Biomedical subjects

Paul Devroey

Publications and source records attributed to Paul Devroey.

At least 91 records · Page 5Linked to original sources

PubMed2002

Effect of repeated assisted reproductive technology cycles on ovarian response.

OBJECTIVE: To assess the effect of repeated assisted reproductive technology (ART) cycles on the ovarian response in patients treated with human menopausal gonadotropins and GnRH agonists. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Three thousand two hundred forty-nine patients who had completed at least two in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles (minimum two, maximum six cycles per patient). INTERVENTION(S): Nine thousand three hundred seventy-nine repeated IVF/ICSI cycles. MAIN OUTCOME MEASURE(S): Mean number of cumulus oocyte complexes (COC) retrieved per cycle, mean number of ampules used per attempt. RESULT(S): Repeated ART cycles did not exert a significant effect on the mean number of COC retrieved per attempt in contrast to maternal age, which was inversely related to the mean number of COC retrieved in all cycles performed. Across repeated ART attempts, an increase in the mean number of ampules used per cycle was observed. This was due to an effect of maternal age, which increased in line with the mean number of ampules used per cycle, as well as to an age-independent effect of repeated cycles. CONCLUSION(S): An age-independent deterioration of the ovarian response appears to occur across repeated ART cycles.

Adult↗

PubMed2002

Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome.

OBJECTIVE: To investigate the endometrial steroid receptors and proliferation index in GnRH analogue/hMG-stimulated cycles in comparison with natural cycles and their relation to clinical pregnancy outcome. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Twenty-seven stimulated patients with GnRH agonist and hMG. Twenty normo-ovulatory patients were the natural cycle controls. INTERVENTION(S): Endometrial aspiration biopsies: in stimulated cycles on the day of oocyte retrieval within the ET cycle (Day OPU) (n = 20) or 2 days later (Day OPU + 2) (n = 7); in natural cycles on the natural day of ovulation (Day NO) (n = 10) or on the day of ovulation + 2 (Day NO + 2) (n = 10). MAIN OUTCOME MEASURE(S): Comparison of endometrial maturation, estrogen (ER) and P receptor (PR), and proliferation index by immunohistochemistry in natural and stimulated cycles, correlation with pregnancy outcome in stimulated cycles. RESULT(S): Stimulated cycles Day OPU showed significantly advanced endometrial maturation compared to natural cycles Day NO; stromal ER and glandular and stromal PR staining was lower in stimulated than in natural cycles, but higher on Day OPU than on Day NO + 2; proliferation index was lower in all stimulated cycles. Steroid receptors and proliferation index in stimulated cycles were unrelated to clinical pregnancy occurrence. CONCLUSION(S): Compared to natural cycles, ovarian stimulation induced an imbalance in endometrial ER and PR and led to a profound antimitotic effect in the peri-ovulatory phase. These parameters were, however, not predictive of clinical pregnancy in cycles with ET.

Adult↗

PubMed2002

Spontaneous pregnancies in couples who discontinued intracytoplasmic sperm injection treatment: a 5-year follow-up study.

OBJECTIVE: To analyze the occurrence of deliveries after spontaneous conception in patients who have discontinued unsuccessful intracytoplasmic sperm injection (ICSI) treatment. DESIGN: Cohort follow-up study. SETTING: Tertiary referral center. PATIENT(S): Between July 1992 and December 1993, 200 Belgian women younger than 37 years underwent 433 consecutive unsuccessful ICSI cycles with freshly ejaculated sperm and eventually discontinued their treatment. INTERVENTION(S): Ultrasound-guided oocyte retrieval and ICSI. MAIN OUTCOME MEASURE(S): Delivery after 25 weeks following a spontaneous pregnancy. RESULT(S): The mean age at the time of the last oocyte pick-up was 31.0 +/- 3.9 years. The mean time interval between the last ICSI and the end of the follow-up period was 47.7 +/- 12.1 months. Twenty-three spontaneous pregnancies ending in delivery after 25 weeks were observed (11.5%). The cumulative delivery rate reached a plateau of 10% after 36 months of follow-up. The mean time interval (from last oocyte retrieval) for spontaneous pregnancy to occur after discontinuing ICSI treatment was 20.2 +/- 13.7 months. Proportional hazards analysis showed that delivery rate was reduced by 2.0% per year of infertility. CONCLUSION(S): This study suggests that duration of infertility appears to be predictive of the likelihood of live delivery after spontaneous conception following an unsuccessful ICSI treatment.

Adult↗

PubMed2002

Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up.

OBJECTIVE: To assess the effect of ovarian stimulation with recombinant FSH, GnRH antagonists, and hCG on endometrial maturation on the day of oocyte pick-up. DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENT(S): Fifty-five women undergoing controlled ovarian hyperstimulation for IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S): [1] Ovarian stimulation with recombinant FSH, starting on day 2 of the cycle and GnRH antagonist, starting after a median of 6 days of recombinant FSH stimulation (range, 5-12 days); [2] hCG administration for ovulation induction; and [3] aspirational biopsy of endometrium at oocyte pick-up. MAIN OUTCOME MEASURE(S): Endometrial histology at oocyte pick-up by Noyes criteria. RESULT(S): Advancement of endometrial maturation (2.5 +/- 0.1 days) as compared to the expected chronological date was observed in all antagonist cycles at oocyte retrieval. Endometrial advancement at oocyte pick-up increased in line with values of LH at initiation of stimulation and the duration of recombinant FSH treatment before the antagonist was started. CONCLUSION(S): The higher the values of LH at initiation of stimulation and the longer the duration of recombinant FSH treatment before the antagonist is started, the more advanced the endometrial maturation at oocyte pick-up.

Adult↗

PubMed2002

Intracytoplasmic sperm injection versus in vitro fertilization: a randomized controlled trial and a meta-analysis of the literature.

OBJECTIVE: To compare ICSI with IVF using two insemination concentrations in moderate male infertility and to compare these data with other randomized controlled trials (RCTs). DESIGN: Prospective, randomized, controlled trial and meta-analysis. SETTING: University-based tertiary referral center. PATIENT(S): Seventy-three couples undergoing ART. INTERVENTION(S): In one IVF group a standard insemination concentration of 0.2 x 10(6)/mL was used, whereas in the other group a high insemination concentration (HIC) of 0.8 x 10(6)/mL was used. Each protocol was compared with ICSI on sibling oocytes. MAIN OUTCOME MEASURE(S): Fertilization, fertilization failure, and embryonic development. RESULT(S): The overall fertilization rate was significantly lower after standard IVF than after ICSI: 37.4% vs. 64.3%. Where HIC IVF was used, the overall fertilization rate was not significantly different from that after ICSI: 59.6% vs. 67.6%. Eight randomized controlled trials were selected and reviewed together with the present randomized controlled trial by meta-analysis. The risk ratio for an oocyte to become fertilized was 1.9 (95% confidence interval of 1.4 to 2.5) in favor of ICSI, and 3.1 ICSI cycles may be needed to avoid one complete fertilization failure after conventional IVF (95% CI of 1.7 to 12.4). CONCLUSION(S): The data from this study and the meta-analysis show that ICSI is a more efficient technique in terms of fertilization, but not in comparison with HIC IVF.

Adult↗

PubMed2002

The luteal phase after ovarian stimulation.

Evaluation of the luteal phase after ovarian stimulation presents several difficulties. Until today, it has not been proved that in cycles stimulated with clomiphene citrate/human menopausal gonadotrophins, luteal supplementation with progesterone significantly increases implantation rate. On the contrary, it is accepted that in cycles stimulated with GnRH agonists/gonadotrophins, support of the luteal phase is essential for the achievement of pregnancy. In GnRH antagonist cycles luteal supplementation, although widely practised, is not at present supported by randomized controlled trials. Finally, it appears that the combination of gonadotrophin stimulation with human chorionic gonadotrophin results in an inadequate luteal phase with or without the use of either agonists or antagonists.

Clomiphene↗

PubMed2002

Preimplantation genetic diagnosis for Huntington's disease with exclusion testing.

Huntington's disease is an autosomal dominant, late-onset disorder, for which the gene and the causative mutation have been known since 1993. Some at-risk patients choose for presymptomatic testing and can make reproductive choices accordingly. Others however, prefer not to know their carrier status, but may still wish to prevent the birth of a carrier child. For these patients, exclusion testing after prenatal sampling has been an option for many years. A disadvantage of this test is that unaffected pregnancies may be terminated if the parent at risk (50%) has not inherited the grandparental Huntington gene, leading to serious moral and ethical objections. As an alternative, preimplantation genetic diagnosis (PGD) on embryos obtained in vitro may be proposed, after which only embryos free of risk are replaced. Embryos can then be selected, either by the amplification of the CAG repeat in the embryos without communicating results to the patients (ie non-disclosure testing), which brings its own practical and moral problems, or exclusion testing. We describe here the first PGD cycles for exclusion testing for Huntington's disease in five couples. Three couples have had at least one PGD cycle so far. One pregnancy ensued and a healthy female baby was delivered.

Female↗

PubMed2002

Children born after assisted reproductive technology.

Since the birth of Louise Brown in July 1978 and the birth of the first intracytoplasmic sperm injection (ICSI) child in January 1992 many couples with longstanding female-factor or male-factor infertility can be helped to overcome their infertility resulting in a delivery and birth of a child. The final and ultimate goal of all infertility treatments has been to give the large population of infertile couples a chance to fulfil their childwish and experience the happiness of having a healthy child. Major advances have been made in the different treatment protocols for infertility during the last 25 years. It is, however, surprising that only a limited number of studies have been carried out assessing the health of the children born after ART. In this review we shall comment on the limitations of follow-up studies on ART children and we shall review existing data on the outcome of in vitro fertilization (IVF) and ICSI pregnancies. The most important outcome data consist of information on minor and major congenital malformations obtained prenatally or after birth, as well as on the further development of the children.

Chromosome Aberrations↗

PubMed2002

Thyroid dysfunction and autoimmunity in infertile women.

A prospective study was undertaken in 438 women (ages, 32 +/- 5 years) with various causes of infertility, and in 100 age-matched (33 +/- 5 years) healthy parous controls with the aim of assessing the prevalence of autoimmune thyroid disease (AITD) and hitherto undisclosed alterations of thyroid function. Female origin of the infertility was diagnosed in 45% of the couples, with specific causes including endometriosis (11%), tubal disease (30%), and ovarian dysfunction (59%). Male infertility represented 38% and idiopathic infertility 17% of the couples. Overall, median thyrotropin (TSH) was significantly higher in patients with infertility compared to controls: 1.3 (0.9) versus 1.1 (0.8) mIU/L. Serum TSH above normal (>4.2 mIU/L) or suppressed TSH (<0.27 mIU/L) levels were not more prevalent in the infertile women than in controls. The prevalence of positive thyroid peroxidase antibody (TPO-Ab) was higher in all investigated women of infertile couples, compared to controls (14% vs. 8%), but the difference was not significant. However, in infertility of female origin, a significant higher prevalence of positive TPO-Ab was present, compared to controls: 18% versus 8%. Furthermore, among the female causes, the highest prevalence of positive antibodies was observed in women with endometriosis (29%). When thyroid antibodies were positive, both hypothyroidism and hyperthyroidism were more frequent in all women of infertile couples and in the women with a female infertility cause, compared to women in the same groups but without positive TPO-Ab. The present study shows that in infertile women, thyroid autoimmunity features are significantly more frequent than in healthy fertile controls and this was especially the case for the endometriosis subgroup.

Adult↗

PubMed2002

Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters.

BACKGROUND: Prenatal testing was offered in all pregnancies obtained after ICSI with ejaculated or non-ejaculated sperm as part of the evaluation of the safety of ICSI. METHODS: Between 1990 and 2001, a chorionic villus sampling (CVS) or amniocentesis was offered for multiple or singleton pregnancies respectively during a genetic counselling session for all couples applying for ICSI. ICSI was carried out using ejaculated, epididymal or testicular sperm. RESULTS: In total, 1586 ICSI fetuses obtained after fresh embryo transfer were tested by CVS (n = 698) or by amniocentesis (n = 888). Abnormal fetal karyotypes were found in 47 samples [3.0%; 95% confidence interval (CI) 2.2-3.9%]; 25 anomalies (1.6%; 95% CI 1.0-2.3%) were de novo. These were 10 sex chromosomal anomalies and 15 autosomal anomalies [either numerical (n = 8) or structural (n = 7)], and 22 inherited abnormalities (1.4%; 95% CI 0.9-2.1%) (21 balanced, one unbalanced). In 17/22 inherited cases the chromosomal structural defect was inherited from the father. A significantly higher percentage of 2.1% de-novo prenatal chromosomal anomalies was observed for sperm concentrations of <20x10(6) sperm per ml, as compared with 0.24% if the sperm concentration was vertical line 20x10(6) sperm per ml (Fisher's exact test, P = 0.006). No statistical difference in frequency of chromosomal anomalies was observed for lower threshold values of sperm concentration (<1x10(6), <5x10(6), <10x10(6) and <15x10(6)). A statistical difference was observed for motility criteria, but not morphology. Three chromosomal anomalies were found prenatally after use of epididymal or testicular sperm in a total of 94 samples; two (of 83 tested) were from patients with obstructive and one (of nine tested) was from a patient with non-obstructive azoospermia. CONCLUSIONS: A significantly higher rate of de-novo chromosomal anomalies (1.6 versus 0.5% in amniocentesis for a mean maternal age of 33.5 years; P < 0.007) was observed in ICSI offspring, relating mainly to a higher number of sex chromosomal anomalies and partly to a higher number of autosomal structural anomalies. This finding was related to sperm concentration and motility. The significantly higher rate of observed inherited anomalies (1.4 versus 0.3-0.4% in prenatal tests in the general population; P < 0.001) was related to a higher rate of constitutional chromosomal anomalies, mainly in the fathers. The hypothesis of a higher risk of post-zygotic events as a consequence of the ICSI procedure leading to a higher proportion of chromosomal mosaicism was not confirmed in this study. Couples should be informed of the risks of an abnormal result related to sperm quality, and of the risk linked to a prenatal procedure as well as about the relatively benign character of some chromosomal anomalies such as de-novo structural anomalies or sex chromosomal anomalies in order to be able to make a choice for prenatal testing, or not.

Adult↗

PubMed2002

Preimplantation genetic diagnosis for fragile Xa syndrome: difficult but not impossible.

BACKGROUND: In this paper, we review our clinical preimplantation genetic diagnosis (PGD) programme for fragile Xa syndrome, analysing if PGD for these couples is still a valuable option, as it is particularly difficult for two reasons. First, the couples have to be informative (the number of triplet repeats on the healthy FMR-1 allele of the mother has to be different from the number of repeats on the healthy FMR-1 allele of the father) and second, women with a premutation are at increased risk of premature ovarian failure. METHODS: A total of 34 couples attended our genetics department between December 1998 and July 2001, requesting information about PGD for fragile Xa syndrome. RESULTS: Eight couples decided not to go further with the procedure and of the 26 remaining couples, 16 were informative (61.5%). Four couples have so far not started ovarian stimulation, one patient was totally refractive to stimulation and 11 couples have had a total of 19 oocyte retrievals. From these, there have been 13 embryo transfers with a clinical pregnancy rate per embryo transfer of 23%; the implantation rate was 13.6% and the live birth rate per couple was 27.3%. CONCLUSIONS: PGD for fragile Xa is feasible for a number of couples. A pre-PGD work-up should include a determination of the premutation or mutation carrier status, the maternal or paternal origin of the premutation and an estimation of the ovarian reserve of the patient. Fragile Xa premutation carriers should be advised not to postpone reproduction for too long.

Adult↗

PubMed2002

Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983-1999).

BACKGROUND: To evaluate the safety of ICSI, this study compared data of IVF and ICSI children by collecting data on neonatal outcome and congenital malformations during pregnancy and at birth. METHODS: The follow-up study included agreement to genetic counselling and eventual prenatal diagnosis, followed by a physical examination of the children after 2 months, after 1 year and after 2 years. 2840 ICSI children (1991-1999) and 2955 IVF children (1983-1999) were liveborn after replacement of fresh embryos. ICSI was carried out using ejaculated, epididymal or testicular sperm. RESULTS: In the two cohorts, similar rates of multiple pregnancies were observed. ICSI and IVF maternal characteristics were comparable for medication taken during pregnancy, pregnancy duration and maternal educational level, whereas maternal age was higher in ICSI and a higher percentage of first pregnancies and first children born was observed in the ICSI mothers. Birthweight, number of neonatal complications, low birthweight, stillbirth rate and perinatal death rate were compared between the ICSI and the IVF groups and were similar for ICSI and IVF. Prematurity was slightly higher in the ICSI children (31.8%) than in the IVF children (29.3%). Very low birthweight was higher in the IVF pregnancies (5.7%) compared with ICSI pregnancies (4.4%). Major malformations (defined as those causing functional impairment or requiring surgical correction), were observed at birth in 3.4% of the ICSI liveborn children and in 3.8% of the IVF children (P = 0.538). Malformation rate in ICSI was not related to sperm origin or sperm quality. The number of stillbirths (born > or =20 weeks of pregnancy) was 1.69% in the ICSI group and 1.31% in the IVF group. Total malformation rate taking into account major malformations in stillborns, in terminations and in liveborns was 4.2% in ICSI and 4.6% in IVF (P = 0.482). CONCLUSIONS: The comparison of ICSI and IVF children taking part in an identical follow-up study did not show any increased risk of major malformations and neonatal complications in the ICSI group.

Child, Preschool↗

PubMed2002

Cumulative delivery rates after ICSI in women aged >37 years.

BACKGROUND: Female patients aged >37 years have a poor prognosis after ICSI. To determine the cumulative delivery rates in these women by life-table analysis, 228 patients aged >37 years who had undergone a total of 437 ICSI cycles were analysed retrospectively. METHODS: Only cycles in which fresh ejaculated sperm was used, and in which at least one oocyte was micro-injected, were analysed. The main outcome measure was cumulative rate of deliveries. Any delivery after 25 weeks gestation was included in the study. RESULTS: In women aged 38-39 years, the real cumulative delivery rate after two cycles was 21%, while the expected delivery rate was 26%. In patients aged 40-43 years, the real and expected cumulative delivery rates were 12 and 17% respectively after three cycles, when they reached a plateau. There was only one delivery in the age group >43 years, which consisted of 26 patients with 66 cycles. In women aged >37 years, an expected cumulative delivery rate of 30% may be obtained at the end of the fourth cycle. Women aged >43 years do not have a realistic chance of achieving a delivery with their own oocytes. CONCLUSIONS: This life-table analysis provides a means by which to counsel couples about their chances of achieving a delivery by ICSI at an age >37 years.

Adult↗

PubMedDate not supplied

Multiple birth resulting from ovarian stimulation for subfertility treatment.

Assisted reproductive technologies (ARTs) aim to increase a woman's chances of becoming pregnant by bringing many female and male gametes into close proximity. Techniques to achieve this objective include ovarian hyperstimulation by maturation of several oocytes, intrauterine insemination (IUI) of concentrated sperm, or in-vitro fertilisation (IVF) by bringing gametes together outside the female body. The very nature of ovarian hyperstimulation--with or without IUI--enhances the risk of multiple pregnancy (eg, two or more babies). In most IVF cycles, more than one embryo is transferred, again resulting in an increased chance of multiple pregnancy. Developed societies have witnessed a large rise in prevalence of twin, triplet, and higher order multiple births, mainly resulting from ARTs. The primary aim of this Review is to increase awareness of the many implications of the present iatrogenic epidemic of multiple births. The background of ovarian hyperstimulation, trends supporting current practice, and strategies to reduce the chance of multiple pregnancy are highlighted.

Female↗

PubMedDate not supplied

Comparison of transfers to Fallopian tubes or uterus after ICSI.

The aim of this study was to compare the implantation rate of tubal-replaced microinjected oocytes (MIFT) versus conventional day 2 intrauterine embryo transfer in patients undergoing intracytoplasmic sperm injection (ICSI). Sixty-three patients in need of ICSI, between 18 and 37 years of age with normal menstrual cycles and fewer than four previous ICSI attempts, were randomized between April 1999 and December 2001. In the MIFT group, up to three micro-injected oocytes were transferred laparoscopically 4 h after microinjection. In the ICSI-embryo transfer group, up to three cleaving embryos were replaced into the uterine cavity 48 h after insemination. Fifty-nine patients reached the stage of oocyte retrieval; 31 patients had a day 2 embryo transfer and 28 patients had MIFT. The ongoing clinical pregnancy and implantation rate (i.e. the total number of gestational sacs with fetal heartbeat divided by the total number of transferred embryos or micro-injected oocytes) was 35 and 24% in the ICSI-embryo transfer group and 29 and 11% in the MIFT group respectively. In conclusion, this study shows a significant decrease in implantation rate in the MIFT group (P < 0.05). In this group of patients there seems to be no advantage to tubal replacement of micro-injected oocytes.

Adolescent↗

PubMedDate not supplied

Rescue IVF and coasting with the use of a GnRH antagonist after ovulation induction.

The major risks of exogenous gonadotrophin therapy for ovulation induction in a patient with polycystic ovaries (PCO) are multiple pregnancies and ovarian hyperstimulation syndrome (OHSS). This case report describes a 23-year-old patient, who was referred to the Centre for Reproductive Medicine in Brussels because of a high risk of developing OHSS and rising LH following ovulation induction with a low-dose step-up protocol using gonadotrophins. After counselling the patient, the decision was made to perform a rescue IVF cycle. The patient was first coasted with 0.25 mg ganirelix; the serum oestradiol concentrations decreased and the LH peak was successfully suppressed. No OHSS occurred. An ongoing twin pregnancy was achieved after the transfer of two embryos. This case report demonstrates the feasibility of coasting with LH-releasing hormone (LHRH) antagonists (0.25 mg ganirelix) and the usefulness of the antagonists for ovulation induction cycles in patients who need rescue IVF.

Adult↗

PubMedDate not supplied

Blastocyst culture: facts and fiction.

The use of sequential media has made extended culture and transfer of blastocysts feasible for human IVF. Embryo transfer on day 5 has been claimed to result in higher implantation rates than transfer on day 3, on the basis of retrospective comparative studies. This is not supported convincingly, however, in randomized controlled trials published to date. Blastocyst culture imposes additional requirements in terms of personnel, equipment, education and cost and is associated with a greater incidence of monozygotic twinning and cycle cancellation rate than in the case of day 3 culture. In order for day 5 transfer to replace day 3 transfer, a convincing comparison between the two methods should therefore demonstrate the superiority of blastocyst transfer. There is still a need for properly designed randomized controlled trials to compare day 3 with day 5 transfer which will also address the effectiveness of a single blastocyst replacement in reducing the incidence of multiple pregnancies as well as the value of blastocyst cryopreservation.

Adult↗

PubMedDate not supplied

Alternative approaches in IVF.

Various new developments in clinical and basic science which may impact on IVF in the near or distant future will be discussed in this review. These key areas include the regulation of early follicle development and the extended in-vitro culture of oocytes and embryos. Moreover, alternative compounds and ovarian stimulation protocols will be discussed, along with highlights in the development of the cryopreservation of excess oocytes or embryos. Finally, the health economics of IVF is addressed.

Cells, Cultured↗