Minidose GnRH-2 for "poor responders." Cloning in place of data torturing?
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Cloning, Molecular↗
Biomedical subjects
I S Tummon
Publications and source records attributed to I S Tummon.
Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis.
OBJECTIVE: To evaluate the efficacy of superovulation and IUI versus no treatment for infertility associated with minimal or mild endometriosis. DESIGN: Randomized trial. SETTING(S): London Health Sciences Centre, University Campus, The University of Western Ontario, London, Ontario; and Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. PATIENT(S): Three hundred eleven cycles in 103 couples in whom minimal or mild endometriosis was the sole identified subfertility factor. INTERVENTION(S): Superovulation with FSH and IUI. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Live birth followed 14 of 127 (11%) superovulation and IUI cycles and 4 of 184 (2%) no-treatment cycles. The odds ratio was 5.6 (95% confidence interval 1.8 to 17.4) in favor of superovulation and IUI. CONCLUSION(S): Treatment with superovulation and IUI was associated with superior outcome both by crude live-birth rates and proportional hazard analysis.
Adult↗
Future in vitro fertilization pregnancy potential of women with variably elevated day 3 follicle-stimulating hormone levels.
OBJECTIVE: To determine the IVF-ET pregnancy potential of women with variably elevated day 3 FSH. DESIGN: Cohort evaluation of 1,868 consecutive IVF-ET cycles January 1991 to December 1994. SETTING: University hospital infertility unit. PATIENTS: Four cohorts of couples were defined based on day 3 FSH determinations with an arbitrary threshold of 20 mIU/mL, only > or = 20 mIU/mL, always < 20 mIU/mL, current < 20 mIU/mL but one previous > or = 20 mIU/mL, and current < 20 mIU/mL but two or more previous > or = 20 mIU/mL (conversion factor to SI unit, 1.00). INTERVENTION: In vitro fertilization-embryo transfer. MAIN OUTCOME MEASURE: Fetal heart activity on luteal day 40 transvaginal ultrasound. RESULTS: No pregnancies occurred in 53 cycles with day 3 FSH only > or = 20 mIU/mL. In 1,750 women whose day 3 FSH levels were always < 20 mIU/mL, the pregnancy rate (PR) per cycle was 16.5%. In 54 cycles in which day 3 FSH was > or = 20 one time only, but < 20 mIU/mL during the treatment cycle, the PR was 5.6%. In 11 cycles where two or more previous FSH determinations were > or = 20 mIU/mL but with a current day 3 FSH < 20 mIU/mL, no pregnancies occurred. CONCLUSION: Our data leads us to the conclusion that day 3 FSH determination precede every IVF cycle and that cycles with FSH > or = 20 mIU/mL be canceled. It also suggests that women with two previous elevations of day 3 FSH be discouraged from future IVF cycles. The 5.6% pregnancy per cycle with one previously elevated FSH warrants extreme pessimism in discussion of further cycles.
Chorionic Gonadotropin↗
Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study.
OBJECTIVES: To study the effect of GnRH agonist (GnRH-a) treatment on memory and to assess the role of psychological factors. DESIGN: A randomized prospective study. SETTING: An academic teaching hospital. PARTICIPANTS: Women with endometriosis and infertility or endometriosis alone. MAIN OUTCOME MEASURES: Memory Observation Questionnaire, Profile of Mood States, Health Concerns scale, a weekly diary of adverse effects. RESULTS: Perceived memory functioning decreased during GnRH-a administration and by the final week of treatment 44% of women reported moderate to marked impairment in comparison to community norms. Prospective memory was most affected and withdrawal of GnRH-a treatment resulted in a return to normal memory functioning. Impairment was not related to excessive health concerns or mood changes and was uncorrelated with other adverse effects. CONCLUSIONS: Memory disruption may be a more common side effect of GnRH-a treatment than currently is recognized. Problems were temporary and more likely a result of rapid estrogen depletion than a consequence of mood, somatic distress, or personality factors.
Adult↗
Confounding variables affecting in vitro fertilization success: a decade of experience.
PURPOSE: To evaluate etiology of infertility, female age, ovarian response and stimulation protocol in affecting in vitro fertilization (IVF) success. METHODS: Retrospective analysis was used. Computer records of all 5209 cycles initiated in 2391 couples from February 1, 1984 to December 31, 1993 were analyzed. RESULTS: There were 644 intrauterine, 24 solely ectopic and 7 heterotopic pregnancies. Pregnancy rates increased with number of embryos transferred with a significant increase still found between transfer of three or four embryos. Multiple gestations also increased in association with an increasing number of embryos transferred. Pregnancy rates per cycle did not decline with repeated cycles. Reduced pregnancy rates were associated with a primary diagnosis of male infertility. Covariates associated with a better pregnancy rate were younger age of the female partner or higher peak preovulatory serum estradiol. Routine administration of GnRH-agonist was associated with a reduced cycle cancellation rate, an increase in oocytes retrieved and an improved pregnancy rate. CONCLUSIONS: Couples with male infertility and increased female age should be counselled regarding the reduced prognosis for success.
Age Factors↗
Nafarelin acetate for pituitary down-regulation in in vitro fertilization. Comparison of two dosages.
The objective of this study was to evaluate the efficacy of intranasal (IN) nafarelin acetate (NA), 400 micrograms/d and 600 micrograms/d, in a luteal-phase-start, long protocol in women undergoing their first in vitro fertilization (IVF) cycle. A sequential comparison of 200 consecutive first IVF cycles, the study was performed in the Department of Gynaecology and Reproductive Medicine, University Hospital, London, Ontario, Canada. The participants were 200 first-cycle IVF patients who were regularly cycling--100 NA 400 micrograms IN followed by 100 NA 600 micrograms IN. Eighty-two percent of the NA 400 micrograms group were adequately suppressed after 11 days of treatment (serum estradiol < or = 150 pmol/L) as compared to 87% with NA 600 micrograms/d. These results compare favorably with those in a historical control group of 179 subjects receiving daily leuprolide acetate (LA), 0.5 mg subcutaneously, in their first cycle of IVF. The amount of human menopausal gonadotropin required for optimal follicular development was similar for the two NA groups. Clinical pregnancy rates were 13% per cycle and 21.7% per embryo transfer (ET) for NA 400 micrograms od and 19% per cycle and 30.1%/ET for NA 600 micrograms od (normal standard dose). No spontaneous luteinizing hormone (LH) surges occurred in any subject. Patient counseling and instruction time for NA use, which required nursing time, averaged five minutes per patient and an additional five minutes of video-viewing time. NA, 400 micrograms and 600 micrograms per day, appear to be acceptable alternate choices for pituitary down-regulation in a luteal-phase-start, long down-regulation protocol for IVF.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Intranasal↗
The pregnancy rates of cohorts of idiopathic infertility couples gives insights into the underlying mechanism of infertility.
OBJECTIVES: To determine causes of "idiopathic" infertility, the IVF-ET experience of three cohorts of couples with this diagnosis was examined. DESIGN: Three cohorts of idiopathic infertility couples undergoing IVF-ET: a "failed IUI" group, three previous controlled ovarian hyperstimulation (COH)-IUI cycles with no pregnancies; a "conversion" group, patients converted during a COH-IUI cycle to IVF-ET because of excess follicle numbers; and a "direct IVF" group, patients proceeding directly to IVF-ET were compared. SETTING: A tertiary referral reproductive medicine unit. PARTICIPANTS: Forty-one idiopathic infertility couples. INTERVENTION: In vitro fertilization-ET. MAIN OUTCOME MEASURES: Number of oocytes retrieved, percent oocytes fertilized, number embryos per ET, implantation rate, percent pregnancy per cycle. RESULTS: The cohorts had similar fertilization rates and mean (+/- SD) number of pre-embryos transferred. The conversion group demonstrated a higher pregnancy rate (PR) per cycle and a higher E2 concentration than the other groups. The PR of 35.0% in the direct IVF group appeared higher than the 16.7% rate observed in the failed IUI group. CONCLUSIONS: Our observation of a lower PR in couples in the failed IUI group (16.7%) than in couples in the direct IVF group (35.0%) suggests pre-embryo developmental problems or implantation problems as likely important etiologies for a large proportion of idiopathic infertility couples. However, as the conversion group demonstrated both a significantly higher E2 concentration ([E2]) and per cycle PR than the other cohorts with similar fertilization and pre-embryo transfer rates. Subjects converted in a COH-IUI cycle to IVF-ET are thus either more likely to produce pre-embryos more genetically capable of continued development to implantation stage (i.e., better oocytes recruited and fertilized) or due to the higher [E2] to have endometrium more receptive to implantation. Neither undiagnosed tubal factors nor fertilization problems appear to be major etiologic contributors.
Adult↗
Randomized trial of partial zona dissection for male infertility.
OBJECTIVES: To compare IVF rates using partial zona dissection versus zona intact insemination in couples with male infertility. To analyze pregnancy rates relative to sperm characteristics, fertilization rates, and treatment. DESIGN: Randomized prospective comparison of fertilization in sibling oocytes. Transfer of the three best quality embryos from one or both treatments. SETTING: Department of Gynaecology and Reproductive Medicine, University Hospital, London, Ontario, Canada. PARTICIPANTS: Thirty-two couples undergoing IVF with a principal diagnosis of male infertility. INTERVENTION: Treatment with partial zona dissection. MAIN OUTCOME MEASURES: Fertilization and pregnancy. RESULTS: Fertilization rates were 26% and 9% after partial zona dissection and IVF, respectively. Polyspermy was < 1% in each treatment. There were five singleton pregnancies in 29 completed cycles, three in cycles with fertilization only by partial zona dissection and two in cycles with both partial zona dissection and IVF fertilization. There were no pregnancies after fertilization by IVF only. Stepwise logistic regression analysis indicated that pregnancy was related to partial zona dissection, initial sperm concentration, and total acrosin activity. CONCLUSION: Partial zona dissection was associated with minimal polyspermic fertilization and higher normal fertilization rates than sibling oocytes treated by modified IVF. Pregnancy occurred only after transfer of embryos from partial zona dissection or combined partial zona dissection and IVF.
Adult↗
Transferring more embryos increases risk of heterotopic pregnancy.
OBJECTIVES: To analyze symptoms and signs that may distinguish heterotopic pregnancy from solely ectopic pregnancy (EP) after IVF. To determine if the number of embryos transferred is a risk factor for heterotopic compared with solely EP. DESIGN: Retrospective cohort of 587 IVF pregnancies, 328 with distorted tubal anatomy. SETTING: University Hospital, London, a referral center for Ontario provincial government-supported assisted reproductive technologies. PARTICIPANTS: Couples undergoing IVF. INTERVENTION: None. MAIN OUTCOME MEASURES: Heterotopic pregnancy, solely EP, intrauterine pregnancy, and distorted pelvic anatomy. RESULTS: Of 587 pregnancies, 7 were heterotopic pregnancies and 24 were solely EP, all in the subset of 328 women with distorted tubal anatomy. Symptoms, signs and time of diagnosis were not different between heterotopic and solely ectopic gestations. Compared with solely EP, heterotopic pregnancies were associated with transfer of more embryos. With four or more embryos transferred, the odds ratio for development of heterotopic versus solely ectopic gestation was 10.0. CONCLUSION: Heterotopic pregnancy occurred in 2% of gestations after IVF, all in women with distorted tubal anatomy. Transfer of four or more embryos was a risk factor for heterotopic pregnancy.
Adult↗
Direct antisperm antibodies using enzyme immunoassay or immunobeads. A prospective cohort comparison.
An enzyme immunoassay for detecting antisperm antibodies directly on sperm was compared to immunobeads in a prospective cohort design. In a series of 112 divided ejaculates evaluated for assisted reproductive technologies, there was moderate overall agreement (kappa = .64) between the methods. All ejaculates positive by immunobeads were also positive by enzyme immunoassay. The enzyme immunoassay could be performed even on oligospermic specimens. When both assays could be employed, the enzyme immunoassay was positive more often (P = .001). Positive specimens by enzyme immunoassay often bound IgA-class antibodies alone, without IgG. Enzyme immunoassay results may represent false-positive results or a new, lower threshold for antibody detection.
Antibodies↗
An aggressive philosophy in controlled ovarian stimulation cycles increases pregnancy rates.
To assess the effect of timing of human chorionic gonadotrophin (HCG) administration in ovarian stimulation cycles, the serum oestradiol concentration and follicle profile were compared with the clinical pregnancy rate in 582 ovarian stimulation-intra-uterine insemination (OS-IUI) cycles and 3917 in-vitro fertilization-embryo transfer (IVF-ET) cycles. The pregnancy rates increased exponentially with increasing oestradiol in both OS-IUI and IVF-ET cycles (R2 = 0.720, P < 0.001) but then decreased in OS-IUI cycles when the oestradiol concentration exceeded 5000 pmol/l (R2 = 0.936, P < 0.004) at HCG administration. In OS-IUI cycles the percentages of cycles with three or more mature follicles (> or = 18 mm diameter) increased up to an oestradiol concentration of 5000 pmol/l then declined, mirroring the pregnancy rate (R2 = 0.900, P = 0.01). The exponential increase in pregnancy rate with increasing oestradiol concentration in IVF-ET cycles suggests that high oestradiol concentration does not have a deleterious effect on endometrial receptivity. The decrease in pregnancy rate in OS-IUI cycles when oestradiol concentration exceeded 5000 pmol/l reflected fewer mature follicles, resulting from premature administration of HCG to avoid severe ovarian hyperstimulation syndrome (OHSS). We recommend that HCG administration be delayed until multiple follicles have reached maturity, and reducing the risk of severe OHSS by converting high risk OS-IUI cycles to IVF-ET, or if funds or facilities are unavailable, transvaginally draining all but four or five mature follicles.
Chorionic Gonadotropin↗
Risk of repeated spontaneous luteinizing hormone surges in ovarian stimulation for in vitro fertilization.
Although spontaneous luteinizing hormone (LH) surges are preventable with gonadotropin releasing hormone agonist (GnRH-a) inclusion in ovarian stimulation protocols, GnRH-a-containing protocols are more expensive and associated with an increased risk of ovarian hyper-stimulation syndrome. The present study assessed whether spontaneous LH surges occur in predictable patterns, allowing GnRH-a to be utilized selectively. We assessed 1,103 patients receiving clomiphene citrate/human menopausal gonadotropin (CC/hMG) without GnRH-a for their first in vitro fertilization (IVF) cycle and observed spontaneous LH surges in 30.4%. When patients who demonstrated a spontaneous LH surge received a second CC/hMG stimulation protocol, 45.9% surged again. Of those patients who did not demonstrate a spontaneous LH surge in their initial CC/hMG cycle, only 23.0%, significantly less (P < .001), surged in their second cycle. Of those patients who did not surge in their first two cycles, only 15.7% had an LH surge in their third cycle (P < .001). Thus, if all patients received CC/hMG without GnRH-a as their first IVF stimulation protocol, GnRH-a could be reserved for patients who have demonstrated a spontaneous LH surge. By tailoring the treatment plan, the pregnancy rate would be optimized while decreasing cycle cancellations due to spontaneous LH surges in those patients susceptible to LH surges and limiting costs and inconvenience for patients unlikely to surge spontaneously.
Female↗
Decreasing quality of semen.
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Fertility↗
Randomized, prospective comparison of luteal leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins in 408 first cycles of in vitro fertilization.
OBJECTIVE: To compare luteal phase leuprolide acetate (LA) initiated pituitary down regulation followed by human menopausal gonadotropins (hMG) versus clomiphene citrate (CC) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization (IVF). DESIGN: Randomized, prospective comparison in first cycles of IVF. SETTING: University Hospital, a tertiary referral center offering assisted reproductive technologies. PARTICIPANTS: Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial. RESULTS: Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation, improved folliculogenesis, and a higher probability of embryo transfer (ET) compared with CC/hMG alone. Implantation rates were not different. CONCLUSION: A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate.
Clomiphene↗
Abbreviated endometriosis-associated infertility correlates with in vitro fertilization success.
The utility of in vitro fertilization (IVF) for refractory infertility associated with endometriosis was studied by reviewing the 6-year experience with IVF and pregnancy follow-up at University Hospital, London, Ontario. Two hundred forty cycles were begun in 124 couples in whom endometriosis was the sole identified cause of infertility. In a program employing predominantly ultrasound-guided transvaginal oocyte retrieval, live birth rates were not reduced with advanced degrees of endometriosis. Live births were positively correlated with a shorter infertility duration.
Adult↗
Total acrosin activity correlates with fertility potential after fertilization in vitro.
OBJECTIVE: To evaluate the possible relationship between total acrosin activity in spermatozoa and fertility potential after fertilization in vitro. DESIGN: Total acrosin activity of spermatozoa was measured in 101 in vitro fertilization (IVF) cases by an observer unaware of fertilization and cleavage results. SETTING: University Hospital is a tertiary referral center offering a government supported In Vitro Fertilization Programme. PARTICIPANTS: Participants were couples undergoing IVF. INTERVENTIONS: A miniature assay measured total acrosin activity in the semen sample used for IVF. OUTCOME MEASURES: The proportion of mature oocytes fertilized, the proportion of mature oocytes transferred, and fertilization of at least one mature oocyte were considered outcomes with fertility potential. RESULTS: Total acrosin activity correlated with both the proportion of mature oocytes fertilized and the proportion of mature oocytes that were transferred as cleaving embryos. Total acrosin activity was higher in cycles when one or more mature oocyte fertilized compared with cycles with failed fertilization of all mature oocytes. CONCLUSIONS: The likelihood ratio for subnormal results indicates that measurement of total acrosin activity is a fair test of the fertilizing capacity of sperm.
Acrosin↗