[Show abstract][Hide abstract] ABSTRACT: The objective was to determine if lower uterine artery vascular impedance is associated with a greater likelihood of multiple gestation. Color Doppler parameters of pulsatility index, resistance index, endometrial thickness and echo patterns were measured in oocyte/retrieval cycles on days of human chorionic gonadotropin injection, oocyte retrieval, and mid-luteal phase in cycles where at least 3 embryos were transferred. Comparisons of these parameters were made in patients with single versus multiple gestations. There was no association between uterine environment as measured by vascular impedance and endometrial thickness and number of embryos implanted. Thus, a more ideal uterine environment, at least as determined by these sonographic parameters, does not seem to facilitate multiple embryo implantations.
Gynecologic and Obstetric Investigation 02/2000; 50(4):242-6. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of intrauterine insemination (IUI) for male or cervical factor by age of female partner was determined in a retrospective analysis. Patients who underwent IUI therapy for cervical and/or male factor (n = 281) were classified by age at first IUI cycle: <40 years (n = 232), > or =40 years (n = 49). The indication for IUI was cervical factor if a postcoital test failed to show sperm with good forward progression at time of mature follicle; male factor was diagnosed if the semen analysis demonstrated either low count, low motility, antisperm antibodies, or subnormal hypoosmotic swelling test. Intrauterine insemination was performed in either natural cycles or following ovarian stimulation for the treatment of anovulation or follicular maturation defects. Cumulative probability of ongoing pregnancy (viable at end of first trimester) following 3 cycles of IUI was evaluated. Cumulative probability of ongoing pregnancy following 3 cycles of IUI was 28.2% for the younger group and 0.0% for the older group. The age groups did not differ in terms of infertility history, use of ovarian stimulation, or baseline semen parameters. Thus, the treatment of male and/or cervical factor by IUI is ineffective for women > or =40 years.
Archives of Andrology 01/2000; 44(3):193-6. · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine the effects of misoprostol on plasma lipoprotein (a) concentrations of ovariectomized rats.
Controlled prospective study.
Animal research laboratory.
Four-month-old female Sprague-Dawley rats.
Blood samples were obtained before and 60 days after ovariectomy, and the rats were divided into three groups. Group I (five rats) was treated with vehicle (water); groups II and III (nine and eight rats, respectively) were treated with oral misoprostol at 100 and 200 microg/kg/d, respectively, for 60 days, after which blood was drawn again.
Serum lipoprotein (a) levels.
The median lipoprotein (a) level before ovariectomy was 10.8 mg/dL (range, 10.6-46.5 mg/dL). Sixty days after ovariectomy, the level increased significantly to 15.9 mg/dL (range, 10.6-36.9 mg/dL). After treatment, there was no change in lipoprotein (a) levels in the vehicle-treated group (range, 16.3-21.1 mg/dL); however, the lipoprotein (a) levels decreased significantly in the group treated with 100 microg/kg/d of misoprostol, from 15.4 mg/dL to 10.8 mg/dL, and in the group treated with 200 microg/kg/d of misoprostol, from 17.1 mg/dL to 10.6 mg/dL.
Misoprostol caused a significant decrease in lipoprotein (a) levels.
Fertility and Sterility 10/1999; 72(3):518-21. · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of the matched, controlled study was to determine whether low-dose aspirin therapy without heparin improves pregnancy rates following frozen embryo transfer.
Thirty-six women who did not achieve a pregnancy following fresh embryo transfer and who had frozen embryos available for another transfer were included. Eighteen women were treated with 81 mg aspirin from day 2 of the cycle through pregnancy testing. If the beta-human chorionic gonadotropin level was positive, aspirin was continued through the pregnancy. Eighteen women were not given aspirin. The mean outcome variables were pregnancy and implantation rates.
The clinical pregnancy rate in the aspirin group was 11.1%, compared with 33.3% for the controls, and implantation rates were 2.9 and 10.9%, respectively.
No positive effects of low-dose aspirin therapy on pregnancy rates following frozen embryo transfer were observed.
Journal of Assisted Reproduction and Genetics 12/1998; 15(10):579-82. · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are data suggesting that patients with elevated early follicular phase serum follicle-stimulating hormone (FSH) levels have a poor fertility outcome. This has been attributed to a high rate of aneuploidy in the oocytes. It is not clear whether the spindle defects leading to nondisjunction are related to the high FSH levels or the age of the oocyte. The study presented herein retrospectively evaluated 6-month pregnancy rates in women with elevated early follicular phase serum FSH levels according to age. Only cases without in vitro fertilization were used, since the elevated FSH levels were deemed likely to interfere with multiple egg recruitment needed for assisted reproductive technology. The 6-month clinical and ongoing pregnancy rates were significantly higher in the women <40 years of age (46.1 and 34.6%, respectively) than in those aged 40 or older (10.5 and 5.3%). These data suggest that women with elevated follicular-phase serum FSH levels have a better fertility prognosis when they are younger.
Gynecologic and Obstetric Investigation 02/1998; 45(4):217-20. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Infertility due to male factor has been associated with reduced implantation rates despite normal fertilization. The mechanism responsible for lower pregnancy rates is not known. One cause of failure to achieve pregnancy despite transfer of embryos is impairment of zona pellucida (ZP) thinning, which inhibits the embryo from hatching despite initial cell cleavage. This study was designed to evaluate whether there is an association between the ability of the ZP to thin, as measured by ZP thickness on day of transfer, and subnormal semen parameters. Significant differences in ZP thickness (p < 0.05, Kruskal-Wallis) were noted according to median concentration of sperm, total motile sperm, and motile density in that these values were the highest in the group of embryos with the thinnest zona pellucida and lowest in the group with the thickest zona pellucida. Thus, some factor may be missing from sperm from subnormal specimens that normally assists in zona thinning.
Archives of Andrology 01/1998; 41(3):145-50. · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 11 beta-Hydroxysteroid dehydrogenase (HSD) activity was measured in freshly frozen granulosa cells isolated from follicles of twenty-one infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET). A total of 213 follicles were analyzed for 11 beta-HSD activity. Both nicotinamide-adenine dinucleotide (NAD) and nicotinamide-adenine dinucleotide phosphate (NADP) dependent 11 beta-dehydrogenase activities were measured in granulosa cells. The activity in reductive direction (11-oxoreductase activity) was not measurable either with NADH or NADPH as cofactors. NAD- and NADP-dependent dehydrogenase activities are in comparable levels at 100 nmol/l and 1 mumol/l corticosteroid concentrations. For comparing enzyme activities of individual follicles, significant enzyme activity was considered to be a level of > 2 nmol/l/min/mg. 41.3% of the follicles demonstrated enzyme activity, 58.7% did not. The mean 11 beta-dehydrogenase (11 beta-DH) activity was calculated for each patient. Those patients with levels > 2 nmol/l/min/mg were considered enzyme positive; those with mean levels < 2 nmol/l/min/mg were considered negative. No significant association was noted between follicle size, oocyte maturity or fertilization rates and 11 beta-DH activity. This study noted the presence of 11 beta-DH activity in granulosa cells, however, no association with oocyte maturity and fertilization was found.
Early pregnancy: biology and medicine: the official journal of the Society for the Investigation of Early Pregnancy 09/1997; 3(3):183-9.
[Show abstract][Hide abstract] ABSTRACT: To compare the survival rate and pregnancy rate (PR) of embryos from intracytoplasmic sperm injection (ICSI) or conventional IVF, which were cryopreserved at the pronuclear stage in cycles where fresh transfer was deferred.
Comparative observational study.
University-associated IVF center.
Ninety-nine patients who deferred ET and had all their embryos cryopreserved at the pronuclear stage after 153 oocyte retrievals. Thirty-nine patients had their oocytes inseminated by ICSI and 60 patients had conventional IVF insemination.
All embryos were frozen-thawed at the two pronuclear stage and allowed to cleave for 2 days before transfer.
Survival rate (morphologically intact after thaw), cleavage rate (cleaved by time of transfer), and the clinical PR after frozen ET.
In the ICSI group, 205 embryos were thawed for use in 57 frozen ETs; in the IVF group, there were 527 embryos thawed for use in 149 frozen ETs. There was no significant difference in any of the outcome measures by insemination method: survival rates (ICSI, 93.2%; IVF, 94.8%); cleavage rates (ICSI, 95.2%; IVF, 94.7%), and clinical PR (ICSI, 14.0%; IVF, 17.4%).
Pronuclear embryos resulting from ICSI can be cryopreserved successfully, thawed, and the survival rate and PR are comparable to conventional IVF.
Fertility and Sterility 05/1997; 67(4):621-4. · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The high rate of multiple gestations following ovulation induction with and without assisted reproductive technologies (ART) has led to an increased interest in selective reduction. The aim of this study was to compare pregnancy outcome of 6 triplet and 2 quintuplet pregnancies following selective reduction to twins to a group of 30 natural twin pregnancies delivered during the same time period. Outcome variables compared included birth weights, gender, gestational age at delivery, route of delivery, and neonatal complications. Results failed to demonstrate an adverse effect of selective reduction on pregnancy outcome.
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to determine whether there were differences in gestational age markers in dizygotic twin pregnancies resulting from in vitro fertilization-embryo transfer (IVF-ET) when compared with dizygotic twin pregnancies spontaneously conceived following ovulation inducing therapy drugs without assisted reproductive techniques (ART). Thirty-one sets of twins conceived by IVF-ET and 33 sets of twins conceived without ART were monitored by serum beta human chorionic gonadotropin (B-hCG) levels and transvaginal sonographic measurements of sac size (SS) and crown-rump length (CRL). Comparison between groups found that SS was significantly smaller in the IVF-ET group as compared to the non-ART group 21-35 days post-ovulation (p < .05). The CRL was similar in both groups as well as the doubling times of B-hCG. These data indicate that in dizygotic twin pregnancies initial development of SS may be slower following IVF-ET than in spontaneously conceived twins.
[Show abstract][Hide abstract] ABSTRACT: Our purpose was to determine if pronuclear-stage embryos (2PN) could be thawed, then frozen again with subsequent survival and cleavage after thawing.
A simplified cryopreservation protocol was used in which a slow cooling program is started at the seeding temperature of -6 degrees C in an alcohol-bath controlled-rate freezer. 1,2-Propanediol (1.5 M) was added to embryos before cooling. A fast thawing technique at room temperature was used. The cryoprotectant was removed in one step using a 1 M sucrose solution.
Three months after refreezing, the three 2PN embryos were thawed and all three cleaved after 24 hr in culture. Following embryo transfer a pregnancy was achieved and a healthy full-term baby girl was born.
This is the third case reported of successful pregnancies after transfer of human embryos that were frozen twice before transfer and the first case where the second freeze occurred at the pronuclear stage. This is also the first successful refreezing of human embryos using a simplified freezing and thawing technique with one-step addition and removal of cryoprotectant.
Journal of Assisted Reproduction and Genetics 11/1996; 13(9):713-5. · 1.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to investigate the association of rapid and linear progressive motility in seminal and Percoll-separated sperm with the outcome of intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles. Motility was graded using the qualitative system proposed by the World Health Organization: grade A, rapid and linear, grade B, slow or nonlinear; grade C, non-progressive; or grade D, nonmotile. Absence of rapid and linear motility was defined as grade A sperm absent. Nine-hundred-fifty IVF and 1,448 IUI cycles were analyzed. In 7.9% (75) of the IVF cycles, grade A sperm were absent in the semen. Although the mean fertilization rate was lower in the absence of grade A sperm in the semen (44.5% vs. 63.4%, P < 0.05), the pregnancy rates were similar irrespective of their presence or absence (18.7% vs. 17.8%). In the cycles in which grade A sperm were absent following Percoll separation (26/950; 2.7%), the fertilization rate (29% vs. 62.8%) and the clinical pregnancy rate/retrieval were significantly lower (3.8% vs. 18.3%, P < 0.05). In 26.4% (382) of the IUI cycles, grade A sperm were absent in the semen and conception occurred in 30 (7.9%), compared to a pregnancy rate of 10.4% in the group with grade A sperm present in the semen. Following Percoll separation, only a 2.5% (2/80) pregnancy rate was observed in the group with no grade A sperm, compared to 10.2% in the group with grade A sperm (P < 0.05). The absence of rapid and linear motile sperm in the Percoll-separated sperm significantly reduced fertilization rates in vitro and pregnancy rates in both IUI and IVF cycles. The use of the total number of grade A sperm was also effective in predicting reduced fertilization in IVF and reduced pregnancy rates in IUI, but no better than the use of the mere presence/absence of grade A sperm. In a clinical situation, the simpler test is preferable. This type of evaluation is available to all centers as opposed to the more expensive computer-assisted semen analysis.
Journal of Andrology 09/1996; 17(5):550-7. · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the pregnancy rates (PRs) after transfer of cryopreserved embryos in patients who have damage to the functional integrity of the sperm membrane as measured by the hypo-osmotic swelling test to those without this defect.
Prospective clinical study.
University-associated IVF center.
Fifty-four patients enrolled in a matched prospective study to evaluate the effects of low HOS scores (<50%) on PRs after IVF-ET were followed to determine the PR after transfer of cryopreserved embryos.
Clinical PRs and implantation rates.
Fourteen patients with low hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved for clinical pregnancies for a PR per cycle of 19.0% and an implantation rate of 7.1%. Twelve patients with normal hypo-osmotic swelling test scores underwent 21 frozen ET cycles, achieved five preganancies for a clinical PR per cycle of 23.8% and an implantation rate of 9.3%.
Previous studies have demonstrated an adverse effect of low hypo-osmotic swelling test scores on PRs after IVF-ET despite normal fertilization. This adverse effect was not found in the transfer of cryopreserved embryos from males with hypo-osmotic swelling test scores. Further investigation is required to determine how cryopreservation improves the chances of implantation of these embryos.
Fertility and Sterility 07/1996; 65(6):1241-4. · 4.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the midcycle endocrine steroidal variables in 32 infertile women with follicular maturation defects treated with ultra-low-dose pure follicle-stimulating hormone (FSH) or human menopausal gonadotropins (hMG).
A crossover design was used in which women were randomly assigned to a treatment modality (pure FSH or hMG) in the first cycle, and the alternative treatment was used in the second cycle. In the ultra-low-dose regimen, the dosage began at 1 ampule/day (75 IU) and could increase to a maximum of 1.5 ampules/day. The mean midcycle serum levels determined at the time of peak follicular maturation and before the administration of human chorionic gonadotropin or gonadotropin-releasing hormone for release of oocytes were compared.
In the pure FSH cycle, the mean estradiol (E2), progesterone, and luteinizing hormone (LH) levels were 316 +/- 119 pg/mL, 0.6 +/- 0.4 ng/mL, and 23 +/- 22 IU/L, respectively; in the hMG cycle, the mean E2, progesterone, and LH levels were 361 +/- 193 pg/mL, 0.5 +/- 0.4 ng/mL, and 21 +/- 18 IU/L, respectively.
Ultra-low-dose gonadotropin therapy produces similar midcycle steroidal levels (E2, progesterone, and LH) whether or not LH is present in addition to FSH in the medications used for follicle stimulation.
Endocrine Practice 05/1996; 2(3):173-5. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship of early follicular phase serum LH levels and pregnancy rates in ovulatory women with regular menstrual cycles.
One hundred consecutive couples seeking help for infertility who had bilateral tubal patency, a minimum motile sperm-density-of 2.5 million/mL, and regular menstrual cycles were enrolled in the study. Baseline serum measurements of LH, FSH, and testosterone were obtained before treatment. Patients were treated with clomiphene citrate, human menopausal gonadotropin, or progesterone supplementation, as needed. Treatment continued for 6 months or until conception occurred. The 6-month pregnancy rates were correlated with baseline early follicular phase serum levels and age.
The 6-month viable pregnancy rates did not decrease with an increase in baseline LH serum levels; they were 50% if LH was 10 mIU/L or less, 15.3% if LH was 11-20 mIU/mL, and 71.4% if LH was more than 20 mIU/mL. The 16.7% pregnancy rate in women whose baseline FSH exceeded 25 mIU/mL was significantly lower than the 56.3% rate in women whose FSH was 25 mIU/mL or lower. The pregnancy rates also declined significantly with age. When we controlled for age, FSH did not have an independent effect on conception rates.
Early follicular phase serum levels of LH were not associated with pregnancy rates in infertile ovulatory women who were treated with progesterone in the luteal phase when needed. However, early follicular levels of FSH and age at treatment were found to be related to pregnancy rates.
Obstetrics and Gynecology 03/1996; 87(2):291-6. · 4.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to determine the mechanism for higher pregnancy rates in oocyte recipients by comparing the pregnancy rates following fresh and frozen embryo transfers in a shared oocyte programme. A prospective study was carried out of 135 matched pairs of donors and recipients who equally share the donors' pool of oocytes. Recipients were subclassified by ovarian function: 69 were in ovarian failure and 66 retained ovarian function. A total of 474 standard in-vitro fertilization cycles using the same ovarian stimulation protocol as the donors were also evaluated. The main outcome measures were the clinical pregnancy and implantation rates for donors and recipients following fresh and frozen embryo transfers. The clinical pregnancy rates per transfer for fresh embryo transfers were 17.5% for donors, 20.4% for recipients with ovarian function and 46.3% for recipients in ovarian failure (P < 0.05). The pregnancy rates for frozen embryo transfers were 15.3% for donors, 17.2% for recipients with ovarian function and 23.8% for recipients in ovarian failure (not significantly different). The implantation rates for fresh transfers were 7.5% for donors, 8.6% for recipients with ovarian function and 15.6% for recipients in ovarian failure (P < 0.05); for frozen cycles, the implantation rates were 5.1, 5.2 and 7.1% respectively (not significantly different). When classified by age and ovarian function, the clinical pregnancy rates per transfer for recipients with ovarian function were 14.0% for those aged > or = 40 and 22.2% for those aged < 40 years. For recipients in ovarian failure, the pregnancy rates were 33.3% for the older group of women and 39.4% for the younger group. A logistic regression analysis found that ovarian function was the only factor to have an independent effect on outcome. The demonstration of higher pregnancy and implantation rates in recipients versus donors following fresh embryo transfer, despite the use of a common pool of oocytes, strongly suggests that the well-known higher fecundity found in recipients is not predominantly related to the use of better quality oocytes. The demonstration of an implantation rate twice as high following fresh versus frozen embryo transfer in recipients with ovarian failure suggests that the frozen embryo is not as hardy as the fresh embryo. Thus, the fact that both the pregnancy and implantation rates in donors were the same with fresh versus frozen embryo transfer suggests that the ovarian stimulation regimen has a negative effect on outcome. However, the clear demonstration of higher pregnancy rates in recipients with ovarian failure compared with those with ovarian function suggests that, in addition, these higher rates may be linked to a superior uterine environment in patients with ovarian failure. Alternatively, the use of gonadotrophin-releasing hormone agonists may have a negative effect on implantation in patients with ovarian function.
Human Reproduction 11/1995; 10(11):3022-7. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether successive cycles of clomiphene citrate affect endometrial thickness.
Thirty-four women presenting for treatment of anovulation, oligoovulation, or follicle maturation defects were given the smallest dose of clomiphene citrate necessary to attain a mature follicle. If no pregnancy ensued, the same dose was continued if a follicle 18-24 mm in diameter and a serum estradiol (E2) level greater than 200 pg/mL were achieved. Ethinyl E2 was supplemented for poor cervical mucus only. Endometrial thickness and echo patterns were measured each cycle at peak follicular maturation.
There was no difference in mean endometrial thickness during the first six cycles of therapy, nor was there a trend for thickness to increase or decrease with successive cycles with or without the addition of ethinyl E2. There was no change in the distribution of echo patterns with successive cycles of clomiphene citrate. Post-treatment measures of thickness and echo pattern did not differ from baseline pre-treatment values. The homogeneous hyperechogenic pattern was the rarest. Mean serum E2 and progesterone levels at mid-cycle did not change with successive cycles.
One proposed mechanism for the dichotomy between ovulation and pregnancy rates after clomiphene citrate therapy is that the drug adversely affects the endometrium. If clomiphene citrate does affect implantation adversely, the mechanism does not seem to be related to thinning the endometrium or causing an echo pattern that indicates a poor prognosis. The data also suggest that estrogen supplementation does not influence endometrial thickness and would best be used exclusively for hostile cervical mucus.
Obstetrics and Gynecology 10/1995; 86(3):341-5. · 4.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The achievement of pregnancies in vivo is rare in couples where the male partner has defective sperm membranes as shown by hypo-osmotic swelling (HOS) test scores of < 50%. However, there have been mixed reports on the value of the HOS test in predicting outcome following invitro fertilization; some studies suggest reduced fertilization rates and others find little, if any, predictability of decreased fertilization. The assumption has been made that fertilization rates are proportional to pregnancy rates; however, this may not necessarily be true since defective spermatozoa could lead to a less viable pre-embryo and therefore a decreased viable pregnancy rate. We performed a comparative prospective study using matched controls to evaluate fertilization rates and to determine subsequent pregnancy rates. The mean HOS scores were 70.0 and 36.7% respectively, with mean motile sperm concentrations of 35.7 and 34.0 x 10(6)/ml in 27 matched pairs. There was no difference in the mean number of oocytes retrieved, fertilization rates or number of embryos transferred between the two groups by HOS score. The clinical and viable pregnancy rates and implantation rates were 25.9, 18.5 and 9.9% for normal versus 3.7, 3.7 and 1.1% for subnormal groups. These data suggest that low HOS scores may be associated with the formation of defective embryos, leading to low pregnancy rates but normal fertilization rates.
Human Reproduction 05/1995; 10(5):1197-200. · 4.59 Impact Factor