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Biomedical subjects

H Tournaye

Publications and source records attributed to H Tournaye.

At least 37 records · Page 2Linked to original sources

Clomiphene citrate versus letrozole for ovarian stimulation: a pilot study.

The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle.

Adult↗

ICSI: a technique too far?

Even now 10 years after its introduction, there is still debate on the possible adverse effects of intracytoplasmic sperm injection (ICSI). ICSI has raised a lot of concerns because of the mechanical perforation of the oocyte, the possible transmission of foreign genetic material, the use of immature or senescent germ cells and the association between genetic disorders and some forms of male infertility. To date, the data available indicate that ICSI is a safe procedure provided this treatment is performed in clinics with the highest standards of expertise and with a continuous follow-up programme for the offspring. It is becoming increasingly apparent that it is not ICSI itself, but the background risks of the ICSI patients that represent the major risk factor with regard to congenital malformations. More sex-chromosome abnormalities have been reported in ICSI offspring. Again, the risk of aneuploidy in ICSI progeny reflects the higher aneuploidy rate in the sperm of ICSI fathers. Whether ICSI will eventually perpetuate male infertility is far from clear, because at present the inheritance pattern of idiopathic male infertility is unknown. All ICSI candidates should nevertheless be thoroughly screened and counselled. As long as follow-up studies have a limited power to detect small increases in malformations and as long as no information is available on long-term and next-generation cohorts, ICSI must be used with caution and only when no alternative evidence-based therapy is available. All ICSI candidates should be rigorously screened and thoroughly informed of the limitations of current screening methods and our limited knowledge of the genetic background to male infertility. They should be told that there might be a slight increase in congenital malformation rate after ICSI, but that this increase is probably the result of their own 'background risk'. Well-informed patients are in the best position to judge whether the concerns outweigh the benefits of ICSI.

Congenital Abnormalities↗

Reproductive capacity of sperm obtained after germ cell transplantation in a mouse model.

BACKGROUND: The testicular stem cell transplantation technique has become an established research model in the mouse. This technique may also become useful for clinical applications. Therefore, it is necessary to investigate whether sperm obtained after testicular stem cell transplantation retain their full functional capacity and whether they are able to produce normally-developing embryos. This study aimed at evaluating the fertilizing and developmental abilities of sperm obtained after stem cell transplantation. METHODS: First, transplanted male mice were mated with females in order to evaluate in-vivo conception. Subsequently, functionality of sperm obtained after testicular germ cell transplantation was investigated by performing both IVF and ICSI. RESULTS: After in-vivo conception we found that in the control group 90% of the mice with a copulating plug became pregnant. In the experimental group only 35% of the mice with a copulating plug became pregnant (P = 0.006). After IVF, fertilization and blastocyst developmental rates were significantly lower in the transplanted group (P < 0.0001). Fertilization and blastocyst developmental rates after ICSI were comparable with control sperm. CONCLUSIONS: Our study showed that in the mouse, sperm obtained after stem cell transplantation are able to fertilize oocytes on the basis of assisted reproduction. It is recommended to further investigate this method in the human, as well as to investigate the post-implantation development of the embryo.

Animals↗

Pregnancy outcome and neonatal data of children born after ICSI using testicular sperm in obstructive and non-obstructive azoospermia.

BACKGROUND: Registries on outcome of ICSI pregnancies obtained with testicular sperm do not differentiate between obstructive (OA) and non-obstructive azoospermia (NOA). We evaluated the pregnancy outcome and neonatal data on children born after ICSI using testicular sperm of men with histologically proven OA or NOA. METHODS: Pregnancies obtained after ICSI using testicular sperm of men with defined NOA (n = 70) were compared with those of men with OA (n = 204). RESULTS: Multiple birth rates in NOA and OA couples, respectively, were 21 versus 27% (P = NS), overall preterm delivery rates were 38 versus 26% (NS), and prematurity rates were 24 versus 13% for singletons (NS) and 86 versus 54% for twins (relative risk 1.59, 95% confidence interval 1.04-2.42). Median gestational age for singletons was 38.3 versus 39.3 weeks, respectively (P < 0.05). The low birth weight rates were 34 versus 31%, respectively (NS). The early perinatal mortality rate was 66 versus 15 per 1000 births, respectively, (NS). Major congenital malformations were observed in 4 versus 3%, respectively, of the live born babies (NS). Prenatal karyotypes showed 7% de-novo abnormalities in the NOA group versus 1% in the OA group (NS). CONCLUSIONS: Our data do not show differences between NOA and OA pregnancies except for a strong tendency towards a lower gestational age in singletons and a higher percentage of premature twins in the NOA group. Although our data are based on a limited sample, the differences observed call for further analysis. Given the low pregnancy rates after ICSI with NOA, a multicentre study, differentiating NOA and OA patients, would be recommended.

Adult↗

Serum inhibin B cannot predict testicular sperm retrieval in patients with non-obstructive azoospermia.

BACKGROUND: Serum inhibin B, a direct product of the Sertoli cells, may serve as a marker of spermatogenesis. The present retrospective study aimed at evaluating the predictive value of inhibin B for retrieving testicular sperm in non-obstructive azoospermic men. METHODS: The serum inhibin B concentration before sperm retrieval was reviewed in 185 non-obstructive azoospermic patients. RESULTS: Testicular sperm were successfully recovered in 92 of 185 patients (49.7%). The mean inhibin B concentration in these patients was 37.3 pg/ml. No sperm were found in 93 patients (50.3%), and the mean serum inhibin B concentration was 44.9 pg/ml. The discrimination between successful and unsuccessful sperm retrieval was analysed using the receiver operating characteristics (ROC) curve analysis. The best discriminating inhibin B concentration was 13.7 pg/ml (sensitivity 44.6%, specificity 63.4%) with an area under the ROC curve (AUC) of 0.51. Combining both serum FSH and inhibin B did not improve the predictive value: the AUC of inhibin B in men with a serum FSH concentration <25 and > or = 25 IU/l (being the best threshold value in the population studied) was respectively 0.53 and 0.50. The AUC of the inhibin B:FSH ratios was 0.55. CONCLUSIONS: This analysis shows that inhibin B, either alone or in combination with serum FSH, fails to predict the presence of sperm in men with non-obstructive azoospermia undergoing testicular sperm extraction.

Adult↗

FISH analysis of chromosome X, Y and 18 abnormalities in testicular sperm from azoospermic patients.

BACKGROUND: Sperm extracted from testicular biopsies of azoospermic men can successfully be used for ICSI. The concern exists that testicular sperm from azoospermic men suffering from severe testicular failure may have a higher frequency of aneuploidy, which may lead to an increased risk for chromosomally abnormal offspring. METHODS: Testicular sperm from patients showing spermatogenic failure (n = 17) and from patients with normal spermatogenesis (n = 26) were analysed by fluorescence in-situ hybridization (FISH). Numerical chromosomal abnormalities for chromosomes X, Y and 18 were evaluated by FISH in a total of 1697 testicular sperm derived from 43 azoospermic patients. RESULTS: No difference was observed between the frequency of chromosomal abnormalities in testicular sperm from patients with normal spermatogenesis (5.6%) and from patients with spermatogenic failure (8.2%). However, the frequency of aneuploidy for chromosome 18 was higher in the group of azoospermic patients with spermatogenic failure than in the group with normal spermatogenesis (3.2 versus 1.3%). Within the obstructive group, sex chromosome aneuploidy (4.5%) occurred more frequently than chromosome 18 aneuploidy (1.3%; P < 0.001). Among testicular sperm derived from patients with spermatogenic failure, sex chromosomal aneuploidy (5.8%) was similar to that for chromosome 18 (3.2%). CONCLUSIONS: So far, no difference in the total frequency of chromosomal abnormalities has been observed between patients with normal spermatogenesis and patients with severe testicular failure. However, aneuploidy for chromosome 18 was higher in the group with spermatogenic failure.

Adult↗

Characterization of the genomic organization, localization and expression of four PRY genes (PRY1, PRY2, PRY3 and PRY4).

PRY (PTP-BL related on the Y chromosome) has been proposed as a candidate spermatogenesis gene. We report the characterization of the genomic structure, the number of copies on the Y chromosome and the expression of the gene. By comparison of the cDNA sequence with the genomic sequence, five exons were identified. Analysis of GenBank-derived clones on the Y chromosome revealed the presence of two full-length copies in azoospermia factor region b (AZFb) (PRY1 and PRY2) and two shorter versions of the PRY gene containing exons 3, 4 and 5 in AZFc (PRY3 and PRY4). A clone containing sequences homologous to exons 3, 4 and 5 is located in area 5L (between AZFa and AZFb), a clone containing a sequence homologous to exon 5 is located in area 5M (in AZFb) and a clone containing a fragment homologous to exon 3 is located in 6F. A repeat structure of exons 1 and 2 is present on the short arm of the Y chromosome as well as on the long arm. PRY1 and PRY2, two gene copies that are located in AZFb, a region often deleted in patients with severe male infertility, were shown to be expressed in the testis. PRY may therefore play an important role in spermatogenesis.

Base Sequence↗

Storing reproduction for oncological patients: some points for discussion.

Since the introduction of sophisticated techniques of assisted reproduction such as IVF and ICSI, all male patients that undergo a cancer treatment jeopardizing their future fertility status should be offered the opportunity to bank their semen. Only azoospermic semen samples are to be rejected for pre-treatment banking. Patients who became severely oligospermic or azoospermic after chemotherapy but did not bank their semen, are often not allowed to have assisted reproduction because of the concerns about the mutagenic aspects of their treatment. In a small case series (n = 10), we recovered testicular sperm for ICSI in 40% of patients who became azoospermic after chemotherapy. Since, so far, the few clinical data available do no not suggest an increased risk for congenital anomalies in children born from patients obtaining a pregnancy during chemotherapy, the question remains whether the concerns raised about treating patients who became oligozoospermic or azoospermic or even about semen banking during chemotherapy are incontestable.

Antineoplastic Agents↗

Management of male infertility by assisted reproductive technologies.

Among the most popular techniques of assisted reproduction for the treatment of male subfertility and infertility are intrauterine insemination, in vitro fertilization and intracytoplasmic sperm injection. The objective of these techniques is to bring more functional spermatozoa closer to the oocyte in order to promote fertilization. These techniques are thus not a cure per se and are only indicated when no specific or effective treatment is available for the male partner, when this treatment has failed or when the improvement of the female fertility status has also failed. While for moderate oligoasthenozoospermia, intrauterine insemination has proved to be a valid treatment, the outcome after conventional in vitro fertilization is limited because of a high incidence of complete fertilization failure. Since the introduction of intracytoplasmic sperm injection, a reliable method has become available in order to achieve fertilization in vitro. Apart from well from ejaculated spermatozoa, epididymal or testicular spermatozoa too can be used successfully for intracytoplasmic sperm injection. The surgical retrieval of spermatozoa for intracytoplasmic sperm injection has therefore become a routine technique in clinical andrology. Although these techniques have been implemented in everyday infertility practice within a few years of their introduction, many concerns about safety continue to exist. Intracytoplasmic sperm injection must be applied with caution, only when no other treatment option is available and when an appropriate prospective follow-up of the offspring is available.

Embryo Transfer↗

Ovarian stimulation during assisted reproduction treatment: a comparison of recombinant and highly purified urinary human FSH. On behalf of The Feronia and Apis study group.

This randomized, single-blind, multicentre, multinational study compared recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c. Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The duration of FSH treatment was significantly shorter with Gonal-F than with Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/- 5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical difference in pregnancy rate was recorded, patients receiving Gonal-F had a higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus 20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and 1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In conclusion, FSH stimulation in combination with a long GnRH agonist protocol is effective in inducing multiple follicular development and embryos with a high implantation potential. However, Gonal-F is clearly more effective than Metrodin HP in inducing multifollicular development.

Adult↗

Validation of a simple Yq deletion screening programme in an ICSI candidate population.

This study reports on the validation of a diagnostic screening programme for Yq deletions in a population of infertile men. First, an unselected group of 402 intracytoplasmic sperm injection (ICSI) candidate patients was screened prospectively by means of three polymerase chain reactions (PCR) each with one marker in the region AZFa, AZFb or AZFc. With this screening strategy, eight males (2.2%) were found to carry a deletion in Yq11. Secondly, a subgroup of males were further analysed by multiplex PCR with 27 sequence-tagged sites. In this group of 229 cytogenetically normal males with azoospermia, cryptozoospermia or extreme oligozoospermia, including some patients with varicocele or a history of cryptorchidism, only one additional microdeleted patient was found with the multiplex PCR. Hence we obtained a frequency of 2.2% (9/402) or 4% (9/229) in the unselected and selected patient groups respectively. We conclude that in a diagnostic programme for Yq deletions in ICSI candidates it might be sufficient to use only four markers representing the three AZF regions and a more distal region in AZFc. In this way, it is possible to detect most, if not all, Yq deletions which might be the causal factor in the patient's infertility.

Gene Deletion↗

Freezing of testicular tissue as a minced suspension preserves sperm quality better than whole-biopsy freezing when glycerol is used as cryoprotectant.

Frozen-thawed testicular spermatozoa have been used successfully for ICSI, especially in cases of obstructive azoospermia with normal spermatogenesis. Fewer attempts, however, have been made to check whether these rather immature spermatozoa, in a different environment with several other cell types present, have cryobiological requirements other than those of ejaculated spermatozoa. This is the reason why the freezing protocols and cryoprotectants (glycerol) used for freezing testicular tissue are based on experience with semen freezing. This study aimed to assess whether cryosurvival and/or motility was influenced by freezing of testicular tissue either as an intact biopsy or as a shredded tissue suspension, when glycerol was used as cryoprotectant. Freezing of testicular tissue as a suspension preserved motility (type B + C) significantly better than freezing of whole biopsies (9.2% vs. 4.0%). Similar observations have been made for vitality (39.3% vs. 25.4%). Centrifugation on 50% Percoll in order to remove the cryoprotectant resulted in a huge loss of spermatozoa (or late spermatids) and should therefore be especially avoided in cases of testicular failure. On the basis of these observations, mincing of the testicular biopsies before freezing may be advocated. Testicular spermatozoa seem to be better preserved when frozen in suspension, at least when slowly permeating glycerol is used as a cryoprotectant.

Biopsy↗

No differences in outcome after intracytoplasmic sperm injection with fresh or with frozen-thawed epididymal spermatozoa.

This retrospective consecutive case series aimed at comparing the results of intracytoplasmic sperm injection (ICSI) with fresh and with frozen-thawed epididymal spermatozoa obtained after microsurgical epididymal sperm aspiration (MESA) in 162 couples. These couples were suffering from infertility because of congenital bilateral absence of the vas deferens (n = 109), failed microsurgical reversal for vasectomy or postinfectious epididymal obstruction (n = 44), irreparable epididymal obstruction (n = 4), ejaculatory duct obstruction (n = 2) or anejaculation (n = 3). Overall, 176 MESA procedures were performed in the husbands, followed by 275ICSI procedures with either fresh (n = 157) or frozen-thawed (n = 118) epididymal spermatozoa. No significant differences were observed in the parameters of spermatozoa used either freshly or frozen-thawed. In the fresh epididymal sperm group 59.4% of all the injected oocytes fertilized normally as compared to 56.2% of all injected oocytes in the frozen-thawed epididymal sperm group, and embryonic development was comparable between the two groups. A total of 245 transfers were performed: 145 after the use of fresh epididymal spermatozoa and 100 after the use of frozen-thawed spermatozoa. The overall pregnancy rate per ICSI cycle was significantly lower when frozen-thawed epididymal spermatozoa were used (26.3 versus 39.5%). However, no significant differences were found either in clinical and ongoing pregnancy rates or in implantation rates. There were no differences in pregnancy outcome. In patients suspected of having obstructive azoospermia with no work-up or an incomplete one, MESA is the preferred method for sperm recovery because a full scrotal exploration can be performed and, whenever indicated, a vasoepididymostomy may be performed concomitantly. Recovery of epididymal spermatozoa for cryopreservation during a diagnostic procedure is certainly a valid option in these patients since ICSI may be performed later or even in another centre using the frozen-thawed epididymal spermatozoa without jeopardizing the ICSI success rate.

Cryopreservation↗

Cumulative delivery rates after intracytoplasmic sperm injection: 5 year follow-up of 498 patients.

The use of life-table analysis for infertility data has the advantages of clarity and ease of application. Success rates per cycle have been reported, but not cumulative delivery rates for intracytoplasmic sperm injection (ICSI). We selected retrospectively 498 Belgian patients <37 years old, who had their first ICSI cycle between July 1992 and December 1993. Follow-up was till the end of October 1997. Outcome measure was any delivery >25 weeks. These couples underwent 963 ICSI cycles using fresh ejaculated spermatozoa. The indications for ICSI were long-standing severe male infertility or fertilization failure after conventional in-vitro fertilization (IVF). Cumulative delivery rates were calculated by life-table analysis and compared according to age groups and sperm quality. There were 298 deliveries within a mean rate per cycle of 31%. The average number of cycles required for a delivery was 3.15 (CI 2.88; 3.43). Twenty-three (4.6%) spontaneous pregnancies occurred after the patients had finished therapy. There was no significant difference between the sperm quality groups but delivery rates decreased significantly with increasing female age. The real delivery rate after six cycles was 60%, while the expected cumulative delivery rate was 86%. This life-table analysis may provide a means by which to counsel couples on the likelihood of a delivery following ICSI.

Adult↗

Luteal phase and clinical outcome after human menopausal gonadotrophin/gonadotrophin releasing hormone antagonist treatment for ovarian stimulation in in-vitro fertilization/intracytoplasmic sperm injection cycles.

The luteal phase hormonal profile and the clinical outcome of 69 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) after ovarian stimulation with human menopausal gonadotrophin (HMG) and the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix were analysed. Twenty-four patients received Cetrorelix 0.5 mg (group I) while in 45 patients Cetrorelix 0.25 mg was administered (group II). Human chorionic gonadotrophin (HCG) was used as luteal support. Nine clinical pregnancies were obtained in group I (37.5%) and 12 in group II (26. 6%). These results were not significantly different. Serum progesterone and oestradiol concentrations did not differ between the two groups either in pregnant or non-pregnant patients. An expected decrease of the same hormones was observed 8 days after the pre-ovulatory HCG injection in non-pregnant women. With regard to serum luteinizing hormone concentrations, a decrease was observed 2 days after the pre-ovulatory HCG injection and was maintained at almost undetectable levels throughout the entire luteal phase in both conception and non-conception cycles of group I and group II. This study demonstrates that different doses of GnRH antagonist do not have any impact on the luteal phase of IVF/ICSI cycles when hormonal support is given.

Abortion, Spontaneous↗

Controlled comparison of conventional in-vitro fertilization and intracytoplasmic sperm injection in patients with asthenozoospermia.

A controlled comparison between conventional in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) has been carried out for patients with </=5% rapid progressive (type A) spermatozoa in their fresh semen. Twenty couples were allocated to the study. All semen samples fulfilled the minimum criteria to be allocated to the conventional IVF programme. The two pronuclear (2PN) fertilization rate per retrieved cumulus-oocyte complex was significantly higher after ICSI (63.4%) than after conventional IVF (22.9%), with complete fertilization failure after IVF in 10 out of the 20 cycles. Embryo quality was similar for both treatments. Sixteen patients received only ICSI embryos, two patients only IVF embryos and two patients received IVF and ICSI embryos. The ongoing clinical pregnancy rate was 45%, the implantation rate was 37%. Comparison of the characteristics of patients/cycles with and without 2PN fertilization revealed a higher proportion of progressively motile spermatozoa in the prepared sperm fraction for the group of patients with fertilization after conventional IVF. It can be concluded from this study that absence of or an extremely low proportion of rapid progressive motility in fresh semen indicates a high risk of complete fertilization failure with conventional IVF.

Embryo Implantation↗