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Clinical and Experimental Obstetrics & Gynecology  2018, Vol. 45 Issue (5): 652-655    DOI: 10.12891/ceog4693.2018
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Pros and cons of the use of progesterone to reduce miscarriage rates
J.H. Check1, 2, *()
1 Cooper Medical School of Rowan University, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology & Infertility, Camden, NJ, USA
2 Cooper Institute for Reproductive and Hormonal Disorders, P.C., Mt. Laurel, NJ, USA
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Purpose: To present flaws in the experimental design of a recent randomized controlled trial (RCT) published in the prestigious journal The New England Journal of Medicine (NEJM) concerning the lack of benefit of using progesterone (P) to prevent miscarriage. Materials and Methods: The RCT started vaginal P not until confirmation of pregnancy up to six weeks gestation. Results: Evidence is provided why a properly designed RCT should initiate P therapy in the early luteal phase to maximally inhibit the increase in cytotoxic leukocytes [especially natural killer (NK) cells] that are in the area of the site of implantation that are needed for uterine remodeling. The cytotoxicity of these cellular immune cells need to be suppressed or they may attack the fetal semi-allograft. Evidence is provided to support the hypothesis that the main effect of P is to stimulate the rise of an immunosuppressive protein called the P-induced blocking factor (PIBF). Conclusions: The RCT published in a late 2015 edition of the NEJM should not be regarded as a conclusive study showing no benefit of P in reducing risk of miscarriage. This is not only because of not starting the P in the early luteal phase, but also the type of P used. Some studies have found that vaginal P does not raise the PIBF levels nearly as well as intramuscular P.
Key words:  Recurrent miscarriage      Vaginal progesterone      Intramuscular progesterone      Progesterone induced blocking factor      Immune rejection     
Published:  10 October 2018     
*Corresponding Author(s):  J.H. CHECK     E-mail:

Cite this article: 

J.H. Check. Pros and cons of the use of progesterone to reduce miscarriage rates. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(5): 652-655.

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[1] J.H. Check, A. DiAntonio, D.L. Check, M.P. Dougherty, G. Diantonio. A study to determine if estrogen (E) is needed to induce de novo progesterone (P) receptors on gamma/delta t cells as evidenced by determining the degree of rise of progesterone induced blocking factor (PIBF) following P exposure in males[J]. Clinical and Experimental Obstetrics & Gynecology, 2020, 47(3): 419-420.
[2] Shun Akaeda, Daiki Kobayashi, Kyoko Shioda, Mikio Momoeda. Relationship between serum progesterone concentrations and pregnancy rates in hormone replacement treatment-frozen embryo transfer using progesterone vaginal tablets[J]. Clinical and Experimental Obstetrics & Gynecology, 2019, 46(5): 695-698.
[3] J.H. Check, J. Aly. Improving the chance of successful implantation – part 2 – Circumventing immune rejection and the fetal semi-allograft[J]. Clinical and Experimental Obstetrics & Gynecology, 2018, 45(1): 9-13.
[4] I. Isidori, C. Spapperi, A. Barbati, A. Mencarelli, G. Stangoni. QF-PCR and MLPA: a reliable molecular system to detect chromosomal alterations in miscarriages[J]. Clinical and Experimental Obstetrics & Gynecology, 2017, 44(2): 220-225.
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