Friday, November 27, 2015

Parasitic worm 'increases women's fertility'

Parasitic worm 'increases women's fertility'

Ascaris lumbricoides credit: (Eye of Science/Science Photo Library)

Prof Aaron Blackwell, one of the researchers , from the University of California Santa Barbara, told the BBC News website : A study of 986 indigenous women in Bolivia indicated a lifetime of Ascaris lumbricoides, a type of roundworm, infection led to an extra two children.

He said women's immune systems naturally changed during pregnancy so they did not reject the foetus.

Prof Blackwell said: "We think the effects we see are probably due to these infections altering women's immune systems, such that they become more or less friendly towards a pregnancy."

He said that "The effects are unexpectedly large."

He said using worms as a fertility treatment was an "intriguing possibility" but warned there was far more work to be done "before we would recommend anyone try this".

Contrary to that Hookworms infestation is known to reduce fertility. They increased the age at which Tsimane women first gave birth and stretched the amount of time between pregnancies. As a result, the team calculated, a woman with hookworms would bear three fewer children in her lifetime than would a woman lacking the parasites.

He also added: "Whilst I wouldn't want to suggest that women try and become infected with roundworms as a way of increasing their fertility, further studies of the immunology of women who do have the parasite could ultimately lead to new and novel fertility enhancing drugs."

  • Science, DOI: 10.1126/science.aac7902 

Monday, November 23, 2015

The New Puberty

The New Puberty

The Book" The new puberty"

This article is based on TEDMED talk 2015 in Palm Springs, California by Pediatric endocrinologist Louise Greenspan and her groundbreaking book, -“The New Puberty: How To Navigate Early Development in Today’s Girls”, along with coauthor Julianna Deardorff, a Berkeley professor of Maternal and Child Health and adolescent psychologist.

Just a generation ago, fewer than 5 percent of girls started puberty before the age of 8, today girls are entering puberty at increasingly younger ages with 10% of girls now showing the first signs of puberty before age 8.

Early puberty can lead to eating disorders, depression, substance abuse, early sexual activity and, later in life, breast cancer.

According to Dr. Greenspan, two important culprits responsible are obesity and family stress.

"We used to say that breast development and pubic hair should not start before age 8. What we know now is that 15% of girls at age 7 are showing breast development," Dr Greenspan reported.

According to Biro.F.M  et al in Pediatrics 2013;132:1019-1027 Girls from racial and ethnic groups with the highest rates of obesity are most at risk for early puberty. In that study, black girls showed breast budding at an average age of 8.75 years, Hispanic girls at an average age of 9.25 years, and white and Asian girls at an average age of 9.75 years.

Higher BMI was the strongest predictor of earlier age at breast stage 2 in this study

The relationship between higher BMI and earlier onset of puberty in girls has been noted previously; in 2 large cross-sectional studies, Pediatric Research in Office Settings (PROS) and the National Health and Nutrition Examination Survey (NHANES) III, earlier maturation occurred in those girls with greater BMI and in those with BMI ≥85th percentile.

Body fat makes estrogens, which are the same kind of hormone that are normally released from the ovaries during puberty. When there is more body fat, there are higher levels of estrogen, which leads to breast budding.

In USA the rate of obesity in children aged 6 to 11 years of age increased from 7% in 1980 to nearly 18% in 2012, according to a report from the Centers for Disease Control and Prevention.

And during the same period, the rate of adolescents 12 to 19 years of age who were obese increased from 5% to nearly 21%.

The trend is not just seen in the U.S., it's seen in multiple countries, probably more so countries closer to the equator than countries in the northern latitudes. But major factor is likely to be, certainly in the developing countries, a switch from a more traditional diet to a more Western diet, which results in greater, perhaps better nutrition or perhaps over-nutrition, and that's certainly a factor.

Stress is the second important factor in causing early puberty; other risk factors are early sexual abuse and toxic levels of family arguments and neighborhood violence.

Dr Greenspan says that “Most notably, a girl who grows up without her biological father is twice as likely to get her period before age 12 as a girl who lives with her biological father.”

She does not refute the endocrine-disrupting chemicals commonly found in plastics and pesticides for early puberty, but it is almost impossible to eliminate endocrine-disrupting chemicals from our environment, and there is no single smoking gun, she explained.

These chemicals can mimic hormones in the body, and some mimic hormones that are important regulators of puberty, particularly estrogen. However, more research is needed on humans.

She noted that "a much more effective public health intervention would be to try to tame the obesity epidemic and put some greater social infrastructure in place to buffer children from the stresses of poverty."

The authors offer highly practical strategies that can help prevent and manage early puberty including limiting exposure to certain ingredients in personal care and household products, which foods to eat and which to avoid, and ways to improve a child’s sleep routine to promote healthy biology.

Moreover, the authors—both mothers of young girls—offer parents, teachers, coaches, and caretakers guidance to initiate and continue the conversation about puberty in an age-appropriate way to support girls as they navigate this complex stage of their lives.


Thursday, November 19, 2015

Uterine Transplant-------Is this the final frontier!

Cleveland Clinic announced Thursday the launch of a “groundbreaking” research study that will perform uterus transplants in 10 women. The first operation is expected to take place within the next few months, the New York Times reports.

Since the 1970s a number of teams around the world have been researching the possibility of developing a womb transplant procedure.

Transplant research, as a whole, has also tended to focus on life-saving transplantation (heart, kidney, liver) with womb transplant research being rather limited especially following advances in IVF techniques.

We have come a long way since 1905 which saw the first successful corneal transplant.

In 2000 the world’s first womb transplant was performed on a 26 year old woman in Saudi Arabia. But, the transplanted womb only lasted for 99 days.

In December 2010, our colleagues in Sweden were able to report a pregnancy as a result of a womb transplant on a rat.

In September 2014, Mats Brännström and colleagues report the first successful birth of a child following uterus transplantation. The recipient, a 35-year-old woman lacking a uterus (Rokitansky syndrome), received a cryopreserved embryo 1 year after transplantation, leading to a livebirth by caesarean section.
The first uterine transplant baby being delivered by Cesarean Section .    

The donated uterus came from the woman’s own mother, so the baby is also the first born to a woman using the same womb from which she emerged herself.

This team has since performed a total of nine uterus transplants that have resulted in five pregnancies and four live births.

This report marks an important development that will give women with congenital or surgical absence of the uterus an opportunity to give birth to a child.

The first clinical trial of uterus transplantation in the United States has begun at Cleveland Clinic in Ohio, where the process of selecting women to participate in the study is now under way.

The ground-breaking study will include 10 women with uterine factor infertility (UFI), a condition in which a woman was born without a uterus, has lost her uterus, or has a uterus that no longer functions.

It's thought that as many as 50,000 U.S. women might be potential candidates for the procedure.

Complex Protocol of the study 
After being approved for the trial, the woman follows a complicated protocol:
  • Clinicians begin the in vitro fertilization process by stimulating the woman's ovaries to produce multiple eggs.
  •  After retrieval of the woman's eggs, they are fertilized with sperm in a laboratory and frozen.
  •  After 10 embryos have been frozen, Lifebanc, an organ procurement agency, starts searching for a donor.
  •  When a uterus donor has been found, that person's next-of-kin signs an informed consent for the organ donation.
  • The donor uterus is transplanted into the patient's pelvis within 6 to 8 hours after harve
  • The transplanted uterus is allowed to fully heal over 12 months.
  •  After 1 year, the woman's frozen embryos are thawed and implanted, one at a time, into the woman until she becomes pregnant.
  • The woman takes Immunosuppressant drugs during her pregnancy.( tacrolimus, azathioprine, and corticosteroids).
  • A high-risk obstetrics team monitors the woman throughout pregnancy and childbirth.
  • The woman undergoes a cervical biopsy each month to monitor for organ rejection
  • An obstetrician delivers the baby by cesarean section.
  • After the woman has one to two babies, she undergoes a hysterectomy and stops taking Immunosuppressant drugs to reduce her long-term exposure to the medications.

Uterine Transplants are Unique in the sense that unlike any other transplants, they are ‘ephemeral,'” Cleveland Clinic lead researcher Andreas Tzakis said in the release. “They are not intended to last for the duration of the recipient’s life.” 

After 1-2 healthy pregnancies the transplanted uterus is either removed or allowed to disintegrate.

Vincent, One year now

Now, Vincent the first Baby born after uterus transplant is healthy one year old and the team of Dr.  Mats Brännström, the Swedish professor in obstetrics and gynecology of the University of Gothenburg and Sahlgrenska University Hospital, are looking forward to improve the technique and reduce the surgical procedure time.


All Photos courtesy by Martin Valigursky/iStock/Getty Images

Friday, November 13, 2015

Gestational Diabetes Mellitus Revisited

Gestational Diabetes Mellitus Revisited 

Today is world diabetes day. The International Diabetes Federation has released new data in support of its campaign against Diabetes quoting that “1 in 7 births is affected by gestational diabetes” and “One quarter of all births are affected by high blood glucose during pregnancy in South-East Asia.”

 This article is based on The International Federation of Gynecology and Obstetrics (FIGO) Initiative on gestational diabetes mellitus: A pragmatic guide for diagnosis, management, and care.

  • The International Diabetes Federation (IDF) estimates that one in six live births (16.8%) are to women with some form of hyperglycemia in pregnancy.
  • While 16% of these cases may be due to diabetes in pregnancy (either preexisting diabetes—type 1 or type 2—which antedates pregnancy or is first identified during testing in the index pregnancy), the majority (84%) is due to gestational diabetes mellitus (GDM).
  • The definition of GDM is still evolving.
  • Hyperglycemia first detected at any time during pregnancy should be classified either as diabetes mellitus in pregnancy (DIP) or GDM.
  • When the level of hyperglycemia first detected by testing at any time during the course of pregnancy meets the criteria for diagnosis of diabetes in the nonpregnant state, the condition is called DIP. Those criteria are:
      1) Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL); and/or
      2) 2-hour plasma glucose ≥11.1 mmol/L (200 mg/dL) following a 75-g oral glucose load; or
      3)Random plasma glucose ≥11.1 mmol/L (200 mg/dL) in the presence of diabetes   symptoms.

  • DIP may either have been pre-existing diabetes (type 1 or type 2) antedating pregnancy, or diabetes first diagnosed during pregnanc.
  • When hyperglycemia detected during routine testing in pregnancy (generally between 24 and 28 weeks) does not meet the criteria of DIP it is called GDM.

            To address the global burden of GDM, FIGO recommendations:

  • Universal testing-- All pregnant women should be tested for hyperglycemia during pregnancy using a one-step procedure and FIGO encourages all countries and its member associations to adapt and promote strategies to ensure this.
  • As per the recommendation of the IADPSG (2010) and WHO (2013), the diagnosis of GDM is made using a single-step 75-g OGTT when one or more of the following results are recorded during routine testing specifically between weeks 24 and 28 of pregnancy or at any other time during the course of pregnancy:
     1)Fasting plasma glucose 5.1−6.9 mmol/L (92−125 mg/dL);
     2)1-hour post 75-g oral glucose load ≥10 mmol/L (180 mg/dL);
     3)2-hour post 75-g oral glucose load 8.5–11.0 mmol/L(153−199 mg/dL)

  • Asian Indians are considered to be at the highest risk of gestational diabetes. Based on studies from India and keeping in mind the already high burden and rising prevalence of diabetes and the realities of resource constraints within the health system in India, as well as the high rate of deliveries (27 million each year), the Diabetes in Pregnancy Study Group in India (DIPSI) developed the following guideline for diagnosis of GDM in the community. This guideline has been endorsed by the Ministry of Health, Government of India, the Federation of Obstetrics and Gynecological Societies of India (FOGSI), and the Association of Physicians of India (API)
  • For Asian Indians Testing for GDM is recommended twice during prenatal care. The first testing should be done during first prenatal contact as early as possible in pregnancy. The second testing should be done ideally during 24−28 weeks of pregnancy if the first test is negative. If women present beyond 28 weeks of pregnancy, only one test is to be done at the first point of contact.
  • The management of GDM should be in accordance with available national resources and infrastructure even if the specific diagnostic and treatment protocols are not supported by high-quality evidence, as this is preferable to no care at all.
  • Life style modification is the corner stone in management of DIP and GDM.
  • Nutritional therapy includes an individualized food plan to optimize glycemic control. Medical nutritional therapy in pregnancy can be described as “a carbohydrate-controlled meal plan that promotes adequate nutrition with appropriate weight gain, normoglycemia, and the absence of ketosis.
  • Daily energy intake of approximately 2050 calories (minimum of 175 g carbohydrates/day) in all BMI categories in women with GDM was reported to reduce weight gain, maintain euglycemia, avoid ketonuria, and achieve average birth weights of 3542 g.
  • Oral antidiabetic agents  Insulin, glyburide, and metformin are safe and effective therapies for GDM  during the second and third trimesters, and may be initiated as first-line treatment after failing to achieve glucose control with lifestyle modification. Among OADs, metformin may be a better choice than glyburide.
  • Insulin should be considered as the first-line treatment in women with GDM who  are at high risk of failing on OAD therapy, including some of the following factors
       • Diagnosis of diabetes <20 weeks of gestation
             • Need for pharmacologic therapy >30 weeks
       • Fasting plasma glucose levels >110 mg/dL
       • 1-hour postprandial glucose >140 mg/dL
       • Pregnancy weight gain >12 kg

  • The postpartum period is crucial, not only in terms of addressing the immediate perinatal problems, but also in the long term for establishing the basis for early preventive health for both mother and child, who are at a heightened risk for future obesity, metabolic syndrome, diabetes, hypertension, and cardiovascular disorders.
  • Progression to diabetes is more common in women with a history of GDM compared with those without a GDM history. 
  • Both “intensive lifestyle” and metformin have been shown to be highly effective in delaying or preventing diabetes in women with IGT and a history of GDM.
  • The current EBCOG proposal is to screen women with a history of GDM at 6−12 weeks postpartum using the 2-hour 75-g OGTT with nonpregnancy diagnostic criteria. Women with a history of GDM should have lifelong screening for the development of diabetes or prediabetes at least every 3 years.


Thursday, November 12, 2015

A New Paradigm for Prevention of Ovarian Cancer

A New Paradigm for Prevention of Ovarian Cancer

This article is based on a paper by Nezhat R et al in September, 2015  issue of American Journal of Obstetrics and Gynecology.

  • It is estimated by American Cancer society that 21,290 new cases of ovarian cancer will be diagnosed in 2015, and 14,180 deaths from ovarian cancer will occur during that period.

  • The incidence of ovarian cancer varies geographically. The incidence is high in the Western world. The age-standardized rate (per 100,000 females) is only 3.8 in China, relatively lower than developed countries such the USA (8.8) and Australia (7.7).

  • A woman has a 1:70 lifetime risk of being diagnosed with ovarian cancer, the second most common gynecologic malignancy, with the highest mortality rate.

  • The majority of ovarian malignancies are epithelial in origin, and within this group the serous type is the most frequent.

  • There is currently no effective screening method available for the detection of this disease, which has an overall five-year survival rate of approximately 45%.

  • Apart from the genetics and modifiable risk factors responsible for causation of cancer, a new theory by Nezhat et al holds that serous ovarian cancer begins in the Fallopian tube from where it spreads onto the ovarian surface.

  • Nezhat and colleagues classify ovarian cancers on the basis of etiology into two groups. Type I cancers originate from various ovarian pathologies (borderline ovarian tumors, endometriomas). These cancers typically have a more favorable prognosis because they are diagnosed at an earlier stage and metastasize more slowly.

  • The more frequent type II tumors originate from the fimbriated end of the Fallopian tube and have a less favorable prognosis because they are often diagnosed at an advanced stage.

  • Two large collaborative studies have recently called attention to the role of tubal ligation on reducing the ovarian cancer risk.

  • The reduction is the greatest for endometrioid and clear-cell carcinoma, and is thought to be associated with the prevention of retrograde menstruation, ovarian seeding by endometrial cells, and inflammation.

  • The Society of Gynecologic Oncology also recommends that for women at average risk of ovarian cancer, risk-reducing salpingectomy should also be discussed and considered in patients at the time of abdominal or pelvic surgery, after completion of child-bearing.

  • The interventions called for salpingectomy at the time of hysterectomy, salpingectomy for permanent sterilization instead of tubal ligation, and referral for all patients with high-grade serous cancer for hereditary cancer counseling and genetic testing for BRCA1 and BRCA2 mutations.

  • Although still in its infancy, these 3 recommendations are projected to reduce ovarian cancer rates in this province by 40% over the next 20 years.

  • These clinical observations and the new recent evidence for the dual pathogenesis of ovarian cancer have set ground for implementing new strategies for screening and prevention programs to reduce the incidence of epithelial ovarian cancer.

  • In light of the accumulated data and observations regarding endometriosis and ovarian cancer, Nezhat R. et al propose that it is time to establish criteria for identifying and monitoring women with endometriosis for risk factors and to pursue risk-reducing medical and surgical treatment options in these women.

  • At the time of surgical diagnosis and treatment, consideration for complete resection of pelvic endometriosis, salpingectomy, oophorectomy, or hysterectomy should be individualized based on a patient’s age, desire for future fertility, and preoperative consultation with the patient.

  • These initiatives, if validated by level 1 evidence, should substantially reduce the risk of ovarian cancer as well as the total mortality risk.

  • For now, however, it seems that we may have tools in the future to combat a disease with a high mortality rate.



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