Guy E. Ringler

Determinants of the outcome of intrauterine insemination: Analysis of outcomes of 9963 consecutive cycles

OBJECTIVE Our aim was to determine which factors influence the effectiveness of intrauterine insemination. STUDY DESIGN This article is a retrospective statistical analysis of outcomes of 9963 consecutive intrauterine insemination cycles. RESULTS Patient age was the main determinant of pregnancy outcome (analysis of variance F ratio = 29, P <.0001), followed by the number of follicles at the time of intrauterine insemination (analysis of variance F ratio = 9, P <.0001) and sperm motility in the inseminate (analysis of variance F ratio = 4, P =.002). A total of 18.9% of all patients <26 years old conceived, compared with 13.9% of those 26-30 years old, 12.4% of those 31-35 years old, 11.1% of those 36-40 years old, 4.7% of those 41-45 years old, and 0.5% of patients >45 years old (P <.001). When analyzed by single years, ongoing pregnancy rates after intrauterine insemination remained high through age 32 years. Across all ages and causes of infertility, 7.6% of patients with 1 follicle at the time of intrauterine insemination conceived, compared with 10. 1% with 2, 14.0% with 4, and 16.9% with 6 follicles (P <.01). When ovulation occurred before intrauterine insemination (ie, no visible follicular structures), 4.6% of patients conceived. The likelihood of pregnancy was maximized when motile sperm numbers were >/=4 million and sperm motility was >/=60%. Differences in pregnancy outcomes between sperm processing options were related to differences in sperm motility after processing; use of methods incorporating motility enhancement with pentoxifylline and motile sperm concentration through silica gradients yielded the highest overall pregnancy rates. CONCLUSION When the results of ongoing retrospective analysis of intrauterine insemination outcomes are applied, overall intrauterine insemination pregnancy rates have increased from 5.8% per cycle in 1991 to 13.4% per cycle in 1996, during which time the average age of patients undergoing intrauterine insemination has increased from 36.1 (+/-0.2) to 39.2 (+/-0.1) years.

Effects of 8-bromo-cAMP on expression of endocrine functions by cultured human trophoblast cells. Regulation of specific mRNAs

There is little information on the molecular events underlying the effects of cAMP on human chorionic gonadotropin (hCG) and particularly steroidal hormone production in normal trophoblasts. We examined the effects of 8-bromo-cAMP on mRNAs encoding two components of the cholesterol side-chain cleavage system, cytochrome P-450scc and adrenodoxin, and the alpha- and beta-subunits of hCG in cultured cytotrophoblasts. cAMP caused an increase in all of these mRNAs within 24 h, whereas actin mRNA declined. alpha-hCG mRNA increased first, followed by adrenodoxin, beta-hCG and cytochrome P-450scc mRNAs. The effects of 8-bromo-cAMP on alpha- and beta-hCG, adrenodoxin, and cytochrome P-450scc mRNAs, in cytotrophoblasts and JEG-3 choriocarcinoma cells, required the catalytic unit of protein kinases since H-7, a kinase inhibitor, blocked the increase in the mRNAs and prevented the stimulation of hCG and progesterone secretion. 8-Bromo-cAMP promoted a rapid increase in alpha-hCG mRNA in cytotrophoblasts in the presence of cycloheximide, an inhibitor of protein synthesis. In cytotrophoblasts, cycloheximide reduced basal and 8-bromo-cAMP-stimulated adrenodoxin mRNA abundance. In contrast, basal and cAMP-stimulated adrenodoxin mRNA was augmented by cycloheximide in JEG-3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Accumulation of colony-stimulating factor 1 in amniotic fluid during human pregnancy.

Colony-stimulating factor 1 is a hematopoietic growth factor that increases 1000-fold in the uteri of pregnant mice, and its receptor is abundantly expressed in the human placenta. The concentration of colony-stimulating factor 1 in amniotic fluid at 33 to 40 weeks (9.0 +/- 1.1 ng/ml) was twofold higher than that at 16 to 18 weeks gestation (4.1 +/- 0.5 ng/ml), whereas maternal serum colony-stimulating factor 1 levels did not rise significantly. Colony-stimulating factor 1 was detected in endometrial extracts from pregnant women and levels were higher than those in extracts from nonpregnant women.

Presented at the Fifty-ninth Annual Meeting of the Pacific Coast Obstetrical and Gynecological Society, Ojai, California, October 1118, 1992.

Objectives: We determined the effect of embryo transfer, zygote intrafallopian transfer, and frozen embryo transfer on clinical outcomes after surrogate gestational transfers. Study Design: Prospective randomization was carried out. Results: Forty-five infertile couples were matched with a gestational surrogate carrier and underwent 81 cycles of embryo transfer with various assisted reproductive technologic procedures. Nineteen cycles produced a clinical pregnancy, with delivery in 15 of 81 cycles (18.5% live-birth rate). Fifteen of the 45 couples (33%) had a child from the surrogate gestational carrier program. Conclusion: No significant differences in clinical outcome were observed on the basis of the type of procedure performed or the age of the patient.

Casting for determinants of blastocyst yield and of rates of implantation and of pregnancy after blastocyst transfers

OBJECTIVE To identify determinants of blastocyst yield, implantation rate, and pregnancy outcome. DESIGN Retrospective analysis of outcomes of 1,653 cycles of IVF. SETTING Private infertility clinic. PATIENT(S) Couples presenting to an infertility clinic for IVF. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Blastocyst yield, implantation rate, and pregnancy. RESULT(S) Of a broad array of potential determinants, only the total numbers of oocytes retrieved and properties of day 3 embryos were consistently predictive of blastocyst formation. Relative to numbers of oocytes fertilized by intracytoplasmic sperm injection (ICSI), yields of quality blastocysts were highest in cycles in which <10 oocytes were retrieved. Blastocyst yield was closely linearly correlated with average numbers of blastomeres in embryos on day 3. As oocyte yields rose, average grades and the implantation potential of the blastocysts selected for transfer increased by approximately 0.015 and 0.15%, respectively, for each additional oocyte. Independently, the implantation potential of blastocysts decreased 1.1% for each advancing year in age of the oocyte provider, and, for autologous transfers, uterine receptivity declined an additional 0.6% per year. Higher yields of blastocysts from cycles with high oocyte numbers afforded better selection of blastocysts for transfer, supporting higher overall implantation and pregnancy rates. CONCLUSION(S) While the proportion of fertilized oocytes that progressed to quality blastocysts diminished as numbers of recovered oocytes rose, rates of implantation and pregnancy after transfer of the selected best blastocysts increased. The age of the oocyte provider and oocyte yields independently impacted blastocyst implantation potential and uterine receptivity after controlled ovarian hyperstimulation, ICSI, and blastocyst transfer.