Peri-implantation glucocorticoid administration for assisted reproductive technology cycles
ABSTRACT In order to improve embryo implantation in in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles, the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intra-uterine environment by acting as immuno modulators to reduce the uterine NK cell count, normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation.
To investigate whether the administration of glucocorticoids around the time of implantation improves clinical outcomes in subfertile women undergoing IVF or ICSI, compared to no glucocorticoid administration.
The Cochrane Menstrual Disorders and Subfertility Group's trials register (February 2006), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2006), MEDLINE (1966 to June 2006), EMBASE (1976 to June 2006), CINAHL (1982 to June 2006) and Science Direct (1966 to June 2006) were searched. Reference lists of relevant articles and relevant conference proceedings were also hand searched.
All randomised controlled trials (RCTs) addressing the research question were included.
Two reviewers independently assessed eligibility and quality of trials and extracted relevant data.
Thirteen studies (1759 couples) were included. Three studies reported live birth rate and these did not identify a significant difference after pooling the (preliminary) results (OR 1.21, 95% CI 0.67 to 2.19). With regard to pregnancy rates, there was also no evidence that glucocorticoids improved clinical outcome (13 RCTs; OR 1.16, 95% CI 0.94 to 1.44). However, a subgroup analysis of 650 women undergoing IVF (6 RCTs) revealed a significantly higher pregnancy rate for women using glucocorticoids (OR 1.50, 95% CI 1.05 to 2.13). There were no significant differences in adverse events, but these were poorly and inconsistently reported.
Overall, there is no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improves clinical outcome. The use of glucocorticoids in women undergoing IVF (rather than ICSI) was associated with an improvement in pregnancy rates of borderline statistical significance. These findings are limited to the routine use of glucocorticoids and cannot be extrapolated to women with auto-antibodies, unexplained infertility or recurrent implantation failure. Further well designed randomised studies are required to elucidate the possible role of this therapy in well defined patient groups.
- SourceAvailable from: Joep Geraedts
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- "Similarly, in the presence of ACA (anti-cardiolipin antibodies ), the use of heparin and aspirin showed no benefit (Stern et al., 2003). Attempts of administering steroids (Boomsma et al., 2007) or low-dose aspirin (Gelbaya et al., 2007) were also negative. "
ABSTRACT: BACKGROUND: The American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) are the two largest societies in the world whose members comprise the major experts and professionals working in the field of reproductive medicine and embryology. These societies have never before had a joint scientific meeting. METHOD(S): A 3-day meeting was planned and took place in March of 2012. The goal was to present and debate key topics, as well as modes of practice in reproductive medicine and to discuss recent developments in the field. RESULT(S): Presentations by members of ASRM and ESHRE were of three types: 'state of the art' lectures, 'back-to-back' presentations of two points of view and debates. CONCLUSION(S): For the first time, ASRM and ESHRE held a joint meeting where a special emphasis was given to presentations on the hottest topics in the field. Although different opinions and approaches sometimes exist on the two sides of the Atlantic, an appreciation and acceptance of these differences was evident, and there was more commonality than divergence of opinion.Fertility and sterility 10/2012; 98(6). DOI:10.1016/j.fertnstert.2012.07.1164 · 4.59 Impact Factor
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- "intravaginal application of exogenous cortisol from Days 15 to 18 post insemination increased the pregnancy rate and reduced TNFαstimulated PGFM levels, whereas the inhibition of local cortisol biosynthesis by intravaginal application of metyrapone decreased the pregnancy rate in heifers. These results agree with those of Boomsma et al. (2007), who reported an increase in pregnancy rate as a result of GC administration . The above results suggest that cortisol plays an important role in maintaining CL function by directly inhibiting uterine PGF 2α secretion to support embryo implantation and early embryonic development. "
ABSTRACT: Cortisol is suggested as anti-inflammatory agent to modulate production and action of cytokines and prostaglandins required for ovulation, luteolysis, successful embryo implantation, pregnancy development and termination. Level of cortisol, is locally regulated by 11-hydroxysteroid dehydrogenase (11β-HSD)s. Although both 11β-HSDs and GC receptors are expressed in the bovine CL and endometrium throughout the estrous cycle and early pregnancy, the function of GC in CL function regulation of is still controversial. The aim of the study was to demonstrate the effect of exogenous locally produced cortisol on the progesterone (P4) secretion, CL function at the estrous cycle and early pregnancy as well embryo implantation and development in cows in vivo. Cortisol (10 mg) or metyrapone (11-HSD-type 1 inhibitor; 500 mg) dissolved in vaseline gel were applied into the vagina of heifers daily on Days 15-18 of the estrous cycle (n=18) or pregnancy (n=36). Doses of GC reagents were establish in preliminary experiments. Progesterone concentration was measured by EIA. The pregnancy rate was confirmed on Day 28-30 after insemination using USG technique. Application of exogenous cortisol at the end of luteal stage shortened CL function through decreasing P4 secretion (P<0.05). Moreover, inhibition of endogenous, local cortisol synthesis by metyrapone prolonged luteal stage (P<0.05). Conversely, during early pregnancy exogenous cortisol stimulated P4 secretion (P<0.05) and increased the pregnancy rate (75 %) compare to control animals (58%; only gel application). Lower level of P4 and fertility rate (16.7 %) were found in heifers treaded with metyrapone (P<0.05). This data suggests that cortisol, dependently on physiological status of cows, modulates CL function influencing P4 secretion. At the end of estrous cycle cortisol can be involved in luteolysis cascade modulating uterine PGF2α secretion and action on the CL. The most important result of this study is that cortisol has positive influence on the CL during pregnancy, supporting embryo implantation and maintaining early pregnancy.3rd Annual COST GEMINI Meeting; 01/2010
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- "For example, in healthy volunteers, daily oral administration of prednisolone halved the total population of lymphocytes within 7 h of the first glucocorticoid treatment, and reduced the proportion of peripheral NK cells (from 16.5 to 9.5% of lymphocytes) over 3 days (Pountain et al., 1993). In light of their immunosuppressant actions, it has been suggested that glucocorticoids might assist in preventing immune rejection of the implanting embryo (Boomsma et al., 2007). Recent studies have implicated uterine NK cells in recurrent miscarriage. "
ABSTRACT: Despite extensive studies of the developmental consequences of increased glucocorticoid exposure in mid- to late pregnancy, relatively little is known regarding the significance of glucocorticoids in early pregnancy. The objective of this review was to consider potential roles for this family of corticosteroids that might relate to early pregnancy. Although this is a narrative review, 249 source articles addressing potential effects of glucocorticoids on aspects of early pregnancy and development (published between 1997 and 2007) were identified using a systematic literature search. Additional articles (115) were identified if cited by the primary reference articles identified in the systematic phase of the review. Much of the evidence to implicate glucocorticoids in early pregnancy comes from studies of steroid receptors and the 11beta-hydroxysteroid dehydrogenase enzymes, which modulate cortisol action in the endometrium/decidua, trophoblast, placenta and embryo/fetus. The evidence reviewed suggests that in early pregnancy the actions of glucocorticoids are balanced between positive effects that would promote pregnancy (e.g. stimulation of hCG secretion, suppression of uterine natural killer cells, and promotion of trophoblast growth/invasion) versus adverse effects that would be expected to compromise the pregnancy (e.g. inhibition of cytokine-prostaglandin signalling, restriction of trophoblast invasion following up-regulation of plasminogen activation inhibitor-1, induction of apoptosis, and inhibition of embryonic and placental growth). Glucocorticoids exert many actions that could impact both negatively and positively on key aspects of early pregnancy. These steroids may also be implicated in obstetric complications, including intra-uterine growth restriction, pre-term labour, pre-eclampsia and chorio-aminionitis.Human Reproduction Update 07/2008; 14(5):497-517. DOI:10.1093/humupd/dmn021 · 8.66 Impact Factor