Does first trimester progesterone prophylaxis increase the live birth rate in women with unexplained recurrent miscarriages?

Coomarasamy, Arri; Truchanowicz, Ewa; Rai, Raj

doi:10.1136/bmj.d1914

Cited by 35 publications

(27 citation statements)

References 5 publications

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“…8,9 Furthermore, previous studies have shown the efficacy of vaginal progesterone in lowering the risk of preterm birth. [16][17][18] We initiated progesterone treatment after pregnancy was confirmed, and thus our study cannot address whether progesterone supplementation could be more effective in reducing the risk of miscarriage if administered during the luteal phase of the cycle, before the confirmation of pregnancy. [19][20][21][22] We discontinued progesterone at 12 weeks of gestation but consider it unlikely that therapy beyond this time would result in better outcomes; it is well documented that corpus luteal function is replaced by placental production of progesterone before the end of the first trimester.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

et al. 2015

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BACKGROUNDProgesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain. METHODSWe conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twicedaily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation. RESULTSA total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, −4.0 to 9.0). There were no significant between-group differences in the rate of adverse events. CONCLUSIONSProgesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages.

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Section: Discussionmentioning

confidence: 99%

A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

et al. 2015

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“…Progesterone supplementation is routinely provided in assisted reproductive treatments (71) and is viewed as a promising therapy for recurrent miscarriage (72). Endogenous and environmental factors are thought to affect macrophage populations in human peripheral tissues.…”

Section: Figurementioning

confidence: 99%

Macrophages regulate corpus luteum development during embryo implantation in mice

et al. 2013

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Macrophages are prominent in the uterus and ovary at conception. Here we utilize the Cd11b-Dtr mouse model of acute macrophage depletion to define the essential role of macrophages in early pregnancy. Macrophage depletion after conception caused embryo implantation arrest associated with diminished plasma progesterone and poor uterine receptivity. Implantation failure was alleviated by administration of bone marrowderived CD11b + F4/80 + monocytes/macrophages. In the ovaries of macrophage-depleted mice, corpora lutea were profoundly abnormal, with elevated Ptgs2, Hif1a, and other inflammation and apoptosis genes and with diminished expression of steroidogenesis genes Star, Cyp11a1, and Hsd3b1. Infertility was rescued by exogenous progesterone, which confirmed that uterine refractoriness was fully attributable to the underlying luteal defect. In normally developing corpora lutea, macrophages were intimately juxtaposed with endothelial cells and expressed the proangiogenic marker TIE2. After macrophage depletion, substantial disruption of the luteal microvascular network occurred and was associated with altered ovarian expression of genes that encode vascular endothelial growth factors. These data indicate a critical role for macrophages in supporting the extensive vascular network required for corpus luteum integrity and production of progesterone essential for establishing pregnancy. Our findings raise the prospect that disruption of macrophage-endothelial cell interactions underpinning corpus luteum development contributes to infertility in women in whom luteal insufficiency is implicated.

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“…The reason for this may be that the evaluation of endometrial samples was done by different pathologists and inadequate care may have been shown for chronological determination. Recent reports have stated that since LPD is a known factor in habitual miscarriages and since it is desired to avoid expensive and invasive procedures for patients, it is recommended when considering LPD to use a simple progesterone determination where the efficiency is well known [17,20,21]. In summary, we conclude that habitual miscarriages have a complex etiology that may be related to different endocrinologic and endometrial factors.…”

Section: Discussionmentioning

confidence: 60%