Publications by authors named "Catherine M Combelles"

Objective: To assess whether co-culture with vitrified-warmed cumulus cells (CCs) in media drops improves rescue in vitro maturation (IVM) of previously vitrified immature oocytes. Previous studies have shown improved rescue IVM of fresh immature oocytes when cocultured with CCs in a three-dimensional matrix. However, the scheduling and workload of embryologists would benefit from a simpler IVM approach, particularly in the setting of time-sensitive oncofertility oocyte cryopreservation (OC) cases.

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Ovarian cells are critical for reproduction and steroidogenesis, which are functions that can be impacted by exposure to xenobiotics. As in other extra-hepatic tissues, biotransformation events may occur at the ovarian level. Such metabolic events deserve interest, notably as they may modulate the overall exposure and toxicity of xenobiotics.

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Bisphenol A (BPA) is detectable in follicular fluid. However, the effect of BPA exposure on human cumulus cells (CC) that surround the oocyte and are crucial for oocyte competence has been largely unexplored. We exposed primary cultures of CC to increasing concentrations of BPA [0,0.

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Study Question: Does bisphenol-A (BPA) affect gene expression in human membrana granulosa cells (MGC)?

Summary Answer: In vitro, short exposure to supra-physiological concentrations of BPA alters human MGC gene expression.

What Is Known Already: Exposure to BPA may interfere with reproductive endocrine signaling. In vitro studies, mostly in animal models, have shown an inverse correlation between exposure to BPA and follicular growth, meiosis, and steroid hormone production in granulosa cells.

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Study Question: Does exposure to bisphenol-A (BPA) affect the maturation of human oocytes in vitro?

Summary Answer: There was a dose-response association of BPA exposure with altered human oocyte maturation in vitro.

What Is Known Already: There is widespread exposure of the general population to BPA. BPA has been detected in the human follicular fluid.

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Improved oncological treatments permit increased survival rates, although cancer patients remain at risk of losing ovarian function. An attractive option for fertility preservation includes the use of immature oocytes, a strategy which can occur on a rapid timeline and without hormonal stimulation. As a result, cancer therapy can proceed promptly even in patients with hormone-sensitive tumors.

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Mammalian reproduction hinges upon the timely ovulation of a fully differentiated oocyte. This event is the culmination of a complex and dynamic developmental relationship between the oocyte and the antral follicle housing it; the antral follicle constitutes a specialized microenvironment or niche, uniquely suited to the needs of the oocyte as it approaches ovulation. During this time, the oocyte must complete its final growth, capacitation, and nuclear and cytoplasmic maturation.

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David Albertini has dedicated his life to illuminating our understanding of the most wondrous of cells--the oocyte. Beyond his powerful scientific contributions, he has mindfully and tirelessly mentored and educated scientists and clinicians in our field. In this essay which reports a dialogue, David Albertini shares some of the key experiences that have governed his career path.

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Purpose: To avoid inducing a state of oxidative stress (OS), assisted reproductive technologies (ART) must maintain a balance of reactive oxygen species (ROS) and antioxidants during the in vitro culture of oocytes. However, oocyte requirements and tolerance thresholds for ROS during in vivo development are still unclear. Previous studies have examined ROS levels in follicular fluid (FF) using pooled samples or according to follicle size.

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Study Question: Is the cytoskeletal and chromosomal organization of failed fertilized oocytes from severely obese patients (BMI ≥ 35 kg/m²) altered compared with that in patients with normal BMI (BMI 18.5-24.9 kg/m²)?

Summary Answer: Compared with normal BMI patients, severe obesity was associated with a greater prevalence of spindle anomalies and non-aligned chromosomes in failed fertilized oocytes.

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Protection of embryos against oxidative insults during culture is necessary to maintain viability. Generation of excessive levels of reactive oxygen species (ROS) is triggered by various components of the in vitro environment, most of which embryos do not normally encounter in vivo. To compensate for these deficiencies in the culture environment, antioxidants and chelators are often used to control or suppress ROS levels as embryos develop.

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Freezing unfertilized oocytes is an option for females without a partner, either to preserve their fertility prior to sterilizing cancer treatment or for social reasons. Our study considered whether it is best to freeze immature human oocytes at the germinal vesicle (GV) stage, prior to in vitro maturation (IVM) or at metaphase-II (M-II), after IVM. Sibling GV-stage oocytes from stimulated ICSI cycles were allocated to freezing either prior to (n=109) or after (n=107) IVM.

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Purpose: To determine if the antioxidant superoxide dismutase-1 (SOD1 or Cu,Zn-SOD) is released by cultured human cleavage-stage embryos and to assess any link between SOD1 and implantation potential.

Methods: Women (n = 91; ≤40 years old) undergoing IVF treatment with transfer of one or two 8-cell embryos that resulted in 0 or 100% implantation were included. Following individual embryo culture, spent medium samples (n = 122) were collected and levels of SOD1 protein were measured by an enzyme-linked immunosorbent assay.

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Purpose: The cryopreservation of immature oocytes permits oocyte banking for patients at risk of losing their fertility. However, the optimum protocol for such fertility preservation remains uncertain.

Methods: The present study investigated the survival, maturation, cytoskeletal and chromosome organization of sibling immature oocytes leftover from controlled ovarian stimulation cycles, that were either slow-frozen (with choline-substitution) or vitrified.

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Follicular fluid is an important environment for oocyte development, yet current knowledge regarding its in vivo oxidant and antioxidant levels remains limited. Examining follicular fluid oxidants and antioxidants will improve understanding of their changes in vivo and contribute to optimisation of in vitro maturation conditions. The aim of the present study was to consider selected markers, namely catalase (CAT) enzyme activity, total antioxidant capacity (TAC) and hydrogen peroxide (H(2)O(2)) in follicular fluid samples (n = 503) originating from bovine antral follicles.

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The oocyte's meiotic spindle is a dynamic structure that relies on microtubule organization and regulation by centrosomes. Disorganization of centrosomal proteins, including the nuclear mitotic apparatus (NuMA) protein and the molecular motor complex dynein/dynactin, can lead to chromosomal instability and developmental abnormalities. The present study reports the distribution and function of these proteins in human oocytes, zygotes and early embryos.

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Unusual and consistent defects in infertility patients merit attention as these may indicate an underlying genetic abnormality, in turn necessitating tailored management strategies. We describe a case of repeated early pregnancy loss from in vivo conceptions, followed by cancelled embryo transfers after one IVF and one ICSI/PGD cycle. Following the unexpected presence of cleaved embryos at the fertilization check in the first IVF attempt, oocytes and embryos were subsequently analyzed in an ICSI/PGD case.

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Article Synopsis
  • Cases of total fertilization failure (TFF) can lead to canceled IVF cycles, with few available solutions.
  • An infertile couple failed to conceive after multiple IVF and ICSI attempts, despite normal sperm morphology and functional tests.
  • The investigation revealed cytoplasmic defects in the oocytes as the main issue, but using the husband's sperm in donor oocytes successfully led to the birth of healthy twins, suggesting a potential strategy for other couples facing TFF.
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The antral follicle constitutes a complex and regulated ovarian microenvironment that influences oocyte quality. Oxidative stress is a cellular state that may play a role during folliculogenesis and oogenesis, although direct supporting evidence is currently lacking. We thus evaluated the expression of the three isoforms (SOD1, SOD2, and SOD3) of the enzymatic antioxidant superoxide dismutase in all the cellular (granulosa cells, cumulus cells, and oocytes) and extracellular (follicular fluid) compartments of the follicle.

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In the efforts aimed at improving the quality of in-vitro-matured human oocytes, the dynamic balance and roles of pro-/antioxidants merit further consideration. In-vitro maturation (IVM) is emerging as a popular technology at the forefront of fertility treatment and preservation. However, standard in-vitro culture conditions exert oxidative stress or an imbalance between oxidants and antioxidants.

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Objective: To determine whether increasing the number of embryos transferred beyond five increases pregnancy rates in women aged > 40 years.

Design: Retrospective analysis of cycles performed between January 1998 and July 2003.

Setting: University-affiliated teaching hospital.

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The interplay between genetic and epigenetic factors plays a central role in mammalian embryo production strategies that superimpose ex vivo or in vivo manipulations upon strain background characteristics. In this study, we examined the relationship between genetic background and the phenotypic properties of mouse metaphase-II (M-II) oocytes that were matured under in vivo (IVO) or in vitro conditions, either in a basal (IVM) or a supplemented (IVM + ) medium. Differences existed amongst inbred (C57BL/6), outbred (CF-1, Black Swiss, NU/NU) and hybrid lines (B6D2F1) induced to superovulate with regard to cytoplasmic microtubule organizing center (MTOC) number but not spindle size or shape, except for larger and asymmetrical spindles in Black Swiss oocytes.

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