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Utilization of in vitro maturation in cases with a FSH receptor mutation

  • Assisted Reproduction Technologies
  • Published:
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Abstract

Purpose

To identify the FSH receptor (FSHR) variant and efficacy of in vitro maturation (IVM) in a 28-year-old woman with secondary amenorrhea, primary infertility, and ovarian resistance to FSH, and to analyze the genotype-to-phenotype relationship in cases of FSHR mutation for the development of an IVM algorithm for use in patients with gonadotropin resistance syndrome (GRS).

Methods

Oocytes retrieved after menstruation induction with norethisterone, followed by daily estrogen and an ovulatory trigger, underwent IVM, ICSI, and culture in a time-lapse (TL) incubator. Embryo transfers were performed on day 2, and after thawing on day 5. Genes associated with disorders of sex development were sequenced for both the patient and her parents. All reported cases of FSHR mutation were analyzed to investigate genotype/phenotypic relationships.

Results

After ovum pickup, seven of 16 oocytes matured and all fertilized. After unsuccessful day 2 transfer, our patient delivered with a thawed day 5 blastocyst, the sole embryo without abnormal TL phenotypes. Genetic analysis revealed a new composite heterozygous FSHR variant. Analysis of our patient case with published cases of GRS revealed associations among FSHR variant genotype, location on the FSHR, functionality of tested variants, and type of amenorrhea. An algorithm for application of IVM for GRS patients was developed.

Conclusions

We report two novel variants of the FSHR. Although IVM successfully matured some oocytes, only one resulted in an embryo with normal TL phenotypes. We recommend FSHR genetic testing in GRS patients, which will help guide their suitability for IVM.

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Authors and Affiliations

  1. Department of Gyneacology, Obstetrics and Reproductive Medicine, Hospital Foch, 92150, Suresnes, France

    Achraf Benammar, Renato Fanchin, Meryem Filali-Baba, Camille Fossard, Jessica Vandame, Paul Pirtea, Catherine Racowsky, Jean-Marc Ayoubi & Marine Poulain

  2. Université Paris-Saclay, INRAE, ENVA, UVSQ, BREED, 78350, Jouy-en-Josas, France

    François Vialard, Jean-Marc Ayoubi & Marine Poulain

  3. Genetics Federation, CHI de Poissy St Germain en Laye, 78303, Poissy, France

    François Vialard

Authors
  1. Achraf Benammar
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  2. Renato Fanchin
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Renato Fanchin, Meryem Filali Baba, Catherine Racowsky, François Vialard, Paul Pirtea, Camille Fossard, Jessica Vandame, Jean Marc Ayoubi, and Marine Poulain. The first draft of the manuscript was written by Achraf Benammar, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Achraf Benammar.

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The study was approved by the Ethics Committee of Hôpital Foch, with the Institutional Review Board Code of 00012437.

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The patient consented to publication of her case.

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The authors declare no competing interests.

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Benammar, A., Fanchin, R., Filali-Baba, M. et al. Utilization of in vitro maturation in cases with a FSH receptor mutation. J Assist Reprod Genet 38, 1311–1321 (2021). https://doi.org/10.1007/s10815-021-02249-3

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  • DOI: https://doi.org/10.1007/s10815-021-02249-3

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