Trisomic pregnancy and elevated FSH: implications for the oocyte pool hypothesis

Kline, Jennie; Kinney, Ann; Levin, Bruce; Kelly, A. Brown; Ferin, Michel; Warburton, Dorothy

doi:10.1093/humrep/der091

Cited by 42 publications

(26 citation statements)

References 61 publications

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“…Within the follicle, the influence of granulosa cells on oocyte function, i.e., the ability to be fertilized and to develop into a healthy embryo and pregnancy, remain to be understood. However, a link between FSH levels and pregnancy outcomes has been found in infertility patients in whom an increased FSH serum level was linked to an increased risk of aneuploidy in the offspring [14,26]. From this perspective, serum FSH would be a better indicator of residual follicular function and quality after CTX exposure, while AMH would be a better indicator of the extent of follicular damage.…”

Section: Discussionmentioning

confidence: 99%

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age

Detti

Uhlmann

Lu³

et al. 2013

J Assist Reprod Genet

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Purpose AMH is used to quantify the extent of follicular pool in postpubertal women, but its value after chemotherapy is unclear. We tested AMH as a marker of follicular reserve in adult mice treated with cyclophosphamide (CTX) in prepubertal age. Methods Mice received placebo or CTX at age 18 days. AMH and FSH were assessed on day 43, 56, and 95 of life. Ovaries were fixed in formalin, embedded in paraffin, and stained with H&E and TUNEL. Follicular apoptosis was graded. Results All mice exposed to CTX had a decreased number of follicles/mm 2 and significantly decreased AMH, but only 48 % of pubertal and 81 % of adult mice had increased FSH. Over time, there was an increase in FSH (p <0.05), but not a concurrent decrease in AMH, while in controls, FSH remained stable and AMH decreased. There was no correlation between histological and serological markers.Conclusions CTX administration to pre-pubertal mice caused various degrees of residual function, which were reflected by FSH, but not by AMH or by the number of ovarian follicles. AMH served as a marker of quantitative, and FSH of qualitative, residual ovarian function.

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Section: Discussionmentioning

confidence: 99%

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age

Detti

Uhlmann

Lu³

et al. 2013

J Assist Reprod Genet

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“…Accordingly, younger poor responding patients (.36 years) who had presumably a reduced ovarian reserve, had a statistically significant increased miscarriage rate, possibly related to an increased aneuploidy rate, compared to normal responders (Haadsma et al, 2010). However, elevated FSH but not AMH related to trisomic conceptions in another study (Kline et al, 2011) suggesting that hormonal imbalance may influence chromosome segregation, for instance, by directly affecting maturing oocytes . In a mouse model, unilateral ovariectomy resulted in increased numbers of spontaneously ovulated metaphase II oocytes with unaligned chromosomes in the middle-aged females with depleted follicle pools, unlike age-matched controls but similar to the advanced aged spontaneously ovulated control oocytes.…”

Section: Introductionmentioning

confidence: 90%

Oocyte ageing and its cellular basis

Eichenlaub-Ritter

2012

Int. J. Dev. Biol.

104

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Aneuploidy is extremely high in aged human oocytes. Its cellular origin has been elusive. Trisomy data implicate predominantly meiosis I errors in the genesis of oocyte aneuploidy. Susceptible recombination patterns increase risks for nondisjunction. Cytogenetic analyses of aged human oocytes and embryos from assisted reproduction (ART) suggest that aneuploidy primarily relates to precocious chromatid separation. Oocytes express a spindle assembly checkpoint (SAC), but do not arrest maturation in the presence of improperly attached or single, unattached chromosomes. The SAC may be more permissive by altered gene expression in aged oocytes. Aged oocytes frequently exhibit precocious loss of chromosome cohesion. In experimental models, cohesion cannot be restored once lost, a process possibly occurring during long meiotic arrest. Maternal age, hormonal stimulation, disturbed metabolism, and depletion of the follicle pool contribute to mitochondrial dysfunction, spindle aberrations, and errors in chromosome segregation. Caloric restriction and antioxidants reduce mitochondrial dysfunction and aneuploidy in aged rodent's oocytes. Loss of chromosome cohesion appears to be a major risk factor for aneuploidy by disturbing the sequential separation of homologs and chromatids. A permissive SAC, the presence of risky meiotic exchanges, changes in expression, and failures to resolve improper chromosome attachments, as well as mitochondrial dysfunction may synergistically increase susceptibility to meiotic errors. A healthy life style, mild stimulation and an optimal environment may delay ageing and sustain control over chromosome disjunction, whereas loss of cohesion appears to be irreversible.

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“…In humans, multiple studies suggest that increased rates of aneuploidy (Kline et al 2000, Haadsma et al 2010, KatzJaffe et al 2013, Grande et al 2015 or an inability to achieve pregnancy (Scott et al 1995, El-Toukhy et al 2002) is associated with low ovarian reserve. Other studies have produced contradictory findings detecting no association between markers of reduced ovarian reserve and aneuploidy rates (Massie et al 2008, Kline et al 2011, Grande et al 2014 or pregnancy rates (van Rooij et al 2003). This has raised questions about the validity of the limited oocyte pool hypothesis, but human studies often involve women seeking fertility treatment, many of whom would have been considered infertile prior to the advent of assisted reproduction technologies.…”

Section: The Effect Of Ovarian Reserve On Declining Fertilitymentioning

confidence: 99%

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

Pankhurst

2017

Journal of Endocrinology

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The mammalian ovary has a finite supply of oocytes, which are contained within primordial follicles where they are arrested in a dormant state. The number of primordial follicles in the ovary at puberty is highly variable between females of the same species. Females that enter puberty with a small ovarian reserve are at risk of a shorter reproductive lifespan, as their ovarian reserve is expected to be depleted faster. One of the roles of anti-Müllerian hormone (AMH) is to inhibit primordial follicle activation, which slows the rate at which the ovarian reserve is depleted. A simple interpretation is that the function of AMH is to conserve ovarian reserve. However, the females with the lowest ovarian reserve and the greatest risk of early reserve depletion have the lowest levels of AMH. In contrast, AMH apparently strongly inhibits primordial follicle activation in females with ample ovarian reserve, for reasons that remain unexplained. The rate of primordial follicle activation determines the size of the developing follicle pool, which in turn, determines how many oocytes are available to be selected for ovulation. This review discusses the evidence that AMH regulates the size of the developing follicle pool by altering the rate of primordial follicle activation in a context-dependent manner. The expression patterns of AMH across life are also consistent with changing requirements for primordial follicle activation in the ageing ovary. A potential role of AMH in the fertility of ageing females is proposed herein.

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Trisomic pregnancy and elevated FSH: implications for the oocyte pool hypothesis

Cited by 42 publications

References 61 publications

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age

Serum markers of ovarian reserve and ovarian histology in adult mice treated with cyclophosphamide in pre-pubertal age

Oocyte ageing and its cellular basis

A putative role for anti-Müllerian hormone (AMH) in optimising ovarian reserve expenditure

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