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Biomedical subjects

P Devroey

Publications and source records attributed to P Devroey.

At least 145 records · Page 8Linked to original sources

The use of testicular sperm for intracytoplasmic sperm injection in patients with necrozoospermia.

OBJECTIVE: To investigate whether intracytoplasmic sperm injection (ICSI) using testicular spermatozoa from necrozoospermic patients results in acceptable fertilization and transfer rates. DESIGN: Retrospective clinical study. SETTING: Tertiary referral center. PATIENTS: Five patients presenting consistently with 100% dead spermatozoa in their ejaculates. INTERVENTIONS: In seven treatment cycles, an open testicular biopsy was performed to increase the chances for retrieving viable spermatozoa which were used for ICSI. MAIN OUTCOME MEASURES: Sperm recovery, fertilization, and transfer rates. RESULTS: Testicular sperm were recovered in all treatment cycles and fertilization occurred in six of seven cycles. Overall normal fertilization and transfer rates were 67% and 71%, respectively. One live birth was obtained after five ETs. CONCLUSION: We recommend testicular sperm recovery for ICSI in patients who invariably or occasionally present with absolute necrozoospermia.

Adult↗

Cytogenetics of infertile men.

Chromosomally derived sterility has long been recognized. A review of the literature of somatic chromosome investigations in infertile males has shown that 13.7% of azoospermic males and 4.6% of oligozoospermic males have an abnormal karyotype. In the first group, sex chromosome abnormalities predominate (mainly 47,XXY), whereas in the latter, autosome anomalies (i.e. Robertsonian and reciprocal translocations) are the most frequent. A similar review on meiotic studies revealed that meiotic chromosome anomalies can explain male infertility in 4.3-40.4% of patients. Recently, fluorescent in-situ hybridization studies on spermatozoa from infertile men were published; it was suggested that both X-Y pairing and pairing of the autosomes were impaired, resulting in spermatogenic disruption. We investigated cytogenetically 694 infertile men with abnormal sperm parameters. More patients are needed for this research to investigate the relationship, if any, between the type of chromosome abnormality and its influence on the number, morphology and motility of spermatozoa. To be able to provide proper counselling for those couples whose male infertility can now be treated by intracytoplasmic sperm injection, it is suggested that clinical investigations should include mitotic and meiotic studies, an analysis of the chromosome content of individual spermatozoa and a DNA analysis of blood and spermatozoa to detect partially deleted Y chromosome material.

Chromosome Aberrations↗

Obstetric outcome of 904 pregnancies after intracytoplasmic sperm injection.

The obstetric data of 904 consecutive pregnancies obtained after intracytoplasmic sperm injection (ICSI) using ejaculated spermatozoa (group I), epididymal spermatozoa (group II), testicular spermatozoa (group III) and after the replacement of frozen-thawed embryos (group IV) are described. In all, there were 785 pregnancies in group I, 37 pregnancies in group II, 30 pregnancies in group III and 52 pregnancies in group IV. A total of 24 pregnancies (2.5%) have so far been lost to follow-up. The incidence of pregnancy loss, i.e. subclinical pregnancies, clinical abortions and ectopic pregnancies were highest in group IV (61.4%). Early pregnancy loss in groups I, II and III were 21.9, 37.8 and 33.3% respectively. Prenatal diagnosis was performed in 64.4% of the clinical pregnancies: amniocentesis in 48.2% and chorionic villus sampling in 16.2%. The karyotypes were normal in 97.6% of the prenatal diagnoses and there were 1.2% de novo and 1.2% inherited chromosome aberrations. Pregnancy complications such as prematurity and low birthweight were related to pregnancy multiplicity. Perinatal mortality occurred in 15 babies (17.1 per thousand), including nine intrauterine fetal deaths after 25 weeks of gestation and six cases of mortality during the first 7 days after birth. There is no evidence that the technique of ICSI using sperm cells of different origins yielded a higher obstetric risk.

Abortion, Spontaneous↗

Prospective follow-up study of 877 children born after intracytoplasmic sperm injection (ICSI), with ejaculated epididymal and testicular spermatozoa and after replacement of cryopreserved embryos obtained after ICSI.

A prospective follow-up study of 877 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones so as to evaluate the safety of this new technique. The follow-up study included agreement to genetic counselling and prenatal diagnosis and was based on a physical examination at the Centre for Medical Genetics (Dutch-speaking Brussels Free University, Brussels, Belgium) at 2 months, 1 year and 2 years, when major and minor malformations and a psychomotor evolution were recorded. Between April 1991 and July 1995, 904 pregnancies obtained after intracytoplasmic sperm injection (ICSI) led to the birth of 877 children (465 singletons, 379 twins and 33 triplets). Prenatal diagnosis determined a total of 486 karyotypes, of which six were abnormal (1.2%) and six (1.2%) were familial structural aberrations, all transmitted from the father. This slight increase in de-novo chromosomal aberrations and the higher frequency of transmitted chromosomal aberrations are probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself. In all, 23 (2.6%) major malformations were observed in the children born, defined as those causing functional impairment or requiring surgical correction. No particular malformation was disproportionately frequent. Compared with most registers of children born after assisted reproduction and with registers of malformation in the general population, the figure of 2.6% was within the expected range. These observations should be further completed by others and by collaborative efforts. In the meantime, patiens should be counselled about the available data before any treatment: the risk of transmitted chromosomal aberrations, the risk of de-novo, mainly sex chromosomal, aberrations and the risk of transmitting fertility problems to the offspring. Patients should also be reassured that there seems to be no higher incidence of congenital malformations in children born after ICSI.

Congenital Abnormalities↗

Cystic fibrosis and infertility caused by congenital bilateral absence of the vas deferens and related clinical entities.

The condition of congenital bilateral absence of the vas deferens (CBAVD) is, in the majority of patients, related to defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CBAVD patients either are compound heterozygotes (carrying different mutations in their two CFTR genes) or carry a mutation in one of their CFTR genes and an intron 8 5T splice variant, associated with low levels of functional CFTR protein, in their second gene. The relationship between cystic fibrosis (CF) and CBAVD requires a proper clinical examination of the patient, a CFTR mutation analysis for himself and his family and genetic counselling. A mutation analysis should also be performed for the wives of CBAVD males because such couples now have the possibility of having their own genetic children but are at increased risk of having children with CF and/or CBAVD. The aetiology of some conditions of CBAVD is not related to CF, especially when CBAVD is associated with urinary tract malformations (up to 20% of cases). In couples with CBAVD not related to CF there is no increased risk of CF children, but it is not known whether they have an increased risk of having sons with CBAVD. In some of the patients with congenital unilateral absence of the vas deferens (CUAVD) the condition is also related to CF, especially in cases where there is an occlusion of the palpable vas. The CFTR gene is probably not involved in the aetiology of Young's syndrome. Follow-up studies of children born to couples where the males have CBAVD, CUAVD or Young's syndrome are mandatory and will help to better define the risk to their offspring of CF and/or of inheriting their paternal infertility condition.

Cystic Fibrosis↗

Correlation between testicular histology and outcome after intracytoplasmic sperm injection using testicular spermatozoa.

A comprehensive study is presented of a series of 124 infertile men undergoing testicular sperm retrieval for intracytoplasmic sperm injection (ICSI). In this study we correlated the histological changes observed in the testicular tissue with the results of the wet preparation and the outcome after ICSI using testicular spermatozoa. In all patients with normal spermatogenesis and hypospermatogenesis spermatozoa were recovered from the wet preparation. The sperm recovery rate as 84% in patients with incomplete germ-cell-aplasia and maturation arrest, while in patients with complete germ-cell aplasia or maturation arrest this figure was 76%. In these patients more specimens were sampled and fewer spermatozoa were recovered. Since no spermatozoa were recovered in only 10 patients, ICSI with testicular sperm was performed in the remaining 114 couples (91.9%). The normal fertilization rate was 57. 8%. The fertilization rate was significantly lower in couples among whom the husband showed germ-cell aplasia and maturation arrest. Overall, 55.2% of normally fertilized oocytes developed into embryos showing <=50% of anucleate fragments. There were no major differences between the different histological categories in terms of embryonic development in vitro. The overall pregnancy rates per testicular sperm extraction (TESE) procedure, per ICSI procedure and per transfer were respectively 36.3, 39.5 and 43.7%. The overall implantation rate per embryo (sacs/embryos replaced) was 20.3%. A lower implantation rate was observed in couples among whom the husband had maturation arrest (not statistically significant). The above data show that testicular biopsies may have an important therapeutic role in the management of infertility in azoospermic patients.

Adult↗

Long-term evaluation of implantation of fresh and cryopreserved human embryos following ovarian stimulation with buserelin acetate-human menopausal gonadotrophin (HMG) or clomiphene citrate-HMG.

This study is a long-term evaluation of the total pregnancy potential of cohorts of fresh and cryopreserved sibling embryos from in-vitro fertilization (IVF) cycles stimulated with either the gonadotrophin-releasing hormone analogue buserelin (BUS) (long protocol) or clomiphene citrate (CC) both in combination with human menopausal gonadotrophin (HMG). Therefore a retrospective analysis was performed on patients who entered the IVF programme between January 1986 and July 1987 and who had triple embryo transfer in the collection cycle. Significantly more fertilized oocytes developed to good-quality embryos in the CC-HMG group (86.1%) than in the BUS-HMG group (80.8%). Transfer of the three morphologically best-looking embryos was performed in day 2 post-insemination in 106 CC-HMG and 80 BUS-HMG cycles. Supernumerary embryos were cultured for a further 24 h and multicellular embryos with up to 20% of fragments were frozen slowly with 1.5 M dimethylsulphoxide on day 3 post-insemination (162 embryos in CC-HMG cycles, 102 embryos in BUS- HMG cycles). Outcome was measured by embryo survival rate, embryo implantation rate and delivery rate in fresh and frozen embryo transfers. Delivery rates were 31.3 and 21.7% per fresh embryo transfer in BUS-HMG and CC- HMG cycles respectively. Fresh embryo implantation rates were significantly higher in collection cycles stimulated with BUS-HMG (17.9%) than in cycles stimulated with CC-HMG (11.3%). Implantation rates were significantly enhanced in embryos transferred in excess of one in cycles leading to pregnancy, perhaps indicative of higher embryo quality in BUS-HMG cycles. Almost all cryopreserved embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated. Overall morphological survival rates of frozen-thawed embryos have by now been thawed, so the contribution of frozen embryos to overall pregnancy rates can be evaluated Overall morphological survival rates of frozen-thawed embryos were similar for 140 embryos from CC-HMG cycles (50%) and 100 embryos from BUS-HMG cycles (46%). The percentage of fully intact embryos was, however, significantly lower in the BUS-HMG group (19%) than in the CC-HMG group (39.5%). Delivery rates were significantly lower following 30 transfers of frozen-thawed embryos from BUS-HMG-stimulated cycles (3.3%) than following 42 transfers of frozen-thawed embryos from CC-HMG cycles (19.1%). Embryo implantation rates were lower for frozen-thawed embryos from BUS-HMG cycles (2.3%) than from CC-HMG cycles (12.7%). Here we demonstrate that ovarian stimulation with the long protocol BUS-HMG instead of the CC-HMG protocol led to higher embryo implantation rates in collection cycles but to lower intact embryo survival rates and to lower embryo implantation rates for frozen sibling embryos. Despite the lower implantation rates with frozen embryos originating from the BUS-HMG protocol, there was no significant difference between total delivery rate per transfer from cycles stimulated with CC-HMG (30.2%) compared with BUS-HMG (33.8%).

Adult↗

Hormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix).

A third generation gonadotrophin-releasing hormone antagonist (Cetrorelix) was used during ovarian stimulation in 32 patients undergoing assisted reproduction, in order to prevent the premature luteinizing hormone (LH) surge. In all patients, ovarian stimulation was carried out with two or three ampoules of human menopausal gonadotrophin (HMG), starting on day 2 of the menstrual cycle. In addition, 0.5 mg of Cetrorelix was administered daily from day 6 of HMG treatment until the day of ovulation induction by human chorionic gonadotrophin (HCG). A significant drop in plasma LH concentration was observed within a few hours of the first administration of Cetrorelix (P < 0.005). Moreover, no LH surge was detected at any point in the treatment period in any of the 32 patients. A mean oestradiol concentration of 2111 +/- 935 ng/l was observed on the day of the HCG administration, indicating normal folliculogenesis. Like LH, progesterone concentration also dropped within a few hours of the first administration of Cetrorelix (P < 0.005). A 0.5 mg daily dose of Cetrorelix prevented a premature LH surge in all the 32 patients treated.

Adult↗

Outcome of intracytoplasmic sperm injection with testicular spermatozoa in obstructive and non-obstructive azoospermia.

From 1 August 1993 until 30 September 1994, 69 couples suffering from azoospermia underwent testicular sperm extraction and intracytoplasmic sperm injection. In 50 couples with obstructive azoospermia a total of 631 metaphase-II oocytes were injected after testicular sperm extraction yielding a 2-PN fertilization rate of 57%. In female patients <40 years of age an ongoing pregnancy rate per transfer of 42% (14/33) was obtained. So far, eight healthy babies have been born, including two singletons and three twin gestations. In 19 couples with non-obstructive azoospermia a total of 264 metaphase-II oocytes were injected after testicular sperm extraction, yielding a 2-PN fertilization rate of 58%. An ongoing pregnancy rate per transfer of 31% (5/16) was established. So far, six healthy babies have been born including one singleton, one twin and one triplet gestation.

Adult↗

Female age predicts embryonic implantation after ICSI: a case-controlled study.

From 1 October 1991 until 31 December 1993, 1270 cycles for intracytoplasmic sperm injection were performed. Of these, 71 (5.6%) were carried out in women >/=40 years of age. The semen characteristics in couples >/=40 years of age or <40 years were similar. The mean male age for the older group of women was 47.1 years (range 34-67) versus 35 years (25-71) for the younger group of women (P < 0.001). The mean female age was 41.9 years (range 40-47) and 31.8 years (range 23-39). The numbers of cumulus-oocyte complexes and metaphase-II oocytes were significantly lower in women >/=40 years of age (P < 0.001). The mean numbers of replaced embryos were respectively 2.3 (133/59) in women >/=40 years of age and 2.5 (160/63) in women <40 years of age. The delivery rate per retrieval and per transfer was significantly lower in women >/=40 years of age (P < 0.05). The delivery rates per retrieval and per transfer were respectively 7% (5/71) and 8.5% (5/59) in the older group of women versus 22.5% (16/71) and 25.4% (16/63) in the younger group. Female age is the predictive factor for embryonic implantation.

Adult↗

Subtle progesterone rise after the administration of the gonadotrophin-releasing hormone antagonist cetrorelix in intracytoplasmic sperm injection cycles.

In the present study, subtle serum progesterone rise (>= 1.1 ng/ml) during the late follicular phase is reported, for the first time to our knowledge, in patients using a potent gonadotrophin-releasing hormone (GnRH) antagonist, Cetrorelix, in combination with human menopausal gonadotrophin (HMG) for ovarian stimulation prior to intracytoplasmic sperm injection (ICSI). In five out of 24 patients (20%) serum progesterone levels were >/= 1.1 ng/ml. The cycle characteristics of the patients were similar in both groups. No premature endogenous luteinizing hormone (LH) surge occurred and the serum LH concentrations were constantly low during the follicular phase. The 17-beta oestradiol and follicle stimulating hormone (FSH) exposure were higher in cycles with premature luteinization. The greater oestradiol and FSH exposure confirm that one of the possible factors inducing subtle serum progesterone rise is the increased oestradiol and FSH-induced LH receptivity in granulosa cells.

Adult↗

Prospective follow-up study of 423 children born after intracytoplasmic sperm injection.

In order to evaluate the safety of the intracytoplasmic sperm injection (ICSI) procedure, a prospective follow-up study of 423 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Before starting the infertility treatment, couples were asked to participate in a follow-up study including genetic counselling and prenatal diagnosis. The follow-up study of the child was based on a visit to the paediatrician-geneticist at birth or at 2 months of age, at 1 year and at 2 years of age when a physical examination for major and minor malformations and a psychomotoric evaluation were done. Between April 1991 and September 1994, 320 pregnancies obtained after ICSI led to the birth of 423 children (222 singletons, 186 twins and 15 triplets). Prenatal diagnosis determined a total of 293 karyotypes, one of which was abnormal (0.3%), and four were benign familial structural aberrations, all inherited from the paternal side. A total of 14 (3.3%) major malformations were observed, defined as those causing functional impairment or requiring surgical correlation. Neurological or developmental problems at the age of 2 months were found in 14 children, four of whom were multiples. Compared to most registers of children born after assisted reproduction and to registers of malformations in the general population, the figure of 3.3% major malformations is within the expected range. Before drawing any firm conclusion, further careful evaluations of the available data are necessary.

Adult↗

Pregnancy and birth in an in-vitro fertilization cycle after controlled ovarian stimulation in a woman with a history of allergic reaction to human menopausal gonadotrophin.

We report a case of allergic reaction to i.m. injections of urinary human menopausal gonadotrophin (HMG) and a successful management of the problem by using recombinant follicle stimulating hormone (rFSH) administered i.m. The patient underwent two zygote intra-Fallopian transfer (ZIFT) cycles, in which ovarian stimulation was carried out by a combination of gonadotrophin-releasing hormone agonist (GnRHa) and HMG. A twin pregnancy was achieved after the first cycle. The patient delivered two premature boys at 28 weeks one of whom died after 25 days from severe respiratory distress. During the second ZIFT cycle the patient developed an allergic reaction with redness and swelling in many parts of her body 30 min after every HMG injection. Despite the allergic reaction, the cycle was completed with a second ZIFT. No pregnancy was achieved in this cycle. The patient came back to our centre for a third attempt during which ovarian stimulation was accomplished with a combination of GnRHa and rFSH. Adverse reaction as well as general discomfort were not reported by the patient during ovarian stimulation with rFSH. A successful singleton pregnancy was achieved after intrauterine embryo transfer with the birth of a healthy girl after 38 weeks. If any allergic reaction is present after injection of HMG it is advisable to stimulate a subsequent cycle with rFSH.

Adult↗

Testicular sperm recovery in nine 47,XXY Klinefelter patients.

Klinefelter's syndrome is generally characterized by hypergonadotrophic hypogonadism and azoospermia. The clinical features, however, are variable, and occasionally severe oligozoospermia may be present. Usually in these cases a 46,XY/47,XXY mosaic karyotype is involved. However, focal spermatogenesis and severe oligozoospermia have been reported in 47,XXY individuals too. In the present study we investigated whether testicular spermatozoa can be recovered in 47,XXY patients with a view to intracytoplasmic sperm injection (ICSI). In four out of nine apparently non-mosaic 47,XXY patients, spermatozoa were recovered from the wet preparations of testicular tissue and ICSI was performed in three couples. In one patient in whom spermatozoa were successfully recovered and used for ICSI, no spermatozoa were retrieved at a second trial. Although these results show that in some 47,XXY individuals testicular spermatozoa can be successfully recovered and even used for ICSI, at present this approach should be considered experimental. There may indeed be some concern about the chromosomal normality of the embryos generated through this infertility treatment. Patients with Klinefelter's syndrome should therefore be counselled about the complexity of this treatment, which involves multiple testicular biopsies from hypogonadal testes, ICSI and preimplantation diagnosis by fluorescence-in-situ hybridization.

Adult↗

Preimplantation diagnosis for X and Y normality in embryos from three Klinefelter patients.

In some 47,XXY Klinefelter patients without evidence of mosaicism, testicular spermatozoa can be successfully recovered and used for intracytoplasmic sperm injection (ICSI). To ensure the replacement of embryos with a normal X and Y chromosome pattern, preimplantation diagnosis can be performed. This paper reports on three 47,XXY Klinefelter patients from whom it was possible to retrieve testicular spermatozoa in order to perform ICSI. From their healthy wives a total of 27 oocyte-cumulus complexes were retrieved from which 22 metaphase-II oocytes were obtained and injected; 19 of these were intact after injection. Two distinct pronuclei were observed in eight oocytes (42.1%) 18 h after injection. On day 3 of development, five embryos (62.5%) had reached at least the 6-cell stage and were of sufficient quality to undergo biopsy and subsequent preimplantation diagnosis for sex chromosome analysis by fluorescent in-situ hybridization. The four embryos diagnosed as normal were transferred to three respective patients, resulting in one biochemical pregnancy. The remaining cells of the fifth embryo were analysed afterwards, revealing a normal X and Y chromosome constitution. So far, in the five embryos diagnosed, a normal sex chromosome pattern has been observed.

Embryo, Mammalian↗

Results of microsurgical epididymal sperm aspiration (MESA) ans testicular sperm extraction (TESE) in azoospermic men using intracytoplasmic sperm injection (ICSI).

The rationale and results of using epididymal and testicular spermatozoa with intracytoplasmic sperm injection (ICSI) for zoospermic patients are reviewed. A total of 128 consecutive ICSI/MESA cycles and a total of 120 consecutive ICSI/TESE cycles were performed up to December 1994. The two-pronuclei fertilization rate per intact oocyte (observed after the injection) was 58% and 60%, respectively, when epididymal and testicular spermatozoa were used. The embryo transfer rate was similar for the two procedures (91% after ICSI/MESA and 90% after ICSI/TESE). Fifty women became pregnant (positive HCG) when epididymal spermatozoa were used (39% per cycle and 40% per embryo transfer). These results are comparable to those obtained when ejaculated spermatozoa are used.

Cell Separation↗