Wednesday, July 18, 2018

Vaginal cleansing with antiseptic solution before cesarean section brings down postoperative infection: Cochrane review

A simple and inexpensive intervention of vaginal cleaning with the chlorhexidine-based or iodine-based solution immediately before cesarean section probably reduces the risk of endometritis after the procedure. The benefit could be more for women who underwent cesarean section while in labor or after rupture of membranes reports the results of a Cochrane review published 17 July 2018.

The current review is the fifth update on vaginal preparation before cesarean section and risk of subsequent infection by Cochrane; the first review was published in 2010 and subsequently updated in 2012, and twice in 2014.

Cesarean section is the most commonly performed operation in obstetrics, with 1 in 3 babies being born by cesarean section. Nearly 25% of women have endometritis and 10% of women develop skin infection after C-section.

Pre-op or intra-op antibiotic prophylaxis has not been able to bring down the rate considerably.

The Cochrane researchers searched the Cochrane Pregnancy and Childbirth’s Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP) (10 July 2017),, and reference lists of retrieved studies.

The review included 11 trials with a total of 3403 women in whom vaginal preparation was done immediately before the start of the cesarean section. Most of the trials used Povidone-iodine (n=8), while the rest used chlorhexidine (n=2) and benzalkonium chloride (n=1).

The control group included women with no vaginal antisepsis preparation (eight trials) or those in whom saline vaginal preparation (three trials) was used.

Vaginal preparation with the antiseptic solution immediately before cesarean delivery probably reduced the risk of endometritis by 64% (average risk ratio (RR) 0.36, 95% confidence interval (CI) 0.20 to 0.63).

It was not possible to separately analyze the risk reduction in a subgroup of women who were in labor or in women whose membranes had ruptured when antiseptics were used. 

Risk of postoperative fever or surgical wound complications may also be brought down by the use of vaginal antisepsis, but the confidence interval around the effects for both outcomes was very wide consistent with insufficient data.

Composite outcome of wound complication or endometritis was reduced by 54% in two trials consisting of 499 women (RR 0.46, 95% CI 0.26 to 0.82).

No adverse effects were reported with either the povidone-iodine or chlorhexidine vaginal cleansing.

The quality of evidence using GRADE was moderate for all reported outcomes. The authors downgraded the outcome for post-cesarean endometritis and composite of wound complications or endometritis because of bias in the involved study and broader CI.

The recommend that healthcare providers may continue using vaginal antisepsis preparation by either using povidone-iodine or chlorhexidine before performing a cesarean delivery.

Tuesday, July 17, 2018

EMA approves Ulipristal for Preop Treatment of Uterine Fibroids

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) grants marketing authorization for Ulipristal Acetate (Gedeon Richter) as pre-operative treatment for uterine fibroids.

Ulipristal is a selective progesterone receptor modulator used for intermittent treatment for moderate to severe symptoms of uterine fibroids in women of reproductive age. It is also used as a pre-operative treatment in women scheduled for a uterine fibroid surgery, where it helps reduce bleeding, anemia and fibroid size. It will be available as 5 mg tablet upon approval.

The application for ulipristal approval was an informed consent application, which means that reference is made to an already authorized medication upon obtaining consent to the use of their dossier in the application procedure. The reference product for Gedeon Richter Ulipristal was Esmya.

The approval further recommends that the drug should only be prescribed by physicians who are experienced in the treatment of fibroids. The common side effects of the drug include endometrial thickening, amenorrhea, and hot flushes.

However, European Union drug regulators have expressed concerns about the side effects on the liver by Esmya in the past. In December 2017, the EMA opened an investigation about liver injury by the drug, followed by a monthly recommendation of liver function test in women taking Esmya by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC).

Meanwhile, the United States FDA announced in February 2018 that it had extended the review of ulipristal new drug application (NDA) to August 2018.

Monday, July 16, 2018

New study opens the door for delaying egg aging by pharmacological treatment

Recently a fascinating paper was published about a novel treatment to increase the fertility lifespan in females. The researchers have achieved a breakthrough in finding a treatment to delay the sharp decrease of fertility in females right before their mid-30s.

Research by Dr. Coleen Murphy, Professor of Molecular Biology and Genomics at Princeton University and her team reported about a protein that can preserve the fertility potential of women in mid-30s and can potentially extend eggs’ life.

The work was recently published in Current Biology, and authors were able to document an extension of eggs’ viability in two separate experiments.

Murphy and colleagues observed that a protein called cathepsin B proteases was present in abundance in aging oocytes of Caenorhabditis elegans, a nematode commonly used as an animal model for a wide variety of studies.

They also observed that many of the genes from the worm were also conserved in humans, thereby providing an important resource on understanding the aging in human’s eggs.

The researcher hypothesized that knocking of cathepsin-B genes in adult worms should result in stalling the oocyte aging and improving its quality.

They knocked down individual genes in adult worm by sing iRNA, and surprisingly the reproductive lifespan increased by 10% and morphology of oocyte also showed improvements.

Once the aging effect of cathepsin-B proteases was documented, they proceeded to treat wild-worms with a potent cell-permeable cathepsin B inhibitor (MDL-28170). This pharmacological treatment was able to slow down the decline in the quality of oocyte as the women age.

Most importantly, the drug-induced decline was achieved even when it was applied around mid-life. This has wider implications for those women who want to delay childbearing because of socio-economic commitments, they can easily gain 3 to 6 years extension in terms of fertility.

Although cathepsin B inhibitor is not yet ready for testing in humans, the research has opened new doors regarding pharmacological therapy for delaying reproductive aging.