On 2014 Feb 13, Bruno Ramalho Carvalho commented:

In their interesting article, Gizzo et al affirmed that modern concepts on fertility sparing consider ovarian reserve to be the most important independent female fertility predictor, even being more important than chronological age. I would say that, based on scientific evidence, such an affirmative is at least controversial.

First of all, that affirmative was attributed to a narrative review article and an article on fertility preservation in women with cancer, which are supposed to be unaproppriate references. Adequate evidences should include prospective and controlled studies, with large populations.

Until today, the bulk of literature supports age as the single most important factor in determining theoretical reproductive capability of women. In historical cohorts, the respective rates of infertility among married women at the age groups of 20-24, 25-29, 30-34, 35-39 and 40-44 years were 6%, 9%, 15%, 30% and 64% [Menken et al, Science 1986].

Women undergoing artificial insemination with donor sperm because of partner azoospermia presented with lower rates of conception or needed more cycles to achieve it after 35 years of age [Schwartz & Mayaux N Eng J Med 1982]. According to recent data, similar results were obtained in in vitro fertilization (IVF) cycles using non donor fresh eggs; birth rates for age groups of < 35, 35-37, 38-40, 41-42 and > 42 years were 36%, 28%, 18%, 10% and 4% per cycle, respectively [CDC, http://apps.nccd.cdc.gov/art/Apps/NationalSummaryReport.aspx].

Data from Red Latinoamericana de Reproducción Asistida demonstrated a significant age-dependent reduction of pregnancy rates per IVF cycle: 38% for women with 30-34 years of age; 31% for women with 35-39 years of age and 16% for older patients [Zegers-Hochschild et al, 2008; http://www.redlara.com/imagens/arq/2008_registro 2008.pdf]. Furthermore, studies have shown that women of advanced maternal age unable to achieve pregnancy through IVF were able to conceive using donor oocytes from younger women [Steiner & Paulson, 2006].

Despite the points enhanced along Gizzo et al discussion, some should note that their results clearly demonstrate that age is the best predictor of IVF results, since they reported ongoing pregnancy rates of 6.7% in the fifth decade of life, with no pregnancy after 46 years of age. It is noticeable that the authors did not mention live birth rates, which should be expected to be lower, as late pregnancy loss are very probable among the study population.

A recent study by Luke et al demonstrated that the results of cycles of IVF/ICSI diminish in direct relationship with increasing maternal age and the number of cycles performed with autologous oocytes. Live birth rates were estimated, respectively, to be of 63.3 % and 74.6 %, in conservative and ideal perspectives for women under 30 years of age, 18.6% and 27.8 % after 41 or 42 years of age, and 6.6% and 11.3 % for women after 43 or more years of age at the end of a third cycle of IVF/ICSI with their own oocytes. However, those rates were higher than 60% and 80% for all ages when donors’ oocytes were used [Luke et al. N Eng J Med 2012].

The literature suggests that follicle development is impaired in women with advanced age, even if they present apparently normal steroidogenesis and regular menstrual cycles. In such a population, deficiencies in insulin-like growth factors (IGF) I and II, and even in the endogenous luteinizing hormone secretion, have been suggested as cofactors to explain the phenomenon [Santoro et al. JCEM 2003].

Finally, it is well known that both the quantity and quality of ovarian follicles significantly decrease as a woman advances in age, and that many women who postpone maternity may be infertile at the time they are willing to become pregnant. The main purpose of ovarian reserve evaluation, especially before ART, is to identify women with poor ovarian reserve for their chronological age. This is exactly the reason why age must always be the first marker to be considered in ovarian reserve assessment.

In my opinion, it is very clear that older women may benefit from ovarian reserve tests and the authors have reinforced it. However, their results do not support to exclude women’s chronological age as the main element to define treatment chances in the management of “elderly” infertile couples. They may help clinicians to find out acceptable chances of pregnancy through IVF, but, until now, it is not acceptable to guarantee positive results based on ovarian reserve tests, alone or in association.

On 2014 Feb 13, Bruno Ramalho Carvalho commented:

In their interesting article, Gizzo et al affirmed that modern concepts on fertility sparing consider ovarian reserve to be the most important independent female fertility predictor, even being more important than chronological age. I would say that, based on scientific evidence, such an affirmative is at least controversial.

First of all, that affirmative was attributed to a narrative review article and an article on fertility preservation in women with cancer, which are supposed to be unaproppriate references. Adequate evidences should include prospective and controlled studies, with large populations.

Until today, the bulk of literature supports age as the single most important factor in determining theoretical reproductive capability of women. In historical cohorts, the respective rates of infertility among married women at the age groups of 20-24, 25-29, 30-34, 35-39 and 40-44 years were 6%, 9%, 15%, 30% and 64% [Menken et al, Science 1986].

Women undergoing artificial insemination with donor sperm because of partner azoospermia presented with lower rates of conception or needed more cycles to achieve it after 35 years of age [Schwartz & Mayaux N Eng J Med 1982]. According to recent data, similar results were obtained in in vitro fertilization (IVF) cycles using non donor fresh eggs; birth rates for age groups of < 35, 35-37, 38-40, 41-42 and > 42 years were 36%, 28%, 18%, 10% and 4% per cycle, respectively [CDC, http://apps.nccd.cdc.gov/art/Apps/NationalSummaryReport.aspx].

Data from Red Latinoamericana de Reproducción Asistida demonstrated a significant age-dependent reduction of pregnancy rates per IVF cycle: 38% for women with 30-34 years of age; 31% for women with 35-39 years of age and 16% for older patients [Zegers-Hochschild et al, 2008; http://www.redlara.com/imagens/arq/2008_registro 2008.pdf]. Furthermore, studies have shown that women of advanced maternal age unable to achieve pregnancy through IVF were able to conceive using donor oocytes from younger women [Steiner & Paulson, 2006].

Despite the points enhanced along Gizzo et al discussion, some should note that their results clearly demonstrate that age is the best predictor of IVF results, since they reported ongoing pregnancy rates of 6.7% in the fifth decade of life, with no pregnancy after 46 years of age. It is noticeable that the authors did not mention live birth rates, which should be expected to be lower, as late pregnancy loss are very probable among the study population.

A recent study by Luke et al demonstrated that the results of cycles of IVF/ICSI diminish in direct relationship with increasing maternal age and the number of cycles performed with autologous oocytes. Live birth rates were estimated, respectively, to be of 63.3 % and 74.6 %, in conservative and ideal perspectives for women under 30 years of age, 18.6% and 27.8 % after 41 or 42 years of age, and 6.6% and 11.3 % for women after 43 or more years of age at the end of a third cycle of IVF/ICSI with their own oocytes. However, those rates were higher than 60% and 80% for all ages when donors’ oocytes were used [Luke et al. N Eng J Med 2012].

The literature suggests that follicle development is impaired in women with advanced age, even if they present apparently normal steroidogenesis and regular menstrual cycles. In such a population, deficiencies in insulin-like growth factors (IGF) I and II, and even in the endogenous luteinizing hormone secretion, have been suggested as cofactors to explain the phenomenon [Santoro et al. JCEM 2003].

Finally, it is well known that both the quantity and quality of ovarian follicles significantly decrease as a woman advances in age, and that many women who postpone maternity may be infertile at the time they are willing to become pregnant. The main purpose of ovarian reserve evaluation, especially before ART, is to identify women with poor ovarian reserve for their chronological age. This is exactly the reason why age must always be the first marker to be considered in ovarian reserve assessment.

In my opinion, it is very clear that older women may benefit from ovarian reserve tests and the authors have reinforced it. However, their results do not support to exclude women’s chronological age as the main element to define treatment chances in the management of “elderly” infertile couples. They may help clinicians to find out acceptable chances of pregnancy through IVF, but, until now, it is not acceptable to guarantee positive results based on ovarian reserve tests, alone or in association.