In vitro fertilization and embryo transfer: an established and successful therapy for endometriosis.
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Adult↗
Biomedical subjects
S Oehninger
Publications and source records attributed to S Oehninger.
Cryopreserved/thawed semen for in vitro fertilization: results from fertile donors and infertile patients.
We evaluated the in vitro fertilization (IVF) outcome in 54 cycles using cryopreserved/thawed semen from fertile donors. Controls were other IVF patients matched by time frame, female age, stimulation protocol, number of pre-embryos transferred, and absence of a male factor using freshly ejaculated normal semen samples. In the study group and controls, respectively, post-thaw swim-up motility was 83.1% and 89.5%; fertilization rate of preovulatory oocytes (91.8%, 95.7%) and ongoing pregnancy rate (PR) per transfer (21.1%, 25.0%) were similar. The excellent fertilization rate with frozen/thawed semen was achieved through high-concentration insemination (0.5 x 10(6) motile sperm/mL). With use of frozen/thawed samples from infertile men (normal and subfertile samples), PR was similar but fertilization rate was lower. Cryopreserved semen is a valuable option for infertile couples in IVF therapy.
Cryopreservation↗
Antagonistic and agonistic properties of saccharide moieties in the hemizona assay.
The hemizona assay (HZA) was used to evaluate the effects of different sugars on human sperm-zona pellucida interactions. In each controlled assay, sperm binding from men of known fertility with/without preincubation with different carbohydrate constituents was compared. We used human prophase I oocytes obtained from surgically removed ovaries; these oocytes were stored in salt solution and later bisected by micromanipulation. Preincubation of sperm (1 hour) with fucoidin (1.0 mg/mL) significantly inhibited binding by more than 85% as compared with controls. Similarly, lesser fucoidin concentrations of 0.5, 0.25, and 0.01 mg/mL were markedly inhibitory. In addition, preincubation times of 60, 30, and 15 minutes were not different in their degree of inhibitory effect. On the other hand, preincubation of the hemizonae with fucoidin before HZA inhibited binding by 43% compared with controls. Here, the fucoidin effect was significantly less inhibitory than the sperm preincubation effect of fucoidin. Preincubation of sperm with d-fucose had no measurable effect on binding, whereas d-glucose (1.0 mg/mL) and 1-fucose (1.0 mg/mL) increased binding. These results indicate: (1) that the HZA provides a unique internally controlled homologous bioassay to evaluate the effects of simple and complex carbohydrates on sperm zona interactions; (2) that fucoidin is an immediate (less than 15 minutes) inhibitor of human sperm binding to the human zona pellucida under HZA conditions.
Anticoagulants↗
The hemizona assay (HZA): a predictor of human sperm fertilizing potential in in vitro fertilization (IVF) treatment.
The hemizona assay (HZA) was developed to assess human sperm fertilizing potential. This blinded study investigated the relationship between sperm binding to the hemizona and in vitro fertilization (IVF) success (36 patients). Nonliving human oocytes were recovered from excised ovaries and stored. Each zona pellucida was cut into equal hemispheres by micromanipulation. For the HZA, one droplet exposed a hemizona to abnormal spermatozoa, while the control droplet contained the matching hemizona and spermatozoa from normal semen. After 4 hr, the number of tightly bound spermatozoa was counted. Binding to the hemizona was significantly higher for those having IVF success (mean of 36.1 +/- 7, versus 10.4 +/- 4 from the failure group; P less than 0.05). Fewer sperm from the failure group had a strictly normal morphology (3.2 versus 12.7%; P less than 0.05, Kruger method). Tight zona binding was significantly correlated with the percentage motile sperm, percentage normal morphology, and seminal sperm concentration. These results enhanced our confidence that the HZA is diagnostic for identification of patients at high risk of failing to achieve fertilization in vitro.
Female↗
Impact of leuprolide acetate on the response to follicular stimulation for in vitro fertilization in patients with normal basal gonadotropin levels.
Fifteen women with normal basal gonadotropin levels and adequate responses to conventional gonadotropin stimulation for in vitro fertilization (IVF) were pretreated with leuprolide acetate (LA) beginning in the midluteal phase prior to a repeat IVF attempt. A significantly longer duration of stimulation requiring a significantly higher total dosage of gonadotropins was observed in LA cycles. The number of preovulatory oocytes retrieved and preembryos transferred was significantly higher in LA cycles. Six of 15 women (40%) had cryopreservation of supernumerary preembryos in LA cycles, versus none in non-LA cycles; 22% of preovulatory oocytes aspirated in LA cycles were available for cryopreservation for future transfer. Five pregnancies occurred in the 15 LA cycles. IVF patients with normal basal gonadotropin levels and normal responses to conventional gonadotropin stimulation benefit from LA pretreatment.
Adult↗
Effects of clomiphene citrate on episodic luteinizing hormone secretion throughout the menstrual cycle.
Pituitary luteinizing hormone secretory dynamics (pulse frequency and amplitude) were evaluated in eight normal women administered clomiphene citrate or placebo. After 5 days of treatment clomiphene citrate was found to increase mean luteinizing hormone secretion by increasing the amount of pituitary luteinizing hormone released per pulse. No change in pituitary luteinizing hormone interpulse interval was found in the follicular phase of the cycle, although a faster pulse frequency in the luteal phase was found after clomiphene citrate when compared with placebo. No differences were found in the luteal phase (pulse frequency, amplitude, and mean luteinizing hormone level) after clomiphene citrate versus placebo in the volunteers. These data suggest that the principal mechanism of action of clomiphene citrate is an increase in the concentration of hypothalamic gonadotropin releasing hormone into the hypothalamic-pituitary portal circulation, with a resultant increase in pituitary luteinizing hormone secretion.
Adult↗
Delayed fertilization during in vitro fertilization and embryo transfer cycles: analysis of causes and impact on overall results.
This study evaluated possible causes of delayed fertilization during in vitro fertilization (IVF) cycles, its repetitiveness, and its influence on IVF results in 23 patients (27 cycles) with delayed fertilization of greater than or equal to 1 preovulatory oocyte(s). In 15 cycles, reinsemination with husband's semen was performed at 18 hours. Possible causes of delayed fertilization were oocyte defects (10 cycles, 37.0%), sperm defects (4 cycles, 14.8%), oocyte and sperm defects (4 cycles, 14.8%), and no detectable gamete defects (9 cycles, 33.3%). Overall fertilization rate was 47.9%. No pregnancies were observed in 10 patients with one embryo transferred. Recurrence rate of delayed fertilization per patient was 17.3%; overall ongoing pregnancy rate/cycle was 10.3%. Although repetitiveness of delayed fertilization is low, it seems to impact negatively on IVF results.
Embryo Transfer↗
Effects of the severity of tubo-ovarian disease and previous tubal surgery on the results of in vitro fertilization and embryo transfer.
The purpose of this study was to evaluate the ovarian response and in vitro fertilization/embryo transfer (IVF-ET) results in patients with tubal infertility and two ovaries, according to (1) the degree and extent of pelvic disease (isolated tubal or tubo-ovarian) and (2) previous adnexal surgical procedures. A total of 549 patients who underwent 1031 IVF-ET cycles were evaluated. Significant findings were as follows: (1) No differences were found in the number of preovulatory oocytes, fertilization rates, or serum estradiol levels in the follicular phase between any classes of tubo-ovarian disease. (2) Patients with a "frozen pelvis" had significantly fewer follicles aspirated than those in any other category, although they had equivalent numbers of preovulatory oocytes retrieved and pregnancy rates. (3) Patients with previous bilateral tubal ligation had higher pregnancy rates than patients with severe tubo-ovarian disease. (4) The type of prior pelvic surgical procedure had no effect on IVF-ET outcome. Although patients with no cause of infertility other than tubal ligation had better results, these patients had previously proven fertility. We conclude that neither the stage of tubo-ovarian disease nor any history of pelvic adhesions or tubal surgery has a significant impact on the efficiency of IVF-ET.
Adult↗
Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome.
Cycle day 3 basal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured in 441 patients in 758 consecutive cycles to determine their predictive value for stimulation quality and pregnancy rates in vitro fertilization (IVF). Patients with low basal FSH levels (less than 15 mIU/ml) had higher pregnancy rates per attempt than those with moderate levels (15 to 24.9 mIU/ml), both of which were higher than those with high FSH levels (greater than 25 mIU/ml). Basal LH and E2 values did not improve the predictive value beyond that provided by FSH. Ongoing pregnancy rates per attempt in the low, moderate, and high FSH groups were 17.0%, 9.3%, and 3.6%, respectively (P less than 0.01). The three groups differed significantly in the percentage of patients having two ovaries, the mean number of follicles aspirated per retrieval, the mean number of preovulatory oocytes obtained, and peak E2 values (P less than 0.01). Cycle day 3 FSH levels are predictive of pregnancy outcome and stimulation characteristics in IVF, and may be useful in counseling patients.
Estradiol↗
Hemizona assay: assessment of sperm dysfunction and prediction of in vitro fertilization outcome.
The hemizona assay (HZA) was used in a prospective, blinded study to assess the relationship between tight sperm binding in the HZA and sperm fertilizing ability in in vitro fertilization (IVF). In each controlled assay, the authors compared sperm binding of proven fertile men with that of patients undergoing IVF. Human oocytes stored in a salt solution were used in the study, and binding results were correlated with the fertilization rate of preovulatory oocytes during IVF. Patients with poor fertilization rates in IVF had significantly lower binding than those cases with successful fertilization (7.3 +/- 1.4 versus 62.1 +/- 10.9, respectively; mean +/- standard error, P less than 0.02). Based on current standards, the HZA was able to predict fertilization accurately in 26 of 28 cases (sensitivity of 83%, specificity of 95%, positive predictive value of 83%). The authors conclude that the HZA is a valuable tool for evaluating dysfunctional sperm-zona pellucida binding, with good predictive value for fertilization in vitro.
Adult↗
In-vitro fertilization and embryo transfer in patients with endometriosis: impact of a gonadotrophin releasing hormone agonist.
In this study, in-vitro fertilization (IVF) cycles were examined in patients with endometriosis who received gonadotrophin releasing hormone agonist (GnRHa) therapy in an effort to improve their response to stimulation. Twelve patients treated with an identical gonadotrophin stimulation protocol, with and without GnRHa, were evaluated using paired analysis. In the GnRHa cycles, the total number of oocytes retrieved and transferred per cycle was higher than in the control cycles. In addition, use of the agonist lowered the cancellation rate from 33 to 0%, while a trend towards better pregnancy results was observed. When analysed according to the stage of the disease, the patients with stage III or IV endometriosis had a more dramatic improvement with GnRHa. These data suggest that GnRHa therapy may be beneficial in some patients with endometriosis undergoing IVF.
Embryo Transfer↗
Assisted reproduction in the diagnosis and treatment of the male factor.
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Fertilization in Vitro↗
Validation of the hemizona assay in a monkey model: influence of oocyte maturational stages.
The hemizona assay (HZA) was used in the monkey model to investigate sperm binding to the zona pellucida and to evaluate binding patterns according to various stages of oocyte development. Adult cynomolgus monkeys were superovulated with human menopausal gonadotropin. The oocytes were retrieved by laparoscopy, stored in salt solution, then cut into hemizonae by micromanipulation. Metaphase II oocytes showed significantly tighter binding than prophase I oocytes (P less than 0.001). Metaphase I oocytes showed intermediate binding, significantly different from the other groups (P less than 0.01). It is concluded that: (1) This study demonstrates the feasibility of HZA as a test to evaluate sperm/zona interactions in the monkey, using standards reported for human studies. (2) Oocyte meiotic competence seems to be accompanied by an increase in zona-binding properties.
Animals↗
Failure of fertilization in in vitro fertilization: the "occult" male factor.
Failure of fertilization in patients undergoing in vitro fertilization (IVF) deserves extensive analysis for better prediction of the success or failure of this therapeutic modality. Consequently, we retrospectively studied the 52 couples in whom fertilization failed during Norfolk series 18 to 25, in an effort to establish the precise causes of failure. In the initial evaluation, pure oocyte abnormalities were identified in 19.2% of the cases; 32.6% showed sperm abnormalities, and a combination of oocyte and sperm anomalies was found in 7.7%. In 40.4% of the cases, failure of fertilization could not be explained. Reassessment of sperm morphology by new, strict criteria increased the identification of sperm abnormalities to 61.5% and of combined sperm and oocyte anomalies to 13.4%, for a total of 74.9% of sperm factors involved, as opposed to 40.3% in the original evaluation. The incidence of unexplained failed fertilization was substantially reduced, to 11.5%. In a control group (tubal infertility) matched by age, date, and stimulation, in whom fertilization occurred, 83.3% had normal sperm parameters as judged by the new criteria for morphology evaluation. This paper emphasizes the need for a more accurate diagnosis of sperm abnormalities to establish the true incidence of this factor in failed fertilization and to obtain information of prognostic value to patients and clinicians.
Adult↗
Significance of the recovery of fractured-zona oocytes in an in vitro fertilization program.
Recovery of fractured-zona oocytes (FZOs) from patients undergoing in vitro fertilization and embryo transfer (IVF/ET) has been previously reported. The present study was undertaken to determine the possible influence of different stimulation protocols and retrieval techniques on the incidence of FZOs, to analyze possible causes, and to evaluate the significance of FZOs in terms of IVF/ET results. Four hundred thirty-three cycles in which one or more FZOs were recovered (fractured-zona cycles; FZCs) and 1114 cycles in which FZOs were not obtained (intact-zona cycles; IZCs) were studied. A significantly higher number of follicles was aspirated in FZCs (7.16 +/- 3.5) than in IZCs (6.43 +/- 3.56), yielding significantly fewer immature oocytes in FZCs (1.58 +/- 1.93 vs 1.88 +/- 2.16) and a significantly higher number of atretic oocytes in FZCs (2.06 +/- 1.36 vs 0.73 +/- 1.21). No statistically significant difference was observed when the number of preovulatory oocytes obtained was compared. Nor were statistically significant differences observed as a result of either the type of stimulation [human chorionic gonadotropin (hMG), follicle-stimulating hormone (FSH), or a combination] or the aspiration technique utilized (laparoscopy vs ultrasonically guided puncture). Peripheral estradiol and progesterone and follicular fluid estradiol, progesterone, and androstenedione comparisons showed no significant differences. However, endocrine and morphologic findings (higher follicular androstenedione levels and estradiol/progesterone ratio, degenerated ooplasms) suggested some degree of late oocyte atresia, possibly due to slight hyperstimulation. In an experimental study, two healthy immature oocytes matured in vitro to the metaphase II stage showed degenerative changes in the ooplasm within 20 min after being subjected to mechanical zona pellucida (ZP) damage (mechanical fracture).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
In vitro fertilization and embryo transfer (IVF/ET): an established and successful therapy for endometriosis.
The purpose of this report is to present a 6-year experience in the management of endometriosis with in vitro fertilization and embryo transfer (IVF/ET). We divided 136 patients who underwent 280 cycles into three groups: (1) previous history of endometriosis but normal pelvis at the time of oocyte retrieval, (2) stages I-II endometriosis (revised AFS classification), and (3) stages III-IV endometriosis. The stimulation protocols, estradiol (E2) responses, and distribution of terminal E2 patterns were similar in all groups. Group 3 had significantly fewer preovulatory and immature oocytes retrieved and fewer embryos transferred. The fertilization rate and the per cycle/per transfer pregnancy rates were similar in all groups. The miscarriage rate was higher in group 3, and the ongoing pregnancy rate per cycle was lower. Luteal phase E2 and progesterone levels were comparable in all groups. No differences were found when groups 2 and 3 were analyzed for the presence of one or two ovaries or the presence/absence of ovarian endometriosis. The overall fertilization rate, the per cycle/per transfer pregnancy rates, and the miscarriage rate were similar to those of tubal factor patients. We underscore the excellent outcome of patients with minimal or mild endometriosis in IVF/ET. We conclude that patients with moderate or severe endometriosis have a compromised reproductive potential, probably because of a reduced oocyte recovery rate and poor embryo quality.
Abortion, Spontaneous↗
Predictive value of abnormal sperm morphology in in vitro fertilization.
In patients with acceptable sperm count and motility, two patterns of abnormal morphology, judged with strict criteria, were identified and described. Patients with less than 4% normal forms and less than 30% morphology index (summation of normal and slightly amorphous forms) had a fertilization rate of 7.6% of the oocytes (P pattern, poor prognosis). Patients with normal morphology between 4 and 14% had a significantly better fertilization rate of 63.9% of the oocytes (P less than 0.0001). Cases with greater than 14% normal forms fertilized within the normal range for the laboratory. By evaluating sperm morphology with the proposed strict criteria, its predictive value in in vitro fertilization is enhanced.
Female↗
The value of in vitro fertilization for the treatment of unexplained infertility.
In 54 patients referred with the diagnosis of unexplained infertility (UI), the diagnosis was confirmed in 26 (strict UI) (48%). Minimal abnormalities (MA) were found in 19 (35%); 9 (17%) had gross abnormalities and were excluded from analysis. Fifty patients with tubal infertility were randomly assigned to form a control group. Mean age and type of stimulation did not differ in the two groups. Peak follicular estradiol (E2) and terminal follicular E2 patterns were comparable. There was no difference in the mean number of oocytes retrieved per cycle. However, the control group had significantly more preovulatory oocytes: 3.6 +/- 2.0 standard deviations versus 2.8 +/- 2.1 in the overall UI group (strict UI + MA groups) and 2.7 +/- 2.2 in the strict UI group. Significantly more fertilized oocytes per cycle were obtained in the control group (P less than 0.05). The per-cycle and per-embryo transfer (ET) pregnancy rates were 32.4 and 37.3% in the overall UI group and 24 and 24.5% in the control group. The miscarriage rate was 12% in the strict UI group, 22% in the overall UI group, and 25% in the control group. It is concluded that patients with UI constitute a favorable group for in vitro fertilization and ET.
Chorionic Gonadotropin↗