The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical ... more The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical examination were evaluated in association with 48 second-look laparotomies of ovarian carcinoma patients treated with cytotoxic chemotherapy. At laparotomy, there were 23 macroscopical and 6 microscopical tumors. Nineteen patients were disease-free. Clinical examination, CA 125, and PIIINP were correctly positive in 93, 92, and 82% of cases, respectively. When CA 125 and PIIINP were used simultaneously this value increased to 100%. The sensitivity of CA 125 (43%) and PIIINP (56%) was unsatisfactory, but with their combination it increased to 62%. The use of CA 125, PIIINP, or both increased the sensitivity of clinical examination by 14, 24, and 27%, respectively. Of all the occult tumors, CA 125 detected 33%, PIIINP 57%, and both 66%. The detection rate of macroscopical tumors missed at clinical examination by both was 71%. Hence, PIIINP may be a clinically valuable complement to CA 125 and clinical examination before second-look laparotomy.
The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, a... more The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, and the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, were evaluated in 111 cervical carcinoma patients. Squamous cell carcinoma antigen was pathologic in 47%, aminoterminal propeptide of type III procollagen in 40%, CA 125 in 13%, CA 15-3 in 30%, and TAG 72 in 9% of the 91 patients with squamous cell carcinoma. The squamous cell carcinoma antigen, aminoterminal propeptide of type III procollagen, and CA 125 correlated with the clinical stage. The predictive value of a pathologic squamous cell carcinoma antigen was 78% and that of a negative result 68%. Squamous cell carcinoma antigen and aminoterminal propeptide of type III procollagen further increased the detection rate by approximately 20% from that obtained by squamous cell carcinoma antigen alone. In 16 patients with advanced disease, squamous cell carcinoma antigen correlated with the behavior of the disease in eight, aminoterminal propeptide of type III procollagen in nine, and CA 125 in six patients. Pathologic squamous cell carcinoma antigen, CA 125, CA 15-3, TAG 72, and aminoterminal propeptide of type III procollagen appeared in 11, 32, 31, 31, and 47% of 19 patients with adenocarcinoma, respectively. Squamous cell carcinoma antigen is clinically useful in squamous cell carcinoma but poor in adenocarcinoma, for which the other markers are better. Squamous cell carcinoma antigen, CA 125, and aminoterminal propeptide of type III procollagen may be used for monitoring the behavior of advanced squamous cell carcinoma.
were managed and analyzed with the Statistical Package for the Social Sciences, version 14.0 (Chi... more were managed and analyzed with the Statistical Package for the Social Sciences, version 14.0 (Chicago, IL). RESULTS: A total of 77 women and 62 men enrolled in the study. Most had attended college (85.7% of women and 81.2% of men). Couples were more worried (4 or 5 on a 5-point scale) about not getting pregnant (85.5% of women and 82.8% of men) and high financial costs of IVF (52.7% of women and 51.6% of men) than about having twins (9.2% of women and 17.2% of men). Women underestimated twin-related risks of very low birth weight, preeclampsia and post-partum depression 19.2%, 61.1% and 70.8% of the time, respectively. Among men, the proportions underestimating these risks were 31.7%, 70.2% and 72.9%, respectively. Among women, 35.1% indicated twins as their first choice for the ideal number of babies to have from this IVF treatment cycle. Men chose twins 20.8% of the time. Incorrect responses were common for numeracy questions. When asked what percent of tickets win a sweepstakes prize if the chance of winning is 1 in 1,000, only 49.4% of women and 44.2% of men answered correctly. Incorrect answers to the sweepstakes question included 0.001%, 0.05%, 2% and 10%. When asked about the number of times in 1,000 coin flips that the result would be heads, 80.5% of women but only 67.5% of men answered correctly. Incorrect answers to the coin flip question included 0, 10, 60, 625 and 700. There was an erroneous belief among 22.5% of the women and 17.9% of the men that there would be the same or lower chance of twins as more embryos are transferred. CONCLUSIONS: Limited numeracy and a low perception of twin-related risks, even among college-educated patients, may pose a challenge during counseling about IVF. More research is needed among populations with lower educational attainment, and to determine whether these factors actually impact treatment decisions or patient satisfaction with care.
Acta Obstetricia et Gynecologica Scandinavica, 1992
The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a ... more The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a measure of the activity of the metabolism of type III collagen, which is a major constituent of soft connective tissues and of the connective tissue stroma of solid tumours. In advanced ovarian carcinoma, serum PIIINP serves as a tumour‐associated antigen, its changes reflecting and preceding changes in the clinical behaviour of the malignancy. Elevated values of serum PIIINP are also observed in endometrial and cervical malignancies, though less frequently than in ovarian tumours. Very high concentrations of PIIINP are found in ovarian carcinoma ascites, suggesting an ongoing fibroproliferative reaction in the peritoneal cavity as a response to the tumour.
The Journal of Clinical Endocrinology and Metabolism, Jul 1, 1998
Previous studies have suggested that metformin is clinically useful in the treatment of polycysti... more Previous studies have suggested that metformin is clinically useful in the treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether the improvement of ovarian function achieved by metformin therapy is associated with changes in leptin concentrations. Twenty-six obese women with PCOS were treated with 500 mg metformin, ϫ 3 daily, for 2 months; and 12 women continued the therapy for 4-6 months. A significant decrease in the serum leptin level was observed after 2 months of treatment in the whole study group (29.2 Ϯ 12.7 ng/mL vs. 25.7 Ϯ 10.9 ng/mL, P ϭ 0.03). In the 12 women treated for 4-6 months, the mean serum leptin concentration decreased after 2 months (38.6 Ϯ 9.3 ng/mL vs. 30.2 Ϯ 8.1 ng/mL; P ϭ 0.004) but slightly increased after 4-6 months of treatment (33.4 Ϯ 15.7 ng/mL; not significant). These results indicate that insulin sensitizing therapy with metformin decreases the leptin concentrations in obese PCOS women.
The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertilit... more The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertility was investigated in a pilot study. A total of 50 infertility patients with normal tubal function verified by laparoscopy or hysterosalpingography were stimulated with clomiphene citrate/human menopausal gonadotrophin. Washed spermatozoa were injected into one to three pre-ovulatory follicles via vaginal puncture 12 or 30 h after human chorionic gonadotrophin administration. Natural progesterone was given for luteal support. The IFI procedure was technically very simple and convenient for the patient and no complications were recorded. One normal intra-uterine pregnancy resulted. The results indicate that by comparsion with other assisted reproductive technologies IFI is very inefficacious for treating non-tubal infertility. Our data suggest that the intrafollicular environment in the preovulatory period is not favourable for fertilization.
The main indications for intracytoplasmic sperm injection (ICSI) are severe male factor and ferti... more The main indications for intracytoplasmic sperm injection (ICSI) are severe male factor and fertilization failure or a low fertilization rate in previous in-vitro fertilization (IVF) treatments. The fertilization and pregnancy rates after ICSI, however, are seldom reported separately for these two different indications. The aim of this study was to compare the treatment outcome and pregnancy rate after ICSI between 65 patients with previous failed fertilization or a low fertilization rate without male factor, and 219 patients with a primary male factor. From the 2726 oocytes collected, 2087 (77%) were micro-injected and 1355 (65%) achieved normal fertilization. The oocyte fertilization rate was similar in the group with previous failed fertilization or a low fertilization rate and the group with a male factor (65 and 65% respectively), as was the cleavage rate of normally fertilized oocytes (92 and 94% respectively). Despite the similar fertilization and cleavage rates and the similar number and morphological quality of embryos transferred in both groups, the pregnancy rate was significantly lower (P Ͻ 0.05) in the group with previous failed fertilization or a low fertilization rate than in the group with a male factor (19.6 versus 33.5% respectively; 95% confidence intervals for the difference, 2-26%). The implantation rate was also lower (P ϭ 0.01) in patients with previous failed fertilization or a low fertilization rate (9.6%) than in the group with a male factor (19.5%). We conclude that patients with previous failed fertilization or a low fertilization rate in standard IVF without male factor have a significantly smaller chance of becoming pregnant after subsequent ICSI than patients with a primary male factor. This poor outcome probably reflects intrinsic oocyte defects not bypassed by ICSI.
Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro ... more Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI), there remain concerns in many countries that it is less effective and more expensive than conventional double embryo transfer (DET). methods: We compared the clinical outcome achieved in the years 1995-1999, in which eSET was rarely used (4.2% of women, DET period) with that of the years 2000-2004, in which eSET was more widely used (46.2%, eSET period). In the DET period, 826 women had 1359 fresh embryo cycles followed by 589 frozen-thawed embryo transfer (FET) cycles. In the eSET period, 684 women had 1027 fresh and 683 FET cycles. The cumulative term live birth rate/woman was the primary clinical outcome measure. An incremental cost-effectiveness ratio of a term live birth was also calculated based on hospital charges and medication prices of IVF/ICSI treatment. results: The cumulative pregnancy rate/oocytes pickup (38.2 versus 33.1%, P ¼ 0.01), cumulative live birth rate/oocytes pickup (28.0 versus 22.5%, P ¼ 0.002) and cumulative live birth rate/woman (41.7 versus 36.6%, P ¼ 0.04) were all higher in the eSET period than in the DET period. The cumulative multiple birth rate was significantly lower in the eSET period than in the DET period (8.9 versus 19.6%, P , 0.0001). A term live birth in the eSET period was 19 889 euros less expensive than in the DET period. conclusions: This study shows that eSET with cryopreservation is more effective and less expensive than DET and should be adopted as a treatment of choice.
We evaluated the clinical usefulness of the squamous cell carcinoma antigen (SCC) and CA 125, ser... more We evaluated the clinical usefulness of the squamous cell carcinoma antigen (SCC) and CA 125, serum markers of epithelial cancer cells, in comparison with the serum concentration and tissue distribution of the aminoterminal propeptide of type III procollagen (PIIINP), a marker of connective tissue metabolism, in 31 patients with vulvar carcinoma. The SCC concentration was increased in 42%, that of CA 125 in 14% and that of PIIINP in 36% of the cases. The combination of SCC and PIIINP increased the detection rate to 57% and that of all three to 64%. None of the tumor markers correlated with the clinical stage of the disease. The initial values of the serum markers did not discriminate between different patterns of the clinical behavior of the disease. Six patients were followed with serial determinations of the markers. In each case at least one of the markers correlated with the clinical course of the disease. SCC did so in 5 cases, PIIINP in 3 cases and CA 125 in 2 cases. The mean concentrations of SCC and CA 125, but not that of PIIINP, were significantly lower during the periods of response to therapy than during the nonresponsive periods. Immunohistochemistry of PIIINP showed vulvar carcinoma to be associated with a distinct collagenous stroma. In the junctional area of the stroma around the malignant epithelium, the PIIINP positive fibers grew more sparse and irregular with decreasing differentiation of the tumor. The present data suggest that SCC, CA 125 and PIIINP are useful, especially SCC, in monitoring the clinical behaviour of the advanced vulvar cancer, less so in predicting its prognosis.
Objective: To compare the reproductive outcome of three protocols for frozen ET treatment. Design... more Objective: To compare the reproductive outcome of three protocols for frozen ET treatment. Design: Retrospective follow-up study. Setting: Two public clinics and one private clinic. Patient(s): Four thousand four hundred seventy frozen ET cycles between 2006 and 2010. Intervention(s): Thawing of embryos and ET. Main Outcome Measure(s): Pregnancy test rate, clinical pregnancy rate, and pregnancy loss rate. Result(s): The natural cycle followed by P (NC þ P) was used in 26% of cycles, the natural cycle with hCG (NC þ hCG) in 10%, and the substituted cycle with estrogen and P (E þ P) in 64% of cycles. The rate of transfers after thawing was similar in all groups (87.2%, 73.9%, and 87.2%, respectively). There was a significantly higher positive pregnancy test rate in the E þ P (34.3%) and NC þ hCG (35.5%) cycles as compared with the NC þ P cycles (26.7%). However, the clinical pregnancy rate was similar in all groups (27.7%, 29.1%, and 24.3%, respectively). Moreover, no differences were seen between groups regarding the live-birth rate (20.1%, 23.5%, and 20.7%, respectively). A logistic regression analysis showed that the type of protocol was the only predictor of pregnancy loss, while age, irregular cycles, endometrial thickness, number, and quality of embryos transferred did not correlate to pregnancy loss. Conclusion(s): A higher positive pregnancy test rate was obtained in E þ P frozen ET cycles in comparison with other protocols; however, due to an increased preclinical and clinical pregnancy loss, comparable clinical pregnancy, and delivery rates are reported for the three protocols. (Fertil Steril Ò 2012;98:1165-9. Ó2012 by American Society for Reproductive Medicine.
BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recogniz... more BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recognized but has not been comprehensively evaluated. In order to determine its importance, the degree of difficulty of 4807 embryo transfers after IVF/ICSI was analysed retrospectively. METHODS: Logistic regression analysis identified the age of the subject, type of treatment (IVF versus ICSI), number of embryos transferred and degree of difficulty of embryo transfer as independent factors predicting pregnancy. The main focus of the study was to evaluate the importance of the difficulty of embryo transfer after taking into account the other confounding variables. RESULTS: Embryo transfer was classified as easy (2821), intermediate (1644) or difficult (342). The transfer was considered difficult if it was time consuming, the catheter met great resistance, there was a need to change the catheter, if sounding or cervical dilatation was needed or if blood was found in any part of the catheter. Easy or intermediate transfers resulted in a 1.7-fold higher pregnancy rate than difficult transfers (P < 0.0001; 95% confidence interval: 1.3-2.2). CONCLUSIONS: This study demonstrates that the degree of difficulty of embryo transfer is an independent factor as regards achieving pregnancy after IVF/ICSI. All efforts should be made to avoid difficult embryo transfers. Physicians should be alert to the factors associated with embryo transfer and should be instructed to use a stepwise approach in difficult transfers.
The age of the patient alone is a weak predictor of the ovarian reserve and responsiveness to IVF... more The age of the patient alone is a weak predictor of the ovarian reserve and responsiveness to IVF stimulation (Check Hannu Martikainen 1 et al., 1994). There are women aged Ͼ40 years who are able for the first time. All patients had both ovaries present. The main indications for treatment were tubal factor (n ϭ 65), male factor (n ϭ or age alone. Patients can be identified with inactive ovaries 40), endometriosis (n ϭ 16), ovulatory dysfunction (n ϭ 11), and which will have a poor response to IVF treatment, a key unexplained infertility (n ϭ 34).
During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronu... more During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronuclei, one arising from the oocyte and the other from the male gamete. Embryos derived from zygotes with a pronuclei number other than two are assumed to possess a ploidy abnormality and their transfer is usually avoided owing to increased risk of implantation failure, miscarriage, and molar pregnancies. Nonetheless, the inclusion of genotyping data in preimplantation genetic testing has revealed that a normal diploid configuration is possible in embryos deriving from zygotes with an abnormal pronuclei number such as tripronuclear and one pronucleus. Here, we present a one-of-a-kind transfer of a tetrapronuclear-derived embryo that was discovered to be diploid and negative for other whole chromosome or segmental aneuploidies during preimplantation genetic testing using a targeted next-generation sequencing approach. The transfer resulted in the live birth of a healthy infant who is now 4 ...
The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical ... more The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical examination were evaluated in association with 48 second-look laparotomies of ovarian carcinoma patients treated with cytotoxic chemotherapy. At laparotomy, there were 23 macroscopical and 6 microscopical tumors. Nineteen patients were disease-free. Clinical examination, CA 125, and PIIINP were correctly positive in 93, 92, and 82% of cases, respectively. When CA 125 and PIIINP were used simultaneously this value increased to 100%. The sensitivity of CA 125 (43%) and PIIINP (56%) was unsatisfactory, but with their combination it increased to 62%. The use of CA 125, PIIINP, or both increased the sensitivity of clinical examination by 14, 24, and 27%, respectively. Of all the occult tumors, CA 125 detected 33%, PIIINP 57%, and both 66%. The detection rate of macroscopical tumors missed at clinical examination by both was 71%. Hence, PIIINP may be a clinically valuable complement to CA 125 and clinical examination before second-look laparotomy.
The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, a... more The epithelial cell tumor markers squamous cell carcinoma antigen, CA 125, CA 15-3, and TAG 72, and the aminoterminal propeptide of type III procollagen, an indicator of collagen metabolism, were evaluated in 111 cervical carcinoma patients. Squamous cell carcinoma antigen was pathologic in 47%, aminoterminal propeptide of type III procollagen in 40%, CA 125 in 13%, CA 15-3 in 30%, and TAG 72 in 9% of the 91 patients with squamous cell carcinoma. The squamous cell carcinoma antigen, aminoterminal propeptide of type III procollagen, and CA 125 correlated with the clinical stage. The predictive value of a pathologic squamous cell carcinoma antigen was 78% and that of a negative result 68%. Squamous cell carcinoma antigen and aminoterminal propeptide of type III procollagen further increased the detection rate by approximately 20% from that obtained by squamous cell carcinoma antigen alone. In 16 patients with advanced disease, squamous cell carcinoma antigen correlated with the behavior of the disease in eight, aminoterminal propeptide of type III procollagen in nine, and CA 125 in six patients. Pathologic squamous cell carcinoma antigen, CA 125, CA 15-3, TAG 72, and aminoterminal propeptide of type III procollagen appeared in 11, 32, 31, 31, and 47% of 19 patients with adenocarcinoma, respectively. Squamous cell carcinoma antigen is clinically useful in squamous cell carcinoma but poor in adenocarcinoma, for which the other markers are better. Squamous cell carcinoma antigen, CA 125, and aminoterminal propeptide of type III procollagen may be used for monitoring the behavior of advanced squamous cell carcinoma.
were managed and analyzed with the Statistical Package for the Social Sciences, version 14.0 (Chi... more were managed and analyzed with the Statistical Package for the Social Sciences, version 14.0 (Chicago, IL). RESULTS: A total of 77 women and 62 men enrolled in the study. Most had attended college (85.7% of women and 81.2% of men). Couples were more worried (4 or 5 on a 5-point scale) about not getting pregnant (85.5% of women and 82.8% of men) and high financial costs of IVF (52.7% of women and 51.6% of men) than about having twins (9.2% of women and 17.2% of men). Women underestimated twin-related risks of very low birth weight, preeclampsia and post-partum depression 19.2%, 61.1% and 70.8% of the time, respectively. Among men, the proportions underestimating these risks were 31.7%, 70.2% and 72.9%, respectively. Among women, 35.1% indicated twins as their first choice for the ideal number of babies to have from this IVF treatment cycle. Men chose twins 20.8% of the time. Incorrect responses were common for numeracy questions. When asked what percent of tickets win a sweepstakes prize if the chance of winning is 1 in 1,000, only 49.4% of women and 44.2% of men answered correctly. Incorrect answers to the sweepstakes question included 0.001%, 0.05%, 2% and 10%. When asked about the number of times in 1,000 coin flips that the result would be heads, 80.5% of women but only 67.5% of men answered correctly. Incorrect answers to the coin flip question included 0, 10, 60, 625 and 700. There was an erroneous belief among 22.5% of the women and 17.9% of the men that there would be the same or lower chance of twins as more embryos are transferred. CONCLUSIONS: Limited numeracy and a low perception of twin-related risks, even among college-educated patients, may pose a challenge during counseling about IVF. More research is needed among populations with lower educational attainment, and to determine whether these factors actually impact treatment decisions or patient satisfaction with care.
Acta Obstetricia et Gynecologica Scandinavica, 1992
The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a ... more The concentration of the aminoterminal propeptide of type III procollagen (PIIINP) in serum is a measure of the activity of the metabolism of type III collagen, which is a major constituent of soft connective tissues and of the connective tissue stroma of solid tumours. In advanced ovarian carcinoma, serum PIIINP serves as a tumour‐associated antigen, its changes reflecting and preceding changes in the clinical behaviour of the malignancy. Elevated values of serum PIIINP are also observed in endometrial and cervical malignancies, though less frequently than in ovarian tumours. Very high concentrations of PIIINP are found in ovarian carcinoma ascites, suggesting an ongoing fibroproliferative reaction in the peritoneal cavity as a response to the tumour.
The Journal of Clinical Endocrinology and Metabolism, Jul 1, 1998
Previous studies have suggested that metformin is clinically useful in the treatment of polycysti... more Previous studies have suggested that metformin is clinically useful in the treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether the improvement of ovarian function achieved by metformin therapy is associated with changes in leptin concentrations. Twenty-six obese women with PCOS were treated with 500 mg metformin, ϫ 3 daily, for 2 months; and 12 women continued the therapy for 4-6 months. A significant decrease in the serum leptin level was observed after 2 months of treatment in the whole study group (29.2 Ϯ 12.7 ng/mL vs. 25.7 Ϯ 10.9 ng/mL, P ϭ 0.03). In the 12 women treated for 4-6 months, the mean serum leptin concentration decreased after 2 months (38.6 Ϯ 9.3 ng/mL vs. 30.2 Ϯ 8.1 ng/mL; P ϭ 0.004) but slightly increased after 4-6 months of treatment (33.4 Ϯ 15.7 ng/mL; not significant). These results indicate that insulin sensitizing therapy with metformin decreases the leptin concentrations in obese PCOS women.
The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertilit... more The effectiveness of intrafollicular insemination (IFI) for the treatment of non-tubal infertility was investigated in a pilot study. A total of 50 infertility patients with normal tubal function verified by laparoscopy or hysterosalpingography were stimulated with clomiphene citrate/human menopausal gonadotrophin. Washed spermatozoa were injected into one to three pre-ovulatory follicles via vaginal puncture 12 or 30 h after human chorionic gonadotrophin administration. Natural progesterone was given for luteal support. The IFI procedure was technically very simple and convenient for the patient and no complications were recorded. One normal intra-uterine pregnancy resulted. The results indicate that by comparsion with other assisted reproductive technologies IFI is very inefficacious for treating non-tubal infertility. Our data suggest that the intrafollicular environment in the preovulatory period is not favourable for fertilization.
The main indications for intracytoplasmic sperm injection (ICSI) are severe male factor and ferti... more The main indications for intracytoplasmic sperm injection (ICSI) are severe male factor and fertilization failure or a low fertilization rate in previous in-vitro fertilization (IVF) treatments. The fertilization and pregnancy rates after ICSI, however, are seldom reported separately for these two different indications. The aim of this study was to compare the treatment outcome and pregnancy rate after ICSI between 65 patients with previous failed fertilization or a low fertilization rate without male factor, and 219 patients with a primary male factor. From the 2726 oocytes collected, 2087 (77%) were micro-injected and 1355 (65%) achieved normal fertilization. The oocyte fertilization rate was similar in the group with previous failed fertilization or a low fertilization rate and the group with a male factor (65 and 65% respectively), as was the cleavage rate of normally fertilized oocytes (92 and 94% respectively). Despite the similar fertilization and cleavage rates and the similar number and morphological quality of embryos transferred in both groups, the pregnancy rate was significantly lower (P Ͻ 0.05) in the group with previous failed fertilization or a low fertilization rate than in the group with a male factor (19.6 versus 33.5% respectively; 95% confidence intervals for the difference, 2-26%). The implantation rate was also lower (P ϭ 0.01) in patients with previous failed fertilization or a low fertilization rate (9.6%) than in the group with a male factor (19.5%). We conclude that patients with previous failed fertilization or a low fertilization rate in standard IVF without male factor have a significantly smaller chance of becoming pregnant after subsequent ICSI than patients with a primary male factor. This poor outcome probably reflects intrinsic oocyte defects not bypassed by ICSI.
Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro ... more Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI), there remain concerns in many countries that it is less effective and more expensive than conventional double embryo transfer (DET). methods: We compared the clinical outcome achieved in the years 1995-1999, in which eSET was rarely used (4.2% of women, DET period) with that of the years 2000-2004, in which eSET was more widely used (46.2%, eSET period). In the DET period, 826 women had 1359 fresh embryo cycles followed by 589 frozen-thawed embryo transfer (FET) cycles. In the eSET period, 684 women had 1027 fresh and 683 FET cycles. The cumulative term live birth rate/woman was the primary clinical outcome measure. An incremental cost-effectiveness ratio of a term live birth was also calculated based on hospital charges and medication prices of IVF/ICSI treatment. results: The cumulative pregnancy rate/oocytes pickup (38.2 versus 33.1%, P ¼ 0.01), cumulative live birth rate/oocytes pickup (28.0 versus 22.5%, P ¼ 0.002) and cumulative live birth rate/woman (41.7 versus 36.6%, P ¼ 0.04) were all higher in the eSET period than in the DET period. The cumulative multiple birth rate was significantly lower in the eSET period than in the DET period (8.9 versus 19.6%, P , 0.0001). A term live birth in the eSET period was 19 889 euros less expensive than in the DET period. conclusions: This study shows that eSET with cryopreservation is more effective and less expensive than DET and should be adopted as a treatment of choice.
We evaluated the clinical usefulness of the squamous cell carcinoma antigen (SCC) and CA 125, ser... more We evaluated the clinical usefulness of the squamous cell carcinoma antigen (SCC) and CA 125, serum markers of epithelial cancer cells, in comparison with the serum concentration and tissue distribution of the aminoterminal propeptide of type III procollagen (PIIINP), a marker of connective tissue metabolism, in 31 patients with vulvar carcinoma. The SCC concentration was increased in 42%, that of CA 125 in 14% and that of PIIINP in 36% of the cases. The combination of SCC and PIIINP increased the detection rate to 57% and that of all three to 64%. None of the tumor markers correlated with the clinical stage of the disease. The initial values of the serum markers did not discriminate between different patterns of the clinical behavior of the disease. Six patients were followed with serial determinations of the markers. In each case at least one of the markers correlated with the clinical course of the disease. SCC did so in 5 cases, PIIINP in 3 cases and CA 125 in 2 cases. The mean concentrations of SCC and CA 125, but not that of PIIINP, were significantly lower during the periods of response to therapy than during the nonresponsive periods. Immunohistochemistry of PIIINP showed vulvar carcinoma to be associated with a distinct collagenous stroma. In the junctional area of the stroma around the malignant epithelium, the PIIINP positive fibers grew more sparse and irregular with decreasing differentiation of the tumor. The present data suggest that SCC, CA 125 and PIIINP are useful, especially SCC, in monitoring the clinical behaviour of the advanced vulvar cancer, less so in predicting its prognosis.
Objective: To compare the reproductive outcome of three protocols for frozen ET treatment. Design... more Objective: To compare the reproductive outcome of three protocols for frozen ET treatment. Design: Retrospective follow-up study. Setting: Two public clinics and one private clinic. Patient(s): Four thousand four hundred seventy frozen ET cycles between 2006 and 2010. Intervention(s): Thawing of embryos and ET. Main Outcome Measure(s): Pregnancy test rate, clinical pregnancy rate, and pregnancy loss rate. Result(s): The natural cycle followed by P (NC þ P) was used in 26% of cycles, the natural cycle with hCG (NC þ hCG) in 10%, and the substituted cycle with estrogen and P (E þ P) in 64% of cycles. The rate of transfers after thawing was similar in all groups (87.2%, 73.9%, and 87.2%, respectively). There was a significantly higher positive pregnancy test rate in the E þ P (34.3%) and NC þ hCG (35.5%) cycles as compared with the NC þ P cycles (26.7%). However, the clinical pregnancy rate was similar in all groups (27.7%, 29.1%, and 24.3%, respectively). Moreover, no differences were seen between groups regarding the live-birth rate (20.1%, 23.5%, and 20.7%, respectively). A logistic regression analysis showed that the type of protocol was the only predictor of pregnancy loss, while age, irregular cycles, endometrial thickness, number, and quality of embryos transferred did not correlate to pregnancy loss. Conclusion(s): A higher positive pregnancy test rate was obtained in E þ P frozen ET cycles in comparison with other protocols; however, due to an increased preclinical and clinical pregnancy loss, comparable clinical pregnancy, and delivery rates are reported for the three protocols. (Fertil Steril Ò 2012;98:1165-9. Ó2012 by American Society for Reproductive Medicine.
BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recogniz... more BACKGROUND: The role of embryo transfer as regards the success of IVF/ICSI treatments is recognized but has not been comprehensively evaluated. In order to determine its importance, the degree of difficulty of 4807 embryo transfers after IVF/ICSI was analysed retrospectively. METHODS: Logistic regression analysis identified the age of the subject, type of treatment (IVF versus ICSI), number of embryos transferred and degree of difficulty of embryo transfer as independent factors predicting pregnancy. The main focus of the study was to evaluate the importance of the difficulty of embryo transfer after taking into account the other confounding variables. RESULTS: Embryo transfer was classified as easy (2821), intermediate (1644) or difficult (342). The transfer was considered difficult if it was time consuming, the catheter met great resistance, there was a need to change the catheter, if sounding or cervical dilatation was needed or if blood was found in any part of the catheter. Easy or intermediate transfers resulted in a 1.7-fold higher pregnancy rate than difficult transfers (P < 0.0001; 95% confidence interval: 1.3-2.2). CONCLUSIONS: This study demonstrates that the degree of difficulty of embryo transfer is an independent factor as regards achieving pregnancy after IVF/ICSI. All efforts should be made to avoid difficult embryo transfers. Physicians should be alert to the factors associated with embryo transfer and should be instructed to use a stepwise approach in difficult transfers.
The age of the patient alone is a weak predictor of the ovarian reserve and responsiveness to IVF... more The age of the patient alone is a weak predictor of the ovarian reserve and responsiveness to IVF stimulation (Check Hannu Martikainen 1 et al., 1994). There are women aged Ͼ40 years who are able for the first time. All patients had both ovaries present. The main indications for treatment were tubal factor (n ϭ 65), male factor (n ϭ or age alone. Patients can be identified with inactive ovaries 40), endometriosis (n ϭ 16), ovulatory dysfunction (n ϭ 11), and which will have a poor response to IVF treatment, a key unexplained infertility (n ϭ 34).
During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronu... more During IVF treatments, normal fertilization is generally evidenced by the appearance of two pronuclei, one arising from the oocyte and the other from the male gamete. Embryos derived from zygotes with a pronuclei number other than two are assumed to possess a ploidy abnormality and their transfer is usually avoided owing to increased risk of implantation failure, miscarriage, and molar pregnancies. Nonetheless, the inclusion of genotyping data in preimplantation genetic testing has revealed that a normal diploid configuration is possible in embryos deriving from zygotes with an abnormal pronuclei number such as tripronuclear and one pronucleus. Here, we present a one-of-a-kind transfer of a tetrapronuclear-derived embryo that was discovered to be diploid and negative for other whole chromosome or segmental aneuploidies during preimplantation genetic testing using a targeted next-generation sequencing approach. The transfer resulted in the live birth of a healthy infant who is now 4 ...
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