No. 346-Advanced Reproductive Age and Fertility

  • Kimberly E. Liu
    Corresponding author: Dr. Kimberly E. Liu, Mount Sinai Hospital, Toronto, ON.
    Toronto, ON
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  • Allison Case
    Saskatoon, SK
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  • Author Footnotes
    ∗ Reproductive Endocrinology and Infertility committee: Anthony P. Cheung, MD (Co-Chair), Vancouver, BC; Sony Sierra, MD (Co-Chair), Toronto, ON; Belina Carranza-Mamane, MD, Sherbrooke, QC; Catherine Dwyer, RN, Toronto, ON; James Graham, MD, Calgary, AB; Sarah Healey, MD, St. John’s, NL; Robert Hemmings, MD, Montréal, QC; Kimberly Liu, MD, Toronto, ON; Tarek Motan, MD, Edmonton, AB; David Smithson, MD, Ottawa, ON; Tannys D.R. Vause, MD, Ottawa, ON; Benjamin Chee-Man Wong, MD, Calgary, AB. Disclosure statements have been received from all members of the committee.



      To improve awareness of the natural age-related decline in female and male fertility with respect to natural fertility and assisted reproductive technologies (ART), provide recommendations for their management, and to review investigations in the assessment of ovarian aging.


      This guideline reviews options for the assessment of ovarian reserve and fertility treatments using ART with women of advanced reproductive age presenting with infertility.


      The outcomes measured are the predictive value of ovarian reserve testing and pregnancy rates with natural and assisted fertility.


      Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in June 2010, using appropriate key words (“ovarian aging,” “ovarian reserve,” “advanced maternal age,” “advanced paternal age,” and “assisted reproductive technology”). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated into the guideline to December 2010.


      The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report.

      Benefits, Harms, and Costs

      Primary and specialist health care providers and women will be better informed about ovarian aging and the age-related decline in natural fertility and about options for ART.


      • 1.
        Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues such as sexual health or contraception are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s (II-2A).
      • 2.
        Because of the decline in fertility and the increased time to conception that occur after age 35, women >35 should be referred for infertility work-up after 6 months of trying to conceive (III-B).
      • 3.
        Ovarian reserve testing may be considered for women aged ≥35 or for women <35 with risk factors for decreased ovarian reserve, such as a single ovary, previous ovarian surgery, poor response to follicle-stimulating hormone, previous exposure to chemotherapy or radiation, or unexplained infertility (III-B).
      • 4.
        Ovarian reserve testing prior to assisted reproductive technology treatment may be used for counselling but has a poor predictive value for non-pregnancy and should be used to exclude women from treatment only if levels are significantly abnormal (II-2A).
      • 5.
        Pregnancy rates for controlled ovarian hyperstimulation are low for women aged >40. Women >40 should consider in vitro fertilization if they do not conceive within 1 to 2 cycles of controlled ovarian hyperstimulation (II-2B).
      • 6.
        The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option because pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman's own eggs (II-2B).
      • 7.
        Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established (II-2A).
      • 8.
        Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women aged 40 (III-B).
      • 9.
        Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men >40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small (II-2C).

      Key Words


      AFC (antral follicle count), AMH (anti-Müllerian hormone), ART (assisted reproductive technology), COH (controlled ovarian hyperstimulation), FSH (follicle-stimulating hormone), IUI (intrauterine insemination), IVF (in vitro fertilization)
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