Scientists Discover Muscular 'Switch' That Controls Birth Contractions

Dr. Enrique Jacome

In a world first, researchers in Australia have discovered an electrical switch in the uterus that does not seem to work properly in overweight pregnant women and may help explain the high rates of cesarean delivery in this group.

The study, led by Helena Parkington, an associate professor in the Faculty of Medicine, Nursing & Health Sciences at Monash University in Melbourne, is published in the journal Nature Communications.

After examining muscle biopsies taken from the uterus of 70 women, the team found an ion channel that sends electrical signals and controls contractions of the uterus.

Prof. Parkington says the switch needs to be turned off for birth contractions to begin, but in overweight women it appears to remain turned on, as she explains:

"The reason it stays on is that the 'molecular hand' that should turn the switch off fails to appear in sufficient quantities in the uterine muscle of overweight women when labor should be occurring."

In their study paper, the researchers describe how the ion channel - a potassium channel called hERG - suppresses contractions before labor. The 'molecular hand' is an inhibitory protein that is markedly enhanced during labor, "resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions."

Overweight women have low levels of protein that turns the switch off

They note that changes in channel activity contribute to "electrophysiological mechanisms" that produce contractions during labor. In their study, they showed this system fails in overweight women, whose hERG channel remains active as a result of low levels of the inhibitory protein.

For example, it should be possible to develop a drug that acts like the molecular hand and turns the switch on so labor and birth can progress normally.

The team believes the discovery significantly improves our understanding of how labor and birth progress, and why women have complicated labors. It should be possible now to develop safe, effective and specific treatments to correct the problem.

Overweight pregnant women often go over their due date or have a slow labor once it begins. They also need more medical help with labor and birth and have higher rates of birth induction and cesarean section - due to failure to progress in labor.

Medical News Today recently reported a study led by Imperial College London that showed how high maternal BMI is linked to poor pregnancy outcomes. The study found that even small increases in maternal BMI were linked to a higher risk of fetal death, stillbirth, neonatal death, perinatal death and infant death.

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Study Shows New Genetic Sequencing Methods Offer Quicker, Cheaper And More Accurate Embryo Screening

Dr. Enrique Jacome

Results from the first study of the clinical application of next generation DNA sequencing (NGS) in screening embryos for genetic disease prior to implantation in patients undergoing in-vitro fertilisation treatments show that it is an effective reliable method of selecting the best embryos to transfer, the annual conference of the European Society of Human Genetics heard. Dr Francesco Fiorentino, from the GENOMA Molecular Genetics Laboratory, Rome, Italy, said that his team's research has shown that NGS, a high throughput sequencing method, has the potential to revolutionise pre-implantation genetic screening (PGS). The technique can result in reduced cost, faster results, and accurate identification of good embryos resulting in more ongoing pregnancies, he will say.

The researchers undertook a prospective, double blind trial using two methods of embryo screening, NGS, and the older method array-comparative genomic hybridisation (Array-CGH) of 192 blastocysts, or early embryos, obtained from 55 consecutive clinical pre-implantation genetic screening (PGS) cycles. Array-CGH was the first technology to be widely available for the accurate analysis of chromosomal abnormalities in the embryo and is used extensively across the world for this purpose.

Fifty five patients with an average age of 40 years were enrolled; in 45 cases they were undertaking IVF because of advanced age and in ten because of repeated IVF failures. Two different teams of researchers carried out biopsies and analysed the genetic make-up of the embryos at between five and six/seven days, depending on the speed of growth, and then measured the consistency of the diagnosis by comparing results from the two sequencing methods.

This comparison showed concordant results for 191 of the 192 embryos analysed. One embryo showed a false positive for three copies of chromosome 22 (trisomy 22) using the NGS technique. But analysis of this embryo also showed concordance between the two methods in detecting several other chromosomal abnormalities, and it would therefore have been ruled for transfer in any event. There were no other false negative diagnoses for chromosome abnormalities, and no inaccurate predictions of gender. NGS also showed itself to be as capable of identifying small, difficult to detect abnormalities.

"We found that results from the NGS and array-CGH diagnostic tests were highly concordant," Dr Fiorentino will say. "NGS allowed us to detect a number of different abnormalities in 4608 chromosomes with a very high degree of accuracy, and following the transfer of 50 healthy embryos in 46 women, 30 pregnancies continued."

These pregnancies were confirmed by the presence of a foetal sac and a heartbeat, and all have now completed at least 20 weeks of gestation.

PGS has been the subject of controversy over recent years. Initially hailed as an opportunity to improve clinical outcome in sub-fertile patients undergoing IVF, a number of studies later appeared to show that it might not help to identify and select chromosomally normal embryos for transfer based on its lack of benefit with respect to improving life birth rates.

"However, these studies used an older screening technique, fluorescent in-situ hybridisation (FISH)," says Dr Fiorentino, "and we hypothesised that NGS might come up with more accurate results. The results of our study have proved this to be the case, and that NGS can improve clinical outcomes. We expect that the use of NGS technologies will increase as evidence of their utility becomes better-known.

"A further advantage of the technique is that it is quicker and cheaper, while remaining just as sensitive as other methods of screening. Our next step will be to participate in a large randomised controlled trial, the results of which will be critical for the acceptance of NGS-based pre-implantation embryo assessment into wider clinical practice."

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Research Shows New Drug Regimen Reduces Early Menopause Risk For Breast Cancer Patients

Dr. Enrique Jacome

For young women undergoing chemotherapy for breast cancer, early menopause and infertility are two of the most distressing side effects. But new research from Loyola University Medical Center in Chicago, IL, finds that adding a drug to a patient's chemotherapy regime - called goserelin - may reduce the risk of such side effects and even improve overall survival.

The research team, including senior study author Dr. Kathy Albain, recently presented their findings at the 2014 American Society of Clinical Oncology 50th Annual Meeting in Chicago, IL.

According to the American Cancer Society, around 232,670 new cases of invasive breast cancer will be diagnosed this year. Although the risk of developing breast cancer increases with age, it still affects 1 in 8 women under the age of 45.

The main treatment for breast cancer is chemotherapy. For young women who undergo this treatment, changes in menstrual periods are common and sometimes they can stop altogether, leading to premature menopause and possible infertility.

Findings 'may change clinical practice'

The Loyola University research team conducted a phase 3 clinical trial to see whether goserelin (brand name Zoladex) - a hormone therapy drug already approved by the US Food and Drug Administration for treatment of prostate cancer and certain breast cancers - could reduce the risk of premature menopause and infertility when added to chemotherapy regimens.

The researchers assessed 257 women under the age of 50 with early-stage breast cancer. Of these, 131 were randomly assigned to receive standard chemotherapy and 126 were assigned to receive standard chemotherapy plus goserelin. All patients were monitored for around 4 years.

Women assigned to the goserelin group received an injection of the drug once every 4 weeks alongside their normal chemotherapy regimen.

At 2 years after treatment initiation, the team found that 45% of the women who received standard chemotherapy had stopped menstruating or had high levels of follicle-stimulating hormone - a sign of decreased estrogen production and egg supply - compared with only 20% of women who received standard chemotherapy plus goserelin.

Furthermore, the researchers found that around 21% of women in the goserelin group experienced pregnancy, compared with 11% in the standard chemotherapy group.

At 4 years after treatment initiation, the team found that 89% of women in the goserelin group had no signs or symptoms of cancer, compared with 78% of women in the standard chemotherapy group. In addition, women in the goserelin group had an overall survival rate of 92%, compared with 82% for those in the standard chemotherapy group.

The researchers explain that goserelin works by temporarily putting the ovaries "at rest" throughout chemotherapy. Side effects of the drug were uncommon, the team says, and side effects that were reported were more related to reduced ovary activity.

Commenting on the findings, Dr. Albain says:

"We found that, in addition to reducing the risk of early menopause, and all of the symptoms that go along with menopause, goserelin was very safe and may even improve survival. I think these findings are going to change our clinical practice."

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