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Cumulus cell microRNA expression when LH is added to the ovarian stimulation protocol: a pilot study

  • Francieli Maria Vigo
    Correspondence
    Corresponding author.
    Affiliations
    Departamento de Ginecologia, Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP-EPM), Rua Napoleão de Barros, 608 Vila Clementino, São Paulo – SP CEP 04024-002, Brazil
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  • Renato Fraietta
    Affiliations
    Setor Integrado de Reprodução Humana – Departamento Cirurgia, Universidade Federal de São Paulo - Escola Paulista de Medicina (UNIFESP-EPM), Rua Botucatu, 725. Vila Vila Clementino, São Paulo - SP CEP 04024-002, Brazil
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  • Fernanda Rodrigues
    Affiliations
    Departamento de Ginecologia, Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP-EPM), Rua Napoleão de Barros, 608 Vila Clementino, São Paulo – SP CEP 04024-002, Brazil

    Huntington - Medicina Reprodutiva. Av. República do Líbano, 529 Ibirapuera, São Paulo – SP CEP 04501-000, Brazil
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  • Cristina V. Carvalho
    Affiliations
    Departamento de Ginecologia, Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP-EPM), Rua Napoleão de Barros, 608 Vila Clementino, São Paulo – SP CEP 04024-002, Brazil
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  • Tatiana C.S. Bonetti
    Affiliations
    Departamento de Ginecologia, Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP-EPM), Rua Napoleão de Barros, 608 Vila Clementino, São Paulo – SP CEP 04024-002, Brazil
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  • Eduardo L.A. Motta
    Affiliations
    Departamento de Ginecologia, Escola Paulista de Medicina da Universidade Federal de São Paulo (UNIFESP-EPM), Rua Napoleão de Barros, 608 Vila Clementino, São Paulo – SP CEP 04024-002, Brazil

    Huntington - Medicina Reprodutiva. Av. República do Líbano, 529 Ibirapuera, São Paulo – SP CEP 04501-000, Brazil
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      Abstract

      Research question

      Recombinant FSH administration in ovarian stimulation for IVF is a standard procedure, whereas the role of LH is controversial. MicroRNAs (mRNA) are small endogenous non-coding transcripts that are involved in the regulation of many cellular processes, including foliculogenesis and gonadotrophin function. The aim was to study the possible role of miRNA in ovarian follicular development in groups having different ovarian stimulation protocols. Are there different miRNA expression profiles in cumulus cells of infertile women undergoing IVF? What are the regulated pathways?

      Design

      This prospective observational study included 13 patients who fulfilled the following inclusion criteria: younger than 38 years of age; a tubal infertility factor; a male factor; or idiopathic infertility. This is a pilot study in which the patients were aleatory enrolled into two groups: seven in FSH group (recombinant FSH, 225 IU) and six in FSH plus LH group (recombinant FSH, 150 IU + recombinant LH, 75 IU). The granulosa cells obtained from the follicular ovarian retrieval were analysed using polyerase chain reaction. Results were analysed using DIANA Tools, an online bioinformatics tool.

      Results

      Among the 84 microRNAs evaluated, 11 were differentially expressed between the groups, all of which were upregulated in the FSH plus LH group, compared with the FSH group. Differentially expressed miRNA profiles are related to oestrogen signalling, oocyte meiosis and pluripotent cells regulation.

      Conclusion

      miRNA overexpression in the FSH plus LH group is consistent with the independent and fundamental role of LH in folliculogenesis, leading to a distinct molecular response between groups.

      KEYWORDS

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      Biography

      Francieli Vigo obtained her medical degree from Federal University of Rio Grande do Sul and undertook her medical residencies at Hospital de Clínicas de Porto Alegre (obsteterics and gynaecology) and Federal University of São Paulo (UNIFESP) (human reproduction). She obtained her doctorate from UNIFESP and is Director of Effetto Reprodução Humana.
      Key message
      This study aimed to demonstrate that microRNAs change during ovarian stimulation protocols; a cohort was upregulated when LH was added. Use of the LH protocol seems to produce an enhanced response in granulosa cells that compose the cumulus, boosting the oestrogen signalling pathways and oocyte meiosis, and possibly enhancing oogenesis.