Peritoneal fluid volume, 17beta-estradiol and progesterone concentrations in women with endometriosis and/or luteinized unruptured follicle syndrome

Data on the presence of an ovulation ostium and the volume and the concentrations of estradiol (17 beta-estradiol) and progesterone In women with endometriosis (n = 80) and women with luteinized unruptured follicle (LUF) syndrome (n = 32) are reported and compared with data obtained from normal ovulatory women, previously reported. in women with endometriosis, less ovulation ostia were observed, the difference being significant in moderate and severe endometriosis. During the luteal phase, no statistical difference was found in the amount of peritoneal fluid of women with endometriosis. Estradiol and progesterone levels in the peritoneal fluid of normal women and women with mild endometriosis were not significantly different. Lower steroid concentrations found in peritoneal fluid of women with moderate (phase days 20-22) and severe endometriosis (phase days 14-19 and 20-22) may explain the high incidence of infertility reported in these women (peritoneal steroids deficiency). During the phases days 14-19 and 20-22, very low peritoneal steroid concentrations were found in women with LUF syndrome. It is suggested that progesterone assay in peritoneal fluid is an aid to diagnose the luteinized unruptured syndrome.     

Ovulation stigma and concentration of progesterone and estradiol in peritoneal fluid: relation with fertility and endometriosis

The relationship between the presence or absence of an ovulation stigma and (1) the fertility status, (2) the incidence of endometriosis, (3) the concentration of progesterone and estradiol in the peritoneal fluid, and (4) the blood levels of luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol in 21 fertile and 45 infertile patients who underwent a laparoscopy in the early (n = 48) or late luteal phase (n = 18) was investigated. An ovulation stigma was observed in about half of the patients, irrespective of their fertility status (past and subsequent), the presence of endometriosis, or the time of the luteal phase. Progesterone and estradiol concentrations in the peritoneal fluid were highest in the early luteal phase, but they were not correlated with the presence or absence of an ovulation stigma. No significant differences were observed in peripheral hormone levels between women with and those without an ovulation stigma nor between women with high or low concentrations of progesterone in the peritoneal fluid. From the data, it is concluded that hormone assays are of no aid in the diagnosis of the luteinized unruptured follicle syndrome and that the absence of an ovulation stigma on laparoscopic examination cannot be equated with the luteinized unruptured follicle syndrome.     

Decreased peritoneal concentrations of interleukin-15 in women with advanced stage endometriosis

OBJECTIVE: To assess the concentrations of interleukin-15 (IL-15) in peritoneal fluid from women with endometriosis and fertile disease-free controls. STUDY DESIGN: Peritoneal fluid samples were obtained from 50 women with endometriosis and 29 fertile women having tubal ligation. Concentrations of IL-15 were measured. RESULTS: The mean (S.D.s) concentration of IL-15 in peritoneal fluid was 11.17 pg/mL (3.89) for women with endometriosis, and 12.59 pg/mL (4.11) for fertile disease-free controls. The difference of peritoneal IL-15 concentrations between endometriosis and control women was not statistically significant. However, peritoneal IL-15 concentrations were significantly lower in women with moderate/severe endometriosis when compared with those in women with minimal/mild endometriosis, and in controls (P<0.05). In addition, peritoneal IL-15 concentrations did not correlate with the phase of menstrual cycle in endometriosis or control women. CONCLUSIONS: Our results suggest that the decreased peritoneal IL-15 concentrations in women with moderate/severe endometriosis imply a role of IL-15 in the pathogenesis of advanced endometriosis as compared to those with minimal/mild endometriosis and fertile disease-free controls.     

Luteinized unruptured follicle syndrome: hormone assay on peritoneal fluid in a laparoscopic study of infertile women

33 infertile women with normal ovulatory cycles were investigated for the presence of a Luteinized Unruptured Follicle Syndrome (L.U.F.) using steroid hormone assays in peritoneal fluid and laparoscopic visualization of ovulation stigmata. We failed to identify a stigma in 36% (12) of the patients in the early luteal phase, 1 subject had a cystic corpus luteum and in 4 cases no diagnosis was made due to the presence of adhesions. The mean hormone concentrations in PF were significantly higher when the stigma was present (17-beta-estradiol, P less than 0,05; progesterone, P less than 0,01; 17-oh-progesterone, P less than 0,05). The two groups (with and without ovulation stigmata) showed no differences in plasma levels of Estradiol (E2) and Progesterone (P). Stigmata were detected only in 17% of subjects with concomitant endometriosis. 3 patients with a luteal phase defect showed low levels of steroids in PF in spite of the presence of an ovulation stigma.     

Effect of ovarian involvement on the frequency of luteinized unruptured follicle in endometriosis.

OBJECTIVE: When we review the current literature on endometriosis and luteinized unruptured follicle (LUF), we see that most of the studies deal with only the association between LUF frequency and the severity of endometriosis. Our purpose was to evaluate the effect of ovarian involvement on LUF frequency in endometriosis and assess the relationship between endometriosis and LUF in infertile women. STUDY DESIGN: This study is a prospective analysis covering a total of 126 infertile women between 22 and 35 years of age who underwent diagnostic laparoscopy from September 1995 to August 1997 in the Department of Obstetrics and Gynecology at Süleyman Demirel University, Isparta, Turkey. Endometriosis was diagnosed in 58 of these patients. All had received a revised American Fertility Society staging score at the time of the laparoscopic diagnosis. Diagnosis of LUF was made when the following criteria were fulfilled: absence of ultrasonic signs of ovulation, and absence of an ovulation ostium on the follicle by laparoscopy, despite increased serum progesterone. Statistical evaluation was performed using chi2 test and Fisher's exact test where appropriate. RESULTS: The prevalence of LUF in mild, moderate and severe endometriosis cases was 13.3, 41.2 and 72.7%, respectively. The LUF frequencies were 45.9% in 37 endometriosis patients with ovarian involvement, 9.5% in 21 cases without ovarian involvement, and 5.9% in 68 cases without endometriosis. A statistically significant difference was observed between the LUF rate in the group with ovarian involvement and that without involvement (chi(2) = 8.06, p < 0.001). CONCLUSION: In summary, in this study we noted a significant increase in LUF frequency in endometriosis patients with ovarian involvement.     

Spontaneous abortion rate in patients with endometriosis treated with progesterone

Several reports suggest that women with endometriosis have a higher risk of spontaneous abortions when left untreated; however, these studies did not control for the presence of possible luteal phase defects. This study was designed to document the frequency of spontaneous abortions in women with endometriosis and ovulation defects treated prophylactically with progesterone, compared with similar patients without endometriosis. All the women had late luteal phase endometrial biopsies dating perfectly normal. Our findings show an increase in the rate of spontaneous abortions (25.7%) in women with endometriosis as compared with the entire group (3.8%). However, when the result for the group with endometriosis is compared with the subgroup of patients at diagnostic laparoscopy not showing endometriosis, the results are similar (30%). We conclude that when properly matched groups are compared, there is no increased risk of spontaneous abortions in women with endometriosis. Since we perform laparoscopies only in women failing to conceive after a reasonable number of seemingly normal cycles, the apparently high incidence of abortions in this group may be secondary to other factors that not only may lengthen the time needed for conception but also increase the abortion risk after conception.     

白血病抑制因子在子宫内膜异位症并发不孕患者黄体中期子宫内膜中的表达

目的:探讨白血病抑制因子(LIF)在子宫内膜异位症(EM)导致不孕机制中的作用。方法:采用原位杂交及免疫组织化学方法对15例异位症并发不孕患者黄体中期子宫内膜中的LIF mRNA及其蛋白的表达进行定位及半定量分析,并以15例有生育妇女作为对照组。结果:子宫内膜异位症组LIF mRNA平均光密度为3.12±0.32,LIF蛋白平均光密度为9.31± 2.10,显著低于对照组的6.25±2.14与15.70±1.52(P<0.05)。结论:子宫内膜异位症组黄体中期子宫内膜LIF表达下降可能是其不孕的原因之一。     

Protein, progesterone, and protease inhibitors in uterine and peritoneal fluids of women with endometriosis

This study was undertaken to determine whether women with endometriosis have altered protein, progesterone (P), and protease inhibitor concentrations in their uterine fluid and peritoneal fluid (PF) compared with controls at different phases of the menstrual cycle. Uterine flushings (UFs), PF, and blood were obtained during the follicular and luteal phases of the cycle from 29 normal women and 16 women who were diagnosed as having endometriosis. Protein content in UF did not change significantly throughout the cycle in either group. However, PF protein in patients with endometriosis was significantly (P less than 0.05) higher than in controls during the luteal phase. Total UF P was significantly (P less than 0.05) reduced in women with endometriosis during the late luteal phase. During the early luteal phase, trypsin inhibitory activity in UF from normal women was significantly (P less than 0.05) higher than at any other phase of the cycle, whereas inhibitory activity in UF from patients with endometriosis remained relatively constant. Patients with endometriosis had significantly (P less than 0.05) higher total activity in PF during the early luteal phase than did controls. These results indicate that women suffering from endometriosis have significantly lower levels of P and less protease inhibitor within their uterine cavity during the luteal phase of the cycle, and significantly higher concentrations of protein and protease inhibitor in PF during the luteal phase.     

Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery

The level of tumor necrosis factor (TNF) in peritoneal fluid (PF-TNF) of 74 women undergoing laparoscopy was determined. The difference between the mean concentration of PF-TNF of women with normal pelvic anatomy and women with moderate or severe endometriosis was significant (P less than 0.01). The proportion of PF-TNF-positive women with PID and those with moderate or severe endometriosis was also significantly higher when compared to women with normal pelvic anatomy (P less than 0.05; P less than 0.02). The proportion of PF-TNF positive women among nulligravid and nulliparous women was significantly higher than that of women with two or more pregnancies (P less than 0.01) and two or more deliveries (P less than 0.005). These results indicate that the presence of PF-TNF is associated with primary infertility and endometriosis.     

Hormonal profiles and embryo quality in women with severe endometriosis treated by in vitro fertilization and embryo transfer

A study was undertaken comparing the outcomes of 30 women with infertility due to untreated severe (grade IV) pelvic endometriosis with a comparable series of 28 women whose infertility was caused solely by irreversible tubal disease. There were no significant differences in either the follicular phase or luteal phase hormonal profiles of estradiol and progesterone, but there was a significantly reduced pregnancy rate in those women with severe endometriosis. In part, this was due to the recovery of fewer oocytes from the endometriosis patients (P less than 0.001) despite the fact that the peak estradiol levels and ovarian accessibility were similar in the two groups. However, there were no significant differences in the proportion of oocytes that fertilized or the number that demonstrated normal embryo growth and high-grade embryo quality. There also appears to be an implantation inhibitory factor in patients with severe endometriosis as the pregnancy rate/embryo transferred and number of gestational sacs identified/embryo transferred were significantly reduced (P less than 0.05).     

Mild endometriosis and luteal function

The luteal function of 27 patients with mild endometriosis and infertility was compared with that of 50 infertile patients without endometriosis. The incidence of endometrial luteal phase deficiency was similar in both groups of patients. Luteal phase length and plasma levels of progesterone (P), estradiol (E2) and prolactin (PRL) in infertile patients (both groups) were similar to those in a group of 10 fertile women. We conclude that luteal phase defects should not be considered as a primary cause of infertility in mild endometriosis.     

Serum and peritoneal fluid proteins in women with and without endometriosis

We examined the proteins in serum and peritoneal fluid of women with endometriosis (and of healthy controls) for evidence of an autoimmune response that might account for their impaired fertility. No antibodies against endometrial glycoproteins or against "progestin dependent endometrial protein" (PEP) were found in any serum or peritoneal fluid sample. Levels of PEP were not different in serum from women with moderate to severe endometriosis (n = 6), with mild endometriosis (n = 21), or from disease-free cycling controls (n = 19). PEP levels in peritoneal fluid from mild endometriosis and from controls did not differ but were elevated ten times in fluid obtained in the secretory phase from women with moderate to severe disease. This suggests that PEP levels in peritoneal fluid reflect the extent of ectopic endometrial growth. The salient finding was a heretofore undescribed protein (mol wt 70,000) in secretory phase peritoneal fluid samples (18/20) and its absence during the proliferative phase (0/35).     

血清抑制素含量在月经周期中的变化及其与卵泡刺激素的相关性

目的了解育龄妇女在月经周期中血清抑制素(INH)含量的变化规律及其与卵泡刺激素(FSH)、黄 体生成素(LH)、雌二醇(E2)及孕酮(P)的相关性。方法建立一种改良的INH放射免疫测定法(RIA),对育龄妇 女正常月经周期中及绝经后妇女血清INH含量的变化进行监测;同时测定血清FSH、LH、E     

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology of endometriosis.     

Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis

OBJECTIVE: To evaluate the presence of macrophage migration inhibitory factor (MIF) in the peritoneal fluid of normal fertile women and patients with endometriosis and its growth-promoting activity toward human endothelial cells. DESIGN: Retrospective study using ELISA to measure peritoneal fluid MIF, and [3H]-thymidine incorporation into the DNA of human endothelial cells to assess its mitogenic activity. SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Thirty-six healthy women and 57 women with endometriosis. INTERVENTION(S): Peritoneal fluid samples were obtained at laparoscopy. MAIN OUTCOME MEASURE(S): Macrophage migration inhibitory factor concentrations in the peritoneal fluid samples and [3H]-thymidine incorporation into the DNA of human microvascular endothelial cells to assess proliferation. RESULT(S): This study demonstrated the presence of MIF in the peritoneal fluid and a 238% increase of MIF levels in women with endometriosis as compared with healthy women. Both fertile and infertile women with endometriosis had significantly higher MIF concentrations than did fertile women with normal gynecological status, but the difference was more significant in infertile endometriosis patients. Anti-MIF antibody significantly inhibited proliferation of human microvascular endothelial cells in response to peritoneal fluids from healthy women and women with endometriosis stages I-II and III-IV, as assessed by [3H]-thymidine incorporation. CONCLUSION(S): This study revealed the presence of MIF in the peritoneal fluid and its increased levels in endometriosis and suggests that MIF may be involved in endometriosis-associated infertility and angiogenesis.     

The influence of bromocriptine treatment on prolactin secretion in infertile women with suspicion of luteal phase insufficiency

There were 30 infertile women with insufficient luteal phase of the cycle under the study. The hyperprolactinemia was diagnosed in 14 from 30 infertile women. In women with normal cycles the ovulation occurred in 18 day of the cycle. During the treatment with Bromocorn it was observed earlier, independently from the prolactin level in blood serum. The luteal phase of the cycle in controls lasted for 9.9 +/- 0.2 days and 11.8 +/- 0.5 days in women after one cycle with Bromocorn and 12.3 +/- 0.2 days after two cycles with Bromocorn. Duration of the cycles in these three studied groups differed statistically significantly (p < 0.001). In women treated with Bromocorn the second cycle phase lasted longer than 11 day and the differences in progesterone and LH levels in the middle of the cycle and at the end of the luteal phase were insignificant. The obtained results show, that Bromocorn could be a suitable method of treatment in the luteal phase insufficiency.     

Relationship between luteal function and prolactin in infertile women with endometriosis

Luteal function in 44 infertile women with endometriosis were studied with reference to prolactin (PRL) and compared with 34 unexplained infertile women without endometriosis. To assess luteal function, serum progesterone (P4) levels were measured on the 3rd, 7th and 10th days of the luteal phase. On the 7th day, serum estradiol (E2) levels and PRL levels were also determined. The response of PRL secretion to TRH was examined at 30 and 60 after following TRH (500 micrograms, im.) administration. The incidence of hyperprolactinemia (basal PRL level greater than or equal to 25 ng/ml) and latent hyperprolactinemia (peak PRL level in TRH challenge test greater than or equal to 150 ng/ml) were 19% and 31%, respectively, in the endometriosis group and 14% and 33%, respectively in the control group. At the midluteal stage, serum P4 levels in endometriosis group were decreased significantly (p less than 0.05), whereas no difference was found between the serum E2 levels in the endometriosis group and the control. In the endometriosis group, there was no correlation between P4 and E2 levels and abnormal secretion of PRL such as hyperprolactinemia and latent hyperprolactinemia. These results indicate the close association of endometriosis with an inadequate luteal phase. However, it seems that the aberrant secretion of PRL has no relation to the impared luteal function in endometriosis.     

Clinical and endocrinological studies on anovulatory women treated with two-step administration of clomiphene citrate

The two step clomiphene citrate (CL) administration therapy was performed in 89 patients with first grade amenorrhea during 1980 through 1983, and clinical data in 89 patients and daily serum hormone levels in 20 patients were investigated. Out of the 89 women, ovulation occurred in 71 (79.8%). As to the treatment cycles, ovulation occurred in 158 cycles (53.4%) out of the total 296 cycles. Pregnancy was achieved in 16 women, among whom 2 women ended in spontaneous abortion and one had a multiple pregnancy. (1) As for 9 women in whom ovulation was induced by this treatment, the serum level of LH in the follicular phase and that of estradiol in the late follicular phase and luteal phase were higher than those of women who had normal ovulatory cycles. (2) No significant differences were observed between the serum levels of FSH and progesterone of the 9 women and those of women with normal ovulatory cycles. (3) As for 11 women in whom ovulation was not induced by this treatment, a transient increase in serum levels of LH and estradiol were observed after the first step administration of CL. This change also appeared soon after completion of the second step administration of CL and became more significant as additional stepwise administration of CL was performed. In view of observations, it was concluded that CL two step administration is effective for anovulatory women who did not respond to one step use of CL. As previously reported, CL exerts its action on the central nervous system to promote ovulation, but it is also strongly suggested that CL has its direct action on the ovary too.     

Prostaglandin F2 alpha in the peritoneal fluid of patients with endometriosis

The amounts of PGF2 alpha in peritoneal fluid were determined by radioimmunoassay in 21 patients undergoing exploratory laparotomy or diagnostic laparoscopy for infertility during the follicular phase of the cycle. Detectable levels of PGF2 alpha were found only in that group with moderate and severe endometriosis who also had blood-tinged or chocolate material in the peritoneal cavity. A patient with blood-tinged peritoneal fluid and pelvic adhesions without endometriosis also had elevated peritoneal fluid PGF2 alpha. In contrast, peritoneal fluid without evidence of old hemorrhage from patients with endometriosis or pelvic adhesions as well as from a group of normal women did not contain PGF2 alpha. None of the endometriosis patients had evidence of a short luteal phase by standard criteria.