Biomedical subjects

Herman Tournaye

Publications and source records attributed to Herman Tournaye.

At least 19 recordsLinked to original sources

PubMed2006

Human chorionic gonadotropin administration vs. luteinizing monitoring for intrauterine insemination timing, after administration of clomiphene citrate: a meta-analysis.

OBJECTIVE: To systematically compare hCG administration as a method for intrauterine insemination (IUI) timing with conservative urinary LH surge detection in infertility treatment. DESIGN: Meta-analysis of prospective and retrospective trials. SETTING: Tertiary fertility and IVF center. PATIENT(S): One thousand four hundred sixty-one patients who received hCG after a clomiphene citrate regimen, compared with 1,162 patients who had an LH surge detection for IUI timing. INTERVENTION(S): Both MEDLINE and Cochrane Collaboration were searched. References of retrieved articles were included in the search. The meta-analysis included all controlled trials examining the effectiveness of hCG administration before IUI on clinical-pregnancy rates in comparison with LH detection. Two independent reviewers performed data extraction. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Seven studies with 2,623 patients were included in the meta-analysis (1,461 patients received hCG, and 1,162 had LH surge detection). When all studies were combined, patients who received hCG before IUI demonstrated lower clinical-pregnancy rates than did women who had IUI after spontaneous ovulation (odds ratio, 0.74; 95% confidence interval, 0.57-0.961). In subgroup analysis of studies that considered ovulatory dysfunction to be the infertility reason, the results favored women who received hCG. In contrast, across studies that reported male factor as the infertility reason, as well as across studies including women with unexplained infertility, results appeared to favor the LH surge detection approach. However, none of those subgroup analyses reached statistical significance. CONCLUSION(S): Available data do not demonstrate a consistent, clinically important benefit of hCG-induced ovulation compared with spontaneous ovulation for IUI timing.

Adult↗

PubMed2006

The luteal phase of recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization cycles during supplementation with progesterone or progesterone and estradiol.

OBJECTIVE: To explore luteal phase hormone profiles in patients stimulated with recombinant FSH and GnRH antagonist for IVF under two different modes of luteal support: P and P with E(2). DESIGN: Prospective randomized study. SETTING: Patients in an academic reproductive medicine unit. PATIENT(S): One hundred and three patients undergoing ovarian stimulation with a fixed dose of 200 IU recombinant FSH and GnRH antagonist. INTERVENTION(S): Patients were randomized to receive luteal phase supplementation, either P vaginally (n = 49) or P and 4 mg E(2) orally (n = 54). MAIN OUTCOME MEASURE(S): Hormonal assessment during the luteal phase on days 1, 4, 7, and 10 after the administration of hCG. RESULT(S): Hormone levels did not differ during the luteal phase between the two groups with the exception of E(2) concentration on day 10 after hCG, which was significantly higher in the E(2)-supplemented group compared with the P group (median 760 pg/mL, range 2,496 vs. median 589.50 pg/mL, range 2,098). CONCLUSION(S): Addition of 4 mg E(2) for luteal support after stimulation with recombinant FSH and GnRH antagonist does not alter significantly the endocrine profile of the luteal phase until day 7 after hCG. At day 10 after hCG, the E(2) levels are significantly higher in the E(2)-supplemented group.

Adult↗

PubMed2006

Evaluation of in vivo conception after testicular stem cell transplantation in a mouse model shows altered post-implantation development.

BACKGROUND: Apart from research applications, testicular stem cell transplantation (TSCT) may one day also have valuable clinical applications. Therefore, it is important to investigate whether this technique is a safe method to have progeny. This controlled study aims at evaluating the fetuses and the live born offspring obtained after TSCT in male mice. METHODS: Male mice were mated with wild-type (WT) females after TSCT to produce offspring. First, fetuses were evaluated on the 17th gestational day. The length, weight and morphological age were compared to those of control mouse fetuses. The live born offspring were then investigated for their reproductive potential over three generations. RESULTS: The litter sizes after TSCT were decreased compared to controls. Fetuses showed developmental retardation of a quarter of a day, but no major external abnormalities were observed. The live born pups were able to produce normal litter sizes, at least until the third generation. CONCLUSIONS: Transplanted animals are able to reproduce naturally. Although litter sizes are lower and development is retarded, no major morphological or procreative abnormalities were observed.

Animals↗

PubMed2006

Chromosomal segregation in spermatozoa of 14 Robertsonian translocation carriers.

Male carriers of Robertsonian (Rob) translocations can have fertility problems associated with low sperm counts and abnormal sperm morphology. In this study, spermatozoa from 14 Rob translocation carriers, seven der(13;14), two der(13;15), two der(14;15), two der(14;21) and one der(21;22), were tested by fluorescence in-situ hybridization (FISH) for the chromosomes involved, to study meiotic segregation behaviour. It was shown that in each type of Rob translocation, meiotic segregation behaviour is similar, comparable and occurs non-randomly. Most of the spermatozoa results from alternate segregation (range: 76-89.47%). There is, however, still much unbalanced spermatozoa resulting from adjacent segregation mode (range: 10.24-23.41%). These data provide useful information for genetic counselling purposes. Moreover, aneuploidy for chromosomes 13,18, 21, X and Y was studied in five patients and suggested an inter-chromosomal effect.

Chromosome Segregation↗

PubMed2006

Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.

OBJECTIVE: To determine the incidence of ovarian hyperstimulation syndrome (OHSS) in a large series of GnRH antagonist-stimulated cycles and to assess the predictive value of E2 and the number of follicles on the day of hCG administration. DESIGN: Prospective cohort study of women undergoing IVF treatment with a GnRH antagonist protocol over a 2-year period. SETTING: Tertiary university hospital. PATIENT(S): One thousand eight hundred one patients who underwent 2,524 cycles. INTERVENTION(S): Multifollicular ovarian stimulation with recombinant FSH and GnRH antagonist for IVF-ICSI treatment. MAIN OUTCOME MEASURE(S): Incidence of OHSS in GnRH antagonist cycles, predictive value of E2, and number of follicles on the day of hCG for OHSS occurrence. RESULT(S): Fifty-three patients were hospitalized because of OHSS (2.1%; 95% confidence interval [CI]:1.6-2.8). Early OHSS presented in 31 patients (1.2%; 95% CI: 0.9-1.8), whereas the late type was a complication in 22 patients (0.9%; 95% CI: 0.5-1.3). Late OHSS cases compared with the early OHSS cases always occurred in a pregnancy cycle (100% vs. 40%); had higher probability of being severe (72.7% vs. 42%), and more often were related to a multiple pregnancy (40% vs. 0). Receiver operating characteristic curve analysis for several E2 concentrations and number of follicles with a diameter of > or =11 mm revealed that the predictive value of the optimal threshold of > or =13 follicles (85.5% sensitivity; 69% specificity) was statistically significantly superior to the optimal threshold of 2,560 ng/L for E2 concentrations (53% sensitivity, 77% specificity) in identifying patients at risk for OHSS. Considering that severe OHSS represents the most clinically significant pattern, the combination of a threshold of > or =18 follicles and/or E2 of > or =5,000 ng/L yields a 83% sensitivity rate with a specificity as high as 84% for the severe OHSS cases. CONCLUSION(S): Clinically significant OHSS still remains a limitation of multifollicular ovarian stimulation for IVF even with the use of GnRH antagonist protocols. The number of follicles can discriminate the patients who are at risk for developing OHSS, whereas E2 concentrations are less reliable for the purpose of prediction. There is more than ever an urgent need for alternative final oocyte maturation-triggering medication.

Adult↗

PubMed2006

Testicular stem cells.

Spermatogenesis originates from a constantly renewing population of testicular stem cells (TSCs). The existence of TSCs offers clinically relevant options for preservation and reestablishment of male fertility. Therefore, it is essential to understand the fundamental biology of TSCs and the basic mechanisms of self-renewal, differentiation, and regulation. Although fundamental knowledge of the biology of TSCs is limited, a number of markers have been identified recently. This article reviews the current knowledge of the biology, proliferation, and regulation of TSCs. In addition, new approaches to preserve male fertility are described. TSC transplantation and grafting can be applied to generate spermatozoa from TSCs. These techniques could therefore prove important for fertility restoration in young cancer patients. Based on this exciting research, this review also focuses on current knowledge and future options for cryopreservation, culture, selection, and transfection of TSCs.

Animals↗

PubMed2006

ICSI: hype or hazard?

Ever since its introduction in clinical practice more than 10 years ago, intracytoplasmic sperm injection (ICSI) has been the subject of ongoing debate regarding its indications and safety. ICSI is hyped because of its potential to give couples with severe male factor infertility a chance to conceive, and because of its apparently low fertilization failure rate compared with 'classic' in vitro fertilization (IVF). Concerns about ICSI are related to technical, biological and genetic hazards. ICSI has been branded 'the ultimate rape of the oocyte', as the oocyte membrane is mechanically pierced, appearing to bypass all biological and genetic selection. ICSI has been linked in a number of reports to an increased incidence of chromosomal anomalies, congenital abnormalities and perinatal hazards in offspring conceived with this technique. The etiology of the increased risk of chromosomal anomalies in ICSI offspring, especially sex-chromosome anomalies, is thought to be partly multifactorial, partly andrological, related to paternal karyotypic abnormalities and/or abnormal sperm. The majority of studies on ICSI and IVF offspring have, setting aside inconsistencies in methodology and classification, not shown significant differences between the two techniques in terms of congenital abnormalities, however, compared to naturally conceived offspring there does show an increased risk. This risk is attributed mainly to parental factors such as maternal age, poor sperm quality and infertility as an independent risk factor. Perinatal hazards may include low birth weight and perinatal mortality. Behavioural and psychological development is carefully monitored in ICSI and IVF children with no significant differences to the development of naturally conceived children, but many factors are involved including demographics. Follow-up studies are essential to the technique of ICSI. It is our duty to inform patients of the concerns and benefits to this treatment, based on the latest data available.

Female↗

PubMed2006

The role of hormones for the treatment of endometrial hyperplasia and endometrial cancer.

PURPOSE OF REVIEW: Hormone therapy has been palliative for advanced/ recurrent endometrial cancer. High remission rates are seen in well-selected stage I, grade 1 endometrial cancer of young women using hormone therapy (usually progestins) as fertility-preserving treatment. Many other hormones, such as gonadotropin-releasing hormone analogs (GnRHa), selective estrogen receptor modulators, aromatase inhibitors, intrauterine progestins, and others are potential modalities. This review updates the recent publications in this area. RECENT FINDINGS: Two reports investigating different scheduling of tamoxifen and progestins indicated that tamoxifen may be a valuable adjunct to progestin therapy. GnRHa has been used adjunctively to tamoxifen as second-line hormone therapy for fertility sparing after progestin failed. Aromatase inhibitors have shown their potential in treating endometrial cancer and endometrial hyperplasia as single agent or in combination with progestins. Intrauterine progestins seem efficacious in treating endometrial hyperplasia; its applications on endometrial cancer patients, however, have been limited to postmenopausal women with poor surgical risk. SUMMARY: Translational research based on molecular mechanisms is mandatory to a more appropriate utilization of hormone therapy. The role of dose, scheduling, route of administration of progestins as well as the addition of other hormonal agents should be further explored by well designed randomized controlled trials.

Aromatase Inhibitors↗

PubMed2006

Alterations of the USP26 gene in Caucasian men.

The Ubiquitin Specific Protease 26 gene is a testis-specific gene that is located on the X chromosome. Sequence variants of this gene were previously reported in men with azoospermia caused by defects at the level of spermatogenesis. Especially a cluster of three changes (c.370_371insACA, c.494T>C and c.1423C>T) was frequently observed. To further define the role of this cluster of sequence variants in the USP26 gene, we have now analysed 202 control samples and 146 patients of Caucasian origin with cryptozoospermia or oligozoospermia. The detection method was based on a restriction reaction, by which the change c.494T>C can be detected. In none of the patients, the change c.494T>C was observed. Only in one man with normal spermatogenesis this sequence variant was detected. Sequencing can confirm the presence of the three changes of the USP26 gene. These data indicate that the cluster of changes is not restricted to men with severe testicular dysfunction.

Amino Acid Sequence↗

PubMed2005

Menstruation-free interval and ongoing pregnancy in IVF using GnRH antagonists.

BACKGROUND: The purpose of this study was to evaluate prospectively the association between the achievement of ongoing pregnancy and the time interval from the end of menstruation until the administration of HCG (menstruation-free interval) in patients treated by IVF. METHODS: A fixed dose of 200 IU of recombinant FSH (rFSH) was started in 90 patients on day 2 of the menstrual cycle and daily GnRH antagonist was initiated on day 6 of stimulation. Triggering of final oocyte maturation was performed with 10,000 IU of HCG as soon as three follicles of > or =17 mm were present at ultrasound. RESULTS: Single embryo transfer was performed in 64.6% of the patients who reached embryo transfer (53/82). Ongoing pregnancy rate per embryo transfer was 18.3% (95% CI 11.4-28.0%). The menstruation-free interval significantly predicted the probability of ongoing pregnancy in a logistic regression analysis, controlling for female age and LH on day 1 of stimulation (odds ratio for the menstruation-free interval: 0.70; 95% CI: 0.54-0.92). CONCLUSION: The longer the interval from the end of menstruation until the administration of HCG, the lower the probability of ongoing pregnancy in patients stimulated with recombinant FSH and GnRH antagonist for IVF.

Adult↗

PubMed2005

Spermatogonial survival after grafting human testicular tissue to immunodeficient mice.

BACKGROUND: The xenografting of pre-pubertal human testicular tissue to an immunodeficient mouse is a theoretical strategy for restoring fertility in childhood cancer patients, while circumventing the risk of malignant recurrence. This study aimed at comparing the grafting of pre-pubertal and adult murine testicular tissue, as well as that of human adult testicular tissue, to two immunodeficient recipients, i.e. Swiss Nude mice and SCID-NOD mice. MATERIALS AND METHODS: In this study, we evaluated the survival of pre-pubertal and adult murine testicular tissues, and that of adult human testicular tissue after subcutaneous grafting to immunodeficient mice. RESULTS: After allografting pre-pubertal testicular tissue pieces, meiotic cells were observed in 69.1% of the grafts, while complete spermatogenesis was observed in 30.9%. All grafts of adult murine testicular tissue and 59.5% of the adult human testicular grafts showed sclerosis. However, in 21.6% of the adult human testicular grafts, spermatogonia were still observed, with increasing sclerosis in time. No significant differences were observed between the two mouse models under evaluation. CONCLUSION: After xenografting human adult testicular tissue to a recipient mouse, spermatogonia were maintained over a period of >195 days. However, in order to prove xenografting as a method for external germ line storage, the transplants should have a more immature developmental stage. Moreover, not only the developmental status of the tissue at the time-point of grafting, but also the structural organisation of the seminiferous epithelium, might influence the development of the testicular tissue.

Animals↗

PubMed2005

Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial.

BACKGROUND: The objective of this randomized controlled trial was to assess the effect of oral contraceptive pill (OCP) pretreatment on the probability of ongoing pregnancy in patients treated with a GnRH antagonist for IVF. METHODS: A fixed dose of 200 IU recombinant FSH (rFSH) was started in 425 patients either on day 2 of the menstrual cycle (non-OCP group: n = 211) or 5 days after discontinuing the OCP (OCP group: n = 214). GnRH-antagonist was initiated on day 6 of stimulation, and triggering of final oocyte maturation was performed with 10,000 IU of HCG. RESULTS: Ongoing pregnancy rates per started cycle in the non-OCP and OCP group were 27.5% and 22.9%, respectively [95% confidence interval (CI) of the difference: -3.7 to +12.8]. Pregnancy loss was significantly increased in the OCP (36.4%) compared with the non-OCP group (21.6%) (95% CI of the difference: -28.4 to -2.3). CONCLUSION: Pretreatment with OCP, as compared with initiation of stimulation on day 2 of the cycle in patients treated with GnRH antagonist and recombinant FSH, appears to be associated with a not significant difference in ongoing pregnancy rates per started cycle and results in a significantly higher early pregnancy loss.

Adult↗

PubMed2005

Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study.

INTRODUCTION: In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3. METHODS: Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group. RESULTS: Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05). CONCLUSIONS: A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.

Adult↗

PubMed2005

Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

BACKGROUND: Prolongation of follicular phase by delaying hCG administration has been reported to result in a significantly lower ongoing pregnancy rate that did not seem to be due to an embryonic factor. The aim of this prospective randomized study was to assess the effect of delaying hCG administration on endometrial histology. METHODS: Ten oocyte donors underwent endometrial biopsy on the day of oocyte retrieval and endometrial histology was assessed by Noyes' criteria. Ovarian stimulation was performed with recombinant (r)FSH and daily GnRH antagonist starting on day 6 of stimulation. Patients were randomized by a computer-generated list to receive 10 000 IU of hCG either as soon as > or =3 follicles > or =17 mm were present on ultrasound (early-hCG group, n = 5) or 2 days after this criterion was met (late-hCG group, n = 5). RESULTS: When hCG was delayed, endometrial advancement was present in all samples examined (median advancement 3 days, range 2-3 days). On the contrary, no secretory changes were observed when the follicular phase was not prolonged (difference in the proportion of patients with advancement between the early-hCG and the late-hCG group: 100%, 95% CI: 38-100). CONCLUSIONS: Prolongation of follicular phase by delaying hCG administration results in a higher incidence of endometrial advancement on the day of oocyte retrieval in GnRH antagonist cycles.

Adult↗

PubMed2005

The choice and outcome of the fertility treatment of 38 couples in whom the male partner has a Yq microdeletion.

BACKGROUND: Patients with Yq microdeletions may suffer from fertility problems. The purpose of this study was to assess the outcome of the fertility treatment of these patients. METHODS: For 38 patients with Yq microdeletions, data were collected about medical history, karyotype, testicular histopathology and the presence of spermatozoa in the ejaculate or testicular biopsies. RESULTS: Sixteen patients with an azoospermia factor region c (AZFc) deletion had at least one cycle with ICSI. The clinical pregnancy outcome was 22% per embryo transfer. Three babies have been born and two pregnancies are ongoing. Sex selection for female embryos in combination with ICSI in order to prevent the transmission of the fertility problems was discussed with 14 couples; eight were in favour of the selection. In addition, eight couples made the decision to use donor sperm because ICSI was impossible or objectionable and, in this group of patients, a total of nine babies were born. CONCLUSIONS: Despite the improvement of assisted reproductive technology, ICSI could be offered only to patients with an AZFc deletion. Insemination with donor sperm is a potential alternative for other patients.

Adult↗

PubMed2005

Steroid receptor expression in late follicular phase endometrium in GnRH antagonist IVF cycles is already altered, indicating initiation of early luteal phase transformation in the absence of secretory changes.

BACKGROUND: Ovarian stimulation for IVF profoundly alters the early luteal phase endometrial development. It has been hypothesized that this process has already started in the late follicular phase, as the endometrium has already been exposed to high steroid concentrations since that phase. The aim of the present study was to prospectively investigate the effect of multi-follicular ovarian stimulation for IVF on the late follicular phase endometrium histology and the expression of estrogen receptor (ER) and progesterone receptor (PR). METHODS: In a cross-over study, 11 infertile women with normal ovulatory function, participating in an IVF programme and treated with GnRH antagonist/recombinant FSH ovarian stimulation, were enrolled in the study. Endometrial biopsies were taken in a natural cycle on the day of the onset of the surge of the LH, and in a subsequent stimulation cycle on the day of hCG administration for final oocyte maturation. Endometrial histological dating was carried out according to Noyes' criteria. Immunohistochemistry was performed, using commercially available antibodies for ER and PR endometrial expression. The immunohistochemical signal was recorded in 1000 epithelial cells in each compartment (glands and stroma). Endometrial expression for each of the two receptors was graded on a scale of 0-3, based on the intensity of nuclear staining. Then a score range between 0 and 3000 was recorded, and expressed as a mean score per 1000 stroma or glandular cells per sample (range: 0-3). RESULTS: Histological examination of biopsies both in natural and stimulated cycles showed no secretory changes. However, in stimulated cycles, PR expression was significantly up-regulated compared to natural cycles in both glands (1.67 versus 1.34, P < 0.05) and stroma (1.98 versus 1.62, P < 0.05), whereas ER was down-regulated in glands (1.15 versus 1.43, P < 0.05). In IVF cycles, the progesterone measurements, although within normal values (range 0.8-1.4 microg/l), were significantly higher than in natural cycles (0.99 vs 0.63 microg/l, respectively, P = 0.008). An ongoing pregnancy rate of 37.5% was achieved in the stimulated cycles. DISCUSSION: Although the current study found no early secretory transformation in stimulated endometria before hCG administration, the ER and PR expression in these endometria is similar to the one described during the first days of the luteal phase in natural cycles. Supraphysiological concentrations of estradiol and subtle progesterone rises in the late follicular phase might be responsible for this modulated steroid receptor profile. This phenomenon indicates accentuated maturation of the endometrium in IVF cycles from the pre-ovulatory phase onwards.

Adult↗

PubMed2005

Thyroid function after assisted reproductive technology in women free of thyroid disease.

OBJECTIVE: To evaluate thyroid function in women undergoing a first assisted reproductive technology (ART) procedure and to compare women with ongoing pregnancy or miscarriage. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENT(S): Seventy-seven women free of thyroid disease. INTERVENTION(S): Serum TSH and FT4 were determined before and 2, 4, and 6 weeks after ET. All women received the same ART protocol. MAIN OUTCOME MEASURE(S): Thyroid function. RESULT(S): Forty-five women had ongoing pregnancies, and 32 suffered a miscarriage after 6.7 weeks (range 5-11). Mean age and number of ET were similar in both groups. Compared with baseline values, TSH and FT4 increased significantly 2 weeks after ET (ongoing pregnancies group: TSH 2.5 +/- 1.3 vs. 1.6 +/- 0.8 mU/L and FT4 13.8 +/- 1.4 vs. 12.4 +/- 1.8 ng/L; miscarriage group: TSH 2.1 +/- 1.0 vs. 1.5 +/- 0.7 mU/L and FT4 14.2 +/- 2.0 vs. 12.4 +/- 1.9 ng/L). Pregnancy outcome did not affect thyroid function and its evolution over time. CONCLUSION(S): In women free of thyroid diseases, thyroid function changed significantly after ART, but these changes were not different between women with ongoing pregnancy and miscarriage.

Abortion, Spontaneous↗

PubMed2005

SYCP3 mutations are uncommon in patients with azoospermia.

Mutation analysis of the SYCP3 gene was performed for 58 patients with a maturation arrest of spermatogenesis. In contrast to the previously reported high frequency of mutations, only polymorphisms were found in the present study.

Cell Cycle Proteins↗