Evidence-based care of recurrent miscarriage
ABSTRACT Between 0.5 and 1.0% of couples experience recurrent pregnancy loss (RPL), which is defined as three or more consecutive miscarriages. Losses are classified as pre-embryonic (<5 weeks), embryonic (5-10 weeks) or fetal (>10 weeks). Genetic abnormalities are responsible for RPL in 2-4% of these couples. Inadequate progesterone production has been proposed a cause of RPL and progesterone is given to prevent miscarriage, despite a lack of supportive evidence. The factor V Leiden and prothrombin G20210A mutations are common inherited thrombophilias also associated with RPL. Antenatal thromboprophylaxis is sometimes recommended although no data exist regarding efficacy. Antiphospholipid syndrome is known to cause RPL and antenatal thromboprophylaxis reduces the risk of miscarriage. Uterine abnormalities might also result in RPL. About 50% of cases of RPL have no identifiable cause. Alloimmune incompatibility has been proposed as a cause for RPL in these women. The concept of alloimmune-related RPL has not been scientifically validated.
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- "Administration of progesterone receptor antagonists within the first 7 weeks of pregnancy induces abortion (Peyron et al., 1993). The potential for implantation is lessened if there is a decrease in the amount or duration of progesterone production by the corpus luteum or if there is poor endometrial response to progesterone (Jones, 1991; Ginsburg, 1992), which may lead to pregnancy failure (Porter and Scott, 2005). Successful implantation involves complex mechanisms that require hormonal synchronization. "
ABSTRACT: ART has evolved over time and frozen-thawed embryo transfer (FET) is now a frequently performed, successful option. During the last decade, cryopreservation techniques have received considerable interest, whereas interest in the priming and preparation of the endometrium prior to and after embryo transfer was more limited. The available evidence for the rationale and timing of progesterone supplementation as well as an understanding of the differences among progesterone formulations with respect to efficacy, optimum use, and patient preference is worth examining. A Summit was convened to review the literature on progesterone supplementation in ART and after FET and to provide guidance on the most clinically relevant issues. Utilizing an innovative consensus-building model to examine the evidence, Summit faculty drafted summit statements prior to the meeting, completed a literature search, and created a presentation based on this. At the conclusion of their discussion the faculty developed final summit statements, evaluating the strength of the evidence supporting each statement, and rating their level of support for each statement. The clinically relevant topic areas were the rationale for progesterone supplementation, timing and appropriate dosing, whether progesterone sérum levels reflect outcomes, and distinguishing among progesterone formulations with respect to efficacy, tolerability, and patient preference/satisfaction. CME INFORMATION: © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. Allrights reserved.Reproductive biomedicine online 12/2014; 29. DOI:10.1016/S1472-6483(14)50063-6 · 2.98 Impact Factor
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- "However, IDO knock-out mice have been shown to undergo normal pregnancy (Baban et al., 2004), a perplexing finding that remains to be fully resolved. Despite the extensive amount of research performed over the past few years, the entire phenomenon involved in pregnancy maintenance is still far from being completely understood and it has been estimated that 50–70% of human conceptions fail and that recurrent pregnancy loss affects 0.5–2% of couples (Clark et al., 2001; Porter and Scott, 2005). In view of these findings, the development of predictive tools to estimate pregnancy outcome is a matter of critical importance. "
ABSTRACT: Tolerance to the developing fetus is thought to be accomplished through the action of several molecules that are able to modulate the maternal immune response. Among several mechanisms involved in pregnancy maintenance, progesterone-induced immunomodulation, asymmetric antibody (AAb) production, indoleamine 2,3-dioxygenase (IDO)-mediated tryptophan catabolism and Th1- to Th2-type cytokine balance have been particularly well studied. However, spontaneous abortions (SA) remain the most common complication of pregnancy, affecting 15% of women, primarily in the first trimester. Development of sensitive methods for the early diagnosis of this condition is therefore a matter of critical importance. In the present study, we investigated AAb production and IDO activity in pregnant women in order to assess their value as early markers for the diagnosis of pregnancy failure. Serum AAb percentages were significantly reduced in women who subsequently suffered from SA compared with controls (p<0.001). Levels of IL-10, IL-12 and IDO activity were also lower in the SA cases, although levels of significance were not reached. In view of these findings, low maternal serum AAb percentages during the first trimester of pregnancy may be indicative of a threat to pregnancy progression.Journal of Reproductive Immunology 03/2009; 79(2):201-10. DOI:10.1016/j.jri.2008.11.002 · 2.37 Impact Factor
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- "Experimental evidences indicate that the endometrium from PCOS women behaves differently from that of normal women, with a potential association between PCOS, hyperplasia and endometrial carcinoma (Balen, 2001; Ehrmann, 2005). Also, a high number of PCOS patients present infertility (Franks, 1995; Porter and Scott, 2005), and when ovulation is restored pharmacologically or spontaneously, these patients exhibit a higher rate of miscarriage (Kastner et al., 1990; Connely and Lydon, 2000; Whiele and Manga, 1995). "
ABSTRACT: The hormonal alterations observed in women with polycystic ovary syndrome (PCOS) may promote implantation failure as well as disruption of their endometrial homeostasis. To evaluate cell survival of mid-secretory endometrium from untreated women with PCOS, we measured the expression of apoptosis and proliferation-related proteins. A case-control study of 11 patients with PCOS and 11 fertile women in the Hospital Research Unit was performed. Endometrial samples were obtained from PCOS women (PCOSE) and fertile healthy women (CE) during the mid-secretory phase of the menstrual cycle. Protein expressions for Akt, p-AktSer473 and p-AktThr308, Bad, p-BadSer136, Bcl-2, Bax and pro-caspase-3/caspase-3, were assessed by western blot, and Ki67 and p-histone-3 (p-H3) by immunohistochemistry. In CE and PCOSE, a predominance of p-AktThr308 over p-AktSer473 is observed; p-BadSer136 expression is higher in PCOSE than in CE (P < 0.05). Also, Bcl-2 protein is overexpressed in PCOSE (P < 0.05), with no changes in Bax expression among the two groups, resulting in a significantly higher Bcl-2/Bax ratio in PCOSE than in CE (P < 0.05). No changes in the expression of caspase-3 are obtained between both groups of endometria. Furthermore, cell proliferation detected by the expression of Ki67 and p-H3 proteins is higher in the epithelia than the stroma of PCOSE versus CE (P < 0.05). The abnormal tissue homeostasis exhibited by the secretory endometrium from PCOS patients with spontaneous ovulation may interfere with their endometrial receptivity.Human Reproduction 12/2006; 21(12):3116-21. DOI:10.1093/humrep/del183 · 4.59 Impact Factor