Friday, January 16, 2009
Thursday, January 15, 2009
Genetic screening fails women trying for IVF birth
Genetic screening, often seen as the best hope for older women undergoing IVF treatment to have a child, is ineffective and actually reduces rates of pregnancies, scientists said on Wednesday.
The surprise finding from a controlled clinical trial involving 408 women is a major setback for a technology that is used increasingly in fertility clinics worldwide.
Couples aiming for a test-tube baby can pay between $3,000 (INR 150,000) and $5,000 (INR 250,000) for a preimplantation genetic screening test. The idea is to study the genetic make-up of embryos before transfer to the womb to make sure they are healthy and likely to survive.
But while the concept is very plausible, Dutch researchers found screening in women aged 35 to 41 years actually made matters worse.
After 12 weeks, only 25 percent of women undergoing in vitro fertilisation (IVF) whose embryos had been screened were pregnant, against 37 percent in the control group. Eventual live birth rates were also lower, at 24 versus 35 percent.
Just why screening cuts the chance of a viable pregnancy is unclear but Sebastiaan Mastenbroek from the Academic Medical Centre of the University of Amsterdam said the test itself might be to blame.
"It is possible that the biopsy of a cell from an early embryo on day three after conception hampers the potential of an embryo to successfully implant, though the effect of biopsy alone on pregnancy rates has not been studied," he said in a statement.
Usually, embryos will have reached the eight-cell stage of development by day three but sometimes there may be as few as four cells, which could in theory make the procedure riskier.
Other factors may be the limited number of chromosomes that can be analysed, which may lead to the transfer of embryos that appear normal but in fact contain faults, and the fact many embryos are "mosaic", where a single cell does not properly reflect the genetic make-up of the whole.
Mastenbroek and colleagues presented their work at the annual meeting of the European Society of Human Reproduction and Embryology (ESHRE) in Lyon, France.
The research was also published online by the New England Journal of Medicine, alongside a recommendation from the team that preimplantation should no longer be performed routinely in older women undergoing IVF therapy.
Fertility experts said the findings were a wake-up call for clinicians and showed the need for more research into the benefits, if any, of preimplantation genetic diagnosis (PGD).
Peter Braude, professor of obstetrics and gynaecology at Kings College London, said the work showed screening did not work in older mothers-to-be and similar studies were needed on whether it helped younger women with repeated IVF failure.
"Vulnerable patients should no longer be exploited financially under the impression that it works," he said.
Joep Geraedts, ESHRE’s chairman elect and a genetics expert at the Dutch-Belgian University Limburg, told Reuters in a telephone interview the new study would come as a shock, particularly in the United States, where PGD is widely used.
"No other medical procedure with such profound medical and ethical consequences has been so poorly studied," Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University, Baltimore, said.
The Aisle Seat
Two Pakistanis boarded a flight out of New Delhi.
One took a window seat and the other sat next to him in the middle
seat... Just before takeoff, a Sikh, an Indian Army NCO sat down
in the aisle seat.
After takeoff, the soldier kicked his milirary shoes off, wiggled his toes and
was settling in when the Pakistani in the window seat said, 'I need to get up
and get a coke.'
Don't get up,' said the Sardar, 'I'm in the aisle seat, 'I'll get it for you.'
As soon as he left, he picked up the Sardar's left shoe and spat in it.
When the Sardar returned with the coke, the other Paki said, 'That looks
good, I'd really like one, too.'
Again, the Sardar obligingly went to fetch it. While he was gone, the
other Paki picked up the Sardar's right shoe and spat in it.
When the Sardar returned, they all sat back and enjoyed the flight, the
Pakis finishing their cokes. As the plane was landing, the Sardar slipped
his feet into his shoes and knew immediately what had happened.
He leaned over and asked his Pakistani neighbors ...
''Why does it have to be this way?''
''How long must this go on . . . ?"
''This fighting between our nations . . . ?''
''This hatred . . . ?''
''This animosity . . . ?''
''This spitting in shoes...
Scroll down for the punch line!
and pissing in cokes . . . ?''
One took a window seat and the other sat next to him in the middle
seat... Just before takeoff, a Sikh, an Indian Army NCO sat down
in the aisle seat.
After takeoff, the soldier kicked his milirary shoes off, wiggled his toes and
was settling in when the Pakistani in the window seat said, 'I need to get up
and get a coke.'
Don't get up,' said the Sardar, 'I'm in the aisle seat, 'I'll get it for you.'
As soon as he left, he picked up the Sardar's left shoe and spat in it.
When the Sardar returned with the coke, the other Paki said, 'That looks
good, I'd really like one, too.'
Again, the Sardar obligingly went to fetch it. While he was gone, the
other Paki picked up the Sardar's right shoe and spat in it.
When the Sardar returned, they all sat back and enjoyed the flight, the
Pakis finishing their cokes. As the plane was landing, the Sardar slipped
his feet into his shoes and knew immediately what had happened.
He leaned over and asked his Pakistani neighbors ...
''Why does it have to be this way?''
''How long must this go on . . . ?"
''This fighting between our nations . . . ?''
''This hatred . . . ?''
''This animosity . . . ?''
''This spitting in shoes...
Scroll down for the punch line!
and pissing in cokes . . . ?''
Wednesday, January 14, 2009
New IVF Progesterone Delivery System Study
A leading Southern California Fertility center esteemed for their excellent IVF success rates and national reputation was recently selected as a participant in a national, multi-center study exploring new progesterone delivery systems to replace intramuscular injections. Patients going through in vitro fertilization (IVF) often describe the progesterone injections as the most difficult and painful part of the IVF cycle. For more than 30 years doctors have been seeking effective alternatives to these painful injections.
The study compares an FDA-approved vaginal progesterone, Endometrin, with a new formulation which is administered subcutaneously, similar to the relatively painless fertility drug injections. Patients will be randomized to receive either the vaginal or subcutaneous progesterone until the pregnancy test and then until about 10 weeks of pregnancy. In case of unacceptable side effects the patient will be offered an alternative medication. Side effects are usually local reactions and mild.
Benefits to patients include free progesterone medications as well as a $1,500 (INR 72,000) honorarium for participating and completing the study questionnaires.
Participating patients will be IVF candidates, including those undergoing ICSI, Blastocyst and PGD, who are age 18-42 who have had less than three prior IVF cycles and an FSH less than 15IU/L and estradiol less than 80 pg/mL. Other exclusion criteria exist.
The study compares an FDA-approved vaginal progesterone, Endometrin, with a new formulation which is administered subcutaneously, similar to the relatively painless fertility drug injections. Patients will be randomized to receive either the vaginal or subcutaneous progesterone until the pregnancy test and then until about 10 weeks of pregnancy. In case of unacceptable side effects the patient will be offered an alternative medication. Side effects are usually local reactions and mild.
Benefits to patients include free progesterone medications as well as a $1,500 (INR 72,000) honorarium for participating and completing the study questionnaires.
Participating patients will be IVF candidates, including those undergoing ICSI, Blastocyst and PGD, who are age 18-42 who have had less than three prior IVF cycles and an FSH less than 15IU/L and estradiol less than 80 pg/mL. Other exclusion criteria exist.
Folate receptor blockade may compromise fertility
Treatment of impaired folate metabolism caused by an autoimmune response might improve the chances of conception among certain women with fertility problems, research suggests.
Michelle Murphy (Universitat Rovira i Virgili, Reus, Spain) and colleagues report women who tested positive for folate receptor (FR)-blocking autoantibodies were 12 times more likely to have fertility problems than those testing negative.
Observing that folate cell delivery is important in reproductive processes, the team tested for the presence of FR-blocking autoantibodies in repeated blood samples collected 10–12 weeks apart from 17 women who had failed to conceive during 12 menstrual cycles and 25 controls who had experienced a normal conception and pregnancy outcome.
Overall, five (29 percent) women with subfertility had at least one positive FR-blocking autoantibody titer, compared with just one (4 percent) women in the control group. Statistical analysis confirmed that testing positive for FR-blocking autoantibodies was a significant risk factor for subfertility (odds ratio = 12).
“Further investigation is required to understand the nature of the association between FR autoimmunity and subfertility and the potential benefits of using immune suppressants, corticosteroids, and high-dose folic acid in this disorder,” the researchers propose.
Source: Fertility and Sterility 2008; Advance online publication
Michelle Murphy (Universitat Rovira i Virgili, Reus, Spain) and colleagues report women who tested positive for folate receptor (FR)-blocking autoantibodies were 12 times more likely to have fertility problems than those testing negative.
Observing that folate cell delivery is important in reproductive processes, the team tested for the presence of FR-blocking autoantibodies in repeated blood samples collected 10–12 weeks apart from 17 women who had failed to conceive during 12 menstrual cycles and 25 controls who had experienced a normal conception and pregnancy outcome.
Overall, five (29 percent) women with subfertility had at least one positive FR-blocking autoantibody titer, compared with just one (4 percent) women in the control group. Statistical analysis confirmed that testing positive for FR-blocking autoantibodies was a significant risk factor for subfertility (odds ratio = 12).
“Further investigation is required to understand the nature of the association between FR autoimmunity and subfertility and the potential benefits of using immune suppressants, corticosteroids, and high-dose folic acid in this disorder,” the researchers propose.
Source: Fertility and Sterility 2008; Advance online publication
Tuesday, January 13, 2009
Study fails to find link between fertility treatment and breast cancer
Fertility treatment does not increase a woman's risk of developing breast cancer, according to a study of more than 25,000 women with fertility problems in the Netherlands.
The study will help to reassure patients concerned that the powerful doses of hormones that are part of fertility treatment might put them at risk of developing cancer in the future.
At the beginning of an IVF treatment cycle, women are given a course of hormone drugs to stimulate their ovaries to produce more eggs than usual so that clinicians can produce several fertilised embryos in vitro.
The treatment causes large spikes in oestrogen levels in the body. In theory this could promote the development of breast cancer, which is sensitive to the hormone.
The Dutch study, carried out by Dr Alexandra van den Belt-Dousebout at the Netherlands Cancer Institute in Amsterdam, examined patient records from all 12 IVF clinics in the country between 1980 and 1995.
Her team compared 18,970 women who had had at least one cycle of IVF treatment and 7,536 other women with fertility problems who had not received fertility treatment. They matched these patients to records in the National Cancer Registry to establish whether they had gone on to develop breast cancer.
Of the 378 women who developed breast cancer, 266 were in the IVF group and 112 were in the non-IVF group. After adjusting for known risk factors such as age, the number of children the women already had, the age they began menstruating, family history of breast cancer and body mass index, the team found no statistical difference between the two groups, suggesting that IVF treatment does not increase a woman's chances of developing breast cancer.
Van den Belt-Dousebout presented her results at the American Society for Reproductive Medicine in San Francisco.
"From 10 years after treatment breast cancer risk was moderately increased in the IVF group but also in the non-IVF group, compared to the general population," van den Belt-Dousebout and her colleagues wrote in their presentation, "This may be explained by a lower number of children compared to the general population."
Having children is known to reduce the risk of breast cancer in women.
The study will help to reassure patients concerned that the powerful doses of hormones that are part of fertility treatment might put them at risk of developing cancer in the future.
At the beginning of an IVF treatment cycle, women are given a course of hormone drugs to stimulate their ovaries to produce more eggs than usual so that clinicians can produce several fertilised embryos in vitro.
The treatment causes large spikes in oestrogen levels in the body. In theory this could promote the development of breast cancer, which is sensitive to the hormone.
The Dutch study, carried out by Dr Alexandra van den Belt-Dousebout at the Netherlands Cancer Institute in Amsterdam, examined patient records from all 12 IVF clinics in the country between 1980 and 1995.
Her team compared 18,970 women who had had at least one cycle of IVF treatment and 7,536 other women with fertility problems who had not received fertility treatment. They matched these patients to records in the National Cancer Registry to establish whether they had gone on to develop breast cancer.
Of the 378 women who developed breast cancer, 266 were in the IVF group and 112 were in the non-IVF group. After adjusting for known risk factors such as age, the number of children the women already had, the age they began menstruating, family history of breast cancer and body mass index, the team found no statistical difference between the two groups, suggesting that IVF treatment does not increase a woman's chances of developing breast cancer.
Van den Belt-Dousebout presented her results at the American Society for Reproductive Medicine in San Francisco.
"From 10 years after treatment breast cancer risk was moderately increased in the IVF group but also in the non-IVF group, compared to the general population," van den Belt-Dousebout and her colleagues wrote in their presentation, "This may be explained by a lower number of children compared to the general population."
Having children is known to reduce the risk of breast cancer in women.
Monday, January 12, 2009
Oocyte electroactivation after ICSI
Electrical activation of oocytes after ICSI can significantly improve the fertilization rate in selected patients, according to the results of a randomized controlled study.
Specialists from the Egyptian IVF-ET Center in Cairo, Egypt, conducted the study to estimate the effect of electrical activation of oocytes in patients with previously failed or limited fertilization after ICSI, and in patients likely to have failed fertilization due to teratozoospermia.
Previous research has suggested that fertilization failure occurs in an estimated 2-3 percent of ICSI cycles and is often due to the failure of oocyte activation. Past studies have provided some evidence to suggest that electrical activation (or electroactivation) of oocytes can improve success rates.
The researchers studied the effect of electrical activation in 241 ICSI cycles involving couples with severe oligoasthenospermia or azoospermia. Poor or failed fertilization was expected in these cycles because of 100 percent abnormal sperm morphology or totally immotile sperm. In all cases the female partner was under 40 years of age and had a normal hormonal profile and no pelvic pathology.
The oocytes from each patient were randomly assigned on a one-to-one basis to either electroactivation (n = 1,640) or no electroactivation (n = 1,435). Electroactivation was performed 30 minutes after ICSI, using a double-square direct current pulse, and embryo transfer was performed with the best available embryos.
The researchers (Mansour R et al) present their findings in a new paper due to be published in the journal Fertility and Sterility. They report that:
The fertilization rate was significantly higher in the electroactivation group, compared with the control group: 68 percent versus 60 percent respectively (odds ratio 1.40; 95 percent confidence interval 1.20-1.63).
There was no significant difference between the two groups in the oocyte degeneration rate (5.9 percent in the electroactivation group and 4.9 percent in the control group).
There were a total of 112 clinical pregnancies in the study. In 15 of these, the embryos transferred were derived solely from the electroactivated group (out of a total of 34 embryo transfer procedures involving such embryos – a clinical pregnancy rate of 44 percent). In 69 of the clinical pregnancies the embryos transferred were derived solely from the control group (out of a total of 69 embryo transfer procedures involving such embryos – a clinical pregnancy rate of 48 percent). In the remaining 64, the embryos transferred were derived from both groups (out of a total of 138 embryo transfer procedures – a clinical pregnancy rate of 46.4 percent).
The miscarriage rates were: 20 percent (3 out of 15 clinical pregnancies) when the embryos transferred were derived solely from the electroactivated group, 9 per cent (3 out of 33 clinical pregnancies) when the embryos transferred were derived solely from the control group, and 9.4 percent (6 out of 64 clinical pregnancies) when the embryos transferred were derived from both groups.
Total fertilization failure did not occur in the study group, but occurred in five cycles in the control group.
Concluding, the researchers write that electroactivation of oocytes after ICSI can significantly improve the chances of fertilization, but stress: “However, more studies are needed to evaluate the clinical significance and safety of this technique.
“It is recommended in cases of previous failure of fertilization or limited fertilization, as well as in cases of severe oligoasthenospermia or azoospermia with 100 percent abnormal forms or zero motility.”
Source: Fertility and Sterility 2008;in press
Specialists from the Egyptian IVF-ET Center in Cairo, Egypt, conducted the study to estimate the effect of electrical activation of oocytes in patients with previously failed or limited fertilization after ICSI, and in patients likely to have failed fertilization due to teratozoospermia.
Previous research has suggested that fertilization failure occurs in an estimated 2-3 percent of ICSI cycles and is often due to the failure of oocyte activation. Past studies have provided some evidence to suggest that electrical activation (or electroactivation) of oocytes can improve success rates.
The researchers studied the effect of electrical activation in 241 ICSI cycles involving couples with severe oligoasthenospermia or azoospermia. Poor or failed fertilization was expected in these cycles because of 100 percent abnormal sperm morphology or totally immotile sperm. In all cases the female partner was under 40 years of age and had a normal hormonal profile and no pelvic pathology.
The oocytes from each patient were randomly assigned on a one-to-one basis to either electroactivation (n = 1,640) or no electroactivation (n = 1,435). Electroactivation was performed 30 minutes after ICSI, using a double-square direct current pulse, and embryo transfer was performed with the best available embryos.
The researchers (Mansour R et al) present their findings in a new paper due to be published in the journal Fertility and Sterility. They report that:
The fertilization rate was significantly higher in the electroactivation group, compared with the control group: 68 percent versus 60 percent respectively (odds ratio 1.40; 95 percent confidence interval 1.20-1.63).
There was no significant difference between the two groups in the oocyte degeneration rate (5.9 percent in the electroactivation group and 4.9 percent in the control group).
There were a total of 112 clinical pregnancies in the study. In 15 of these, the embryos transferred were derived solely from the electroactivated group (out of a total of 34 embryo transfer procedures involving such embryos – a clinical pregnancy rate of 44 percent). In 69 of the clinical pregnancies the embryos transferred were derived solely from the control group (out of a total of 69 embryo transfer procedures involving such embryos – a clinical pregnancy rate of 48 percent). In the remaining 64, the embryos transferred were derived from both groups (out of a total of 138 embryo transfer procedures – a clinical pregnancy rate of 46.4 percent).
The miscarriage rates were: 20 percent (3 out of 15 clinical pregnancies) when the embryos transferred were derived solely from the electroactivated group, 9 per cent (3 out of 33 clinical pregnancies) when the embryos transferred were derived solely from the control group, and 9.4 percent (6 out of 64 clinical pregnancies) when the embryos transferred were derived from both groups.
Total fertilization failure did not occur in the study group, but occurred in five cycles in the control group.
Concluding, the researchers write that electroactivation of oocytes after ICSI can significantly improve the chances of fertilization, but stress: “However, more studies are needed to evaluate the clinical significance and safety of this technique.
“It is recommended in cases of previous failure of fertilization or limited fertilization, as well as in cases of severe oligoasthenospermia or azoospermia with 100 percent abnormal forms or zero motility.”
Source: Fertility and Sterility 2008;in press
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