Study Shows New, Successful IVF Technique Could Make Treatment Safer

Dr. Enrique Jacome

Approximately 3% of infertile women in the US undergo IVF in an attempt to get pregnant. But for some, such treatment can result in severe side effects. Now, a new study published in the Journal of Clinical Investigation details a new, safer technique that has been found to successfully boost ovulation in women undergoing IVF, resulting in 12 newborn babies.

Around 1 in 8 couples in the US have problems getting pregnant or sustaining a pregnancy, and around a third of these cases are attributable to the female partner. Most infertility cases are treated with medication or surgery, but when these fail, assisted reproductive therapies - such as IVF (in vitro fertilization) - become an option.

IVF involves manually inserting sperm into an egg in a laboratory dish. If fertilization is successful, the embryo is then physically placed in the uterus. Prior to this procedure, patients may be required to take injectable fertility drugs - such as a hormone called hCG - to trigger egg production.

But the research team, led by Prof. Waljit Dhillo of the Department of Medicine at Imperial College London in the UK, notes that as a result of such drugs, some IVF patients experience ovarian hyperstimulation syndrome (OHSS).

OHSS is a condition that triggers overstimulation of ovaries, causing them to become swollen and painful. In some cases, women may experience rapid weight gain, shortness of breath, abdominal pain and vomiting.

"OHSS is a major medical problem," says Prof. Dhillo. "It can be fatal in severe cases and it occurs in women undergoing IVF treatment who are otherwise very healthy."

Kisspeptin results in 'good outcome' compared with standard IVF treatment

For their study, Prof. Dhillo and colleagues tested a naturally occurring hormone called kisspeptin on 53 women undergoing IVF to see whether it could trigger ovulation induction in a safe and effective manner.

After each woman received one injection of kisspeptin, 51 out of 53 developed mature eggs, and 49 had either one or two fertilized embryos that could be transferred to the uterus. Of these women, 12 became pregnant, which the researchers say is a "good outcome" when compared with standard IVF therapy using hCG.

One of the participants, Alison Harper, gave birth to a baby boy, Owen, in October last year. She says that after several cycles of IVF, the one used in this study was the least uncomfortable, causing less pain and swelling.

The research team explains that kisspeptin does not stay in the blood for long periods like hCG. This means the hormone is broken down faster, reducing the occurrence of ovary overstimulation.

Commenting on the team's findings, Prof. Dhillo says:

"Our study has shown that kisspeptin can be used as a physiological trigger for egg maturation in IVF therapy. It's been a joy to see 12 healthy babies born using this approach. We will now be doing more studies to test whether kisspeptin reduces the risk of OHSS in women who are most prone to developing it, with a view to improving the safety of IVF therapy."

The researchers now plan to conduct a second study among women with polycystic ovary syndrome, who have the highest risk of OHSS as a result of treatment with fertility medication.

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For Women Taking Certain Kinds Of Pain Relievers, A Heart Attack Could Be Waiting In Their Medicine Cabinets

Dr. Enrique Jacome

A University of Florida study has found that the regular use of some non-steroidal anti-inflammatory drugs, or NSAIDs, increases the risk of stroke, heart attack and death in postmenopausal women. The study was published this week in the journal Circulation: Cardiovascular Quality and Outcomes.

The researchers found that regular use of the NSAID naproxen, the active ingredient in medications such as Aleve, is associated with a 10 percent increased risk of heart attack, stroke and death in postmenopausal women, said UF cardiologist Anthony Bavry, M.D., the study's lead author. Regular use was defined as at least twice per week for the previous two weeks.

"That is counter to the medical community's perception of NSAIDs, in which most people believe naproxen to be safer," Bavry said. "Our study showed naproxen was not safer - it was actually harmful."

Bavry, in collaboration with researchers from Harvard and other universities, combed through data from more than 160,000 postmenopausal women who were surveyed as part of the Women's Health Initiative - a 15-year research study funded by the National Institutes of Health. Of these women, 53,142 regularly used NSAIDs. Even after controlling for obesity, hypertension, diabetes, use of aspirin and other health factors, the researchers found the increased risk for heart attack, stroke or death among the women who used certain types of NSAIDs.

One of the study's co-authors, Marian Limacher, M.D., has been the UF principal investigator for the Women's Health Initiative since 1994. She emphasized that the study was observational in nature, which helped the researchers find associations between use of NSAIDs and cardiovascular impacts. Limacher also noted that this was the first study of its size to examine the effects of regular NSAID use on women.

"When we study agents such as aspirin, we have found differential effects in men and women," Limacher said. "Men had reduction in heart attack, and older women had a reduction in stroke but not heart attack, which is part of the reason those of us studying women feel we really need to have adequate information on commonly used drugs for both men and women."

NSAIDs include over-the-counter medications such as naproxen and ibuprofen as well as prescription drugs such as rofecoxib, commercially branded as Vioxx, and celecoxib, branded as Celebrex. Because of its association with increased risk of heart attack or stroke, Vioxx was taken off the market in 2004.

The study's main finding confirmed that the regular use of any NSAID was associated with harm such as digestive bleeding. Although it found for the first time that the risk of heart attack, stroke or death was associated with the use of naproxen, the study found no cardiovascular or stroke harm associated with ibuprofen.

NSAIDs work by inhibiting two enzymes responsible for inflammation, called cox-1 and cox-2. They also can cause bleeding in the stomach and digestive tract. NSAIDs that target just the cox-2 enzyme, which is present mainly at the site of inflammation, are designed to prevent bleeding in the digestive tract, Bavry said.

However, previous studies showed that NSAIDs that solely target the cox-2 enzyme, which include Vioxx and Celebrex, have been associated with adverse cardiovascular events such as heart attack or stroke. Bavry thinks the culprit in naproxen is also cox-2 inhibition.

"People will have to think about what they have in their own medicine cabinet," Bavry said. "Do they have naproxen, ibuprofen or something else?"

The study looked only at the association between cardiovascular events and use of NSAIDs - not the effects of NSAIDs on the kidneys, for example.

"We would encourage patients to use medications for as short a time as they need, and to be sure they follow up with their physicians regularly to monitor for effects on the kidneys, and potentially for risk for heart disease," Limacher said.

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The Contraceptive Microchip: Could It Revolutionize Global Birth Control?

Dr. Enrique Jacome

MicroCHIPS, an IT start-up company with links to Massachusetts Institute of Technology, is developing a radical new contraceptive - a tiny microchip implanted under the skin that can be operated wirelessly by remote control.

In the 1990s, Robert S. Langer - the David H. Koch Institute Professor at Massachusetts Institute of Technology (MIT) and reportedly "the most cited engineer in history" - and his colleagues Michael Cima and John Santini, developed a microchip technology that could release controlled amounts of chemicals.

Fast-forward to 2012, and Langer's MIT lab received a visit from Bill Gates, who inquires with Langer whether it would be feasible to create a new method of birth control that a woman could turn on and off as she likes and which she can use for many years.

Langer proposed that his controlled release microchip might offer a solution. Leasing the technology to MicroCHIPS, the company have developed a device measuring just 20 x 20 x 7 mm designed to be implanted under the skin of the buttocks, abdomen or upper arm.

The chip contains tiny reservoirs of the hormone levonorgestrel, which is already used in some contraceptives. The chip dispenses 30 mcg of levonorgestrel every day, and can hold enough of the hormone to do this for up to 16 years.

When a woman wishes to conceive, she simply turns off the device with a remote. The chip would not need to be removed from the woman until 16 years of use have elapsed. By contrast, current hormonal birth control implants last a maximum of 5 years.

The levonorgestrel is contained on the chip using a hermetic titanium and platinum seal developed by MicroCHIPS. The hormone is released by passing an electric current from an internal battery through the seal, which melts it temporarily, allowing a small dose of levonorgestrel to be released each day.

According to MicroCHIPS president Robert Farra, "the idea of using a thin membrane like an electric fuse was the most challenging and the most creative problem we had to solve."

Speaking to BBC News, Farra suggested "the ability to turn the device on and off provides a certain convenience factor for those who are planning their family."

Although some critics of the device are worried about the potential for the microchip to be "hacked," Farra claims that the communication between the remote and implant "has to occur at skin contact level distance," so "someone across the room cannot reprogramme your implant."

"Then we have secure encryption," he says. "That prevents someone from trying to interpret or intervene between the communications."

MIT Technology Review points out that recently an international coalition of governments, companies, philanthropies and nonprofit organizations committed to providing family planning to 120 million more women in the world by 2020.

As new birth control options are rarely produced by private companies, MIT believe that the MicroCHIPS implant could play an important role in this mission.

MicroCHIPS, with the backing of Bill Gates, plan to submit the implant for preclinical testing in the US next year, and believe that the device could go on sale by 2018.

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Researchers Discover Potential New Treatment For Aggressive Breast Cancer

Dr. Enrique Jacome

Researchers have discovered a "viable" new target for the treatment of a particularly aggressive form of breast cancer. The molecule, known as alpha-v-beta-6, could also be used to identify those women with HER2-positive breast cancer who have a higher risk of developing secondary tumors.

The researchers found they could stop cancer cells invading, which these could do only with the help of alpha-v-beta-6 (αvβ6). Using the experimental antibody 264RAD, the team publishing in the Journal of the National Cancer Institute, found they could block the assistance given by the αvβ6 molecule.

Over 2,000 breast cancer patients gave samples for analysis, which revealed that there was no trace of αvβ6 in normal breast tissue but high levels of it in 40% of tumors from HER2-positive patients. The researchers found that the molecule was also a marker of poor chances of survival due to cancer spread.

UK breast cancer research charity the Breast Cancer Campaign, which funded the work, says the results offer hope that an effective treatment could be developed for the group of women with HER2-positive breast cancer who fail to respond to the first-line drug trastuzumab (Herceptin).

Trastuzumab blocks the signals sent from HER2 that promote tumor growth, but "up to 70% of patients either do not respond to Herceptin, or develop a resistance to the therapy," says the research advocate.

The authors of the research paper add:

"The results of this pre-clinical study suggest that targeting the αvβ6 molecule may enhance the effectiveness of Herceptin - and that a combination treatment could be effective for patients where Herceptin alone has not worked."

Early-stage experiments

The research was pre-clinical - that is, it was early-stage research that did not test any treatments in humans. Both laboratory cell analyses and tests in mice were undertaken.

The laboratory work analysed the αvβ6 molecule in tissue from breast cancer patients, and the role of αvβ6 in relation to HER2 effects on tumor expression, proliferation, invasion and growth was assessed in the mice.

The mice were randomized to receive 264RAD (the antibody that blocked αvβ6), trastuzumab, or both 264RAD and trastuzumab. This last group with combined blockade of αvβ6 and HER2 showed eradication of the tumors in all the mice treated.

The authors conclude that "simultaneous antibody targeting of αvβ6 (with 264RAD) and HER2 (with trastuzumab) statistically significantly improves the therapeutic effect of trastuzumab alone and statistically significantly increases survival."

The results on the tissue sample investigations, says Dr. John Marshall, reader in tumor biology at Queen Mary University of London's Barts Cancer Institute, UK, mean that:

"High αvβ6 levels could be tested for in routine biopsies to identify which women are at a high risk of metastasis, ensuring these women can receive personalised treatment, improving their chances of survival."

The Medical Research Council also provided grants for the research alongside the Breast Cancer Campaign, whose chief executive Baroness Delyth Morgan says:

"There is a desperate need for drugs which work in new ways to give the thousands of women diagnosed with HER2-positive breast cancer the best possible chances of surviving the disease.

"This study could pave the way for new treatments and bring us closer to our goal of preventing half of the deaths from breast cancer by 2025, through improved and personalised treatments."

Dr. Marshall and his team are building on their findings by investigating the most effective time to use 264RAD against tumors and potentially stop the spread of HER2-positive breast cancer.

In other recent news about potential new targets for the fight against breast cancer, researchers announcing their results in June 2014 found that a cholesterol-busting compound may halt breast cancer.

Early menopause and infertility can be side effects for younger women undergoing chemotherapy for breast cancer but May 2014 findings indicate that new drug regimen 'reduces early menopause risk'.

Finally, you may be interested in our recent analysis, What is science doing to improve the health and lives of cancer survivors?

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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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