Luteal phase dysfunction in endometriosis: elevated progesterone levels in peripheral and ovarian veins during the follicular phase

Endometriosis has been associated with corpus luteum inadequacy and abnormalities of luteal phase progesterone (P) secretion. In this study, abnormal luteolysis, as a second factor of luteal dysfunction, was assessed in 13 women with endometriosis and 25 control patients by measurement of ovarian vein estradiol (E2) and P during the follicular phase. The results reveal that women with endometriosis have (1) significantly lower ovarian vein E2, (2) significantly higher both peripheral and ovarian vein P, and (3) threefold higher P/E2 ratios than controls during the follicular phase. These data support the concept of continued P production from an active corpus luteum well into the follicular phase of the following cycle in women with endometriosis. Failure of adequate luteolysis is a second aspect of luteal dysfunction in endometriosis and strongly supports the growing body of data confirming ovulatory asynchrony in the minimal; endometriosis infertility syndrome.     

CA 125 levels in endometriosis patients before, during and after treatment with danazol or LHRH agonists

The levels of CA 125 in the serum of 54 patients with endometriosis were measured before, during and after treatment with Danazol or LHRH analogues. Patients with minimal and mild endometriosis had mean pre-treatment values significantly higher than control subjects in the luteal phase of the cycle or postmenopausal women (p less than 0.05), but levels were within the overall control range. In contrast, 78.6% of patients with moderate or severe endometriosis had levels in excess of 30 mu/ml and the mean values for these groups were significantly elevated (p less than 0.005). Levels of CA 125 fell, to those found in normal controls, during treatment, but rose again following cessation of treatment. Six of 12 subjects whose follow-up values of CA 125 exceeded 30 U/ml had a proven recurrence of endometriosis, whilst only 2 of 31 patients with values less than 30 U/ml had laparoscopically proven recurrence.     

细胞间粘附分子-1在子宫内膜异位症在位内膜、腹腔液及异位灶中的表达及分析

目的:探讨ICAM 1与子宫内膜异位症的关系。方法:收集子宫内膜异位症患者(研究组)腹腔液30份、在位子宫内膜2 1份、异位病灶组织8份及非子宫内膜异位症患者中正常盆腔(对照组)腹腔液2 5份、子宫内膜2 0份。应用酶联免疫吸附试验双抗体夹心法测定腹腔液sICAM 1和免疫组化方法测定在位内膜、异位灶内膜ICAM 1表达。结果:子宫内膜异位症患者腹腔液中sICAM 1水平明显高于对照组(P <0 .0 1 ) ,子宫内膜的ICAM 1表达低于对照组同期子宫内膜的表达(P <0 .0 5 ) ,异位灶组织ICAM 1表达明显高于其在位内膜(P <0 .0 1 )及对照组内膜(P <0 .0 5 )。结论:子宫内膜异位症患者子宫内膜、腹腔液、异位灶内膜细胞间粘附分子的异常表达可能与子宫内膜异位症的发生发展关系密切。     

CA-125 and placental protein 14 concentrations in plasma and peritoneal fluid of women with deeply infiltrating pelvic endometriosis.

OBJECTIVE: To investigate the plasma and peritoneal fluid (PF) concentrations of CA-125 and placental protein (PP14) in women with deeply infiltrating endometriosis. DESIGN: Plasma and PF were collected during 384 consecutive laparoscopies for pelvic pain or infertility. MAIN OUTCOME MEASURE: The presence and extent of endometriosis were carefully assessed, including the area, depth of infiltration, and volume of subtle lesions, typical lesions, and endometriomas. The day of the menstrual cycle was ascertained by endometrial biopsy and/or basal body temperature charts. RESULTS: Peritoneal fluid concentrations were some 100 and 10 times higher than plasma concentrations for CA-125 and PP14, respectively. Cyclic variations of CA-125 concentrations were only found in women with endometriosis showing increased plasma concentrations at the end of the cycle and increased PF concentrations in the early follicular phase. Cyclic variations of PP14 concentrations were found in women with and without endometriosis both in plasma and PF showing increased concentrations in the late luteal and early follicular phases. In women with endometriosis the increased plasma concentrations of PP14 and CA-125 correlated with the presence and volume of endometriomas and of deeply infiltrating endometriosis. The increased concentrations in PF correlated only with the pelvic area of subtle endometriotic lesions. The diagnostic sensitivity and specificity of CA-125 for endometriosis were 25% and 87%, respectively, and for endometriomas and/or deeply infiltrating endometriosis 36% and 87%, respectively, for a cutoff concentration of 25 U/mL. CONCLUSION: Superficial pelvic endometriosis secretes PP14 and CA-125 mainly toward the PF, whereas endometriomas and deeply infiltrating endometriosis secrete mainly toward the plasma. The increased plasma concentrations of CA-125 are most pronounced during the late luteal phase, and endometriomas and/or deeply infiltrating endometriosis can be detected with a sensitivity of 36% and a specificity of 87%.     

Effects of prolactin and bromocriptine on the luteal phase in infertile women

Infertile women with regular periods but with shortened luteal phases were found to have higher mean levels of serum prolactin and lower serum progesterone levels in the midluteal phase than women with apparently normal ovarian function (P less than 0.001). Serum estrogens and gonadotropins did not differ from the reference group but the ratio FSH/LH was reduced in the midluteal phase (P less than 0.05). LHRH-loading test in the midfollicular phase also resulted in a lower ratio of FSH/LH (P less than 0.05). Thirty-six infertile women with short luteal phases were treated with bromocriptine in a double-blind fashion. The drug moderately reduced the length of the cycle (P less than 0.01). The hyperthermia of the luteal phase was measured planimetrically. Both the total area and the area per day of the luteal phase were significantly increased during the cycles of active treatment (P less than 0.02 and 0.05, respectively). Prolactin was depressed by the drug. After cessation of therapy a very significant rebound elevation of prolactin for at least 2 wk was noted. Bromocriptine therapy further reduced FSH levels at midcycle. Estrogens were elevated during the midluteal phase whereas progesterone was not affected by the treatment. Seven conceptions occurred during the study, six of which during placebo treatment. The conception cycles were characterized by significantly higher levels of progesterone and estrogens during the luteal phase as opposed to the infertile cycles. Four of the pregnancies terminated in spontaneous abortion. The endocrine data of these conception cycles did not differ from those of the successful ones.     

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.     

Endometrial tissue in peritoneal fluid

Peritoneal fluid (PF) was studied for the presence of endometrial tissue in a consecutive series of 67 women (with documented tubal patency) undergoing diagnostic laparoscopy, tubal lavage, and hysteroscopy. PF was completely aspirated from the cul-de-sac both before and after uterine irrigation. The PF was then analyzed for the presence of endometrial tissue. In native PF no significant difference in the incidence of endometrial tissue between patients with (19%) and without (11%) endometriosis (P = 0.6) was observed. Refluxed PF, obtained after uterine irrigation, showed a significantly higher incidence of endometrial tissue in women with endometriosis (76%) as compared to controls (42%) (P = 0.03). We propose two models to explain the development of endometriosis. These are not mutually exclusive, may be independent of each other, and may represent two distinct pathophysiologic disease processes.     

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.     

Malonyldialdehyde and total antioxidant status in the peritoneal fluid of infertile women]

OBJECTIVE: To estimate the concentration of malonyldialdehyde (MDA) and total antioxidant status in the peritoneal fluid (PF) of patients with unexplained infertility (UI) and infertile women with minimal and mild endometriosis. MATERIALS AND METHODS: PF was obtained during laparoscopy from 8 women with UI, 12 infertile women with endometriosis (I degree and II degrees rAFS) and 10 women with benign noninflammatory ovarian tumours. All laparoscopies were performed in the follicular phase of the cycle. MDA concentration was measured according to Ledwozyw method, TAS was measured spectrophotometrically using RANDOX diagnostic reagent system. RESULTS: We found significantly higher concentration of MDA in PF from both patients with UI (p = 0.03) and with endometriosis (p = 0.046) compared to the control group. TAS was significantly (p = 0.027) higher in PF of women with UI but did not differ significantly (p = 0.49) between patients with endometriosis and controls. CONCLUSIONS: Our results show that an imbalance between lipid peroxides and the antioxidant system in PF environment may be one of the main factors responsible for the UI. In the group with endometriosis a marginally significant difference in MDA levels, no significant differences in TAS and data from the literature, suggest that accelerated lipid peroxidation in PF doesn't appear to play a role in the endometriosis associated infertility.     

Elevations in peritoneal fluid macrophage migration inhibitory factor are independent of the depth of invasion or stage of endometriosis

OBJECTIVE: To quantify levels of macrophage migration inhibitory factor (MIF) in the peritoneal fluid (PF) of women with endometriosis, and to correlate these levels with the extent of disease. DESIGN: Controlled clinical study. SETTING: Academic medical center. PATIENT(S): Peritoneal fluid samples were collected during laparoscopic surgery in 60 women with endometriosis and 16 controls undergoing tubal ligation; 52 of the women with endometriosis had received no hormonal treatment in the 6 months prior to surgery, while 8 were using gonadotropin-releasing hormone (GnRH) agonists. MAIN OUTCOME MEASURE(S): Peritoneal fluid migration inhibitory factor (PF MIF) levels. RESULT(S): Women with endometriosis had significantly higher PF MIF levels (10.8 +/- 0.9 ng/mL) than controls (3.0 +/- 0.7 ng/mL). However, no correlation existed between MIF levels and the stage of disease (r = 0.05) or the depth of endometriotic invasion (r = 0.08). Moreover, treatment with a GnRH agonist did not suppress PF MIF levels. Peritoneal fluid MIF levels did not vary significantly between the proliferative and secretory phases of the cycle, and did not distinguish women with endometriosis-associated infertility from women with endometriosis-associated pain. CONCLUSION(S): Peritoneal fluid migration inhibitory factor levels are markedly elevated in women with endometriosis but are independent of the extent of disease.     

Transvaginal color Doppler study of uterine blood flow in primary dysmenorrhea

BACKGROUND: The pain in primary dysmenorrhea is caused by excessive prostaglandin production that leads to vasoconstriction and uterine ischemia. Changes in uterine blood flow are important factors in pathophysiology of primary dysmenorrhea. The aim of the study was to determine if vasoconstriction of the uterine vessels in patients with primary dysmenorrhea is detectable by transvaginal color Doppler ultrasound. METHODS: Forty-two women with primary dysmenorrhea and fifty healthy controls were included in this prospective study. Women were examined with transvaginal color Doppler ultrasound on first day of the cycle, once in the follicular and once in the luteal phase. Measurements of pulsatility index in uterine, arcuate, radial and spiral arteries were performed. Student's t-test was used to establish statistical significance between groups. RESULTS: Women in dysmenorrhea group had significantly higher uterine blood flow indices than healthy controls in all three measurements periods. This includes all vessels studied on the first day of the cycle, the radial and spiral arteries during the follicular phase and the arcuate, radial and spiral arteries during the luteal phase. CONCLUSIONS: We found that women with primary dysmenorrhea have elevated Doppler indices in uterine arteries not only on first day of the cycle but throughout the whole cycle. Therefore we postulated that primary dysmenorrhea is not only the disorder of menstruation but also a disease of a menstrual cycle as a whole.     

Elevated peritoneal fluid luteinizing hormone and prolactin concentrations in infertile women with endometriosis

In this study, we compared (Mann-Whitney U-test) the peritoneal fluid FSH, LH and PRL levels, measured by RIA, at the follicular and luteal phases of the menstrual cycle in women with (n = 43; age 25-44 years) and with no evidence of endometriosis (n = 35; age 25-39 years) who were considered as controls. Both follicular and luteal phase FSH concentrations of women with endometriosis were not statistically different (n = 22 vs 18; 0.32-5.8 vs 0.50-8.2 IU/l, P = 0.247; n = 13 vs 14; 0.6-6.5 vs 0.66-6.7 IU/l, P = 0.604) compared to their respective controls. In contrast to FSH, the concentrations of LH at follicular (n = 19 vs 17; 3.1-34.2 vs 2.3-12.2 IU/l, P = 0.01) and luteal (n = 17 vs 15; 2.1-95.4 vs 1.3-17.9 IU/l, P = 0.02) phases of the test group was significantly elevated at both phases of the cycle. With respect to differences in PRL concentrations at follicular phase no significant change (n = 21 vs 16; 1030-5800 vs 1305-4650 mIU/l; P = 0.255) was observed. The greatest difference in luteal PRL concentrations (P = 0.007) was obtained between the women with endometriosis and controls (n = 17 vs 17; 1895-8600 vs 1041-5000 mIU/l). The results suggest that disordered synchronization of neuroendocrine mechanisms controlling LH and PRL may be the underlying abnormality causing infertility in our group of patients with 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).     

Incidence of the luteinized unruptured follicle syndrome in fertile women and in women with endometriosis

One-hundred normal fertile women with normal luteal phase and 118 women with endometriosis underwent luteal phase laparoscopy before day 22. The luteal phase was ascertained by the presence of secretory endometrium and serum progesterone levels higher than 3 ng/ml. The ovaries were carefully inspected for the presence or absence of an ovulation ostium. The percentage of ostii that was observed in fertile women (91%) was similar to that observed in women with mild endometriosis (85%). However, in women with moderate and severe endometriosis, significantly less ostii were noted, respectively 72 and 51%. It is therefore argued that the absence of an ovulation ostium (so-called luteinized unrupted follicle syndrome, LUF) is more frequent in women with moderate and severe endometriosis and may contribute to infertility in this group of women.     

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.     

Peritoneal fluid prostaglandins in various stages of the menstrual cycle: role in infertile patients with endometriosis

Thirty-nine patients with pelvic endometriosis and 45 patients with no evidence of endometriosis were entered in this study. The mean age was 29 years for each group. The volume of peritoneal fluid showed an increase towards the end of the cycle in both groups. Although the volume was higher in the endometriosis group than the control group, the difference between them was not significant. The concentration of prostaglandins F2 alpha and E2 was higher in patients with endometriosis than in the control group. The difference was significant (P less than 0.05) during days 9-16 and 17-24 for both prostaglandins, and during days 1-8 for prostaglandin F 2 alpha only. The high concentration of prostaglandins in the periovulatory and early luteal phases of the cycle may have adverse effects on tubo-ovarian function in endometriosis patients. Prostaglandin studies in peritoneal fluid are of significance during days 9-24 of the cycle when the effect of regurgitated menstrual fluid in the early phase of days 1-8 may be avoided.     

白细胞介素1α、β及γ干扰素mRNA在子宫内膜异位症患者异位和在位子宫内膜巨噬细胞中的表达

目的探讨白细胞介素(IL)1α、β mRNA和γ干扰素(IFN-γ)mRNA在子宫内膜异位症(内异症)患者异位和在位内膜巨噬细胞中的表达变化及意义.方法采用原位杂交技术检测40例内异症患者(内异症组)异位和在位内膜(增生期18例,分泌期22例)和15例子宫肌瘤患者(对照组)的内膜(增生期8例,分泌期7例)巨噬细胞中IL-1α、β和IFN-γmRNA表达水平.结果(1)内异症组患者异位、在位内膜及对照组内膜巨噬细胞中IL-1α mRNA阳性表达率分别为70%(28/40)、38%(15/40)和20%(3/15),表达水平分别为3.12±0.32、2.65±0.34、1.32±0.23;IL-1βmRNA阳性表达率分别为75%(30/40)、40%(16/40)和20%(3/15),表达水平分别为3.45±0.43、2.74±0.39、1.45±0.18;内异症组IL-1α、β mRNA的表达水平较对照组明显升高,内异症组异位内膜较在位内膜的表达水平也明显升高,差异均有统计学意义(P＜0.05).(2)内异症组在位内膜和对照组内膜巨噬细胞中IL-1α、β mRNA表达分泌期高于增生期,差异也有统计学意义(P＜0.05).(3)内异症组内膜巨噬细胞中IFN-γmRNA的表达水平与对照组比较,差异无统计学意义(P＞0.05),且无周期性变化.结论内异症患者在位内膜和异位内膜巨噬细胞IL-1表达明显增强,而IFN-γ表达则无明显变化,推测内膜巨噬细胞及其分泌的细胞因子,可能参与了内异症的发生、发展过程.     

Effect of an in vitro fertilization program on serum CA 125, tumor-associated trypsin inhibitor, free beta-subunit of human chorionic gonadotropin, and common alpha-subunit of glycoprotein hormones

OBJECTIVE: To investigate the impact of an IVF program on serum levels of tumor markers CA 125, tumor-associated trypsin inhibitor, free hCG beta-subunit, and free glycoprotein hormone alpha-subunit. DESIGN: A prospective controlled clinical study. SETTING: Outpatient university infertility clinic. PATIENT(S): Seventy-one infertile patients (with tubal occlusion, pelvic endometriosis, or unexplained infertility) undergoing IVF and nine control women with regular menstrual cycles. INTERVENTION(S): Serial blood sampling before, during, and after IVF, or during one ovulatory menstrual cycle in the controls. MAIN OUTCOME MEASURE(S): Serum levels of CA 125, tumor-associated trypsin inhibitor, hCG-beta, and glycoprotein hormone-alpha. RESULT(S): Before IVF, all tumor markers were within the normal range except for CA 125, which was elevated in patients with endometriosis. IVF led to significant increases in CA 125 and glycoprotein hormone-alpha that differed from the changes seen during normal menstrual cycles. The luteal phase increase in CA 125 correlated with levels of E(2) and P and the number of follicles. Two months after IVF, levels of CA 125 were 12% higher than levels before treatment. Tumor-associated trypsin inhibitor and hCG-beta revealed no cyclicity. CONCLUSION(S): An IVF regimen increased the release of CA 125 and glycoprotein hormone-alpha. The CA 125 elevation after IVF implies a persistent effect of ovarian hyperstimulation on CA 125 release.     

Eicosanoids in primary dysmenorrhea, endometriosis and menstrual migraine

This paper summarizes what has been learned over the years about the role of eicosanoids in the pathogenesis of primary dysmenorrhea, endometriosis and menstrual migraine. The role of prostaglandins (PGs) in the pathogenesis of primary dysmenorrhea is inferred from four main observations: firstly, the clinical symptoms of primary dysmenorrhea are similar to those induced by the administration of PGF2 alpha and PGE2 for the induction of labour; secondly, the increased production of PGs by the endometrium during the luteal and menstrual phases of ovulatory cycles is consistent with the occurrence of primary dysmenorrhea mainly in ovulatory cycles; thirdly, the concentrations of PGF2 alpha and PGE2 in the endometrium and menstrual fluid of dysmenorrheic women are significantly higher than in controls; fourthly, certain PG inhibitors have been proved to be effective in the treatment of dysmenorrhea. The change in PG production can explain the major symptoms of primary dysmenorrhea, including the increased uterine contractility, uterine ischemia and the lowering of the pain threshold to chemical and physical stimuli in the pelvic nerve terminals. Moreover, recent experimental data suggest that leukotrienes (LTs) might be among the alternative pathogenetic causes of primary dysmenorrhea. The data which support a relationship between eicosanoids and endometriosis are as follows: endometriotic tissue produces PGs; the peritoneal fluid concentration of PGF2 alpha increases significantly after the induction of endometriosis in laboratory animals; the concentration of PGs in peritoneal fluid of some patients with endometriosis is greater than in controls and, finally, the number and activation of pelvic macrophages which are able to synthesize eicosanoids increase in patients with endometriosis. Possible roles for eicosanoids in the pathogenesis of infertility and secondary dysmenorrhea induced by endometriosis have been suggested. Eicosanoids are probably also involved in the pathogenesis of menstrual migraine. Different types of PGs might play a role both in the initial vasoconstriction during the prodromal phase of migraine and in the vasodilation and sensitization to pain typical of the pain phase.     

Peritoneal fluid fractions from patients with endometriosis do not promote two-cell mouse embryo growth

Peritoneal fluid (PF) from 10 infertile patients with endometriosis, obtained during the follicular phase of the cycle during laparoscopy, did not promote two-cell mouse embryo growth to the extent observed by fluid obtained from seven normal controls. Five molecular weight (MW) fractions were obtained by ultrafiltration, and each was used as media supplement in the assay and compared with PF fractions from normal controls. All fractions of PF from patients with endometriosis inhibited mouse embryo growth to a greater extent than did normal controls. However, the MW fractions greater than 100,000 daltons showed greater inhibition of embryo development than did fractions less than 100,000 daltons. This study of cell-free PF suggests the presence of a humoral factor greater than 100,000 daltons that is inhibitory on mouse embryo growth.