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Biomedical subjects

Andre Van Steirteghem

Publications and source records attributed to Andre Van Steirteghem.

At least 19 recordsLinked to original sources
PubMed2006

Preimplantation genetic diagnosis for Marfan syndrome.

OBJECTIVE: To develop and apply efficient and reliable protocols for preimplantation genetic diagnosis (PGD) for Marfan syndrome. DESIGN: Two mutation-specific protocols were developed, and the markers D15S1028, D15S992, D15S196, D15S576, D15S123, and D15S143 were used to set up four multiplex polymerase chain reactions (PCRs). SETTING: Research Center Reproduction and Genetics. PATIENT(S): Ten couples carrying mutations in the FBN1 gene. INTERVENTION(S): Six PGD protocols were developed for 10 couples, and 7 of them underwent a total of 16 clinical cycles. MAIN OUTCOME MEASURE(S): Amplification, allele drop-out (ADO), and contamination rates during the preclinical assays. DNA analyses of blastomeres from embryos biopsied during PGD cycles. RESULT(S): Six different protocols were set up, with the main objective being to to use one protocol for several couples. A total of 16 PGD cycles were performed, which resulted in the delivery of an unaffected boy and three ongoing pregnancies. CONCLUSION(S): The development of single-cell multiplex PCRs for linked markers and its use in PGD reduce the workload of the genetic diagnostic laboratory as well as the average waiting time for patients. This approach also allows for the simultaneous and accurate detection of recombination, contamination, and ADO, thereby increasing the reliability of the diagnosis.

Adult↗
PubMed2006

Single-cell chromosomal imbalances detection by array CGH.

Genomic imbalances are a major cause of constitutional and acquired disorders. Therefore, aneuploidy screening has become the cornerstone of preimplantation, prenatal and postnatal genetic diagnosis, as well as a routine aspect of the diagnostic workup of many acquired disorders. Recently, array comparative genomic hybridization (array CGH) has been introduced as a rapid and high-resolution method for the detection of both benign and disease-causing genomic copy-number variations. Until now, array CGH has been performed using a significant quantity of DNA derived from a pool of cells. Here, we present an array CGH method that accurately detects chromosomal imbalances from a single lymphoblast, fibroblast and blastomere within a single day. Trisomy 13, 18, 21 and monosomy X, as well as normal ploidy levels of all other chromosomes, were accurately determined from single fibroblasts. Moreover, we showed that a segmental deletion as small as 34 Mb could be detected. Finally, we demonstrated the possibility to detect aneuploidies in single blastomeres derived from preimplantation embryos. This technique offers new possibilities for genetic analysis of single cells in general and opens the route towards aneuploidy screening and detection of unbalanced translocations in preimplantation embryos in particular.

Aneuploidy↗
PubMed2006

Spuriously elevated serum estradiol concentrations measured by an automated immunoassay rarely cause unnecessary cancellation of in vitro fertilization cycles.

OBJECTIVE: To report a case of a patient in whom serum E2, as measured by an automated E2 assay, remained elevated at levels corresponding to the periovulatory phase (>380 pg/mL), despite 3 weeks of treatment by a GnRH agonist (GnRH-a). DESIGN: Case report. SETTING: Tertiary-care academic center. PATIENT(S): A 39-year-old patient accepted for IVF treatment. In view of controlled ovarian hyperstimulation, down-regulation by a GnRH-a was monitored by serum E2 measurement. INTERVENTION(S): Obvious causes for high serum E2 levels (pregnancy, E2-producing ovarian cysts, and noncompliance of the patient) were excluded. The IVF cycle was canceled. MAIN OUTCOME MEASURE(S): Serum samples were analyzed retrospectively by radioimmunoassay (RIA), and ether extraction of the samples was performed before measurement by the automated E2 assay. RESULT(S): Radioimmunoassay revealed adequately suppressed serum E2 levels under GnRH-a treatment (<15 pg/mL). Ether extraction revealed an interfering component that was soluble in the aqueous phase. CONCLUSION(S): If a patient on a long controlled ovarian hyperstimulation IVF protocol still has high serum E2 levels after 2 to 3 weeks of down-regulation, and obvious reasons for this (pregnancy, E2 producing ovarian cysts, noncompliance of the patient) are excluded, E2 immunoassay interference should be excluded to avoid unnecessary cancellation of the IVF cycle.

Adult↗
PubMed2006

In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos.

BACKGROUND: Single-embryo transfer has been recommended to reduce the incidence of multiple gestations when in vitro fertilization is performed in women under 36 years of age. We designed a prospective, randomized, controlled trial to determine whether there were any differences in the rates of pregnancy and delivery between women undergoing transfer of a single cleavage-stage (day 3) embryo and those undergoing transfer of a single blastocyst-stage (day 5) embryo. METHODS: We studied 351 infertile women under 36 years of age who were randomly assigned to undergo transfer of either a single cleavage-stage embryo (176 patients) or a single blastocyst-stage embryo (175 patients). Multifollicular ovarian stimulation was performed with a gonadotropin-releasing hormone antagonist and recombinant follicle-stimulating hormone. RESULTS: The study was terminated early after a prespecified interim analysis (which included 50 percent of the planned number of patients) found a higher rate of pregnancy among women undergoing transfer of a single blastocyst-stage embryo (P=0.02). The rate of delivery was also significantly higher in this group than in the group undergoing transfer of a single cleavage-stage embryo (32.0 percent vs. 21.6 percent; relative risk, 1.48; 95 percent confidence interval, 1.04 to 2.11). Two multiple births occurred, both of monozygotic twins, both of which were in the group undergoing transfer of a single cleavage-stage embryo. CONCLUSIONS: These findings support the transfer of a single blastocyst-stage (day 5) embryo in infertile women under 36 years of age.

Adult↗
PubMed2006

Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.

OBJECTIVE: To determine the incidence of ovarian hyperstimulation syndrome (OHSS) in a large series of GnRH antagonist-stimulated cycles and to assess the predictive value of E2 and the number of follicles on the day of hCG administration. DESIGN: Prospective cohort study of women undergoing IVF treatment with a GnRH antagonist protocol over a 2-year period. SETTING: Tertiary university hospital. PATIENT(S): One thousand eight hundred one patients who underwent 2,524 cycles. INTERVENTION(S): Multifollicular ovarian stimulation with recombinant FSH and GnRH antagonist for IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Incidence of OHSS in GnRH antagonist cycles, predictive value of E2, and number of follicles on the day of hCG for OHSS occurrence. RESULT(S): Fifty-three patients were hospitalized because of OHSS (2.1%; 95% confidence interval [CI]:1.6-2.8). Early OHSS presented in 31 patients (1.2%; 95% CI: 0.9-1.8), whereas the late type was a complication in 22 patients (0.9%; 95% CI: 0.5-1.3). Late OHSS cases compared with the early OHSS cases always occurred in a pregnancy cycle (100% vs. 40%); had higher probability of being severe (72.7% vs. 42%), and more often were related to a multiple pregnancy (40% vs. 0). Receiver operating characteristic curve analysis for several E2 concentrations and number of follicles with a diameter of > or =11 mm revealed that the predictive value of the optimal threshold of > or =13 follicles (85.5% sensitivity; 69% specificity) was statistically significantly superior to the optimal threshold of 2,560 ng/L for E2 concentrations (53% sensitivity, 77% specificity) in identifying patients at risk for OHSS. Considering that severe OHSS represents the most clinically significant pattern, the combination of a threshold of > or =18 follicles and/or E2 of > or =5,000 ng/L yields a 83% sensitivity rate with a specificity as high as 84% for the severe OHSS cases. CONCLUSION(S): Clinically significant OHSS still remains a limitation of multifollicular ovarian stimulation for IVF even with the use of GnRH antagonist protocols. The number of follicles can discriminate the patients who are at risk for developing OHSS, whereas E2 concentrations are less reliable for the purpose of prediction. There is more than ever an urgent need for alternative final oocyte maturation-triggering medication.

Adult↗
PubMed2006

Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study.

This prospective randomized pilot study was aimed at investigating the effect of the novel addition of aromatase inhibitors to an ovarian stimulation protocol for IVF or intracytoplasmic sperm injection, on endocrine parameters including serum androgen, oestrogen, progesterone, LH and FSH concentrations. The patients were randomized to receiving letrozole (group A; n = 10), versus no letrozole (group B; n = 10) in an ovarian stimulation protocol with recombinant FSH 150 IU/day starting on day 2 of the cycle, and gonadotrophin-releasing hormone antagonist 0.25 mg/day starting on day 6 of the cycle. Median LH concentrations were significantly higher (P < 0.01) in group A versus group B during letrozole administration. Median serum oestradiol concentrations were lower in group A versus group B, and median serum FSH, testosterone and androstenedione concentrations were higher in group A versus group B, throughout the follicular phase, without reaching significance. Median endometrial thickness was significantly higher (P < 0.05) in group A versus group B on the day of human chorionic gonadotrophin administration. Pregnancies were achieved. This pilot study supports the idea that aromatase inhibitors can contribute to normal potential of implantation and follicular response, without having negative anti-oestrogenic effects.

Adult↗
PubMed2006

Early pregnancy loss is significantly higher after day 3 single embryo transfer than after day 5 single blastocyst transfer in GnRH antagonist stimulated IVF cycles.

The current study aimed to investigate whether single day-3 embryo transfer (SET) results in higher early pregnancy loss (EPL) than single blastocyst transfer (SBET). A total of 896 patients underwent 1103 IVF cycles with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. In 603 cycles (D3 group) a single embryo on day 3 of the embryo culture was transferred, whereas in the remaining 500 cycles a single blastocyst was transferred on day 5 (D5 group). Multifollicular ovarian stimulation was performed with a GnRH antagonist protocol starting on day 6. SET resulted in 209 pregnancies (34.7%), compared with 221 pregnancies (44.2%) for SBET. Early pregnancy loss rate was significantly higher with SET compared with SBET (26.8% versus 17.2%, P = 0.017) and ongoing implantation rate was also significantly higher with day 5 compared with day-3 embryo transfer (OR:1.68, 95% confidence interval:1.31-2.18). Sub-optimal embryo selection for transfer on day 3, in addition to asynchronization between altered endometrium and early exposure of cleavage-stage embryos, might explain the above difference. Nevertheless, the higher implantation potential of the blastocyst questions the rationale behind performing single embryo transfer on day 3 of embryo culture in women under 36 years old.

Adult↗
PubMed2005

Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study.

INTRODUCTION: In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3. METHODS: Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group. RESULTS: Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05). CONCLUSIONS: A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.

Adult↗
PubMed2005

Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages.

OBJECTIVE: To determine the aneuploidy rate in embryos of women with idiopathic recurrent miscarriages and to evaluate whether preimplantation genetic diagnosis for aneuploidy screening could be a feasible approach to improve the possibility of successful pregnancy in these couples. DESIGN: Prospective cohort study. SETTING: Tertiary university referral center. PATIENT(S): Women (n = 49) with recurrent idiopathic miscarriages. INTERVENTION(S): In vitro fertilization with preimplantation genetic diagnosis for aneuploidy screening. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate (PR) and aneuploidy rate. RESULT(S): The aneuploidy rate was, respectively, 43.85% and 66.95% in the younger and older group. The ongoing PR per cycle was 25.71% in the younger and 2.94% in the older patients. CONCLUSION(S): There is no therapeutic evidence to prescribe IVF with or without preimplantation genetic diagnosis for aneuploidy screening for this heterogeneous group of patients.

Abortion, Habitual↗
PubMed2005

Preimplantation genetic diagnosis for aneuploidy screening in women older than 37 years.

OBJECTIVE: To provide background information about the average aneuploidy and implantation rates of older patients after IVF with preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) when the patients are subdivided into age categories; and to compare pregnancy outcome data after PGD-AS in this group of patients with a similar control group. DESIGN: Retrospective clinical study. SETTING: Patients in an academic reproductive medicine unit. PATIENT(S): All patients 37 years or older who had PGD-AS between October 1999 and December 2003 and all pregnant patients 37 years or older who had IVF/intracytoplasmic sperm injection without PGD-AS during the same period of time. INTERVENTION(S): IVF with PGD-AS. MAIN OUTCOME MEASURE(S): Aneuploidy rate, miscarriage rate, live birth rate, implantation rate, multiple pregnancy rate, and prenatal testing. RESULT(S): Three hundred ninety-four PGD-AS cycles of patients between 37 and 46 years of age were analyzed. The aneuploidy rate gradually increased with age. The implantation rate remained similar over all age groups. There was a trend to a lower miscarriage and multiple pregnancy rate in the PGD-AS group and a higher delivery/live birth rate. There were five elective terminations of pregnancy after prenatal testing and three late miscarriages due to prenatal testing in the control group. CONCLUSION(S): Preimplantation genetic diagnosis for aneuploidy screening can give valuable information to older patients concerning the reason why their IVF cycles are unsuccessful and whether it is worthwhile to continue IVF treatment, and it can help patients to avoid the emotional trauma that can occur after prenatal testing during the second trimester of pregnancy.

Adult↗
PubMed2004

Early and late ovarian hyperstimulation syndrome: early pregnancy outcome and profile.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in IVF/ICSI cycles may occur either as an early (early onset) or a late pattern (late onset). This observational study was designed to identify whether the onset pattern of OHSS is associated with the occurrence of pregnancy and the early pregnancy outcome. METHODS: Among 4376 consecutive IVF/ICSI cycles, 113 patients were hospitalized for OHSS after IVF/ICSI treatment and were included in the study. The setting was the Dutch-speaking Brussels Free University Hospital, between June 2000 and September 2002. RESULTS: Early OHSS occurred in 53 patients, and late OHSS complicated 60 patients. A total of 96.7% of the late OHSS cases occurred in a pregnancy cycle and were more likely to be severe than the early cases (P < 0.05). Although in the early group there initially was a 41.5% positive HCG rate per cycle, the clinical pregnancy rate fell to 28.3% as a result of a significantly (P < 0.05) increased preclinical pregnancy loss rate compared with the non-OHSS patients (31.8 versus 88.3%, respectively). The ongoing pregnancy rate per cycle was 14.4% in the early and 26.4% in the late group. Multiple pregnancy rates were high in both groups (40 and 45.5%, respectively), but only in the late group did the incidence reach significance compared with the non-OHSS population (45.5 versus 29.1%, P = 0.02). Estradiol levels and number of follicles on the day of HCG were significantly higher in the early OHSS group. However, there was no difference in estradiol values on the day of hospital admittance between the two groups. In addition, the number of follicles on the day of HCG administration appears to be a better prognostic indicator for the occurrence of severe OHSS than the estradiol values (87% of the severe cases had > or = 14 or follicles of a diameter > or = 11 mm, whereas only 50% of them had an estradiol value > or = 3000 ng/l). CONCLUSIONS: The early OHSS pattern is associated with exogenously administered HCG and a higher risk of preclinical miscarriage, whereas late OHSS may be closely associated with the conception cycles, especially multiple pregnancies, and is more likely to be severe. Further clarification of these two different clinical entities could have implications for research protocols as well as for preventive and management strategies for OHSS.

Abortion, Spontaneous↗
PubMed2004

Cumulative live birth rates after transfer of cryopreserved ICSI embryos.

A cohort follow-up study was designed to assess the efficacy of an intracytoplasmic sperm injection cryopreservation programme through analysis of cumulative live birth rates in successive frozen-thawed cycles in a tertiary referral centre. There were 2013 patients and they underwent 2680 frozen-thawed embryo transfer cycles. The follow-up period was between 1992 and 2001. Only frozen-thawed embryo transfer cycles up to the fourth trial were included. Crude cumulative live birth rates were calculated in five age subgroups, i.e. <30, 30-34, 35-37, 38-39 and >/=40 years old and in surgically or non-surgically retrieved sperm subgroups. Expected cumulative live birth rates were calculated only for the total number of patients. Outcome measure was a live birth occurring after 25 weeks of gestation. Overall, the expected cumulative live birth rate was as high as 26.7% after four cycles while the crude cumulative delivery rate was 10.5%. Multiple cryopreserved embryo transfer cycles increase the chance of a couple to achieve a live birth.

Adult↗
PubMed2004

Quintuplet pregnancy following transfer of two blastocysts: Case report.

A 36-year-old single woman presented at the out-patient clinic in March 2000 requesting donor insemination. Between May 2000 and May 2001 she underwent six cycles of intrauterine insemination with donor sperm after clomiphene citrate stimulation without achieving a pregnancy. In January 2002, ICSI was performed; two embryos were transferred on day 3 and a dizygotic bichorionic pregnancy was achieved, which ended in a miscarriage at 21 weeks of gestation. After a second unsuccessful ICSI attempt in which a single embryo transfer was performed, she embarked upon her third attempt in March 2003 at 39 years of age. Two blastocysts were transferred after ICSI, resulting in a quintuplet gestation consisting of a monochorionic biamniotic pregnancy and a monochorionic triamniotic pregnancy. The current case report indicates that monozygotic pregnancies consisting of both twins and triplets are possible after treatment by assisted reproductive technologies. An association between extended culture, manipulation of the zona pellucida, ovarian stimulation and occurrence of monozygotic pregnancies has been suggested by retrospective studies. However, in order to identify more reliably predictive factors for the occurrence of monozygotic pregnancies, it is necessary to perform prospective trials.

Abortion, Spontaneous↗
PubMed2003

Outcome for donors and recipients in two egg-sharing policies.

OBJECTIVE: To assess the effect of two different donation policies on results of egg-sharing. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): One hundred five donor-recipient pairs participating in an egg-sharing program between 1998 and 2001. INTERVENTION(S): Egg-sharing was performed according to policy A (retrieval of at least 12 oocytes, with more oocytes allocated to the donor) or policy B (retrieval of at least 8 oocytes, with equal distribution of oocytes between donors and recipients). MAIN OUTCOME MEASURE(S): Delivery rate and cycle cancellation rate. RESULT(S): Policy B resulted in a decreased cycle cancellation rate in the recipient group compared with policy A (9.7% vs. 29.7%, respectively; P<or=.01). No significant difference in delivery rate per fresh transfer was observed between policy A and policy B in donors (30.2% vs. 27.8%, respectively) or recipients (28.2% vs. 25.7%, respectively). CONCLUSION(S): Decreasing the number of oocytes required to perform egg sharing from 12 to 8 and dividing the oocytes equally between donors and recipients significantly reduces the cycle cancellation rate while it does not appear to affect adversely the probability of delivery.

Adult↗
PubMed2003

Prenatal genetic testing by amniocentesis appears to result in a lower risk of fetal loss than chorionic villus sampling in singleton pregnancies achieved by intracytoplasmic sperm injection.

OBJECTIVE: To compare pregnancy outcome after prenatal genetic testing by chorionic villus sampling (CVS) or amniocentesis in singleton pregnancies achieved by intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Eight hundred twenty-eight patients with singleton gestations achieved by ICSI. INTERVENTION(S): Midtrimester amniocentesis (685 patients) and first-trimester CVS (143 patients). MAIN OUTCOME MEASURE(S): Fetal loss rate, preterm delivery rate, and proportion of babies born with low or very low birth weight. RESULT(S): A significant difference was observed in fetal loss rate between CVS and amniocentesis (3.7% vs. 0.9%, respectively). On the other hand, a similar preterm delivery rate was present between the two methods (11.2% vs. 12.4%, respectively). No significant difference was observed between amniocentesis and CVS in the proportion of babies with birth weight of either <1,500 g (1.8% vs. 3.8%, respectively) or between 1,500 and 2,500 g (8.2% vs. 4.6%, respectively). CONCLUSION(S): Amniocentesis appears to result in a lower risk of fetal loss as compared with CVS in patients with a singleton pregnancy achieved by ICSI.

Abortion, Spontaneous↗
PubMed2003

Reproductive outcome of polycystic ovarian syndrome patients treated with GnRH antagonists and recombinant FSH for IVF/ICSI.

The purpose of this prospective study was to assess the reproductive outcome of patients with polycystic ovarian syndrome (PCOS) treated by in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with recombinant FSH (rFSH) and gonadotrophin releasing hormone (GnRH) antagonists. One hundred and ten patients were evaluated. The starting dose of rFSH was 100 IU in 67 women with body mass index (BMI) </=29 kg/m(2) and 200 IU in 43 women with BMI >29 kg/m(2). GnRH antagonist was started by the detection of a follicle of a 15mm in ultrasound scan. A significantly lower ongoing pregnancy rate per oocyte retrieval (25.6% versus 46.7%, P = 0.04) and a higher occurrence of ovarian hyperstimulation syndrome (16.3% versus 3.0%, P = 0.03) was observed in the group of patients with BMI >29 kg/m(2) as compared with the group of patients with BMI </=29 kg/m(2), respectively. In conclusion, in GnRH antagonist cycles a worse reproductive outcome is expected in PCOS patients with BMI >29 kg/m(2) in whom stimulation is initiated with 200 IU of rFSH as compared with PCOS patients with BMI </=29 kg/m(2) in whom stimulation is initiated with 100 IU of rFSH.

Adult↗