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.

The use of surrogate gestational carriers for assisted reproductive technologies.

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.

Evaluation of midforceps delivery as an alternative.

The fetal intrapartum condition as well as maternal and immediate neonatal outcome of 274 consecutive midforceps rotations (head in transverse or posterior position and below + 1 station but without reaching the perineum) were compared with 106 cesarean sections done for arrest of progress for more than two hours and cervical dilatation of at lest 7 cm. It was found that there were more nulliparous among cesarean section patients, that their fetuses weighed near 400 gm more on the average, and that their time in labor was 200 minutes longer. On the other hand, the midforceps group had a higher incidence of spontaneous labor, conduction anesthesia, and intraprtum fetal distress (37%). There were no differences in fetal outcome, other than admission to NIC and/or NIM among C-section infants. This latter group had a higher postdelivery maternal complication rate (hemorrhage and infection), as well as longer than expected hospital stay. These findings are discussed. It appears that midforceps rotation, properly indicated and executed, offers a safe alternative to C-section for delivery of the infant.

Regulation of the gene for estrogenic 17-ketosteroid reductase lying on chromosome 17cen----q25.

17-Ketosteroid reductase (17KSR), also known as 17 beta-hydroxysteroid dehydrogenase, catalyzes the reversible interconversion of estradiol to estrone and of androstenedione to testosterone. Using a recently cloned human placental 17KSR cDNA, we show that the 1.4-kilobase mRNA for this enzyme is detected only in tissues producing estrogens, and a 2.4-kilobase mRNA is detected in some estrogenic tissues and some androgenic tissues. This tissue distribution suggests that the interconversion of androstenedione and testosterone may be mediated by a different enzyme. Southern blotting studies show that the mRNA for this estrogenic 17KSR is encoded by two very similar genes localized to chromosome 17cen----q25 by analysis of DNA from mouse/human somatic hybrid cell lines. 8-Br-cAMP increases the abundance of estrogenic 17KSR mRNA as well as mRNAs for other steroidogenic enzymes in JEG-3 choriocarcinoma cells. By contrast, cAMP decreases estrogenic 17KSR mRNA in primary cultures of human cytotrophoblasts and human granulosa cells, a pattern of tropic regulation that differs from other steroidogenic enzyme mRNAs.

A case report of three synchronous stage I malignant neoplasms.

A patient with three synchronous, Stage I neoplasms of the ovary, kidney, and lung, who underwent resection of all lesions at the same operative procedure, is presented. The incidence of multiple primary malignancies and the prognosis for Stage I cancers of the ovary, kidney, and lung are reviewed.

Regulation of human trophoblast function by glucocorticoids: dexamethasone promotes increased secretion of chorionic gonadotropin.

Steroid hormones are thought to play a role in controlling placental endocrine function. Since maternal free cortisol levels increase during gestation, and glucocorticoid receptors have been identified in placental tissue, we examined the effects of glucocorticoids on the production of CG by cultured human cytotrophoblasts. Treatment of cytotrophoblasts with 1 microM dexamethasone increased CG secretion by 6- to 10-fold over a 72-h period, whereas progesterone (1 microM) had no effect. The stimulatory effects of dexamethasone were blocked by the glucocorticoid antagonist RU 486, indicating a requirement for the glucocorticoid receptor. Intracellular accumulation of the CG alpha-subunit in response to dexamethasone was demonstrated by immunocytochemistry, and Northern blot analyses revealed that dexamethasone treatment increases CG alpha- and beta-subunit mRNA levels. Dexamethasone also enhanced the stimulatory effects of 8-bromo-cAMP on CG secretion. We conclude that glucocorticoids as well as cAMP modulate human trophoblast endocrine functions.

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.

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)

Control of the steroidogenic machinery of the human trophoblast by cyclic AMP.

Human cytotrophoblasts express adenylate cyclase activity and possess membrane-bound regulatory proteins that bind guanine nucleotides (G proteins). Stimulation of the cyclase by forskolin or addition of 8-bromo-cAMP augments progesterone secretion by cultured cytotrophoblasts at least in part, by promoting accumulation of components of the cholesterol side-chain cleavage system. This is the consequence of increased synthesis of the proteins participating in steroidogenesis as a result of the 8-bromo-cAMP-provoked increase in their respective mRNAs. We propose that progesterone synthesis by cytotrophoblasts is up-regulated by cyclic AMP, which acts to increase expression of genes encoding the steroidogenic machinery. Paracrine or autocrine factors may initiate this cascade by stimulating the cytotrophoblast adenylate cyclase.

Modified human fibrinogen labeled with 111In.

A method for the labeling of human fibrinogen with 111In is reported. The cyclic anhydride of DTPA, either dissolved in dimethyl sulfoxide or as the solid, is first covalently attached to the protein. The modified fibrinogen is then labeled with [111In]acetate, with an average yield of 90 +/- 3%. The product obtained is highly clottable and stable in vitro and has potential applications in imaging studies.