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Article| Volume 44, ISSUE 3, P469-477, March 2022

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Low serum progesterone affects live birth rate in cryopreserved blastocyst transfer cycles using hormone replacement therapy

  • Author Footnotes
    # Contributed equally.
    Chloé Maignien
    Footnotes
    # Contributed equally.
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France
    Search for articles by this author
  • Author Footnotes
    # Contributed equally.
    Mathilde Bourdon
    Footnotes
    # Contributed equally.
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France

    Department “Development, Reproduction and Cancer”, Cochin Institute, INSERM U1016 (Professor Batteux), 27 Rue du Faubourg Saint-Jacques 75014 Paris, France
    Search for articles by this author
  • Louis Marcellin
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France

    Department “Development, Reproduction and Cancer”, Cochin Institute, INSERM U1016 (Professor Batteux), 27 Rue du Faubourg Saint-Jacques 75014 Paris, France
    Search for articles by this author
  • Christelle Laguillier-Morizot
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Biological Endocrinology (Professor Guibourdenche), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 27 Rue du Faubourg Saint-Jacques 75014 Paris, France
    Search for articles by this author
  • Didier Borderie
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Automated Biological Diagnosis (Professor Borderie), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 27 Rue du Faubourg Saint-Jacques 75014 Paris, France
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  • Ahmed Chargui
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Histology and Reproductive Biology (Professor Patrat), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France
    Search for articles by this author
  • Catherine Patrat
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Histology and Reproductive Biology (Professor Patrat), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France
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  • Geneviève Plu-Bureau
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France

    Equipe EPOPE, INSERM U1153
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  • Author Footnotes
    † Contributed equally.
    Charles Chapron
    Footnotes
    † Contributed equally.
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France

    Department “Development, Reproduction and Cancer”, Cochin Institute, INSERM U1016 (Professor Batteux), 27 Rue du Faubourg Saint-Jacques 75014 Paris, France
    Search for articles by this author
  • Author Footnotes
    † Contributed equally.
    Pietro Santulli
    Correspondence
    Corresponding author.
    Footnotes
    † Contributed equally.
    Affiliations
    Université de Paris, Faculté de Santé, 12 Rue de l'Ecole de Médecine 75006 Paris, France

    Department of Gynecology Obstetrics II and Reproductive Medicine (Professor Chapron), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Paris Centre (HUPC), Centre Hospitalier Universitaire (CHU) Cochin, 123 Boulevard de Port Royal 75014 Paris, France

    Department “Development, Reproduction and Cancer”, Cochin Institute, INSERM U1016 (Professor Batteux), 27 Rue du Faubourg Saint-Jacques 75014 Paris, France
    Search for articles by this author
  • Author Footnotes
    # Contributed equally.
    † Contributed equally.
Published:November 17, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.11.007

      Abstract

      Research question

      Does serum progesterone concentration on the day of vitrified–warmed embryo transfer affect live birth rate (LBR) with hormonal replacement therapy (HRT) cycles?

      Design

      Observational cohort study of patients (n = 915) undergoing single autologous vitrified–warmed blastocyst transfer under HRT using vaginal micronized progesterone. Women were included once, between January 2019 and March 2020. Serum progesterone concentration was measured by a single laboratory on the morning of embryo transfer. The primary end point was LBR. Univariate and multivariate logistic regression models were used for statistical analyses.

      Results

      Median (25th–75th percentile) serum progesterone concentration on the day of embryo transfer was 12.5 ng/ml (9.8–15.3). The LBR was 31.5% (288/915) in the overall population. No significant differences were found in implantation rates (40.7% versus 44.9%); LBR was significantly lower in women with a progesterone concentration ≤25th percentile (≤9.8 ng/ml) (26.1% versus 33.2%, P = 0.045) versus women with a progesterone concentration >25th percentile. This correlated with a significantly higher early miscarriage rate (35.9% versus 21.6%, P = 0.005). After adjusting for potential confounding factors in multivariate analysis, low serum progesterone levels (≤9.8 ng/ml) remained significantly associated with lower LBR (OR 0.68 95% CI 0.48 to 0.97).

      Conclusion

      A minimum serum progesterone concentration is needed to optimize reproductive outcomes in HRT cycles with single autologous vitrified–warmed blastocyst transfer. Whether modifications of progesterone administration routes, dosage, or both, can improve pregnancy rates needs further study so that treatment of patients undergoing HRT cycles can be further individualized.

      KEYWORDS

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        • Zegers-Hochschild F.
        • Adamson G.D.
        • Dyer S.
        • Racowsky C.
        • de Mouzon J.
        • Sokol R.
        • Rienzi L.
        • Sunde A.
        • Schmidt L.
        • Cooke I.D.
        • Simpson J.L.
        • van der Poel S.
        The International Glossary on Infertility and Fertility Care, 2017.
        Hum. Reprod. Oxf. Engl. 2017; 32: 1786-1801https://doi.org/10.1093/humrep/dex234

      Biography

      Professor Pietro Santulli graduated from the University Paris Descartes. He was appointed Professor in 2018. He oversees the Reproductive Medicine Unit in the department headed by Professor Chapron, Cochin University Hospital, Paris. His main research activities focus on assessment and management of endometriosis and assisted reproductive technologies.
      Key message
      Serum progesterone levels below a critical threshold (≤9.8 ng/ml) on the day of vitrified–warmed blastocyst transfer led to lower live birth rates in artificial cycles. Further studies need to evaluate whether modification of progesterone administration (route, dosage, or both) can improve live birth rates in this subgroup of patients.