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Infertility and IVF Treatment in Women After 35 Years

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The management of infertility (defined clinically as 12 or more consecutive months of sexual intercourse without contraception and without achieving pregnancy) is part of comprehensive primary care. Fertility care is a fundamental part of the family planning spectrum, involves both women and men, and provides insight into a patient’s overall health, including underlying health problems that increase women’s long-term risk of ischemic heart disease or cancer.

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Women at ages 40–45 years in the US represent the most rapidly growing age group going through pregnancy

Together with the demographic fact that the last vestiges of the large baby boomer generation are now aging beyond their reproductive life spans (with use of autologous oocytes), this observation points towards increasing demand for in vitro fertilization (IVF) at advanced female ages, as, indeed, has been observed in the last few years. A shift towards more “older” patients in IVF programs can also be expected from improving pregnancy rates. As a consequence of quick pregnancy success in younger women, the more difficult cases (such as older patients) remain disproportionally in the system, while younger patients are quickly discharged. The success of IVF, of course, declines with older female age. This is believed to be a reflection of declining female fecundity (and increasing miscarriage rates) with advancing age. Declining female fertility has statistically been correlated to the decrease in ovarian follicle numbers. Indeed, when female age-dependent fertility and national age-based IVF outcome curves are compared, they are practically identical. Both suggest a steady decline from early age, which accelerates at 37–38 years of age, when approximately 25,000 follicles are left within ovaries.

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Despite the improvement of the diagnostic armamentarium in reproductive medicine, infertility remains unexplained in about one quarter of cases (Evers, 2002; Practice Committee of the American Society for Reproductive Medicine, 2006). In fact, several crucial steps of the fertility process cannot be accurately investigated (Practice Committee of the American Society for Reproductive Medicine, 2015). Fallopian tubes may be patent but not functional because of microscopic alterations impacting on the function of the tubal epithelium (Lyons et al., 2006). Despite its critical and complex role in storing spermatozoa and allowing them to regularly ascend, no reliable tests currently exist to investigate the function of the cervix (Martyn et al., 2014)

Embryo implantation is pivotal for conception but, to date, there is no validated test to examine this function (Cakmak and Taylor, 2011). Finally, male factor infertility is also poorly defined and the reliability of the semen analysis to predict fertility remains low (Wang and Swerdloff, 2014). Despite its heterogeneous pathology, couples with unexplained infertility enter a specific and definite therapeutic strategy (Practice Committee of the American Society for Reproductive Medicine, 2006; NICE, 2013).

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Ultimately, both the self-selected nature of recruitment and the retrospective design can result in biases due to memory limitations or participant assimilation and/or contrast of past events with current moods. As attitudes of older women who were unsuccessful after attempting IVF in their late 30s or early 40s are not represented, it is possible (if not likely) that the recollections of women who did not conceive after IVF would have been more strongly influenced by feelings of regret or efforts to deflect blame for their inability to conceive.

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Eijkemans MJ , van Poppel F, Habbema DF, Smith KR, Leridon H, te Velde ER. Too old to have children? Lessons from natural fertility populations. Hum Reprod2014

ESHRE Capri Workshop Group. Economic aspects of infertility care: a challenge for researchers and clinicians. Hum Reprod2015.

Evers JL . Female subfertility. Lancet2002;360:151–159.

Gameiro S , Boivin J, Dancet E, de Klerk C, Emery M, Lewis-Jones C, Thorn P, Van den Broeck U, Venetis C, Verhaak CMet al.

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