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Full length article| Volume 216, P164-168, September 2017

Optimal routes of administration, vehicles and timing of progesterone treatment for inhibition of delivery during pregnancy

  • Dajun Fang
    Affiliations
    Southern Medical University, Guangzhou, China

    Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
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  • Mario Moreno
    Affiliations
    Stanford University School of Medicine, Stanford, CA, USA
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  • Robert E. Garfield
    Affiliations
    Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China

    Department of Obstetrics and Gynecology, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USA
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  • Ruben Kuon
    Affiliations
    Universitätsfrauenklinik Heidelberg, Abteilung für Gynäkologische Endokrinologie und Fertilitätsstörungen, 69120 Heidelberg, Germany
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  • Huimin Xia
    Correspondence
    Corresponding author at: Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
    Affiliations
    Southern Medical University, Guangzhou, China

    Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China
    Search for articles by this author

      Abstract

      Objectives

      Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone.

      Study design

      Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve® (also known as Crinone®), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied.

      Results

      Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P < 0.05–<0.001) delay delivery, but vaginal Prochieve® did not. Administration of P4 in late gestation also prevented (P < 0.001) delivery even when given 8 h before delivery.

      Conclusions

      Prochieve® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration.

      Keywords

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