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

Chloé Maignien; Mathilde Bourdon; Louis Marcellin; Christelle Laguillier-Morizot; Didier Borderie; Ahmed Chargui; Catherine Patrat; Geneviève Plu-Bureau; Charles Chapron; Pietro Santulli

doi:10.1016/j.rbmo.2021.11.007

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

Reprod Biomed Online. 2022 Mar;44(3):469-477. doi: 10.1016/j.rbmo.2021.11.007. Epub 2021 Nov 18.

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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. Electronic address: pietro.santulli@aphp.fr.

PMID: 34980570
DOI: 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: Hormonal replacement therapy; Live birth; Micronized vaginal progesterone; Serum progesterone level; Vitrified–warmed embryo transfer.

Publication types

Observational Study

MeSH terms

Birth Rate*
Blastocyst
Cryopreservation
Embryo Transfer
Female
Hormone Replacement Therapy
Humans
Live Birth / epidemiology
Pregnancy
Pregnancy Rate
Progesterone*
Retrospective Studies

Substances

Progesterone