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Low serum progesterone on the day of frozen blastocyst transfer is associated with a lower live birth rate in hormonal replacement therapy cycles

  • Author Footnotes
    Ϯ Chloé Maignien and Mathilde Bourdon contributed equally to this work.
    Chloé Maignien
    Footnotes
    Ϯ Chloé Maignien and Mathilde Bourdon contributed equally to this work.
    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
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  • Author Footnotes
    Ϯ Chloé Maignien and Mathilde Bourdon contributed equally to this work.
    Mathilde Bourdon
    Footnotes
    Ϯ Chloé Maignien and Mathilde Bourdon contributed equally to this work.
    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
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  • 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
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  • 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
    Search for articles by this author
  • 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
    ‡ Charles Chapron and Pietro Santulli contributed equally to this work.
    Charles Chapron
    Footnotes
    ‡ Charles Chapron and Pietro Santulli contributed equally to this work.
    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
    ‡ Charles Chapron and Pietro Santulli contributed equally to this work.
    Pietro Santulli
    Correspondence
    Corresponding Author: Prof. Pietro Santulli, M.D. Ph.D., Département de Gynécologie Obstétrique II et Médecine de la Reproduction (Professeur Chapron), Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Paris Centre, Centre Hospitalier Universitaire Cochin, Bâtiment Port-Royal, 123 Boulevard de Port Royal, 75014 Paris, France. Phone: +33-1-58-41-36-83; Fax: +33-1-58-41-36-72.
    Footnotes
    ‡ Charles Chapron and Pietro Santulli contributed equally to this work.
    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
    Ϯ Chloé Maignien and Mathilde Bourdon contributed equally to this work.
    ‡ Charles Chapron and Pietro Santulli contributed equally to this work.
Published:November 17, 2021DOI:https://doi.org/10.1016/j.rbmo.2021.11.007

      Abstract

      Research question

      Does the serum progesterone (P) level on the day of frozen embryo transfer (FET) affect the live birth rate (LBR) with hormonal replacement therapy (HRT) cycles?

      Design

      Observational cohort study at university hospital. Patients undergoing single autologous blastocyst FET under HRT using vaginal micronized P. Women were only included once, between January 2019 and March 2020. The serum P level was measured by a single laboratory on the morning of the FET. The primary endpoint was the LBR. Statistical analyses were conducted using univariate and multivariate logistic regression models.

      Results

      The study included 915 patients. Median (25th-75th percentile) serum P level on the day of FET was 12.5 ng/mL (9.8-15.3). The LBR was 31.5% (288/915) in the overall population. Despite similar implantation rates (40.7% vs. 44.9%, p>0.05), the LBR was significantly lower in women with a P level ≤25th percentile (≤9.8 ng/ml) (26.1% vs. 33.2%, p=0.045) compared with women with P level over Centile 25, and this correlated with a significantly higher early miscarriage rate (35.9% vs. 21.6%, p=0.005). Even after adjusting for potential confounding factors in multivariate analysis, low serum P levels (≤9.8 ng/ml) remained significantly associated with lower LBR.

      Conclusion

      This study suggests that a minimum serum P level is needed to optimize reproductive outcomes in HRT-cycles with single autologous blastocyst FET. Further studies are required to evaluate whether modifications of P administration routes and/or the dosage can improve pregnancy rates. This would allow further individualization of the management of patients undergoing HRT-FET cycles.

      Keywords

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      Biography

      Pr Pietro Santulli graduated from the University Paris Descartes. He was appointed Professor in 2018. He is in charge of the Reproductive Medicine Unit in the department headed by Professor Chapron at Cochin University Hospital in Paris. His main research activities focus on assessment and management on endometriosis and assisted reproductive technologies.
      KEY MESSAGE
      Serum progesterone levels below a critical threshold (≤ 9.8 ng/mL) on the day of frozen blastocyst transfer led to significantly lower live birth rates, in hormonal replacement therapy cycles.