Overweight women are at greater risk of miscarrying a genetically normal
baby in the early stages of pregnancy than women who maintain a healthy
weight, according to a new study by scientists at the Stanford University
School of Medicine in California, US. The researchers, presenting at the
annual American Society for Reproductive Medicine (ASRM) conference,
suggested that this indicates that a mother’s weight can affect the outcome
of an otherwise healthy pregnancy.
The UK’s National Health Service (NHS) estimates that around a quarter
of all pregnancies in the UK end in miscarriage. The majority of these occur
in the first 12 weeks of pregnancy, but can occur up to 24 weeks. The cause
of miscarriage is not always known, but it is thought that between 50 and 70
per cent occur as a result of chromosomal abnormalities (genetic defects) in
the fetus. The California researchers tested DNA from 204 fetuses miscarried
in the first eight weeks of pregnancy. They compared the rate of chromosomal
abnormalities in the fetuses from women with a normal body mass index (BMI)
with the rate of abnormalities in fetuses from women with a BMI that
classified them as overweight or obese. They found that 53 per cent of
babies lost by overweight women had no chromosomal abnormalities compared to
just 37 per cent of babies lost by women of a more healthy BMI.
Dr Inna Landres, who led the research team, said that these findings
indicate that ‘obesity predisposes women to miscarry normal babies.’ The
reason for this is not yet understood, but Dr Landres suggested that one
explanation could be altered levels of hormones such as oestrogen and
androgens seen in overweight women. She emphasised: ‘It’s important to
identify elevated BMI as a risk factor for miscarriage and counsel those
women who are affected on the importance of lifestyle modification.’
An individual’s BMI is calculated by dividing their weight in kilograms
by their height in metres squared. A BMI of 18 to 25 is considered normal,
whilst over 25 is classed as overweight and over 30 as obese. All the women
in the current study were attending an academic centre for fertility
counselling and had their BMI calculated before conception.
Dr Mark Hamilton, chairman of the British Fertility Society (BFS), said:
‘It is recognised that women who are overweight are at a greater risk of
miscarriage. It has not been defined if that risk is related to genetic
problems for the embryos or the obesity itself is linked to implantation
mechanisms. This study will aid our understanding of the known association
with being overweight and reproductive loss.’
Tag Archives: Implantation
Overweight women are at greater risk of miscarrying a genetically normal
Scientists at the University of Oxford, UK, believe they have identified the way in which embryos implant in the uterus, providing essential information which may be used in the future for infertility treatments and offering hope to thousands of infertile couples. Implantation of an embryo to the lining of the mother’s uterus is an essential process that takes place at an early stage of development. The embryo initially attaches and forms a contact with the uterus lining, which triggers a cascade of signals in both the embryo and the uterus. This allows cells from the embryo to start moving across into the uterus, finding blood vessels in the mother and eventually forming the placenta. Problems in the implantation process can lead to loss of potential pregnancies, even in couples trying to conceive without infertility problems. Current estimates suggest that infertility affects one in seven couples in the UK, with around 32,000 couples seeking infertility treatment each year. It is thought that a significant number of these patients could be infertile as a result of implantation problems.
The team of scientists, led by Professor Helen Mardon from the Nuffield Department of Obstetrics and Gynaecology at Oxford, along with Professor Anne J Ridley at King’s College, London, added embryos to a layer of cells from uterus lining in a culture dish to mimic events in the womb. They were then able to video embryos implanting themselves in the cell layer, allowing the scientists to dissect the molecular processes involved. Their findings were published in the journal Proceedings of the National Academy of Sciences.Their investigation led them identify two proteins that are essential players in the implantation process. They are from the Rho GTPase family of proteins, and ensure that cells in a particular part of the uterus lining move out of the way of the ‘invading’ embryonic cells. Professor Mardon said: ‘We have shown that two proteins, called Rac1 and RhoA, control the invasion. The first stimulates cells in the womb lining to move and allow the embryo to invade and implant properly while the second inhibits this. We believe this controlled balance of the two proteins is critical for successful implantation of the embryo. If the balance of RhoGTPases is altered, the cells of the womb lining don’t migrate and the embryo doesn’t implant’.
The findings bring new hope to people with infertility issues. The new information will help the understanding of how this process works, and therefore aid ‘the development of drugs to help embryos implant properly’, said Prof Mardon.
Research studies have documented the correlation between stress and infertility since the 1980s. The usefulness of such information has lagged because the focus has been on vague definitions of anxiety, rather than symptoms of depression. Recently, however, a refined look at depressive symptoms and their impact on biology has been enlightening, offering new hope and a mind/body approach that has proved to be a heartening success for some men and women.
Consider these findings:
0.Women with a history of depressive symptoms reported twice the rate of subsequent infertility (Psychosomatic Medicine, 1995, vol. 57)
0.Women with depression, when treated showed a 60 percent viable pregnancy rate within six months, contrasting with 24 percent when depression went untreated. (Journal of American Medical Womens Association, 1999, vol.54)
0.Women who experienced depression following the failure of their first in vitro fertilization (IVF), had much lower pregnancy rates that their non depressed counterparts during their second IVF cycle (Journal of Psychosomatic Research, 1993, vol. 37)
0.A mind/body program can be a helpful adjunct to IVF. A study in Fertility Sterility (1998, vol. 69) suggests that because mind/body programs are effective for reducing negative emotions that may impair IVF success, IVF patients should be offered this type of program.
The Mind/Body Connection Between Depression and Fertility Stress brought on by anxiety and/or depression can alter immune function. We have all heard about how the effects of depression can lower our immunity, making us more vulnerable to colds and other viruses during emotionally stressful periods. It is not such a stretch to discover that a suppressed immune system can adversely affect our ability to conceive.
Reproduction is one of our most delicately balanced biological systems. Psychological stress can affect our ability to get pregnant on multiple levels, including inhibition of the hypothalamus that helps regulate hormonal levels, or over activation of the hypothalamus which can change the pituitary and adrenal responses. Since the pituitary regulates both how much of a hormone is made and how much is released in the body, its alteration can have dramatic effects on the hormonal balance necessary for ovulation, fertilization, tubal functioning or even successful implantation of the egg once it reaches the womb.
Infertility causes depression, but what about prevention? The bad news is that even when women have not been depressed previously, depression often occurs by the second to third year of infertility and does not return to normal levels until six years later. The good news is that researchers have recently become proactive in studying the effects of treatment for non depressed women BEFORE they get depressed.
A study reported in Reproductive Endocrinology (April 2000, vol. 73, issue 4), treated women who were in their second year of infertility and not yet depressed. The women who received group psychological interventions to stem the tide of depression caused by infertility, had significantly increased viable pregnancies compared to those who did not receive preventative treatment for depression.
5 Ways to Increase Your Chances of Getting Pregnant
The following activities were part of the treatment program that the women in the prevention study received. Consider these five guidelines for a mind/body approach to help you conceive — whether or not you suffer from depression:
1. Practice Relaxation Techniques Yoga, meditation, and visualization increase the body’s resources for achieving balance. Consider a daily activity that calms the mind, but do not stop there. I have had success in my own psychotherapy practice using a body-centered hypnosis, which utilizes imagery, not only for childbirth, but for infertility, too. The hypnotic effects of visualization, coupled with relaxation can be a powerful technique for communicating with the emotional center of the brain (limbic system) that regulates hormonal activity and balance.
Visualize your womb in a state of fertile health and readiness. Make a relaxation tape, or have a professional assist you in creating an audiotape in which imagery and sound helps you experience the sensation of conception and pregnancy.
2. Allow Yourself Emotional Expression Releasing feelings is essential for deep relaxation. Do not use visualization as a form of “positive thinking” alone. Without releasing the “negative” feelings and fears you experience, you will be likely to repress your fears and disappointment, resulting in depression.
Acknowledge your anger, grief, disappointment and fear. Share your anxieties and feelings with others who may feel similarly. Cry when you are disappointed and verbalize anger when it arises, rather than hold it in. Releasing feelings will allow you to feel better later, allowing you to be hopeful instead of hopeless.
3. Take a Fresh Look Practice cognitive restructuring. Write your feelings in a personal journal, but with an eye towards releasing your disappointment and continuing towards your desired goal. For example: When writing you may find yourself saying, “I will never have a child”. When you are tempted to express your feelings as a negative projection of your destiny, remind yourself that you are deeply disappointed, even angry. Stop short of crystal-ball interpretations that lead to depression. Acknowledge the feelings, rather than project them onto a future event. Instead, bring yourself back to reality and write the truth of your actions, “I am doing everything I can to conceive.”
4. Get the Support You Need Your desire to become pregnant and your inability to “make it happen” may bring up emotions that surprise you. It is common for women to harbor feelings of inadequacy that effect their self esteem and performance at work as well as their marital relationships. Anticipate your needs. Do not let these feelings overwhelm you. Instead, use this opportunity to get the support you need from others, friends or professionals, to make this an opportunity for learning and growth.
Supportive group therapy was a part of the treatment in the study correlated with increased pregnancy. Sharing feelings can help you feel less alone and allow you to work through discouragement. These groups focused on the impact of infertility on self esteem, marriage, family, friends and work. Find ways to share your feelings rather than hold them inside.
5. Do Not Delay! Seeking treatment may not only help you conceive, but may prevent an even greater spiral of depression that can result from protracted infertility. Treating your depression now may help stem a vicious cycle.
Posted by : Goral Gandhi, MSc,
Rotunda – Center for Human Reproduction (Pvt) Ltd
According to a team of European researchers, it has long been known that smoking affects female fertility. However this is believed to be the first study to show that the habit actually damages the lining of the uterus, making it less receptive and reducing the chances that an embryo will implant itself in the wall of the womb.
The study looked at the impact of women who had received donated oocytes – the cells from which eggs develop. According to the researchers, this situation allows the most objective assessment of the role of the uterus in the outcome of IVF (in vitro fertilisation).
They looked at IVF treatments carried out at a clinic between early 2002 and June 2005 – 741 of these were in non-heavy smokers (less than 10 cigarettes a day) and 44 were in heavy smokers (over 10 a day). None of the women’s partners were smokers and none of the oocyte donors were heavy smokers.
The researchers found that ‘heavy smokers have a much lower chance of achieving pregnancy’. However in those who did become pregnant, the multiple pregnancy rate was higher.
“The fact that we see this result in a situation in which the oocytes were donated by other women demonstrates that cigarette smoking negatively affects the receptiveness of the uterus independently of its effect on ovarian function and this is a new finding”, explained lead researcher, Dr Sergio Soares.
He suggests that heavy smoking ‘disrupts the stability of cells in the lining of the uterus differently in some women or triggers a response in the embryo itself’.
“This could result in a reduced general pregnancy rate overall, but an increased chance of multiple pregnancy in those who do become pregnant”, he explained.
He added that while more research is needed in this area, patients who are heavy smokers should be told that even if fertilisation takes place, they have ‘less chance of achieving a successful pregnancy, whether they are trying to conceive naturally or through IVF’.
Posted by : Goral Gandhi, MSc,
Rotunda – Center for Human Reproduction (Pvt) Ltd
UK doctors are expected to receive permission to help a couple avoid passing on a hereditary condition that causes very high blood cholesterol to their children, according to the Times. The newspaper reports that a team lead by Paul Serhal, of University College London, will be granted a license by the Human Fertilisation and Embryology Authority (HFEA) this week. This will enable them to use preimplantation genetic diagnosis (PGD) to select embryos free from the gene mutation that causes both the mild and severe forms of familial hypercholesterolaemia (FH). One in 500 people in the UK has inherited the mild form of FH, although many of those with the condition are thought to remain undiagnosed. The condition can increase the risk of a heart attack in men under fifty by ten-fold. However, if treated through diet, exercise, lifestyle changes and – in some cases – with statin drugs, this risk can be drastically reduced. FH also increases the risk of strokes and blood vessel failure, which can lead to limb amputations. In contrast to the mild form of the condition, which affects people who inherit just one copy of the faulty gene, there is also a severe form of FH that affects children who inherit a ‘double dose’ of the mutation. This ‘homozygous’ form of the disease leads to very high levels of cholesterol from the age of around five, and can often cause death in childhood. Unlike the mild form, it does not always respond well to treatment with statins or other drugs.
The couple seeking treatment at UCL both have mild FH, which they discovered only after having a daughter with the homozygous, severe form of the disease. There is a 25 per cent risk that any subsequent child will also inherit the severe form of FH, who, unlike their first child, may not respond well to treatment. There is also a 50 per cent chance that they will pass on the mild form of the condition to their next and subsequent child, and a 25 per cent chance that each will be unaffected.
PGD involves taking a single cell from a 2-4 day old IVF embryo, performing a genetic or chromosome test on that cell, and then returning one or two unaffected embryos to the womb. In the UK, the use of PGD is regulated by the HFEA, which licenses the procedure on a case-by-case basis. The couple approached Mr Serhal after learning that his clinic offered PGD for hereditary breast cancer. If the procedure is successful, then the couple will be able to select one or more unaffected embryos to implant. However, if there are no unaffected embryos, then the couple will have to decide whether or not to select embryos that have the milder form of FH. Mr Serhal told the Times: ‘This obnoxious disease can cause cardiovascular accidents at a very young age. Ideally, we will find embryos with no FH genes, but it is possible we will not and it will be up to the patients to choose. Some people would think twice about using embryos that they know have a risky gene, and others would say you shouldn’t screen out a condition that can be managed so people can live with it. It will be an awkward choice’.
Mitochondria are tiny structures that provide cells with energy. Every cell in the body has between 1000 and 10,000 mitochondria. Whilst the vast majority of a cell’s DNA is contained inside its nucleus, a handful of genes are found in the mitochondria – just 37 genes out of around 25,000 genes in total. Mutations in mitochondrial genes cause a range of disorders that affect one person in every 6,500 and include fatal liver failure, stroke-like episodes, blindness, deafness, diabetes and forms of epilepsy and muscular dystrophy. Sperm do not contribute any mitochondria to the embryo (as they are all present within the tail, which falls off after fertilisation) and, consequently, children inherit all their mitochondrial genes from their mother.
The Newcastle researchers are working on a technique that takes the DNA from the nucleus of a newly-fertilised egg, and transplants it into an egg from another woman which has had all of its nuclear DNA removed. The resulting embryo would have mitochondria from one woman, but its remaining 25,000 or so genes would come from the mother and father who provided the fertilised egg. In this way, a mother could have a child without passing on her faulty mitochondrial genes.
The work is as yet unpublished, but at a recent scientific meeting of the researchers reported successful transplants in ten embryos, which were then grown in the laboratory for five days before they were destroyed. However, all these experiments were done by exchanging DNA between two ‘failed’ embryos left-over from IVF, which have abnormal amounts of nuclear DNA and so are inappropriate for implantation. It is not yet known if the technique will work with healthy embryos and eggs, although experiments in mice have been successful. Team leader Professor Patrick Chinnery said: ‘there are still a number of scientific issues we’ve got to resolve, in terms of efficiency, and in terms of whether we can do this in eggs rather than in other embryos’.