Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome

Madkour, Aicha; Bouamoud, Nouzha; Kaarouch, Ismail; Louanjli, Noureddine; Saadani, Brahim; Assou, Saïd; Aboulmaouahib, Smahane; Sefrioui, O; Amzazi, Saaïd; Copin, Henri; Benkhalifa, Moncef

doi:10.1016/j.fertnstert.2018.04.038

Cited by 24 publications

(16 citation statements)

References 90 publications

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“…Human oocyte quality can be improved with IVM/PMC manipulation of the LH signaling pathway ( Table 2). Human oocyte IVM cultures supplemented with PDE-I [95], AREG [98], CNP [99], and heterologous follicular fluid/CGC [100] improve oocyte maturation and embryo quality. Experimental IVM oocyte maturation rates (range, 70-81.6%) are approaching standard IVF maturation rates.…”

Section: Discussionmentioning

confidence: 99%

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Luteinizing Hormone Action in Human Oocyte Maturation and Quality: Signaling Pathways, Regulation, and Clinical Impact

Arroyo

Kim²,

Yeh

2020

Reprod. Sci.

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The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic maturation have recently been identified. The LH signal reduces preovulatory follicle cyclic nucleotide levels which releases oocytes from the first meiotic arrest. In the ovarian follicle, the LH signal reduces cyclic nucleotide levels via the CNP/NPR2 system, the EGF/EGF receptor network, and follicle/oocyte gap junctions. In the oocyte, reduced cyclic nucleotide levels activate the maturation promoting factor (MPF). The activated MPF induces chromosome segregation and completion of the first and second meiotic divisions. The purpose of this paper is to present an overview of the current understanding of human LH signaling regulation of oocyte meiotic maturation by identifying and integrating the human studies on this topic. We found 89 human studies in the literature that identified 24 LH follicle/oocyte signaling proteins. These studies show that human oocyte meiotic maturation is regulated by the same proteins that regulate animal oocyte meiotic maturation. We also found that these LH signaling pathway molecules regulate human oocyte quality and subsequent embryo quality. Remarkably, in vitro maturation (IVM) prematuration culture (PMC) protocols that manipulate the LH signaling pathway improve human oocyte quality of cultured human oocytes. This knowledge has improved clinical human IVM efficiency which may become a routine alternative ART for some infertile patients.

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Section: Discussionmentioning

confidence: 99%

“…Madkour et al reported a new rescue IVM approach [100]. All patients were stimulated with standard FSH doses, triggered with HCG, and oocyte retrieval was performed 36 h post-HCG.…”

Section: Lh Signaling: Experimental Human Ivm Studiesmentioning

confidence: 99%

Luteinizing Hormone Action in Human Oocyte Maturation and Quality: Signaling Pathways, Regulation, and Clinical Impact

Arroyo

Kim²,

Yeh

2020

Reprod. Sci.

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“…This suggests that the normal ''dialogue'' between oocyte and granulosa cells in these early growing follicles is altered. Several studies of messenger RNA (mRNA), miRNA, and long noncoding RNA expression profiles of PCOS have investigated the different human ovarian components, such as granulose cells and follicular fluid (2,10,12,25,26). Also, the involvement of circRNAs in the pathogenesis of conditions resulting in infertility in women has been studied, including in endometriosis (27) and age-related oocyte competence decrease (28).…”

Section: Discussionmentioning

confidence: 99%

“…Cumulus cells are a subset of granulosa cells that are intimately associated with oocytes. They express functional characteristics distinct from the mural granulosa cells of preovulatory follicles during folliculogenesis and follicle maturation (9,10). Communication between oocytes and cumulus cells is complex and involves paracrine signaling factors.…”

Section: P Olycystic Ovary Syndrome (Pcos)mentioning

confidence: 99%

Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome

Che

Liu

et al. 2019

Fertility and Sterility

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Objective: To determine aberrant circular RNA (circRNA) expression profiles in cumulus cells from polycystic ovarian syndrome (PCOS) patients and identify their potential biological functions. Design: Circular RNAs microarray analysis of human tissue. Setting: University hospital. Patient(s): A total of 40 women, including 20 PCOS patients and 20 non-PCOS patients. Intervention(s): None. Main Outcome Measure(s): A circRNA microarray containing probes that interrogate 21,442 human circRNAs to investigate differentially expressed circRNAs in cumulus cells, with potential target genes of significantly changed circRNAs and biological functions measured by microRNA support vector regression (mirSVR) and gene ontology (GO) analysis, with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Result(s): A total of 1,032 circRNAs were identified that were differentially expressed in PCOS cumulus cells, including 311 circRNAs increase and 721 circRNAs decrease (fold change R2). Four aberrantly expressed circRNAs reached a statistically significant result after Bonferroni correction (with Bonferroni correction, only circRNAs for which P < .05/21,442 ¼ 2.3 Â 10 À6 were considered statistically significant). Further analysis showed that aberrantly expressed circRNAs harbored microRNA binding sites, and some microRNAs were associated with PCOS. The GO and KEGG biological pathway analysis indicated that the genes with protein binding, mitotic nuclear envelope disassembly and metabolic pathways were statistically significantly enriched. Conclusion(s):Our data suggest that the aberrantly expressed circRNAs and their targeted genes might be associated with PCOS, providing new clues to find key diagnostic and therapeutic molecular biomarkers for PCOS patients.

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“…Novel rescue IVM approaches are being developed, including the use of heterologous follicular fluid and supernatant of cumulus-granulosa cells in culture medium in order to mimic the intact follicular microenvironment (Madkour et al, 2018). While results appear promising, more data are required to understand the contribution of such approaches to improving clinical outcomes (Escrich et al, 2018).…”

Section: Rescue Of Oocytes Which Have Failed To Mature In Stimulated mentioning

confidence: 99%

The Place of In Vitro Maturation in Assisted Reproductive Technology

Vuong

Gilchrist

et al. 2019

FandR

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In vitro maturation (IVM) is an assisted reproductive technology (ART) whereby immature cumulus-oocyte complexes are collected and matured in vitro, without need for controlled ovarian stimulation and ovulation triggering. Advantages of IVM over in vitro fertilization (IVF) include mild or no stimulation, lower medication costs and less patient burden. However, early clinical outcomes with IVM were suboptimal. More recently, clinical studies reported live birth rates after IVM of about 40%. New IVM culture systems are being used to improve the efficacy of IVM. These have been in widespread use for animals for many years and are now showing promise in the clinical setting. Patients more likely to benefit from IVM over IVF include those at risk of OHSS (e.g. women with polycystic ovary syndrome), when the time for ovarian stimulation is limited, or where sustained elevations of estradiol are contraindicated (e.g. oncofertility indications). The main barrier to use of IVM to date was its relative efficacy compared with IVF, and there have also been concerns over the health of infants born following IVM. However, no differences in congenital abnormalities between IVM and other ARTs have been identified. In addition, there is a lack of both experience and standardized protocols. Strategies to overcome barriers to the use of IVM include better training for clinicians, more and better funded research in the field, and improved recognition of IVM by fertility specialists. Overall, IVM offers a valuable alternative for ART in select patient populations. New approaches to IVM appear to have the potential to achieve pregnancy outcomes equivalent to those after IVF. Increasing the use of IVM in the future can be achieved with improved training and education for fertility specialists, and increased funding for IVM research, with the ultimate goal of improving fertility outcomes.

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Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome

Abstract: This adapted IVM system could be used to reach an acceptable result in meiotic competence and competent metaphase II oocytes capable of developing into intact embryos after fertilization and before transfer.

Cited by 24 publications

References 90 publications

Luteinizing Hormone Action in Human Oocyte Maturation and Quality: Signaling Pathways, Regulation, and Clinical Impact

Luteinizing Hormone Action in Human Oocyte Maturation and Quality: Signaling Pathways, Regulation, and Clinical Impact

Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome

The Place of In Vitro Maturation in Assisted Reproductive Technology

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