Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation

Navot, Daniel; Drews, M.R.; Bergh, Paul A.; Guzman, Ida; Karstaedt, Alexis; Scott, Richard T.; Garrisi, G. John; Hofmann, Glen E.

doi:10.1016/s0015-0282(16)56459-0

Cited by 209 publications

(83 citation statements)

References 21 publications

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“…This is largely attributed to females producing eggs of compromised developmental competence, particularly with spindle/chromosome anomalies (Luke et al., 2012; Navot et al., 1994). Although multiple molecules have been identified to contribute to the maternal age effect, additional factors remain to be explored for the clinical management of fertility issues.…”

Section: Discussionmentioning

confidence: 99%

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

Zeng

Jiang²,

et al. 2018

Aging Cell

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SIRT4 modulates energy homeostasis in multiple cell types and tissues. However, its role in meiotic oocytes remains unknown. Here, we report that mouse oocytes overexpressing SIRT4 are unable to completely progress through meiosis, showing the inadequate mitochondrial redistribution, lowered ATP content, elevated reactive oxygen species (ROS) level, with the severely disrupted spindle/chromosome organization. Moreover, we find that phosphorylation of Ser293‐PDHE1α mediates the effects of SIRT4 overexpression on metabolic activity and meiotic events in oocytes by performing functional rescue experiments. By chance, we discover the SIRT4 upregulation in oocytes from aged mice; and importantly, the maternal age‐associated deficient phenotypes in oocytes can be partly rescued through the knockdown of SIRT4. These findings reveal the critical role for SIRT4 in the control of energy metabolism and meiotic apparatus during oocyte maturation and indicate that SIRT4 is an essential factor determining oocyte quality.

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Section: Discussionmentioning

confidence: 99%

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

Zeng

Jiang²,

et al. 2018

Aging Cell

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“…Sauer et al (12), Abdalla et al (13), Navot et al (14), and Check et al (15) found an effect of the woman's age on the quality of the oocyte, but no or only a negligible effect on uterine receptivity. In more re cent studies, Sauer and co-workers (16,17) have con firmed th at there is no aging effect of the uterus in women undergoing donor IVF.…”

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confidence: 99%

“…Most of the studies that used data from donor IVF (12,14,15,17,18,(20)(21)(22) only examined differ ences in IVF results between two age groups. Ex isting age effects might have been missed because the chosen cutoff point did not maximize the differ ences between the two age groups.…”

mentioning

confidence: 99%

The impact of the woman's age on the success of standard and donor in vitro fertilization

Stolwijk¹,

Zielhuis²,

Sauer³

et al. 1997

Fertility and Sterility

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Objective:To study the effect of the age of the woman who provides the oocytes 01 who receives the embryos on results of IVF-ET.Design: Historical cohort study. Multi vai'iate regression analysis was used to study the ago effect continuously and after adjustment for confounding. Result(s):The number of oocytes decreased with aging of the oocyte provider. More women who received oocytes from donors aged 20 to 23 years had at least one good embryo transferred than women who received oocytes from older donors. The age of the woman who received the embryos had no effect on IVF outcomes. In women > 40 years who underwent standard IVF, the probability of pregnancy decreased. No such relationships were observed for donor IVF, but all the oocyte donors were younger.Conclusion(s): An age effect for ongoing pregnancy was only found in women > 40 years who underwent standard IVF independent of the lower number of oocytes and suggests decreas ing oocyte quality. (Fertil Steril® 1997; 67:702" 10

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“…Although the primary cause for this decline is the gradual depletion of oocytes in aging ovary, it has been suggested that the decline of oocyte quality is also an important contributing factor [7]. Studies of older women (>40 years of age) undergoing IVF of donation with young oocytes indicated that oocyte quality decline is the major cause for infertility in older women, and oocyte age can even compensate for other age-related changes in the endocrine system and reproductive tract [8,9]. Therefore, it appears that the quality of oocytes declines with maternal aging and affects embryonic development [3,10,11].…”

Section: Introductionmentioning

confidence: 99%

Cryo-survival, fertilization and early embryonic development of vitrified oocytes derived from mice of different reproductive age

Yan

Suzuki

et al. 2010

J Assist Reprod Genet

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Purpose To evaluate the effect of female reproductive age on oocyte cryo-survival, fertilization and the subsequent embryonic development following vitrification using the mouse model in order to address the question of how maternal reproductive age is related to fertility preservation. Methods Oocytes were collected from mice of different reproductive age: (1) 8-10 weeks, (2) 16-20 weeks, (3) 32-36 weeks, and (4) 44-48 weeks. Following vitrification and warming, the oocytes in each group were assessed for cryo-survival, fertilization and embryonic development as well as for the quality of blastocysts. Fresh oocytes without undergoing vitrification were used in each age group as controls. ResultsThe mean number of oocytes retrieved following superovulation was found to reduce significantly (P<0.05) in mice from 32-36 weeks of age (18.1±8.5) compared with 8-10 weeks of age (26.8±9.8) and 16-20 weeks of age (23.9±4.2) respectively. The cryo-survival rate of oocytes was reduced significantly (P<0.05) in mice of 44-48 weeks of age (90.4%±7.9) compared with the other 3 groups (98.8%±2.1, 98.0%±3.3 and 98.5%±2.2, respectively). The cleavage rate of vitrified oocytes declined significantly following the increase in maternal age in mice of 32-36 weeks of age (69.7%±20.8) forward (63.6%±9.2). However, no significant difference in the cleavage rate was found among the control groups of different maternal ages. The rate of embryo development to the blastocyst stage in the vitrified oocytes also significantly declined following the increase in maternal age (71.8%± 8.8, 66.4%±10.7, 64.2%±17.4 and 4.1%±8.3 respectively).There were no such differences in the rates of embryo development to the blastocyst stage among the control groups following the increase in maternal age (75.9%±12.2, 79.5%±28.9, 70.2%±17.4 and 69.3%±19.0 respectively). However, the quality of blastocysts produced from 32-36 weeks and 44-48 weeks of ages was significantly poor in term of total cell numbers and the ratio of inner cell mass(ICM) / trophectoderm (TE) compared to younger age in both vitrified and control groups Conclusions Cryo-survival of oocytes following vitrification and warming procedures is associated with female reproductive age. There is a more negative impact on the oocytes following vitrification and warming with the increase of maternal age.Keywords Female reproductive age . Oocytes . Cryo-survival . Fertilization . Embryonic development . Blastocyst Capsule Reduction in fertilization rate and poor embryonic development following vitrification procedure has been found to be associated with increased reproductive age.

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Age-related decline in female fertility is not due to diminished capacity of the uterus to sustain embryo implantation

Cited by 209 publications

References 21 publications

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

SIRT4 is essential for metabolic control and meiotic structure during mouse oocyte maturation

The impact of the woman's age on the success of standard and donor in vitro fertilization

Cryo-survival, fertilization and early embryonic development of vitrified oocytes derived from mice of different reproductive age

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