Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility.

OBJECTIVE: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART). DESIGN: Case series. SETTING: University fertility program. PATIENT(S): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility. INTERVENTION(S): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF. MAIN OUTCOME MEASURE(S): Pregnancy and pregnancy outcome. RESULT(S): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. CONCLUSION(S): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.

Ovulation induction.

In the woman with anovulation and polycystic ovarian syndrome, there are many options for ovulation induction. Treatment should be individualized, but clomiphene citrate is an excellent first-line agent. In the woman resistant to clomiphene citrate, combination therapy often results in pregnancy. Some women with PCOS only respond to gonadotropin therapy. These women are at a higher risk for multiple pregnancy and ovarian hyperstimulation syndrome. In the woman with anovulation and hypothalamic amenorrhea, the options for ovulation induction are limited. The luteal phase must be supported. The hypothalamus is unable to support the corpus luteum or early pregnancy.

Effect of exogenous gonadotropins on endometrial maturation in oocyte donors.

OBJECTIVE: To determine the effects of controlled ovarian hyperstimulation (COH) on endometrial maturation. DESIGN: Prospective, before and after evaluation of midluteal endometrial biopsies in oocyte donor's spontaneous and subsequent COH cycles. SETTING: Tertiary academic medical center assisted reproductive technologies clinic. PATIENT(S): Nineteen oocyte donors. INTERVENTION(S): Exogenous gonadotropins, endometrial biopsies. MAIN OUTCOME MEASURE(S): Endometrial histology and an immunohistochemical marker of uterine receptivity, the alphavbeta3 vitronectin. RESULT(S): Glandular and stromal dyssynchrony was more common after COH in 16 (80%) of 20 cycles than 6 (30%) of 20 spontaneous cycles (P <.05). Glandular lag was more frequent in COH cycles and unaffected by progesterone administration. The beta3 subunit of the alphavbeta3 vitronectin receptor was present in 9 (45%) of 20 spontaneous and 2 (10%) of 20 COH cycles (P <.05). CONCLUSION(S): Exogenous gonadotropin use in healthy reproductive age women did not result in endometrial evidence of a luteal phase defect. A greater incidence of glandular-stromal dyssynchrony resulted from the use of exogenous gonadotropins. The presence of alphavbeta3 was noted in most endometrial specimens demonstrating in phase glandular maturation. We conclude that endometrial dyssynchrony that results from delayed glandular development most likely represents a normal histologic variant.

Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section.

This study was undertaken to investigate the effect of pregnancy on the disposition of thiopental and to determine the major factors which influence the placental transfer of the drug to the fetus. Maternal venous (MV) and umbilical venous (UV) and arterial (UA) blood samples were collected at delivery from 11 pregnant women at term who received thiopental for induction of anesthesia for elective cesarian section. A detailed study of the pharmacokinetics of thiopental was carried out in 7 of these subjects and blood samples were collected for 80 to 100 hours following thiopental administration. A transient rise in thiopental plasma concentration was observed at delivery. Mean values of pharmacokinetic parameters (plus or minus SD) were: initial distribution volume (V1) 17.31 (plus or minus 8.5), apparent volume of distribution (Vdbeta) 564 1 (plus or minus 343), volume of distribution at steady state (Vss) 2881 (plus or minus 180), systemic plasma clearance (Clp) 0.286 l/min (plus or minus 0.156), rate of change of volume of distribution at zero time (RVd0) 1.03 l/min (plus or minus 0.36) and elimination half-life (t1/2) 26.1 h (plus or minus 12.6). Comparison of these data with our previously reported data in nonpregnant surgical patients shows that Vdbeta, Vss, T1/2 are significantly greater at cesarian section (P less than 0.05) and that systemic plasma clearance shows a similar trend. UA and UV values at delivery were similar within individuals. There was no correlation between the ratio UV/MV at delivery and the dosing-delivery interval (delta t), or between UV and the administered dose or delta t. There were good correlations between UV (corrected for dose) and the reciprocals of V1, Vdbeta, Vss, and plasma clearance of thiopental. This demonstrates that differences in maternal distribution and elimination characteristics of thiopental may be more important determinants of intersubject differences in fetal drug exposure than differences in dose or delta t.

Pharmacokinetics and plasma binding of thiopental. I: Studies in surgical patients.

The pharmacokinetics and plasma protein binding of thiopental were investigated in 5 female patients who received a bolus intravenous dose of the drug for induction of anesthesia for gynecologic surgery. Blood samples were collected for 3 to 4 days after the dose. Plasma protein binding determinations were also carried out by ultrafiltration and equilibrium dialysis on samples from a panel of healthy volunteers. Plasma concentrations of thiopental were determined by reverse-phase, high-performance liquid chromatography. The coefficient of variation of the method was 2.8 per cent (n equals 10). In healthy volunteers, the plasma protein binding of thiopental was concentration dependent. Percentage bound ranged from 96.7 (n equals 4, SD equals 0.8) at 150 micrograms/ml. Therefore, saturation of binding sites on rapid administration of the drug may occur, exposing vital organs to unexpectedly high concentrations of free drug. Values of the fraction of thiopental bound in plasma obtained from the surgical patients during the hour following drug administration were similar to values obtained in healthy volunteers at comparable concentrations. Mean pharmacokinetic parameters obtained for thiopental in the surgical patients were as follows: initial distribution volume 13.81 (SD equals 9.4), apparent volume of distribution 233 1 (SD equals 98), volume of distribution at steady state 97.51 (SD equals 40), elimination half-life 11.5 h (SD equals 1.0) and systemic plasma clearance 0.150 l/min (SD equals 0.063). None of these parameters correlated with body weight. Values reported by other workers vary from ours and this variation may be explained by the much shorter duration of blood collection used in those studies.