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Fluorescence spectroscopy of the cervix has been shown to be an effective noninvasive diagnostic tool for cervical intraepithelial neoplasia (precancer). To assess the effect of the menstrual cycle on fluorescence spectroscopy, daily measurements were made on ten subjects for the length of their cycle. These measurements were analyzed to determine if there was a statistically significant signal associated with the menstrual cycle. A signal was found for emission wavelengths between 425 and 445 nm inclusive—near the main hemoglobin absorption band, the Soret band, at 420 nm. We suspect that the slight displacement of the Soret band is due to the nearby dominant NAD(P)H peak, which increases the signal-to-noise ratio and affects statistical significance. The signal consists of a reduction in fluorescence intensity for the first few days of the cycle. This analysis indicates that hemoglobin absorption is the main menstrual-cycle effect on the use of fluorescence spectroscopy on the cervix. The effect is confined to a small set of excitation/emission wavelengths and to approximately the first 8 days of the cycle. This suggests that any problems from the menstrual cycle can be avoided with a simple requirement that the device not be used during the period of menstrual bleeding.

To review and organize the science related to cyclic perimenstrual pain and discomfort for the fifth research-based practice project of the Association of Women's Health, Obstetric and Neonatal Nurses.Computerized searches in CINAHL, MEDLINE, and the Cochrane Library, as well as hand searches of cited references. Keywords included cyclic pelvic pain, comfort, pain guidelines, and dysmenorrhea.All relevant articles prior to 1999 were considered. Thirty-three research-based articles (1992-1999) were reviewed for relevance by the science team as part of the fifth research-based practice project of the Association of Women's Health, Obstetric and Neonatal Nurses.The literature review and synthesis resulted in a cogent description of cyclic perimenstrual pain and discomfort and the development of three nursing diagnoses: perimenstrual cyclic pelvic pain, perimenstrual discomfort, and perimenstrual negative affect. Cyclic pelvic pain is a new concept, developed by the science team during the project. Perimenstrual cyclic pelvic pain is an acute, subjective experience defined by pelvic pain that presents in a repeating time frame associated with the menstrual cycle. It is usually clustered with other discomforts and appreciably affects a woman's quality of life. Because the science about interventions is complex and extensive, data synthesis led to organization of the interventions within seven categories.Translation of research into practice is essential. Cyclic perimenstrual pain and discomfort is an important clinical issue, yet the science had not previously been comprehensively reviewed with the mission to translate it for nursing practice. Translation of this complex literature was accomplished though an innovative clinical practice guideline and subsequently evaluated in nursing practice through the research-based practice project.

Objective: To review and organize the science related to cyclic perimenstrual pain and discomfort for the fifth research-based practice project of the Association of Women's Health, Obstetric and Neonatal Nurses. Data Sources: Computerized searches in CINAHL, MEDLINE, and the Cochrane Library, as well as hand searches of cited references. Keywords included cyclic pelvic pain, comfort, pain guidelines, and dysmenorrhea. Data Extraction: All relevant articles prior to 1999 were considered. Thirty-three research-based articles (1992–1999) were reviewed for relevance by the science team as part of the fifth research-based practice project of the Association of Women's Health, Obstetric and Neonatal Nurses. Data Synthesis: The literature review and synthesis resulted in a cogent description of cyclic perimenstrual pain and discomfort and the development of three nursing diagnoses: perimenstrual cyclic pelvic pain , perimenstrual discomfort , and perimenstrual negative affect . Cyclic pelvic pain is a new concept, developed by the science team during the project. Perimenstrual cyclic pelvic pain is an acute, subjective experience defined by pelvic pain that presents in a repeating time frame associated with the menstrual cycle. It is usually clustered with other discomforts and appreciably affects a woman's quality of life. Because the science about interventions is complex and extensive, data synthesis led to organization of the interventions within seven categories. Conclusions: Translation of research into practice is essential. Cyclic perimenstrual pain and discomfort is an important clinical issue, yet the science had not previously been comprehensively reviewed with the mission to translate it for nursing practice. Translation of this complex literature was accomplished though an innovative clinical practice guideline and subsequently evaluated in nursing practice through the research-based practice project.

OBJECTIVE: The study determined the expression of oxytocin receptor and its gene in human uterine leiomyoma compared with the adjacent myometrium. STUDY DESIGN: Paired samples of leiomyoma and the adjacent myometrium from 20 women through the menstrual cycle, menopause, and various hormone treatments were studied. Oxytocin receptor was immunohistochemically localized with use of the specific antibody (2F8) to human oxytocin receptor. Oxytocin receptor protein was determined by Western blotting, whereas reverse transcription–polymerase chain reaction was used for oxytocin receptor messenger ribonucleic acid expression. RESULTS: Immunohistochemistry showed positive staining in all tissues examined, relatively more intense in the myometrium than in the adjacent leiomyoma, and in tissues from the preovulatory than the postovulatory phase. Western blotting showed a single 70-kd band corresponding to the oxytocin receptor. The relative abundance of oxytocin receptor in both leiomyoma and myometrium was significantly higher during the preovulatory ( n = 5) than the postovulatory ( n = 5) phase ( P = .034 and .05). In women receiving gonadotropin-releasing hormone agonist ( n = 1) or oral contraceptives ( n = 1), after the menopause ( n = 2), and with irregular vaginal bleeding ( n = 1), oxytocin receptor levels in leiomyoma and myometrium were unchanged but were reduced in anovulatory cycles (amenorrhea, n = 2). Reverse transcription–polymerase chain reaction showed messenger ribonucleic acid for oxytocin receptor as a 391-bp band in all leiomyomas and myometrium examined. CONCLUSIONS: Leiomyoma and myometrium express the gene and protein for oxytocin receptor, which is probably partially regulated by ovarian sex steroids during the menstrual cycle. (Am J Obstet Gynecol 1998;179:620-7.)

Menstruation, which occurs if pregnancy is not established, is a tightly-controlled, highly-synchronized physiological event confined to a few days and a small blood loss. The initial dissolution of endometrial extracellular matrix, vasoconstriction followed by secondary vasodilation and tissue sloughing, ends in postmenstrual repair and regeneration, in which angiogenesis is a key process in re-establishing endometrial vascular function. The two principal conductors for this coordinated sequence of events are oestrogen and progesterone, which act on the endometrium to regulate the expression of a variety of molecular events that enable endometrial shedding and complete regeneration. Some of the putative factors produced by and acting on the endometrium as well as uterine vascular flow include prostaglandins, matrix metalloproteinases, endothelins, reninangiotensin, vascular-endothelial growth factors and inhibitors of angiogenesis. Prostaglandins, prostacyclins, thromboxanes and endothelins are vasoactive substances that provide a changing balance between vasoconstriction and vasodilatation. Matrix metalloproteinases are indispensable for degrading the extracellular matrix such as collagens, gelatins, proteoglycans, and laminin so that endometrial shedding, breakdown and tissue remodelling are facilitated. Putative angiogenic factors in the endometrium II, vascular-endothelial growth factors, and other growth factors. Together, this ensemble of molecules regulates uterine vascular function and menstruation.

Objective To determine and compare the concentrations of epidermal growth factor (EGF) and basic fibroblast growth factor (FGF) in the peritoneal fluid (PF) of women with and without endometriosis. Design Prospective study. Setting Tertiary care center affiliated with university medical school. Patients Forty-two women with endometriosis and 34 women without endometriosis confirmed by laparoscopy. Main Outcome Measures Epidermal growth factor and basic FGF concentrations were determined by highly sensitive enzyme immunoassays using monoclonal antibodies. Result Approximately 50% of the PF samples had EGF concentrations of >0.4 pg/mL (conversion factor to SI unit, 0.17) and 90% had basic FGF concentrations of >1 pg/mL (conversion factor to SI unit, 0.058). Concentrations of EGF or basic FGF in PF did not differ significantly between the two groups. In normal women, there was a significant correlation between EGF and basic FGF during the luteal phase. In women with endometriosis, EGF levels were higher during the luteal phase, but there was no correlation of either EGF or basic FGF levels with the severity of endometriosis. Conclusions The concentrations of EGF and basic FGF were highly variable in the PF of women with or without endometriosis and did not differ significantly. The concentrations were so low that neither EGF nor basic FGF in PF could bind to its receptor.

The ovary is a complex organ composed of cells of diverse lineages. Therefore, in this study we examined whether immunolocalization of various cytoskeletal, epithelial, immune-cell, and neural-associated proteins can differentiate various cells in the baboon and human ovaries. Surface epithelial cells exhibited immunoreactivity for cytokeratin and desmin, however, they did not immunostain for other epithelial markers such as carcinoembryonic antigen or epithelial membrane antigen. Smooth muscle actin was distributed apically whereas vimentin was localized basally in these cells. Ova exhibited strong immunoreactivity for S-100, Leu-M1, and neurofilament and did not show immunoreactivity for epithelial and cytoskeletal proteins. In antral follicles and theca cells, and after formation of corpus luteum, both granulosa and theca cells expressed immunoreactivity for vimentin. Cytokeratins were absent in the preantral and antral follicles. However, atresia and development of apoptosis was associated with expression of immunoreactive cytokeratins in atretic follicles. Development of corpus luteum led to major changes in the immunophenotype of follicular cells. The mere presence of immunoreactivity for cytokeratin and a strong immunoreactivity for desmin in the luteinized granulosa and not in the theca cells allowed discrimination of these cells from each other and from their ancestral cells. Proliferating cell nuclear antigen was present in various ovarian cells except for ovum. The distinct patterns of expression of cytoskeletal, epithelial, and neural-associated proteins in various cells of the ovary facilitates their identification and discrimination.

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 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 (>7weeks) and term intrauterine pregnancies had undetectable hCG binding. Corpus luteum from early tubal pregnancies ( Conclusions Significant reduction of hCG receptors with accelerated binding dissociation may be the basis of CL dysfunction in some EPs.

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 3hours at 37°C with melatonin (0.001 to 1.0ng/mL) (basal) or with melatonin and 10IU 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 1.0ng/mL) inhibited basal P production in all the CL (41.8±9.9ng P without melatonin compared with 32.2±2.0ng P, 28.4±2.1ng with 0.01 and 1.0ng/mL melatonin, respectively). Human chorionic gonadotropin-stimulated P production was significantly inhibited with as little as 0.01ng of melatonin (150.8±11.4ng with 10IU hCG versus 120.3±6.4ng with 10IU hCG and 1.0ng melatonin). The degree of inhibition in the hCG-stimulated cells was greater than in the nonstimulated cells. Melatonin at a concentration of 0.001ng/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 α -hydroxyprogesterone (17 α -OHP) levels. Design Women undergoing bilateral tubal ligation were divided into two groups. One group received no medication (controls) and the other took 50mg 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 37years of age requesting bilateral tubal ligation were studied. Interventions Four women were given 50mg/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 9days after midcycle urinary (LH) surge. Main Outcome Measures Insulin-like growth factor receptor concentrations and binding characteristics and cytosol P and 17 α -OHP levels in individual CL. Results Optimal binding for 125 I-IGF-I with membrane fractions of homogenized CL was obtained with incubation at 4°C for 16hours. Specific binding (mean±SEM) was significantly higher in CC-treated (53.6%±4.8%) than in control cycles (25.9%±5.5%, P P α -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.

Objective To determine the histologic development of midluteal corpus luteum (CL) and endometrium in normal fertile women after induction of ovulation with clomiphene citrate (CC). Design, Patients, Interventions Twelve normally cycling women planning to undergo an elective tubal ligation were treated with 50 to 150 mg of CC daily on days 5 through 9 of the cycle. Luteectomy and endometrial biopsy were performed simultaneously 7 days after the urinary luteinizing hormone surge. Results Because polyovulation occurred in 10 of the 12 women, 22 CL and 12 endometrial biopsies were studied. Ten women had luteal and endometrial histology that were within 2 days of the ovulation to biopsy interval. The 2 remaining women had endometrial histology that lagged 3 days behind the chronological postovulatory date. In these women, out-of-phase endometrium occurred despite polyovulatory cycles in which two and three histologically normal CL lutea were present and associated with elevated progesterone concentrations. Conclusions In CC-induced ovulatory cycles: (1) midluteal CL histology is normal and (2) apparently out-of-phase preimplantation endometrium occurs in midluteal phase.

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 α -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 × 10 − 10 M, respectively, in controls to 112 ± 6 fmol/mg protein and 2.1 ± 0.1 × 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 α -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 μ g/g) during the midluteal phase (days 15 to 19) rather than the early (2.2 ± 0.8 μ g/g, days 20 to 25) and late luteal phases (1.8 ± 0.8 μ g/g, days 26 to 30). Cytosol 17-OHP concentrations also were 3.3 ± 0.5, 4.3 ± 0.6, and 3.3 ± 1.0 μ g/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 μ g/g) and 17-OHP (0.9 ± 0.6 μ g/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.

Objective To evaluate the effect of oxytocin, its antagonist antocin, and agonist decomoton on baboon luteal cell P secretion. Design Prospective study. Setting Academic department of obstetrics and gynecology in a US medical school. Animal(s) Luteal-phased timed corpora lutea (CL) from a cohort of adult cycling baboons (Papio anubis). Intervention(s) Dispersed luteal cells from luteal phase baboon CL were cultured and treated with nothing (control), oxytocin (4–400 mU), antocin (4–400 μg), oxytocin with antocin, decomoton (4–400 μg), or oxytocin with decomoton. Main Outcome Measure(s) Basal and hCG (10 U)-stimulated P were measured in the incubate. Result(s) Basal P secretion did not change significantly with all peptides studied. The hCG-stimulated P secretion was significantly inhibited by oxytocin (4–400 mU), antocin (4–400 μg), and antocin combined with oxytocin, and with oxytocin, decomoton, and decomoton combined with oxytocin. Antocin (−12%) was less inhibitory than oxytocin (−25% to −22%). Antocin combined with oxytocin enhanced the inhibition to −35% to −39%. Decomoton had stronger (not significant) inhibition than oxytocin. Mean inhibition was 28%–35% with all doses of oxytocin, decomoton, or combined together. Conclusion(s) Although decomoton, an oxytocin agonist inhibited hCG-stimulated luteal cell P secretion in vitro, antocin also acted like an agonist, rather than an antagonist, in inhibiting P secretion.

Objective To determine the size of the baboon corpus luteum (CL) and levels of plasma P, 17α-hydroxyprogesterone (17-OHP), and E 2 in the ovarian vein draining it, the contralateral ovarian vein, and peripheral blood throughout the luteal phase of the menstrual cycle. Design Prospective study. Setting Academic department of obstetrics and gynecology in a US medical school. Animal(s) Corpora lutea from a cohort of 27 adult cycling baboons ( Papio anubis ). Intervention(s) Timed luteectomy. Main Outcome Measure(s) The authors weighed 166 CL and measured plasma P, 17-OHP, and E 2 in the blood samples obtained at luteectomy. Result(s) Early luteal phase corpora lutea weighed 189.1 ± 12.3 mg (mean ± SEM); their weight significantly increased to 239.4 ± 8.4 mg at mid luteal phase and significantly declined to 188.3 ± 14.0 mg in late luteal phase. Plasma P draining the CL (134.4 ± 20.5 ng/mL in early, 167.4 ± 18.7 ng/mL in mid, and 126.4 ± 23.4 ng/mL in late luteal phase) was significantly higher than that in contralateral ovarian (11.0 ± 1.4 ng/mL) and peripheral plasma (7.1 ± 0.9 ng/mL). Similarly, levels of both plasma 17-OHP (10.9 ± 1.5 to 15.9 ± 2.4 ng/mL) and E 2 (1.6 ± 0.2 to 2.6 ± 0.6 ng/mL) draining the CL were significantly higher than those from the contralateral ovary and peripheral blood (17-OHP, 1.1 ± 0.2 ng/mL; E 2, 0.2 ± 0.05 ng/mL). Conclusion(s) Largest in mid luteal phase, the baboon CL secretes P, 17-OHP, and E 2 throughout the luteal phase, with the highest levels seen in the ovarian vein draining the CL in the mid compared with the early and late luteal phases.

Eleven women with primary dysmenorrhea completed a randomized, double-blind, placebo-controlled, three-way cross-over study comparing 200 and 400mg suprofen. Menstrual fluid volume did not change. Mean+/-S.E.M. menstrual fluid PGF2a was significantly suppressed from 18.9+/-1.9 microg (placebo) to 10.9+/-1.7 and 9.3+/-2.1 microg with 200 and 400 mg suprofen, respectively (p=

Objective The purpose of this study was to compare acetaminophen with ibuprofen for pain relief and menstrual fluid prostaglandin F 2α (PGF 2α ) suppression in primary dysmenorrhea. Study design Twelve subjects were randomized to placebo, acetaminophen (1000 mg orally, 4 × daily for 3 days) or ibuprofen (400 mg orally, 4 × daily for 3 days), once during each cycle in a prospective, double-blinded, crossover study. Using preweighed super absorbent tampons, menstrual fluid was collected, extracted, and PGF 2α radioimmunoassayed. Results Ten patients completed the study. Ibuprofen ( P = .002) and acetaminophen ( P = .022) were rated significantly better than placebo. Total menstrual fluid PGF 2α with placebo was 36.2 + 6.1 μg but were 14.8 + 3.0 μg with ibuprofen ( P = .001) and 21.4 + 3.4 μg with acetaminophen ( P = .008). PGF 2α concentrations with placebo were 0.34 + 0.054 μg/mL, with ibuprofen 0.16 + 0.026 μg/mL ( P = .001), and with acetaminophen 0.23 + 0.029 μg/mL ( P = .016). Conclusion Both ibuprofen and acetaminophen were superior to placebo for pain relief and menstrual fluid PGF 2α suppression, with ibuprofen being more potent.

This study assesses one possible cause of inter-patient varia- tion in fluorescence spectroscopy of the cervix: the menstrual cycle. Ten patients with no history of an abnormal Pap smear were seen daily throughout 30 consecutive days of their cycle. Fluorescence excitation-emission matrices were measured from three cervical sites on each patient. Principal component analysis was used to determine which spectral regions varied with the day of the cycle. Classification was performed to assess the influence of menstrual cycle on precan- cer diagnosis. Variations in the principal component scores and the redox ratio values show that the fluorescence emission spectra at 340-380 nm excitation appear to correlate with the cell metabolism of the cervical epithelium throughout the menstrual cycle; these changes do not affect diagnostic classification. The menstrual cycle affects intra-patient variation but does not appear to cause a signifi- cant level of inter-patient variation. It does not need to be controlled for in optical detection strategies based on fluorescence spectroscopy.

Objective(s): To determine [1] vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels in peritoneal fluid from women with endometriosis and compare them with those from oral contraceptive (OC) users and normal cycling women and [2] any correlation between VEGF and IL-6 concentrations. Design: Controlled clinical study. Setting: University medical center. Patient(s): Patients undergoing laparoscopy for infertility or other benign gynecologic conditions. Intervention(s): Peritoneal fluid samples were collected. Main Outcome Measure(s): Levels of VEGF and IL-6 in peritoneal fluid were determined. Result(s): Compared with normal controls or women with less severe endometriosis (implant scores of 5 or less), women with more advanced endometriosis (implant scores of 6 or more) have elevated VEGF and IL-6 levels in peritoneal fluid. Compared with normal controls, markedly suppressed IL-6 but similar VEGF levels were found in peritoneal fluid from OC users. Neither VEGF nor IL-6 varied cyclically in normal women or those with endometriosis. There was no correlation between levels of VEGF and IL-6 in peritoneal fluid. There was no correlation between implant scores and VEGF or IL-6 levels. Conclusion: The inflammation associated with endometriosis, through increased levels of peritoneal fluid VEGF, may promote angiogenesis for the progressive growth of endometriosis. Effective treatment of endometriosis by combination estrogen–progestin pills may involve the suppression of such inflammatory responses.

Objectives: This study was undertaken to determine expression levels of oxytocin receptor and its gene in peri-implantation phase human endometrium during clomiphene-treated cycles compared with control cycles. Study Design: Oxytocin receptor and its messenger ribonucleic acid in peri-implantation phase endometrium during control and clomiphene-treated (50 mg days 5 to 9) cycles of 5 healthy fertile women were determined by immunohistochemical methods, Western blot analysis with monoclonal antibody against amino acids 20 through 40 of the extracellular N-terminal human oxytocin receptor, and reverse transcription–polymerase chain reaction with oligonucleotide primers to amplify the 391–base pair fragment of the oxytocin receptor gene. Results: Oxytocin receptor and its messenger ribonucleic acid were expressed in human peri-implantation phase endometrial samples from both control and clomiphene-treated cycles. The receptor was localized predominantly in the epithelial cells and glands, with little or none detected in the stroma. Oxytocin receptor protein was separated out as a single 70-kd band by Western blot analysis; its relative abundance was significantly reduced during clomiphene-treated cycles. The messenger ribonucleic acid was detected in all endometrium during control and clomiphene-treated cycles, with greater expression during control cycles. Conclusions: The expressions of oxytocin receptor and its gene in luteal phase human endometrium suggest a functional relevance in modulation of biochemical changes for implantation. (Am J Obstet Gynecol 1999;181:50-6.)

OBJECTIVE: The purpose of this investigation was to determine whether treatment with clomiphene citrate, which is estrogenic and antiestrogenic, affects the expression of the cell adhesion molecule E-cadherin in human periimplantation phase endometrium. STUDY DESIGN: Five healthy women were studied for two cycles each, a control and a treated (clomiphene 50 mg daily, days 5 through 9) cycle. A biopsy specimen of endometrial tissue was studied (8 to 10 days post luteinizing hormone surge) for immunohistochemical localization, Western analysis of E-cadherin with use of a highly specific monoclonal antibody to human E-cadherin, and determination of messenger ribonucleic acid for E-cadherin by reverse transcription–polymerase chain reaction by use of oligonucleotide primers specific to E-cadherin and amplifying a 432 bp fragment. RESULTS: Luteal phase plasma progesterone levels were significantly higher in clomiphene cycles. E-cadherin was immunocytochemically present in endometrium of control and treated cycles with no apparent difference in staining intensity. Western blots revealed the presence of E-cadherin. It was relatively more abundant in clomiphene-treated than control cycles but not significantly different. The message for E-cadherin gene is expressed in endometrium of control ( n = 5) and clomiphene cycles ( n = 4). CONCLUSIONS: E-cadherin and its gene transcripts are expressed in periimplantation phase endometrium and are not significantly affected by clomiphene treatment. (Am J Obstet Gynecol 1998;178:996-1001.)

OBJECTIVE: Our purpose was to determine and compare the efficacy and hormonal and metabolic effects of 1.25 mg with 2.5 mg of gestrinone given twice a week in the treatment of mild and moderate pelvic endometriosis. STUDY DESIGN: A phase II, prospective, randomized, double-blind study involving 11 patients given gestrinone 1.25 mg (five patients) or 2.5 mg (six patients) orally twice a week for 24 weeks was performed. Revised American Fertility Society scores were determined by laparoscopy before and at the end of treatment. Serum hormone (free thyroxine, free testosterone, estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone), sex hormone binding globulin, and lipid concentrations were measured before, throughout, and for 6 months after treatment. Quantitated computerized tomography of thoracic 12 through lumbar 4 vertebral bodies were determined before, at the end of, and 6 months after treatment. RESULTS: Gestrinone 2.5 mg significantly reduced the endometriosis implant score from 10.3 ± 2.8 to 3.8 ± 0.8 ( p = 0.05). Both doses significantly reduced serum progesterone and sex hormone binding globulin levels. Estradiol, free testosterone, free thyroxine, follicle-stimulating hormone, and luteinizing hormone levels were not significantly affected. Spinal bone increased significantly by 7.1% with 2.5 mg but lost significantly by 7.1% with 1.25 mg gestrinone; these changes had not reversed completely 6 months after stopping treatment. CONCLUSION: In mild to moderate pelvic endometriosis 2.5 mg of gestrinone twice a week was more effective and had a more positive effect on bone mass than did 1.25 mg of gestrinone. (Am J Obstet Gynecol 1997;176:387-94.)

Using saturation binding assays and Scatchard analyses, we determined the concentrations and binding affinities of epidermal growth factor (EGF) receptors in human myometrium (n = 13) and decidua (n = 10) before and during labor and in placenta (n = 15), chorion (n = 17), and amnion (n = 17) before labor, during labor, and after vaginal delivery. Each tissue was individually assayed. In myometrium and chorion, EGF receptors increased significantly from 5.6 +/- 0.8 and 13.5 +/- 1.7 fmol/mg protein (mean +/- SEM) before labor to 11.1 +/- 2.8 and 26.7 +/- 3.0 fmol/mg protein, respectively, after the onset of labor (P < 0.05). In amnion, EGF receptors increased from 12.8 +/- 2.7 fmol/mg protein before labor to 33.0 +/- 2.3 fmol/mg protein during labor, but decreased significantly (5.9 +/- 1.2 fmol/mg protein) with vaginal delivery (P < 0.05). Decidual and placental concentrations of EGF receptors did not change significantly with labor. The binding affinity of EGF receptors in all tissues studied did not change significantly with labor, as reflected by their respective association and dissociation constants. Up-regulation of EGF receptors in myometrium, chorion, and amnion with spontaneous labor may enhance stimulation of prostanoid production and stimulate uterine activity.

Baboon corpora lutea (two each from the early, mid- and late luteal phases) were individually microretrodialyzed in vitro for 48 h, 12 h initial baseline, 12 h retrodialysis with OT (9 mU/h), 12 h without OT and 12 h with cAMP (5 mmol/h). Progesterone (P) was measured by a sensitive and specific radioimmunoassay in 10-min fractions of retrodialysates and analyzed for P peaks by PC-pulsar 3.0. Neither OT nor cAMP had any effect on the characteristics of P pulses. In early and late luteal phase CL, OT inhibited P secretion within 1 h of administration followed by increased P secretion late during OT perfusion. In midluteal phase, OT did not affect P secretion. In all CL, P secretion was sustained or further increased during the 12 h after stopping OT. cAMP also sustained baseline or stimulated P secretion. In contrast, OT either increased total P output/12 h (28 to 49% above baseline) with a further increase of 21% to 296% above baseline after stopping OT, or inhibited total P output by 4% to 13% percent with a further decline of 51% to 61% after stopping OT. Thus, while overall OT is lutcotropic, its dual effect (initial inhibition followed by stimulation) suggests direct and indirect effects through paracrine-autocrine mechanisms.

We have previously shown that the protein connexin-43 which forms the connexons in gap junctions is present in the human corpus luteum. Abundant expression of connexin-43 is seen in the mid-luteal phase corpora lutea. Since the formation of gap junctions in a tissue requires the presence of adherens junctions formed by the cadherins, our aim in these studies was firstly to localize immunocytochemically E-cadherin and beta-catenin (a cytoplasmic protein associated with E-cadherin) in the human corpus luteum, and secondly to determine the concentrations of these proteins in the early, mid- and late luteal phase human corpora lutea. E-cadherin was localized to the periphery of luteal cells and was not detected in non-luteal tissue. beta-catenin was observed in the cytoplasm of the luteal cells. Abundant expression of E-cadherin was observed by Western analysis in the early luteal phase and the level of expression was significantly different from that observed in the mid- and late luteal phase corpora lutea. In contrast the concentrations of beta-catenin were higher in the mid-luteal phase compared to the early luteal phase. The differential expression of the cell adhesion molecule E-cadherin suggests that it may play a significant role in cell-to-cell communication in the corpus luteum, and in the cyclic development and demise of this tissue.

OBJECTIVE: The purpose of this article was to review the efficacy and potential hazards of assisted conception. STUDY DESIGN: A review of pertinent scientific articles published in English was done. RESULTS: There are no adequate prospective, randomized, controlled, or comparative studies of sufficient power on the efficacy of in vitro fertilization, gamete intrafallopian transfer, and superovulation with intrauterine insemination in well-defined infertile couples. In vitro fertilization can overcome tubal sterility. The pregnancy per cycle is 19.8% and delivery per cycle is 16.0% for in vitro fertilization (all indications) and 29.5% and 19.8%, respectively, for gamete intrafallopian transfer. In limited prospective studies, in vitro fertilization, gamete intrafallopian transfer, and superovulation with intrauterine insemination have similar fecundity. Multiple births from in vitro fertilization and gamete intrafallopian transfer are increased, whereas preterm labor and low-birth-weight babies are significantly more common, even in singletons. CONCLUSION: The efficacy or relative superiority of IVF, gamete intrafallopian transfer, and superovulation with intrauterine insemination in nontubal subfertility remains to be shown by properly designed, prospective, randomized, controlled, or comparative studies. Therefore less invasive and less expensive methods such as expectant management or superovulation with intrauterine insemination should be used before embarking on in vitro fertilization and gamete intrafallopian transfer. Further studies on the outcome of babies delivered after assisted conception are required. (AM J OBSTET GYNECOL 1996;174:1208-17.)

Objective To determine changes in trabecular vertebral bone mass, serum E 2 , 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 3.75mg IM depot LA given every month and daily placebo tablets (n=6) or 800mg 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 E 2 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 E 2 levels usually were 47.3pg/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 determine plasma levels of insulin-like growth factor-I (IGF-I), CA-125, estrone (E 1 ), E 2 , 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>14weeks 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 E 1 , E 2 , P, CA-125, and IGF-I were determined by specific and sensitive RIAs and immunoradiometric assays. Results Plasma IGF-I levels were 2,006±185mU/mL (mean±SEM, n=35) and 2,335±287mU/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±239mU/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 E l , E 2 , and P levels during the follicular phase (91.9±11.5pg/mL; conversion factor to SI unit, 3.699; 94.6±19.0pg/mL; conversion factor to SI unit, 3.671; and 1.5±0.4ng/mL; conversion factor to SI unit, 3.180, respectively) and the luteal phase (105.8±11.2pg/mL; conversion factor to SI unit, 3.699; 128.7±24.8pg/mL; conversion factor to SI unit, 3.671; and 9.6±1.6ng/mL; conversion factor to SI unit, 3.180) similar to normal women. Conclusion Plasma levels of IGF-I, CA-125, E 1 , E 2 , and P are normal in women with leiomyomas.

Five postmenopausal women received single doses of a 0.675 mg estradiol hydroxypropyl-beta-cyclodextrin (estradiol-HP beta CD) sublingual tablet by the sublingual and oral route. A single dose of a 1 mg micronized estradiol tablet was given orally for comparison. Blood samples were obtained over 48 hours for measurement of estradiol, estrone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Sublingual administration produced faster and significantly higher peak estradiol concentrations than after oral administration of either estradiol-HP beta CD or micronized estradiol. The concentration-time area under the curve of estradiol after sublingual estradiol-HP beta CD was also significantly larger than after oral administration of either estradiol-HP beta CD or micronized estradiol, reflecting a larger estradiol bioavailability. The estradiol/estrone concentration ratio after sublingual estradiol-HP beta CD revealed a predominance of estradiol for the first 2 hours after the dose, followed by an estrone predominance. Both oral doses produced a predominant delivery of estrone to the systemic circulation. There was not difference in time-averaged LH suppression between the three phases. However, estradiol-HP beta CD sublingually produced greater FSH suppression than oral micronized estradiol.

A review of studies examining the effect of medical therapy of endometriosis on bone mass and potential approaches to preventing bone loss was undertaken. Studies specifically examining bone density in women with endometriosis treated medically were used. Reports on effects of oral contraceptives and progestins on bone mass were derived from women using them for contraception. Oral contraceptives and medroxyprogesterone acetate apparently did not adversely affect bone mass. While initial studies with dual-photon absorptiometry were unable to detect appreciable bone loss with gonadotropin-releasing hormone agonist, subsequent studies have invariably found significant bone loss beginning as early as 3 months of treatment. Quantitated computerized tomography always shows significant trabecular bone loss of the vertebrae and hip with gonadotropin-releasing hormone agonist. Depot preparations appear to produce more marked loss than daily injections of intranasal spray. Recent studies indicate recovery of bone loss may take longer than 6 months or even 1 year after discontinuation of therapy with considerable individual variation. Danazol produced bone gain. Bone loss with gonadotropin-releasing hormone agonists could be prevented or attenuated with progestins, and this is worthy of further studies. Impact of medical therapy on bone mass should be a practical consideration in the selection of patients, in repeat medical therapy for recurrence of endometriosis, and in formulation of medical therapy so as to attenuate or overcome such silent adverse effects.

Midluteal phase endometrium was histologically dated with midcycle luteinizing hormone surge time in 29 cycles from 10 parous women during untreated cycles (control) and treatment with clomiphene citrate 50 mg and 150 mg daily on days 5 through 9. Integrated progesterone output for 7 days after luteinizing hormone surge calculated from the daily plasma progesterone levels was 66.6 +/- 9.8 ng/ml in the control group compared with 117.5 +/- 18.6 ng/ml for clomiphene citrate 50 mg treatment and 152.1 +/- 11 ng/ml for clomiphene citrate 150 mg treatment (p less than or equal to 0.05). Only one cycle (clomiphene citrate 150 mg) had an out-of-phase endometrium and a significantly reduced integrated progesterone output of 28 ng/ml. All other cycles showed synchronous endometrial maturation. We conclude that luteal insufficiency as a result of clomiphene citrate treatment in ovulatory women is infrequent and is more likely to be a result of functional outcome of a relative lack of luteal phase progesterone output.

In a prospective, randomized study, 106 patients underwent induction of labor with either pulsed (every 8 minutes) (n = 50) or continuous (n = 56) intravenous infusion of oxytocin. Maternal characteristics, gestational age at induction, induction-delivery interval, analgesia for labor, cesarean section rates, and newborn characteristics were similar in both groups. The mean +/- SEM total oxytocin administered was significantly less in the pulsed group (3564 +/- 487 mU) than in the continuous group (7684 +/- 844 mU; p less than 0.0001); the average dose of oxytocin administered per minute was significantly lower in the pulsed group (3.9 +/- 0.3 mU/min) than in the continuous group (7.8 +/- 0.4 mU/min; p less than 0.0001); the peak or highest administered dose of oxytocin expressed per minute was also signficantly lower in the pulsed group (9.6 +/- 0.8 mU/min) than in the continuous group (14.1 +/- 0.7 mU/min; p less than 0.0001). These significant differences persisted even when controlled for parity, Bishop's score of the cervix, and number of days induction of labor was carried out. Uterine hyperstimulation occurred infrequently in both groups (3.6% to 4.0%). The pulsed group required a significantly smaller infusion volume (25 +/- 14 ml) than the continuous group (780 +/- 84 ml; p less than 0.0001). Thus pulsatile administration uses significantly less oxytocin and infusion fluid but is as effective and safe as continuous infusion.

A review of the clinical features, diagnosis and management of primary and secondary dysmenorrhea updates some old views. Dysmenorrhea is painful menstruation, either cramps with no visible cause, primary dysmenorrhea, or secondary to specific pelvic pathology. Primary dysmenorrhea occurs in as many as 50% of young women, only in ovulatory cycles, and usually limited to the first 48 or 72 hours of menstruation. Secondary dysmenorrhea can be caused by any of a dozen or so disorders such as endometriosis, pelvic inflammatory disease, IUDs, irregular cycles or infertility problems, ovarian cysts, adenomyosis, uterine myomas or polyps, intrauterine adhesions or cervical stenosis. Psychological factors are now known not to cause dysmenorrhea, only to add to the reactive component of the pain. The pain is due to uterine cramps, hypoxia or ischemia, due to overproduction of prostaglandins, leukotrienes or vasopressin. Thus, primary dysmenorrhea can be treated with oral contraceptives if the women wishes to take pills for contraception and they are not contraindicated, or with non-steroidal antiinflammatory agents for the full 72 hours after pain begins. Calcium channel-blockers are also used on a research basis; transcutaneous electrical nerve stimulation is sometimes effective. If these treatments are not effective, investigation for causes of secondary dysmenorrhea is indicated, preferably for laparoscopy.

To characterize and determine the concentration of LH/hCG receptors in human corpora lutea of the menstrual cycle, we measured occupied and unoccupied receptors and determined the association (Ka) and dissociation (Kd) constants individually in 23 corpora lutea (CL) and 4 corpora albicantia obtained at the time of tubal ligation from 25 normal cycling women. We found no [125I]hCG binding in any of the corpora albicantia. Scatchard plot analysis for each CL revealed a linear binding plot indicative of a single set of LH/hCG receptors. The mean concentration of unoccupied receptors was 36 +/- 10 (+/- SE) fmol/mg protein in the early luteal phase (days 15-19; n = 5), 64 +/- 11 fmol/mg protein in the midluteal phase (days 20-25; n = 13), and 42 +/- 19 fmol/mg protein in the late luteal phase (days 26-30; n = 5). The concentrations of occupied receptors were 56 +/- 8, 46 +/- 6, and 54 +/- 12 fmol/mg protein in the early, mid-, and late luteal phases, respectively. Total (occupied plus unoccupied) receptor concentrations reached maximum levels of 110 +/- 11 fmol/mg protein in the midluteal phase. Ka increased progressively from 12 +/- 4 X 10(9) mol/L-1 in the early luteal phase to 19 +/- 7 X 10(9) and 21 +/- 8 X 10(9) mol/L-1 in the mid- and late luteal phases. We conclude that in normal CL, 1) total and unoccupied LH/hCG receptor levels parallel progesterone secretion; 2) changes in the binding affinity may be important in sustaining and/or rescuing the CL; and 3) loss of LH/hCG receptors is probably related to luteolysis.

We have measured the concentrations of circulating oxytocin and the 13, 14-dihydro, 15-keto-metabolite of prostaglandin F2 alpha (PGFM) in women during preterm labor. Twelve women were given intravenous ethanol and 11 women received intravenous ritodrine for the prevention of preterm birth. Blood samples were obtained before and 1/2, 1, 2, 4, 12, and/or 24 hours after treatment began. On admission, the plasma concentrations of both oxytocin and PGFM were raised over levels observed in women with normal pregnancies of similar gestational age, 25 to 36 weeks. The initial oxytocin level was 58.5 +/- 8.2 pg/ml (mean +/- SE, n = 23) and the mean initial PGFM level was 264 +/ 33.1 pg/ml (n = 15); both values were significantly higher than in 10 control subjects (17.4 +/- 4.8 and 156 +/- 21.8 pg/ml, respectively). During infusion of ethanol, the plasma oxytocin level fell rapidly, the levels at 1/2 and 1 hour after infusion being significantly lower than before the infusion (29.0 +/- 5.5 and 27.8 +/- 3.5 pg/ml, respectively). The plasma oxytocin level remained low in women in whom the treatment arrested labor and prevented preterm birth (n = 8) but rose 2 to 4 hours after the infusion began in women in whom the treatment failed to arrest labor (n = 4). Ritodrine, on the other hand, had no significant effect on circulating oxytocin levels. The plasma PGFM level decreased significantly during ritodrine treatment only in the successfully treated patients. Ethanol had no consistent effect on plasma PGFM levels in the four patients in whom PGFM levels were measured. In the ritodrine-treated patients, the plasma PGFM level was positively correlated with the frequency of uterine contractions whereas in the ethanol-treated patients a correlation of plasma oxytocin to the frequency of contractions was observed. Thus, oxytocin secretion is increased during preterm labor, and the release of prostaglandin F is also increased. While it is not possible to determine whether any or both of these oxytocic agents actually trigger preterm labor, both seem to play a role in its mechanism.

The prostaglandin synthetase inhibitor ibuprofen was evaluated for relief of severe primary dysmenorrhea in a controlled, double-blind, cross-over study in seven patients for a total of 23 menstrual cycles. In eight untreated cycles, the amount of prostaglandin (PG) in the menstrual fluid was higher than in nondysmenorrheic subjects. There was good to excellent relief of dysmenorrhea in seven ibuprofen-treated cycles, which was associated with a threefold to fourfold reduction in menstrual PG released. When a placebo was given in five cycles, only poor or minimal relief of dysmenorrhea was obtained and the menstrual PG released was similar to that in control cycles. In individual patients, there was a remarkable correlation between the severity of menstrual pain as assessed daily by the patient and the level of menstrual PG released during the corresponding period. The effect of ibuprofen therapy on menstrual fluid volume was inconsistent. The study shows that in severe primary dysmenorrhea there is increased release of PG in the menstrual fluid; this can be effectively suppressed with ibuprofen, which provides excellent relief from the symptoms of dysmenorrhea.

To assess fetal oxytocin release in relation to maternal oxytocin, serial paired maternal (femoral artery) and fetal (aorta) plasma oxytocin were determined by a specific and sensitive radioimmunoassay during pregnancy and parturition in the sheep. The maternal oxytocin level was 29.1 +/- 2.6 pg/ml (mean +/- SE) but was significantly lower than fetal oxytocin levels of 45.8 +/- 4.3 pg/ml (p less than 0.001). There was a significant correlation between paired maternal oxytocin and fetal oxytocin levels throughout late pregnancy (r = 0.2523, p less than 0.05). Maternal oxytocin levels calculated for every 5 days' gestation ranged from 15.8 +/- 2.7 to 32.7 +/- 5.6 pg/ml while the corresponding fetal oxytocin levels (21.6 +/- 3.5 to 62.5 +/- 21.6 pg/ml) were always higher (92 to 135 days) but not significantly different. However, at 136 to 142 days' gestation, fetal oxytocin levels (63.9 +/- 14.1 pg/ml) were significantly higher than maternal oxytocin levels (20.1 +/- 3.3 pg/ml) (p less than 0.01). Based on observations in two animals, fetal oxytocin levels appeared higher than maternal oxytocin levels at parturition with an increase a few days before labor. Our findings indicate that, in the sheep, fetal oxytocin levels were usually higher than but not significantly different from maternal oxytocin levels and that fetal oxytocin levels changed in relation to labor, suggestive of fetal release of oxytocin.

Serum progesterone was assayed by the competitive protein-binding technique in 20 cases of gestational choriocarcinoma and one case of nongestational choriocarcinoma. Serum human chorionic gonadotropin (HCG) was simultaneously measured from the same blood samples by the hemagglutination-inhibition technique. Serum progesterone in choriocarcinoma ranged from 1.3 to 182.9 ng. per milliliter with a mean ± standard error of the mean of 36.2 ± 10.2 ng. per milliliter. Serum HCG ranged from 0.6 to 1,280 I. U. per milliliter. In 11 patients with choriocarcinoma, serum progesterone levels were indistinguishable from values obtained during the luteal phase of the normal menstrual cycle; six patients had values similar to those found in early normal pregnancy and four patients with postmolar villous choriocarcinoma had elevated serum progesterone. There was a significant correlation between serum HCG and serum progesterone ( r = + 0.5652, p = 0.005). The significance of these findings is discussed with reference to the likely source of progesterone in choriocarcinoma.

The mechanisms controlling luteal function may involve factors that are produced both within the corpus luteum and outside the ovary. The process of luteal control appears to involve a series of molecular species, proteins, peptides, steroids and prostaglandins. Each of these factors may act independently or in concert modifying the actions of one another. The effect of GnRH on luteal function has not been completely examined and thus its significance is unclear. The neurohypophyseal peptides, oxytocin and arginine vasopressin, in combination with LH, prolactin, oestrogens and prostaglandins may play an important regulatory role on the corpus luteum.

To determine the temporal relationship between immunoreactive chorionic gonadotropin, chorionic gonadotropin receptors, and implantation of the rabbit blastocyst, (1) immunoreactive chorionic gonadotropin in plasma, uterine flushings and blastocysts; (2) chorionic gonadotropin receptors on blastocysts (day 5 and 6) and embryonic and interembryonic segments of the uterus (day 7); and (3) chorionic gonadotropin receptors on the endometrium and myometrium (day 1 through 6) were measured. Binding of I125-labeled beta-subunit of human chorionic gonadotropin (hCG) by cell membranes from blastocysts increased significantly from 6.0 +/- 1.1 fmol/mg of protein (mean +/- SE) on day 5 (N = 6) to 16.1 +/- 1.3 fmol/mg of protein on day 6 (n = 6) (P less than 0.001). Immunoreactive chorionic gonadotropin levels in blastocyst fluid increased from 0.3 ng/ml of day 5 to 0.65 ng/ml on day 6. Specific binding of I125-labeled hCG was absent in endometrial and myometrial cell membranes before implantation (days 1 to 6) but was found in decidual cells from embryonic segments on day 7. Plasma immunoreactive chorionic gonadotropin or chorionic gonadotropin--like material increased from 6 ng/ml of day 1 to 52 ng/ml on day 7. Uterine flushings had chorionic gonadotropin levels of 0.4 ng/ml of day 2, which increased slowly to 1.0 ng/ml on day 7. Intrauterine instillation of hCG into nonpregnant uterine horns demonstrated transuterine absorption of hCG with plasma hCG levels showing a dose-related response. Our findings demonstrate that (1) immunoreactive chorionic gonadotropin or chorionic gonadotropin--like material is detectable in plasma, uterine flushings, and blastocyst fluid before implantation, (2) chorionic gonadotropin receptors are present on the blastocyst cells before implantation, and (3) the uterus can absorb chorionic gonadotropin from its lumen.

Summary: Serum oestradiol-17-β was measured by a radioimmunoassay method as described by Hotchkiss et al. (1971), using antiserum against 6-oxo-oestradiol succinyl bovine serum albumin conjugate raised in sheep. One hundred and fifty-eight determinations of serum oestradiol were performed on normal pregnancy cases between the 30th and 42nd weeks of gestation. Serial serum oestradiols were assayed in 5 cases of hypertensive disorder of pregnancy in the third trimester. Serum oestradiol-17-β rose from a mean value of 12.01 ± 3.80ng./ml. (± 1 S.D.) at 30 weeks of gestation to a peak of 66.72 ± 31.39 ng./ml. (±1 S.D.) at 40 weeks. Thereafter serum oestradiol fell to 66.02 ± 26.48 ng./ml. (± 1 S.D.) at 41 weeks and 42.77 ± 18.53 ng./ml. (± 1 S.D.) at 42 weeks of gestation. In 3 out of 5 cases of severe hypertensive disorder of pregnancy, which ended in delivery of normal healthy babies, serial serum oestradiol fell within the range of values for normal pregnancy. In 2 hypertensive cases, where the babies showed evidence of intrauterine growth retardation, serial serum oestradiol values were consistently below the range of serum oestradiol for normal pregnancy. Thus serum oestradiol 17-β could be a useful indicator of fetal well-being in pregnancies complicated by hypertension.

Seventeen human fetal and neonatal pituitary glands were removed at necropsy, and analyzed for oxytocin content by a specific and sensitive radioimmunoassay, after homogenization in 0.4M acetic acid. Serial dilution of the pituitary extract showed parallelism with the oxytocin standard curve on the radioimmunoassay. Column chromatography of the pituitary gland extract gave a single peak of immunoreactive oxytocin as determined by the radioimmunoassay. In eight fetuses, 14 to 17 weeks' gestation, pituitary gland oxytocin was 10.2 ± 5.9 ng/gland (mean ± SE), whereas an 18-week fetus had 5.8 ng of oxytocin per gland. Pituitary gland oxytocin content increased to 38.4 ng/gland in a 20-week fetus removed at hysterectomy, and 31.6 ng/gland in a 26-week fetus. Fetal pituitary gland oxytocin values were 22.1 ng/gland and 57.0 ng/gland at 32 weeks and increased significantly to 544.3 ± 33.8 ng/gland in 1- to 5-day-old term newborn infants (n = 3). However, a 13-day-old term newborn infant had 3.7 ng of oxytocin per pituitary gland. The increased pituitary gland oxytocin content with advancing gestation was due to a significant increase in oxytocin concentration rather than to an increase in the weight of the pituitary gland. The findings indicate that oxytocin is present in fetal pituitary glands as early as 14 to 17 weeks' gestation and increases at term to 50 and 13 to 14 times more than in early midtrimester and early third-trimester pregnancy, respectively.

To elucidate the role of prolactin in the control of pituitary-ovarian function, eight healthy women were given 80 mg of synthetic thyrotropin-releasing hormone (TRH) orally on two consecutive days during the luteal phase of their menstrual cycle. TRH elevated serum prolactin to a mean concentration of 43.8 ng/ml on the first day and to 15.5 ng/ml on the second day. The reduced response to the second TRH dose was statistically significant (p < 0.05). Accompanying changes in concentrations of gonadotropins or ovarian steroids were not consistent. Short-term oral administration of TRH and/or the temporary hyperprolactinemia induced by its use do not modify the pituitary-ovarian function during the luteal phase of the menstrual cycle.

The diagnostic accuracy and therapeutic value of hysterosalpingography (HSG), laparoscopy, and hysteroscopy were evaluated in 77 women who underwent these procedures as part of their infertility evaluation. HSG revealed in 32 women (42%) evidence of tubal or peritoneal disease, and 16 other women (21%) had radiographic evidence of intrauterine abnormalities. These findings were confirmed by laparoscopy in 84% of patients and by hysteroscopy in 69%, giving false-positive rates of 16% and 31% for HSG. HSG had a false-negative rate of 13% for tubal or peritoneal disease as subsequently uncovered by laparoscopy, and 1.3% for intrauterine lesions as revealed by hysteroscopy. The data suggest that while laparoscopy is of value in detecting previously unsuspected tubal disease, hysteroscopy adds little information in the management of the infertile patient. For optimum evaluation, a combined approach using all three procedures is recommended, especially in patients with a history of uterotubal and peritoneal lesions.