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Paul Devroey

Publications and source records attributed to Paul Devroey.

At least 19 recordsLinked to original sources
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

Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study.

BACKGROUND: The contribution of the LH activity in menotrophin preparations for ovulation induction has been investigated in small trials conducted versus FSH preparations. The objective of this study was to demonstrate non-inferiority of highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with respect to the primary outcome measure, ovulation rate. METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-HMG (n=91) or rFSH (n=93) using a low-dose step-up protocol. RESULTS: The ovulation rate was 85.7% with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority was demonstrated. Significantly fewer intermediate-sized follicles were observed in the HP-HMG group (P<0.05). The singleton live birth rate was comparable between the two groups. The frequency of ovarian hyperstimulation syndrome and/or cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH (P=0.058). CONCLUSIONS: Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.

Adolescent↗
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

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

Menstruation-free interval and ongoing pregnancy in IVF using GnRH antagonists.

BACKGROUND: The purpose of this study was to evaluate prospectively the association between the achievement of ongoing pregnancy and the time interval from the end of menstruation until the administration of HCG (menstruation-free interval) in patients treated by IVF. METHODS: A fixed dose of 200 IU of recombinant FSH (rFSH) was started in 90 patients on day 2 of the menstrual cycle and daily GnRH antagonist was initiated on day 6 of stimulation. Triggering of final oocyte maturation was performed with 10,000 IU of HCG as soon as three follicles of > or =17 mm were present at ultrasound. RESULTS: Single embryo transfer was performed in 64.6% of the patients who reached embryo transfer (53/82). Ongoing pregnancy rate per embryo transfer was 18.3% (95% CI 11.4-28.0%). The menstruation-free interval significantly predicted the probability of ongoing pregnancy in a logistic regression analysis, controlling for female age and LH on day 1 of stimulation (odds ratio for the menstruation-free interval: 0.70; 95% CI: 0.54-0.92). CONCLUSION: The longer the interval from the end of menstruation until the administration of HCG, the lower the probability of ongoing pregnancy in patients stimulated with recombinant FSH and GnRH antagonist for IVF.

Adult↗
PubMed2005

Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial.

BACKGROUND: The objective of this randomized controlled trial was to assess the effect of oral contraceptive pill (OCP) pretreatment on the probability of ongoing pregnancy in patients treated with a GnRH antagonist for IVF. METHODS: A fixed dose of 200 IU recombinant FSH (rFSH) was started in 425 patients either on day 2 of the menstrual cycle (non-OCP group: n = 211) or 5 days after discontinuing the OCP (OCP group: n = 214). GnRH-antagonist was initiated on day 6 of stimulation, and triggering of final oocyte maturation was performed with 10,000 IU of HCG. RESULTS: Ongoing pregnancy rates per started cycle in the non-OCP and OCP group were 27.5% and 22.9%, respectively [95% confidence interval (CI) of the difference: -3.7 to +12.8]. Pregnancy loss was significantly increased in the OCP (36.4%) compared with the non-OCP group (21.6%) (95% CI of the difference: -28.4 to -2.3). CONCLUSION: Pretreatment with OCP, as compared with initiation of stimulation on day 2 of the cycle in patients treated with GnRH antagonist and recombinant FSH, appears to be associated with a not significant difference in ongoing pregnancy rates per started cycle and results in a significantly higher early pregnancy loss.

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

Slow controlled-rate freezing of sequentially cultured human blastocysts: an evaluation of two freezing strategies.

BACKGROUND: To optimize blastocyst cryopreservation, the prerequisite is to develop a better understanding of factors that influence their survival and implantation potential. Therefore, the aim of the present work was to evaluate, retrospectively, the outcome of blastocyst cryopreservation in a day 2/3 fresh embryo transfer programme. METHODS: Two different freezing strategies were compared: a first strategy (strategy A: 3007 blastocysts frozen) consisted of freezing those blastocysts that had at least a cavity; a second strategy (strategy B: 3831 blastocysts frozen) consisted of freezing only more advanced stage blastocysts with a good quality inner cell mass and trophectoderm. The outcome of cryopreservation, as related to the two different freezing strategies, was analysed. In addition, after freezing and thawing, we evaluated the influence of blastocyst developmental characteristics on immediate morphological survival and further development in vitro. RESULTS: The immediate morphological survival after thawing was higher for early blastocysts as compared to advanced and hatching blastocysts. The further developmental potential in vitro of thawed blastocysts was higher for advanced and hatching blastocysts as compared to early blastocysts. As a result, the percentage of deliveries, calculated as a percentage of started thawing cycle, and the percentage of children born, calculated as a percentage of embryos transferred, was not different for strategies A and B. CONCLUSION: The results clearly indicate that culture conditions and cryopreservation procedures of blastocysts need to be further improved.

Blastocyst↗
PubMed2005

Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

BACKGROUND: Prolongation of follicular phase by delaying hCG administration has been reported to result in a significantly lower ongoing pregnancy rate that did not seem to be due to an embryonic factor. The aim of this prospective randomized study was to assess the effect of delaying hCG administration on endometrial histology. METHODS: Ten oocyte donors underwent endometrial biopsy on the day of oocyte retrieval and endometrial histology was assessed by Noyes' criteria. Ovarian stimulation was performed with recombinant (r)FSH and daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized by a computer-generated list to receive 10 000 IU of hCG either as soon as > or =3 follicles > or =17 mm were present on ultrasound (early-hCG group, n = 5) or 2 days after this criterion was met (late-hCG group, n = 5). RESULTS: When hCG was delayed, endometrial advancement was present in all samples examined (median advancement 3 days, range 2-3 days). On the contrary, no secretory changes were observed when the follicular phase was not prolonged (difference in the proportion of patients with advancement between the early-hCG and the late-hCG group: 100%, 95% CI: 38-100). CONCLUSIONS: Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

Adult↗
PubMed2005

Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes.

BACKGROUND: Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR). METHODS: In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3). RESULTS: Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles. DISCUSSION: Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.

Adult↗
PubMed2005

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Administration, Oral↗
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

Blastocyst formation in in vitro fertilization versus intracytoplasmic sperm injection cycles: influence of the fertilization procedure.

OBJECTIVE: To compare the quality of early cleaving embryos and blastocysts obtained by IVF or intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective study. SETTING: Tertiary infertility center. PATIENT(S): Sibling oocytes of 104 patients in 104 IVF vs. ICSI cycles. INTERVENTION(S): Cumulus oocyte complexes (n = 1,358) were randomly subjected to ICSI or IVF. MAIN OUTCOME MEASURE(S): Embryo development and blastocyst formation rate. The blastocyst quality and cycle efficiency were also evaluated. RESULT(S): Early embryo cleavage was higher after ICSI (37.1%) compared to IVF (14.1%). The percentage of > or =4-cell embryos on day 2 and > or =8-cell embryos on day 3 was similar for both procedures. The overall blastocyst formation was not different between ICSI (50.2%) and IVF (54.8%), neither was the percentage of good-quality blastocysts (31.3% for ICSI and 36.0% for IVF). The total cycle efficiency (percentage of embryos transferred and frozen per two pronuclei [2PN]) was comparable for the two techniques (51.7% for ICSI and 57.4% for IVF). CONCLUSION(S): No differences were found on sibling oocytes in the embryo development and blastocyst formation, irrespective of the fertilization procedure. Earlier suggestions that the ICSI technique may result in impaired blastocyst development were not confirmed in this study.

Adult↗
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↗
PubMed2005

GnRH antagonists in IVF.

The present review summarizes existing knowledge on the use of gonadotropin releasing hormone (GnRH) antagonists based on experience gathered after the completion of phase III comparative trials with GnRH agonists. Available data suggest that prolongation of the follicular phase significantly decreases the probability of pregnancy. Moreover, patients with elevated progesterone at initiation of stimulation have significantly fewer chances of achieving an ongoing pregnancy. Luteal support remains mandatory, while the replacement of human chorionic gonadotrophin by GnRH agonist does not appear to be feasible. Although not conclusive, existing data are not in favour of increasing the starting dose of gonadotrophins, of LH supplementation or of using a flexible antagonist protocol.

Dose-Response Relationship, Drug↗
PubMed2005

Achievement of pregnancy three times in the same patient during luteal GnRH agonist administration.

Gonadotrophin-releasing hormone agonist (GnRHa) administration from the mid-luteal phase onwards is considered the gold standard of ovarian stimulation for IVF treatment. It might, however, coincide with an implanting spontaneous pregnancy. Concerns have therefore been raised with regard to the evolution of the resulting pregnancies and long-term outcome of the children born. The current case report describes the achievement of three pregnancies in the same patient during luteal administration of GnRHa. One pregnancy ended in spontaneous abortion and the other two resulted in the delivery of two female infants. The children have so far been followed for 3.5 and 7 years. The physical examination of both children was unremarkable. However, the older child has recently been diagnosed with attention deficit hyperactivity disorder and dyslexia.

Adult↗