[New developments in labor induction].

INTRODUCTION: Misoprostol is a prostaglandin E1 analogue. During the last 8 years it has been examined in clinical trials in obstetrics for the induction of labor and cervical ripening. AIM: To review the current literature concerning its efficacy, safety and dosage for induction of labor. MATERIALS AND METHODS: This review is based on the results of 33 articles published during the years 1993-2001. Data was gathered by searching the internet at Pubmed, Medline and the list of references in the relevant articles. RESULTS: Misoprostol is a highly effective medication for the induction of labor in comparison to prostaglandin E1 or oxytocin. It is stable for years and the cost of treatment is low. Its disadvantage is based on its tendency to evoke increased uterine activity such as tachysystole and hyperstimulation and the fear of uterine rupture. These disadvantages can be overcome by safety measures such as decreasing the dose, increasing time intervals between doses and careful selection of patients. CONCLUSIONS: Misoprostol is an important and efficient medication in obstetrics for cervical ripening and induction of labor. Therefore, we believe it is appropriate to start clinical trials in Israel too.

Substituting human chorionic gonadotropin by gonadotropin-releasing hormone agonist to trigger final follicular maturation, during controlled ovarian hyperstimulation, results in less systemic inflammation.

BACKGROUND: To investigate the degree of systemic inflammation, as reflected by serum C-reactive protein (CRP) levels, associated with controlled ovarian hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist for the induction of final follicular maturation. DESIGN: Prospective, observational study. SETTING: An in vitro fertilization (IVF) unit of an academic medical center. PATIENTS: Twenty-four women undergoing COH and IVF with the flexible GnRH antagonist protocol were prospectively assigned to receive hCG or GnRH agonist for the induction of final follicular maturation. METHODS: Blood was drawn three times during COH for measurement of sex-steroid and CRP levels: the day on which adequate suppression was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time points in the two groups. RESULTS: No between-group differences were observed in terms of patient age, gonadotropin dosage, duration of stimulation or number of oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0, but the difference was significant only in the hCG group (p<0.03 for both). The percentage change in CRP levels after hCG administration (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%). CONCLUSION: Administration of GnRH agonist in patients undergoing COH for IVF yields a lesser degree of systemic inflammation, as reflected by CRP levels, than hCG.

Soluble CD40 ligand levels during controlled ovarian hyperstimulation--a possible culprit of systemic inflammation.

AIM: To investigate the behavior and association of serum sex-steroids and serum CD40 ligand in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Prospective, observational study. SETTING: The IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 17 patients undergoing the long gonadotropin-releasing hormone-analog protocol: (i) day on which adequate suppression was obtained (Day-S); (ii) day of or prior to administration of human chorionic gonadotropin (Day-hCG); and (iii) day of ovum pick-up (Day-OPU). Levels of sex steroids and serum CD40 ligand were compared among the three time points. RESULTS: During gonadotropin treatment, serum ovarian sex steroids (estradiol, progesterone, free testosterone and androstenedione) significantly increased while CD40 ligand levels nonsignificantly decreased. After hCG administration, there was a significant increase in the levels of serum CD40 ligand, ovarian androgens, and progesterone, with a significant decrease in estradiol levels. No correlations were observed between CD40 ligand and ovarian sex-steroid levels or other treatment variables. CONCLUSION: The administration of hCG leads to activation of systemic inflammation, as reflected by CD40 ligand levels. This, in turn, may lead to the development of ovarian hyperstimulation syndrome via several mechanisms, including an increase in several angiogenic factors.

Ovarian androgens but not estrogens correlate with the degree of systemic inflammation observed during controlled ovarian hyperstimulation.

AIM: To investigate the behavior and association of serum androgen and serum C-reactive protein (CRP) in patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: Prospective, observational study.Setting. An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 15 patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum CRP were compared among the three time points. RESULTS: There was a significant increase in serum ovarian androgen levels during gonadotropin treatment. After hCG administration, there was a significant increase in the levels of both serum CRP and ovarian androgens (testosterone, androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone). Significant correlations were observed between CRP and ovarian androgen levels but not with dehydroepiandrosterone sulfate or estradiol levels. CONCLUSION: In patients undergoing COH for IVF, ovarian androgen levels increase in correlation with the degree of inflammation, as reflected by CRP levels. Further studies are necessary to elucidate whether androgens play a role in or are predictive of the systemic inflammatory response in COH.

Serum androgen levels in patients undergoing controlled ovarian hyperstimulation for in vitro fertilization cycles.

AIM: To investigate androgen behavior during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). DESIGN: A prospective, observational study. SETTING: An IVF unit of an academic medical center. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from 17 consecutive patients undergoing the long gonadotropin-releasing hormone-analog protocol: the day on which adequate suppression was obtained (Day-S); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). RESULTS: There was a significant increase in serum sex steroid levels during gonadotropin treatment. After hCG administration, there was a significant increase in levels of serum 17-hydroxyprogesterone (17-OHP) and ovarian androgens (total and free testosterone and androstenedione), with no significant change in adrenal androgen (dehydroepiandrosterone sulfate). Significant correlations were observed between plasma estradiol (E(2)) and androgen levels during COH and until hCG administration, but not after hCG administration. The E(2)/testosterone ratio increased significantly during COH and until hCG administration, and then decreased significantly. The number of oocytes retrieved correlated significantly with serum 17-OHP, E(2) and E(2)/testosterone ratio. The number of gonadotropin ampoules used correlated inversely only with serum E(2) levels. CONCLUSION: In patients undergoing COH for IVF, androgen levels increase in response to gonadotropin, and then again after hCG administration. Although the E(2)/testosterone ratio correlates with the number of oocytes retrieved, androgen levels do not.

Controlled ovarian hyperstimulation: does prolonged stimulation justify cancellation of in vitro fertilization cycles?

BACKGROUND: In daily practice, assisted reproductive technology (ART) cycles are often cancelled under the assumption that a prolonged stimulation period lowers the likelihood of an appropriate ovarian response. The aim of the present study was to determine whether a prolonged cycle has an adverse effect on achievement of pregnancy. METHODS: The study sample included consecutive women enrolled in our ART unit between 1999 and 2001 who were treated with the mid-luteal long suppressive gonadotropin-releasing hormone protocol. Data were collected prospectively on a computerized database and evaluated at the end of the study. Prolonged stimulation was defined as a stimulation period of more than two standard deviations (SD) above the mean. Outcome was compared between patients who required prolonged stimulation and those who did not. RESULTS: A total of 1015 consecutive in vitro fertilization (IVF) cycles were performed with the mid-luteal long suppressive protocol during the study period. Thirty-four women required prolonged stimulation. No difference in clinical pregnancy rate was detected between women who received prolonged stimulation and those who did not (9/34, 26.5% vs. 291/981, 29.7%), despite the significantly fewer oocytes retrieved in the prolonged-stimulation group (7.1 +/- 5.2 and 11.6 +/- 6.7 (mean +/- SD), respectively, p < 0.001). CONCLUSION: The likelihood of achieving pregnancy is not influenced by the length of stimulation. We recommend that IVF cycles should not be discontinued on the grounds of prolonged stimulation alone.