Is the measurement of placental protein-14 and CA-125 in plasma and uterine flushings useful in the evaluation of peri-menopausal and post-menopausal bleeding?

In this prospective study, we examined the possible diagnosticvalue of the measurement of two endometrial proteins, placentalprotein-14 (PP14) and CA-125, in the evaluation of pre- andpost-menopausal bleeding. Concentrations of these two proteinswere measured in plasma and uterine flushings obtained from139 pre- and post-menopausal women with bleeding problems, and26 normal post-menopausal control women without bleeding. Endometrialbiopsy samples were also obtained for histological study. Concentrationsof PP14 in both the plasma and uterine flushings in post-menopausalwomen were significantly lower (P < 0.001) than those ofcontrol pre-menopausal women. In post-menopausal women, theconcentrations of PP14 (mean ± SEM) in both plasma andflushing were significantly higher (P < 0.001) in women withendometrial adenocarcinoma (46.9 ± 7.5 ng/ml plasma;3350 ± 1711 ng/ml flushing) than in the controls (7.6± 1.3 ng/ml plasma; 125 ± 27 ng/ml flushing) orin women with post-menopausal bleeding and atrophic endometrium(20.4 ± 2.1 ng/ml plasma; 453 ± 167 ng/ml flushing).In contrast CA-125 concentrations in plasma and flushings weresimilar in post-menopausal and pre-menopausal women. Plasmaconcentrations of CA-125 were higher in post-menopausal womenwith adenocarcinoma (29.1 ± 7.4 IU/ml) than in thosewith post-menopausal bleeding and atrophic endometrium (21.8± 2 IU/ml) (P < 0.05) or control post-menopausal subjects(16.1 ± 2.1 IU/ml) (P < 0.01). CA-125 concentrationsin uterine flushings were not significantly different in anygroup of post-menopausal women. The results show that concentrationsof PP14 are correlated more strongly to endometrial histopathologythan those of CA-125 in pre- and post-menopausal women. ElevatedPP14 concentrations are also associated with the presence ofendometrial adenocarcinoma and may have a potential to be usedas a marker for this disease.     

Implantation: The correlation of placental protein 14 concentrations in uterine flushing and endometrial morphology in the peri-implantation period

The relationship between the concentrations of placental protein14 (PP14) in uterine flushing and the endometrial morphologyin the mid-luteal phase was assessed in a prospectively designedstudy involving the precise timing of all samples by the luteinizinghormone (LH) surge. A total of 29 regularly cycling women withunexplained infertility or recurrent miscarriage were studied.To flush the uterine cavity, 10 ml of physiological saline solutionwas used immediately prior to sampling of an endometrial specimenfor morphological study, in the mid-luteal phase. PP14 concentrationswere measured by radioimmunoassay in uterine flushings and plasmasamples; the endometrium was assessed by the use of histologicaldating criteria and morphometric techniques. PP14 levels inuterine flushings were correlated with endometrial dating andvolume fraction measurement of the glands. They were consistentlybelow the sensitivity of the assay with histological datingof < day LH +5, or when the glandular lumen occupied <20%of the gland. In contrast, PP14 concentrations in plasma werenot related to histological dating or morphometric analyses,and did not differ in patients with normal endometrial development(20.8 ng/ml) and in those with retarded endometrial development(22.5 ng/ml). The presence of detectable concentrations of PP14in uterine flushing was significantly associated with normalhistological dating. Uterine flushing may therefore providea reliable, non-invasive alternative to endometrial biopsy inthe evaluation of endometrial function in the peri-implantationperiod.     

The measurement of CA 125 and placental protein 14 in uterine flushings in women with recurrent miscarriage; relation to endometrial morphology

The concentrations of CA 125 and placental protein 14 (PP14)were measured in uterine flushings obtained throughout the lutealphase of the cycle from eight normal fertile women. The concentrationsof both proteins increased in a similar pattern throughout theluteal phase of the cycle, with the most dramatic increase occurring6 days after their luteinizing hormone surge (day LH +6). However,a greater variation in CA 125 concentrations was seen comparedto that seen for PP14. The concentrations were compared to thoseobtained on day LH + 7 of the cycle from a group (n equals;35) of women with recurrent miscarriage. The ranges in concentrationof PP14 and CA 125 in the flushings of fertile and recurrentmiscarriage patients were very similar. However, a greater proportionof women with recurrent miscarriage (55%) had low concentrations(<5 ng/ml) of PP14 than in the control group (12.5%) andthe concentrations of PP14 in the uterine flushings were significantlyless (P < 0.05) in women with recurrent miscarriage comparedto the normal fertile group. There was no significant differencein the concentrationof CA 125 in the uterine flushings betweenthe two groups. Histological observation of the endometrialbiopsy samples from recurrent miscarriage patients gave menstrualcycle datings that ranged from day LH +2.5 to LH +6.5 with retardedendometrium (;day LH +5) in 12 of 35 (34%) patients. Of these12 patients, 10 (83%) had low PP14 concentrations and six (50%)had low CA 125 concentrations in their uterine flushings. Inthe recurrent miscarriage patients with histologically normal(sequals; day LH +5) endometrial development, 10 out of 23 (43%)also had low PP14 concentrations and 8 out of 23 (35%) had lowCA 125 in their uterine flushings. The results suggest thatPP14 is better than CA 125 as a marker for endometrial functionin this group of women. In some cases (52%) the low concentrationsof PP14 in the uterine flushings couldbe explained by retardedendometrial development but for the others the reduction inPP14 concentration in the uterine flushing was not associatedwith retardation of endometrial development.     

Concentrations of endometrial protein PP 14 and CA-125 in uterine flushings performed in natural and stimulated cycles

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be attributed to abnormal endometrial development. This study compared concentrations of endometrial proteins in uterine flushings of infertile patients between natural and stimulated cycles. METHODS: Patients received a standard regimen of ovarian stimulation. Seven days after the LH surge in natural cycles or the hCG injection in stimulated cycles, uterine flushings were performed by slowly injecting and aspirating normal saline through a paediatric Foley catheter. Natural cycles were considered as group A whereas stimulated cycles with serum E(2) <20 000 pmol/l and serum E(2) >20 000 pmol/l were classified as groups B and C respectively. PP 14 and CA-125 in uterine flushings were measured and expressed per total protein content. RESULTS: Concentrations of the total protein, PP 14 and CA-125 in the uterine flushings were similar among the three groups. PP 14 per total protein in the uterine flushings was significantly correlated with serum E(2) on the day of hCG (r = 0.459; P = 0.009) in natural cycles only but not in stimulated cycles. CONCLUSION: There was no significant difference between natural and stimulated cycles in concentrations of PP 14 and CA-125 in uterine flushings performed in the mid-luteal phase.     

Endometrial protein PP14 and CA-125 in recurrent miscarriage patients; correlation with pregnancy outcome

The concentrations of endometrial proteins PP14 and CA-125 were measured in uterine flushings taken on days LH+10 and LH+12 (10 and 12 days after luteinizing hormone surge) of the menstrual cycle from 15 normal, fertile women and 49 women who suffered recurrent miscarriage. The concentration of PP14 was significantly lower in the flushings from the recurrent miscarriage patients than in those from fertile controls on both day LH+10 (median: 1300, range: 3-10 300 ng/ml versus median: 13 933, range: 2174-40 404 ng/ml; P < 0.01) and LH+12 (median: 1560, range: 820-12 100 ng/ml versus median: 14 047, range 1402-62 108 ng/ml; P < 0.05). Similarly concentrations of CA-125 were significantly lower in flushings from recurrent miscarriage women compared to controls on both day LH + 10 (median: 1555, range: 47-6710 U/ml versus median: 6385.5, range 2884-27 731 U/ml, P < 0.01) and LH+12 (median: 2892, range: 956-9974 U/ml versus median: 7127.5, range: 1591-21 343 U/ml; P < 0.05). In contrast there was no significant difference in the concentration of PP14 in plasma samples taken on the same days as the flushings from recurrent miscarriage patients and fertile controls. The concentrations of PP14 in uterine flushings obtained on day LH + 10 or LH + 12 from recurrent miscarriage women during a pre-pregnancy investigative cycle were significantly lower (P < 0.05) in patients who went on to miscarry (median: 1000, range: 9-2900 ng/ml) than those who went on to have a live birth (median: 1440, range: 4-12 100 ng/ml) during a subsequent pregnancy. In contrast there was no significant difference in uterine CA-125 or plasma PP14 concentrations between these two groups of recurrent miscarriage patients. The results suggest that measurements of uterine PP14 and CA-125 may be useful in the assessment of endometrial development in recurrent miscarriage patients and suggest the importance of PP14 in preparing the endometrium for embryo implantation. In addition pre-pregnancy uterine PP14 measurements may be useful in predicting subsequent pregnancy outcome.      

Non-surgical flushing of the uterus for pre-embryo recovery: possible clinical applications

Growing interest in preimplantation genetic diagnosis has indicated uterine flushing as one method for obtaining human preimplantation embryos. To date, our institution has performed non-surgical uterine flushing to donate the recovered embryos to infertile recipients. We performed 127 flushings in 127 cycles using a modified urinary bladder catheter. Using the donors' natural cycles, a single ovum was recuperated in 37 out of 88 flushings. In 17 flushings, clomiphene citrate was given to the donors and 14 ova were found in nine positive recoveries. Human menopausal gonadotrophins were administered to the donors in 22 flushings and 22 ova were located in 14 positive recoveries. In total, 22 blastocysts, 11 morulae and 13 pre-embryos at the 2- to 16-cell stages were found. When transferred, these embryos gave rise to 18 clinical pregnancies in the recipients (40.9% of the transfers; 14.1% of the flushings). In comparison with natural cycles, superovulation of donors did not significantly increase the recipients' pregnancy rate. At present, non-surgical recovery of uterine pre-embryos does not seem to carry much potential as a tool for infertility treatment, or for genetic diagnosis. This is because currently available alternative methods are more successful.     

Relationships between the uterine environment and maternal plasma concentrations of insulin-like growth factor binding protein-1 and placental protein 14 inearly pregnancy

Blood was obtained from 218 women between 6 and 13 weeks ofgestation. Measurements of serum insulin-like growth factorbinding protein-1 (IGFBP-1) and placental protein 14 (PP14)concentrations were compared withmaternal weight and height,maternal smoking habit, indices of maternal haematological statusand two placental hormones [human chorionic gonadotrophin (HCG)and human placental lactogen (HPL)]. IGFBP-1 concentration wasnegatively correlated with maternal weight (P < 0.001) andbody mass index (P <0.001); PP14 concentration was not correlatedwith these measurements. PP14 concentration was negatively correlatedwith maternal haemoglobin concentration (P equals; 0.010), meancorpuscular volume (P equals; 0.003) and serum ferritin concentration(P equals; 0.016). The concentrations of PP14 were significantlyless among smokers (P < 0.001); IGFBP-1 concentrations wereuninfluenced by smoking. IGFBP-1 concentration was positivelycorrelated with maternal serum HCG (P equals; 0.003) and maternalserum HPL (P equals; 0.002). PP14 concentration was positivelycorrelated with maternal serum HCG (P < 0.0001) but not withHPL. These findings demonstrate that the maternal environmenthas an early influence on both endometrial and placental function.     

A prospective randomized controlled study comparing two doses of gestodene in cyclic combined HRT preparations on endometrial physiology

Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.     

The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture

The concentration of leukaemia inhibitory factor (LIF) was measured in uterine flushings obtained from normal fertile women, from women with unexplained infertility and from women who suffered recurrent miscarriage. In normal fertile women, LIF was not detected in flushings obtained on days luteinizing hormone (LH)+0 to LH+6 of the cycle, but concentrations gradually increased from day LH+7 to a maximum at day LH+12. The amount of LIF in flushings obtained from women with unexplained infertility was significantly lower than in those from normal fertile women on day LH+10 (P < 0.05). The production of LIF by cultured human epithelial and stromal cells was also investigated. LIF was not detectable in the supernatants of cultured stromal cells. Basal LIF production by epithelial cells varied according to the stage in the cycle at which the biopsy was taken. Significantly more LIF was produced by epithelial cells from late proliferative and early secretory endometrium compared with amounts produced by cells from early proliferative (P < 0.001) and late secretory (P < 0.01) endometrium. High doses of progesterone and oestradiol caused a small decrease in epithelial cell LIF production: the combined effect of progesterone and oestradiol (P < 0.01) was greater than the effect of either steroid alone (P < 0.05). The results show, for the first time, the capability of human endometrium to produce LIF in vivo. The fact that maximum LIF concentrations are present at implantation and that decreased concentrations occur in women with unexplained infertility suggest the importance of this cytokine in embryo implantation.      

The Presence of the Fifth Component of Complement (C5) in Rabbit Uterine Flushings in Relation to Reproductive State

The fifth component of complement (C5) has been detected in rabbit uterine flushings. The C5 activity was evaluated using a hemolytic assay which requires the use of a C5-depleted reagent (C5D) prepared by affinity chromatography of normal human serum. In the absence of C5D, there was no hemolysis of antibody-sensitized erythrocytes by rabbit uterine flushings, whereas the presence of the C5D reagent resulted in substantial hemolysis. The amount of hemolysis was correlated with the reproductive state of the rabbits, with higher amounts of hemolysis (expressed per mg uterine flushing protein) evident in estrous rabbits. In addition, the amounts of immunoglobulin G (IgG), albumin, and total protein were also determined in the uterine flushings. The amounts of total protein and IgG were increased in day-6 pregnant animals compared to estrus while the amount of albumin per ml uterine flushing was not significantly changed.     

Glycodelin levels in uterine flushings and in plasma of patients with leiomyomas and polyps: implications for implantation

BACKGROUND: Glycodelin, a glycoprotein, is present in both blood plasma and uterine flushings. It has been implicated in the process of implantation and angiogenesis. During the secretory phase, progesterone secretion is related to glycodelin production. METHODS AND RESULTS: We obtained uterine flushings, prospectively, from 47 infertile patients during the proliferative phase. Patients were recruited from our university practice. Transvaginal ultrasound and sonohysterography permitted the stratification of patients into control, leiomyoma or polyp groups. Total plasma and uterine flushing glycodelin was measured with enzyme-linked immunosorbent assay. Blood was also analysed for progesterone. Uterine flushing glycodelin levels were significantly increased in patients with polyps when compared with controls. An increase in uterine flushing glycodelin levels was noted in patients with leiomyomas compared with controls, though not statistically significant. Plasma glycodelin levels were significantly increased in patients with leiomyomas and polyps when separately compared with controls. There was a significant relationship between plasma glycodelin production and progesterone levels in patients with polyps. CONCLUSIONS: Leiomyomas and polyps are growing tumours and thus produce significant plasma glycodelin levels. Uterine glycodelin flushings are elevated in patients with both polyps and leiomyomas. Elevated glycodelin levels in the follicular and peri-ovulatory period may impair fertilization and implantation.     

Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis

BACKGROUND: Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. METHODS: Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. RESULTS: No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. CONCLUSIONS: There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.     

In-vitro synthesis of total protein and placental protein PP14 by the Fallopian tube mucosa: variation in relation to anatomical site, the ovarian cycle and the menopause

De-novo synthesis and secretion of protein by short term explantsof mucosa from each anatomical section of the Fallopian tubeand endometrium of pre-menopausal (n = 25) and tubal mucosaof post-menopausal (n = 5) women were studied by demonstrationof incorporation of radiolabelled L-[³⁵S]methionine and one-dimensionalSDS — polyacrylamide gel electrophoresis. A consistentfinding in 25 pre-menopausal women was the presence of a 25kDa protein band synthesized by tissue obtained throughout theovarian cycle. Western blotting demonstrated that this proteinband contained placental protein 14 (PP14)-like immunoreactivityin the proliferative (n = 2) and luteal phase (n = 2) of theovarian cycle. To determine if there is quantitative variationin total protein and PP14 synthesis and secretion during theovarian cycle, the total quantities of protein and PP14 synthesizedwere determined by Coomassie Brilliant Blue staining and radioimmunoassayrespectively. Analysis of the results of total protein assayrevealed statistically significant differences in relation tothe anatomical origin of the study tissue (P < 0.01), thestage of the ovarian cycle (P < 0.04) and the manner in whicheach anatomical site varied during the ovarian cycle (P <0.01), the endometrium being significantly different from theFallopian tube. When the data for PP14 synthesized by the Fallopiantube mucosa were analysed, these effects were not seen. PP14was not detected in the culture media of Fallopian tube mucosaobtained from post-menopausal women.     

The impact of leukemia inhibitory factor in uterine flushing on the reproductive potential of infertile women--a prospective study

PROBLEM: To determine the value of leukemia inhibitory factor (LIF) assessment for predicting the reproductive outcome. METHOD OF STUDY: Two phase study. Phase I: assessment of LIF in uterine flushing. Phase II: 1,5 years after examining the last patient, a questionnaire was sent to all participants of the phase I. Phase I: Uterine flushing and endometrial samples were collected during implantation window from infertile patients with stage I/II endometriosis (n = 14), patients with idiopathic infertility (n = 27), luteal phase deficiency (n = 13), and fertile control (n = 21). LIF was assessed in uterine flushings in all patients by ELISA. In endometrium, semiquantitative RT-PCR was performed for LIF mRNA expression. Phase II: questionnaire has been sent to all infertile women taking part in the first phase of the experiment, regarding their reproductive outcome. RESULTS: 65.4% patients who had returned the questionnaire did get pregnant. LIF concentration at a cut-off point of 2.31 pg/ml had a 95.7% sensitivity and 81.8% specificity in predicting the reproductive outcome. CONCLUSION: This prospective study for the first time in literature indicates that the LIF assessment can be used as a predictor of reproductive success.     

Secretory endometrial protein PP14 in women with early pregnancy bleeding.

The decidualized endometrium produces secretory proteins of which secretory endometrial protein PP14 is the major product during the first trimester of pregnancy. The protein is secreted into the uterine lumen as well as into the peripheral blood. The purpose of this study was to examine whether decidual function, evaluated by the serum concentration of PP14, was different in women with early pregnancy bleeding compared to normal pregnant women. A reference range for serum PP14 was established on the basis of single samples from 236 normal pregnant women with ultrasonically confirmed gestational age. All the women were delivered of a normal child at term. The study comprised 128 pregnant women admitted because of vaginal bleeding between 6 and 18 weeks gestation. At ultrasonography, intrauterine fetal heart activity was either present or was confirmed at a subsequent examination. No difference was found in the serum level of PP14 compared to that in normal pregnancies, but women with vaginal bleeding and depressed PP14 levels appeared to have a 5-fold higher risk of preterm delivery than women with bleeding and normal PP14 levels.     

A biochemical test for the direct assessment of endometrial function: measurement of the major secretory endometrial protein PP14 in serum during menstruation in relation to ovulation and luteal function

Circulating PP14 was measured by radioimmunoassay in ovulating (n = 12) and anovulatory (n = 3) women throughout the menstrual cycle, the highest levels of serum PP14 being seen during menstruation and in the late luteal phase in ovulating women. Mean serum PP14 levels on days 1-7 and 24-28 of the menstrual cycle were significantly higher than those observed from days 8 to 23 (P less than 0.0005 and P = 0.005 respectively). There was no difference in mean PP14 levels observed in the menstrual and luteal phase. By contrast, serum PP14 was rarely detected in anovulatory cycles. During the luteal phase, mean serum PP14 levels were apparently not related to serum progesterone levels. However, mean PP14 levels during the menstrual phase were significantly higher in the group of women with the highest progesterone production (Pmax greater than 39 nmol/l) (P less than 0.002) in comparison with levels seen in ovulating women with lower progesterone production (Pmax less than 32 nmol/l). These findings suggest that the synthesis and secretion of PP14 is influenced by ovulation and luteal function. Serum PP14 measurements may provide useful information about the endometrium in relation to fertility, and that these measurements during the menstrual cycle may distinguish between ovulatory and anovulatory cycles.     

Elevated Amniotic Fluid Interleukin-6 Levels During the Early Second Trimester Are Associated With Greater Risk of Subsequent Preterm Delivery

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14–20 weeks in a group of women subsequently delivering at ≤ 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15–20 weeks and gestational age at delivery (r = ?0.16, P = 0.03). Women delivering at ≤ 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at ≥ 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at ≤ 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15–20 weeks can identify patients at risk for PTD at ≤ 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester. CAPSULE: Midtrimester amniotic fluid IL-6 concentrations are significantly higher in women subsequently delivering preterm at ≤34 weeks compared with those delivering at term.     

Placental protein 14 in cycles with normal and retarded endometrial differentiation

The purpose of this study was to investigate whether endometriumwith retarded development differs, functionally, from endometriumwith normal ’in-phase‘ development. Precisely timedendometrial biopsies were obtained from 24 women suffering fromunexplained infertility at 4, 7, 10 and 13 days following theluteinizing hormone(LH)surge. Frozen sections were labelledwith an anti-placental protein(pp)14 monoclonal antibody usingan avidin-biotin peroxidase technique and semi-quantificationof endometrial PP14 was performed using one-and two wat analysisof variance. Normal and retarded endometrium were identifiedin 16(group 1) and eight (group II)women respectively. Bothgroups demonstrated a significant increase of the area of precipitatemeasured for PP14 form day LH +13. However, two-way analysisof variance showed that endometrial PP14 was significantly(P< 0.05)lower in the retarded endometrium group at LH+10 andLH+13. Serum PP14 was also significantly lower(P< 0.01) inwomen withretarded endometrial development had significantlyhigher (P< 0.05)concentration of cumulative saliva progesteronefrom LH +3 to LH +5. This study indicates that there are functionaldifferences between normal and retarded endometrium. These differencesmay adversely affect uterine receptivity during implantationand the early placentation stage     

Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization

The objective of this study was to determine the predictive value of the number of follicles seen by transvaginal ultrasound before gonadotrophin stimulation on the ovarian responsiveness of 166 infertile women undergoing in-vitro fertilization (IVF) treatment. The main variables were patient age, ovarian volume and number of ovarian follicles measuring 2-5 mm on transvaginal ultrasound before gonadotrophin stimulation. Based on the sum of ovarian follicles in both ovaries the patients were divided into three groups of inactive (<5 follicles), normal (5-15 follicles) or polycystic (PCO)-like ovaries (>15 follicles). The main outcome measure was the number of recovered oocytes. The number of follicles was correlated more strongly with the number of recovered oocytes (r2 = 0.131; P = 0.0001) than age alone (r2 = -0.053; P = 0.005). Fewer oocytes were recovered from patients with inactive ovaries (5.4 +/- 2.5; P = 0.006) than with normal (7.5 +/- 4.5) or PCO-like ovaries (10.5 +/- 5.1). Ovarian volume was correlated with the number of follicles before stimulation (P = 0.0001), but not with the number of oocytes. The number of small follicles present before ovarian stimulation was a better predictor of the outcome than ovarian volume or age alone. Patients can be identified with inactive ovaries which will have a poor response to IVF treatment, a key factor for counselling couples and optimizing resources.      

The post-menopausal uterus: the effect of hormone replacement therapy on the serum levels of secretory endometrial protein PP14/{beta}-lactoglobulin homologue

The effect of cyclical oestrogen-progestogen replacement onthe levels of endometrial secretory protein PP14 (placentalprotein 14) was studied in 39 post-menopausal women, l3 of whomhad had a hysterectomy. In those women with an intact uterus,the average rise of the late hteal phase serum PP14 concentrationwas from 29 to 45 µg/l, a 55% rise (P < 0.001). Onlya slight rise (from 27 to 30 µg/l) was observed in hysterectomizedwomen. Cyclical replacement with oestrogen and levonorgestrelcaused a greater rise in serum PP14 level than did replacementwith the same dose of oestrogen plus medroxyprogesterone acetate(P < 0.05). Because PP14 is found also in the serum of hysterectomizedpost-menopausal women, the uterus cannot be the only sourceof circulating PP14. But, the difference between hysterectomizedand non-hysterectomized women indicates that the quiescent post-menopausaluterus responds to oestrogen—progestogen replacement byincreased PP14 secretion, which can be detected and quantifiedby a blood test. The measurement of PP14 in serum may also becomeuseful for kdng the effect of various progestogens.