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Biomedical subjects

P Devroey

Publications and source records attributed to P Devroey.

323 records · Page 18Linked to original sources

Counselling lesbian couples: requests for donor insemination on social grounds.

Fertility centres are increasingly involved in dealing with requests from lesbian couples for donor insemination (DI). Data were collected on 95 Belgian lesbian couples who applied for DI. The majority of couples were well integrated in a social environment (family, friends and work) that consisted mainly of heterosexuals. They tended to be open about their homosexuality and most couples considered the social environment to be tolerant towards their homosexual orientation. Couples who considered alternatives to DI would have liked to have had more information on the donor and were more inclined to introduce a 'godfather' who would take special interest in the child. Couples who considered DI to be the best solution considered the absence of a father to be less of a problem for the child and wished to have no information at all as regards the donor. Approximately half the couples considered their family a two-mother unit. For the other couples, the family unit consisted of a mother and her partner who shared parental responsibility for the child equally. The issues that are considered important to cope with and on which lesbian couples should be counselled are presented in the discussion.

Adult↗

Cystic fibrosis, Duchenne muscular dystrophy and preimplantation genetic diagnosis.

Cystic fibrosis (CF) is the most common genetic disease among Caucasians. Duchenne muscular dystrophy (DMD) is one of the most common X-linked genetic disorders. The CF and DMD genes were discovered a few years ago, which provided the possibility for prenatal diagnosis and preimplantation diagnosis of CF and DMD by using specific DNA analysis. In this article, CF, DMD, the process of the identification of the genes of CF and DMD and preimplantation genetic diagnosis are briefly described.

Blastocyst↗

Preparation of endometrium for egg donation.

Nowadays oocyte donation is a well established method of assisted reproduction and offers the unique opportunity to treat patients with various clinical indications, with or without ovarian function, in a novel way. In women with ovarian failure, artificial menstrual cycles are required before proceeding to oocyte donation. Oestrogen may be delivered in the form of oral tablets, transdermal patches in order to bypass the gastrointestinal tract thus avoiding first pass metabolism and by vaginal application. Our regimen is oestradiol valerate given in various concentrations, in order to mimic the regular cyclic fluctuations throughout the cycle. Progesterone may be administered in the form of oral tablets, intravaginal suppositories or rings and i.m. injections. Our results, as of most other groups, strongly support the vaginal route of progesterone administration. In women with retained ovarian function, synchronization of donor-recipient cycle presents a special problem, as there is strong evidence that a temporal window of maximal endometrial receptivity exists. Cryopreservation of donated embryos may be used to overcome the problem, but this approach has the important drawback of embryonic loss occurring after freezing and thawing. The method of choice is the administration of gonadotrophin-releasing hormone agonists (GnRHa) to render the patients functionally agonadal in order to circumvent cycle asynchrony between the donor and recipient.

Cryopreservation↗

Comparison between different routes of progesterone administration as luteal phase support in infertility treatments.

Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.

Administration, Intravaginal↗

The Brussels' experience of more than 5 years of clinical preimplantation genetic diagnosis.

This paper describes the 5 years' experience of preimplantation genetic diagnosis (PGD) at the Brussels Free University. Our first PGD was carried out in February 1993. Up to October 1998, we carried out 183 PGD cycles on fresh cleavage embryos of 92 couples for 25 different conditions. Patients were treated for autosomal recessive (n = 39), autosomal dominant (n = 65) and X-linked recessive (n = 47) monogenic disorders as well as for autosomal structural aberrations (n = 10), sex chromosome numerical and structural aberrations (n = 21) and a combination of the two latter (n = 1). Specific diagnosis was carried out by polymerase chain reaction (n = 108). Fluorescence in-situ hybridization was used for sexing (n = 64) and structural aberrations (n = 11). We transferred 1.6 +/- 1.1 embryos per cycle, resulting in an implantation rate of 12.0% per replaced embryo. Ongoing pregnancies were achieved in 29 cycles, i.e. 23 singletons, five twins and one dichorionic triplet with an acardius acranius. The ongoing pregnancy rates per cycle, per transfer and per couple were 16.4, 19.9 and 31.5% respectively. While 28 ongoing pregnancies resulted in the births of 34 infants, one pregnancy was terminated after misdiagnosis. The results of 24 PGD were confirmed by prenatal diagnosis or after birth while no information was available in four pregnancies. Our series demonstrates that PGD is a feasible technique by which to avoid the birth of genetically affected children to couples at risk.

Adult↗

Clinical implications of uterine malformations and hysteroscopic treatment results.

Uterine malformations consist of a group of miscellaneous congenital anomalies of the female genital system. Their mean prevalence in the general population and in the population of fertile women is approximately 4.3%, in infertile patients approximately 3.5% and in patients with recurrent pregnancy losses approximately 13%. Septate uterus is the commonest uterine anomaly with a mean incidence of approximately 35% followed by bicornuate uterus (approximately 25%) and arcuate uterus (approximately 20%). It seems that malformed uterus and especially septate uterus is not an infertility factor in itself. However, it may have a part in the delayed natural conception of women with mainly secondary infertility. On the other hand, patients with uterine malformations seem to have an impaired pregnancy outcome even as early as their first pregnancy. Overall term delivery rates in patients with untreated uterine malformations are only approximately 50% and obstetric complications are more frequent. Unicornuate and didelphys uterus have term delivery rates of approximately 45%, and the pregnancy outcome of patients with untreated bicornuate and septate uterus is also poor with term delivery rates of only approximately 40%. Arcuate uterus is associated with a slightly better but still impaired pregnancy outcome with term delivery rates of approximately 65%. Women who have undergone hysteroscopic septum resection and have been reported in the different series comprise a highly selected group of symptomatic patients with term delivery and live birth rates of only approximately 5%. Hysteroscopic treatment seems to restore an almost normal prognosis for the outcome of their pregnancies with term delivery rates of approximately 75% and live birth rates of approximately 85%. It seems, therefore, that hysteroscopic septum resection can be applied as a therapeutic procedure in cases of symptomatic patients but also as a prophylactic procedure in asymptomatic patients in order to improve their chances for a successful delivery.

Female↗

Follow-up of children born after ICSI.

The comparison of outcome of assisted reproductive technology (ART) children and naturally conceived children may be hampered by the difference in characteristics of the infertile patients such as age and genetic risks. Follow-up studies are further hampered by the type of neonatal surveillance protocol, the number of individuals lost to follow-up, the size of the cohort study, and the lack of standardization, for example to define major anomalies. The limited available data on ICSI fetal karyotypes reveal that, in comparison with a general neonatal population, there is: (i) a slight but significant increase in de-novo sex chromosomal aneuploidy (0.6% instead of 0.2%) and structural autosomal abnormalities (0.4% instead of 0.07%); and (ii) an increased number of inherited (mostly from the infertile father) structural aberrations. Available data indicate that in 8319 liveborn ICSI children, the mean percentage who do not originate from singleton pregnancies was 40% (range 32.6-60.8% according to centre). Most multiples are twins, but there are also 4.4% triplets (in one survey 13.2%). This substantial increase in multiple pregnancies must be considered the most important complication of ART. The different percentages of major and minor congenital malformations cannot be compared, but overall the data in large and reliable surveys does not indicate a higher rate of malformations in ICSI children than in naturally conceived children. To date, only three studies have examined the medical and developmental outcome of ICSI children at 1 and 2 years. These do not reveal obvious problems, but in future further comparison of matched cohorts of children and case-control studies are needed before final conclusions can be drawn.

Aneuploidy↗

PGD in 47,XXY Klinefelter's syndrome patients.

The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis, may benefit from the ICSI technique in order to father a child. As ICSI use has become more common, centres have introduced infertility treatment for Klinefelter patients. To date, 34 healthy children have been born using ICSI without PGD, and the conception of one 47,XXY fetus has been reported. In view of the possible risk of an increased gonosome number in the spermatozoa of Klinefelter patients, a safer approach--offering these couples ICSI combined with PGD--has been used, and has resulted in the birth of three healthy children. Couples in which the male suffered from Klinefelter's syndrome were first treated in 1995; these patients were offered ICSI + PGD using FISH technology, notably to enumerate the X and Y chromosomes. ICSI + PGD was performed in 32 cycles of 20 couples with spermatozoa originating from a fresh ejaculate (n = 1), testicular biopsy (n = 21) or frozen-thawed testicular biopsy (n = 10). Normal fertilization occurred in 56.0 +/- 22.4% of the successfully injected oocytes. On day 3 of development, 119 embryos from 29 cycles were of sufficient quality to undergo biopsy and subsequent PGD; a positive result was obtained in 113 embryos. Embryos were available for transfer in 26 cycles, with a mean of 1.6 +/- 0.6 embryos per transfer. Eight pregnancies were obtained, and five resulted in a delivery. A total of 113 embryos from couples with Klinefelter's syndrome was compared with 578 embryos from control couples with X-linked disease where PGD was used to determine gender. A significant fall occurred in the rate of normal embryos for couples with Klinefelter's syndrome (54.0%) compared with controls (77.2%). Moreover, a significantly increased risk of abnormalities was observed for sex chromosomes and autosomes; for each autosome separately, this reached significance level for chromosomes 18 and 21 only. Hence, a cautious approach is warranted in advising couples with non-mosaic Klinefelter's syndrome. Moreover, the use of ICSI + PGD or prenatal diagnosis should be carefully considered.

Embryonic and Fetal Development↗

A review of ten years experience of ICSI.

This review summarizes the introduction of ICSI in the early 1990s as an assisted fertilization procedure in couples with severe male factor infertility, who could not be helped by conventional IVF. As for current practice, the indications for ICSI using fresh or frozen-thawed ejaculated, epididymal or testicular sperm are reviewed as well as some reports on the use of ICSI in non-male infertility. The main steps in an ICSI cycle are well standardized by now; it is rare that ICSI cannot be carried out and the results in terms of fertilization, embryo transfer and clinical pregnancy rate have been consistent for many years, indicating that a substantial number of couples can now have their own genetic child instead of having to use artificial insemination with donor sperm. This review also emphasizes the importance of assessing the risk of ICSI for the children: there is a slight increase in de novo chromosomal abnormalities, the major congenital malformation rate is similar for IVF and ICSI (between 3 and 4%), and at approximately 2 years of age the developmental outcome as assessed by the Bayley scale is similar for IVF and ICSI. Recent publications mention that a few children are affected by diseases caused by imprinting disorders. Future studies are needed to assess the association between assisted reproductive technologies and imprinting disorders. ICSI is frequently used in couples undergoing preimplantation genetic diagnosis. PGD stricto sensu as well as PGD for aneuploidy screening and for Klinefelter patients are reviewed using the ESHRE PGD Consortium data.

Embryo Implantation↗

Progesterone administration in patients with absent ovaries.

Forty-four women with absent ovaries who were referred to our centre for oocyte donation were treated with oestradiol valerate and natural progesterone. Serum concentrations and endometrial changes were evaluated on day 21 of stimulated luteal phases after the daily administration of 100 mg of natural progesterone in oil injected intramuscularly or after the ingestion of 300 mg of micronized progesterone or after vaginal administration of 300 mg or 600 mg micronized progesterone, respectively. Endometrial tissue did not show evidence of an adequate secretory pattern after orally administered progesterone. However, after intramuscular injection of 100 mg of natural progesterone and after the vaginal administration of 300 to 600 mg of micronized progesterone, the histologic and electron microscopic pictures were similar in all treatment groups and were close to the expected day 21 of the cycle. Serum levels of progesterone after intramuscular injection were five times higher than after vaginal administration.

Administration, Intravaginal↗

Follicular rupture changes the endocrine profile of peritoneal fluid.

We determined the concentration of progesterone (P) and 17 beta-estradiol (E2) in peritoneal fluid 32 hours after endogenous luteinizing hormone surge (LH) or 34 hours after injection of human chorionic gonadotropin (hCG) in 4 groups of patients: group A: 5 natural cycles, unruptured follicles, mean concentrations of P (1.48 micrograms/l) and E2 (169 ng/l); group B: 28 stimulated cycles, unruptured follicles after an endogenous LH surge, mean concentrations of P (5.33 micrograms/l) and E2 (1 344 ng/l); group C: 13 stimulated cycles, ruptured follicles after endogenous LH surge, mean concentrations of P (446 micrograms/l) and E2 (59 500 ng/l); group D: 8 stimulated cycles, unruptured follicles after injection of hCG, mean concentrations of P (8.21 micrograms/l) and E2 (551 ng/l). The variations of the hormonal concentrations in peritoneal fluid are discussed.

Ascitic Fluid↗

Success of in vitro fertilization and embryo transfer in relation to the causes of infertility.

In 1984 163 patients were treated in our in vitro fertilization program, including 4 patients accepting embryos from the oocyte and embryo donation program. Twenty pregnancies were achieved with an average chance per transfer of 16,6%. The final success of IVF strongly depends on the cause of infertility. The best results were obtained for patients with tubal infertility, with a pregnancy rate of 15% per laparoscopy and 19% per transfer. There is a significant decrease in oocyte cleavage rate from tubal (61%) to male infertility (13%). Once the barrier of embryo formation is taken, there is no marked difference in the mean number of embryos transferred on the pregnancy rate after transfer, among the different patient groups. In patients with tubal infertility the pregnancy rate per cycle remains constant, resulting in a cumulative pregnancy rate of 40% after 3 cycles.

Antibodies↗

Ovarian adhesions impair ovulation.

The concentration of progesterone in peritoneal fluid, aspirated from the pouch of Douglas by laparoscopy, 72 hours after the peak of the luteinizing hormone in serum is believed to indicate whether the ovarian follicle has ruptured or not. Twenty six patients were studied. The volume of peritoneal fluid 72 hours after the peak of the luteinizing hormone was markedly decreased when bilateral ovarian adhesions were present. Progesterone concentrations, assayed during the early luteal phase in peritoneal fluid of women with bilateral ovarian adhesions, were significantly lower than in women with a corpus luteum presenting an ovulation stigma and even significantly lower than in those without ovulation stigma (luteinized unruptured follicle syndrome). The assay of progesterone in peritoneal fluid during the early luteal phase may be of value in women with ovarian adhesions.

Estradiol↗

Incidence, recurrence and treatment of the luteinized unruptured follicle syndrome.

The frequency of the luteinized unruptured follicle (LUF) was determined in a population of 220 regularly cycling women, infertile for at least two years. Laparoscopy was performed during the very first days of the luteal phase. In 26 women without other demonstrable cause of infertility, a diagnosis of LUF was made based on the absence of an ovulation stigma and the low concentrations of progesterone (P) and 17 beta-oestradiol (E2) in peritoneal fluid (PF). Twenty of these 26 women underwent a culdocentesis 72-96 hours after the serum LH-rise in a following cycle. In 19 out of 20, low P and E2 concentrations in PF were again found, suggesting the recurrence of LUF. Subsequently, ovulation was induced with human menopausal gonadotrophins (hMG) alone (n = 4), or in combination with human chorionic gonadotrophin (hCG, n = 9). At carefully timed culdocentesis (at LH/hCG + 72-96 hours), P concentration in PF was high in the hMG-hCG treated women but remained low in those given hMG alone. The combination of hMG and hCG may be a valuable treatment of LUF.

Anovulation↗

A survey of four years of experience with intracytoplasmic sperm injection.

The present report covers the results of a 38-month period in which 2853 consecutive intracytoplasmic sperm injection (ICSI) cycles were performed in 1953 couples. These couples were afflicted with male factor infertility and had at least one previous failed conventional in vitro fertilization (IVF) treatment cycle. In other couples, the husband had semen parameters incompatible with conventional IVF or suffered from excretory or secretory azoospermia where it was possible to recover spermatozoa by microsurgical epididymal sperm aspiration (mesa) or by testicular sperm extraction (tese) procedure. Overall, the 2-PN fertilization rate was 62% per retrieved metaphase II oocyte and 70% per successfully injected metaphase II oocyte. Embryo transfer was performed in 91% of started cycles. The cumulative pregnancy rate (positive HCG) was 34% per started ICSI treatment and 37% per embryo transfer.

Adult↗