The management of patients with premature rupture of membranes (PROM) poses one of the most serious dilemmas in obstetrics since PROM significantly increases the likelihood of prematurity and serious perinatal infection. Early infection is not reliably predicted nor detected by standard laboratory parameters. Serum C-reactive protein (CRP) levels were assayed along with white blood cell count, differential, and temperature course in patients with PROM and controls. Elevated CRP very accurately divided patients with evidence of infectious morbidity from those without such evidence (p < 0.001). In 109 patients there were 11 false negatives and no false positives. In 14 of 20 patients followed with serial comparisons who developed morbidity, CRP became elevated at least 12 hours prior to any other parameter measured. Changes in the other six patients were concurrent. The results suggest that CRP may be a reliable, early predictor of infectious morbidity and thus may be of benefit in the selective management of patients with PROM.
Wedge resection was performed in 12 patients with polycystic ovarian disease, and cell samples from the cystic follicles were assayed for LH(hCG) receptor using [125I]iodo-hCG as a ligand hormone. Simultaneously to wedge resection, blood samples were taken for serum FSH, LH, 17 beta-estradiol, progesterone, and testosterone RIA measurements. Serum LH was regularly elevated (16.0-57.1 U/liter), whereas FSH (5.2-11.5 U/liter) was within the normal reference range. The LH to FSH ratio was between 2.1-7.8. The 17 beta-estradiol concentrations (0.12-0.23 nmol/liter) were within the normal reference range found during the early follicular phase. Only 3 patients had progesterone levels exceeding the assay sensitivity limit of 0.1 nmol/liter. Ony 3 of the 11 patients assayed for serum testosterone had values exceeding the upper limit of the reference range. Seventy-seven percent of the ovarian follicular samples showed specific binding of [125I]iodo-hCG. The number of receptors in positive samples averaged 0.67 +/- 0.11 fmol/mg homogenate protein, which is clearly lower than that in normal preovulatory follicles. Scatchard analyses revealed a single class of binding sites, with a mean equilibrium association constant of 5.4 X 10(9) M-1 at 37 C. These results suggest that the derangement of follicular development in patients with polycystic ovarian disease probably is not due to the lack of appearance of the LH(hCG) receptor. It is possible that the tonic elevation of serum LH results in a decrease in the number of available receptor sites; this would be one step in the process leading to ovarian changes characteristic of this disease.
Leyendecker G et al., 1980·J Clin Endocrinol Metab
In previous studies it could be demonstrated that in severe hypothalamic amenorrhea, which is associated with absent or deficient hypothalamic secretion of Gn-RH, ovarian function could be restored by chronic intermittent (pulsatile) administration of Gn-RH. In order to apply chronic intermittent administration of Gn-RH as a new mode of treatment of infertility in hypothalamic amenorrhea on an outpatient basis a portable device ("Zyklomat") was constructed consisting of a peristaltic pump, a computerized timing device and a Gn-RH containing bag, which delivers 50 microliters of a Gn-RH containing solution once every 90 minutes via an i.v. catheter into the circulation. It is the purpose of this communication to present this new method of treatment and the successful induction of the first two pregnancies with this method in two patients with severe hypothalamic amenorrhea.
The luteinized unruptured follicle syndrome is a frequent phenomenon, occurring in half of our women with regular cycles and infertility. Progesterone concentrations and 17 beta-oestradiol concentrations were assayed in peritoneal fluid of women during the luteal phase. Up to day 20 of the cycle, the concentrations were significantly higher in women with an ovulation stigma than in women without an ovulation stigma on their corpus luteum. The range of concentrations was sufficiently different in the early luteal phase to be used diagnostically, the only limitation being the presence of a cystic corpus luteum. We suggest that the assay of progesterone and 17 beta-oestradiol in peritoneal fluid should be done in all women with infertility and biphasic basal body temperature charts in order to diagnose the luteinized unruptured follicle syndrome.
The treatment of hirsute women is controversial and often presents a therapeutic dilemma. Mechanical methods (such as shaving or using depilatories) are safe but often unacceptable to the patient, whereas suppression of adrenal or ovarian function may not be effective and may have undesirable side effects. An alternative approach is the use of a drug that blocks androgen action at the hair follicle. Such blocking should be successful whether the source of the excess androgen is ovarian or adrenal. Because cimetidine has recently been found to have antiandrogenic activity, 1 2 3 we used it to treat severely hirsute women and assessed its . . .
PregnancyTocolytic TherapyPreterm Birth PreventionProgesterone Supplementation in Pregnancy
A shift in progesterone-to-estradiol balance to estradiol dominance is assumed to be a prerequisite for regular uterine contractions. To antagonize this effect in premature labor 24 consecutive women were treated with intravenous cortisol for 3 days and with weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate (17 OHP-C). Twenty-four similar patients treated with ritodrine served as a reference group. The delivery was postponed by at least 1 week in 21 patients (87.5%) in the steroid treatment group and in 18 patients (75%) in the ritodrine group. The premature labor lasted for 5.1 +/- 0.4 hours (mean +/- SEM) with steroid therapy and for 2.2 +/- 0.3 hours with ritodrine. In singleton pregnancies the gestational length and birth weight of the newborn infants were greater in the steroid treatment group (N = 23, 39.1 +/- 0.3 weeks, 3,460 +/- 119 gm) than in the ritodrine group (N = 24, 37.7 +/- 0.4 weeks, 3,106 +/- 118 gm). Steroid treatment suppressed serum estradiol concentrations (maximally by 60%) and, to a lesser extent, testosterone, estriol, and progresterone levels (maximally by 30%).
Cytogenetic analysis of 1000 spontaneous abortions showed 463 to have an abnormal chromosome constitution. The proportion of chromosome abnormalities varied with the gestational age of the abortus and the type of tissue cultured but was not significantly different among the five racial groups represented in the study population. It was suggested that differences in the rate of chromosome abnormalities among cytogenetic studies of spontaneous abortions were the result of methodological differences in sample selection rather than real biological variation among study populations. The only factor found to be unequivocally associated with the aetiology of chromosome abnormalities in spontaneous abortions was increasing maternal age in trisomies.
Dommisse J, 1980·South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
A historical review reveals that Naegele's rule was based on anecdotal evidence. This rule should be reviewed and calculations of true gestational age should be based on the probable date of ovulation and conception.
Body LiteracyHospital-Based NFP ProgramsProgram DevelopmentHealthcare Settings
Now that principles of NFP have been established specific programs are necessary to disperse information and to teach techniques. The hospital-based NFP program offers the community a needed service and benefits the hospital.
Purpose Endometriosis is a benign estrogen-responsive disease which shares some characteristics with malignant tumors such as invasion and unrestrained growth. In this respect, the epidermal growth factor receptor family (EGFR or erbB-1 and erbB-2 to -4) is known to play an important role in tumor biology. The 1) to investigate the expression patterns of the four erbB receptors, 2) to ascertain if there was a correlation between the EGFR family expression and the expression of the estrogen receptor α (ERα). 48 peritoneal and 12 ovarian human endometriotic lesions were analyzed by immunohistochemistry. The confirmation of the immunohistochemical findings was made by Western blot analysis. Using the Mann-Whitney-U test, statistical analysis was performed. Results In peritoneal and ovarian endometriosis, all members of the EGFR family and ERα are detectable in stromal and epithelial cells, but the expression is different within the tissues. Only in ovarian endometriosis was a statistical association observed between EGF receptor and ERα expression (p<0.017). Conclusions The differential expression of the erbB receptors suggest that the erbB family might play an important role in the pathogenesis of endometriosis. A significant association between EGF receptor expression and the ERα expression was only found in ovarian endometriosis.
EndometriosisAdolescent EndometriosisPelvic Pain in AdolescentsOvulation Suppression and Surgery
Endometriosis was encountered in 66 of 140 patients (47%) who underwent laparoscopy for chronic pelvic pain at Boston Children's Hospital Medical Center. Pelvic pain associated with this diagnosis was both cyclic and acyclic and typically began 2.9 years after menarche. Other symptoms included irregular menses, gastrointestinal and bladder symptoms, and increased vaginal discharge. The diagnosis of endometriosis had not been made preoperatively in the majority of patients despite repeated pelvic examinations and thorough evaluation of the gastrointestinal and urinary tracts. Psychiatric referral had been recommended for 10 patients. The most constant physical finding preoperatively was tenderness with or without cul-de-sac nodularity. Eleven patients (17%) with biopsy-proved endometriosis has normal pelvic examinations. Fifty-eight percent of patients had early and minimal disease (stage I). In the remaining patients, the disease was more extensive, involving the ovaries, tubes, and/or adjacent pelvic structures (stages II-IV). Although in most instances the implants were typical in appearance, in 13 patients (20%) the disease was not recognizable grossly, but was confirmed morphologically. The regimens utilized as primary treatment were based on the stage of the disease and consisted of either ovulation suppression alone or surgery with or without subsequent ovulation suppression. A satisfactory outcome was achieved in 47 patients (71%). The remaining 19 patients (28%) who did not respond to primary treatment were either operated on or treated symptomatically and are being carefully followed.
InfertilityLuteal Phase DefectProgesterone MeasurementLuteal Phase Dating
Plasma progesterone concentrations drawn at the time of endometrial biopsy in 26 infertility patients with histologically documented luteal phase inadequacy were compared with those of 26 infertility patients with normal biopsies. Although as a group the former patients had lower progesterone values and shorter cycles, there was considerable overlap. Therefore, although plasma progesterone determinations and temperature charts are useful in the detection of ovulation and in the interpretation of the biopsy results, a properly obtained endometrial biopsy is essential for the diagnosis of luteal phase inadequacy.
Healthy volunteers with regular ovarian function, women taking oral contraceptives, and infertile patients being treated with clomiphene were studied longitudinally from day 7 of the cycle to menstruation. The main objective was to determine whether ovulation or failure to ovulate could be detected accurately by the use of ultrasound. The ovaries were scanned with a Kretz Combison 100 sector scanner every 1 to 3 days for morphologic changes consistent with follicle development, ovulation, and development of the corpus luteum. The morphologic changes were correlated with daily urinary hormone profiles. The estimated times of ovulation according to ultrasound and luteinizing hormone peak overlapped by 24 hours in 19 of 23 normal cycles and in 5 of 6 cycles of patients treated with clomiphene. Both techniques indicated that three of three women taking oral contraceptives did not ovulate. The ultrasound studies indicated a wide range in the diameter of the preovulatory follicle, which precludes follicular diameter as a single index for prediction of ovulation. However, by measuring the maximal diameter of the follicle and observing the morphologic changes within the ovary from follicle to corpus luteum, it was possible to detect ovulation in more than 80% of cycles studied. This technique was found to be quick, inexpensive, and efficient.
Three hundred and ninety-six patients were evaluated for primary and secondary infertility between December 1976 and May 1979 at a large referral center. Timed late luteal endometrial biopsies were routinely obtained as part of the work-up and were repeated for confirmation if subsequent menses did not occur within 2 days of the expected date. If both biopsies were abnormal, a diagnosis of luteal phase defect (LPD) was made and patients were treated with vaginal progesterone suppositories for a minimum of 6 months. LPD was discovered in 32 of 396 patients (8.1%); among those patients whose infertility was not complicated by other abnormalities, 9 of 13 conceived (70%) and 7 of 13 carried to term (54%). These data suggest an incidence higher than generally recognized and a very encouraging response to replacement therapy.
Crowley WF Jr et al., 1980·J Clin Endocrinol Metab
The administration of small doses of LHRH at 2-hourly intervals over a 27 day period to a 24-year old patient with Kallman's syndrome resulted (1) a biphasic temperature response, (2) anatomical changes in the ovaries demonstrated by ultrasound, and (3) the pattern of circulating gonadotropin and gonadal steroid concentrations.
Lönnerdal B et al., 1980·The American journal of clinical nutrition
Nitrogen and protein composition was determined in milk from women using oral contraceptives during lactation. Total nitrogen and nonprotein nitrogen as well as lactose and the individual milk proteins lactoferrin, alpha-lactalbumin, and serum albumin were analyzed before introduction of oral contraceptives and thereafter throughout the lactation period. Twenty-four hour milk volumes were registered by weighing the infant before and after each feeding. The four oral contraceptives used consisted of different combinations of d-norgestrel, megestrolacetate, and ethinylestradiol. Significant changes were observed between groups and controls for all parameters studied. However, the changes observed were generally within the physiological variation of normal breast milk. It is suggested that the use of oral contraceptives during lactation should be limited.
In rhesus monkeys with hypothalamic lesions (which appear to abolish the endogenous production of gonadotropin-releasing hormone), normal ovulatory mestrual cycles were reestablished by an unvarying, long-term replacement regimen consisting of one intravenous pulse of synthetic gonadotropic-releasing hormone per hour. This finding is in accord with the hypothesis that the pattern of pituitary gonadotropin secretion throughout the menstrual cycle (basal secretion interrupted, once every 28 days on the average, by a preovulatory surge) is not directed by alterations in hypothalamic gonadotropin-releasing hormone secretion but by the ebb and flow of ovarian estrogens acting directly on the pituitary gland.
Fertility AwarenessBillings Ovulation MethodComparison of NFP MethodsMucus-Based Fertility Monitoring
Myometrial tissues from pregnant and nonpregnant mature and immature rats were examined for the presence of gap junctions by thin section and freeze-fracture microscopy before and after incubation in vitro. Gap junctions were not present in any tissues fixed in situ or shortly after removal from animals. The junctions were present in tissues incubated for 2 h in vitro, and the number and size of the junctions increased with increasing incubation times up to 48 h. Tissues from immature rats incubated in vitro formed gap junctions in much reduced numbers as compared to tissues from pregnant or nonpregnant mature animals. Injection of immature animals with estrogen with or without progesterone, but not with progesterone alone, increased the number of gap junctions found in tissues when incubated in vitro. In vitro treatment of tissues from immature animals with estrogen also stimulated the formation of gap junctions. Progesterone treatment in vitro had no effect on gap junction formation in any myometrial tissues. However, progesterone added in vitro in the presence of estrogen decreased the number of gap junctions as compared to the numbers formed with addition of estrogen alone in treated tissues from immature or pregnant animals. The addition of indomethacin 5,8,11,14-eicosatetraynoicacid and arachidonic acid partially inhibited the formation of gap junctions in tissues from pregnant animals incubated in vitro. A stable endoperoxide of PGH2 and arachidonic acid, but not PGE1, PGE2, PGF(2α), or thromboxane β2, overcame the inhibition of gap junction formation produced by indomethacin. These results are consistent with the hypothesis that steroid hormones and prostaglandin interact to modulate gap junction formation in the myometrium.
Fertility AwarenessSperm-Mucus InteractionHormonal Effects on CervixSemen Quality and Cervical Transport
Twenty-five women scheduled for hysterectomy for nonmalignant disease participated in the study. Sperm storage in endocervical crypts was examined nine women pretreated with estrogen and inseminated with normal semen, nine women pretreated with gestagen and inseminated with normal semen, and seven women pretreated with estrogen and inseminated with abnormal semen. The number of crypts containing spermatozoa (colonized crypts) and the sperm density per crypt were examined in serially sectioned cervices. In estrogen-pretreated cervices both the percentage of colonized crypts and the sperm density were significantly higher than in gestagen-pretreated cervices. Large and giant crypts proved to be the main storage facility for spermatozoa. The localization of crypts along the endocervical canal did not influence sperm storage. The quality of semen appeared to be of critical importance to sperm storage. The percentage of colonized crypts and sperm density were severly reduced in patients inseminated with abnormal semen.
Fertility AwarenessOvulation DetectionTemperature-Based Ovulation EstimationHormonal Correlation with BBT
Four points on the basal body temperatures (BBT) curve have been correlated with the estimated time of ovulation (ETO), as determined by indirect hormonal parameters, in 74 menstrual cycles from 24 subjects. Only 10 of 66 hormonally
NaProTECHNOLOGYPeak Mucus Symptom DefinitionUse-Effectiveness MethodologyQuality Control in NFP Trials
I read with interest the recent article by Wade and associates, "A randomized prospective study of the use-effectiveness of 2 methods an interim report" (134: 628, 1979). In reference to the study of the ovulation method, the authors noted that abstinence begins on the 1st day of mucus secretion and continues until the evening of the 4th day beyond the peak or maximal mucus secretion. In the ovulation method, the peak symptom is not the same as maximal mucus secretion as was indicated in the paper. The peak symptom is defined as the last day of the mucus discharge that is clear and/or stretchy and/or lubricative. In the definition of peak symptom, the amount of mucus discharge is not specifically important and may often be misleading. I had the opportunity to do a site visit at this study at the request of the National Institutes of Health while the study was in progress. I analyzed several pregnancies which occurred in users of this ovulation method. Some of the pregnancies occurred as the result of poor teaching of the concept of peak symptom. In the ovulation method, proper understanding and teaching of that concept are essential to the measurement of its effectiveness. Noticeably missing from this interim report was any discussion of the quality control procedures which were utilized to guarantee a high-quality educational service to the people entered into the study. While the authors claim that the methods were taught by professional teachers, these teachers were actually women who had previously used the method and/or had formalized training in teaching the method. Simple use of either of the methods certainly does not qualify an individual to teach natural family planning. For those with formalized teaching, such training should have been outlined since judgment on the effectiveness of the teaching cannot be made; such a judgment is essential to the proper analysis of results. Finally, while the study claims to be a use-effectiveness study, it is rather a modified version of extended use-effectiveness. No objective definition of "user failure" is provided. One cannot ascertain how many pregnancies were related to poor teaching, nor can one tell how many occurred as the result of the couples' last minute exercise of their freedom to use their fertility. The use-effectiveness of the 2 methods under study as a means to achieve a pregnancy have been ignored. In doing so, the investigators have ignored use-effectiveness reality.
The volume of peritoneal fluid was measured after laparoscopic aspiration in 303 women. Contamination with blood was estimated at 4.2 per cent by haemoglobin assay. In 120 women with regular menstrual cycles, the volume of peritoneal fluid increased progressively during the follicular phase, was highest during the early luteal phase (20.0 +/- 6.3 ml) and declined thereafter. In 89 women with moderate and mild endometriosis the amounts of peritoneal fluid were similar, but 9 women with severe endometriosis had lower (P less than 0.05) volumes during the luteal phase. Women with inactive ovaries had uniformly low 4.2 +/- 2.3 ml in 31 women taking combined oral contraceptive pills; 4.7 +/- 5.8 ml in 17 women taking 5 mg of lynoestrenol daily and 1.2 +/- 1.9 ml in 20 postmenopausal women with an inactive endometrium. In contrast, two postmenopausal women with proliferative endometrium had 7 and 10 ml of peritoneal fluid. Women with active ovaries, 5 with absent or distally occluded Fallopian tubes and 7 without a uterus had normal amounts of peritoneal fluid. The volume of peritoneal fluid was not affected by pelvic varicose veins, a visible corpus luteum or an ovulation stigma. Peritoneal fluid appears to be predominantly an ovarian exudate, neither an exudate from the pelvic peritoneum nor a tubal secretion.
One hundred and forty-nine patients presenting with infertility underwent two hundred and ten endometrial biopsies as part of a routine infertility evaluation. The initial biopsy was out of phase in 44 (29.5%), confirmed by subsequent biopsy to yield a total of 28 (19%) patients with luteal phase inadequacy. Of 44 patients taking clomiphene citrate, 13 (29.5%) had out-of-phase biopsies. Although hyperprolactinemia, recurrent miscarriages, extremes of reproductive life, and clomiphene citrate administration have been associated with an increased incidence of the defect, in this series a predisposing cause could not be detected in approximately one-half of the patients. The routinely obtained endometrial biopsy provides a safe, reproducible, and adequate means of providing histologic evidence for normal endometrial development for subsequent implantation.
Contraception/ComparisonCerebrovascular DiseaseStroke RiskCardiovascular Complications of Contraceptives
3 cases of stroke in young women of childbearing age are presented to show the severity of illness and mortality in women using oral contraceptives. All 3 patients smoked more than 15 cigarettes a day. The mortality rate from cerebrovascular disease in OC users has been estimated as 4.7 times that of nonusers. The risk of developing a thrombotic stroke is 9.5 times greater than a control group's. Cerebral infarction has a relatively low mortality rate in young women, 9%, but a nonfatal stroke can have a devastating effect on the patient and her family. While there were no deaths among the 3 cases, each was left with a varying degree of neurological deficit while still in the peak of a normal life span. The possibility of synergistic potentiation of OC-associated cerebral thrombosis by cigarette use is uncertain but studies have noted some correlation between the 2. It is not clear that reduction in estrogen dosage has reduced the risk of cardiac or cerebral disease. The first patient developed extreme symptoms after a heavy drinking session, thereby raising the question of alcohol as a precipitating factor.
Tubal abrasions were surgically induced in 25 rhesus monkeys following demonstration of tubal patency. Five monkeys received dexamethasone, promethazine, and ampicillin perioperatively, five received intraperitoneal 10% dextran 40, five received intraperitoneal 32% dextran 70, and 10 received no additional therapy. Fimbrial biopsies were obtained from two additional monkeys treated with 32% dextran 70 before and postoperatively on days 2, 5, and 7. Only those treated with 32% dextran 70 retained tubal patency and avoided development of adhesions, involving fimbria, omentum, ovary, uterus, and bladder. Histologic examination of fimbrial biopsies demonstrated sufficient epithelial repair to have occurred during the 5 days 32% dextran 70 remained in the pelvin cavity to prevent adhesion formation.
Progesterone and human chorionic gonadotrophin (HCG) in serum and pregnandiol in urine were measured in 64 patients admitted to hospital because of threatened abortion. Blood samples were taken and urine specimens collected at regular intervals during admission and after discharge during the rest of the pregnancy. A reference range was worked out for each hormone based on the hormone values obtained from the pregnancies proceeding to term. The predictive significance of values within and below the reference range was determined, for the initial sample and for serial samples. An association between hormone levels and outcome of pregnancy was observed but it is concluded that both single and serial determinations of progesterone and pregnandiol and serial determinations of HCG are unsatisfactory for the evaluation of threatened abortion. However, an initial progesterones value below the reference range and HCG values below 10,000 mIU/ml between the 8th and 15th week of pregnancy was in every case always followed by spontaneous abortion. A hormonal test of fetoplacental origin is recommended for monitoring threatened abortion.
Bone HealthDialysis-Related Bone DiseaseResistant Mineralizing Defects
5 patients are described who developed severe osteomalacia with spontaneous fractures after 2-4 years on dialysis. Phosphate control, vitamin D2 therapy and parathyroidectomy were ineffective. These individuals showed a hypercalcemic tendency but little histologic or radiographic evidence of osteitis fibrosa. After parathyroidectomy, the hypercalcemic tendency remained and bone biopsy revealed gross osteomalacia. A 6to 12-month therapeutic trial with 1,25-dihydroxycholecalciferol (1,25[OH]2D3) in 3 did not arrest skeletal deterioration. 4 subsequently developed dialysis encephalopathy. These patients appear to have a unique mineralizing defect unresponsive to 1,25(OH)2D3. This "dialysis osteomalacic syndrome" may result from toxic substances associated with uremia or the hemodialysis regimen.
The concentration of human beta-endorphin (beta h-EP)) was measured in various hypothalamic nuclei, in extrahypothalamic brain regions and in the anterior and posterior lobes of the pituitary using a specific radioimmunoassay (RIA) The beta h-EP concentrations in the arcuate nucleus (169 +/- 35 pg/100 micrograms protein, n = 7) and median eminence (163 +/- 32 pg/100 micrograms protein, n = 6) were among the highest in the 17 brain areas examined. The immunoreactive beta h-EP in the hypothalamus corresponded to authentic beta h-EP, as determined by gel exclusion chromatography. By chromatography and RIA the beta h-EP concentrations in anterior (1.53 X 10(5) +/- 0.51 X 10(5) pg/100 micrograms protein, n = 3) and posterior (1.41 X 10(5) +/- 0.38 X 10(5) g/100 micrograms protein, n - 5) pituitary were found to be approximately 1,000-fold higher than in hypothalamus. Within the pituitary beta h-EP was localized throughout the anterior lobe, in the pars intermedia and in that part of the posterior lobe nearest the pars intermedia, as judged by immunocytochemistry. Dense immunocytochemical staining was found along the perimeter of many blood vessels. Beta h-EP and adrenocorticotropin (ACTH) were co-localized in the same pituitary cells. The present data represent the first unequivocal localization and quantitation of beta h-EP in human brain and in the separate lobes of the human pituitary.
It is commonplace for gynecologists to refer to "midcycle" ovulation of women. This concept has often led to the routine diagnosis of ovulatory status on day 14 of what is expected to be a 28-day menstrual cycle. For example, the postcoital test in an infertile patient, or intercourse to achieve pregnancy in a normally fertile patient, is often timed around day 14 under the assumption that ovulation is occurring then. Advocates of natural family planning (NFP) have criticized the concept of "midcycle" ovulation, because their clinical experience suggests that the natural irregularity of menstrual-cycle length militates against ovulation's occurring with any great frequency on day 14.
This report analyzes the relationship of day 14 and the actual midcycle of the menstrual cycle to each other and to indirect hormonal parameters that more directly estimate the time of ovulation.
We describe the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin, a novel porcine pituitary endorphin. It contains [Leu]enkephalin. In the guinea pig ileum longitudinal muscle preparation it is about 700 times more potent than [Leu]enkephalin. Its effects in this tissue are blocked completely by naloxone, but the apparent affinity of naloxone is 1/13th that for blockade of [Leu]enkephalin or normorphine. In the mouse vas deferens, this peptide is 3 times more potent than [Leu]enkephalin. Well-washed rat brain membranes degrade the peptide rapidly, suggesting the presence of a membrane-bound degradative enzyme. The peptide displays considerable immunoreactivity in assays with antisera that have been used for the immunohistochemical localization of [Leu]enkephalin. The remarkable enhancement of the potency of [Leu]enkephalin by the COOH-terminal extension -Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-OH suggests new interpretations concerning the structure of opiate receptors and the function of the enkephalin pentapeptides.
The plasma concentrations of progesterone and 5-alpha-pregnane-3,20-dione (5-alpha-dihydroprogesterone) were measured from as early as 12 weeks through 41 weeks of gestation in primigravid women. Two groups of primigravid women were assessed, those with uncomplicated pregnancies and those who developed pregnancy-induced hypertension. Plasma levels of progesterone and 5-alpha-dihydroprogesterone rose progressively throughout gestation in both groups of women. The ratio of the level of progesterone to that of 5-alpha-dihydroprogesterone in individual plasma samples of women with uncomplicated pregnancies was 7.0 from 12 to 15 weeks' gestation while at 35 to 41 weeks' gestation the ratio had declined to 4.6. Similar results were obtained in plasma samples of women who ultimately developed pregnancy-induced hypertension. Since no differences in plasma levels of progesterone or 5-alpha-dihydroprogesterone were detected between primigravid women with uncomplicated pregnancies and those who developed pregnancy-induced hypertension, we conclude that neither progesterone nor 5-alpha-dihydroprogesterone concentrations in plasma are of value in identifying women at risk of developing pregnancy-induced hypertension.
In this report, the ultrastructure of eM was studied by cryo-scanning electron microscopy (cryo-scan), which enabled us to observe the sample while it still contained water. … It was then placed in a specially made chamber which was part of the cryo-scanning electron microscope model JSM-50A (JEOL, Tokyo). The eM was examined after etching and coating with gold. A human cervical mucus specimen as observed by cryo-scan. The 3-dimensional netlike structure was characteristic (original magnification x 10,000).
General OB/GYNCultural PracticesTraditional Abstinence PracticesReproductive Behavior Surveys
Six long-term hemodialysis patients with progressive skeletal deterioration during long-term pharmacologic vitamin D2 therapy were treated for six to 12 months with oral 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to determine its therapeutic effectiveness in vitamin D2-unresponsive osteodystrophy. On bone biopsy, three of the patients had severe osteomalacia and three showed predominant osteitis fibrosa. Previous therapies, including phosphate binders and dialysis schedules, were maintained. The three patients with osteomalacia and the two with osteitis fibrosa showed clinical deterioration. There was no significant change in serum calcium, phosphate, alkaline phosphatase, bone densitometry, immunoreactive parathyroid hormone levels or bone histology. Roentgenograms showed multiple new fractures of ribs and femoral necks in the patients with osteomalacia and increased bone resorption in two of three patients with osteitis fibrosa. 1,25-(OH)2D3 dosage had to be decreased in all patients because of hypercalcemia with a mean tolerated dose of 0.22 microgram/day. In these patients, 1,25-(OH)2D3 was not effective therapy for progressive osteodystrophy unresponsive to pharmacologic vitamin D2.
PregnancyPreterm Labor PreventionSupplementation in PregnancyProgesterone and Preterm Birth
Studies have been undertaken regarding the efficacy and modus operandi of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHP-C) in preventing premature labor in high-risk patients. In a total of 70 patients, the treated patient population had a prematurity rate (12.8%) and a perinatal mortality rate (5%) which were significantly lower than those of the total placebo or untreated patient group (40.9 and 25%, respectively). In addition, sequential plasma steroid values were determined in 21 patients, 10 of whom delivered prematurely. The results indicate that low plasma progesterone (P) and 17 alpha-hydroxyprogesterone (17 alpha-OHP) levels precede the onset of preterm labor by weeks. Successful treatment with 17 alpha-OHP-C was characterized by elevated P levels. Plasma estradiol (E2) and cortisol (C) values did not vary with time of delivery or treatment. These findings support the progesterone block theory as an important mechanism affecting preterm delivery in this high-risk population.
Patients with premenstrual syndrome recorded their symptoms daily using menstrual distress questionnaires. These were analysed by a least mean square method of fitting sine waves. After recording an untreated cycle, patients were given progesterone 200 mg b.d. and placebo in a double-blind crossover manner; 75 per cent of patients were then given progesterone 400 mg b.d. and placebo in a similar manner. Treated cycles were rated by both daily menstrual distress questionnaires and retrospective self-assessment. Both rating methods showed there was no significant difference between progesterone and placebo in reducing symptoms of premenstrual syndrome, and in the majority of cases placebo was more effective, although never significantly so.
Lack of standardization in analytic methods for assigning infertility data is attributed to inadequate classification of fertility problems, and a lack of consistent methodology in evaluating outcome of infertility therapy. A classification scheme ideally should consider types of fertility problems as well as clinical assessment of its severity. Until an adequate classification system is developed, researchers are encouraged to describe fully the nature of infertility problem examined, and present results for homogenous groups of patients. The life-table method of analysis is a useful technique for assessing infertility statistics. The starting point of this method should depend on the group examined and may be either the date of 1st visit to the clinic or the date that therapy is instituted. Approximate date of conception should be the endpoint. A mathematical model of infertility predicated on the assumption that there is a constant monthly probability of conception of fecundability can be used to derive equations with potential for clinical application.
Patients with different types of luteal phase defects were studied with the use of the radioimmunoassay for the beta subunit of human chorionic gonadotropin (hCG) to determine if unsuspected subclinical pregnancies were more common in a particular type of defect. A type I luteal phase defect is always characterized by a chronologic lag in endometrial development when repeatedly studied with timed endometrial biopsies. A type II luteal phase defect is always characterized by an in phase endometrium when repeatedly studied by timed endometrial biopsies but always has less than a 14 day luteal span. All blood samples were drawn at least 7 days after ovulation/conception. In 22 cycles in which patients had a type I luteal phase defect, no subclinical pregnancies were detected. In 18 cycles in which a type II luteal phase defect was present, 12 instances of unsuspected subclinical pregnancy were detected and all ended in spontaneous abortion. This study shows that unsuspected subclinical pregnancies ending in abortion do occur and are quite commonly associated with the type II luteal phase defect.
Daily (12-hour) urine collections taken throughout the menstrual cycle were obtained from 30 young women who by genetic analysis were at risk for familial breast cancer, and from 30 control women carefully matched for age, height, and reproductive history. Steroids in the urine were extracted by glucuronidase hydrolysis, and the primary glucocorticoid, androgen, and estrogen hormones and their metabolites were measured by radioimmunoassay. Highly significant differences were observed only in the case of estrone and estradiol, with the high-risk subjects exhibiting lower values that the controls. This endocrine abnormality in young women at risk for breast cancer may be a potential discriminant for identifying women at risk for the disease in the population at large.
InfertilityClomiphene OutcomesDrug-Related Gestational RiskClomiphene vs Surgical
The experience of the gynecologic endocrinology and infertility clinic at The Johns Hopkins Hospital has been subjected to a nonconcurrent prospective analysis in an attempt to evaluate the gestational fate of clomiphene-related conceptions (study series, n = 86). This latter series was contrasted with a series of pregnancies following bilateral ovarian wedge resection (BOWR) (n = 51) in a comparative analysis of gestational outcome event rates. Post-therapy follow-up was available for varying time spans of up to 15 years. A 12.8% twinning rate constituted the single most important complication of clomiphene therapy, resulting in measurable increments in perinatal morbidity and mortality rates. The observation of a 26.5% spontaneous abortion rate would seem to suggest that clomiphene-related conceptions are at little or more risk for spontaneous abortion than would have been expected from the infertile population under discussion. A 3.1% incidence of post-clomiphene birth defects was not increased as compared with commonly quoted rates for the population at large. The corresponding incidence rates of twinning, spontaneous abortion, and birth defects for the BOWR series were 0%, 21.6%, and 0%, respectively.
Lymphocyte reactivity was measured in human mixed lymphocyte (MLC) and mitogen-stimulated cultures in the presence of various steroids. When present during the entire culture period at concentrations between 1 and 20 µg/ml progesterone, estradiol, and testosterone blocked 3H-thymidine (3H-TdR) incorporation. Estriol and 16 α-hydroxy progesterone were without suppressive effects. The kinetics of steroid mediated suppression of thymidine incorporation and DNA synthesis was investigated at various times during lymphocyte activation. When progesterone was present only at the beginning of culture, subsequent DNA content, but not thymidine incorporation was suppressed. However, if added late during the activation process, progesterone reduced thymidine incorporation independent of cellular DNA content. If present during the entire culture period both were suppressed. Cortisol, but not progesterone irreversibly inhibited lymphocyte thymidine incorporation if added during the first 12 hr of culture. A reversible blockade of lymphocyte thymidine uptake could be observed with progesterone even during the final hours of mitogen or MLC cultures. Thus, effects of steroid hormones on cellular DNA synthesis and thymidine incorporation appear to be independent processes. Cell fractionation experiments demonstrated that progesterone blocked the uptake of 3H-TdR into the lymphocyte nucleoside pool thereby reducing its availability for incorporation into DNA. This study is consistent with the hypothesis that lymphocyte proliferation at the maternal fetal-interface during pregnancy may be under specific regulation by progesterone. The relatively high local concentrations of the hormone produced by trophoblast are immunosuppressive whereas the substantially lower peripheral steroid levels are entirely inadequate to suppress systemic immunity. We suggest that at least one important role of progesterone in maintaining pregnancy is its regulation of cellular immunity in the maternal-fetal bed.
Fertility AwarenessClinical IndicatorsProgesterone CriteriaBasal Body Temperature
This study was designed to test the assumption that women with regular menstrual cycles and premenstrual symptoms are ovulatory. 40 women aged 20-40 years were selected as probably ovulatory on the basis of their recent histories of regular menstrual cycles consistently accompanied by premenstrual molimina. Each subject recorded menses and (BBT) basal body temperature for 1-3 consecutive menstrual cycles during which luteal phase serum (P) progesterone concentrations were determined by radioimmunoassay. All subjects were rated ovulatory or anovulatory by each of several espoused P criteria which confirmed 39/40 subjects (98%) to be ovulatory by a 3 ng/ml criterion; 38/40 subjects (95%) by a 5 ng/ml criterion; and 36/40 (90%) by a 15 ng/ml criterion. Thus P measurements confirmed the clinical impression of ovulation in 90-98% of subjects depending on which P criterion was selected. BBT correlated well with P measurements in that 61/66 cycles (92%) displayed a biphasic BBT pattern 2/66 cycles (3%) displayed a monophasic BBT pattern and 3/66 cycles (5%) were uninterpretable. Only 1 subject was not ovulatory in either of 2 consecutive cycles by even the most liberal P criterion and both cycles were abnormally long and would have been suspected of being anovulatory on clinical grounds. We conclude that patients presenting with a history of regular menstrual cycles accompanied by premenstrual molimina are identifiable as ovulatory without the necessity of measuring luteal phase serum P concentrations. (Authors modified)