Poor oocyte quality rather than implantation failure as a cause of age‐related decline in female fertility

Navot, Daniel; Bergh, PA; D, Ma. Cristina Williams Ph.; Garrisi, G. John; Guzmán, Luis; Sandler, Bernard; Grunfeld, L.

doi:10.1016/0020-7292(92)90759-c

Cited by 85 publications

(105 citation statements)

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“…Higher mean quality of oocytes from young healthy donors in comparison with oocytes from infertile patients is indisputable. A vast body of the literature shows that the decline in ART outcome observed in women older than 35 years is completely overcome by the use of oocytes from donors bellow this age (Navot et al, 1991). In our study, oocyte donation cycles obtained higher pregnancy and implantation rates than patients using their own oocytes, confirming that oocyte quality is better in young, healthy donors.…”

Section: Discussionsupporting

confidence: 77%

High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected

Esbert

Pacheco

Soares³

et al. 2018

Andrology

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Background: Time-lapse monitoring (TLM) technology has been implemented in the clinical setting for the culture and selection of human embryos. Many studies have assessed the association between sperm DNA fragmentation (sDNAf) and clinical outcomes after ART, but little is known about the influence of sDNA on embryo morphokinetics. Objectives: The objective of this retrospective study, which includes 971 embryos from 135 consecutive ICSI cycles (56 cases with own oocytes, 79 with oocytes from young and healthy donors), was to assess if sDNAf has an impact on embryo morphokinetics. Materials and methods: Samples used to perform ICSI were analyzed by the flow cytometry TUNEL assay, and embryo development was assessed through an EmbyoScope â system. The association between sDNAf and the timings of cell cleavage was analyzed by categorizing the first variable into quartiles: ≤6.50%; 6.51-10.70%; 10.71-20.15%; >20.15%. Results: In cases where sDNAf was above 20.15% (the upper quartile), embryos derived from donated oocytes (n = 644) showed significantly slower divisions. Such association was not observed in embryos obtained from the patients' own oocytes (n = 327). The embryo cleavage pattern (either normal, direct from 1 to 3 blastomeres, direct from 1 to 4 blastomeres, incomplete, reversed or asynchronous) was independent of the sDNAf level. Blastocyst arrival rate was 63.0% and the rate of good quality embryos (transferred and frozen embryos divided by the number of zygotes) was 45.49%. Neither parameter was related to the levels of sDNAf. Discussion: According to our results, the association between high sDNAf and donated oocytes led to delayed cell division. To our knowledge, this is the first study suggesting that sDNAf can delay human embryo cleavage timings when oocytes from donors are inseminated.Conclusions: This finding may indicate that, in the presence of increased DNA damage, time is needed before the first embryonic cell division for the activation of the optimal DNA repairing machinery in higher quality oocytes.

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Section: Discussionsupporting

confidence: 77%

High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected

Esbert

Pacheco

Soares³

et al. 2018

Andrology

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“…Considerable evidence, largely derived from studies of assisted reproduction, has established beyond question that fecundity decreases as women age (Albrecht et al, 1982;DeCherney and Berkowitz, 1982;Federation CECOS et al, 1982;Virro and Shewchuk, 1984;Padilla and Garcia, 1989;Edvinsson et al, 1990;Sauer et al, 1990;Levran et al, 1991;Navot et al, 1991;Pearlstone et al, 1992;FIVNAT, 1993;Meldrum, 1993). Changes in ovarian endocrine function documented here are consistent with observations of lower fecundity in older women.…”

Section: Discussionsupporting

confidence: 81%

Ovarian function in the latter half of the reproductive lifespan

O'Rourke¹,

Lipson²,

Ellison³

1996

Am. J. Hum. Biol.

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The relationship of age to four aspects of ovarian function was investigated: daily progesterone levels, pulsatile progesterone secretion, foHicular and luteal estradiol levels, and preovulatory estradiol levels. Daily progesterone levels decrease after age 40. Pulsatile progesterone secretion remains approximately stable with age, though older women have somewhat higher late luteal activity. Daily follicular and luteal estradiol levels decrease with advancing age, but preovulatory peak estradiol remains stable. Some of these changes undoubtedly have negative effects on fecundity, such as lower follicular estradiol and average progesterone, via effects on endometrial development and support. But other changes identified, such as stability of preovulatory estradiol levels and thereby presumptive capacity to stimulate a luteinizing hormone (LH) surge despite lower follicular and luteal levels, as well as increased pulsatile progesterone secretion around the time of implantation, appear designed t o conserve and maintain function. Thus, ovarian endocrine function over the course of reproductive life represents a process of change, but not one of generalized functional decline. Rather, aging with respect to ovarian endocrine function may proceed on a track, or on multiple tracks, which are largely separable from the continual depletion of oocyte stores which occurs over the lifetime. c 1996 Wlley-Llss, IncThe ovary is a n organ with two related functions: manufacture, storage, and release of oocytes, and production of reproductive hormones, especially estradiol and progesterone. Oocytes with their enclosing follicles are formed during prenatal life, and a woman's supply of gametes is continuously, indeed exponentially (Block, 1952;Baker, 1963;Richardson et al., 1987), depleted over her lifetime, with ultimate exhaustion or near exhaustion leading to menopause. Ovarian endocrine function is closely tied to the cyclic, monthly process of follicular maturation and ovulation. Yet, as we will show here, hormone production as women age does not follow a trajectory paralleling that of declining gamete supply over the life course, which suggests that endocrine function is not linked to oocyte stores in a simple mechanistic fashion.During the first portion, or follicular phase, of the menstrual cycle, developing follicles secrete increasing amounts of estradiol. After ovulation occurs at about midcycle, the remaining follicular cells form the corpus luteum, which secretes progesterone and estradiol during the latter portion, or luteal phase, of the cycle. Both estradiol and progesterone regulate their own production by exerting negative feedback on the stimulatory hormones of the hypothalamus and pituitary. Follicular estradiol promotes endometrial proliferation and affects the maturation and ultimate fertilizability of the oocyte (Yoshimura and Wallach, 1987;Kreiner et al., 1987; Maslar, 1988;Zelinski-Wooten et al., 1994). As titers become sufficiently high, estradiol ceases to suppress hypothalamic and pituitary act...

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“…Numerous clinical studies have shown that the fertility of women starts to decrease at the age of 35, and, concomitantly, the oocyte quality also starts to decline. [40][41][42][43] A transcriptome study showed that 40 of 78 downregulated genes in the ovaries of ageing mice were ribosome-related genes, 43 indicating that downregulation of ribosome function might have a significant impact on fertility. Thus, we next investigated whether ageing could alter 5.8S rRNA maturation and whether the level of MPP6, the 5.8S pre-rRNA maturation factor, could be affected by ageing.…”

Section: The Ageing-associated Decrease In Oocyte Quality Partiallymentioning

confidence: 99%

The 5.8S pre‐rRNA maturation factor, M‐phase phosphoprotein 6, is a female fertility factor required for oocyte quality and meiosis

et al. 2020

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Objectives M‐phase phosphoprotein 6 (MPP6) is important for 5.8S pre‐rRNA maturation in somatic cells and was screened as a female fertility factor. However, whether MPP6 functions in oocyte meiosis and fertility is not yet known. We aimed to address this. Materials and Methods Mouse oocytes with surrounded nucleus (SN) or non‐surrounded nucleus (NSN) were used for all experiments. Peptide nanoparticle‐mediated antibody transfection was used to deplete MPP6. Immunofluorescence staining, immunohistochemistry and live tracker staining were used to examine MPP6 localization and characterize phenotypes after control or MPP6 depletion. High‐fidelity PCR and fluorescence in situ hybridization (FISH) were used to examine the localization and level of 5.8S rRNAs. Western blot was used to examine the protein level. MPP6‐EGFP mRNA microinjection was used to do the rescue. Results MPP6 was enriched within ovaries and oocytes. MPP6 depletion significantly impeded oocyte meiosis. MPP6 depletion increased 5.8S pre‐rRNA. The mRNA levels of MPP6 and 5.8S rRNA decreased within ageing oocytes, and MPP6 mRNA injection partially increased 5.8S rRNA maturation and improved oocyte quality. Conclusions MPP6 is required for 5.8S rRNA maturation, meiosis and quality control in mouse oocytes, and MPP6 level might be a marker for oocyte quality.

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Poor oocyte quality rather than implantation failure as a cause of age‐related decline in female fertility

Cited by 85 publications

References 0 publications

High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected

High sperm DNA fragmentation delays human embryo kinetics when oocytes from young and healthy donors are microinjected

Ovarian function in the latter half of the reproductive lifespan

The 5.8S pre‐rRNA maturation factor, M‐phase phosphoprotein 6, is a female fertility factor required for oocyte quality and meiosis

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