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Objective: To investigate the relationship between the number and sequence of preceding miscarriages and antiphospholipid syndrome (APS)., Design: Retrospective cohort study., Setting: Recurrent miscarriage (RM) clinic., Patient(s): Women who attended the RM clinic from 1988 to 2006., Intervention(s): None., Main Outcome Measure(s): Number, type, and sequence of previous pregnancies were compared between women with APS and women with unexplained RM., Result(s): A total of 1,719 patients were included; 312 (18%) had APS, and 1,407 (82%) had unexplained RM. The mean maternal age (32.6 years) did not differ between women with and without APS. The median number of miscarriages was three in both groups. A total of 865 women (50%) had a history of at least one live birth, with no difference between the two groups. In both groups, 97% of the women had a history of consecutive miscarriages., Conclusion(s): The number of preceding miscarriage, type and sequence of previous pregnancies, and maternal age were not associated with APS in women with RM. There is no increased diagnostic yield for APS after three miscarriages rather than after two miscarriages and no increased diagnostic yield for APS after consecutive miscarriages rather than after nonconsecutive miscarriages. Therefore, APS testing should be considered for all women with two or more miscarriages., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the presence and compare the relative abundance of messenger RNA for epidermal growth factor receptor (EGFR) in baboon corpora lutea of different luteal ages., Design: Prospective controlled nonhuman primate study., Setting: Animal facility in an academic research institution., Participants: Six adult female baboons with well-defined regular menstrual cycles. Stage of the menstrual cycle was determined by observation and scoring of perineal turgescence. The day of maximal turgescence was referred to as the day of LH surge., Intervention: Ten corpora lutea were obtained by luteectomy during early (LH + 1 to 5 days, n = 3), midluteal (LH + 6 to 10 days, n = 3), and late (LH + 11 to 15 days, n = 4) luteal phases., Main Outcome Measure: Relative levels of messenger RNA for EGFR as determined by ribonuclease protection assay using RNA probe generated from complementary DNA for human EGFR., Results: Messenger RNA for EGFR is present in baboon corpora lutea with relative levels of 0.51 +/- 0.18 (mean +/- SEM) in the early, 0.43 +/- 0.17 in the midluteal, and 0.50 +/- 0.17 arbitrary units in the late luteal phase., Conclusion: Baboon corpus luteum is a site of EGFR production; the levels of its messenger RNA did not change appreciably throughout the luteal phase.

Objective: To determine changes in trabecular vertebral bone mass, serum E2, and serum calcitonin during and after therapy of pelvic endometriosis with depot leuprolide acetate (LA) or danazol., Design: Prospective, randomized, double-blind study., Setting: Academic university hospital and department of obstetrics and gynecology., Patients: Twelve women with symptomatic pelvic endometriosis diagnosed and staged by laparoscopy., Interventions: All patients received blinded treatment with either 3.75 mg JM depot LA given every month and daily placebo tablets (n = 6) or 800 mg oral danazol daily with a monthly placebo injection (n = 6) for 24 weeks., Main Outcome Measures: Quantitated computerized tomography of bone density of thoracic 12 to lumbar 4 vertebral bodies were determined before, at the end of 24 weeks of treatment, and 6 and 12 months after completing treatment. Gain or loss of bone mass was based against pretreatment levels. Serial serum levels of E2 and calcitonin before, throughout, and after therapy were compared with changes in bone mass., Results: Bone loss with LA was 14.0% +/- 0.5% (mean +/- SEM), recovering to a deficit of 4.2% +/- 3.8% and 3.3%, 6 and 12 months after stopping therapy. Danazol increased bone by 5.4% +/- 2.2%, with a further gain to 8.2% +/- 3.5% and 7.5%, 6 and 12 months after stopping treatment. Serum E2 levels usually were < 25 pg/mL (conversion factor to SI unit, 3.671) with LA but > 47.3 pg/mL with danazol. Calcitonin levels did not change significantly with either treatment., Conclusion: Depot LA produced marked sustained hypoestrogenemia and significant bone loss with incomplete recovery 1 year after stopping treatment. Danazol maintained normoestrogenemia and increased bone mass with the gain maintained even 1 year after stopping therapy.

Objective: To examine hCG receptor levels and binding kinetics in corpora lutea (CL) from tubal pregnancies., Design: Corpus luteum from tubal pregnancies, term normal pregnancies, and midluteal phase were obtained and compared for hCG binding., Setting: Department of Obstetrics and Gynecology, University Hospital., Interventions: Corpus luteum were obtained at elective cesarean section at term, tubal ligation, or surgery for ectopic pregnancy (EP)., Main Outcome Measures: Human chorionic gonadotropin receptor levels, dissociation and association constants using saturation binding assay, and Scatchard analysis., Results: Corpus luteum from late tubal pregnancies (> 7 weeks) and term intrauterine pregnancies had undetectable hCG binding. Corpus luteum from early tubal pregnancies (< 6 weeks) had significantly reduced hCG receptors with higher dissociation constants than from midluteal phase CL., Conclusions: Significant reduction of hCG receptors with accelerated binding dissociation may be the basis of CL dysfunction in some EPs.

Objective: To determine plasma levels of insulin-like growth factor-I (IGF-I), CA-125, estrone (E1), E2, and P in women with uterine leiomyomas compared with normal women., Design: Women with leiomyomas were compared with normal women (control)., Setting: University Department of Obstetrics and Gynecology., Patients: Fifty-one premenopausal women with uterine myomas > 14 weeks gestation and 30 normal fertile women (controls) were studied. Peripheral blood samples were obtained before myomectomy or hysterectomy and during the nonmenstruating phase in the controls., Main Outcome Measures: Plasma levels of E1, E2, P, CA-125, and IGF-I were determined by specific and sensitive RIAs and immunoradiometric assays., Results: Plasma IGF-I levels were 2,006 +/- 185 mU/mL (mean +/- SEM, n = 35) and 2,335 +/- 287 mU/mL (n = 16) in women with leiomyomas during the follicular and luteal phases, respectively, whereas the corresponding values for normal women were 1,702 +/- 120 (n = 30) and 1,774 +/- 239 mU/mL (n = 30). Similarly, plasma CA-125 levels were unchanged in women with leiomyomas (myomas: 18.8 +/- 2.4, 21.5 +/- 3.7 U/mL; normal: 15.9 +/- 1.5, 15.8 +/- 1.3 U/mL during follicular and luteal phases, respectively). Women with leiomyomas had plasma E1, E2, and P levels during the follicular phase (91.9 +/- 11.5 pg/mL; conversion factor to SI unit, 3.699; 94.6 +/- 19.0 pg/mL; conversion factor to SI unit, 3.671; and 1.5 +/- 0.4 ng/mL; conversion factor to SI unit, 3.180, respectively) and the luteal phase (105.8 +/- 11.2 pg/mL; conversion factor to SI unit, 3.699; 128.7 +/- 24.8 pg/mL; conversion factor to SI unit, 3.671; and 9.6 +/- 1.6 ng/mL; conversion factor to SI unit, 3.180) similar to normal women., Conclusion: Plasma levels of IGF-I, CA-125, E1, E2, and P are normal in women with leiomyomas.

Objective: To determine the effect of melatonin on baboon corpus luteum (CL) cell progesterone (P) production., Design: Five baboon CL obtained during the midluteal phase by luteectomy were dissociated using collagenase, and incubations were performed (50,000 cells per plate) in quadruplicate for 3 hours at 37 degrees C with melatonin (0.001 to 1.0 ng/mL) (basal) or with melatonin and 10 IU of human chorionic gonadotropin (hCG) (hCG-stimulated). Total P was measured by a specific radioimmunoassay., Main Outcome Measures: Progesterone concentrations measured in the presence and absence of melatonin and hCG., Results: Melatonin (0.01 to 1.0 ng/mL) inhibited basal P production in all the CL (41.8 +/- 9.9 ng P without melatonin compared with 32.2 +/- 2.0 ng P, 28.4 +/- 2.1 ng with 0.01 and 1.0 ng/mL melatonin, respectively). Human chorionic gonadotropin-stimulated P production was significantly inhibited with as little as 0.01 ng of melatonin (150.8 +/- 11.4 ng with 10 IU hCG versus 120.3 +/- 6.4 ng with 10 IU hCG and 1.0 ng melatonin). The degree of inhibition in the hCG-stimulated cells was greater than in the nonstimulated cells. Melatonin at a concentration of 0.001 ng/mL did not affect P production in both stimulated and nonstimulated cells. Serotonin in similar concentrations had no effect on luteal cell P production., Conclusion: These findings indicate that melatonin exerts a suppressive effect on baboon dispersed luteal cell P production and thus may play a role in luteal function.

Objective: To determine the presence and binding characteristics of insulin-like growth factor (IGF) receptors in corpora lutea (CL) of spontaneous and clomiphene citrate (CC)-induced cycles and to identify any relationship between IGF receptors and cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17 alpha-OHP) levels., Design: Women undergoing bilateral tubal ligation were divided into two groups. One group received no medication (controls) and the other took 50 mg of CC. Midluteal phase CL were recovered at tubal ligation for hormone and receptor analysis., Setting: Patients were recruited from a university hospital setting., Patients: Eleven fertile women 26 to 37 years of age requesting bilateral tubal ligation were studied., Interventions: Four women were given 50 mg/d of CC from days 5 through 9 of study cycle. Seven women did not take any medication. Minilaparotomy bilateral tubal ligation and luteectomy were performed 7 to 9 days after midcycle urinary (LH) surge., Main Outcome Measures: Insulin-like growth factor receptor concentrations and binding characteristics and cytosol P and 17 alpha-OHP levels in individual CL., Results: Optimal binding for 125I-IGF-I with membrane fractions of homogenized CL was obtained with incubation at 4 degrees C for 16 hours. Specific binding (mean +/- SEM) was significantly higher in CC-treated (53.6% +/- 4.8%) than in control cycles (25.9% +/- 5.5%, P less than 0.001). Receptor concentrations were also significantly higher in CL from CC-induced (145.6 +/- 21.8 pmol/mg protein) than from control cycles (74.8 +/- 15.2 pmol/mg protein, P less than 0.02). Insulin-like growth factor receptor levels correlated with neither serum nor cytosol P and 17 alpha-OHP in CL from either cycles., Conclusion: Specific IGF-I receptors are present in human CL of the menstrual cycle with higher concentrations present in CC-induced cycles. Thus IGF may express its action on luteal function through its receptors in CL.

Midluteal phase corpora lutea (CL) obtained from women induced with 50 mg (n = 5), 100 mg (n = 5), and 150 mg (n = 5) of clomiphene citrate (CC) were measured for luteinizing hormone/human chorionic gonadotropin (LH/hCG) concentrations and cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) and compared with midluteal phase CL from eight normal women (controls). More CL (26) that were significantly heavier (2.0 +/- 0.3 g, [mean +/- SEM]) were obtained with CC than in controls (10). Clomiphene citrate treatment increased LH/hCG receptor concentrations and the dissociation constant significantly from 69 +/- 12 fmol/mg protein and 1.1 +/- 0.2 x 10(-10) M, respectively, in controls to 112 +/- 6 fmol/mg protein and 2.1 +/- 0.1 X 10(-10) M. Cytosol P and 17-OHP levels were not significantly increased. Cumulatively these cellular effects may be responsible for increasing serum P and responsiveness to hCG and for correcting luteal dysfunction.

Cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) levels and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors were measured in 27 corpora lutea and four corpora albicantia. Cytosol P concentrations were highest in corpora lutea (mean +/- SEM, 3.1 +/- 0.8 micrograms/g) during the midluteal phase (days 15 to 19) rather than the early (2.2 +/- 0.8 micrograms/g, days 20 to 25) and late luteal phases (1.8 +/- 0.8 micrograms/g, days 26 to 30). Cytosol 17-OHP concentrations also were 3.3 +/- 0.5, 4.3 +/- 0.6, and 3.3 +/- 1.0 micrograms/g in early, midluteal, and late luteal phases, respectively, and was significantly inversely correlated with occupied LH/hCG receptors in midluteal phase. Corpora albicantia had the lowest P (0.3 +/- 0.05 microgram/g) and 17-OHP (0.9 +/- 0.6 micrograms/g) concentrations. Cytosol P and 17-OHP may therefore reflect the balance between the luteal cell production and secretion, whereas the amount of occupied and unoccupied LH/hCG receptors may partially explain the relationship between LH and P secretion.

Thirty-one normal women were studied daily in 41 cycles. Venous blood samples were taken for measurements of luteinizing hormone (LH), estradiol (E2), and progesterone (P), and vaginal examinations were done to obtain cervical mucus and vaginal fluid. The specific activity of guaiacol peroxidase (GP), extracted from cervicovaginal secretions with 0.5 M CaCl2, was determined in the vaginal samples. In the follicular phase, from day -7 to day 0 (the LH +1 day, when ovulation presumably occurred), there was a strong negative correlation between GP and the rising E2 (r = -0.94). On days 1 to 10 after ovulation, there was a strong positive correlation between GP and P (r = 0.84). In nine ovulatory cycles in which P levels did not exceed 8 ng/ml on any day, indicating possible luteal phase inadequacy, there were significantly lower GP levels than in another 32 ovulatory cycles with higher P (P = 0.04). These results suggest that (1) at midcycle, E2 seems to "down-regulate" the GP specific activity; and (2) in the luteal phase, serum P levels parallel those of GP activity, even in the presence of high luteal E2. GP activity profiles during the menstrual cycle can be used to define the fertile period, may prove useful in diagnosing pregnancy, and may be a simple, convenient test for an inadequate corpus luteum.

Six corpora lutea (day 17 to day 25) of the menstrual cycle and four ovarian stromal tissues from seven cycling women were examined for the presence of epidermal growth factor (EGF) by immunocytochemistry with the use of the indirect peroxidase-antiperoxidase (PAP) procedure. After tissue sections of 4 micron were mounted, endogenous peroxidases were removed with hydrogen peroxide, and the sections were incubated for 1 hour at room temperature followed by 16 hours at 4 degrees C with a highly specific antisera for mouse EGF (mEGF), nonimmunized normal rabbit serum, or antiserum preadsorbed with excess antigen. After the reaction with the second antibody (goat antirabbit IgG) for 1 hour at room temperature, the peptide was localized by use of PAP and 3.3'-diaminobenzidine as the chromogen. EGF could be localized in the luteal cells of five corpora lutea (day 17 to day 25) but not in a corpus luteum of day 22 and all ovarian stromal tissue examined. The localization of immunoreactive EGF in the human corpus luteum demonstrates directly for the first time the presence of this growth-promoting peptide in this tissue, which suggests its local production.

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

Clomiphene citrate (CC) has been used to influence the timing of ovulation. To evaluate the effects of CC on the timing of the luteinizing hormone (LH) surge, we examined the LH surge in 10 cycling normal women for 3 cycles each, during an untreated cycle (control) and during treatment with 50 mg CC (CC 50) and 150 mg CC (CC 150) daily on days 5 to 9. Length of control cycles (mean +/- standard error of the mean) was 28.5 +/- 1.1 days and was not significantly different from either CC 50 (28.2 +/- 0.6 days) or CC 150 cycles (29.0 +/- 0.4 days). LH surge occurred on day 16.4 +/- 1.2 in control, 16.5 +/- 0.5 in CC 50, and 17.1 +/- 0.7 in CC 150 cycles. Similarly, luteal phase lengths were not significantly affected by CC treatment. Individually, however, the effect of CC on the timing of the LH surge depended on when the LH surge occurred in corresponding control cycles. If the control cycle LH surge occurred on day 16 or earlier, CC significantly delayed it. If the normal LH surge occurred on day 18 or later, CC advanced it. During CC 50 treatment, the LH surge was advanced by 1 to 7 days in 3 cycles, unchanged in 2, and delayed in 5 cycles by 1 to 9 days. Detection of urinary LH surge was reliable in CC-treated cycles and correlated well with the day of plasma LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial paired plasma and salivary progesterone (P) levels were determined in 21 ovulation-induced cycles of 13 women and in 162 luteal saliva samples of 21 normal cycling women. Mean +/- standard error of the mean (SEM) salivary P levels in all ovulation-induced cycles were similar to normal cycles and were 294 +/- 31.5 to 499 +/- 75 pg/ml, whereas the corresponding plasma P levels were 24.9 +/- 5.0 to 51.4 +/- 16.6 ng/ml. Paired plasma and salivary P levels correlated significantly in women induced with clomiphene citrate (r = 0.82), follicle-stimulating hormone (r = 0.80), human menopausal gonadotropins (r = 0.78), and in those who became pregnant (r = 0.95). Luteal phase salivary P levels were 1.0% to 1.3% of the corresponding plasma levels in ovulation-induced cycles. These findings indicate that salivary P may be a useful and convenient alternative to plasma P for assessing ovulation.