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Biomedical subjects

P Devroey

Publications and source records attributed to P Devroey.

At least 37 records · Page 2Linked to original sources

A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.

BACKGROUND: Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed. METHODS: 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. RESULTS: No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). CONCLUSIONS: Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.

Adult↗

Is chromosome analysis mandatory in the initial investigation of normovulatory women seeking infertility treatment?

BACKGROUND: There is no agreement about the frequency of chromosomal abnormalities (CAs) in the female partner of an infertile couple and therefore there is no evidence base for determining whether karyotype analysis is mandatory before the initiation of infertility treatment. The aim of this prospective study was to estimate the prevalence of karyotype abnormalities in normovulatory women attending an infertility clinic and compare it to that known to be present in the newborn female population. METHODS: Cytogenetic testing was performed in 1206 women with normal ovulatory cycle seeking infertility treatment. At least 15 GTG-banded metaphases were analysed in each case. In the case of a structural abnormality, fluorescent in situ hybridization (FISH) analysis and high resolution banding (HRB) were performed on a new blood sample to elucidate the aberration. When mosaicism was suspected, the number of analysed metaphases was increased to a total of 115 and an additional analysis of 200 metaphases was done on a second blood sample. RESULTS: A chromosomal abnormality was demonstrated in 0.58% (95% CI: 0.28-1.19) of cases which did not differ significantly from that reported in female newborns (0.79%; 95% CI: 0.68-0.94). Balanced reciprocal translocation was observed in 0.4% of patients (n = 5), paracentric inversion of chromosome X in 0.08% (n = 1) and gonosomal mosaicism in 0.08% (n = 1). However, chromosomal aberrations were less common among females with primary infertility compared to those with secondary infertility (0.25 versus 1.25%, P = 0.04). CONCLUSIONS: The present study suggests that routine cytogenetic analysis cannot be advocated in normovulatory infertile women. Nevertheless, the relatively higher frequency of abnormal karyotypes in women with secondary infertility indicates that this subgroup of patients might benefit from a routine karyotype analysis.

Adult↗

Preimplantation genetic diagnosis for neurofibromatosis type 1.

PGD is an alternative to prenatal diagnosis that circumvents therapeutic abortion. Diagnosis is carried out on single cells obtained from three-day-old embryos, and only those that are free of the disease under consideration are transferred to the mother. Neurofibromatosis type 1 (NF1) is a common neurocutaneous disorder, inherited as an autosomal dominant trait and caused by mutations in the NF1 gene. For some patients, PGD may be the only acceptable manner to ensure the birth of unaffected children. Because of the large number of known NF1 mutations, the development of mutation-specific single-cell protocols is impractical, labour-intensive and expensive. This paper discusses the development of five PGD protocols, three of which are based on multiplex PCR for microsatellite-markers linked to the NF1 gene. After a linkage study, the diagnosis can be established through the markers, thereby obviating the need to detect the mutation itself. This not only ensures the accurate diagnosis of the embryos, but also a prompt acceptance of PGD referrals since one protocol can be useful for several couples. In addition, two mutation-specific PCRs were developed for two couples where a marker-based protocol was not applicable. In total, 16 PGD cycles were carried out for six couples, which resulted in one ongoing pregnancy and the delivery of a healthy unaffected boy.

Adult↗

Fertility and ageing.

The late 20th century trend to delay birth of the first child until the age at which female fecundity or reproductive capacity is lower has increased the incidence of age-related infertility. The trend and its consequences have also stimulated interest in the possible factors in the female and the male that may contribute to the decline in fecundity with age; in the means that exist to predict fecundity; and in the consequences for pregnancy and childbirth. In the female, the number of oocytes decreases with age until the menopause. Oocyte quality also diminishes, due in part to increased aneuploidy because of factors such as changes in spindle integrity. Although older male age affects the likelihood of conception, abnormalities in sperm chromosomes and in some components of the semen analysis are less important than the frequency of intercourse. Age is as accurate as any other predictor of conception with assisted reproductive technology. The decline in fecundity becomes clinically relevant when women reach their mid-30s, when even assisted reproduction treatment cannot compensate for the decline in fecundity associated with delaying attempts at conceiving. Pregnancies among women aged >40 years are associated with more non-severe complications, more premature births, more congenital malformations and more interventions at birth.

Adult↗

Taskforce 9: the application of preimplantation genetic diagnosis for human leukocyte antigen typing of embryos.

This 9th statement of the ESHRE Taskforce on Ethics and Law considers ethical questions and specific dilemmas concerning preimplantation genetic diagnosis for human leukocyte antigen typing of embryos. This application is particularly complex because the interests of the sick child needing a transplantation should be balanced against the interests of the future donor child who may result from the technique. It is concluded that, if parents intend to love the child, the creation and use as a donor is not inherently disrespectful.

Cloning, Organism↗

HLA-matched embryos selected for siblings requiring haematopoietic stem cell transplantation: a psychological perspective.

Allogeneic haematopoietic stem cell transplantation (HSCT) is a treatment for a number of acquired and congenital diseases. An important factor in the outcome of the treatment is the degree of human leukocyte antigen (HLA) compatibility between patient and donor. HLA identical siblings therefore provide the best chance for the recipient. Preimplantation genetic diagnosis (PGD) can be used to select HLA identical embryos if there is no HLA compatible sibling in the family. The Centre for Reproductive Medicine considered it morally justified to give medical assistance to couples in need of an HLA matched sibling. Two considerations played an important role in this respect: (i) the use as a donor should not be the only parents' motive for having the child and (ii) IVF and HLA typing on the embryos would be less of a burden for the parents than other alternatives. Since the first request in 2000, 12 couples have been referred for psychological counselling. The motivation of four couples will be discussed in depth. The validity of the arguments will be checked against the experience of the actual cases. The consequences of the treatment on the welfare of the future donor child will be discussed.

Adult↗

Successful treatment of an aggressive recurrent post-menopausal endometriosis with an aromatase inhibitor.

The current case report describes the development and medical treatment of an aggressive pelvic endometrioma in a post-menopausal patient, who had undergone abdominal hysterectomy and salpingo-oophorectomy a decade earlier. The patient was referred to the authors' centre because of right-sided sciatic pain. Three months before her admission she was hospitalized elsewhere due to subacute bowel obstruction. She was operated on and a resection of a part of sigmoid colon and an endometrioma, which was the cause of the subobstruction, was carried out. During the clinical investigation for the right-sided sciatic pain, an intrapelvic mass was found, which was compressing the lumbo-sacral plexus mimicking sciatica. The diagnosis of recurrent endometrioma was confirmed by a computerized tomography-guided biopsy and the decision was made to treat it with an aromatase inhibitor (letrozole). Eighteen months later, the endometrioma was almost completely regressed and the patient was free of symptoms. Medical management of recurrent post-menopausal endometriosis with aromatase inhibitors seems to be an effective alternative treatment to surgery.

Aromatase Inhibitors↗

Economic evaluation of the administration of follitropin-beta with a pen device.

Previous studies suggest that administration of follitropin-beta with a pen device (Puregon Pen(R)) is more convenient, less painful and 16-18% more efficient. The aim of this study was to perform an economic evaluation of the administration of follitropin-beta by this pen device against follitropin-alpha by multidose and highly purified (HP) HMG by conventional syringe in IVF treatment by comparing the process utilities and the costs for the Dutch setting. Conjoint analysis assessed the process utilities for the three administration modes on a scale from 0 to 1. A decision analytic model estimated the costs of an average IVF cycle from a societal perspective. Patients estimated the process utility at 0.96 for the pen, 0.53 for the multidose and 0.36 for the conventional syringe. Additional costs were estimated at 0 Euros and 194 Euros, comparing the pen with multidose or conventional methods respectively. Assuming a 16% efficiency gain of the pen, costs ranged from Euros-135 (savings) to 60 Euros (extra costs). In conclusion, patients perceive sufficient benefits to the pen device to choose it over other dosing methods. Dominance of the pen device over the multidose method was shown. Compared with the conventional administration method, the added value of the pen device was 2.7 (0.96/0.36) times higher.

Adult↗

Immature oocyte in-vitro maturation: clinical aspects.

The development of immature oocyte collection techniques for in-vitro maturation (IVM), combined with novel culture techniques, opens new possibilities for assisted reproductive technology. Optimization of clinical management of IVM cycles will enhance pregnancy outcome, so that IVM might become an effective alternative assisted reproduction treatment for infertile patients irrespective of the cause of infertility. Parameters such as age and baseline antral follicular count are predictive of outcome and should be used as selection criteria for IVM treatment. Women with polycystic ovary disease and normo-ovulatory patients at risk of developing ovarian hyperstimulation syndrome might benefit from earlier retrieval of oocytes followed by IVM and embryo transfer. HCG priming before oocyte retrieval seems beneficial in terms of oocyte yield and maturational competence, and may increase the harvest of mature oocytes and lead to better endometrial synchronization with the developing embryo. The timing of aspiration may be crucial in IVM and selection criteria for follicle size at aspiration need defining prospectively for infertility type. Finer calibre aspiration needles and low aspiration pressure yield more oocytes. A combination of natural cycle IVF with IVM is a promising, mild and inexpensive assisted reproduction treatment, widely accessible the infertile population.

Animals↗

Reproductive decisions by couples undergoing artificial insemination with donor sperm for severe male infertility: implications for medical counselling.

Since 1992, ICSI has been introduced as a successful treatment for male infertility, including azoospermia. The present study is aimed at evaluating the practice of insemination with donor sperm (AID) in infertile couples who may benefit from the new developments that ICSI has brought in the last decade. AID was performed in 440 heterosexual couples. Twelve couples were lost for follow-up (3%). In 128 (29.9%) and 229 (53.5%) of the couples the husband was either oligozoospermic (OAT) or azoospermic. In 60 couples (14.0%) the man had a transmissible genetic trait. In 11 couples (2.6%) there were other indications for performing AID. In the OAT group 36 couples never had ICSI treatment (28.1%) because they had already an AID child born before the introduction of ICSI (n = 16), the burden of ICSI treatment was too high (n = 9) or they considered that ICSI success rate was too low (n = 7). Ninety-two couples tried ICSI treatment before opting for AID (71.9%), mainly because ICSI failed (n = 43). In 229 couples the husband had azoospermia (53.5%). In 112 couples (49%) no sperm or too few testicular sperm were found at testicular biopsy (TESE) and 15 couples (6.5%) had more than three failed ICSI-TESE attempts. Eighty-one azoospermic men refused TESE (35.4%) because of an anticipated low success rate (n = 28) or the burden of this approach (n = 23). Although a majority of patients could opt for ICSI, our results show that AID is still an option for many couples for whom these techniques were either not feasible or not successful. A substantial proportion of patients (33%) did not even opt for these advanced fertility treatments.

Counseling↗

Should diagnostic testicular sperm retrieval followed by cryopreservation for later ICSI be the procedure of choice for all patients with non-obstructive azoospermia?

BACKGROUND: This was a retrospective study to determine if diagnostic testicular biopsy followed by cryopreservation should be the procedure of choice for all patients with testicular failure. METHODS: The first part of the study analysed 97 ICSI cycles scheduled with frozen-thawed testicular sperm for 69 non-obstructive azoospermia (NOA) patients. The second part focused on a subgroup of 32 patients who underwent 42 ICSI cycles with frozen and 44 cycles with fresh testicular sperm. Sperm characteristics, fertilization, embryo quality, pregnancy and implantation rates were evaluated. RESULTS: Part I: The average time needed to find sperm was 113 min per cycle and 17 min per individual sperm. Fertilization rate, embryo transfer rate, ongoing pregnancy and implantation rates were 58.4%, 83%, 20.8% and 11.3%, respectively. Part II: The search time per sperm was higher (P=0.016) in frozen (18 min) than in fresh suspensions (13 min). A higher embryo transfer rate was observed in fresh cycles than in frozen cycles (93.2% vs 76.2%, P=0.028). Fertilization, ongoing pregnancy and implantation rates were comparable for the two groups. CONCLUSIONS: Even in a programme with low-restrictive criteria for patient allocation and for sperm cryopreservation, diagnostic testicular biopsy followed by cryopreservation can be the procedure of choice for patients with testicular failure.

Adult↗

Taskforce 8: ethics of medically assisted fertility treatment for HIV positive men and women.

In this 8th statement of the ESHRE Taskforce on Ethics and Law, the focus is on the ethical issues raised by (assisted) reproduction for HIV positive men and women. Due to treatment improvements, their life expectancy has increased substantially. This, in combination with the reduction of perinatal transmission to the child, makes the creation of a family more acceptable. Recommendations are made concerning methods of avoiding HIV transmission in the couple and to their offspring. It is concluded that, if certain precautions are taken, medical assistance to reproduction of HIV positive people is ethically acceptable. For the time being, only cases of serodiscordant couples should be considered.

Anti-Retroviral Agents↗

Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF.

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.

Adult↗

Outcome of testicular sperm recovery and ICSI in patients with non-obstructive azoospermia with a history of orchidopexy.

BACKGROUND: Little is known about sperm recovery and ICSI using testicular sperm from men with non-obstructive azoospermia who had a previous orchidopexy. We therefore studied the sperm recovery in this subgroup and evaluated clinical parameters predicting successful sperm retrieval and the outcome of ICSI. METHODS: A total of 79 non-obstructive azoospermic men with a history of orchidopexy underwent a sperm recovery procedure. The predictive value of clinical parameters such as age at sperm retrieval, age at orchidopexy, testicular volume, FSH, FSH/LH ratio, testosterone and androgen sensitivity index (LH x testosterone) for successful testicular sperm retrieval was evaluated using receiver operating characteristics (ROC) curve analysis. A comparison between 64 ICSI cycles performed in these couples and 92 cycles performed in couples in which the men had an unexplained non-obstructive azoospermia was carried out. RESULTS: Testicular spermatozoa were recovered in 41 patients (52%). The mean age at orchidopexy of the patients with a positive sperm recovery was 10.6 years [95% confidence interval (CI) 7.3-13.8] versus 15.5 years (95% CI 11.3-19.8) for those where no spermatozoa were found. The mean testicular volume of the largest testis of patients with spermatozoa found was 10 ml (95% CI 8.3-11.9) versus 8.5 ml (95% CI 5.8-11.1) in patients with no spermatozoa found. The mean FSH and testosterone value for patients with successful and unsuccessful sperm recovery, respectively, was 24.1 IU/l (95% CI 17.9-30.3) and 4.4 ng/ml (95% CI 3.7-5.1) versus 28.8 IU/l (95% CI 19.4-38.2) and 3.4 ng/ml (95% CI 2.2-4.5). All clinical and biological parameters examined failed to predict the outcome of the testicular sperm extraction. No differences were observed between the orchidopexy and unexplained group for the number of oocytes retrieved, fertilization rate, embryo quality, pregnancy rate and implantation rate. CONCLUSIONS: As in the population of men with non-obstructive azoospermia, the sperm recovery rate for patients with a history of orchidopexy is approximately 50% and there are currently no clinical parameters predicting successful sperm retrieval in this subpopulation of patients. The outcome of the ICSI cycles is comparable with that in the population of men with non-obstructive azoospermia.

Adult↗

Should we advise patients undergoing IVF to start a cycle leading to a day 3 or a day 5 transfer?

BACKGROUND: The aim of this study was to compare ongoing pregnancy rates per started cycle between patients randomized at consultation to have embryo transfer either on day 3 or on day 5 of in-vitro culture. METHODS: All patients <43 years of age for whom IVF was indicated were allowed to participate in the study (day 3 group, 234 patients; day 5 group, 226 patients). Ovarian stimulation was performed either using GnRH antagonists/recombinant FSH (rFSH) (day 3, 70.1% of patients; day 5, 72.6% of patients) or using the long GnRH agonist protocol/urinary gonadotropins (day 3, 29.9% of patients; day 5 27.4% of patients). RESULTS: The random decision to initiate a cycle leading to day 5 as compared with a day 3 transfer was associated with a significantly lower chance of embryo cryopreservation (day 3, 61.5%; day 5, 50.4%; P<0.02). Ongoing pregnancy rate per started cycle did not differ between the two groups compared [day 3, 32.1%, 95% confidence interval (CI) 26.4-38.2%; day 5, 33.2%, 95% CI 27.3-39.5%]. CONCLUSIONS: Advising patients at consultation to initiate an IVF cycle leading to a day 5 as compared with a day 3 transfer does not appear to increase the probability of ongoing pregnancy, and is associated with a significantly lower probability of obtaining cryopreserved embryos.

Adult↗

Elevated progesterone at initiation of stimulation is associated with a lower ongoing pregnancy rate after IVF using GnRH antagonists.

BACKGROUND: The objective of this prospective study was to assess the impact of elevated serum progesterone levels on day 2 of the cycle on pregnancy rates in patients treated by IVF using GnRH antagonists. METHODS: Ovarian stimulation was started on day 2 of the cycle if progesterone levels were normal (normal-P group, n = 390). In the presence of elevated progesterone, initiation of stimulation was postponed for 1 or 2 days (high-P group, n = 20) and was started if repeat progesterone levels returned to normal range (n = 16). Stimulation was performed with recombinant FSH (rFSH) and GnRH antagonist was always started on day 6 of stimulation. RESULTS: A significantly higher exposure to progesterone and a significantly lower exposure to estradiol was present in the high-P as compared with the normal-P group from day 1 to day 8 of stimulation. In addition, a significantly lower ongoing pregnancy rate both per started cycle (5.0% versus 31.8%; P = 0.01) and per embryo transfer (6.3% versus 36.9%; P = 0.01) was present in the high-P compared with the normal-P group, respectively. CONCLUSIONS: The presence of elevated serum progesterone on day 2 of the cycle is associated with a decreased chance of pregnancy in patients treated with rFSH and GnRH antagonists.

Adult↗

Comparison of the aneuploidy frequency in embryos derived from testicular sperm extraction in obstructive and non-obstructive azoospermic men.

BACKGROUND: The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis (not sufficient to spill over into the ejaculate) may benefit from the technique. Previous reports suggest a higher pregnancy rate after ICSI treatment in patients with obstructive azoospermia (OA) compared to their non-obstructive azoospermia (NOA) counterparts, which could be due to a higher aneuploidy frequency in the embryos of the latter group. We therefore conducted a prospective cohort study to compare the aneuploidy frequency of the screened embryos between the two groups. METHODS: From May 2001 until September 2003, we offered couples with an OA or NOA partner ICSI in combination with preimplantation genetic diagnosis for aneuploidy screening. RESULTS: No difference in age (30.6 and 33.5 years) or stimulation parameters was observed between the two groups; 53 and 60% of the embryos were abnormal in the NOA and OA groups respectively (P = not significant). CONCLUSIONS: The aneuploidy frequency in embryos obtained from NOA as well as OA men is similar and very high, despite the young age of their female partners.

Adult↗

Can biological or clinical parameters predict testicular sperm recovery in 47,XXY Klinefelter's syndrome patients?

BACKGROUND: Contradictory results are available regarding prediction of testicular sperm extraction in 47,XXY patients. This study, therefore, aimed at assessing the availability of testicular sperm and evaluates clinical parameters predicting successful sperm retrieval in azoospermic 47,XXY Klinefelter's syndrome patients. METHODS: Sperm recovery procedures were performed in 50 non-mosaic azoospermic Klinefelter patients. The facial hair pattern and the presence of gynaecomastia in men with successful and unsuccessful sperm recovery were compared using Fisher's exact test. The predictive value of clinical parameters such as age, testicular volume, FSH, FSH:LH ratio, testosterone and androgen sensitivity index (LH x testosterone) for successful testicular sperm retrieval was evaluated using the receiver operating characteristics (ROC) curve analysis. RESULTS: In 24 patients (48%) testicular sperm were recovered. Ninety-four per cent of the men in whom sperm was found had a normal facial hair pattern compared to 93% in whom no sperm was recovered (not significant, NS). Seventeen percent of the men with successful testicular sperm extraction had gynaecomastia compared to 31% of the men with failed testicular sperm extraction (NS). The mean testicular volume of the largest testis in patients with sperm found was 4.2 ml compared to 3.6 ml in patients with no sperm found (NS). The mean FSH and testosterone values in patients with sperm recovered were 31.2 IU/l and 3.1 ng/ml versus 40.4 IU/l (P = 0.04) and 3.2 ng/ml (NS) in patients without sperm recovered. All examined clinical and biological parameters failed to predict the outcome of the testicular sperm extraction using ROC curve analysis. CONCLUSION: As in the general population of men with non-obstructive azoospermia, there are currently no clinical parameters predicting successful sperm retrieval in the subpopulation of patients with non-mosaic Klinefelter syndrome.

Gynecomastia↗