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Biomedical subjects

Paul Devroey

Publications and source records attributed to Paul Devroey.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2005

Estrogen and folliculogenesis: is one necessary for the other?

PURPOSE OF REVIEW: During folliculogenesis the primordial follicle undergoes several steps of maturation in order to develop into a preovulatory follicle. The exact role of estrogen during this process has not yet been fully assessed. RECENT FINDINGS: Estrogen appears to regulate cyclic gonadotropin release via its action on estrogen receptor alpha in the hypothalamus/hypophysis axis and to enhance folliculogenesis through its actions via estrogen receptor beta in the ovary. In addition, a role of estrogen during the very early stages of folliculogenesis is possible. However, it is likely that oocyte quality and developmental potential are not estrogen dependent. This might explain the lack of association between estrogen and in-vitro fertilization outcome in humans. SUMMARY: The advent of knockout mice models has enhanced our understanding of the role of estrogen during folliculogenesis. Existing data suggest that estrogen might be involved in the very early steps of this process, but its role in sustaining ovulation is mainly central.

Animals↗
PubMed2005

Emerging drugs in assisted reproduction.

Infertility affects approximately 15% of couples of reproductive age. In assisted reproductive technology (ART), medications play a crucial role in stimulating ovaries to produce several oocytes and prepare the endometrium to be receptive after replacing one or more embryos into the uterine cavity. The availability of recombinant human follicle stimulating hormone, luteinising hormone and human chorionic gonadotrophin; of gonadotrophin-releasing hormone (GnRH) agonists and antagonists; and of luteal supplementation with progesterone have allowed the tailoring of several stimulation schemes, which have enhanced the pregnancy outcome after ART treatment. However, the remaining risk of ovarian hyperstimulation syndrome, the still low implantation rates, the unacceptably high rates of multiple pregnancies and the daily parenteral administration of medications do not constitute the features of a patient-friendly procedure. Therefore, a number of molecules with gonadotrophin-like activity, inhibition of GnRH receptor ability, or endometrium receptivity enhancement properties are currently under active investigation. Orally bioactive therapeutic preparations, in particular, may revolutionize in vitro fertilisation (IVF) treatment in the near future. Nevertheless, the implementation of mild ovarian stimulation protocols with single embryo transfer policy and further development of oocyte in vitro maturation techniques may lead to a less drug orientated IVF treatment.

Clinical Trials as Topic↗
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

Modified natural cycle for IVF does not offer a realistic chance of parenthood in poor responders with high day 3 FSH levels, as a last resort prior to oocyte donation.

BACKGROUND: The purpose of this study was to evaluate the use of the modified natural cycle (MNC) for IVF in poor responders as a last resort prior to oocyte donation. METHODS: Thirty-two patients with a regular menstrual cycle, FSH levels on day 3 of the cycle >12 IU/l and one or more failed IVF cycles with five or fewer cumulus-oocyte complexes (COCs) retrieved were included in this prospective study. Recombinant FSH 100 IU and GnRH antagonist 0.25 mg/day were started concomitantly when a follicle with a mean diameter of 14 mm was present at ultrasound. HCG 10 000 IU was administered as soon as the mean follicular diameter was > or =16 mm. RESULTS: Twenty-five out of 78 cycles performed (32.1%) did not result in oocyte retrieval. In nine out of 53 cycles (16.9%) in which oocyte retrieval was performed, no COCs were retrieved. Following fertilization, embryo transfer was performed in 19 out of 44 cycles in which COCs were retrieved (43.2%). No ongoing pregnancy was achieved in 78 MNCs (0.0%; 95% confidence interval 0.0-4.7). CONCLUSIONS: MNC does not offer a realistic chance of parenthood in patients with high levels of FSH on day 3 of the cycle and previous poor response to ovarian stimulation, when offered as a last resort prior to oocyte donation.

Chorionic Gonadotropin↗
PubMed2004

Association of estradiol levels on the day of hCG administration and pregnancy achievement in IVF: a systematic review.

BACKGROUND: Evaluation of the association between estradiol (E2) levels on the day of hCG administration and pregnancy achievement in IVF has so far yielded conflicting results. The purpose of the present study was to systematically review the above association in cycles down-regulated with GnRH analogues. METHODS: Literature search was performed using Medline, Embase (1978-2004) and the Cochrane Library. Additionally, references of retrieved articles were hand-searched. Only full articles published in peer-reviewed medical journals were considered for analysis. RESULTS: All the eligible studies (n=9) involved the use of GnRH agonists and were retrospective. Two studies (including 191 patients) suggested that the higher the E2 levels on the day of hCG administration, the higher the probability of pregnancy. However, five studies (including 1875 patients), did not support an association between E2 levels on the day of hCG administration and pregnancy rates. Moreover, two of the studies including (1286 patients) suggested that high E2 levels on the day of hCG administration are associated with a decreased probability of pregnancy. If we consider only studies in which criteria used for administering hCG include follicular development but not E2 levels (including 2687 patients), there is no study suggesting a positive association between E2 levels on the day of hCG administration and pregnancy achievement. CONCLUSIONS: Currently there is no high-quality evidence to support or deny the value of E2 determination on the day of hCG administration for pregnancy achievement in IVF cycles, where pituitary down-regulation is performed with GnRH agonists. Existing retrospective studies suggest that there is no positive association. However, in order to arrive at recommendations for clinical practice, there is a need to perform well-designed prospective studies in both agonist and antagonist cycles.

Chorionic Gonadotropin↗
PubMed2004

Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial.

BACKGROUND: It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate. Therefore, advanced maternal age (AMA) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening (PGD-AS) on the outcome after assisted reproductive technology (ART). METHODS: A prospective randomized controlled clinical trial (RCT) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization (FISH) for the chromosomes X, Y, 13, 16, 18, 21 and 22 in AMA couples (aged > or =37 years) with a control group without PGD-AS. From the 400 (200 for PGD-AS and 200 controls) couples that were allocated to the trial, an oocyte pick-up was performed effectively in 289 cycles (148 PGD-AS cycles and 141 control cycles). RESULTS: Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls: 35.8% (19.6%) [%/per embryo transfer (per cycle)] and 32.2% (27.7%), respectively (NS). Significantly fewer embryos were transferred in the PGD-AS group than in the control group (P<0.001). The implantation rate (with fetal heart beat) was 17.1% in the PGD-AS group versus 11.5% in the control group (not significant; P=0.09). We observed a normal diploid status in 36.8% of the embryos. CONCLUSIONS: This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred.

Adult↗
PubMed2004

Preserving the reproductive potential of men and boys with cancer: current concepts and future prospects.

The introduction of ICSI has totally changed the reproductive prospects for boys and men who are treated for cancer. With post-pubertal boys and adult men, semen cryopreservation should be offered to every patient undergoing a cancer treatment since preservation of fertility cannot be guaranteed for an individual patient and treatment may shift to a more sterilizing regimen. In the ICSI era, all semen samples, even those containing only a few motile sperm, should be accepted for cryopreservation. Patients who are azoospermic at the time cancer is diagnosed may be offered testicular sperm extraction and cryopreservation of testicular tissue. With pre-pubertal boys, no prevention of sterility by sperm banking is possible since no active spermatogenesis is present. However, in the next decade, prevention of sterility in childhood cancer survivors will become a major challenge for reproductive medicine. In theory, testicular stem cell banking is the only way of preserving the future fertility of boys undergoing a sterilizing chemotherapy. In animal models, testicular stem cell transplantation has proved to be effective; however, it remains to be shown that this technique is clinically efficient as well, especially when frozen-thawed cells are to be transplanted. Malignancy recurrence prevention is an important prerequisite for any clinical application of testicular stem cell transplantation. Although still at the experimental stage, cryobanking of testicular tissue from pre-pubertal boys may now be considered an acceptable strategy.

Adolescent↗