Early versus delayed follow-up after misoprostol treatment for early pregnancy loss.

RESEARCH QUESTION: Does extending the follow-up after misoprostol treatment for early pregnancy loss increase the success rate? DESIGN: Patients who had experienced early pregnancy loss (<12 weeks) and were treated with misoprostol in a single university-affiliated medical centre were prospectively followed before and after the implementation of a new treatment protocol extending the follow-up from 1 to 2 weeks. All patients received misoprostol 800 µg vaginally on day 1 and a second dose, when needed, on day 4 or 8. Patients underwent surgical aspiration after 1 week in the early follow-up group (n = 84) or 2 weeks in the delayed follow-up group (n = 85) if complete expulsion was not achieved (defined as endometrial thickness ≤15 mm and absence of gestational sac on transvaginal sonography). The primary outcome was treatment success, defined as no need for surgical aspiration. RESULTS: Women in the delayed follow-up group had a higher rate of successful treatment compared with women in the early follow-up group (88.2% versus 76.2%, respectively; P = 0.040), and a lower rate of second dose administration (32.9% versus 51.2%, respectively; P = 0.016). The incidence of non-expulsion of the gestational sac was also lower in the delayed follow-up group (1.2% versus 10.7%; P = 0.009). Treatment acceptability did not differ between the study groups. CONCLUSION: In women with early pregnancy loss treated with misoprostol, extending the follow-up protocol from 1 to 2 weeks resulted in an increase in treatment success.

Nicotinamide benefits both mothers and pups in two contrasting mouse models of preeclampsia.

Preeclampsia (PE) complicates ∼5% of human pregnancies and is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in prematurity, and in severe early-onset cases may lead to fetal death. Many currently available antihypertensive drugs are teratogenic and therefore precluded from use. Nonteratogenic antihypertensives help control maternal blood pressure in PE, but results in preventing preterm delivery and correcting fetal growth restriction (FGR) that also occurs in PE have been disappointing. Here we show that dietary nicotinamide, a nonteratogenic amide of vitamin B3, improves the maternal condition, prolongs pregnancies, and prevents FGR in two contrasting mouse models of PE. The first is caused by endotheliosis due to excess levels in the mothers of a soluble form of the receptor for vascular endothelial growth factor (VEGF), which binds to and inactivates VEGF. The second is caused by genetic absence of Ankiryn-repeat-and-SOCS-box-containing-protein 4, a factor that contributes to the differentiation of trophoblast stem cells into the giant trophoblast cells necessary for embryo implantation in mice; its absence leads to impaired placental development. In both models, fetal production of ATP is impaired and FGR is observed. We show here that nicotinamide decreases blood pressure and endotheliosis in the mothers, probably by inhibiting ADP ribosyl cyclase (ADPRC), and prevents FGR, probably by normalizing fetal ATP synthesis via the nucleotide salvage pathway. Because nicotinamide benefits both dams and pups, it merits evaluation for preventing or treating PE in humans.

Embryonic toxicity of sanguinarine through apoptotic processes in mouse blastocysts.

In this study, we examined the cytotoxic effects of sanguinarine, a phytoalexin with antimicrobial, anti-oxidant, anti-inflammatory and pro-apoptotic effects, on the blastocyst stage of mouse embryos, subsequent embryonic attachment and outgrowth in vitro and in vivo implantation via embryo transfer. Blastocysts treated with 0.5-2 µM sanguinarine exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with sanguinarine were lower than that of their control counterparts. Moreover, in vitro treatment with 0.5-2 µM sanguinarine was associated with increased resorption of post-implantation embryos and decreased fetal weight. Our results collectively indicate that sanguinarine induces apoptosis and retards early post-implantation development in vitro and in vivo. In addition, sanguinarine induces apoptotic injury effects on mouse blastocysts through intrinsic and extrinsic apoptotic signaling processes to impair sequent embryonic development. However, the extent to which sanguinarine exerts teratogenic effects on early human development is not known at present, and further studies are required to establish effective protection strategies against its cytotoxic effects.

Reduced stathmin-1 expression in natural killer cells associated with spontaneous abortion.

Female CBA/J mice impregnated by male DBA/2J mice (CBA/J×DBA/2J matings) are prone to spontaneous abortion, although the reason for this is unclear. In this study, the stathmin-1 expression pattern was evaluated in uterine natural killer (uNK) cells purified from CBA/J×DBA/2J matings. Results were compared with those in a CBA/J×BALB/c control group that yields successful pregnancies. The mean ± SD percentage of stathmin-1(+) cells in the CD49b(+) uNK cell population was lower in CBA/J×DBA/2J mice (0.7% ± 0.4%) than in control CBA/J×BALB/c mice (4.9% ± 1.5%, P < 0.01) using flow cytometry, and the intracellular stathmin-1 level in uNK cells was lower in CBA/J×DBA/2J mice than in control mice using Western blot analysis. Co-localization of lectin from Dolichos biflorus agglutinin (DBA-lectin) and stathmin-1 was confirmed using multivision immunohistochemical analysis. The frequency of stathmin-1(+)DBA-lectin(+) cells was lower in CBA/J×DBA/2J mice than in CBA/J×BALB/c mice. A similar trend in the frequency of stathmin-1(+)CD56(+) cells was seen in patients with unexplained spontaneous abortion compared with normal early pregnancy. A neutralizing antibody against stathmin-1 further increased the percentage of embryo loss in CBA/J×DBA/2J matings. These results provide evidence that stathmin-1 expression in uNK cells at the maternal-fetal interface may help modulate uNK cell function and may be beneficial for a successful pregnancy.

LMWH have no place in recurrent pregnancy loss: debate-against the motion.

The SPIN and ALIFE intervention trials apparently support that LMWHs should not be advocated in patients with idiopathic RPL. There are however some concerns. Epidemiology implies that most of the included patients shared recurrent regulatory embryonic losses associated with isolated cytogenetics defects, a dominant good prognosis entity which doesn't have to be treated. The real PL illness, idiopathic foetal loss with normal karyotypes, was a minority. Primary and secondary RPL cases were included, whose prognostic, applied to non-sporadic PLs, cannot be similar. Thrombophilic patients were a minority, despite existing data suggesting a LMWH beneficial effect. LMWHs were associated with LDA, previously suspected to be deleterious in PL patients with thrombophilia. The two indubitably planned-to-be negative trials will positively contribute to limit aberrant LMWH treatments in non-selected RPL women cared without comprehensive clinical categorisation. This is not the real clinical target for LMWHs, which still has to be fully investigated.

Consultative hematology: the pregnant patient pregnancy loss.

The presence of antiphospholipid antibodies has been associated with an increased risk of recurrent pregnancy loss, and there is evidence to suggest that antithrombotic therapy improves the likelihood of a successful outcome in affected women. Recent studies suggest an association between hereditary thrombophilia and pregnancy loss, although a causal role remains controversial. Although the available data are limited and flawed, there is increasing use of antithrombotic therapy in thrombophilic women with a history of pregnancy failure. Given the absence of proven effective therapy in women with unexplained recurrent loss, there is also growing pressure to intervene with antithrombotics in women with no known underlying thrombophilia. This article reviews the evidence for an association between thrombophilia and recurrent pregnancy loss and the data regarding the use of antithrombotic therapy for prevention of loss-an area that remains particularly challenging because of the paucity of good quality data upon which to base clinical decisions.

A randomized controlled trial comparing powdery sublingual misoprostol and sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy.

OBJECTIVES: To compare complete abortion rate, duration of abortion, and side effects between 600 microg powdery sublingual misoprostol and 600 microg sublingual misoprostol tablet for management of embryonic death or anembryonic pregnancy. MATERIALS AND METHODS: Fifty-four pregnant women up to 13 weeks of gestation diagnosed with embryonic death or anembryonic pregnancy were randomized to receive 600 microg powdery sublingual misoprostol or 600 microg sublingual misoprostol tablet. Complete abortion was evaluated by transvaginal ultrasound at 48 h. RESULTS: Twenty-six patients received 600 microg powdery sublingual misoprostol and 28 patients received 600 microg sublingual misoprostol tablet. Complete abortion rate was 34.6% in powdery sublingual misoprostol group and 32.1% in sublingual misoprostol tablet group (P = 0.847). Duration of abortion in powdery sublingual misoprostol group and sublingual misoprostol tablet group was similar (34.7 +/- 18.8 vs. 36.9 +/- 17.8 h, respectively, P = 0.656). There was no significant difference in the side effects between both groups. CONCLUSIONS: Single dose of 600 microg of powdery sublingual misoprostol does not improve its efficacy for management of embryonic death or anembryonic pregnancy when compared to sublingual misoprostol tablet.

Influence of clinical and ultrasound factors on the efficacy of misoprostol in first trimester pregnancy failure.

An observational study including 276 patients with early pregnancy failure was performed to evaluate the clinical and ultrasound factors influencing the efficacy of misoprostol in the treatment of first trimester pregnancy failure. Gestational age did not influence the efficacy of this treatment and the success rate was inversely proportional to parity.

IVIg therapy in autoimmunity and related disorders: our experience with a large cohort of patients.

Intravenous immunoglobulin (IVIg) is used to treat a number of immune-deficiencies and autoimmune diseases. It has been shown that IVIg contains anti-idiotypic antibodies, which explains its immunomodulatory action. In murine models, recent investigations have demonstrated that IVIg can prevent and reduce the affliction by systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and scleroderma. Relevant disease-specific fractions of IVIg were able to reproduce and even enhance the therapeutic effect in a murine model.IVIg treatment before tumor resection in rodents inoculated with melanoma and sarcoma cells dramatically improved the cure rate (50%) in comparison to the control group (0%). In patients affected by SLE, several clinical manifestations responded to IVIg treatment including serositis, hematological manifestations, treatment-resistant nephritis and central nervous system involvement. Similarly, in women with recurrent fetal loss due to APS, IVIg was able to diminish the abortion rate. Vasculitides such as Churg-Strauss' and Wegener's and skin fibrosis in patients affected by scleroderma improved after IVIg treatment. In agreement with in vitro investigations, prolonged survival has been noted in cancer patients treated with IVIg. We suggest that in the presence of a steroid and immunosuppressive-resistant autoimmune disease, IVIg is a rational and safe choice.