Monday, July 31, 2017

Ultrasound is sufficient for prenatal diagnosis of placenta previa accreta: a systematic review and meta-analysis

Ultrasound is highly sensitive and specific in diagnosing placenta previa accreta, after previous cesarean section when performed by skilled sonologist reports the results of a systematic review and meta-analysis by Jauniaux and Bhide published in July issue of Obstetrics and Gynecology.

Placenta accreta is a potential life-threatening condition and requires multidiscipline involvement for successful management and reducing maternal and neonatal morbidity and mortality. Because of increasing incidence of cesarean sections, the incidence of morbidly adherent placenta is on rise.

The incidence of placenta previa accreta was 4.1% in women with 1 prior cesarean and 13.3% in women with ≥2 previous cesarean deliveries.

Prenatal diagnosis of placenta accreta allows for sufficient time and planning by involving the concerned discipline to be prepared in advance.

The researchers included data from 14 cohort studies with 3889 pregnancies presenting with placenta previa or low-lying placenta and 1 or more prior cesarean deliveries in the quantitative analysis.

There were 328 (8.4%) cases of placenta previa accreta, 90% (298 cases) of which were diagnosed with ultrasound.

Two hundred and eight patients underwent cesarean hysterectomy out of 232 cases (89.7%)
The odds of diagnosing placenta accreta were higher in prospective studies (odds ratios = 228.5) as compared to retrospective studies (odds ratio=80.8). Sonography was more accurate in diagnosing placenta accreta as the depth of villous invasion increased.

The authors stressed the need of developing screening protocols for better management of this increasingly common and life threatening obstetric complication.

Placental Accreta Index (PAI) was recently proposed to predict individual risk for morbidly adherent placenta using 2-D and color Doppler sonographic exam. It includes 5 parameters: 2 or > cesarean delivery, lacunae, myometrial thickness, anterior placenta previa and bridging vessels.

Each parameter was weighted to create a 9-point scale in which a score of 0-9 provided a probability of invasion that ranged from 2–96%, respectively. The probability of invasion increases with increasing PAI score, such that a score of 9 confers a 96% chance of histologic placental invasion.

But, the score needs further validation before it can be used as a standardized method in prediction of placenta accreta, but it definitely improved the  antenatal detection.

Sunday, July 30, 2017

In case you missed it: Here are the top 5 posts this month

Double layer vs single layer uterine closure in cesarean results in stronger uterine scar and increases chances of vaginal birth in future pregnancies.
Double layer closure of uterus during previous cesarean section results in thicker third-trimester lower uterine segment and decreases rate of uterine rupture by 3 to 5fold during trial of labor after cesarean (TOLAC) and vaginal birth after cesarean reports results of multicenter prospective cohort study published in July issue of Journal obstetrics and gynecology.

New treatment option for recurrent implantation failure on the horizon: Short term copper IUD
Placement of Cu-IUD during hysteroscopy for two cycles can up the pregnancy rates in patients with RIF says results of a study published in July issue of Journal Fertility and Sterility.
Recurrent Implantation Failure (RIF) is very frustrating for patients and physician both. Over the decades, few research study have emerged forward about the etiology and therapeutic options.
 Constitutive, as well as mature defects of endometrium have been put forward as one of the etiology. 

Aspirin in combination with heparin results in more live births in Repeated Pregnancy Loss: a systemic review and meta-analysis
Aspirin in combination with heparin ups the odds of live births 2.5 times as compared to aspirin alone among women with antiphospholipid syndrome (APS) who had experienced repeated pregnancy loss says the result of a systematic review and meta-analysis.

The prevalence of APS in women with RPL varies according to studies, from as low as 6% to as high as 42%, but it is generally accepted to be 5%–20%.

The results were presented at the International Society on Thrombosis and Haemostasis (ISTH)2017 Conference.

A minimal invasive approach in management of symptomatic post–cesarean section isthmocele: a video case report.
The cesarean section scar defect, also known as an isthmocele, is a reservoir-like pouch defect on the anterior wall of the uterus, located at the site of a previous cesarean delivery scar. It exact incidence is unknown because of scarcity of data about the condition.

It is commonly found on ultrasound examination (24%-88%). It could range from just thinning of the uterine myometrium to large defects leading to complete absence of myometrium.

Eating your own placenta: CDC issues warning against this latest craze!
Center for Disease Control(CDC) issued a warning in the weekly Morbidity and Mortality Weekly Report (MMWR) against consumption of placenta pills, after an Oregon infant recurrent illness was tied to maternal consumption of placenta pills.

Consumption of placenta in the form of pills or smoothies is called as Placentophagy and has become a recent trend, after it was touted by many celebrities to help mothers overcome postpartum depression, increase milk production and speeds up uterus involution, boosts energy, promotes skin elasticity, enhances maternal bonding and replenishes iron in the body.

Saturday, July 29, 2017

Now a Microchip for Nonivasive Prenatal Diagnosis by a simple and quick blood test

The researchers have developed a new class of NanoVelcro microchips that are reproducible and faster using nano-imprinting fabrication process. The cells were coated with an antibody to a marker for capturing the fetal cells.

Circulating fetal nucleated cells (CFNCs) in maternal blood are rich source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD).

The NanoVelcro microchip was developed to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood. The researchers then isolate single cTBs cell on the imprinted nanoVelcro microchips with the help of laser capture microdissection (LCM) technique.
cTB-based array comparative genomic hybridization (aCGH) and short tandem repeats analysis was done to detect fetal genders and chromosomal aberrations.

The team tested the blood samples of 15 pregnant women, carrying a single fetus and accurately determined genetic conditions that were previously diagnosed by other invasive methods in nine of the fetuses.

The paper was published July 19, 2017 in American Chemical Society Journal NANO.

Currently most of the tests available for routine Prenatal Diagnosis are accurate but invasive like amniocentesis and chorionic villus sampling. Researchers are looking at ways to isolate fetal DNA circulating in mother’s blood, but it comes in small pieces and the amount is also not adequate to run diagnostic tests.

Whole fetal cells are also present in maternal blood but, we lack ideal methods to capture them for genetic testing. Hsian-Rong Tseng and her colleagues at California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles have previously developed a ‘NanoVelcro' microchip assay for capturing circulating tumor cells. So, in this new paper they are looking to apply the same technique for capturing circulating fetal cells.

Photo credit: American Chemical Society

Friday, July 28, 2017

Statins in combination with chemotherapy improves survival in ovarian cancer

Women diagnosed with ovarian cancer could survive longer when a statin is added to the treatment regimen, in addition to the cancer-specific treatment says the results of a new research study led by Keele University and published recently in Scientific Reports.

This is in contrast to earlier research studies, in which statins in laboratory studies were effective against ovarian cancer but did not show the same efficacy when tested in real human participants.

Ovarian cancer accounts for only 3 percent of all cancers in women, but it causes more deaths in women than any other reproductive system cancer because it is often diagnosed at a very late stage.

The Centers for Disease Control and Prevention (CDC) estimate that in 2014, 21,161 women in the U.S. found out that they had ovarian cancer and 14,195 died of the disease.

Dr Alan Richardson, a reader in pharmacology in the School of Pharmacy, who led the research at Keele and co-authored the paper, explained:
“We believe we have found the answer to the paradox: for statins to be effective as a cancer therapy, the right statin needs to be used, it needs to be delivered at the right dose and interval, and diet needs to be controlled to reduce sources of geranylgeraniol, which can limit the statin’s effect on cancer cells.”

The researchers at Keele University have identified a particular statin called pitavastatin, which has a long metabolic half-life, necessary for continuous inhibition of tumor growth. It was also seen that diet affects the action of pitavastatin on tumor cells.

The apoptosis of ovarian cancer cells was inhibited in the presence of dietary geranylgeraniol. Geranylgeraniol is present in various foods like sunflower seeds and some varieties of rice.

Statins have shown to be effective in other cancers also. In fact, Pitavastatin was effective in killing cancer cells, even after they have developed drug resistance. This raises the possibility that statins may be useful to treat patients who have developed resistance to chemotherapy.

The inhibitory effect of dietary geranylgeraniol on actions of pitavastatin may explain the discrepancies observed in efficacy of the drug between pre-clincal lab studies and human studies.

The next stage of research is to conduct full clinical trials in humans. Dr Richardson is already planning clinical trials at Keele University. He commented “The key message of our work is that clinical trials of pitavastatin can now be properly designed, and we are in the very early stages of developing trials with our colleagues at Keele University and Birmingham University. It is also noteworthy that pitavastatin is available in a generic form, potentially making this a relatively inexpensive treatment.”

The research also opens new possibilities for use of statins to prevent ovarian cancer. The use of statins in reducing morbidity and mortality in CVDs is well documented. Further targeted clinical trials are needed before it can be clinically prescribed as anticancer.

The Keele University press release can be accessed here.
Full text of the article in Scientific Reports can be accessed here.

Thursday, July 27, 2017

Hypertensive disorders during pregnancy predisposes to future hypertension and the risk persists for more than 20 years.

Women face substantially high risk of post pregnancy hypertension in the first year after the index pregnancy and the risk persists for more than 20 years, with 14- 32% for the first decade reports the result of a nationwide register based cohort study published in July issue of BMJ.

Nearly one third of women with hypertensive disorder of pregnancy will develop hypertension within 10 years of the affected pregnancy, so blood pressure monitoring should be initiated immediately after delivery.  

What is already known:
Women who have a history of hypertensive disorders while pregnant have 2 to 4-fold increased risk of developing essential hypertension, and a subsequent CV event.

But the data about the timing of developing hypertension and the time at which the screening of these at-risk women should begin is not known.

What the study adds:
This study gives us the chronology of events: How soon the women may develop hypertension, how long the risk will persist after the affected pregnancy and when to start monitoring these women for development of hypertension.

The study identified 482972 women through Danish civil registration system, of these 23235 (4.8%) women developed hypertensive disorder of pregnancy and 16611 developed hypertension during follow-up.

In a cohort of more than one million women delivering in Denmark from 1978-2012, the investigators formed two cohorts and followed them for estimation of cumulative incidence of post-pregnancy hypertension and the other cohort for the estimation of hazard ratios for post-pregnancy hypertension.

Women with chronic hypertension were excluded from the study.

In women who had normotensive first pregnancy in 20s, 30s, or 40s, the cumulative incidences of hypertension in the first 10 years after delivery were 4.0%, 5.7%, and 11.3%, respectively, whereas in women with hypertensive disorder the corresponding incidence were 13.7%, 20.3%, and 32.4%, respectively.

In women with history of hypertensive disorder in most recent pregnancy, the rates of developing hypertension were 12-fold to 25-fold higher in the first-year after delivery and up to 10-fold higher in the coming 10 years.

Women face 2 fold increase risk of developing hypertension, that lasts for the next 20 years, if they have a previous history of hypertensive disorder in pregnancy as compared to women who had normal blood pressure while pregnant.

Why this study is important:
Large cohort, elimination of selection and recall bias.

Data adjusted for age, parity, smoking status, diabetes and BMI.

Immediate post-partum period is very important: The risk of developing hypertension is highest shortly after an affected pregnancy but persists for more than 20 years.

The higher risk of hypertension in a decade after the affected pregnancy also indicates that the etiopathological process causing hypertension in later life, are already at play during the affected pregnancy.

A hypertensive disorder of pregnancy in the second pregnancy was more strongly associated with later hypertension than a hypertensive disorder of pregnancy in the first pregnancy.

Initiation of regular blood pressure assessments should begin soon after a pregnancy complicated by a hypertensive disorder of pregnancy for prompt identification of hypertension in these women.

What is needed in the future:
An algorithm to identify those at greatest risk (the subgroup most likely to benefit from screening) is urgently needed; identification of biomarkers that predict which women will develop hypertension after an affected pregnancy would be very useful.

Quantification of cardiovascular events that can be prevented by early identification of these at-risk women is also needed.

More randomized control trials to form policies on clinical follow up of such women.

Wednesday, July 26, 2017

Aspirin in combination with heparin results in more live births in Repeated Pregnancy Loss: a systemic review and meta-analysis

Aspirin in combination with heparin ups the odds of live births 2.5 times as compared to aspirin alone among women with antiphospholipid syndrome (APS) who had experienced repeated pregnancy loss says the result of a systematic review and meta-analysis.

The prevalence of APS in women with RPL varies according to studies, from as low as 6% to as high as 42%, but it is generally accepted to be 5%–20%.

The results were presented at the International Society on Thrombosis and Haemostasis (ISTH)2017 Conference.

Researchers at Leiden University Medical Center in the Netherlands conducted a systematic literature search for randomized controlled trials that compared low dose aspirin (LDA), low-molecular-weight heparin (LMWH)or unfractionated heparin (UFH), or both on the effect of live birth in women with APS and recurrent pregnancy loss.

The investigators identified 939 research studies, full text review resulted in 9 studies, of which only 5 were included in the final analysis. Combined data resulted in a total of 398 women. Studies were excluded if they did not meet the diagnostic criteria   for APS.

The study results showed that:

LDA alone did not have much potential benefits in increasing the live birth rates as compared to a placebo.

Heparin of any kind resulted in live birth rate 2.5 times that of LDA alone (odds ratio [OR] 2.51; 95% CI 1.48–4.25, P<0.001).

When unfractionated heparin (UFH) was combined with LDA the likelihood of live birth rates increased to 3.75 times as compared to LDA alone in an analysis of pooled data from three studies. (odds ratio [OR] 3.75; 95% CI 2.04–6.90, P<0.001).

However, when LMWH was paired with LDA in two studies, there was no significant difference in odds of having a live birth.

This systematic review and meta-analysis findings were limited by sample size, lack of adverse effects reporting of heparin and aspirin in the original studies, dose disparities. Mauritia Marijnen from Academic Medical Center, Amsterdam, the Netherlands stressed on urgent need of rigorous randomized controlled trials, particularly on the use of LMWH.

Unfractionated heparin (UFH) is an older drug with side effects, but in this meta-analysis it appeared to be more effective in increasing the odds of live birth rates. It maybe because of some other confounders which were not analyzed in this study, which makes it all the more important to carry out future studies with LMWH.

The authors concluded, “Heparin plus aspirin compared with aspirin improves live birth in women with APS and recurrent pregnancy loss. This effect is driven by studies that investigated UFH and not LMWH.”

All the abstract presented at the conference can be accessed here.

Primary source: Marijnen MC, Scheres LJJ, Middeldorp S, et al. Aspirin, heparin or both to improve live birth in women with antiphospholipid syndrome and recurrent pregnancy loss. ISTH 2017; July 11, 2017; Berlin, Germany. Abstract ASY 22.3.

Tuesday, July 25, 2017

New surgical glue that works well in wet environment on the horizon.

Staples and surgical sutures will soon be a thing of past. Researchers at Purdue University have developed a nontoxic, biocompatible glue from adhesive proteins produced by mussels and other creatures.

The paper was published in April in Journal Biomaterials.

The material is unique because it is able to work while immersed in a water environment, and have shown to be far better than other current commercially available products.

The material is currently named ELY16, is constructed from an elastin-like polypeptide (ELP) that can be produced in high quantity from Escherichia coli and can coacervate in response to environmental factors such as temperature, pH, and salinity.  

ELY16 is rich in tyrosine and after reaction with tyrosine kinase it is changed into mELY16, converting the tyrosine residue into 3,4-dihydroxyphenylalanine (DOPA).

Both these compounds (ELY16 and mELY16) are cytocompatible and exhibit significant dry strength. Addition of DOPA makes them adherent in humid environment.

Julie Liu, an associate professor of chemical engineering and biomedical engineering at Purdue University said, “Sutures and staples have several disadvantages relative to adhesives, including patient discomfort, higher risk of infection and the inherent damage to surrounding healthy tissue.”
It is estimated that 230 million major surgeries are performed worldwide every year and 12 million trauma patients are treated in USA each year. About 60% of these wounds are closed by surgical suture or staples.

“Current biomedical adhesive technologies do not meet these needs,” she said. “We designed a bioinspired protein system that shows promise to achieve biocompatible underwater adhesion coupled with environmentally responsive behavior that is ‘smart,’ meaning it can be tuned to suit a specific application.”

The initial tests were done aluminum substrates, but the researchers will soon start testing with soft body tissue like substrates to make it suitable for biomedical purposes.

“To our knowledge, mELY16 provides the strongest bonds of any engineered protein when used completely underwater, and its high yields make it more viable for commercial application compared to natural adhesive proteins,” she said. “So it shows great potential to be a new smart underwater adhesive.”

Here is the YouTube video ‘Non-toxic underwater adhesive could bring new surgical glue’


Monday, July 24, 2017

Guidelines issued for standardized care to patients with severe hypertension during pregnancy

The National Partnership for Maternal Safety, under the guidance of the Council on Patient Safety in Women’s Health Care, has issued a patient safety bundle that assists the healthcare professionals in providing a standardized care to patients with severe hypertension during pregnancy and the postpartum period.

The consensus  bundle was published online  ahead of print in Journal of Obstetrics and Gynecology. The safety bundle is organized into 4 domains and outlines clinical practices that should be practiced at every maternity unit.

The four domains are: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning.

The readiness domain consists of 5 key components to prepare each maternity unit for prompt and effective management of women with hypertension in pregnancy. It includes:

Each maternity setting should have standardized criteria for recognizing the warning signs, to diagnose, monitor and treat preeclampsia and eclampsia.

The staff should undergo regular drills to practice the protocols.

The maternity unit, along with the OPD and ER should be well equipped for dealing with patients with severe preeclampsia or eclampsia.

All the medications used in emergency treatment should be readily available and stocked continuously.

Appropriate consultations from various concerned department and means of transportation to tertiary center should be available all the time.

Recognition and Prevention
All women should be educated about the warning signs of hypertension in pregnancy.

Standard protocols should be developed for measuring B.P and urine analysis for all women during pregnancy and postpartum period.

Standard protocols should be developed and followed for investigating all women with hypertension in pregnancy. The investigations should include complete blood count with platelets, aspartate transaminase, and alanine transaminase.

Response (Every Case of Severe Hypertension or Preeclampsia)
Each facility should be well equipped with management of severe hypertension, Eclampsia, seizure prophylaxis, and magnesium over dosage and recognizing symptoms of postpartum hypertension.

The concerned physician or primary care provider should be immediately notified if systolic blood pressure is 160 mm Hg or greater or diastolic blood pressure is 110 mm Hg or greater for two measurements within 15 minutes.

If the second blood pressure reading is also high, treatment should be initiated immediately. Guidelines for initiation and maintenance of Magnesium Sulfate should be readily available everywhere.

Escalation measures should be lined out for patients unresponsive to initial treatment along with follow up and education protocols at 7-14 days postpartum.

Reporting and Systems Learning (Every Unit)
All the members of the multidisciplinary team should receive debriefing about the way the emergency was handled, what went well along with areas of improvement.

The team should also review all other patients admitted with severe hypertension and eclampsia about the outcome. Robust data system should be present to report accurate outcomes to all the concerned persons. The review should include all the measures taken since the woman arrived in emergency room till postpartum education and follow-up.

One very important key element in reducing maternal morbidity and mortality and neonatal morbidity and mortality is time to treatment after the recognition of severe hypertension.

The full text of the article can be accessed here.

Saturday, July 22, 2017

CompuFlo precise computer-controlled Epidural anesthesia system won clearance from the FDA.

Milestone Scientific, Inc., a company based at Livingston, New Jersey, has designed CompuFlo® Epidural instrument that uses dynamic pressure sensing (DPS) to help anesthesiologists to quantitatively determine and document the pressure at the needle tip in real-time.

The computerized system provides visual and audible feedback of the pressure which enables the anesthetist to correctly identify the epidural space and significantly reduce complications in real-time, according to Milestone.

Leonard Osser, Chief Executive Officer of Milestone Scientific commented, "We are delighted to receive marketing clearance from the FDA, which is considered globally to be the regulatory gold standard in premarket review."

The clearance was based on results of the COMPASS Study (CompuFlo Assessment Study), which was a prospective, randomized, controlled, parallel group, multicenter, pivotal study to assess the safety and effectiveness of epidural space verification with the CompuFlo Epidural Instrument.

The study enrolled 400 patients, of whom 240 required epidurals as a relief from chronic pain and 160 patients were women, requiring epidural for pain management in labor and delivery.

The technique also showed the same efficacy in 21 obese patients with BMI > 31.

The application benefits of Milestone's CompuFlo-based Epidural Injection System are numerous and well defined, and include:
  • materially reducing, and possibly eliminating, existing medical risks and complications associated with administering epidurals
  • improving patient safety and comfort
  • reducing liability to medical care providers/institutions
  • reducing malpractice clams and related insurance premiums for anesthesiologist

The CompuFlo Epidural with Dynamic Pressure Sensing Technology is contraindicated in patients with prior back surgery in lumbar area, skin condition in their lumbar region greater than 4 sq cm and to infuse medication.

Media Courtesy: Milestone Scientific, Inc.

Friday, July 21, 2017

A minimal invasive approach in management of symptomatic post–cesarean section isthmocele: a video case report.


The cesarean section scar defect, also known as an isthmocele, is a reservoir-like pouch defect on the anterior wall of the uterus, located at the site of a previous cesarean delivery scar. It exact incidence is unknown because of scarcity of data about the condition.

It is commonly found on ultrasound examination (24%-88%). It could range from just thinning of the uterine myometrium to large defects leading to complete absence of myometrium.

It could present with abnormal uterine bleeding(AUB), pelvic pain and infertility in post-operative period. Several obstetric complications such as scar dehiscence, placenta accreta, and ectopic scar pregnancy are increasingly reported along with rising cesarean rates.

It is commonly repaired by vaginal surgery, operative hysteroscopic, combined laparoscopic-vaginal, or minimal invasive laparoscopic approach.  In absence of randomized studies, the efficacy of these approaches or superiority of one over another is not known.

A review of data showed that hysteroscopy is able to correct the scar defect but does not increase the uterine wall thickness, whereas laparoscopy is able to increase the uterine wall thickness.  

This video case report by Aimi G. et al. published in June issue of Fertility and Sterility describes a minimal invasive laparoscopic approach for correcting the scar defect.

A 36-year-old woman with history of 2 previous section presented with persistent postmenstrual spotting and chronic pelvic pain. A transvaginal sonography identified a 20.0 × 15.6 mm defect at the place of previous scar with a 2.6 mm remaining myometrial thickness over the defect.

In this case Isthmocele excision and myometrial repair was performed laparoscopically. After mobilization of the bladder, the isthmocele was identified by transrectal intraoperative sonography. Once identified, the isthmocele pouch was excised and contents drained. The cesarean section scar is excised with the help of cold scissors till healthy myometrium is visible. The defect was closed with a single layer of interrupted 2-0 Vycril sutures. A Hegar dilator was placed in cervix to maintain the continuity of uterus with the cervix.  Finally, visceral peritoneum was closed. Total operative time was 70 minutes.

Post operatively the patient made an uneventful recovery and was discharged home on 2 post-op day. A follow up sonography at 40 days after surgery with transvaginal and transabdominal route showed a complete repair of defect. At 3 months follow-up, postmenstrual spotting and chronic pelvic pain also resolved completely.

The authors concluded that, a laparoscopic approach is procedure of choice when repairing large isthmocele with severe myometrial thinning.  

Here is the video of the surgery

Thursday, July 20, 2017

Early menopause ups the risk of developing type 2 diabetes

Women who have an early natural menopause have 2.5 times the risk of developing type 2 diabetes as compared to women who have normal menopause reports the results of a large population based study published online July 18, 2017 in Journal Diabetologia.

Taulant Muka, MD, PhD, of Erasmus University Medical Center, Rotterdam, Netherlands, and colleagues write, "In this large population-based study of postmenopausal women free of type 2 diabetes at baseline, we showed that early onset of natural menopause is associated with an increased risk of type 2 diabetes, independent of potential intermediate risk factors for type 2 diabetes (including body mass index [BMI], glucose, and insulin levels) and levels of endogenous sex hormones and SHBG [sex hormone-binding globulin]."

Menopause is a major transition point in women’s life and declining estrogen levels predispose her to increase risk of cardiovascular disease. But, few studies have examined the association between age at menopause and risk of developing type 2 diabetes. Few cross-sectional studies have yielded conflicting results because beside declining hormonal levels, menopausal weight gain, increase in visceral fat and impaired glucose metabolism may also play a part.

This study examined data from Rotterdam study and recruited 3639 women in the final analysis. The Rotterdam Elderly Study is a prospective cohort study in the Ommoord district in the city of Rotterdam, the Netherlands aimed to investigate the risk factors of cardiovascular, neurological, ophthalmological and endocrine diseases in the elderly.

All the women in the current study have attained natural menopause and did not have diabetes at the time of enrollment. The mean age at of woman  was 66.9 (9.6) years, the mean age at natural menopause was 50.0 (4.4) years with median time elapsed since menopause was 15.0 years. The women were stratified into 4 groups according to age at menopause: premature (< 40 years), early (40–44 years), normal (45–55 years), or late (> 55 years).

An analysis of the study cohort showed that 348 women (9.6%) developed type2 diabetes during a median follow up of 9.2 years after adjusting for confounders like age, BMI, glucose and insulin levels, smoking, HRT and genetics. Late menopause is a significant protective factor as compared to premature and early menopause.

Women with late menopause were protected against developing diabetes, and the risk increased as the age at natural menopause decreased. The risk was nearly 4 times higher in women with premature menopause (HR, 3.7)  twice   in women with early menopause (HR, 2.4) and 60% more in women with normal menopause (HR, 1.6; P < 0.001) .

For each 1year delay in onset of menopause, the risk of developing diabetes was lowered by 4% (HR, 0.96).

The authors could not account for the mechanism linking age at natural menopause with development of type 2 diabetes. Earlier data have shown that natural early menopause is a sign of not only reproductive aging but also early somatic aging and all its cardiometabolic consequences. Hence, early menopause can be a good predictor of future general health including type 2 diabetes.

But, the results remained the same after adjusting for the shared genetic factors, so the pathophysiology is unclear and requires more studies in future.

The authors concluded,” The Early onset of natural menopause is an independent marker of type 2 diabetes risk in postmenopausal women. Future studies are needed to examine the mechanisms behind this association and explore whether the timing of natural menopause can add value to diabetes prediction and prevention.”

The full text can be accessed here.

Wednesday, July 19, 2017

North American Menopause Society (NAMS) video series about important midlife health topics: Hormone therapy timing hypothesis and cognition

In this latest video, Hormone Therapy and Cognition, Dr. Shapiro interviews Dr. Pauline Maki, Past President of NAMS, Professor of Psychiatry and Psychology, Director of Women’s Mental Health Research, and Research Director at UIC Center for Research in Women and Gender at the University of Illinois at Chicago. Dr. Maki discusses the hormone therapy timing hypothesis and cognition, the relationship between cognition and cardiovascular protection, and the latest cognition trials and studies.

Timing of initiation of hormone therapy in relation to age or time since final menstrual period modify the effect of hormone therapy on cognition as documented now by three very well-known clinical trials. Dr. Maki explains the timing hypothesis very well in this latest NAMS video.

Tuesday, July 18, 2017

The USPSTF maintains its recommendation against screening for ovarian cancer in average risk women

The U.S. Preventive Services Task Force today released a draft recommendation statement and evidence review on ovarian cancer screening that is in line with its final recommendation in 2012.

The USPSTF has given a ‘D’ grade for screening recommendation for ovarian cancer in asymptomatic women, that means “The USPSTF recommends against screening for ovarian cancer in asymptomatic women.”

The USPSTF found adequate evidence that screening with transvaginal ultrasound, testing for the serum tumor marker cancer antigen (CA)–125, or a combination of both does not reduce the number of deaths from ovarian cancer in women.

The current evidence was insufficient to assess the balance of benefits and harms of performing screening pelvic examination in asymptomatic, nonpregnant adult women.

The screening tests also have a low positive predictive value, which means that most women who receive a positive diagnosis of ovarian cancer do not have one.

It also leads to unnecessary surgery and psychological harm.

This screening guidelines are not for women with BRCA 1 and BRCA2 mutation, Lynch, Li-Fraumeni, or Peutz-Jeghers syndrome. Women with BRCA1 and BRCA2 mutations have an average risk of 44% and 17% for developing ovarian cancer. Mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers.

USPSTF also does not advice routine screening in women with family history breast and ovarian cancer, as a higher incidence of cancer incidence in family may results in greater number of patients diagnosed with ovarian cancer but it does not necessary translate into saving lives.

These women can be referred  for genetic counseling and, if indicated, genetic testing.

USPSTF chair David Grossman, MD, MPH, senior investigator at Kaiser Permanente Washington Health Research Institute, said in a statement, “The current screening tests do not do a good job of identifying whether a woman does or does not have ovarian cancer. The Task Force hopes that in the future, better screening tests for ovarian cancer will be developed.”

The draft recommendation was supported by results of two large clinical trials United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial which both showed that screening for ovarian cancer does not decrease deaths from ovarian cancer in asymptomatic women not known to be at high risk for ovarian cancer.

The recent draft recommendation is in consensus with guidelines issued by other major medical and public health organizations like American College of Obstetricians and Gynecologists, American Cancer Society, American College of Radiology and American Academy of Family Physicians.

The draft recommendation statement is open to public comments till August 14, 2017.

The full text of the recommendations can be accessed here. 

Monday, July 17, 2017

Artificial sweeteners are now linked to increased cardio-metabolic risk and gain in weight -Not weight loss.

Artificial sweeteners are now linked to significantly higher risks of diabetes, heart disease and increased weight gain according to results of a systematic review and meta-analysis published today in Canadian Medical Association Journal.

Artificial sweeteners are synthetic food additives that we all are familiar with, they provide a sweet taste to the food without adding significant calories to it.

They are found in many common products we consume in our daily life Diet Soda, cough syrup, salad dressings, yoghurts and many more.

It is frequently added to tea, coffee and other sweet dishes to reduce the daily calorie consumption.
The present review was conducted by researchers from the University of Manitoba, Canada and reviewed data from 37 randomized control trials (RCTs) and prospective cohort studies which analyzed more than 406,000 people for an average period of 10 years.

Seven studies were RCTs, considered a gold trials in research arena.

The primary outcome that the researchers were interested was BMI, while secondary outcomes included weight, obesity and other cardiometabolic end points.

The data analysis of included RCTs shows that artificial sweeteners had no significant effect on BMI, whereas the analysis of cohort study showed a moderate increase in BMI over the course of years.

Further analysis of data from RCTs showed no further effect on other parameters of body composition or risk of cardiometabolic diseases. However, the data from cohort studies was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events.

Because the data from RCTs does not resulted in increased weight gain and higher risk of cardiometabolic events, the systematic review does not prove causation.  

Meghan Azad, lead study researcher and an assistant professor in the department of pediatrics and child health at the University of Manitoba in Canada said, “I think there’s an assumption that when there are zero calories, there is zero harm. This research has made me appreciate that there’s more to it than calories alone.”

Susan Swithers, a professor in the department of psychological studies at Purdue University said, “Unfortunately, the quality of evidence that would support using sweeteners is not really strong. I think we are at a place where we can say that they don’t help.”

The current USDA guidelines allows for 10 teaspoons of sugar a day for average person, that equals to just one 16-ounce bottle of regular soda.

There are just five sweeteners approved by the Food and Drug Administration for use in the United States: acesulfame potassium (sold as Sunett and Sweet One), aspartame (sold as Equal, Nutrasweet and Sugar Twin), neotame (sold as Newtame), saccharin (sold as Sweet'N Low, Sweet Twin and Necta Sweet) and sucralose (sold as Splenda).

“More research is definitely needed,” says Azad. “You need a long-term study.” But, lack of proven benefits does make people pause and think, before choosing an artificial sweetener.

In the meantime, researcher’s advice that reducing your taste for sweet altogether rather than choosing between a sugar-sweetened or artificially sweetened drink or food is the best choice at present.

The FDA strongly believes that  use of these sweetener in moderation will not do much harm, till results of more studies proving the harms and benefits are available.  

Stevia, a natural sweetener derived from plants, was not included in the study. 

New treatment option for recurrent implantation failure on the horizon: Short term copper IUD

Placement of Cu-IUD during hysteroscopy for two cycles can up the pregnancy rates in patients with RIF says results of a study published in July issue of Journal Fertility and Sterility.

Recurrent Implantation Failure (RIF) is very frustrating for patients and physician both. Over the decades, few research study have emerged forward about the etiology and therapeutic options.
 Constitutive, as well as mature defects of endometrium have been put forward as one of the etiology.

Treatments have largely been costly and empirical, mainly consisting of hysteroscopy, controlling endometrial infections, evaluating and treating any structural defects of the uterine cavity, changing the endometrial milieu, alternative medicines, Low molecular weight heparin and controlled endometrial injury and immunomodulation. 

Controlled endometrial injury or endometrial scratch has long been used as a treatment option in recurrent pregnancy loss. The injury results in increased vascularity and bring about implantation. However, a systematic literature review failed in establishing definite therapeutic benefits. Diagnostic hysteroscopy also works along the same line but still lacks robust evidence in its favor.

In this retrospective study Mao et al. from Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China have evaluated an offbeat approach for the treatment of RIF. 

The team of researchers placed Cu-IUD for two cycles in women with RIF while they were undergoing hysteroscopy.

They postulated that even after removing the IUD after two cycles, the altered endometrial environment because of foreign body persists much like the ‘endometrial scratch.’

The study recruited 440 women, with a history of at least two failed embryo transfers with good quality embryos. At the time of diagnostic hysteroscopy, the patients were offered a choice of getting a IUD for two months.

Out of which, 382 patients opted for IUD, while 58 patients refused the treatment option. All 382 patients underwent a repeat diagnostic and, if needed, therapeutic hysteroscopy followed by frozen embryo transfer cycle.

The demographics of both the groups were similar. Women who opted for IUD had a significantly higher implantation rate (29.29% vs. 16.56%), chemical pregnancy rate (53.25 vs. 41.38%), and clinical pregnancy rate (45.13% vs. 26.44%) than the non-IUD group.

After multivariate regression analysis, chemical pregnancy rates were significantly more in IUD users. It was also interesting to note a higher number of IUD users suffered from some kind of uterine pathology like polyps, endometritis and polypoid proliferations but, they did not affect the clinical pregnancy rate.

The study has several limitations in the way of sample size, selection bias and retrospective nature along with confounding effect of second look hysteroscopy in IUD users. The IUD use also may have prevented further adhesions formation in that group.

The question about the type of endometrial injury, duration of foreign body in situ and type of changes in the endometrium that is beneficial in increasing endometrial receptivity remain unanswered.

But, this study does bring forward a novel treatment option that is worth investigating in future.

Primary Source: Novel approach to recurrent implantation failure: short-term copper intrauterine device placement
Goodman, Linnea R. et al.
Fertility and Sterilit , Volume 108 , Issue 1 , 42 - 43