Scientists have developed a ground-breaking method for testing the quality of a sperm before it is used in IVF and increase the chances of conception.
Researchers at the University of Edinburgh, funded by the EPSRC (Engineering and Physical Sciences Research Council), have created a way of chemically 'fingerprinting' individual sperm to give an indication of quality. Scientists can then consider whether the sperm is healthy enough to be used to fertilise an egg as part of an IVF treatment.
The sperm are captured in two highly focussed beams of laser light. Trapped in what are essentially 'optical tweezers', an individual sperm's DNA properties are identified by the pattern of the vibrations they emit in a process known as Raman spectroscopy. This is the first time this process has been used to evaluate DNA damage in sperm.
Dr Alistair Elfick, lead scientist on the project, said: "In natural conception the fittest and healthiest sperm are positively selected by the arduous journey they make to the egg. What our technology does is to replace natural selection with a DNA based 'quality score'. But this is not about designer babies. We can only tell if the sperm is strong and healthy not if it will produce a baby with blue eyes."
In the past quality tests of sperm have mostly been carried out on the basis of shape and activity. While these do give some indication of health of the sperm they do not give its DNA status.
There are established tests for sperm DNA quality but they work by cutting the cells in half and tagging them with fluorescent dye a process that kills the sperm and renders it useless. This new process does not destroy the sperm, so if it is found to have good DNA quality, it can still be used in IVF treatment.
Conception rates in both IVF treatment and intercourse are at around one in four. By selecting the best quality sperm it is hoped this new process could both increase a couple's chances of conception and give the child the best potential start in life.
The research is currently in a pre-clinical phase, and if successful could be available to patients in the next five to ten years.
Tuesday, February 3, 2009
Monday, February 2, 2009
IVF treatments often work for women under 35
Women under 35 who undergo six cycles of in vitro fertilization have up to an 86 percent chance of giving birth, a new study found.
But for women over 40, the odds are less than 50 percent -- in some cases, significantly less.
"IVF is a mainstay of the treatment of infertility, and it can overcome most causes of infertility for those under 40," said study senior author Dr. Alan S. Penzias, surgical director of Boston IVF, and an associate professor of obstetrics, gynecology and reproductive biology at Harvard Medical School.
But, he added, "Fertility is a function of age. It starts to decline at age 27, and the most pronounced decline is above age 40."
"Unfortunately, there's no test that shows when fertility starts to decline," said Dr. Jamie Grifo, program director for the New York University Langone Medical Center's fertility clinic, who added that this study could serve as a reminder to women to "be really thoughtful about the decisions you make about the reproductive process. Don't expect to be able to get pregnant at any time. You don't have to be pessimistic, but the older the patient, the lower the chance of success, unless a couple is willing to consider donor eggs."
The new study, published in the Jan. 15 issue of the New England Journal of Medicine, looked at IVF success in a different way. Traditionally, IVF success is reported as the number of pregnancies per cycle of IVF treatment, but that doesn't let couples know the exact odds of having a pregnancy that ends up with a healthy baby. And that information is exactly what people want to know, Penzias said.
"Couples really want to figure out how likely it is that they'll have a baby if they undergo IVF," he said.
To give people a better idea of the live-birth rates, Penzias and his colleagues followed more than 6,000 women undergoing IVF at a large center. Almost 15,000 cycles of IVF were completed. A cycle is the implantation of one or more eggs. Penzias said for this study, an average of 2.3 eggs were transferred for the first cycle and 2.8 for the sixth.
The overall live-birth rate after six cycles of IVF was between 51 percent and 72 percent. For women under 35, the rate was 65 percent to 86 percent. The rates differed, because not all women returned for all six cycles, the researchers said.
So, the researchers developed a best-case and worst-case scenario to account for these women. The highest number assumes that the women who stopped IVF treatments would have had a baby, and the lower number assumes that none of them would have. The actual number likely lies somewhere in between those two scenarios.
Penzias said that means that women under 35 who go through IVF have roughly the same chance of having a baby as someone who's a similar age in the general population.
The live-birth rate decreased as the age of the women increased, and women over 40 had only between a 23 percent to 42 percent chance of having a baby.
Overall, about 70 percent of the women had one baby, and less than 30 percent had twins. Fewer than 2 percent had triplets, according to the study.
"It's not a surprise to know that if you do more than one IVF cycle, you have a better chance of having a baby, but this study gives an indication of what one can expect if one is going to do IVF and try it multiple times," said Grifo, who added that the bottom line is, "that for any one woman, each cycle is either 100 percent or zero percent."
But for women over 40, the odds are less than 50 percent -- in some cases, significantly less.
"IVF is a mainstay of the treatment of infertility, and it can overcome most causes of infertility for those under 40," said study senior author Dr. Alan S. Penzias, surgical director of Boston IVF, and an associate professor of obstetrics, gynecology and reproductive biology at Harvard Medical School.
But, he added, "Fertility is a function of age. It starts to decline at age 27, and the most pronounced decline is above age 40."
"Unfortunately, there's no test that shows when fertility starts to decline," said Dr. Jamie Grifo, program director for the New York University Langone Medical Center's fertility clinic, who added that this study could serve as a reminder to women to "be really thoughtful about the decisions you make about the reproductive process. Don't expect to be able to get pregnant at any time. You don't have to be pessimistic, but the older the patient, the lower the chance of success, unless a couple is willing to consider donor eggs."
The new study, published in the Jan. 15 issue of the New England Journal of Medicine, looked at IVF success in a different way. Traditionally, IVF success is reported as the number of pregnancies per cycle of IVF treatment, but that doesn't let couples know the exact odds of having a pregnancy that ends up with a healthy baby. And that information is exactly what people want to know, Penzias said.
"Couples really want to figure out how likely it is that they'll have a baby if they undergo IVF," he said.
To give people a better idea of the live-birth rates, Penzias and his colleagues followed more than 6,000 women undergoing IVF at a large center. Almost 15,000 cycles of IVF were completed. A cycle is the implantation of one or more eggs. Penzias said for this study, an average of 2.3 eggs were transferred for the first cycle and 2.8 for the sixth.
The overall live-birth rate after six cycles of IVF was between 51 percent and 72 percent. For women under 35, the rate was 65 percent to 86 percent. The rates differed, because not all women returned for all six cycles, the researchers said.
So, the researchers developed a best-case and worst-case scenario to account for these women. The highest number assumes that the women who stopped IVF treatments would have had a baby, and the lower number assumes that none of them would have. The actual number likely lies somewhere in between those two scenarios.
Penzias said that means that women under 35 who go through IVF have roughly the same chance of having a baby as someone who's a similar age in the general population.
The live-birth rate decreased as the age of the women increased, and women over 40 had only between a 23 percent to 42 percent chance of having a baby.
Overall, about 70 percent of the women had one baby, and less than 30 percent had twins. Fewer than 2 percent had triplets, according to the study.
"It's not a surprise to know that if you do more than one IVF cycle, you have a better chance of having a baby, but this study gives an indication of what one can expect if one is going to do IVF and try it multiple times," said Grifo, who added that the bottom line is, "that for any one woman, each cycle is either 100 percent or zero percent."
Sunday, February 1, 2009
Saturday, January 31, 2009
Friday, January 30, 2009
Thursday, January 29, 2009
Sperm DNA Damage Linked To Increased Risk of Pregnancy Loss after IVF and ICSI
Earlier studies have indicated that spermatozoa of infertile men possess considerably more sperm DNA damage than that of fertile men, which could adversely affect both natural reproduction and assisted reproduction technology (ART) outcomes. Since the use of ART to treat infertility has increased substantially from its introduction in the US, in 1981, there is a huge concern regarding the safety of using DNA-damaged spermatozoa. Now, a recent study published online in the journal, Human Reproduction, demonstrates that sperm DNA damage is associated with a significantly enhanced risk of pregnancy loss following in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI).
Armand Zini from the St Mary’s Hospital Center, Canada and coworkers conducted a systematic review and meta-analysis of studies involving sperm DNA damage and pregnancy loss after IVF and/or ICSI treatment to determine the relationship between the two. The researchers analyzed 11 studies, which included 808 IVF and 741 ICSI cycles of treatment, resulting in 640 pregnancies (345 with IVF and 295 with ICSI) and 122 pregnancy losses. From the estimates of pregnancy loss, two by two tables were constructed and odds ratios (ORs) were calculated to examine the association. It was found that the combined odds ratio was 2.48, suggesting that damage to spermatozoa DNA raises the risk of pregnancy loss in IVF and ICSI cycles. The data indicates that sperm DNA damage has to be evaluated prior to ARTs to achieve better outcomes and also forms a basis for further investigations to validate the findings.
Recently, Bhattacharya SM (International Urology and Nephrology, 2008) conducted a study to examine the link between different sperm parameters and repeated unexplained early pregnancy loss. Semen samples obtained from male partners of 74 couples with a history of repeated pregnancy loss were assessed according to WHO criteria and the DNA integrity in each case was evaluated using Acridine Orange staining test. A comparison of the results was also drawn by studying semen samples obtained from 65 husbands of proven fertility. It was noted that there were a lack of statistically significant differences between the two groups in the following criteria: age of husbands, total count per ejaculate, sperm concentration, and rapid progressive motility of sperms. However, DNA integrity value, percentage of motile sperm and total motile sperms per ejaculate, were different in the two groups. Based on the findings, it was concluded that repeated embryonic or early fetal loss is associated with sperm DNA-integrity damage, implying that sperm DNA damage may be a key paternal factor for predicting pregnancy outcomes.
To determine the relationship between sperm DNA fragmentation in IVF/ICSI patients, ART outcome, and sperm parameters, Borini and colleagues (Human Reproduction, 2006) conducted a study on 132 men undergoing ART. The scientists found that the embryo post-implantation development in ICSI procedures is affected by sperm DNA fragmentation; with a high fragmentation rate compromising embryo viability, and thereby leading to pregnancy loss.
Sperm DNA damage is attributed to various intra-or extratesticular factors such as chemotherapy, radiation therapy, genital tract inflammation, testicular hyperthermia, varicoceles, cigarette smoking and environmental toxins. Although previous studies have found no consistent relation between sperm DNA damage and fertilization rates during IVF or ICSI, the recent research provides evidence that sperm DNA damage may be associated with an increased risk of significant spontaneous abortion. Substantiating the current research with further larger trials may help in the development of stringent processes for selecting sperms and embryos during ART to alleviate the adverse effects related to sperm DNA damage.
References
1. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008 Dec;23(12):2663-8. Epub 2008 Aug 29.
2. Bhattacharya SM. Association of various sperm parameters with unexplained repeated early pregnancy loss–which is most important? Int Urol Nephrol. 2008;40(2):391-5.
3. Borini A, Tarozzi N, Bizzaro D, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006 Nov;21(11):2876-81. Epub 2006 Jun 22.
Armand Zini from the St Mary’s Hospital Center, Canada and coworkers conducted a systematic review and meta-analysis of studies involving sperm DNA damage and pregnancy loss after IVF and/or ICSI treatment to determine the relationship between the two. The researchers analyzed 11 studies, which included 808 IVF and 741 ICSI cycles of treatment, resulting in 640 pregnancies (345 with IVF and 295 with ICSI) and 122 pregnancy losses. From the estimates of pregnancy loss, two by two tables were constructed and odds ratios (ORs) were calculated to examine the association. It was found that the combined odds ratio was 2.48, suggesting that damage to spermatozoa DNA raises the risk of pregnancy loss in IVF and ICSI cycles. The data indicates that sperm DNA damage has to be evaluated prior to ARTs to achieve better outcomes and also forms a basis for further investigations to validate the findings.
Recently, Bhattacharya SM (International Urology and Nephrology, 2008) conducted a study to examine the link between different sperm parameters and repeated unexplained early pregnancy loss. Semen samples obtained from male partners of 74 couples with a history of repeated pregnancy loss were assessed according to WHO criteria and the DNA integrity in each case was evaluated using Acridine Orange staining test. A comparison of the results was also drawn by studying semen samples obtained from 65 husbands of proven fertility. It was noted that there were a lack of statistically significant differences between the two groups in the following criteria: age of husbands, total count per ejaculate, sperm concentration, and rapid progressive motility of sperms. However, DNA integrity value, percentage of motile sperm and total motile sperms per ejaculate, were different in the two groups. Based on the findings, it was concluded that repeated embryonic or early fetal loss is associated with sperm DNA-integrity damage, implying that sperm DNA damage may be a key paternal factor for predicting pregnancy outcomes.
To determine the relationship between sperm DNA fragmentation in IVF/ICSI patients, ART outcome, and sperm parameters, Borini and colleagues (Human Reproduction, 2006) conducted a study on 132 men undergoing ART. The scientists found that the embryo post-implantation development in ICSI procedures is affected by sperm DNA fragmentation; with a high fragmentation rate compromising embryo viability, and thereby leading to pregnancy loss.
Sperm DNA damage is attributed to various intra-or extratesticular factors such as chemotherapy, radiation therapy, genital tract inflammation, testicular hyperthermia, varicoceles, cigarette smoking and environmental toxins. Although previous studies have found no consistent relation between sperm DNA damage and fertilization rates during IVF or ICSI, the recent research provides evidence that sperm DNA damage may be associated with an increased risk of significant spontaneous abortion. Substantiating the current research with further larger trials may help in the development of stringent processes for selecting sperms and embryos during ART to alleviate the adverse effects related to sperm DNA damage.
References
1. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008 Dec;23(12):2663-8. Epub 2008 Aug 29.
2. Bhattacharya SM. Association of various sperm parameters with unexplained repeated early pregnancy loss–which is most important? Int Urol Nephrol. 2008;40(2):391-5.
3. Borini A, Tarozzi N, Bizzaro D, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006 Nov;21(11):2876-81. Epub 2006 Jun 22.
Wednesday, January 28, 2009
Dominant Follicle Diameter Helps Select Optimal Day for Oocyte Retrieval in IVM Cycles
In vitro maturation (IVM), a novel assisted reproduction technique, reduces risks associated with in vitro fertilization (IVF) as the eggs are retrieved, matured and fertilized in vitro prior to implantation, thereby eliminating ovarian stimulation. However, the factors predisposing the success or failure of IVM cycles are unclear. Now, a recent study published in the December issue of the journal, Human Reproduction suggests that dominant follicle (DF) size of ≤14mm at oocyte retrieval following human chorionic gonadotropin (hCG) priming improves pregnancy outcomes in cycles programmed for IVM treatment.
Weon-Young Son from the McGill University, Montreal, and coworkers conducted a study on 160 women with polycystic ovaries (171 cycles) to compare the DF size at oocyte retrieval after hCG priming with IVM outcome. When the endometrial thickness reached a minimal of 6 mm, the researchers subcutaneously administered 10,000 IU hCG, 35 to 38 hours prior to oocyte collection. The retrospective analysis was performed in 3 study groups based on the DF diameter: group 1, with a diameter of ≤10 mm; group 2, between 10 and 14 mm; and group 3 of >14mm. In the corresponding 3 groups, 6.9%, 10.6%, and 15.1% of the in vivo matured oocytes were collected, suggesting a positive correlation between the size and number of oocytes.
Results showed that among the sibling immature oocytes extracted in the 3 groups, the rates of IVM, fertilization and embryo development were similar. It was found that group 3 exhibited a lower clinical pregnancy rate (17.1%) compared to group 2 (40.3%). Furthermore, groups 1 (13.6%) and 2 (14.3%) had higher implantation rates than group 3 (4.9%). Based on the study findings, the researchers proposed DF ≤14mm as the optimal oocyte retrieval time for IVM cycles, as DF >14 mm may detrimentally affect the sibling immature oocytes.
Earlier, the same group of researchers conducted a retrospective study (Human Reproduction, 2008) to investigate if an extension in the time interval between hCG priming and immature oocyte retrieval enhances the oocyte maturation rate after IVM. The assisted reproduction technique was performed on 113 polycystic ovary syndrome patients (120 cycles) and the oocytes were collected at either 35 hours (group 1=76) or 38 hours (group 2 = 44) following 10,000 IU of hCG priming. The oocyte maturity was analyzed after the retrieval and the culture of the immature oocytes was performed till day 2 using IVM medium. It was found that the number of in vivo matured oocytes was considerably lower in group 1 (13.6%) compared to group 2 (7.3%). Also, group 2 exhibited a higher oocyte maturation rate after day 1 (46.3 vs. 36.0%), clinical pregnancy (40.9 vs. 25%) and implantation rates (15.6 vs. 9.6%) than group 1. Based on the findings, the scientists suggested that extending the time of hCG priming from 35 hours to 38 hours for oocyte retrieval could improve the pregnancy outcome of IVM cycles.
In vitro maturation of immature oocytes collected from unstimulated ovaries is an assisted reproduction technology that is extensively being studied. Some of the advantages of IVM over IVF are that it is less expensive, has shorter treatment regimen, and does not require the use of hormonal fertility drugs for ovarian stimulation. It may thereby eliminate the risk of developing ovarian hyperstimulation syndrome and multiple pregnancies.
Several previous studies have indicated that controlled ovarian stimulation in combination with in vitro fertilization cycles provide better results compared to in vitro maturation techniques. Now, the identification of the optimal hCG priming time and dominant follicle size for oocyte retrieval may help in enhancing the success rates of the novel IVM technique with fewer adverse effects compared to IVF.
References
1.Son WY, Chung JT, Herrero B, et al. Selection of the optimal day for oocyte retrieval based on the diameter of the dominant follicle in hCG-primed in vitro maturation cycles. Hum Reprod. 2008 Dec;23(12):2680-5. Epub 2008 Sep 4.
2.Son WY, Chung JT, Chian RC, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008 Sep;23(9):2010-6. Epub 2008 Jun 12.
Weon-Young Son from the McGill University, Montreal, and coworkers conducted a study on 160 women with polycystic ovaries (171 cycles) to compare the DF size at oocyte retrieval after hCG priming with IVM outcome. When the endometrial thickness reached a minimal of 6 mm, the researchers subcutaneously administered 10,000 IU hCG, 35 to 38 hours prior to oocyte collection. The retrospective analysis was performed in 3 study groups based on the DF diameter: group 1, with a diameter of ≤10 mm; group 2, between 10 and 14 mm; and group 3 of >14mm. In the corresponding 3 groups, 6.9%, 10.6%, and 15.1% of the in vivo matured oocytes were collected, suggesting a positive correlation between the size and number of oocytes.
Results showed that among the sibling immature oocytes extracted in the 3 groups, the rates of IVM, fertilization and embryo development were similar. It was found that group 3 exhibited a lower clinical pregnancy rate (17.1%) compared to group 2 (40.3%). Furthermore, groups 1 (13.6%) and 2 (14.3%) had higher implantation rates than group 3 (4.9%). Based on the study findings, the researchers proposed DF ≤14mm as the optimal oocyte retrieval time for IVM cycles, as DF >14 mm may detrimentally affect the sibling immature oocytes.
Earlier, the same group of researchers conducted a retrospective study (Human Reproduction, 2008) to investigate if an extension in the time interval between hCG priming and immature oocyte retrieval enhances the oocyte maturation rate after IVM. The assisted reproduction technique was performed on 113 polycystic ovary syndrome patients (120 cycles) and the oocytes were collected at either 35 hours (group 1=76) or 38 hours (group 2 = 44) following 10,000 IU of hCG priming. The oocyte maturity was analyzed after the retrieval and the culture of the immature oocytes was performed till day 2 using IVM medium. It was found that the number of in vivo matured oocytes was considerably lower in group 1 (13.6%) compared to group 2 (7.3%). Also, group 2 exhibited a higher oocyte maturation rate after day 1 (46.3 vs. 36.0%), clinical pregnancy (40.9 vs. 25%) and implantation rates (15.6 vs. 9.6%) than group 1. Based on the findings, the scientists suggested that extending the time of hCG priming from 35 hours to 38 hours for oocyte retrieval could improve the pregnancy outcome of IVM cycles.
In vitro maturation of immature oocytes collected from unstimulated ovaries is an assisted reproduction technology that is extensively being studied. Some of the advantages of IVM over IVF are that it is less expensive, has shorter treatment regimen, and does not require the use of hormonal fertility drugs for ovarian stimulation. It may thereby eliminate the risk of developing ovarian hyperstimulation syndrome and multiple pregnancies.
Several previous studies have indicated that controlled ovarian stimulation in combination with in vitro fertilization cycles provide better results compared to in vitro maturation techniques. Now, the identification of the optimal hCG priming time and dominant follicle size for oocyte retrieval may help in enhancing the success rates of the novel IVM technique with fewer adverse effects compared to IVF.
References
1.Son WY, Chung JT, Herrero B, et al. Selection of the optimal day for oocyte retrieval based on the diameter of the dominant follicle in hCG-primed in vitro maturation cycles. Hum Reprod. 2008 Dec;23(12):2680-5. Epub 2008 Sep 4.
2.Son WY, Chung JT, Chian RC, et al. A 38 h interval between hCG priming and oocyte retrieval increases in vivo and in vitro oocyte maturation rate in programmed IVM cycles. Hum Reprod. 2008 Sep;23(9):2010-6. Epub 2008 Jun 12.
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