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Biomedical subjects

S Oehninger

Publications and source records attributed to S Oehninger.

At least 127 records · Page 7Linked to original sources

Fucoidin inhibits the zona pellucida-induced acrosome reaction in human spermatozoa.

We recently reported that fucoidin (a polymer of predominantly sulfated L-fucose) significantly inhibits tight binding of human sperm to the human zona pellucida in vitro and that several oligosaccharides obtained after acid hydrolysis possess sperm-zona pellucida binding inhibitory activity equal to the original fucoidin. This inhibition may be specific to sperm-zona interactions or may be the consequence of the interruption of capacitation, a series of biochemical and physiological events leading to final sperm maturation, that must occur for successful fertilization. Completion of capacitation is most often determined by assessing two end-points of the process: acquisition of hyperactivated motility and ability to complete the acrosome reaction. Here, we examined the effects of fucoidin on these two end-points of capacitation in vitro. Fucoidin did not affect the proportion of sperm with hyperstimulated motility. Neither did fucoidin cause an increase in sperm that had spontaneously acrosome-reacted at 4.5 hours compared to controls as evaluated by indirect immunofluorescence using the acrosomal marker, monoclonal antibody, T-6. Comparable percentages of sperm had completed the acrosome reaction when exogenously stimulated by calcium ionophore A23187 with and without the addition of fucoidin. However, in the presence of fucoidin, stimulation of the acrosome reaction by acid solubilized human zonae pellucidae was significantly inhibited. These data indicate that fucoidin does not impede the normal progression of capacitation. These results provide strong evidence to support the hypothesis is that the inhibitory effect of fucoidin is at the level of the sperm membrane since inhibition can be bypassed by increasing intracellular calcium directly with a calcium ionophore.

Acrosome↗

Alterations in luteal phase progesterone and estradiol production after leuprolide acetate therapy before ovarian stimulation for in vitro fertilization.

The impact of pituitary suppression with a gonadotropin-releasing hormone agonist (GnRH-a) on the luteal phase of in vitro fertilization (IVF) cycles was examined in 21 women who underwent identical stimulation regimens with and without leuprolide acetate pretreatment. The areas under the serum progesterone curves, measured over the 1st 10 days of the luteal phase, were significantly greater in the GnRH-a cycles compared with the non-GnRHa cycles, but when calculated per oocyte retrieved were similar in GnRH-a and non-GnRH-a cycles. In contrast, the areas under the luteal phase serum estradiol curves were significantly less in the GnRH-a cycles. These data suggest that GnRH-a treatment is accompanied by potentially beneficial alterations in the systemic steroidal milieu of the luteal phase of IVF cycles.

Adult↗

Possible role of pure human follicle-stimulating hormone in the treatment of severe male-factor infertility by assisted reproduction: preliminary report.

OBJECTIVE: Experimental clinical trial assessing the potential of systemic follicle-stimulating hormone (FSH) to improve sperm fertilizing ability in in vitro fertilization (IVF). DESIGN: Retrospective clinical evaluation of severe male factor patients failing fertilization in IVF or showing severe sperm defects. SETTING: Academic tertiary clinical care unit. PATIENTS, PARTICIPANTS: Fourteen patients (41 cycles) who failed IVF, 22 patients (32 cycles) with severe quantitative and qualitative semen abnormalities indicating poor fertilization. INTERVENTIONS TREATMENT: FSH 150 U IM three times a week for 3 months. MAIN OUTCOME MEASURE(S): Pretreatment and post-treatment evaluation of endocrine profile, basic semen analysis, and fertilization and pregnancy rates. HYPOTHESIS: FSH treatment may improve spermatogenesis quality by its multiple actions on the Sertoli-gamete cell compartment without interfering with testicular hormonogenic function. RESULTS: No significant changes were observed in the endocrine profile or in semen parameters; individual cases showed improvements in sperm concentration and motility. Significant increase in fertilization rate of preovulatory oocytes was demonstrated; seven term pregnancies were achieved. CONCLUSIONS: A multicenter randomized, double-blind trial with crossover is needed to demonstrate the benefit of systemic FSH administration and if this effect is FSH exclusive.

Female↗

Human preovulatory oocytes have a higher sperm-binding ability than immature oocytes under hemizona assay conditions: evidence supporting the concept of "zona maturation".

OBJECTIVE: The purpose of this study was to investigate the sperm-binding potential of human oocytes at different stages of nuclear maturation under hemizona assay (HZA) conditions. DESIGN: This was a prospective study designed in a blinded fashion. SETTING: Academic research environment approved by the Institutional Review Board. PATIENTS: Surplus oocytes, donated by patients undergoing in vitro fertilization therapy after gonadotropin stimulation, were analyzed. Semen from a fertile donor was used in all assays. INTERVENTIONS: Five groups of oocytes were considered: (1) immature, prophase I; (2) metaphase I; (3) metaphase II; (4) inseminated, unfertilized metaphase II; and (5) immature, prophase I oocytes matured in vitro to metaphase II. Oocytes were stored in salt solution (pH 7.2) and microbisected before assay. MAIN OUTCOME MEASURE(S): Tight binding of sperm to the zona pellucida under HZA conditions was evaluated after 4 hours of gametes coincubation. RESULTS: Metaphase II oocytes (groups 3 and 4) had significantly higher binding than other groups (P = 0.0001). The mean value of the difference between the two halves (hemizona) was not significant, thus showing a small intra-assay variation for all maturational stages. CONCLUSIONS: Full meiotic competence of human oocytes is associated with an increased zona pellucida-binding potential.

Double-Blind Method↗

Combined impact of the number of pre-ovulatory oocytes and cryopreservation on IVF outcome.

Three hundred and twenty-seven consecutive in-vitro fertilization (IVF) cycles in which luteal-phase leuprolide had been given were ranked according to the number of pre-ovulatory oocytes obtained (1-5, 6-10, greater than 10). Excess pre-embryos were cryopreserved at the pronuclear stage and later transferred into monitored natural cycles on the day after ovulation. The results indicate that the retrieval of large numbers of pre-ovulatory oocytes (greater than 10) has a small negative impact on oocyte quality as judged by fertilization rates (4% lower). However, implantation was not impaired compared to lower levels of retrieval in either the original IVF or subsequent cryo-thaw cycles. Overall, despite the small reduction in fertilization rate, the retrieval of many pre-ovulatory oocytes has produced a 'take-home baby rate' per stimulation cycle of 28.3% when 6-10 pre-ovulatory oocytes were retrieved and 41.5% when greater than 10 were retrieved: even higher rates are anticipated when the remaining cryopreserved pre-embryos are ultimately thawed.

Adult↗

Controlled preparation of the endometrium with exogenous steroids for the transfer of frozen-thawed pre-embryos in patients with anovulatory or irregular cycles.

We have reported a 36% pregnancy rate (eight of 22 transfers) with the transfer of cryopreserved-thawed embryos in patients with anovulatory or irregular cycles following a protocol using pituitary suppression with leuprolide acetate after preparation of the endometrium with transdermal E2 and i.m. P. This protocol is simple, easy to follow, and safe and could be used in future for all patients with cryopreserved pre-embryos.

Adult↗

Ultrasonographic appearance of the endometrium in natural and stimulated in-vitro fertilization cycles and its correlation with outcome.

Ultrasonographic evaluation of the endometrium in 56 IVF patients was performed prospectively. Endometrial thickness and pattern were analysed in 18 natural-cycle and 38 stimulated-cycle patients. Thickness was measured from the echogenic interface of the endometrium-myometrium junction on a transverse section at the level of the fundus. Patterns were classified as A (homogeneous, hyperechogenic), B (mixed, with an outer hyperechogenic and inner hypoechogenic layer) or C (fluid-filled cavum with ring configuration). The thickness and pattern distributions were similar in natural- and stimulated-cycle patients. There was no correlation between thickness and serum oestradiol levels, the diameter of the largest follicle or the pregnancy outcome in either group. However, the occurrence of endometrial pattern A on the day prior to oocyte retrieval had a predictive value of 100% for a non-conceptional cycle. In contrast, pattern B occurred in a significantly greater proportion of pregnant than non-pregnant patients.

Adult↗

Nature of the inhibitory effect of complex saccharide moieties on the tight binding of human spermatozoa to the human zona pellucida.

Fucoidin and heparin sulfate inhibit binding of human sperm to the human zona pellucida under hemizona assay (HZA) conditions. Here we used the HZA to further assess tight sperm binding with/without preincubation of the sperm with other sulfated and nonsulfated glycoconjugates and charged polymers. Fucoidin significantly inhibited binding compared with controls (greater than 75% inhibition), even if sperm were washed after preincubation with the saccharide. Dextran sulfate also produced significant inhibition, although to a lesser extent (54% inhibition). Chondroitin sulfates A and B, heparin, and dextran did not affect binding. Sodium sulfate and polyglutamic acid did not affect HZA results; polyphosphates produced only moderate inhibition. The potent inhibitory effect of the sulfated carbohydrates fucoidin and dextran is probably competitive (receptor-ligand type) in nature. However, the lack of significant effects of simple charged molecules (nonspecific effects) suggests that the degree of sulfation (charge) may not be crucial to its inhibitory action.

Adult↗

Male infertility: the focus shifts to sperm manipulation.

Few systemic approaches for treatment of the infertile male are available. Therefore, the focus has shifted to studies of sperm maturation in the female tract, tests of sperm function, and assisted reproduction. New methods of sperm evaluation allow a better determination of those samples that will and will not fertilize ova. These methods include the strict morphology examination, biochemical approaches such as evaluation of creatine kinase levels, and the hemizona assay. Computer assisted semen analysis has not yet proved important for diagnosis but has provided important research information. For example, the drug pentoxifylline significantly increases velocity and has also been shown to enhance in vitro fertilization. The term subfertile is extensively used in the literature but its clear definition and the prognosis for subfertile men have not been established. Approaches that may increase fertilization rates include reducing the gamete culture volume and removal of cumulus oophorus. Assisted reproductive technologies for patients with ejaculatory dysfunction have also been expanded. The use of improved semen processing techniques, advanced oocyte retrieval, and well-timed intrauterine insemination are enabling physicians to use decreasing numbers of viable sperm to achieve pregnancies.

Humans↗

Ovarian stimulation for in vitro fertilization using pure follicle-stimulating hormone with and without gonadotropin-releasing hormone agonist in high-responder patients.

There is a distinct pattern of response to gonadotropin stimulation in some patients marked by high peak estradiol (E2) levels, multifollicular ovarian response, and elevated basal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios. We reviewed the stimulation profiles of five such high-responder patients who failed to conceive during in vitro fertilization with ovarian stimulation using pure FSH. All patients had baseline LH/FSH greater than 1.5 and peak E2 greater than 800 pg/ml. One cycle was canceled prior to hCG administration because of marked ovarian response (E2 greater than 2500 pg/ml, multiple small follicles). In a subsequent cycle, all patients were pretreated with the gonadotropin releasing-hormone agonist (GnRHa) leuprolide acetate for 10-14 days prior to initiation of FSH for ovarian stimulation. Leuprolide was continued until the day of hCG administration. During cycles using GnRHa, there was a statistically significant decrease (P less than 0.05) in serum FSH on day 3 (less than 5 vs 8.3 mIU/ml), serum E2 on day 3 (14.6 vs 34.6 pg/ml), and peak serum E2 (1197.6 vs 1923.0 pg/ml). Patients during cycles with GnRHa had a greater number of preovulatory (8.6 vs 3.0) and total (12.4 vs 6.0) oocytes retrieved (P less than 0.05). The fertilization rate of preovulatory oocytes was also higher during cycles using GnRHa (83 vs 64%). Two pregnancies occurred in the cycles pretreated with GnRHa. These preliminary data indicate that in high-responder patients, a combination of GnRHa and pure FSH results in lower E2 levels during the stimulation cycle and a greater number of total and mature oocytes retrieved and fertilized.

Adult↗

Preclinical abortions: incidence and significance in the Norfolk in vitro fertilization program.

Clinical and prognostic significance of preclinical abortions in assisted reproduction is ill defined. Strict diagnostic criteria include a transient and synchronous elevation of serum beta-human chorionic gonadotropin (hCG), estradiol, and progesterone levels 13 days after hCG administration, ending in a bleeding episode no more than 14 days after the missed period. The preclinical abortion study group (54 patients, 178 cycles) was compared with matched control groups A (54 patients, 132 cycles) and B (54 patients, 155 cycles), representing normal term pregnancies and all outcomes, respectively. Control group C included the overall population during the study period. The abortion rate per transfer (preclinical abortion and total miscarriage rates) and total pregnancy wastage in the study group were significantly higher; the ongoing pregnancy rate was significantly lower. Preclinical abortion should be considered as a true reproductive failure with similar implications.

Abortion, Spontaneous↗

Survival of the cornual pregnancy in a heterotopic gestation after in vitro fertilization and embryo transfer.

We present a case of combined intrauterine and cornual (interstitial) pregnancy after IVF-ET, with survival of the infant after the cornual pregnancy. The diagnosis of this rare phenomenon is difficult; a high index of suspicion and frequently ultrasound monitoring may enable early diagnosis in other forms of heterotopic pregnancy. Although the benefits of IVF-ET far outweight the risks of ectopic pregnancy, it is imperative that physicians who care for these patients be fully aware of the possibility of such a complication in this high-risk population.

Adult↗

Gonadotropin stimulation for in vitro fertilization and embryo transfer in insulin-dependent diabetics: follicular response, oocyte quality, embryo development, and follicular environment.

Two IDD patients were stimulated with gonadotropins for IVF and ET. Both patients had high E2 response and greater than or equal to 5 preovulatory oocytes retrieved, normal fertilization and cleavage rates, and transfer; neither conceived. Follicular fluid showed levels of E2, P, A, hCG, and PRL similar to non-IDD. Epidermal growth factor could not be detected in FF. Insulin-dependent diabetes patients can undergo gonadotropin stimulation for IVF with customary responses. Their follicular milieu resembles that of non-IDD patients except for a lack of EGF.

Adult↗

Intercycle variability of day 3 follicle-stimulating hormone levels and its effect on stimulation quality in in vitro fertilization.

Prior studies have demonstrated that gonadotropin stimulation quality and pregnancy rates are better in in vitro fertilization (IVF) patients with low basal cycle day 3 follicle-stimulating hormone (FSH) levels. The records of 81 patients who had undergone three or more IVF attempts during a 2-year period were studied to determine the degree and potential impact of intercycle variability in basal FSH concentrations. The mean of the individual standard deviations for all 81 patients was 4.2 +/- 0.4 mIU/mL. However, the patients with a mean basal FSH of less than 15 mIU/mL had a mean deviation of only 2.6 +/- 0.2 mIU/mL, whereas those with a mean basal FSH of greater than or equal to 15 mIU/mL had a mean deviation of 7.3 +/- 0.7 mIU/mL. Intercycle variability in basal FSH values did not predict changes in ovarian response to gonadotropin stimulation and thus may not be used to select an optimal cycle in which to stimulate an individual patient. Furthermore, patients with large intercycle variation responded poorly to gonadotropin stimulation independent of their basal FSH concentration. This information allows more precise counseling of patients regarding their appropriateness for assisted reproduction.

Animals↗

Hemizona assay and teratozoospermia: increasing sperm insemination concentrations to enhance zona pellucida binding.

This study aimed: (1) to evaluate the zona-binding capacity of patients with abnormal sperm morphology, using standard hemizona assay (HZA) conditions and increasing sperm insemination concentration during the assay and (2) to determine the insemination concentration needed to obtain equality in the number of tightly bound sperm to matching hemizonae, using sperm from teratozoospermic patients versus proven fertile controls. The minimum concentration of motile sperm from fertile controls necessary to validate HZA results was 250,000/mL (35.4 +/- 5.6 tightly bound sperm; mean +/- SE). The "effective number of sperm" (morphologically normal with high motility) was 60,750/mL. Each teratozoospermic patient had a unique, (higher) sperm insemination concentration (range: 0.5 X 10(6) to 2.0 X 10(6) motile sperm/mL) necessary to equal the number of tightly bound sperm representing the lower 95% confidence interval for the control sample (at 0.5 X 10(6) motile sperm/mL) with the matching hemizona. These results suggest that the HZA may be used as an indicator of the sperm insemination concentration during in vitro fertilization in patients with teratozoospermia.

Female↗

Induction of ovulation for assisted reproduction programmes.

The decision to use enhancement of the natural ovarian/menstrual cycle to attempt collection of several oocytes during IVF and GIFT cycles has dramatically increased the pregnancy rates. Furthermore, the recovery of multiple fertilizable oocytes allows for cryopreservation of extra or surplus pre-embryos (or embryos), with the consequent reduction in the risk of multiple pregnancies and the improvement of the cumulative pregnancy rate following IVF and GIFT cycles. Here, we have reviewed the underlying physiological mechanisms in the natural ovarian-menstrual cycle. Subsequently, we have analysed the more frequently utilized ovarian stimulatory regimens with special emphasis on the use of gonadotrophins. Several conclusions may be drawn from the experience to date with these methods of ovarian stimulation. Primarily, lower doses of medication, when used appropriately, may result in a more favourable outcome. Most significant, it seems to be beneficial to tailor the dosages and timing of drug administration to the patient's individual response to medication. Because ovarian stimulation therapy is difficult to manage, a major challenge in reproductive endocrinology has been to develop stimulation protocols that would 'ideally' synchronize the development of a cohort of follicles. The development of GnRH analogues (agonists and antagonists) and the experience (both in women and macaques) gained so far when these drugs are used in combination with gonadotrophins, have helped both in the understanding of the underlying physiology and in the improvement of clinical results.

Female↗

Therapeutic intrauterine insemination (TII)--controversial treatment for infertility.

The literature on therapeutic intrauterine insemination (TII) is confused because of lack of homogeneity in case selection, differences in executing the procedural steps, and the manner of evaluating and reporting results. This review compares results from Norfolk with those in the English literature. Special emphasis has been placed on separately analyzing each step of the procedure and presenting results of different authors in a comparable fashion. Including all etiologic factors and types of cycles, the term pregnancy rate per cycle was 3% for Norfolk, 2.6% to 6.2% elsewhere. Patients receiving TII in stimulated cycles did significantly better than those receiving TII in natural cycles, in terms of total pregnancy rate per cycle (p = 0.002). In male factor infertility, term pregnancy rate per cycle was 1.1% in Norfolk, 4.7% to 6.2% elsewhere (perhaps because of stricter criteria in Norfolk). In cervical factor infertility, term pregnancy rate per cycle was 4.5% in Norfolk, 2.7% to 11% for others. For unexplained infertility, Norfolk had 5.8% term pregnancy rate per cycle for natural cycles, 8.3% for stimulated cycles. Best published prospective results were 23% for stimulated cycles. TII seems to have a very low efficiency rate judging from term pregnancy rates per cycle. There are clear data indicating the need for redefining the indications.

Adult↗