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Biomedical subjects

J Gunby

Publications and source records attributed to J Gunby.

At least 19 recordsLinked to original sources
PubMed2004

Day three versus day two embryo transfer following in vitro fertilization or intracytoplasmic sperm injection.

BACKGROUND: Embryo transfer (ET) was traditionally performed two days after oocyte retrieval; however, developments in culture media have allowed embryos to be maintained in culture for longer periods. Delaying transfer from day two to day three would allow for further development of the embryo and might have a positive effect on pregnancy outcomes. OBJECTIVES: To determine if there is any difference in live birth and pregnancy rates when ET is performed on day three, compared with day two, in infertile couples undergoing treatment with in vitro fertilization (IVF), including intracytoplasmic sperm injection (ICSI). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (17th December 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and Biological Abstracts Databases (1980 to 2003), the National Research Register (NRR), the Medical Research Council's Clinical Trials Register, the NHS Centre for Reviews and Dissemination, citation lists of relevant publications, review articles and included studies, as well as abstracts of appropriate scientific meetings. SELECTION CRITERIA: Randomized controlled trials that compared day three versus day two embryo transfer after oocyte retrieval during an IVF or ICSI treatment cycle in subfertile couples. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. The primary outcome measures were live birth rate and ongoing pregnancy rate. MAIN RESULTS: Ten studies involving 2027 women were included, but only three studies reported live birth and four reported ongoing pregnancy rates. The pooled odds ratios (day three compared to day two) were 1.07, 95% CI 0.84 to 1.37 for live birth and 1.05, 95% CI 0.83 to 1.32 for ongoing pregnancy. From ten studies, the pooled odds ratio for clinical pregnancy was 1.26, 95% CI 1.06 to 1.51. Sub-group analysis revealed that this advantage occurred in those undergoing ICSI cycles. A higher miscarriage rate with day 3 ET in ICSI cycles works to negate the increased clinical pregnancy rate, in agreement with the finding of no significant difference between treatments in live birth rate. REVIEWERS' CONCLUSIONS: Although an increase in clinical pregnancy rate with day three embryo transfer was demonstrated, at present there is not sufficient good quality evidence to suggest an improvement in live birth when embryo transfer is delayed from day two to day three.

Embryo Transfer↗
PubMed2004

Luteal phase support in assisted reproduction cycles.

BACKGROUND: The aspiration of the granulosa cells that surround the oocyte and the use of gonadotropin releasing hormone agonists (GnRHa) during assisted reproduction technology (ART) treatment can interfere with the production, during the luteal phase, of progesterone, which is necessary for successful implantation of the embryo. Providing hormonal supplementation during the luteal phase with either progesterone itself, or human chorionic gonadotropin (hCG), which stimulates progesterone production, may improve implantation and, thus, pregnancy rates. OBJECTIVES: To determine (1) if luteal phase support after assisted reproduction increases the pregnancy rate, (2) the optimal hormone for luteal phase support, i.e. hCG, progesterone, or a combination of both, and (3) the optimal route of progesterone administration. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1971 to Dec 2003), EMBASE (1985 to Dec 2003). We handsearched reference lists of relevant articles were scanned, and abstract books from scientific meetings up to December 2003. SELECTION CRITERIA: Randomized controlled trials of luteal phase support after ART treatment, comparing hCG or progesterone with placebo or no treatment, comparing progesterone with hCG, progesterone plus hCG, or progesterone plus estrogen, or comparing different routes of progesterone administration. Quasi-randomized trials were excluded from the main analyses, but included in a secondary analysis for each comparison. DATA COLLECTION AND ANALYSIS: For each comparison, data on live birth, ongoing and clinical pregnancy per embryo or gamete transfer procedure, miscarriage per clinical pregnancy, ovarian hyperstimulation syndrome (OHSS) per transfer, and multiple pregnancy per clinical pregnancy were extracted into 2 x 2 tables and subgrouped by use of GnRHa in the ovarian stimulation regimen. The odds ratio (OR) and risk difference (RD) were calculated. MAIN RESULTS: Fifty-nine studies were included in the review. Luteal phase support with hCG provided significant benefit, compared to placebo or no treatment, in terms of increased ongoing pregnancy rates (odds ratio (OR) 2.38, 95% confidence interval (CI) 1.32 to 4.29) and decreased miscarriage rates (OR 0.12, 95% CI 0.03 to 0.50), but only when GnRHa was used. The odds of OHSS increased 20-fold when hCG was used in cycles with GnRHa. Progesterone use resulted in a small but significant increase in pregnancy rates (OR 1.34, 95% CI 1.01 to 1.79) when trials with and without GnRHa were grouped together, but no effect on the miscarriage rate was observed. No significant difference was found between progesterone and hCG or between progesterone and progesterone plus hCG or estrogen in terms of pregnancy or miscarriage rates, but the odds of OHSS were more than 2-fold higher with treatments involving hCG than with progesterone alone(OR 3.06, 95% CI 1.59 to 5.86). Comparing routes of progesterone administration, reductions in clinical pregnancy rate with the oral route, compared to the intramuscular or vaginal routes, did not reach statistical significance, but there was evidence of benefit of the intramuscular over the vaginal route for the outcomes of ongoing pregnancy and live birth. No significant difference in pregnancy rate was observed between vaginal progesterone gel and other types of vaginal progesterone. REVIEWERS' CONCLUSIONS: Luteal phase support with hCG or progesterone after assisted reproduction results in an increased pregnancy rate. hCG does not provide better results than progesterone, and is associated with a greater risk of OHSS when used with GnRHa. The optimal route of progesterone administration has not yet been established.

Chorionic Gonadotropin↗
PubMed2001

Potential dangers in the customary methods of conducting meta-analyses. Lack of bias in the meta-analysis of recombinant versus urinary follicle stimulating hormone.

In a meta-analysis of randomized trials comparing recombinant and urinary FSH for ovarian stimulation in infertility treatment cycles, the clinical pregnancy rate per cycle started was significantly higher with recombinant FSH. Before the results of the different trials can be pooled, it is important to determine whether the results are homogeneous so that one can obtain an overall treatment estimate that is without bias. There are several methods to ascertain lack of homogeneity, including logistic regression analysis, sensitivity analysis comparing fixed-effect and random-effect models, testing based in the chi2 distribution, and graphical methods comparing event rates in experimental and treatment groups. These methods all confirmed that the treatment effect was homogeneous across all trials thereby providing assurance that the overall conclusion of the superior efficacy of recombinant FSH compared with urinary FSH is based on an unbiased analysis.

Bias↗
PubMed2000

Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction cycles.

BACKGROUND: Until recently, the main source of exogenous follicle stimulating hormone (FSH) for therapeutic use in infertility had been the urine of postmenopausal women. New developments have resulted in the production of FSH in vitro by recombinant DNA technology. The extremely high purity and batch-to-batch consistency of recombinant FSH (rFSH) make it an attractive alternative to urinary FSH (uFSH). OBJECTIVES: To conduct a systematic review and meta-analysis of randomized trials comparing the effectiveness of rFSH with uFSH in ovarian stimulation protocols in in vitro fertilization (IVF) or intra-cytoplasmic sperm injection (ICSI) treatment cycles. SEARCH STRATEGY: Search strategies included on-line searching of the MEDLINE and EMBASE databases from 1985 to 1999, hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings, peer consultation and contacting the pharmaceutical companies that manufacture the gonadotropins under consideration. SELECTION CRITERIA: Randomized trials comparing rFSH with uFSH for ovarian stimulation in IVF or ICSI treatment for infertility. DATA COLLECTION AND ANALYSIS: The main outcome measure was clinical pregnancy per cycle started. Also considered were clinical pregnancy per cycle reaching oocyte retrieval and per cycle reaching embryo transfer (ET), ongoing pregnancy per cycle started, spontaneous abortion, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), number of follicles and serum estradiol level on the day of human chorionic gonadotropin administration day, total dose of FSH, and number of oocytes retrieved. Common odds ratios (OR) and risk differences for rFSH relative to uFSH were calculated after testing for homogeneity of treatment effect across all trials. The fixed effects model was used, unless significant heterogeneity was present, in which case the random effects model was used. MAIN RESULTS: The overall odds ratio for clinical pregnancy per cycle started was 1.21 (95% confidence limits (CL) 1.04,1.42) for rFSH compared to uFSH. The risk difference was a 3.7% (0.8,6.7) absolute increase in clinical pregnancy rate with rFSH. The OR for ongoing pregnancy per cycle started was 1.29 (1.08,1.54). There was no significant difference between rFSH and uFSH in the rates of spontaneous abortion, multiple pregnancy or OHSS. The total dose of FSH was lower by 406 (185,627) IU with rFSH, but there was no significant difference in the number of follicles or serum estradiol on hCG day or in the number of oocytes retrieved. REVIEWER'S CONCLUSIONS: This review has demonstrated a statistically significant increase in clinical pregnancy rate with rFSH compared to uFSH, when used for ovarian stimulation in assisted reproduction. This benefit was observed only in standard IVF cycles and not in cycles in which ICSI was used.

Adult↗
PubMed1999

Recombinant versus urinary follicle stimulating hormone for ovarian stimulation in assisted reproduction.

The recent availability of recombinant follicle stimulating hormone (rFSH), with its high level of purity and batch-to-batch consistency has made it an attractive alternative to urinary FSH (uFSH) for ovarian stimulation. Several trials have compared the two preparations, but none had sufficient power to detect a clinically meaningful difference in pregnancy rates. The purpose of this study was to determine the clinical pregnancy rates per started cycle by pooling data from randomized trials which compared the use of rFSH and uFSH in treatment cycles using in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). A thorough search of the literature identified 12 trials which met the inclusion criteria. In four trials, both IVF and ICSI were performed, in seven trials only IVF was performed and in one trial only ICSI was performed. Data were extracted and pooled using the principles of meta-analysis. There was no significant heterogeneity of treatment effect across the trials. The common odds ratio and the risk difference (and their 95% confidence intervals), obtained by pooling the data using a fixed effects model, were 1.20 (1.02-1.42) and 3.7% (0.5-6.9%) respectively, in favour of rFSH. The pregnancy rate with the alpha preparation of rFSH was statistically significantly higher than with uFSH in IVF cycles. The overall conclusion from this meta-analysis is that the use of rFSH in assisted reproduction is preferred over uFSH.

Female↗
PubMed1998

A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility.

This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility.

Adult↗
PubMed1998

Intravenous immunoglobulin therapy for recurrent spontaneous abortion: a meta-analysis.

PROBLEM: Published randomized trials of the use of intravenous immunoglobulins (IVIG) as a treatment for recurrent spontaneous abortion (RSA) have produced conflicting results. The purpose of this study was to conduct a systematic review of the current evidence to evaluate the effectiveness of IVIG for RSA. METHOD OF STUDY: After a thorough search of the literature, four randomized, double-blind trials comparing IVIG with placebo for treatment of RSA were included in the meta-analysis. Live birth rates for each treatment group were extracted, and the overall odds ratio (OR) and absolute treatment effect for IVIG were calculated. RESULTS: Two of the trials showed an increase in successful pregnancy outcome with IVIG treatment and two did not. The overall OR was 1.48 (95% CI, 0.84-2.60) in favor of IVIG, with an absolute treatment effect of 10.1% (95% CI, -4.8-24.6). Excluding pregnancy failures with an obvious cause produced statistically significant results, but this approach may be subject to bias. CONCLUSION: This meta-analysis suggests that IVIG may have a role in the treatment of recurrent abortion, but as yet no conclusive evidence is available.

Abortion, Habitual↗
PubMed1997

The cost of infertility diagnosis and treatment in Canada in 1995.

The objectives of this study were to estimate the direct cost of infertility management, including diagnosis and treatment, in Canada during 1995, and the relative cost per live birth by treatment category. The analysis was based on the following estimates: the prevalence of infertility in Canada in 1995; the volume and distribution of infertility services; and the effectiveness and cost of specific infertility treatments. In 1995 there were approximately 330,000 couples experiencing infertility in Canada. It is estimated that <50% (150,000) sought medical advice or treatment during that year. A total of 13 diagnostic and treatment categories account for nearly all of the treatments received, and these categories form the treatment model. The cost of treatment per live birth ranges from Cdn$650 for clomiphene treatment of unexplained infertility to Cdn$41,000 for in-vitro fertilization. For a hypothetical group of 100 couples, the annual cost of diagnosis and treatment would be Cdn$77,000 and Cdn$200,000 respectively for a total of Cdn$277,000, or an average of Cdn$2770 per couple. After 1 year of treatment, it is expected that 26 of these 100 couples would achieve a live birth. The total annual cost of infertility management in Canada, estimated to be approximately Cdn$415 million, is 0.6% of the annual cost of health care.

Adult↗
PubMed1996

Semen parameters as predictors of in-vitro fertilization: the importance of strict criteria sperm morphology.

This study evaluated 120 couples undergoing in-vitro fertilization treatment to determine which semen parameter(s) predicted fertilization and whether there was any consistent relationship between strict criteria and standard assessment of sperm morphology. Strict criteria morphology was the only significant predictor of fertilization (P = 0.0006, r2 = 0.09), with a sensitivity of 94% and a specificity of 40%. A 12% cut-off point presented a negative predictive value of 98% and a positive predictive value of 22%. The probability of satisfactory fertilization is 40% with morphology <4%, which increases to 97% with normal morphology (>=12%). The receiver operating characteristic curve deviated significantly from the diagonal with a 76% area under the curve, making this a superior predictive test. This was augmented by likelihood ratios (LR) of 8. 25 (LR+) for results with <4% normal morphology and 0.15 (LR-) for results with >/= 12% normal morphology by strict criteria. While there was some correlation between strict criteria and standard assessment of morphology (r = 0.35), the former explained only 12% (r2 = 0.12) of the variability in the latter. This study concludes that strict criteria morphology predicts fertilization, while other semen parameters do not. A 12% cut-off point makes strict criteria morphology an excellent predictor of satisfactory fertilization, while a value <4% is a good predictor of poor fertilization.

Cohort Studies↗
PubMed1995

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization.

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6)). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Androgens↗
PubMed1995

Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome.

Improvements in oocyte culture technique, sperm preparation, oocyte retrieval method and ovarian stimulation regimens have produced higher pregnancy rates with in-vitro fertilization (IVF) treatment. However, because ovarian stimulation is expensive and not without risk, there is increasing interest in the option of using natural cycles for IVF. This study was performed to document the experience and outcome in 240 natural cycles. Cancellation occurred in 28 cycles (12%), and LH surge was observed in 56 (23%), leaving 156 (65%) cycles which progressed to oocyte retrieval. No oocytes were retrieved in 26 cycles. Among the successful oocyte retrievals, the majority yielded one oocyte. There was no evidence of fertilization in 26 cases, and triploid fertilization was observed in 12 cases. Embryos suitable for transfer were available in 92 cycles in which 11 (12%) clinical pregnancies were confirmed. Despite the high failure rate at each step in the process, natural cycles are more cost-effective than stimulated cycles which incur an incremental cost per live birth of $48,000. Natural cycles offer a low-cost alternative that may be more accessible to patients.

Adult↗
PubMed1995

Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To conduct a systematic overview of available data comparing FSH with hMG in IVF treatment cycles. DESIGN: A meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Search strategies included on-line searching of the National Library of Medicine MEDLINE data base from 1975 to 1993 and hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings. Common odds ratio (OR) and overall absolute treatment effect were calculated after demonstrating homogeneity of treatment effect across all trials. MAIN OUTCOME MEASURES: Clinical pregnancy rates per cycle start, per cycle reaching oocyte retrieval, and per cycle reaching ET. RESULTS: Eight trials met the inclusion criteria. The overall OR in favor of FSH for cycle start, oocyte retrieval, and ET were 1.71, 1.69 and 1.70, respectively, and represented an overall absolute treatment effect of 8.5%, 8.0% and 8.3%, respectively. CONCLUSIONS: This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.

Abortion, Spontaneous↗
PubMed1994

The effectiveness of allogeneic leukocyte immunization in unexplained primary recurrent spontaneous abortion. Recurrent Miscarriage Immunotherapy Trialists Group.

PROBLEM: Unexplained primary recurrent spontaneous abortion (RSA) can be viewed as a partner-specific problem for which immunization with allogeneic leukocytes is being offered as therapy. Published data from randomized controlled trials have produced conflicting results regarding treatment effectiveness. The aim of this study was to perform a subgroup analysis of the data from a recent worldwide collaborative meta-analysis using the raw data for patients with primary RSA entered into randomized controlled trials of immunotherapy. METHODS: Data from randomized controlled trials in eight centers were included in this analysis. Individual patients were included only if they had had three or more spontaneous abortions, no previous pregnancy beyond 20 weeks' gestation, no identifiable cause for the abortions, and no evidence of antipaternal antibodies. Meta-analysis by centre and logistic regression analysis were performed to determine the overall effect of treatment in achieving live birth and to identify variables that affect the prognosis for a successful outcome. RESULTS: In the meta-analysis by center, immunotherapy significantly improved the live birth rate (common odds ratio = 1.94, 95% confidence interval (CI) = 1.20 to 3.12). In the analysis by patient, the likelihood of a successful outcome was also significantly better with treatment (relative risk = 1.46, 95% CI 1.19 to 1.69). The absolute treatment effect was 16.3% producing a number needed to treat of 6. The number of previous abortions had a significant negative correlation with live birth rate, such that for each additional pregnancy loss beyond three, the likelihood of live birth was reduced by 23%. CONCLUSION: Allogeneic leukocyte immunization is an effective treatment for unexplained primary RSA when pretreatment antipaternal antibodies are absent. Better diagnostic tests are required to identify patients who may derive maximal benefit from this therapeutic approach.

Abortion, Habitual↗
PubMed1993

Cycle characteristics and outcome in relation to ovarian response during in vitro fertilization.

PURPOSE: This retrospective analysis of 148 non-male factor couples sought to determine whether oocyte or embryonic quality was compromised by the magnitude of the ovarian response following clomiphene citrate/human menopausal gonadotropin stimulation for in vitro fertilization. METHODS: Increased oocyte numbers were associated with decreased fertilization rates (r = -0.36, P < 0.001) and estradiol/follicle ratios (r = -0.443, P < 0.001), although the quality of the resulting embryos was not affected. Despite reduced fertilization, higher oocyte numbers yielded additional healthy embryos (r = 0.70, P < 0.001) for immediate replacement or cryopreservation. Implantation rates did not differ among groups and no predictive variables were identified. RESULTS: These results suggest that endometrial receptivity and implantation were not adversely affected by increasing estradiol levels. The decline in oocyte quality associated with the retrieval of larger numbers of oocytes appeared to be offset by the availability of additional embryos for immediate replacement and cryopreservation.

Adult↗
PubMed1990

Influence of blood clots in the cumulus complex on oocyte fertilization and cleavage.

Since multiple ovarian punctures are performed during oocyte retrieval, the likelihood of blood contaminating the follicular fluid is high. The purpose of this study was to determine whether the presence of blood clots, which are frequently seen in the cumulus of oocytes retrieved under ultrasound guidance, has any effect on fertilization and subsequent embryo cleavage and to identify oocyte characteristics which may predict these events. Oocytes were morphologically graded and the presence of blood clots in the cumulus was recorded. Cases in which the male partner had a total motile sperm count less than 20 x 10(6) on the day of insemination were excluded from the logistic regression analysis. The presence of blood clots in the cumulus was a negative predictor of cleavage [odds ratio (OR) = 0.54]. The results indicate that an oocyte with optimal quality is one which is spherical (OR = 5.45), has an expanded corona (OR = 3.80) and has no blood clots in the cumulus complex.

Cleavage Stage, Ovum↗
PubMed1989

Semen predictors of in vitro fertilization and embryo cleavage.

In vitro fertilization treatment for male infertility is not very successful because fertilization is known to be affected by semen quality. Information on fertilizing ability may provide prognostic information for couples contemplating such treatment. The purpose of this study was to identify semen variables that would predict fertilization and embryo cleavage. Sperm was prepared by the swim-up method before insemination of oocytes obtained by laparoscopy after ovulation induction. Routine semen analysis and the hypoosmotic swelling test for assessment of sperm membrane integrity were performed on aliquots of prepared sperm. Logistic regression and receiver-operator characteristic curve analyses were performed to determine the overall best-fitting model and discriminatory level of variables that would predict cleavage. The results indicate that after the swim-up procedure, at least 10 million sperm/ml, capable of undergoing swelling in hypoosmotic medium, are necessary to increase the likelihood of in vitro fertilization and cleavage.

Cleavage Stage, Ovum↗