Expression of voltage-dependent potassium channels in first trimester human placentae

Potassium channel α-subunits encoded by KCNQ1-5 genes form voltage-dependent channels (K_V7), modulated by KCNE1-5 encoded accessory proteins. The aim was to determine KCNQ and KCNE mRNA expression and assess protein expression/localisation of the KCNQ3 and KCNE5 isoforms in first trimester placental tissue. Placentae were obtained from women undergoing elective surgical termination of pregnancy (TOP) at ≤10 weeks' (early TOP) and >10 weeks' (mid TOP) gestations. KCNQ1-5 expression was unchanged during the first trimester. KCNE5 expression increased in mid TOP vs. early TOP samples (P = 0.022). This novel study reports mRNA and protein expression of K_V7 channels in first trimester placentae.     

Medical abortion in the first trimester

Pregnancy can be terminated safely by inducing abortion medically at any stage of gestation. Antagonists such as mifepristone block the action of progesterone and hence result in uterine contractions and increase the sensitivity of the uterus to prostaglandins. In the last 15 years the combination of a single dose of mifepristone (600 mg) followed 48 hours later with a suitable prostaglandin (1 mg gemeprost vaginal pessary or 400 microg oral misoprostol) has been licensed in most countries in Europe and the USA for induction of abortion in the early weeks of pregnancy. The safety and efficacy of these methods is comparable to vacuum aspiration at the same gestation. The complete abortion rate is related to the type and dose of prostaglandin, the route of administration as well as the gestation and parity. Published data suggest that the dose of mifepristone can be reduced from 600 mg to 200 mg without loss of efficacy. Although misoprostol tablets are formulated for oral use, extensive clinical experience has demonstrated vaginal administration is more effective and is associated with fewer side-effects. Successful abortion using medical methods requires a well organized service which includes referral without delay and a robust system of follow up to identify failures. The failure rate as reflected by the number of women who require surgical intervention falls with increasing experience. In those countries where medical abortion has been freely available for about 10 years, such as France, Scotland and Sweden, about 60-70% of eligible women elect for this method.     

Misoprostol and first trimester pregnancy termination

OBJECTIVE: To investigate the efficacy of vaginal administration of 800 microg misoprostol as a single dose without performing post expulsion systematic curettage in first trimester pregnancy termination. METHOD: 113 women, aged 16-44, who requested first trimester pregnancy termination, received 800 microg of vaginal misoprostol. All examined women were divided into two groups depending on gestation age. The first group included of 67 women with up to nine weeks and the second of 46 with up to 12 weeks of pregnancy. RESULTS: Abortion occurred within 24 hours and was completed in 74.3% of the cases. The mean induction-abortion interval was 5.9 +/- 1.7 hours (median 5.5 hours). Side-effects were experienced by 24 women (21.2%). There was no significant difference between groups in the success rate, induction-abortion interval, number of previous deliveries and side-effects. CONCLUSION: Misoprostol is an effective agent for first trimester medical termination.     

Methods used in first trimester abortion

In 1990 over 175 000 women underwent legal first trimester abortion in the UK, 98% of which were performed using vacuum aspiration. In developed countries where abortion is legal, this procedure is extremely safe and effective. Maternal mortality occurs in approximately 1 in 100 000 cases. Other serious complications occur in less than 1% of cases and minor complications, including psychological disturbances, in 10% of cases. The procedure has no effect on subsequent fertility or pregnancy outcome, and leads to complete abortion in 95–98% of cases. Cervical priming is consistently associated with decreased morbidity.Medical abortion, using mifepristone in combination with the prostaglandin analogue gemeprost, provides a real alternative which is preferred by at least one-fifth of women. The procedure is as effective as vacuum aspiration and may be more so at very early gestations. There are no major differences in medical, psychological or acceptability outcomes when the procedures are compared. Medical abortion compares favourably with surgical abortion on cost-effectiveness analysis and may be the method of choice at less than 50 days gestation.In the UK other methods of first trimester abortion should be avoided in routine practice. Prompt referral of women with unplanned pregnancies to fertility control services must remain a primary objective in order to minimise adverse maternal health consequences.     

Melatonin prevents preeclamptic sera and antiphospholipid antibodies inducing the production of reactive nitrogen species and extrusion of toxic trophoblastic debris from first trimester placentae

BackgroundThe exact cause of preeclampsia is unknown. However a “toxin” from the placenta triggers the condition via activation of the maternal endothelium. Extracellular vesicles (EVs) from the syncytiotrophoblast, may be an endothelial-activating toxin. Antiphospholipid antibodies (aPL) and preeclamptic sera both induce the production of endothelial cell-activating EVs by mechanisms which may produce excess free-radicals in the placenta. Melatonin is produced by the human placenta and has both direct and indirect anti-free-radical properties and may therefore counter the effects of aPL and preeclamptic sera.MethodsFirst trimester placental explants were exposed to preeclamptic sera or aPL in the presence or absence of melatonin. Nitrosylative damage was assessed in the explants by immunohistochemistry and the effect of EVs from these explants on endothelial cell activation determined by ICAM-1. Release of nitrosylated proteins from the explants was also measured.ResultsPlacental explants showed reduced secretion of melatonin after treatment with preeclamptic sera. Nitrosylated proteins were more abundant in placentae that had been treated with aPL or preeclamptic sera and EVs from such placentae induced endothelial cell activation. Adding melatonin to the aPL or preeclamptic sera reversed the protein nitrosylation and production of endothelial-activating EVs.DiscussionOur data are consistent with reports that the levels of circulating melatonin are reduced in preeclampsia and suggest that aPL and factors in preeclamptic sera induce free-radical-mediated damage in the placenta leading to the production of endothelial-activating EVs. Melatonin reversing production of endothelial-activating EVs indicates that melatonin may have therapeutic benefits in women with preeclampsia and/or aPL.     

Metronidazole prophylaxis in elective first trimester abortion

In a double-blind controlled trial, the efficacy of prophylactic metronidazole in elective first trimester abortions was assessed. Of 119 randomized women, 100 followed the protocol. Fifty-one women received 400 mg metronidazole one hour before and again four and eight hours after abortion; 49 women received a placebo. In the placebo group 20.4% contracted postabortal genital infection compared with 3.9% in the metronidazole group (P less than .025). Of 25 women with a positive history of pelvic inflammatory disease, six contracted postabortal infection, which was a significantly increased frequency compared with women without previous episodes of pelvic inflammatory disease (P less than .05). The administration of prophylaxis, however, did not significantly influence the frequency. The number of hospital days was not significantly lower in the prophylaxis group (P greater than .05). The total amount of metronidazole prescribed in the study group was significantly larger than in the placebo group (P less than .05), whereas the amount of ampicillin/pivampicillin prescribed in the placebo group was significantly larger (P less than .05). The difference between the penicillin doses given in the treatment and placebo groups was not significant (P greater than .1).     

Co-variables in first trimester maternal serum screening

The objective of this study was to determined the influence of maternal weight, maternal smoking habits, gravidity, parity and fetal gender on the level of maternal serum marker used in first trimester screening for Down syndrome. A total of 2449 singleton unaffected pregnancies from two centres were studied. Maternal serum free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) concentrations had been measured in all pregnancies, and pregnancy associated plasma protein (PAPP)-A levels had been measured in 924. All results were expressed as multiples of the gestation specific median (MoM) values after regression, using each centre's own medians. Information on maternal weight was available in 2259 pregnancies, on self-reported current cigarette smoking in 1364 (of whom 117 (8.6%) were smokers), on gravidity in 1371, parity in 1303 and fetal gender in 253. All three markers showed a statistically significant negative association with maternal weight (p<0.0005) and in the subsequent analyses MoM values were weight adjusted using standard methods. The median PAPP-A level in smokers was 0.81 MoM, a significant reduction (p<0.005); free beta-hCG was also reduced (median 0.89 MoM) but not significantly (p=0.17), and AFP was unaltered. The median AFP level in primagravidas was highly significantly greater than that in gravid women (p<0.0005). In PAPP-A the reverse effect was seen but it did not reach statistical significance (p=0.15) and there was no effect for free beta-hCG. Results of a similar magnitude and direction were found for parity. The median level of free beta-hCG was higher (p=0.0005), and the median AFP lower in female pregnancies. Maternal weight and, for PAPP-A, maternal smoking are important first trimester screening co-variables. Gravidity, parity and fetal gender also seem to influence one or more first trimester markers.     

Fetal heart scanning in the first trimester

The detailed study of the fetal cardiac anatomy in the first trimester of pregnancy by means of ultrasound, transvaginally or transabdominally, is feasible and remains a safe procedure provided thermal and mechanical indices are taken into account. Optimal time for successful imaging of the four chambers and great arteries in early gestation appears to be between 13 to 14 weeks. In experienced hands, first-trimester fetal echocardiography is accurate in detecting major structural cardiac abnormalities and yields a high negative predictive value. Thus, in a clinical setting, it can be offered to families considered to be 'at risk' of cardiac defects (e.g. those with previous family history or when fetal nuchal translucency is increased) and can be a powerful tool to reassure families regarding normality of major cardiac structures and connections. However, the early detection of an important structural abnormality (chromosomally normal or not) may be associated with a high termination rate if this is an acceptable option. The high prevalence of associated chromosomal and extracardiac abnormalities for many of the high-risk families, who may benefit from this approach, cannot be ignored. Therefore, fetal heart scanning in the first trimester should be performed in conjunction with detailed first-trimester obstetric scanning.     

Fetal syphilis in the first trimester.

Evidenc of first-trimester fetal syphilis was sought in the products of conception in a therapeutic abortion clinic. During two collection periods of one week, five patients with serologic and clinical data consistent with recent syphilitic infection were identified. Their conceptuses were carefully examined by silver and immunofluorescent stains for the presence of Treponema pallidum. Two of these five conceptuses (9 and 10 weeks' gestation) were found to contain T. pallidum by these methods. The literature supporting the Langhans layer/five months' placental barrier theory is reviewed and discussed in view of these two first-trimester cases.