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PubMed1993

The likelihood of pregnancy with IVF and GIFT in Australia and New Zealand.

OBJECTIVE: To determine the likelihood of pregnancy for couples entering the New Reproductive Technology (NRT) programs in Australia and New Zealand, by combining the data from nearly all the practising units. DESIGN: All units practising in-vitro fertilisation (IVF) and/or gamete intrafallopian transfer (GIFT) were contacted and asked to provide data on patients treated and pregnancy rates. These figures were then combined to produce life tables to determine the likelihood of pregnancy with repeated attempts. SETTING: IVF/GIFT units in five States of Australia, the Australian Capital Territory and New Zealand. Eighteen of the 22 units provided data to be analysed. PATIENTS: Data were available for analysis on 18,089 cycles of IVF resulting in 3034 clinical pregnancies, and 6308 cycles of GIFT resulting in 1724 clinical pregnancies. MAIN OUTCOME MEASURES: This was either "clinical pregnancy" (the presence of products of conception on ultrasound examination), or "viable pregnancy" (a pregnancy developing to at least 20 weeks of gestation). RESULTS: After four attempts at IVF, half the couples achieved a pregnancy, whereas four attempts at GIFT resulted in two-thirds of the couples achieving pregnancy. CONCLUSION: Both IVF and GIFT are effective and successful options for infertile or subfertile couples. New Reproductive Technology should be readily available in every advanced clinic dealing with subfertile couples in the 1990s.

Australia↗
PubMed1990

Immunosuppressive activity in human embryo growth media is associated with successful pregnancy: effect of gonadotropin releasing hormone agonist (GnRHa) treatment of patients undergoing in vitro fertilization and embryo transfer (IVF-ET).

The aim of the present study was to determine whether the secretion of embryo-associated immunosuppressor factor (EASF) by preimplantation embryo correlates with pregnancy outcome and whether this relationship is influenced by pretreatment of gonadotropin releasing hormone agonist (GnRHa) in patients undergoing in vitro fertilization and embryo transfer (IVF-ET). EASF activity was measured using concanavalin A-induced human lymphocyte proliferation assay in 256 embryo growth media obtained from 61 patients undergoing IVF-ET. EASF activity was then correlated with GnRHa treatment and pregnancy outcome in these IVF patients. Results indicate that (i) the presence of immunosuppressive activity in human embryo growth media is associated with success of pregnancy in GnRHa nontreated patients and (ii) serum factors present in GnRHa-treated patients may affect the EASF secretion by preembryos in vitro.

Blastocyst↗
PubMed1990

The impact of embryo quality on pregnancy outcome in elderly women undergoing in vitro fertilization-embryo transfer (IVF-ET).

Most IVF-ET units limit the procedure to women below age 38. Nevertheless, demands for infertility treatment, including IVF therapy, are more frequent nowadays. We compared 46 cycles for ovulation induction for IVF in 46 women aged 40 or more (Group I) to 51 induced cycles for this procedure in younger women of mean age 30.2 years (Group II). Cancellation rates due to early luteinization or ovulation were significantly higher in group I than in group II (28.2 and 17.6%, respectively) (P less than 0.001). Also, significantly higher abortion rates were observed in older women (62.5%), in comparison to the younger control group, (25%), (P less than 0.001). It is suggested that the high abortion rate considered to be due to genetic factors in older women, may possibly also be due to the aging uterine environment. Furthermore, while embryos with fragmentations may often produce clinical pregnancies in the young, the aging uterus in the elderly woman does not encourage the development of clinical pregnancies in such embryos. Consequently the higher abortion rate in the elderly woman.

Abortion, Spontaneous↗
PubMed1990

Psychiatric morbidity in parents of twins born after in vitro fertilization (IVF) techniques.

A matched comparison was made of 158 parents of preschool twins conceived under three conditions; spontaneously, after infertility workup including drug treatment, and after in vitro fertilization (IVF). Indications of probable psychiatric caseness were obtained using the 60-item General Health Questionnaire. IVF parents' mean scores were similar to those of parents who spontaneously conceived, and both were significantly greater than those who conceived after an infertility workup. Mothers and fathers overall had similar scores, contrary to previous community findings of higher rates of psychiatric disorder among females. The prevalence of probable psychiatric caseness was less for IVF and spontaneously conceiving mothers, but greater for the respective fathers, than in an English community sample and greater than in an Australian community sample. The extent to which the self-reports of current psychiatric disturbance can be ascribed to any preexisting psychopathology is unknown. Indications of increased psychiatric disturbance found in this investigation warrant further prospective investigations, especially of the difficulties of rearing twins when couples are vulnerable in having this degree of psychiatric morbidity.

Australia↗
PubMed1990

Physicochemical properties of follicular fluid and their relation to in vitro fertilization (IVF) outcome.

Despite the limited data that are available concerning FF physicochemical properties, the following conclusions can be drawn. (1) FF temperature is lower than ovarian stroma and body temperatures. The physiological significance of this gradient is unknown. (2) Follicular size increases exponentially prior to ovulation. The relationship between FF volume and successful IVF outcome is well established. (3) A highly significant association exists between fertilization (but not embryo cleavage) and FF spectrophotometric absorbance at delta optic density of 455 nm. (4) FF behaves as a non-Newtonian fluid--its viscosity changes at different shear rates. Neither FF viscosity nor its refractive index was found to correlate with the presence of oocytes, their maturation grade, or their fertilizing capacity. (5) FF osmolarity is similar to that of the plasma. There is no information linking variations in FF osmolarity to IVF outcome. (6) FF pH is acidic, probably due to acid mucopolysaccharides. It appears that the intact follicle is capable of buffering any carbon dioxide which diffuses through its wall at the time of intraperitoneal insufflation. The transvaginal aspiration technique eliminates any possible effect of exogenous gas on FF pH. (7) Regarding the intact follicle, it was shown that (a) there is a small potential difference across the follicle wall, and (b) intrafollicular pressure remains steady prior to ovulation. This information may shed some light on mechanisms underlying FF formation and ovulation. No experiments relating these properties to IVF outcome have been performed.

Animals↗
PubMed1992

Relationship among serum levels of luteinizing hormone, estradiol, and progesterone during follicle stimulation and results of in vitro fertilization and embryo transfer (IVF-ET).

Eighty-eight IVF-ET cycles were classified into four groups according to the results of IVF-ET (Group A-conceptional cycles, 10 cycles; Group B-cycles with cleaved oocytes, 58 cycles; Group C-cycles with fertilized oocytes, 9 cycles; Group D-cycles without fertilization, 11 cycles). Serum luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels during follicle stimulation were studied in these groups. Patients participated in our IVF-ET program due to irreparable tubal damage. Follicle development was stimulated with a clomiphene-human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG) regimen. Group C showed a low E2 response to follicle stimulation. Groups B and D showed significantly higher serum P levels on day 0 (the day of hCG injection) than Group A (Group A, 0.73 +/- 0.11, vs Groups B and D, 1.43 +/- 0.15 and 2.17 +/- 0.42 ng/ml; P less than 0.01). The effects of serum P and LH levels on the fertilization and pregnancy rates were studied. The pregnancy rate was not affected by the serum LH level but was only 2.7% in cycles in which serum P was 1.2 ng/ml on day 0, which was significantly lower than that in cycles in which serum P was less than 1.2 ng/ml on day 0 (19.1%) (P less than 0.05). The fertilization rate was significantly lower in the cycles with higher levels of serum P and/or LH than in cycles in which serum P was less than 1.2 ng/ml and serum LH was normal (50.5 vs 78.8%; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clomiphene↗
PubMed1992

Luteinizing response to human chorionic gonadotropin does not predict outcome in gonadotropin releasing hormone agonist-suppressed/human menopausal gonadotropin-stimulated in vitro fertilization (IVF) cycles.

OBJECTIVE: The purpose of this study was to determine if early luteinizing potential in gonadotropin releasing hormone agonist (GnRH-a)-suppressed/human menopausal gonadotropin (hMG)-stimulated IVF cycles is predictive of cycle outcome. DESIGN, PATIENTS: The study was a prospective evaluation of 41 women beginning a GnRH-a-suppressed/hMG-stimulated IVF cycle. SETTING: The in vitro fertilization program of a tertiary care institution was the study setting. MAIN OUTCOME MEASURES: The main outcome measures were (1) estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration and the following day and (2) the ovarian response to ovulation induction and clinical outcome. RESULTS: Ten of the 41 women achieved a clinical pregnancy (24.4%). There was no significant difference in progesterone (P) levels on the day of or the day following hCG administration between the pregnant and the nonpregnant groups. Both groups exhibited a significant rise in P level in response to hCG. There was no significant difference in E2 levels on the day of hCG between the two groups. The serum E2 did not rise significantly in response to hCG in either group. Patients who became pregnant had significantly more oocytes retrieved, fertilized, cleaved, and transferred. CONCLUSIONS: Clinical response and outcome in GnRH-a-suppressed/hMG-stimulated IVF cycles are not predicted by early luteinizing potential as indicated by the response of E2 or P to hCG.

Adult↗
PubMed1993

A modest increase in serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration may influence pregnancy rate and pregnancy loss in in vitro fertilization-embryo transfer (IVF-ET) patients.

PURPOSE: Our purpose was to study the effect of a modest increase in preovulatory serum progesterone (P4) levels in hyperstimulated patients and its association with pregnancy rate and pregnancy loss following in vitro fertilization (IVF) and embryo transfer (ET). PATIENTS: Only patients with mechanical factor and three transferred embryos were included in the present study. They were divided into two groups according to two critical breakpoints for P4 serum levels on the day of hCG administration: serum P4 below 0.6 ng/ml in 28 cycles (group I) and > 0.6 ng/ml in 80 cycles (group II). SETTING: The setting was the IVF program at Carmel Medical Center, Haifa, Israel. RESULTS: The pregnancy rate per embryo transfer was 53% (15/28) in group I and 10% (8/80) in group II (P < 0.025). Of 15 pregnancies achieved in group I, 14 were ongoing pregnancies, compared to 4 of 8 ongoing pregnancies in group II (P < 0.03). CONCLUSIONS: Our findings suggest that a very modest increase in serum P4 levels on the day of hCG administration is associated with lower pregnancy and ongoing pregnancy rates in IVF-ET.

Adult↗
PubMed1996

Success rates following intracytoplasmic sperm injection are improved by using ZIFT vs IVF for embryo transfer.

PURPOSE: The purpose of this study was to analyze whether the mode of embryo transfer (ZIFT vs IVF) affected the outcome in intracytoplasmic sperm injection (ICSI) cycles. METHODS AND RESULTS: Eighty-two ICSI cycles (42 ZIFT and 40 IVF) were analyzed. Several variables, including patient age and weight, numbers of mature eggs collected, injected, and fertilized, fertilization rate, number of fertilized eggs obtained per cycle, numbers of zygotes/embryos transferred, clinical pregnancy rate, and implantation rate, were compared. Mean patient age and weight were identical. The mean number of mature eggs collected and injected and fertilization rate were significantly higher in the ZIFT group, however, the mean numbers of zygotes/embryos transferred were identical. The clinical pregnancy and implantation rates in ZIFT cycles (52.3 and 23.2% respectively) were significantly higher than in IVF cycles (17.5 and 9.7%). CONCLUSIONS: These data suggest that ZIFT is the more appropriate method for transfer of ICSI-derived embryos.

Adult↗
PubMed1996

High levels of spermine in IVF medium as a negative predictor of subsequent success of embryo transfer.

PURPOSE: Our purpose was to test the prediction that spermine levels in IVF culture supernatants measure by rapid ELISA assay correlate with subsequent success or failure to establish a pregnancy. RESULTS: Forty-nine patients undergoing gonadotropin-stimulated ovulation after LHRH analogue treatment in the current study succeeded and 57 failed. With the exception of the first 4 hr of culture, where polyamine levels were slightly (but not significantly) higher in supernatants associated with subsequent success, higher levels of polyamines were predictive of failure. CONCLUSIONS: The result in this study differs from previous data obtained with women ovulated using clomiphene where low spermine levels (assayed in an immunosuppression assay in vitro) correlated with failure to establish pregnancy, and detectable levels correlated with success. Supplementation of IVF culture medium with spermine and/or spermidine appears unlikely to improve IVF success rates, where the success rate is already very good, and may possibly do harm. The possibility that different methods of ovulation affect subsequent polyamine production in vitro by fertilized oocytes merits further study.

Culture Media, Conditioned↗
PubMed1996

Clinical experience with synthetic serum substitute as a protein supplement in IVF culture media: a retrospective study.

OBJECTIVE: Our objective was to evaluate the efficacy of Synthetic Serum Substitute (Irvine Scientific--Materials Section, Santa Ana, CA), a globulin-enriched protein preparation containing human serum albumin for supplementation of IVF culture media. DESIGN: We retrospectively analyzed IVF cycles performed at MacDonald Womens Hospital between January 1992 and November 1994. IVF cycles were reviewed and classified according to the nature of protein supplementation used in the embryo culture medium. Three protein supplements utilized during this time period were compared: Synthetic Serum Substitute (SSS), Plasmanate (PL), and maternal serum (MS). RESULTS: Although clinical pregnancy rates among the three treatment groups were not statistically different, there was a definite trend toward a higher pregnancy rate with SSS supplementation (SSS, 38.2%; MS, 28.0%; and PL, 24.9%). Embryos grown in SSS-supplemented culture media had a significantly higher implantation rate (17.8 vs 10.4 and 10.3%, respectively, for MS and PL). Preliminary data also suggest that human embryo development and blastulation in vitro were enhanced by this protein supplement. CONCLUSIONS: The higher implantation rate with SSS suggests that it may be superior to both maternal serum and Plasmanate in supporting human embryo development in vitro. Whether blastocysts derived from PL- and SSS-supplemented media are able to implant and give rise to clinical pregnancies remains to be seen.

Adult↗
PubMed1996

Cytogenetics of uncleaved oocytes and arrested zygotes in IVF programs.

PURPOSE: Cytogenetic studies of arrested oocytes and zygotes were used to understand in vitro fertilization (IVF) failures. METHODS: We investigated the cytogenetics (Giemsa banding and FISH) of 710 uncleaved oocytes and 94 arrested zygotes from 208 patients undergoing IVF procedures. RESULTS AND CONCLUSIONS: Of uncleaved oocytes without a polar body, 39% were judged cytogenetically abnormal (17% unbalanced predivision and 21.5% diploid). Of 575 oocytes with a polar body, 124 (21.5%) showed numerical or structural chromosome aberrations. In arrested zygotes, approximately equal cases were found with separate condensed haploid complements (no syngamy), nuclear asynchrony and pulverized DNA, and apparently cytogenetically normal zygotes arrested at mitosis. These data on chromosome abnormalities were also analyzed with respect to two ovarian stimulation protocols and to maternal age. Both ovarian stimulation protocols and to maternal age. Both ovarian stimulation protocols showed the same levels of chromosome abnormalities. Overall chromosome abnormalities and premature chromosome condensation were also unchanged with maternal age. These data illustrate the significance of chromosome aberrations in IVF failures.

Adult↗
PubMed1995

Evaluation of hormonal testing in the screening for in vitro fertilization (IVF) of women with tubal factor infertility.

PURPOSE: To evaluate the frequency of abnormal prolactin and thyroid stimulating hormone (TSH) test results in ovulatory women with tubal factor infertility who were screened for in vitro fertilization (IVF). METHODS: Charts were identified from 112 ovulatory women with follicle stimulating hormone (FSH) < 20 mIU/ml who were diagnosed with tubal factor infertility and were screened for IVF with thyroid stimulating hormone (TSH) and prolactin levels. Women previously diagnosed with thyroid disease were subsequently excluded and 98 subjects remained. All subjects were determined to be ovulatory by biphasic basal body temperature (BBT) charts, luteal phase progesterone > 4 ng/ml, or endometrial biopsy revealing secretory endometrium. Results of cycle day 3 serum TSH and prolactin concentrations were recorded. The normal range for each test reflects the geometric mean +/- 2 standard deviations (i.e., 95% interval), as obtained from the reference laboratory. Under this construct, hypothesis tests were performed to determine whether or not our study population was consistent with the reference range of normal hormone levels. Under the null hypothesis (normal levels), we expected 5% of the TSH tests to be abnormal (i.e., high or low levels), and 2.5% of the prolactin tests to be abnormal (i.e., high levels). Exact bionomial confidence intervals and P-values were calculated. We also tested for age trend in the proportion of abnormal results. RESULTS: Study subjects had an age range of 25-43. In the study group, 4 (0.041) out of the 98 women screened had abnormal TSH levels. Of these four abnormal TSH results, three were elevated (i.e., TSH > 4.6 microIU/ml) and one was low (i.e., TSH < 0.6 microIU/ml). The frequency of an abnormal TSH value was not significantly different from that expected from the reference laboratory normal values (95% CI 0.011, 0.101). Of the 98 subjects, 7 (0.071) had abnormal prolactin levels, which was significantly different from that expected from the reference laboratory normal values (95% CI 0.029, 0.142; P = 0.023). When stratified by age, there was no observed trend of abnormalities for TSH or prolactin levels with increasing age. CONCLUSIONS: In ovulatory women presenting for IVF with tubal factor infertility, our results show that routine screening with a TSH test does not yield a significantly higher proportion of abnormal results than that expected from the reference laboratory normal values. However, prolactin level screening was found to yield a higher incidence of abnormal tests than expected from the reference laboratory normal values.

Adult↗
PubMed1995

Hormone release from cultured luteinized-granulosa cells mimics differences seen in vivo in patients undergoing IVF-ET.

OBJECTIVES: Previous research from this laboratory has suggested that a relationship exists between the increase in circulating progesterone concentrations at the time of hCG administration and cycle outcome in patients undergoing IVF. Progesterone (P) increases of threefold or better within the 24-h period surrounding hCG administration appeared to be associated with a higher pregnancy rate. These data suggest a functional difference in the luteinized-granulosa of patients undergoing IVF. To test this hypothesis: DESIGN: A split-split plot arrangement of treatments with two cell sources under five hormonal stimulations at four time points. METHODS: Luteinized-granulosa cells (LGC) were collected from patients with either a normal increase (> or = threefold = NC) in circulating P (n = 4) or those with lower P increases (AC; n = 4). The cells were isolated by Ficoll gradient centrifugation and then cultured in 24-well culture plates using a modified media 199 containing 100 mIU/ml of hMG, FSH, LH, hCG, or a nonhormonal control to stimulate steroid-hormone production. At time points 2, 4, 6, and 8 days, media from each well was frozen for later hormone assay and replaced with fresh media containing the same stimulating factor. After all the media had been collected, P and estradiol (E2) released into the media were measured using radioimmunoassay. RESULTS: Results indicate a higher media concentration of P (P < 0.001), but not E2 (P = 0.254), from NC, regardless of hormone stimulation or time in culture, when compared to the media from AC. Media concentrations of E2 were affected by a cell source by hormone stimulation by time interaction (P < 0.001) with varying effects. Media from NC maintained a constant E2 of between 1000-3000 pg/ml over the 8-day period (P = 0.163). However, media from AC demonstrated a stimuli-dependent E2 release (P < 0.001) ranging from < 1000 to over 11,000 pg/ml. CONCLUSIONS: These data appear to support the existence of functionally different populations of luteinized-granulosa cells from patients undergoing IVF-ET.

Adult↗
PubMed1995

Pituitary down-regulation in IVF cycles: is it necessary to use strict criteria?

PURPOSE: In a retrospective study we have reviewed the data of 570 consecutive IVF cycles in which a GnRH agonist (GnRHa) was started in the early follicular phase (long protocol). Cycles were divided in groups according to estradiol levels before HMG administration: A, < 20 pg/ml; B, 20 to 50 pg/ml; C, 51 to 100 pg/ml. Our objective was to determine if the degree of pituitary suppression had any effect on the ovarian response to stimulation by exogenous gonadotropins, and/or on the IVF outcome. RESULTS: There were no significant differences in cycle cancellation rates, no. of days of stimulation and ampoules of HMG, serum estradiol after HMG, no. of oocytes retrieved and fertilization rates between groups. Pregnancy rates (19.4%, 21% and 31.8%/cycle, and 24.1%, 27.5% and 37.8% / embryo transfer, respectively) and live-birth rates (16.2%, 16.1% and 25.0%/cycle, 20.1%, 21.2% and 29.7%/embryo transfer, respectively) were also not significantly different. CONCLUSIONS: The degree of pituitary suppression had no effects on either the ovarian response to gonadotropins (including HMG requirements) or the overall IVF results.

Adult↗
PubMed1995

Comparison between depot leuprorelin and daily buserelin in IVF.

OBJECTIVES: To compare the effects of depot and daily forms of GnRH analogs in IVF programs. METHODS: One hundred seventeen patients undergoing IVF, with no severe male factor, were randomized between two treatment groups. Pituitary desensitization was obtained in group 1 (60 patients) with a single IM injection of leuprorelin (3.75 mg), and in group 2 (57 patients) with buserelin (0.3 mg SC twice daily). In a subgroup of 10 patients (5 for the depot form and 5 for the daily form) several GnRH tests were performed to investigate pituitary desensitization. RESULTS: No differences were found in the time to reach desensitization. Resumption of pituitary activity occurred in 7 days with the daily form and in about 2 months with the depot form. No significant differences were found in the stimulation pattern, oocyte quality, percentage of fertilization. The pregnancy rate per transfer was slightly, but not significantly, better in the depot group (29.4% vs 25.9%). Implantation rate (11.9% vs 12.3%) and the percentage of miscarriages (26.6% vs 28.5%) were similar. CONCLUSION: Depot and daily forms of GnRH analogs are equally effective in superovulation induction for IVF. Considering improved patient compliance and preference, depot forms are advantageous.

Abortion, Spontaneous↗
PubMed1994

Effect of chlamydial antibodies on the outcome of in vitro fertilization (IVF) treatment.

OBJECTIVE: Our objective was to study the relationship between the presence of Chlamydia trachomatis antibodies and the success of IVF treatment. DESIGN: We evaluated 118 in vitro fertilization and embryo transfer (IVF-ET) treatment cycles from 51 couples with a history of infertility lasting for at least 2 years. All women starting a treatment cycle had their serum chlamydial antibody titers measured by indirect immunofluorescent technique. All patients received similar ovarian stimulation regimens and the oocytes collected were inseminated with similar concentrations of motile sperm. Clinical data from couples where the female partner had C. trachomatis ab titers > or = 40 have been compared with the equivalent data from couples where the female partner had C. trachomatis ab titers < 40. RESULTS: There was no statistically significant difference between the two groups concerning age, infertility period, oocytes collected, oocytes fertilized, and fertilization rate, and the pregnancy rates were comparable. CONCLUSION: Previous exposure to C. trachomatis did not alter the success rate of IVF-ET.

Adult↗
PubMed1998

Zona pellucida thickness variation and occurrence of visible mononucleated blastomers in preembryos are associated with a high pregnancy rate in IVF treatment.

PURPOSE: The ability of six morphological criteria (embryo development rate, fragmentation, regularity of blastomere shape, equality of blastomere size, zona pellucida thickness variation [ZPTV], and visible mononucleated blastomeres [VMBs]) to predict pregnancy in IVF treatment cycles was evaluated. METHODS: In order to select a homogeneous study group, 85 consecutive nulliparous couples with single tubal infertility undergoing their first IVF treatment and receiving three preembryos at embryo replacement 2 days after ovum pickup were included. RESULTS: A total of 255 preembryos was replaced two days after ovum pickup and resulted in 34 clinical pregnancies (40%). By logistic regression analysis, ZPTV and VMBs showed highly significant and strong predictive values, whereas none of the other parameters was a significant predictor of pregnancy. In the treatments in which all replaced preembryos had a ZPTV of less than 15%, the pregnancy rate was extremely low (1/22). If the maximum ZPTV of any of the replaced preembryos was in the interval between 15 and 20%, the pregnancy rate was 24.1% (7129). In the treatments in which at least one preembryo had a ZPTV of more than 20%, the pregnancy rate was 76.5% (26/34). When VMBs were added to the results of the ZPTV analysis, the pregnancy rate was as high as 92.3% (24/26). CONCLUSIONS: ZPTV and VMBs seem to be strong predictors of pregnancy in IVF treatment and thus important indicators of good embryo quality.

Adult↗