Our aim was to examine the relationship between the levels of cytokines in peritoneal fluid and its embryo toxicity.
Study Design
The levels of interleukin-1 and tumor necrosis factor were measured in peritoneal fluid from infertile women who did not have endometriosis (n = 21), who had untreated endometriosis (n = 19), and who had undergone medical treatment for endometriosis (n = 10). Embryo toxicity was investigated in mouse two-cell embryos cocultured with the oviducts in culture media that contained various concentrations of peritoneal fluid.
Results
The levels of cytokines were significantly higher in the peritoneal fluid from women who had untreated endometriosis than in women who did not have endometriosis, but they were extremely low in women who had undergone medical treatment with either danazol or buserelin. The peritoneal fluid from women who had untreated endometriosis adversely affected the cleavage of mouse two-cell embryos. After medical treatment the embryo toxicity of the peritoneal fluid was almost undetectable.
Conclusion
These results offer some theoretic bases in support of medical treatment to improve reproductive performance in infertile women who have endometriosis.
PMID 1442940 1442940 DOI 10.1016/s0002-9378(11)91672-x 10.1016/s0002-9378(11)91672-x Taketani et al. 1992, Taketani 1992
Cite this article
Taketani, Y., Kuo, T. M., & Mizuno, M. (1992). Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis. American journal of obstetrics and gynecology, 167(1), 265-270. https://doi.org/10.1016/s0002-9378(11)91672-x
Taketani Y, Kuo TM, Mizuno M. Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis. Am J Obstet Gynecol. 1992;167(1):265-270. doi:10.1016/s0002-9378(11)91672-x
Taketani, Y., et al. "Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis." American journal of obstetrics and gynecology, vol. 167, no. 1, 1992, pp. 265-270.
The use of hormonal treatments for endometriosis has increased in recent years. Their effectiveness lies in creating a stable hormonal environment, reducing peripheral estrogen levels, and suppressing ovulation and menstruation. Although these agents do not cure endometriosis and symptoms often return after discontinuation, they effectively relieve pain in most cases and help prevent disease progression or recurrence. Women are therefore typically managed with long-term hormonal treatments, with or without surgery. However, this approach is unsuitable for those seeking natural pregnancy or undergoing IVF, as all hormonal treatments hinder conception. For women pursuing natural pregnancy, these treatments should be discontinued for about 1 year, the time needed to diagnose infertility. However, this suspension exposes women to the risk of recurrence or progression and is therefore clinically acceptable only if the woman has a reasonable likelihood of achieving pregnancy naturally. In women with endometriosis who are infertile and therefore require IVF, ovarian stimulation significantly raises estrogen levels-up to 10 times those of a natural cycle-potentially boosting the risk of endometriosis relapse. Evidence is reassuring on this issue even if some limited data suggest that ovarian stimulation may promote deep invasive endometriosis progression. Overall, physicians and patients must balance the chances of natural or ART-assisted pregnancy against the risk of disease recurrence or progression during treatment discontinuation or IVF. This choice is also complicated by the increased risk of severe pregnancy complications in women with endometriosis, possibly depending on the conception method. This review discusses the available evidence that can be helpful in guiding the decision-making process.
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
To investigate the effect of short-term glucocorticoid administration on embryotoxicity of sera from infertile patients with mild to moderate endometriosis. Prospective longitudinal study. SETTING, Eight infertile patients with mild to moderate endometriosis and a control group of eight infertile patients with tubal infertility were selected on the basis of laparoscopic examination. Basal (B) serum collection and day 1 (T1), day 3 (T2), day 6 (T3), and day 12 (T4) serum drawn after a 3-day glucocorticoid treatment in endometriosis patients. Embryotoxicity of endometriosis sera, before and after glucocorticoid treatment, was investigated using a bioassay performed on two-cell mouse embryos. Interleukin 1 alpha (IL-1 alpha) and antismooth muscle, antimitochondrial, and antinuclear autoantibodies were also tested in these sera. At 50% concentration, endometriosis serum is embryotoxic in comparison with control; 0% versus 61% of the embryos reached the blastocyst stage at 72 hours, respectively (basal versus control, P less than 0.001). However, this embryotoxicity significantly decreases 12 days after glucocorticoid treatment in comparison with untreated sera; 32.4% versus 0% of the embryos reached blastocyst stage at 72 hours, respectively (T4 versus basal, P less than 0.001), although they did not reach nontoxic levels (greater than 50%). Interleukin 1 alpha was undetectable in all samples analyzed. In endometriosis sera, antismooth muscle antibody was detected. At 50% concentration, serum from infertile patients with minimal to moderate endometriosis appears to be embryotoxic to the in vitro development of two-cell mouse embryos. However, this embryotoxicity significantly decreases 12 days after a 3-day treatment with glucocorticoids.
Whitley J et al., 2025·American journal of obstetrics and gynecology·
Open Access
Our objective was to determine if oxytocin discontinuation in the active phase of labor impacts the rate of cesarean delivery compared to continuation of oxytocin. This study was a systematic review and meta-analysis of randomized controlled trials. A research librarian performed a database search using a combination of standardized terms and keywords related to oxytocin discontinuation and stages of labor from database inception until February 2024. This protocol was registered in The International Prospective Register of Systematic Reviews (PROSPERO). Randomized controlled trials of pregnant patients who received oxytocin for induction or augmentation of labor, whose outcomes compared discontinuation and continuation of oxytocin in active labor, were included. We defined "active phase of labor" as defined by each trial. Nonrandomized trials, quasi-randomized trials, and animal models were excluded. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included postpartum hemorrhage, total blood loss, and infectious outcomes. Secondary neonatal outcomes included Apgar score at 5 minutes <7, umbilical arterial pH <7.10, neonatal therapeutic hypothermia, neonatal intensive care unit admission, neonatal resuscitation at birth, and neonatal death. STUDY APPRAISAL The risk of bias in each study was assessed using the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Heterogeneity was measured using Higgins I2. Meta-analysis was performed in Review Manager 5.4.1 and StataSE 16 to determine summary treatment effects in terms of relative risk or mean difference with 95% confidence intervals. The adherence of each included trial to the trustworthiness criteria outlined by the OBGYN Editors' Integrity Group was assessed, and a leave-1-out analysis was performed to evaluate the effect of studies with concerns regarding trustworthiness. Fifteen randomized controlled trials, including 5734 patients, were ultimately included in the meta-analysis. The rate of cesarean delivery, reported in 13 studies, was lower with discontinuation of oxytocin in the active phase of labor (relative risk=0.80; 95% confidence interval, 0.66-0.97; 95% prediction interval, 0.38-1.22). Discontinuation of oxytocin was also associated with a lower risk of uterine tachysystole (relative risk=0.45; 95% confidence interval, 0.34-0.60; I2, 26%), and nonreassuring fetal heart rate tracing (relative risk=0.64; 95% confidence interval, 0.49-0.82; I2, 41%). Discontinuation of oxytocin increased the duration of active labor by an average of 30 minutes and second stage of labor by an average of 6 minutes. Although associated with an extension of labor by half an hour, discontinuation of oxytocin in the active phase of labor was associated with a 20% decreased risk of cesarean delivery and a lower risk of uterine tachysystole and nonreassuring fetal heart rate tracing. While the pooled analysis suggests a beneficial effect, this finding is dependent on the inclusion of studies with concerns regarding trustworthiness.
Reproductive Immunology · Inflammation and Reproduction
To elucidate the role of peritoneal macrophages in infertility, we investigated how the presence of peritoneal macrophages would affect fecundity in mice. Moreover, we also studied the effects of interleukin-1 on embryonic development. Mice were administered OK-432 intraperitoneally to induce macrophage infiltration of the peritoneal cavity; ovulation was then induced and animals were mated. On day 13 of gestation, fetuses were counted. After injection of OK-432 or interleukin-1, the mice were mated. Three days later, embryos were collected and the stage of embryo development was determined. In mice given OK-432 (n = 33), four (12%) became pregnant and the mean litter number was 6.0 +/- 3.6, whereas in the control group 23 of 30 mice (77%; p < 0.01) became pregnant and the litter number was 14.1 +/- 5.3 (p < 0.01). OK-432 and interleukin-1 administered intraperitoneally significantly suppressed embryo development (p < 0.01). Increased numbers of peritoneal macrophages negatively affect fecundity, probably by suppressing embryonic development.