive Technology Surveillance - United States, 2015.
        MMWR Surveill. Summ. 2018; 67: 1-28
        • van Eekelen R.
        • Tjon-Kon-Fat R.I.
        • Bossuyt P.M.M.
        • van Geloven N.
        • Eijkemans M.J.C.
        • Bensdorp A.J.
        • van der Veen F.
        • Mol B.W.
        • van Wely M.
        Natural conception rates in couples with unexplained or mild male subfertility scheduled for fertility treatment: a secondary analysis of a randomized controlled trial.
        Hum. Reprod. 2018; 33: 919-923
        • Van Voorhis B.J.
        Clinical practice. In vitro fertilization.
        N. Engl. J. Med. 2007; 356: 379-386
        • Vercellini P.
        • Somigliana E.
        • Viganò P.
        • Abbiati A.
        • Barbara G.
        • Crosignani P.G.
        Surgery for endometriosis-associated infertility: a pragmatic approach.
        Hum. Reprod. 2009; 24: 254-269

      Biography

      Edgardo Somigliana graduated in obstetrics and gynaecology in 1999 and completed a PhD in prenatal medicine in 2006. He is currently Associate Professor in Obstetrics and Gynaecology at the Università degli Studi di Milano, Italy. He is author or co-author of more than 300 articles in international journals.
      Key message
      In older women, it is generally recommended to commence infertility work-up after only 6 months of trying to conceive naturally. This may expose couples to over-diagnosis and over-treatment. Theoretical modelling was used to show that early initiation of clinical management may not be justified and can waste resources.