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Biomedical subjects

R Felberbaum

Publications and source records attributed to R Felberbaum.

At least 19 recordsLinked to original sources

Luteal phase support using either Crinone 8% or Utrogest: results of a prospective, randomized study.

The Crinone 8% preparation makes it possible to administer natural progesterone (90 mg) vaginally once daily for luteal phase support (LPS). Until now, no prospective, randomized studies have directly compared this new preparation with widely used Utrogest capsules, which were originally designed for oral administration but are used routinely as a vaginal preparation. A prospective, randomized study investigated 126 patients undergoing cycles of in vitro fertilization (IVF) and IVF/intracytoplasmic sperm injection (ICSI). Patients received either Crinone 8% (n = 73) vaginally once daily or two Utrogest capsules (n=53) vaginally three times daily (600 mg). Clinical pregnancy rates were comparable (28.8 versus 18.9%), as were clinical abortion rates until 12 weeks of gestation (14.3 versus 10.0%) and clinical ongoing pregnancy rates (24.7 versus 17.0%) in the Crinone 8% and Utrogest groups, respectively. Forty-seven non-pregnant patients were randomly selected to answer questions regarding comfort during LPS. Crinone 8% had a clear advantage over Utrogest as it resulted in less vaginal discharge (P < 0.01) and fewer application difficulties (P<0.05). Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone 8% was easier to apply (P < 0.01) and less time consuming (P < 0.05) to use than Utrogest.

Abortion, Spontaneous↗

Use of cetrorelix in combination with clomiphene citrate and gonadotrophins: a suitable approach to 'friendly IVF'?

BACKGROUND: With the recently introduced GnRH antagonists, soft stimulation protocols on the basis of clomiphene pretreatment should be possible as the pituitary remains fully sensitive at the beginning of the cycle. METHODS: A prospective trial was carried out on 107 patients undergoing IVF treatment using the multiple dose GnRH antagonist protocol (cetrorelix), clomiphene citrate, and either HMG (n = 54) or recombinant FSH (rFSH) (n = 53). Different stimulation protocols were used to find the most appropriate one for clinical application. RESULTS: Both treatment groups, HMG and rFSH, yielded comparable results concerning gonadotrophin dose, stimulation days and pregnancy rate. A mean number of 6.34 +/- 4.4 metaphase II oocytes was retrieved and a mean number of 2.45 +/- 0.65 embryos was transferred. However, the overall rate of premature LH surges was 21.5% (defined as measurement of LH >10 IU/l and progesterone >1 ng/ml) which is unacceptable for clinical practice. CONCLUSIONS: Increasing the daily cetrorelix dose from 0.25 to 0.5 mg might decrease the number of premature LH surges. Soft stimulation protocols with clomiphene should be used cautiously.

Adult↗

Gonadotropin-releasing hormone antagonist protocol: a novel method of ovarian stimulation in poor responders.

OBJECTIVE: To estimate the efficacy of gonadotropin-releasing hormone (GnRH) antagonist 'Cetrorelix' in poor responders comparing with the standard long protocol. DESIGN: The study population consisted of 21 poor responders who underwent ICSI and treated with Cetrorelix according to the multiple-dose protocol and who were compared with 21 poor responders treated according to the long protocol and who also underwent ICSI. Patients in both groups were matched for chronological age, the number of follicles found by ultrasound at the retrieval day and cause of infertility. Fifteen patients of GnRH antagonist group were treated with the combination of GnRH antagonist with clomiphene citrate (CC) plus gonadotropins, while six patients were treated with the combination of GnRH antagonist plus gonadotropins, but without CC. RESULTS: The use of GnRH antagonist in a multiple dose protocol gave a pregnancy rate of 14.28% which was in the range expected for patient with poor response, but with shorter treatment duration and with fewer ampoules of gonadotropins as compared with the use of a GnRH agonist protocol in a depot formulation. Within Cetrorelix group patients who received CC had a significant shorter duration of stimulation and needed fewer ampoules as compared with patients in the same group who did not receive CC. CONCLUSIONS: A GnRH antagonist multiple dose protocol may be the protocol of choice for the treatment of poor responders. The use of GnRH antagonist Cetrorelix ended with significantly less ampoules of gonadotropins and a shorter duration of stimulation.

Adult↗

Actions of gonadotropin-releasing hormone antagonists on steroidogenesis in human granulosa lutein cells.

OBJECTIVE: GnRH antagonists have recently been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). We have here investigated whether the GnRH antagonists cetrorelix and ganirelix exert effects on ovarian steroidogenesis. Since there is some controversy about the action of GnRH agonists in the human ovary we also tested the effect of triptorelin on steroid production in cultured human granulosa lutein cells. METHODS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue. RESULTS: Such in vivo treatment did not result in significant effects of triptorelin or the two GnRH antagonists on spontaneous or human chorionic gonadotropin (hCG)-stimulated steroidogenesis. To exclude the possibility that the in vivo treatment might not affect in vitro steroid production because of low or absent peptide activity, we performed in vitro treatments with triptorelin, cetrorelix and ganirelix for up to 96 h. However, these treatment paradigms did not influence basal or hCG-stimulated steroid production. CONCLUSIONS: We conclude that GnRH antagonists do not exert any significant effects on ovarian steroidogenesis in vitro and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Cells, Cultured↗

Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support.

BACKGROUND: A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70). METHOD: All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was > or = 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n=83) or progesterone only (group V, n=121). For vaginal progesterone Utrogest was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). RESULTS: Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p<0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. CONCLUSION: Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient.

Administration, Intravaginal↗

No significant leukocytosis under controlled ovarian stimulation using the LHRH antagonist Cetrorelix and recFSH.

OBJECTIVE: To study the influence of an LHRH (luteinizing hormone releasing hormone) antagonist protocol (Cetrorelix) and the use of recombinant follicle-stimulating hormone (FSH) on the development of leukocytosis, compared to the use of urinary HMG (human menopausal gonadotrophin). DESIGN: Prospective, randomized phase III clinical trial. SETTING: Infertility day clinic, Department of Gynecology and Obstetrics. PATIENTS: Thirty patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment following controlled ovarian stimulation using a multiple dose protocol and the LHRH antagonist Cetrorelix. MAIN OUTCOME MEASURE: Differences in white blood cell (WBC) count before stimulation, during the follicular phase and in the midluteal phase. RESULTS: Statistically significant increase in WBC count in the HMG group from the start of stimulation to the midluteal phase. No statistically significant increase in the recFSH group, but only a trend towards higher values was observed. CONCLUSION: The development of a leukocytosis in controlled ovarian stimulation does not depend on the protocol used. Urinary gonadotrophins seem to have a greater potential to increase WBC count compared to recombinant gonadotrophins.

Estradiol↗

Comparison of cryopreservation outcome with human pronuclear stage oocytes obtained by the GnRH antagonist, cetrorelix, and GnRH agonists.

This retrospective study was performed to examine the implantation and pregnancy rates of frozen-thawed pronuclear stage oocytes obtained with the use of a GnRH antagonist, Cetrorelix (Cetrotide((R)) ASTA-Medica, Frankfurt/M, Germany) used in a multidose protocol with hMG, and to compare these results with those obtained after a conventional long GnRH analogue protocol (Decapeptyl-Depot, Ferring, Kiel, Germany). The study population consisted of 31 infertile couples with frozen-thawed pronuclear stage oocytes after ICSI treatment using the GnRH antagonist Cetrorelix (Cetrorelix((R))) and 31 infertile couples with frozen-thawed pronuclear stage oocytes after ICSI treatment using the long GnRH analogue protocol. Patients underwent ICSI after down regulation with a GnRH agonist (Decapeptyl) and stimulation with hMG, or a GnRH antagonist (Cetrorelix) and hMG. The supernumerary pronuclear stage oocytes were cryopreserved and transferred in a later mildly stimulated cycle. The implantation and pregnancy rates for frozen-thawed pronuclear stage oocytes derived from the GnRH antagonist compared with the GnRH agonist were 3.26% versus 3.73% (P=1.0000) and 8.33% versus 10.25% (P=1.0000), respectively. To our knowledge we report here the first pregnancies obtained by the transfer of cryopreserved pronuclear stage embryos generated from ICSI using a GnRH antagonist in the collecting cycle. The use of Cetrorelix in a multiple dose protocol in combination with hMG does not demonstrate a negative effect on viability, implantation potential or pregnancy outcome as compared to 2PN conceptuses obtained from a long GnRH agonist-hMG protocol.

Abortion, Spontaneous↗

HELLP syndrome with haemaglobin vasospasm.

The syndrome of haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) is a life threatening, severe complication of pre-eclampsia with typical laboratory findings. An unusual case of a 36-year-old woman with HELLP syndrome and the initial complication of intracerebral haemorrhage is presented. The diagnosis of HELLP syndrome was confirmed by elevated liver enzymes, low platelets, increased total bilirubin and increased lactate dehydrogenase. The intracranial haematoma was removed with good neurological recovery ensuing. However, this case was complicated by cerebral vasospasm on the eleventh day, confirmed by cerebral angiography and computer tomographic findings. The patient died from brain swelling. Possible vasospam should be considered during the treatment of patients with HELLP syndrome.

Adult↗

Transcervical falloscopic dilatation of proximal tubal occlusion. Is there an indication?

Proximal tubal occlusion (PTO), until recently a domain of microsurgery, can also be treated by a transcervical balloon dilatation and/or tubal recanalization. The aim of our study was to evaluate the possibility of transcervical tubal dilatation during transcervical Falloposcopy. Transcervical Falloposcopy and tubal dilatation was performed under laparoscopic control. During a period of 48 months a total of 157 Falloposcopies was performed. Out of a total of 157 patients, 42 patients had PTO confirmed by dye-pertubation during laparoscopy. All patients were referred because of primary or secondary tubal infertility. A total of 18 patients had bilateral PTO by dye-pertubation and of these six patients had successful bilateral and seven patients successful unilateral recanalization. The remaining five patients were unable to recanalize. A total of 24 patients had an unilateral PTO by dye-pertubation, 13 of these patients had a contralateral diseased tube, seven of which could be recanalized. Four patients had contralateral normal tubes, with successful recanalization in one patient. Seven patients had an occluded or missing contralateral tube, five of which could be recanalized. A total of 60 tubes with PTO were diagnosed, of which 32 (53.3%) tubes could be recanalized. 20 of these had normal tubes. Only patients with healthy Fallopian tubes carried pregnancies to term (five pregnancies, 12% of all patients). All patients conceived within a period of 3-6 months. We observed no ectopic pregnancy.

Adult↗

New aspects of cryopreservation of oocytes and embryos in assisted reproduction and future perspectives.

Cryopreservation of human gametes and tissue has been introduced into assisted reproduction in recent years. The current status as well as new developments of cryopreservation, especially in conjunction with new techniques, are reviewed. Cryopreservation of pronuclear stage oocytes or embryos at the cleavage stage are routine procedures worldwide after conventional in-vitro fertilization (IVF). The data on children born show no increase in malformation rates, or any impaired psychomotor development. The combination of cryopreservation with intracytoplasmic sperm injection (ICSI) has given the same results. Cryopreservation of unfertilized mature and immature oocytes has lead only to a few pregnancies until now. It is still unknown whether ICSI may help to improve these results. Experience using cryopreservation of blastocysts is still limited, with a wide range of pregnancy rates (0-53 %) being reported. Further studies are required before exact numbers for these procedures can be given. The combination of biopsy and cryopreservation appears to have a different impact for subsequent embryo development in animals and humans. Possibly, there is a reduction in embryo developmental potential after these procedures. Currently, the most promising technique is the cryopreservation of ovarian tissue, which has already led to the birth of lambs, mice and rats. The future development of cryopreservation is discussed.

Cryopreservation↗

Ovarian stimulation for in-vitro fertilization/intracytoplasmic sperm injection with gonadotrophins and gonadotrophin-releasing hormone analogues: agonists and antagonists.

The gonadotrophin-releasing hormone (GnRH) antagonists Cetrorelix and Ganirelix have been used in recent years in clinical studies to prove that these compounds reliably prevent the onset of premature luteinizing hormone (LH) surges during ovarian stimulation. Cetrorelix has been applied in single and multiple dose protocols, while Ganirelix has until now only been used in the multiple dose protocol. In the latter protocol, ovarian stimulation is started on day 2 or 3 of the spontaneous cycle with human menopausal gonadotrophin or recombinant follicle stimulating hormone. Daily administration of the GnRH antagonist at its minimum effective dose (0.25 mg/day s.c.) occurs from the sixth day of stimulation onwards until ovulation induction by human chorionic gonadotrophin. In the single dose protocol, 3 mg of the GnRH antagonist Cetrorelix was injected on day 8 of the stimulation cycle. Both protocols have been proven to be safe and effective. Fertilization rates of >60% in in-vitro fertilization and >70% in intracytoplasmic sperm injection, as well as clinical pregnancy rates of approximately 30% per transfer, sound most promising. The incidence of a premature LH surge is below 2%. The incidence of severe ovarian hyperstimulation syndrome seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened.

Female↗

A simple, inexpensive and effective artificial cycle with exogenous transdermal oestradiol and vaginal progesterone for the transfer of cryopreserved pronucleated human oocytes in women with normal cycles.

Supernumerary pronucleated stage oocytes (PN) are usually cryopreserved. PN are transferred in spontaneous, stimulated or artificial cycles. In this study, an artificial cycle with a transdermal therapeutic system was used for oestradiol release (Estraderm TTS 100) in combination with a targeted drug delivery system for vaginal progesterone release (Crinone 8%). Patients started transdermal 17beta-oestradiol treatment on cycle day 1. Only one clinical monitoring was necessary on day 14 for confirmation of satisfactory endometrial development and exclusion of ovulation by transvaginal ultrasound and endocrine determinations (oestradiol, progesterone and luteinizing hormone). Embryo transfer was performed on the third day of progesterone treatment (day 17). The first 25 cycles were recently completed in a prospective study; no cycles were cancelled due to ovulation or unsatisfactory endometrial development. In comparison with the previous protocol of embryo transfer in stimulated cycles in our clinic which required extensive ultrasound and endocrine monitoring, the pregnancy rate in these oestrogen- and progesterone-supplemented cycles was nearly twice as high (34.8%). Two pregnancies were even achieved with zygotes after micro-injection of frozen-thawed late spermatids extracted from testicular tissue (cryo-TESE). In these cycles, the Estraderm TTS 100/Crinone 8% protocol seems to be superior to stimulation protocols and even to other protocols reported so far for artificial cycles with exogenous oestradiol and progesterone treatment.

Administration, Cutaneous↗

Fertilization potential of spermatozoa with abnormal morphology.

One of the best discriminators for the fertilization potential of human spermatozoa is sperm morphology. The problem in the assessment of the sperm morphological characteristics is their pleiomorphism. Examination of spermatozoa with the light microscope can provide only limited information on their internal structure. More detailed examination of sperm structure using electron microscopy can reveal major, often unsuspected ultrastructural abnormalities. Results and cut-off values for sperm analysis depend on the criteria for normal morphology. World Health Organization recommendations provide a classification suitable for clinical practice. Clinically reliable cut-off limits for normal sperm morphology according to strict Tygerberg criteria were suggested to be 4% in in-vitro fertilization procedures. Patients with severe sperm head abnormalities have a lower chance of establishing successful pregnancies, even though fertilization may be achieved. The outcome of intracytoplasmic sperm injection is not related to any of the standard semen parameters or to sperm morphology. Sperm decondensation defects and DNA anomalies may be underlying factors for the unrecognized derangements of the fertilizing capacity of spermatozoa, regardless of sperm morphology. Centrosome dysfunction may also represent a class of sperm defects that cannot be overcome simply by the insertion of a spermatozoon into the ooplasm. In this article an overview on the composition and ultrastructure of spermatozoa is presented, while emphasizing sperm ultrastructural and sperm DNA anomalies and their effects on fertilization.

DNA↗

New approaches to ovarian stimulation.

Suppression of endogenous hormone production by gonadotrophin-releasing hormone (GnRH) agonists followed by controlled ovarian hyperstimulation (COH) with human gonadotrophins, especially the so-called 'long protocol' has developed from second-line into first-line therapy. Due to this attitude premature luteinization can be safely avoided, enhancing therapeutic efficacy. Recombinant preparations of human follicle stimulating hormone (FSH) have been proven to be effective within COH according to the long protocol. The high purity of these compounds may have clinical advantages. GnRH antagonists could be successfully introduced in COH protocols. Also, daily injections in the midcycle phase according to the 'Lübeck protocol', as single or only dual administrations around day 9 seem to abolish any premature LH rises. Due to their different pharmacological mode of action, based on a classic competitive receptor blockage GnRH antagonists avoid any flare-up period and allow ovarian stimulation to start within the spontaneous cycle. Pregnancy rates are comparable to those after long protocol stimulation. Combination of softer stimulation regimes like clomiphene citrate and low dose HMG with midcycle administration of GnRH antagonists may be the way to a cheap, safe and efficient ovarian stimulation. It seems to be high time for modest forms of ovarian stimulation, lowering burden and risk for our patients.

Female↗

Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH)-antagonist Cetrorelix at different dosages.

PURPOSE: The premature LH surge in ART programs seems to be avoided by daily administration of the GnRH-antagonist Cetrorelix during the midcycle phase in controlled ovarian hyperstimulation with hMG. The dosage necessary for sufficient suppression of the pituitary gland is not yet defined. METHODS: To elucidate this question three daily dosages (3, 1, 0.5 mg) were administered and the hormone profiles obtained as well as the number of oocytes retrieved, the fertilization rate, and the consumption of HMG were compared. RESULTS: No premature LH surge could be observed at any of the three dosages administered. Both gonadotropins were deeply suppressed. The fertilization rates of the oocytes obtained were 45.3% in the 3-mg group, 53.1% in the 1-mg group, and 67.7% in the 0.5-mg group. The average uses of hMG ampoules were 30 in the 3-mg group, 27 in the 1-mg group, and 26 in the 0.5-mg group. CONCLUSIONS: Cetrolix, 0.5 mg/day, administered during the midcycle phase of controlled ovarian hyperstimulation with hMG is enough to prevent completely the premature LH surge. Perhaps even lower dosages would be sufficient. Regarding fertilization rates and use of hMG, the lower dosage seems to be the most favorable.

Adolescent↗

Small-diameter laparoscopy (SDL) using a microlaparoscope.

PURPOSE: To determine the ability of new sub-2.0-mm-diameter microlaparoscopes to be used for diagnostic laparoscopy, 28 small-diameter laparoscopies (SDL) were performed during a 4-month-period. METHODS: These cases were performed under general anesthesia, with immediate follow-up confirmation with conventional laparoscopic equipment. An additional 13 SDL procedures were performed under analgosedation plus local anesthesia and were well tolerated by the patients. RESULTS: For the cases performed with conventional laparoscopic control, the visualization results were comparable in 27 of 28 procedures. In the nongeneral anesthesia SDL group, patients were highly satisfied and reported less post-procedural discomfort and minimal scar formation due to the smaller access ports. In this study, two types of microlaparoscopes were used. CONCLUSIONS: While both were adequate, the newer high-resolution microlaparoscope delivered an image much more similar to that which conventional laparoscopy and required little or no change in technique in order to obtain images. With the advent of this new endoscope technology with optics performance comparable to that of conventional laparoscopes, SDL has demonstrated to be a useful procedure for certain clinical indications.

Evaluation Studies as Topic↗