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 accessOne-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 OnlineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Female age-related fertility decline. Committee Opinion No. 589.Obstet. Gynecol. 2014; 123: 719-721
- The High Costs of Unnecessary Care.JAMA. 2017; 318: 1748-1749
- Age-related infertility.Obstet. Gynecol. Clin. North Am. 2015; 42: 15-25
- 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
- Cost-effectiveness of 'immediate IVF' versus 'delayed IVF': a prospective study.Hum. Reprod. 2017; 32: 999-1008
- Economic aspects of infertility care: a challenge for researchers and clinicians.Hum. Reprod. 2015; 30: 2243-2248
- A prognosis-based approach to infertility: understanding the role of time.Hum. Reprod. 2017; 32: 1556-1559
- Female subfertility.Lancet. 2002; 360: 151-159
- 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
- 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
- Sperm morphology, motility, and concentration in fertile and infertile men.N. Engl. J. Med. 2001; 345: 1388-1393
- Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies.Reprod. Med. Biol. 2015; 14: 159-169
- Development of a Conceptual Map of Negative Consequences for Patients of Overuse of Medical Tests and Treatments.JAMA Intern. Med. 2018; 178: 1401-1407
- Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation.Hum. Reprod. 2015; 30: 299-307
- 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
- Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment.Hum. Reprod. 2004; 19: 1548-1553
- 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
- Why do people postpone parenthood? Reasons and social policy incentives.Hum. Reprod. Update. 2011; 17: 848-860
- Fertility: assessment and treatment for people with fertility problems.2013 Feb.: 63 (London (UK)(Clinical guideline; no. 156))
- Demographic and medical consequences of the postponement of parenthood.Hum. Reprod. Update. 2012; 18: 29-43
- Age-related infertility and unexplained infertility: an intricate clinical dilemma.Hum. Reprod. 2016; 31: 1390-1396
- Assisted Reproductive Technology Surveillance - United States, 2015.MMWR Surveill. Summ. 2018; 67: 1-28
- 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
- Clinical practice. In vitro fertilization.N. Engl. J. Med. 2007; 356: 379-386
- Surgery for endometriosis-associated infertility: a pragmatic approach.Hum. Reprod. 2009; 24: 254-269
Biography

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.
Article info
Publication history
Published online: December 17, 2019
Accepted:
December 10,
2019
Received in revised form:
November 12,
2019
Received:
July 14,
2019
Declaration: The study was partly supported by the European COUNCIL grant agreement n. 803959 (PI: Alice Goisis). The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.