Human Reproduction Update Advance Access originally published online on November 22, 2007
Human Reproduction Update 2008 14(1):27-35; doi:10.1093/humupd/dmm035
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Progestagen therapy for recurrent miscarriage
1 Department of Medical Microbiology and Immunology, Medical School, Pecs University, H-7643 Pecs, Hungary 2 Institut Clinic of Gynecology, Obstetrics and Neonatology, Faculty of Medicine, University of Barcelona, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Casanova 143, 08036 Barcelona, Spain
3 Correspondence address. Department of Medical Microbiology and Immunology, Medical School, Pecs University, 12 Szigeti Street, H-7624 Pecs, Hungary. Tel: +3672-536262; Fax: +3672-536253; E-mail: julia.szekeres{at}aok.pte.hu
BACKGROUND: Recurrent pregnancy loss (RM) affects 0.5–1% of couples. The pathophysiology of RM is complex. The suggested causes include anatomical, genetic and molecular abnormalities, endocrine disorders, thrombophilias and anti-phospholipid syndrome. In 
50% of the cases neither of the above can be identified. We aimed at examining the evidence on the role of progesterone in the pathophysiology of RM, and the clinical evidence on effectiveness of progestogen treatment.
METHODS: We searched PubMed and the Cochrane database covering the period of 1968–2007. The search terms progestogens and recurrent miscarriage, NK cells and recurrent miscarriage as well as cytokines and recurrent miscarriage were used.
RESULTS: Progesterone is indispensable for creating a suitable endometrial environment for implantation. RM may be due to subnormal progesterone secretion and retarded endometrial development in the peri-implantation period. Progesterone also acts on the immune system, mainly by affecting cytokine synthesis and the function of NK cells. A recent meta-analysis showed that though progesterone treatment did not affect pregnancy outcome in women with miscarriages in general, separate analysis of three small and dated studies including altogether 91 patients with RM revealed a small but significant effect. It is noteworthy that the design of these 40 years old studies does not meet modern requirements.
CONCLUSION: Standardized laboratory protocols for identifying potential targets of progestogen treatment as well as implementation of well-designed randomized studies are needed to establish the usefulness of progesterone supplementation in the treatment of RM.
Key words: recurrent miscarriage / progesterone / endometrial defect / decidual NK cells / cytokines
Received on July 5, 2007; revised September 14, 2007; accepted on October 10, 2007