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Biomedical subjects

L Van Waesberghe

Publications and source records attributed to L Van Waesberghe.

At least 19 recordsLinked to original sources

A randomized comparison of the cryopreservation of one-cell human embryos with a slow controlled-rate cooling procedure or a rapid cooling procedure by direct plunging into liquid nitrogen.

We conducted a randomized prospective study of the cryopreservation of one-cell human embryos, comparing a slow controlled-rate freezing procedure with a rapid cooling procedure by direct plunging into liquid nitrogen. We analysed the numbers of embryos that were recovered immediately after thawing (= recovery), the number of embryos morphologically intact after thawing and subsequent dilution of the cryoprotectants (= survival), the numbers of embryos undergoing further cleavage after 24 h of in-vitro culture (= cleavage) and the implantation of transferred embryos (= children born per frozen-thawed embryo transferred). We demonstrated that the recovery of embryos was greater after slow controlled-rate freezing. Survival was greater after rapid cooling and the number of embryos undergoing further cleavage was higher after slow controlled-rate freezing. Although the birth rate was twice as high after slow controlled-rate freezing as after rapid cooling, this difference was not statistically significant. In conclusion, our results show clearly that for the freezing of one-cell human embryos, slow controlled-rate freezing is more efficient than rapid cooling. Before rapid cooling is used routinely in clinical in-vitro fertilization programmes, its safety and reproducibility must be convincingly demonstrated.

Cleavage Stage, Ovum↗

Viability of partially damaged human embryos after cryopreservation.

In our centre, embryos are judged to have survived cryopreservation if at least half of the initial number of blastomeres remain intact. Therefore both fully intact and partially damaged embryos are transferred. The aim of this study was to investigate the viability of partially damaged human embryos after cryopreservation. We retrospectively analysed the implantation and in-vivo development of embryos which were either fully intact or had lost some blastomeres after cryopreservation. Oocytes were collected following stimulation with the gonadotrophin-releasing hormone (GnRH)-agonist Buserelin and human menopausal gonadotrophin. Supernumerary multicellular embryos with not more than 20% of their volume filled with anucleate fragments were frozen on day 2 or day 3 of the cycle using a slow cooling procedure with dimethylsulphoxide as the cryoprotectant. Following slow thawing, 431 fully intact embryos were transferred in 314 embryo transfer procedures and 488 partially damaged embryos were transferred in 327 such procedures. The percentage of gestational sacs with fetal heartbeat obtained after transfer of fully intact embryos was almost three times higher than that after transfer of partially damaged embryos (11.4 versus 3.5%). Forty-five children (birth rate 10% per embryo transfer) were born after transfer of fully intact embryos and 14 after transfer of embryos from which some blastomeres had been lost following cryopreservation. In conclusion, although children have been delivered after transfer of partially damaged embryos, the aim of a cryopreservation programme must be to obtain fully intact embryos after thawing.

Blastomeres↗

A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation.

A prospective randomized study was conducted to evaluate the use of adding oestradiol valerate 6 mg per os daily to intravaginal micronized progesterone (600 mg daily) as luteal supplements. The study comprised 378 infertile women superovulated with a gonadotrophin releasing-hormone agonist (GnRHa) and human menopausal gonadotrophins (HMG) for in-vitro fertilization (IVF) or zygote intra-Fallopian transfer (ZIFT). The clinical pregnancy rate was similar (29%) whether or not oestradiol valerate was added to intravaginal progesterone. Eighteen out of twenty-two endometrial biopsies were in phase, and morphological evaluations of the two luteal supplementation groups were not different. Serum hormone profiles in singleton pregnancies showed a similar day of appearance of human chorionic gonadotrophin (HCG) in both protocols but significantly lower oestradiol concentrations arose in the group without oestradiol valerate. In 32% of the singleton pregnancies, the first appearance of HCG occurred later than day 12 after HCG injection; in those ongoing pregnancies, corpus luteum rescue--as measured by significantly lower serum oestradiol and progesterone concentrations--was compromised. This study provided no evidence of any benefit of routinely supplementing GnRHa/HMG cycles with oestradiol valerate in addition to intravaginal micronized progesterone.

Administration, Intravaginal↗

Oocyte and embryo donation: evaluation of 412 consecutive trials.

A total of 199 patients (412 consecutive cycles) were treated by oocyte-embryo donation in 336 replacement cycles. Of these, 296 involved intra-uterine embryo transfers, 38 zygote intra-Fallopian transfers (ZIFT) and two gamete intra-Fallopian transfers (GIFT). Of the 336 replacements, 244 (73%) constituted transfers of fresh concepti and 92 (27%) of frozen-thawed ones. A total of 85 pregnancies were achieved of which 16 ended in preclinical abortions, giving a clinical pregnancy rate of 34.7% per patient, 20.5% per transfer and a take-home baby rate of 29.1% per patient. The pregnancy rate was significantly higher (P less than 0.05) following fresh gamete or embryo replacement (23%; 56/244) than following that of frozen-thawed embryos (14.1%; 13/92). No significant difference was observed when intra-Fallopian replacement was applied (27.5%; 11/40) as opposed to intra-uterine (19.6%; 58/296). Ovarian function was not found to be of significant importance to the achievement of pregnancies after oocyte donation since comparable pregnancy rates per replacement and per started cycle were obtained in patients with ovarian failure and in those with functional ovaries (19% and 15.4%; 24.2% and 20.2% respectively). Comparison of the implantation and abortion rates between these two groups did not reveal any significant difference (11.1% and 11.1% versus 14.8% and 16.6%). The highest pregnancy rate among patients with ovarian failure was observed in those with primary ovarian failure (26.4%; 14/53), while the lowest was among women who had received chemotherapy and/or radiotherapy (9%; 1/11).(ABSTRACT TRUNCATED AT 250 WORDS)

Embryo Transfer↗

Placental production of estradiol and progesterone after oocyte donation in patients with primary ovarian failure.

After oocyte donation 18 pregnancies were established in 17 patients with the absence of ovaries. Eight patients were delivered of nine healthy infants including one set of twins, six pregnancies were progressing normally, and four pregnancies were aborted. Four pregnancies were established after transfer of frozen-thawed embryos. In the simulated luteal phases, replaced with estradiol valerate and progesterone, pregnancies could be established and maintained as indicated by the profile of serum human chorionic gonadotropin concentrations. Weekly determinations of serum 17 beta-estradiol levels indicated significantly higher values at 7 weeks' gestation, as compared with week 5. This observation precludes that the luteoplacental shift occurred before 7 weeks' gestation. The weekly serum determinations of progesterone were significantly higher week 9, as compared with week 5. Two pregnancies were achieved after the vaginal administration of micronized progesterone.

Adult↗

Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure.

In 43 patients without ovaries, endometrial biopsies at day 21 of 75 substituted cycles were studied by light and electron microscopy. The morphology of the endometrium was compared after oral, vaginal or intramuscular administration of progesterone, and correlated with the serum levels of 17-beta oestradiol and progesterone and the pregnancies obtained after oocyte donation. After vaginal application of micronized progesterone, endometrial morphology closely matched that of a natural cycle. This therapy was able to support two ongoing pregnancies. No adequate endometrial response was noted after oral ingestion of progesterone. The maturation of the endometrium after intramuscular injections of progesterone in oil was heterogeneous. It was concluded that the vaginal route for administering micronized progesterone can be advised as the treatment of choice in patients without ovarian function.

Administration, Oral↗

An 18-month survey of infertility treatment by in vitro fertilization, gamete and zygote intrafallopian transfer, and replacement of frozen-thawed embryos.

An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N = 793) or ultrasonically guided (N = 342) ovum pickup, gamete intrafallopian transfer (GIFT; N = 284), or zygote intrafallopian transfer (ZIFT; N = 15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure one-third of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.

Adult↗

Human embryo viability after freezing with dimethylsulfoxide as a cryoprotectant.

This study concerns the effects of a slow freezing and thawing protocol using dimethylsulfoxide (DMSO) as a cryoprotectant on the survival and viability of 319 supernumerary human embryos produced after in vitro fertilization. One hundred twenty-one transfers were performed in a natural cycle and 18 pregnancies were achieved (15%), from which 14 were ongoing (12%). Overall, 52% of the thawed embryos retained at least 50% of their initial blastomeres intact after thawing, and were replaced. Survival was strongly correlated to prefreezing embryonic quality, as 78% of type I embryos, 55% of type II, 40% of type III, and none of type IV could be transferred. Implantations were obtained from type I embryos (21% per embryo replaced) and from type II (14.5%), whereas none of the type III embryos resulted in a pregnancy. In the authors' experience, using the DMSO protocol, the best pregnancy rates were achieved when replacing 8-cell embryos of high morphologic prefreezing quality. No statistically significant difference could be demonstrated, however, in implantation rates between 8-cell and 4-cell embryos, or between synchronously and asynchronously dividing concepti.

Blastomeres↗

Synchronization of donor's and recipient's cycles with GnRH analogues in an oocyte donation programme.

In this oocyte donation programme nine female donors were stimulated using a combination of GnRH analogues and human menopausal gonadotrophins. A total of 149 oocytes were retrieved. Thirty fresh embryos were transferred in 14 uterine replacements, resulting in four pregnancies and 15 fertilized oocytes were placed in the Fallopian tube of six recipients, yielding two pregnancies. A mean number of 2.2 embryos was replaced. The implantation rate per embryo was 13%. Furthermore 36 embryos were cryopreserved for later use. Following 20 replacements, six pregnancies were established (30% per transfer); since two patients aborted, the ongoing pregnancy rate was 20%.

Adult↗

Chromosome studies and fertility treatment in women with ovarian failure.

In vitro fertilization and embryo transfer or gamete (or zygote) intra-Fallopian transfer after ovum donation were performed in 16 patients with primary or secondary amenorrhea, associated with chromosome abnormalities. The patients showed the wide range of (mostly X) chromosome abnormalities characteristic for women with primary or premature ovarian failure. Four of these patients became pregnant and three of them have delivered healthy infants with a normal karyotype. This pregnancy rate is far superior to the accepted fertility figure in these patients. When these results were compared with the fertility treatment results of three other groups of women with absent ovarian function (1. ovarian dysgenesis; 2. surgical castration; 3. premature menopause) but with a normal 46,XX karyotype, no difference in treatment efficiency could be detected. These results offer a promising approach for the treatment of infertility in agonadal patients with chromosome aberrations.

Adult↗

Perurethral ultrasound-guided ovum pickup.

Either a percutaneous-transvesical, a transvaginal, or a perurethral-transvesical approach can be used for oocyte recovery under ultrasound guidance in an in vitro fertilization and embryo transfer program. After having experienced these three different approaches in our program, we preferentially used the perurethral-transvesical approach as our routine technique for oocyte recovery under ultrasound guidance. We feel that this method is easier to perform and also carries less risk for contamination. From January to December 1986, 186 oocyte retrievals under ultrasound guidance were performed. In 7 cases no oocytes were found despite normal ovarian stimulation. A total of 767 oocytes was collected; the fertilization rate was 71.8%. Forty pregnancies were achieved (21.5% per attempt or 27.7% per embryo replacement). Except for transient hematuria, no complications were observed.

Chorionic Gonadotropin↗

Inhibition of gonadotropic and ovarian function by intranasal administration of D-Ser (TBU)6-EA10-LHRH in normo-ovulatory women and patients with polycystic ovary disease.

We investigated the effectiveness of D-Ser (TBU)6-EA10-LHRH (Buserelin) intranasally 600 micrograms/day given 6 times daily in desensitizing normal ovulatory women and patients with polycystic ovarian disease (PCOD) before initiation of ovarian stimulation for in vitro fertilization. We found that this regimen was sufficient to suppress the gonadotrophs in the normal women and in 8 out of 10 PCOD patients. In PCOD ovarian hormones became normal after Buserelin administration. Adrenal steroidogenesis was not affected by the GnRH agonist. We suggested that the frequency of administration of Buserelin was important to achieve a constant receptor binding and consequently a rapid desensitization. The choice of a monoclonal immunoradiometric assay for luteinizing hormone (LH) and follicle stimulating hormone (FSH) in association with the estradiol-benzoate provocation test were essential in evaluating desensitization.

Administration, Intranasal↗

Hormonal monitoring for in-vitro fertilization and related procedures.

Details of the endocrine monitoring of patients during in-vitro fertilization are analysed. Hormones usually measured are 17 beta-oestradiol, FSH, LH, progesterone and HCG. The assays must be rapid, robust, and have satisfactory precision and reproducibility. Radioimmunoassays have become standardized but immunoradiometric assays are being introduced, where the antibodies can be more easily labelled than antigens, but need care with very high concentrations of antigen. Enzyme immunoassays also have advantages: they are less hazardous than radioimmunoassays and the labelled materials have longer shelf-lives. Chemiluminescence has also been introduced, together with time-resolved fluoroimmunoassays, representing simpler, perhaps cheaper and improved methods. Immunoassays by latex particle counting offer the advantage of being completely automated. Practical examples of these methods are given with details of the treatment of individual patients.

Chorionic Gonadotropin↗

Addition of Buserelin to human menopausal gonadotrophins in patients with failed stimulations for IVF or GIFT.

The combined therapy of a gonadotrophin-releasing hormone agonist (GnRHa) D-Ser(TBU)6-EA10-LHRH (Buserelin) and human menopausal gonadotrophins (HMG) for ovarian stimulation for in-vitro fertilization and gamete intra-Fallopian transfer was evaluated during 84 cycles. All women selected for this therapy had previously failed stimulations with clomiphene citrate/HMG. The GnRHa prevented spontaneous luteinizing hormone surges and premature luteinization in all patients. After addition of the agonist to HMG, the cancellation rate dropped from 17 to 7% and improved the results in 72.6% of the cycles. Twenty-six per cent of the started cycles resulted in a pregnancy. Eighteen healthy children were born at term.

Buserelin↗

Hyperstimulation: the need for cryopreservation of embryos.

Successful application of in-vitro fertilization (IVF), zygote intra-Fallopian transfer (ZIFT) and gamete intra-Fallopian transfer (GIFT) requires ovarian hyperstimulation for the maturation of multiple follicles. To control the risk of multiple pregnancies, the number of gametes (GIFT) or embryos (IVF, ZIFT) replaced is limited to three. For the supernumerary embryos resulting from IVF, ZIFT or GIFT, the strategy is cryopreservation for a later transfer. Cryopreservation was performed using either dimethylsulphoxide or 1,2-propanediol as a cryoprotective agent. Embryos were frozen either in the pronucleate stage with 1,2-propanediol or in the multicellular stage with dimethylsulphoxide or 1,2-propanediol. Survival after thawing was scored for both cryoprotective agents as a function of the developmental stage of the embryo and the embryonic quality. Evaluation of survival after thawing was performed on the basis of morphological intactness of the 1-cell pronucleate embryo or of the blastomeres of multicellular embryos. For pronucleate stage embryos, the use of 1,2-propanediol resulted in a 60% survival after thawing. For 2-cell stage embryos the survival was similar for dimethylsulphoxide and 1,2-propanediol. Later stage embryos survived better when dimethylsulphoxide was the cryoprotectant. For all stages, embryo quality before freezing was a crucial factor in survival after thawing. The pregnancy rate (12.2%) was similar for the two cryopreservation protocols. In conclusion, the choice of an appropriate cryoprotective agent can increase the survival after thawing when embryos are of good quality before freezing.

Cryoprotective Agents↗

Embryo donation in patients with primary ovarian failure.

Thirty-six infertile patients with primary ovarian failure, who were referred for oocyte (embryo) donation are reported. After substitution therapy with oestradiol valerate (per os) and progesterone (i.m. or per os), endometrial tissue was made receptive for embryonic implantation, although the endometrial biopsies on day 21 demonstrated a certain delay in development (of 1.6-2.4 days). Six patients became pregnant, three of them delivered four healthy babies, one pregnancy is progressing normally and two ended in an early clinical abortion.

Chromosome Aberrations↗

In-vitro fertilization with husband and donor sperm in patients with previous fertilization failures using husband sperm.

When previous attempts at in-vitro fertilization using semen from the husband failed, a subsequent IVF attempt was performed using husband and donor sperm in order to compare fertilization and embryo formation after insemination with husband and donor sperm of the same oocyte population. Significantly more eggs were fertilized in patients suffering from andrological and idiopathic infertility when donor sperm were used. No differences were seen in patients with tubal infertility. In the andrological group, the embryos fertilized by the husband showed significantly more fragmentation. No pregnancies were established when husband-fertilized oocytes (embryos) were replaced in the andrological and idiopathic infertility group. This study suggested that an IVF trial using husband and donor sperm might be indicated in couples suffering from andrological or idiopathic infertility in whom no fertilization occurred in a previous cycle using sperm from the husband.

Adult↗

The luteal phase after in-vitro fertilization and related procedures.

To evaluate any beneficial effect of progesterone supplementation during the luteal phase of GIFT or IVF cycles stimulated by clomiphene citrate and HMG, two random prospective studies were performed. In the first study, a group of patients received a luteal phase supplement of 50 mg natural progesterone i.m. daily from the day of oocyte retrieval onwards. Initial results on 168 patients indicated that the pregnancy rate was similar in patients with or without progesterone supplements. No differences were found between the two groups in an analysis of pregnant and failed cycles. In a second study two different protocols of luteal phase supplementation after Buserelin-HMG stimulation were compared: natural progesterone in combination with oestradiol valerate (50 patients) or HCG supplements (41 patients). A 32% pregnancy rate per cycle was encountered in both groups. Endometrial biopsies, taken during the luteal phase from patients who did not undergo embryo replacement, revealed retarded endometrial development in most of the biopsies.

Buserelin↗