A clinical comparison of two triphasic oral contraceptives with levonorgestrel or norethindrone: a prospective, randomized, single-blind study

Menstrual bleeding patterns were investigated in young women taking either a levonorgestrel triphasic, Triquilar, or a norethindrone triphasic, Ortho 7/7/7, two commonly prescribed low-dose oral contraceptives. The levonorgestrel triphasic contains ethinyl estradiol (EE) 30 micrograms + levonorgestrel (LNG) 50 micrograms for the first six days, EE 40 micrograms + LNG 75 micrograms for the following five days, and EE 30 micrograms + LNG 125 micrograms for the last ten days. The norethindrone triphasic contains EE 35 micrograms + norethindrone (NET) 0.5 mg for the first seven days, EE 35 micrograms + NET 0.75 mg for the following seven days and EE 35 micrograms + NET 1.0 mg for the last seven days. Three hundred women from 16 to 25 years of age were randomized to the levonorgestrel triphasic (n = 150) or the norethindrone triphasic (n = 150) groups. Assessments were made from daily diary cards and from bimonthly investigator interviews over 6 pill cycles. The results showed a higher incidence of intermenstrual bleeding (breakthrough bleeding and/or spotting) in the norethindrone triphasic group (NET group) than in the levonorgestrel triphasic group (LNG group): 44.9% of patients (66/147) randomized to the LNG group reported intermenstrual bleeding one or more times during the study compared with 61.9% (91/147) randomized to the NET group (p = 0.0036). Furthermore, in subjects who did not miss any pills, the proportion of patients with intermenstrual bleeding in each cycle was significantly greater (p < 0.02, cycles 1-4, 6; p > 0.05, cycle 5) and was experienced for more days per cycle (p < 0.05, cycle 1) and for more cycles per patient (p < 0.05, 5 cycles) in the NET group compared with the LNG group. Intermenstrual bleeding was also less frequently observed in the LNG group than in the NET group in patients who missed pills (p < 0.05, cycles 3, 5 and 6). In addition, early withdrawal bleeding occurred more often in the NET group than in the LNG group (p < 0.05, cycles 1, 3 and 4). The incidence of amenorrhea was similar in both groups. These results demonstrate a significantly lower incidence of intermenstrual bleeding and therefore better cycle control with the levonorgestrel triphasic Triquilar, compared with the norethindrone triphasic Ortho 7/7/7.     

Correlation between endometrial dating of luteal phase days 6 and 10 of the same menstrual cycle

CONTEXT: Endometrial maturation, important in the diagnosis of infertile couples, has been evaluated since 1950 using the Noyes criteria. Nevertheless, there is no consensus regarding the most suitable period of the luteal phase for performing the biopsy. OBJECTIVE: This study evaluated the correlation between the histological dating of two endometrial biopsies performed in the same menstrual cycle, on luteal phase days six and ten. DESIGN: Prospective study. SETTING: Human Reproduction Division of the Federal University of S?o Paulo, referral center. PATIENTS: Twenty-five women complaining of infertility had their menstrual cycles monitored by ultrasound and LH plasma levels, to obtain evidence of ovulation. PROCEDURES: Endometrial biopsies were performed on luteal phase days LH + 6 and LH + 10 (luteal phase day 1 = LH + 1 = the day that follows LH peak). Dating was done according to morphometric criteria, in which an endometrium sample is considered out of phase if the minimum maturation delay is one day. On day LH + 6, blood was drawn for plasma progesterone level determination. RESULTS: All patients had an ovulatory cycle (mean LH peak: 47.4 U/L; mean follicular diameter on LH peak day: 18.9 mm; mean endometrial thickness on LH peak day: 10.3 mm; mean plasma progesterone level on day LH + 6: 14.4 ng/ml). 14 patients had both biopsies in phase; 5 patients had out of phase biopsies only on day LH + 6; 3 had out of phase biopsies only on day LH + 10 and 3 patients had out of phase biopsies on both days. McNemar's test showed no statistical difference between these data (p > 33.36%). CONCLUSIONS: The correlation found between the endometrial datings suggests that biopsies performed on either of these two days are suitable for evaluation of endometrial maturation.     

Epstein-Barr virus and AIDS-related primary central nervous system lymphoma. Viral detection by immunohistochemistry, RNA in situ hybridization, and polymerase chain reaction

The efficacy of a low dose of mifepristone, 5 mg/day for the first 15 days of the menstrual cycle, followed by medroxy-progesterone acetate (MPA), 10 mg/day for the next 13 days, for inhibiting ovulation was assessed in ten volunteers who were treated for three successive cycles. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 21-24 of the third treatment cycle were used to monitor the cycles. Ovulation was confirmed in 11 of the 30 treated cycles and, in these 11, the LH peak and follicular rupture occurred during MPA treatment periods. Out of 19 anovulatory cycles, 16 had no increase in progesterone levels and another 3 developed a luteinized unruptured follicle. Progestin administration induced secretory changes in the endometrium, but irregular or delayed development was found. Regular withdrawal bleeding occurred in all subjects. These data indicate that the sequential regimen can suppress ovulation while maintaining regular bleeding but increased efficacy is needed for phase II clinical trials.     

Positron emission tomography in the detection and management of metastatic melanoma

OBJECTIVE: In women who use oral contraceptives with low estrogen doses, a quiescent endometrium is frequently produced. Further reduction of the estrogen dose would not be expected to alter this effect. In this open-label study, the effects on the endometrium of a monophasic oral contraceptive containing 75 micrograms gestodene and 20 micrograms ethinylestradiol were assessed. METHOD: Biopsies were performed on 25 women on therapy. The biopsies were performed during the late luteal phase (last 7 days) in the pretreatment cycle and during days 15-21 in cycle 6 for 13 subjects (Group A) and during days 15-21 in cycle 3 and during the late luteal phase (last 7 days) in the post-treatment cycle for 12 subjects (Group B). RESULTS: All subjects completed six cycles of treatment. Nine of 13 subjects pretreatment and nine of 12 subjects at cycle 3 were characterized by the pathologist as having a secretory endometrium. Four of 13 subjects at cycle 6 and ten of 11 subjects post-treatment also demonstrated a secretory endometrium. Pre-decidual changes were seen in one, two, two and zero subjects at pretreatment, after three cycles, six cycles, and post-treatment, respectively. Six subjects had an atrophic endometrium at cycle 6. CONCLUSIONS: With monophasic gestodene/ethinylestradiol 75 micrograms/20 micrograms, a secretory or inactive endometrium was present in most subjects. Thus, the effects on the endometrium of this oral contraceptive containing a reduced estrogen dose are consistent with those produced by other low-estrogen-dose combination oral contraceptives.     

Endometrial responses to hormone replacement therapy: histological features compared with those of late luteal phase endometrium

We evaluated the histological features of the endometrium in relation to the bleeding pattern in a group of women receiving oral cyclical combined hormone replacement therapy (HRT), and compared the histological features with those of luteinizing hormone (LH)-dated endometrial biopsies obtained from healthy women at the time of sterilization. A total of 103 women completed 6 months of HRT therapy. All received a regimen of 2 mg oestradiol valerate daily, with 1 mg norethisterone added for the last 12 days of every 28-day cycle. Endometrial biopsies were scheduled for the end of the study (days 27-29 of the last cycle of therapy). Using the classical histological criteria, secretory endometrial changes were demonstrated in the majority (n = 89) of cases. The remaining were insufficient or inactive (n = 12), proliferative (n = 1) or atrophic (n = 1). Forty-nine women had a mean cycle length of less than 29 days (early bleeders), 50 women experienced cycles of more than 29 days (late bleeders) and four did not experience any bleeding. When the individual histological structures were examined, using image analysis, there were no statistically significant differences in the histological features when the long cycles in early bleeders were compared with those in late bleeders. LH-dated endometrium showed a high degree of homogeneity that was consistent with cycle day as described by the classic criteria, but HRT-treated endometrium exhibited a wide range of variability. HRT-treated endometrium from the subset of women who bled on or after day 29, and whose biopsies were obtained before the onset of bleeding, differed significantly from the endometrium taken at the corresponding phase of the physiological cycle. We conclude that the use of classical histological criteria, which are used in relation to the physiological cycle, in the study of HRT-treated endometria is inappropriate.     

Endometrial thickness is predictive of histologic endometrial maturation in women undergoing hormone replacement for ovum donation

OBJECTIVE: To determine if ultrasonographic endometrial pattern or thickness is predictive of histologic endometrial maturation in women undergoing hormone replacement for ovum donation. DESIGN: Ultrasonographic endometrial thickness and pattern were determined and compared with histologic assessment of endometrial maturation. PATIENTS: Forty-six women underwent 52 preparatory cycles for ovum donation. Transvaginal ultrasound (US) was performed after 14 days of E2 replacement and, after 12 days of P, an endometrial biopsy was performed. In 12 cycles, a continuous dose of 2 mg/d E2 was administered. In cycles with out-of-phase biopsies (dated earlier than day 24) and in the last 34 cycles, all women received an escalating dose of E2 before initiation of P. Additionally, the 46 women underwent 55 ETs with USs performed on cycle day 15. RESULTS: Six women had abnormal biopsies in their first preparatory cycle on the continuous E2 protocol, which normalized with the escalating protocol. All other women had normal biopsies. Women with abnormal biopsies had significantly thinner endometrium (< or = 6 mm) but similar endometrial patterns compared with women with normal biopsies. In women having US in preparatory and transfer cycles, there were no differences in endometrial thickness or pattern between examinations. CONCLUSIONS: Endometrial thickness > or = 7 mm in hormone replacement cycles predicts in phase endometrial histology and can replace the endometrial biopsy.     

The ultrastructure of human endometrium is altered by administration of intrauterine levonorgestrel

We studied the effect of intrauterine administration of levonorgestrel (LNG) on the ultrastructure of the endometrium. Twenty-one endometrial biopsy specimens, collected from nine fertile women during normal menstrual cycles and after 1, 3 or 6 months of use of a levonorgestrel-releasing intrauterine contraceptive system (LNG IUS), were studied using transmission and scanning electron microscopy. During the 6 month exposure to LNG IUS, changes took place in the endometrium. The glandular epithelial cells became lower. The junctional complexes between epithelial cells remained unchanged, whereas the lateral microvillar interdigitations became more prominent. The basal lamina under the epithelium became wavy but remained uniform and practically uninterrupted; only solitary epithelial cell protrusions through the basal lamina were seen. The stromal cells were largely decidualized. We conclude that in parallel with the generally known cellular effects, the use of the LNG IUS results in distinct changes in the basal lamina between the endometrial epithelial and stromal cells. The especially well-developed and uninterrupted basal lamina may be involved in the mechanism of the LNG IUS-induced endometrial suppression. Furthermore, the complex intercellular junctions between the epithelial cells, normally loosening around the time of implantation, persist during the local administration of levonorgestrel. This may have a pivotal role in the contraceptive effect of the LNG IUS.     

What alters physicians'' decisions to admit to the coronary care unit?

OBJECTIVES: To determine the endometrial response and bleeding patterns in post-menopausal women who were given a sequential hormone replacement regimen with estradiol 2 mg and dydrogesterone 10 mg. METHODS: One-hundred-and-eighty-eight (188) post-menopausal women with amenorrhea of 6 months or longer, with FSH/estradiol (E2) levels in the post-menopausal range and normal endometrium were entered in the study. All patients received a daily dose of 2 mg E2 during day 1-14 of each 28 day cycle and 2 mg E2 combined with 10 mg dydrogesterone during cycle day 15-28. The total duration of treatment was 12 months (13 cycles of 28 days). RESULTS: The rate of adequate progestational response (secretory or atrophic) in the 146 patients who remained in the study for at least 356 days with 90% study medication compliance and received an endometrial biopsy after 13 cycles of study medication was 97.2%. Three patients had proliferative endometrium and one simple hyperplasia. Cyclic bleedings in the 153 women who remained on study medication for at least 76 days occurred in over 85% of all cycles; the day of onset occurring regularly on day 13 or 14 of the combined period; the mean duration of bleeding per cycle was approximately 5 days with most patients having (very) slight bleeding. Sixty percent of patients had no intermittent bleedings over the whole 12-month study period. The average incidence of intermittent bleeding in the remaining patients was only 2.7 and generally of very slight quantities and of short duration. Per evaluable cycle the percentage of patients with an intermittent bleeding varies from 4.6 to 9.8%. Only two patients discontinued therapy because of bleeding problems. A clear decrease in the incidence of typical menopausal symptoms, i.e. hot flushes and night sweats was observed by the first visit after 6 weeks of treatment. CONCLUSIONS: The endometrial safety of 2 mg E2 sequentially combined with 10 mg dydrogesterone is very good as determined by the histologic response of the endometrium. The incidence of cyclic bleedings with this combination therapy is very high as is the regularity of day of onset and duration of bleeding. Blood loss during intermittent bleedings was mild and of short duration.     

The efficacy of drugs in the management of endometriosis

STUDY OBJECTIVE: To establish the crude effects of danazol and gonadotropin-releasing hormone (GnRH) analogs in the management of endometriosis. DESIGN: Prospective case-control study. SETTING: Unit of the Pathophysiology of Reproduction outpatient department. PATIENTS: Two groups of 110 women each with endometriosis (American Fertility Society score 1-3) who received danazol and GnRH analogs, and a control group who did not receive any drugs. INTERVENTIONS: Women in the treatment groups received danazol 200 mg every 8 hours for 6 months, or a different GnRH agonist at standard dosages for 6 months. Laparoscopy was performed twice, at the time of diagnosis and just before the end of treatment (or no therapy for controls). Surgical treatment of the implants was performed at the second laparoscopy. MEASUREMENTS AND MAIN RESULTS: Samples of both eutopic and ectopic endometrium were collected during both laparoscopies. Both danazol and GnRH agonists were useful in reducing the AFS scores to inactive endometriotic implants, and there were no significant differences between the effects (p <0.001). Fibrosis was found after 6 months of observation in the implants in one control woman (0.9%), in 20 patients (18.2%) treated with danazol (p <0.001 vs controls), and in 4 patients (3.6%) treated with GnRH agonists (NS vs controls). A correlation between a clinical diagnosis of AFS score zero and histologic features of fibrosis in the ectopic specimens after therapies was observed in 28% of women, with poor agreement (k = 0.07). CONCLUSIONS: Fibrosis, which represent the absence of endometrial cells within the specimens of endometriotic lesions or eutopic endometrium, did not appear in eutopic endometria but it was found in some endometriotic implants. Danazol and GnRH agonists reduced the clinical AFS scores of endometriosis, but their histologic effects in completely and permanently eliminating endometriotic implants were unacceptable.     

Response of the primate secretory endometrium to subchronic hypercortisolemia

OBJECTIVE: To assess the impact of subchronic and moderate hypercortisolism on the secretory endometrium of the cynomolgus monkey. METHODS: Osmotic pumps containing hydrocortisone phosphate (HP) were implanted subcutaneously in each monkey on the first day of the menstrual cycle; each monkey also received pumps containing saline in another cycle. Blood was obtained three times per week and urine was collected daily for hormone analyses. Endometriectomy was performed 13 +/- 1 days after the serum estradiol (E2) peak in each study cycle. RESULTS: Infusion of HP elevated serum cortisol levels by an average of 70%. Mean serum progesterone (P) levels were decreased by 50% during the secretory phase of HP-treatment cycles by comparison with self-control cycles (P < .01); as a result, the mean endometrial glycogen concentration was reduced by 30% (P < .05) and the activity of 17 beta-hydroxysteroid dehydrogenase was decreased by 70% (P < .05). Serum E2 levels were not consistently elevated by HP treatment, but cytosolic estrogen receptor levels of the endometrium were decreased by 50% (P < .01), indicating increased estrogenic stimulation. Histologic development of the secretory endometrium was retarded, but the length of the secretory phase was not affected by the treatment. CONCLUSION: A moderate elevation of serum cortisol levels over one menstrual cycle consistently produced a reduction in serum P and a hypoprogestogenic-hyperestrogenic response of the secretory endometrium in the cynomolgus monkey.     

Placental protein 14 in endometrium during menstrual cycle and effect of early luteal phase mifepristone administration on its expression in implantation stage endometrium in the rhesus monkey

Placental protein 14 (PP14) is a glycoprotein which is secreted by secretory phase endometrium and decidua in women. Despite the suggestion that PP14 is involved in the process of endometrial maturation for blastocyst implantation, our understanding in this regard is poor. In the present study, the concentrations and distribution patterns of immunodetectable PP14 in the endometrium during proliferative and secretory phases of normal ovulatory menstrual cycles, as well as in implantation stage endometrium in naturally mated ovulatory cycles with or without early luteal phase mifepristone treatment, were investigated using the rhesus monkey as a primate model. Immunopositive PP14 was observed mainly in epithelial cells of glands and it was detected in one major immunopositive band at Mr 28 kDa in tissue homogenate and spent medium. The area of immunopositive precipitation of PP14 in glands was minimal in follicular phase endometrium, and was higher (P < 0.01) in early, mid- and late luteal phase endometrium compared with that in pre- and periovulatory phases of the cycle, but there was no change in its area profile in the glandular compartment throughout the luteal phase. Immunopositivity for PP14 in luminal contents of gland displayed an increasing profile from early to late secretory phases. Thus, the concentrations and the distribution of immunodetectable PP14 in luteal phase endometrium of the rhesus monkey showed marked similarity with those of human endometrium during the natural menstrual cycle. Although there was no marked change in the band characterstics for the protein in implantation stage endometrium following early luteal phase mifepristone treatment, it was markedly decreased (P < 0.01) in tissue homogenate and in vitro spent medium along with a lesser (P < 0.02) degree of immunoprecipitation in the glands in implantation stage samples of mifepristone treatment group compared with that in control group samples. Thus, the contragestional effect of early luteal phase mifepristone treatment appears to be associated with a decrease in the concentration of immunodetectable PP14 in implantation stage endometrial glands and its secretion in the rhesus monkey. It remains to be seen whether this decline is caused from direct antiprogesterone action on endometrial glands during progesterone dominance, or secondarily from associated retarded development of endometrium.     

Histological evaluation of endometrium on the day of oocyte retrieval after gonadotrophin-releasing hormone agonist-follicle stimulating hormone ovulation induction for in-vitro fertilization

The objective of this study was to evaluate the histopathological characteristics of endometrial biopsies taken on the day of oocyte recovery in in-vitro fertilization (IVF) cycles with a satisfactory response to ovulation induction. A group of 33 patients who went through ovulation induction for IVF, and in whom an endometrial polyp was suspected on transvaginal ultrasonography during the monitoring phase, were studied. Following oocyte recovery, hysteroscopy, polypectomy and endometrial curettage were performed. Dating of endometrial glands and stroma was carried out in the tissue not containing the polyps. The total dose of follicle stimulating hormone (FSH), duration of ovulation induction, peak oestradiol and luteinizing hormone (LH) concentrations, thickness of endometrium and number of oocytes were recorded and compared to the endometrial dating of the specimens. In 15 cycles (45.5%), the endometrium was classified as 'in phase' (group I), 'advanced' by 2-4 days in a further 15 (45.5%, group II), and in the remaining three cycles (9%) it was delayed in maturation (group III). Younger age was correlated with advanced staging of the endometrium (r = -0.42; P = 0.015). Women with 'in phase' and 'advanced' maturation were similar in their response to ovulation induction; however, there was a strong correlation between advanced dating of endometrium and number of oocytes retrieved (r = 0.49; P = 0.04). Endometrial staging on the day of oocyte retrieval varied widely in patients treated by the same gonadotrophin-releasing hormone agonist (GnRHa)/FSH protocol for ovulation induction. This difference was not predictable by parameters monitored through the cycles.     

Bovine cyclic endometrium contains high-affinity luteinizing hormone/human chorionic gonadotropin binding sites

High-affinity LH/hCG binding sites have been characterized in porcine, lepine, and murine uteri. In the present study, LH/hCG binding sites were characterized in bovine endometrium. Radioreceptor assays were performed with membrane homogenates of endometrial tissues and analyzed for binding site specificity and capacity. There was little competition for receptor occupancy between hCG and ovine FSH (5%) or ovine prolactin (< 0.1%), but there was a 20% cross-reaction with eCG. There was no affinity for LH/hCG in crude membrane preparations of kidney, skeletal muscle, or vascular tissues. Concentrations of endometrial LH/hCG binding sites were determined during the bovine estrous cycle. LH/hCG receptors were found in cell preparations from Days 2-4 and 15-17 of the cycle, but not in preparations from the other stages of the cycle tested (Days 8-12, pre- and post-estrus, and ovulation). The concentration of uterine LH/hCG receptor varied during the estrous cycle, with higher values at Days 15-17 (3.1 fmol/mg protein) and lower values at Days 2-4 (1.2 fmol/mg protein). However, the binding capacity of hCG by luteal cells (9.7 fmol/mg protein) was 3-fold higher (p < 0.01) than that by endometrial tissue on any day studied. No differences in affinity constant (Ka) were seen between endometrial LH/hCG receptors (either) from Days 2-4 or 15-17) and mid-cycle luteal cells (0.60 x 10(11) M-1). Using Western blot analysis, we determined the expression of cyclooxygenase (COX) during the estrous cycle of the cow. It was found that the signal for COX was strongest at 15-17 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

The follicle-stimulating hormone (FSH) threshold/window concept examined by different interventions with exogenous FSH during the follicular phase of the normal menstrual cycle: duration, rather than magnitude, of FSH increase affects follicle development

According to the threshold concept, FSH concentrations need to surpass a distinct level to stimulate ovarian follicle growth. The window concept stresses the significance of a limited duration of elevated FSH levels above the threshold for single dominant follicle selection. The aim of this study was to investigate effects on follicle growth of increased FSH levels, differing in duration and magnitude of elevation, during the follicular phase. Twenty-three normo-ovulatory (cycle length, 26-31 days), young (age, 20-31 yr) women volunteered for this study. In all subjects a series of daily transvaginal sonography scans of the ovaries and blood sampling [for FSH and estradiol (E2) determinations] were performed during two consecutive cycles. The first study cycle (control cycle) started 10 days after urinary assessment of the LH surge in the preceding cycle (DayLH) and was concluded on the day of ovulation assessed by transvaginal sonography scans. The second series of daily monitoring (intervention cycle) started 10 days after DayLH in the control cycle. After randomization, subjects received either 375 IU urinary FSH, s.c., as a single injection on Day(LH+14) (group A; n = 11) or 75 IU daily from Day(LH+19) until Day(LH+23) (group B; n = 12). In group A, FSH levels increased on the day after injection to a median concentration of 10.1 IU/L, which was 1.9 times higher (P < 0.01) than levels on matching days during the control cycle. Concentrations returned to basal levels 3 days after injection. In group B, a moderate elevation of FSH concentrations (15% increase; P < 0.05) was observed compared to levels during the control cycle. In group A, E2 concentrations increased (P = 0.03) 1 day after FSH injection and returned to baseline levels within 2 days. In group B, E2 levels started to increase after the first injection of FSH and remained significantly higher (P < 0.01) during the following 5 days compared to those on matching days in the control cycle. Compared to matching days in the control cycle an increased number of follicles 8-10 mm in size was found in group A (P < 0.01) during the period from Day(LH+14) until Day(LH+19), without an increase in follicles 10 mm or larger thereafter. In contrast, in group B, the numbers of both 8- to 10-mm and 10-mm or larger follicles were higher during the period from Day(LH+19) until Day(LH+24) in group B (P = 0.02 and P < 0.01, respectively). Results from the present study suggest that a brief, but distinct, elevation of FSH levels above the threshold in the early follicular phase does not affect dominant follicle development, although the number of small antral follicles did increase. In contrast, a moderate, but continued, elevation of FSH levels during the mid to late follicular phase (effectively preventing decremental FSH concentrations) does interfere with single dominant follicle selection and induces ongoing growth of multiple follicles. These findings substantiate the FSH window concept and support the idea of enhanced sensitivity of more mature follicles for stimulation by FSH. These results may provide the basis for further investigation regarding ovulation induction treatment regimens with reduced complication rates due to overstimulation.     

Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium

OBJECTIVE: To study the effects of clomiphene citrate (CC) on the endometrium by ultrasound and to reveal the echogenic difference between the control cycle and the CC cycle. DESIGN: Retrospective study of patients before and during a CC treatment. SETTING: Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan. PATIENT(s): Seventy-nine infertile women who had a spontaneous ovulation and a normal luteal function. INTERVENTION(s): Patients received 50 mg/d CC between days 5 and 9 of the menstrual cycle. MAIN OUTCOME MEASURE(s): Endometrial thickness, echogenic pattern of the endometrium, serum E2 content, and E2 and P receptor contents in the endometrium. RESULT(s): Endometrial thickness was significantly thinner during the CC cycle (7.6 +/- 1.4 mm, mean +/- SD, n = 79) than during the control cycle (8.5 +/- 1.7 mm, n = 79) on late proliferative days, but there was no significant difference on midsecretory days (10.8 +/- 2.2 mm during the CC cycle, n = 79; 11.2 +/- 2.2 mm during the control cycle, n = 79). The echogenic patterns, however, were different between the two cycles on midsecretory days. Moreover, the incidence in which patients showed a grade 3 endometrium on midsecretory days was significantly higher during the conceived CC cycle compared with the not-conceived CC cycle. Serum E2 levels were significantly higher, but E2 receptor contents in the endometrium were significantly lower during the CC cycle (67 +/- 46 fmol/mg, n = 13) compared with the control cycle (123 +/- 89 fmol/mg, n = 15) on late proliferative days. CONCLUSION(s): Clomiphene citrate affected the echogenic pattern of the endometrium, and most of the endometrium showed a grade 3 pattern on midsecretory days during the conceived CC cycle. Under the CC treatment, the comfortable endometrium for embryos might be different from the control cycle.     

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.     

A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception

A prospective randomized study was conducted at the Family Planning Association of Hong Kong to compare the efficacy of the Yuzpe regimen and levonorgestrel (0.75 mg for two doses 12 h apart) in post-coital contraception. A total of 424 subjects were recruited into the Yuzpe group and 410 subjects into the levonorgestrel group; 77 subjects in the Yuzpe group and 79 subjects in the levonorgestrel group had further acts of intercourse during the treatment cycle. Fifteen pregnancies (3.5%) occurred in the Yuzpe group and 12 pregnancies (2.9%) in the levonorgestrel group. After excluding the patients who had further acts of intercourse, the failure rates in the Yuzpe group and the levonorgestrel group were 2.6 and 2.4% respectively. The incidence of nausea, vomiting and fatigue in the Yuzpe group was significantly higher than those in the levonorgestrel group. We conclude that levonorgestrel is an effective drug for post-coital contraception with a lower incidence of side-effects than the Yuzpe regimen.