Progesterone as a bone-trophic hormone

Progesterone as a bone-trophic hormone

Abstract: Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency disease."


Let's get rid of the term "Braxton Hicks contractions"

Abstract: The early detection of preterm labor and the prevention of preterm birth require special attention to early subtle signs and symptoms of preterm labor. The concept of "Braxton Hicks contractions" may negate these early signs and symptoms by falsely reassuring patients, thus encouraging them not to seek medical care promptly.


Pharmacokinetics of estrogen

Pharmacokinetics of estrogen

Abstract: The main types of pharmacologic therapy used to treat the hormone deficiency of menopause are parenteral and oral administrations of estrogen. Parenteral administration results in predictable absorption without major intermediary metabolism, whereas all oral estrogens are subject to intestinal metabolism before entering the systemic circulation. Various options are available. Injectable estrogens, because of rapid absorption and metabolism, are impractical for long-term replacement therapy. The primary drawback to subcutaneous estradiol pellets is the surgical procedure required for their insertion and removal. Vaginal epithelium is an effective pathway for absorption of estrogen given by solution, tablet, or cream, although only the latter is currently approved for clinical use; relatively constant serum levels of estradiol can be obtained with vaginal rings. Transdermal patches provide controlled hormone levels for up to 3.5 days. Although oral conjugated equine estrogens have been used extensively, they introduce types of estrogen, such as equilin, that are not naturally found in humans and that can produce a pronounced hepatic response. Micronized estradiol, oral estrone, and other estrogens have been used as alternatives to equine estrogens. Clinicians should understand the pharmacokinetics of the various options for replacement therapy and select a course of treatment that is safe, effective, and convenient for the patient.


Selective osteal salpingography and transvaginal catheter dilatation in the diagnosis and treatment of fallopian tube obstruction

Abstract: Selective salpingography and transvaginal catheter dilatation were performed in 157 women with infertility to diagnose, localize, and classify obstructive diseases of the fallopian tubes and to correct obstruction of the proximal (uterine-end) tube. In 61 (39%) of the patients, the selective salpingograms showed patent tubes despite the fact that two previous hysterosalpingograms showed obstruction of the proximal (uterine-end) tube. Transvaginal catheter dilatation successfully recanalized the proximal portion of the tubes in 79 (82%) of 96 patients with obstructed tubes. In 18 of 25 with successful transvaginal catheter dilatation and 6-month follow-up salpingography, the tubes remained patent. Coexisting disease of the distal (ovarian-end) tubes was diagnosed in 29 (18%) of the patients. Pregnancy was achieved in 11 of the 157 patients (six in whom obstructions were corrected by transvaginal catheter dilatation and five in whom selective salpingograms showed patent tubes). There were no complications due to the procedure. The excellent diagnostic and therapeutic yield, lack of complications, and low cost justify the use of these percutaneous techniques to investigate female infertility and to treat obstruction of the uterine end of the fallopian tube.


Luteal support after luteinizing hormone-releasing hormone agonist for in vitro fertilization: superiority of human chorionic gonadotropin over oral progesterone

Irène Buvat

Association pour l'Utilisation du Rein Artificiel dans la région Lyonnaise

J Buvat

Association pour l'Etude de la Pathologie de l'Appareil Reproducteur et de la Psychosomatique, Lille, France.

Abstract: It has been reported that the pregnancy rate after in vitro fertilization (IVF) after pituitary desensitization with luteinizing hormone-releasing hormone agonist (LH-RH-a) is twice as low if the luteal phase is not supported. We therefore tested the respective advantages of luteal support using human chorionic gonadotropin (hCG, 1,500 IU three times) and progesterone (P, micronized, oral administration, 400 mg/d) after 171 embryo transfers (ET) in which the cycle was stimulated with the LH-RH-a triptoreline. The type of luteal phase support was randomly selected except when the estradiol level exceeded 2,700 pg/mL. The clinical pregnancy rate and the ongoing pregnancy rate were significantly higher using hCG (after the transfer of 3 embryos, 45% and 43% with hCG versus 23% and 17% with P). The same results were noted for the embryo implantation rate per ET (19% of embryos are viable after 6 months of pregnancy after hCG versus 7.5% after P). Adequate luteal support, therefore, significantly improves the results of IVF when LH-RH-a are used. The poor results obtained with P in this study might be related to its poor bioavailability after oral administration.


An analysis of antenatal tests to detect infection in preterm premature rupture of the membranes

Abstract: The purpose of this study was to critically review published studies regarding sensitivity, specificity, and positive and negative predictive values of antenatal tests to diagnose chorioamnionitis or fetal-neonatal sepsis in preterm premature rupture of the membranes. A Medline Data-Base computer program search from 1980 to 1988 identified 39 studies, 23 of which were accepted after independent review with preset criteria. An ideal test to predict chorioamnionitis or neonatal sepsis was not found. The low success rate for amniocentesis and the need for repeat taps preclude the acceptance of tests on the basis of amniotic fluid. Single, small studies, the precision of which has never been tested, show good indices for repeatedly increased serum levels of C-reactive protein (greater than 20 mg/L), a high level of C-reactive protein greater than 40 mg/L, or a day-to-day coefficient of variation for C-reactive protein of greater than 30% in the prediction of histologic or clinical chorioamnionitis. Ultrasonographic observation of fetal activity, if published study results are confirmed, may be of value to predict amniotic fluid bacterial colonization.

American Journal of Obstetrics and Gynecology


The correlation between Chlamydia antigen, antibody, vaginal colonization and  contraceptive method in young unmarried women

Abstract: In a group of 55 unmarried women, mean age 25 years, attending a family planning clinic and having minor gynecological complaints, the correlation between Chlamydia trachomatis (CT) antigen, CT antibodies, vaginal colonization by Candida or bacteria and the method of contraception was investigated. The correlation between CT antigen and CT antibodies (IgG) was significant in oral contraceptive users (p = 0.003), as was the correlation with vaginal colonization by Candida and potential pathologic bacteria. In the group using the natural family planning method, a statistically significant correlation was found between CT antigen, IgG (p = 0.002), IgA (p = 0.02) antibodies, and vaginal candidiasis (p = 0.002), but not with bacterial colonization (p = 0.90). The discrepancy between CT antigen and antibodies is discussed. Differences in the prevalence of Chlamydia trachomatis infection were found among groups using different birth control methods, indicating an association between Chlamydia infection and the contraceptive method used.

Advances in Contraception : the Official Journal of the Society for the  Advancement of Contraception


Demographic and historic variables in women with idiopathic chronic pelvic pain

Abstract: A comprehensive historic, demographic, and medical questionnaire was administered to 106 women referred to a multidisciplinary clinic for evaluation of idiopathic chronic pelvic pain and to 92 age-matched, pain-free control patients presenting for routine annual examination. Although racial distribution, mean gravidity and parity, and rates of elective abortion were similar in both groups of respondents, spontaneous abortion was reported significantly more frequently among women with pelvic pain. Patients in the study group were also more likely to be on active military duty, to have undergone previous nongynecologic surgery, and to have sought treatment for unrelated somatic complaints. Finally, although the mean ages at first intercourse were similar, women with idiopathic pelvic pain reported a higher total number of sexual partners and were significantly more likely to have experienced previous significant psychosexual trauma. These findings confirm that predisposing psychosocial variables are important in the pathogenesis of idiopathic pelvic pain and emphasize the significance of multidisciplinary evaluation and management.


Contraceptive failure of the ovulation method of periodic abstinence

James Trussell

Princeton University; Office of Population research; Wallaca Hall Princeton New Jersey USA NJ 08544

Abstract: Previously published estimates of probabilities of method and user failure for all contraceptive methods suffer from a serious methodological error and are biased downward, with the extent of bias unknown. Data from a World Health Organization clinical trial of the ovulation method of periodic abstinence were used to provide the first correctly calculated measures of method and user efficacy and to determine the characteristics that distinguish women who consciously take risks from those who do not. Probabilities of pregnancy during the first year are 3.1 percent during perfect use (method failure) and 86.4 percent during imperfect use (user failure). Thus, if used perfectly, the ovulation method is very effective. However, it is extremely unforgiving of imperfect use. Because perfect compliance is difficult for many couples who desire intercourse when it is forbidden by ovulation method rules, and because the risk of pregnancy during imperfect use is so great, the ovulation method cannot be considered an ideal contraceptive method for the typical couple, who are likely to be less compliant than couples who volunteer for a clinical trial. The probability of an accidental pregnancy is greatest when any of the three most serious rules--no intercourse during mucus days, within three days after the day of peak fecundity or during times of stress--are broken. Those who have a poor attitude toward the rules are more likely to take risks, including serious risks. Those who get away with taking a risk (i.e., do not get pregnant) are very likely to take risks again. Because breaking the most serious rules entails a 28 percent risk of pregnancy per cycle, those likely to take risks should be counseled about the probable consequences.


Diagnosis and treatment of cornual obstruction using a flexible tip guidewire

Abstract: Proximal tubal obstruction, either unilateral or bilateral, is a frequent finding on hysterosalpingogram (HSG). Approximately two-thirds of the fallopian tubes resected for proximal tubal obstruction reveal an absence of luminal occlusion. The distinction between true pathologic occlusion and either spasm or plugging is crucial in determining therapy. We combined hysteroscopic cannulation of the proximal fallopian tube with laparoscopy in 11 patients with proximal tubal obstruction diagnosed by HSG and confirmed at laparoscopy. Hysteroscopic cannulation was able to be performed in 72% of the fallopian tubes attempted, and there was a postcannulation patency rate by HSG of 73%. Six of the 11 patients became pregnant after tubal cannulation and adjunctive distal tubal surgery. Hysteroscopic cannulation of the fallopian tube is a safe diagnostic procedure that can be used to identify those patients with true proximal occlusion, and may also serve as a therapeutic procedure in some of these patients.


Differential regulation of luteinizing hormone, follicle-stimulating hormone, and free alpha-subunit secretion from the gonadotrope by gonadotropin-releasing hormone (GnRH): evidence from the use of two GnRH antagonists

Abstract: To examine the differential regulation of glycoprotein hormone secretion from the gonadotrope by GnRH, the Nal-Glu GnRH antagonist was administered to euthyroid women in the early follicular phase (days 1-5) of the menstrual cycle, and the results compared to previous studies with the Nal-Arg GnRH antagonist. After a 4-h period of baseline sampling at a frequency of every 10 min, a single sc dose of the GnRH antagonist was administered to each subject. Frequent sampling continued for 8 h, followed by hourly sampling for a further 16 h. LH, FSH, and free alpha-subunit were measured serially in assays with high specificity. There was a 90% concordance of LH and free alpha-subunit pulses during the baseline sampling period. Pulsatile secretion of LH and free alpha-subunit was immediately abolished at the highest dose of the Nal-Glu antagonist for at least 8 h. The maximum percent suppression of LH after administration of the Nal-Glu GnRH antagonist was 70 +/- 4%, 80 +/- 4%, and 83 +/- 1% at doses of 15, 50, and 150 micrograms/kg, respectively, compared to 51 +/- 10%, 70 +/- 5%, and 69 +/- 5% at doses of 50, 150, and 500 micrograms/kg Nal-Arg antagonist. Decreases in FSH were 28 +/- 2%, 32 +/- 7%, and 39 +/- 2%, with increasing doses of the Nal-Glu antagonist compared with 25 +/- 6%, 17 +/- 6%, and 28 +/- 4% reductions at increasing doses of the Nal-Arg antagonist. Free alpha-subunit decreased 22 +/- 4%, 23 +/- 4%, and 28 +/- 3% at increasing doses of the Nal-Glu antagonist and 12 +/- 4%, 27 +/- 4%, and 30 +/- 7% with increasing doses of the Nal-Arg antagonist. For the Nal-Glu antagonist, suppression of LH was greater than that of FSH and free alpha-subunit at all doses (P less than 0.001), while FSH suppression was greater than that of free alpha-subunit at the highest dose only (P less than 0.05). For the Nal-Arg antagonist, LH suppression was greater than that of FSH or free alpha-subunit at all doses (P greater than 0.01), and FSH suppression exceeded that of free alpha-subunit at the 50 micrograms/kg dose. Suppression of LH was greater with the Nal-Glu antagonist than with the Nal-Arg antagonist at doses of 50 and 150 micrograms/kg (P less than 0.05), and FSH suppression was greater with the Nal-Glu antagonist at 150 micrograms/kg (P less than 0.01), while the degrees of maximum suppression were similar for the two different GnRH antagonists for free alpha-subunit.(ABSTRACT TRUNCATED AT 400 WORDS)

The Journal of Clinical Endocrinology and Metabolism


Perineal endometriosis. A case report

Perineal endometriosis. A case report

Abstract: Perineal endometriosis was found unexpectedly in a 32-year-old woman with primary infertility. Since there had been no prior perineal trauma, the transport of endometrium through a venous or lymphatic route could have accounted for the location of the endometriosis.


Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist

Abstract: Nine obese and ten non-obese women with polycystic ovarian disease (PCO), and seven obese and eight non-obese normal women, had an oral glucose tolerance test (OGTT) before and after treatment with GnRH agonist (buserelin 400 micrograms/day s.c. for 8 weeks) in order to investigate the effect of ovarian suppression on their insulinaemic secretion. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), androstenedione (A), testosterone (T), DHEAS, cortisol and insulin (I) were measured at time 0 of OGTT; in all samples of OGTT, E2, T, A and I were also assayed. PCO patients showed higher basal androgen levels than control patients. All subjects showed a normal glycaemic response to OGTT. The mean fasting and areas under the curve (ISA) of plasma I were significantly greater in the obese PCO women than in non-obese PCO, the normal obese and non-obese women. All PCO patients showed significantly higher fasting I and ISA values in respect to all control patients. Hyperinsulinaemic responses were 89% in PCO obese, 30% in non-obese PCO and 29% in obese control patients. After buserelin treatment, these values did not change significantly in respect to pretreatment in all groups, in spite of a significant decrease of androgen secretion. During OGTT, no variations of steroid plasma concentrations were seen in both normal or hyperinsulinaemic PCO patients. The data of this study show that hyperandrogenism, hyperinsulinism and obesity were associated with different modalities in PCO patients and that a marked decrease of androgen secretion did not restore a normal insulinaemic response to OGTT, suggesting that hyperandrogenism does not produce hyperinsulinism.


Progestogen administration in pregnancy may prevent preterm delivery

Abstract: Two recently published meta-analyses of controlled trials of a wide variety of progestational agents, used in pregnancy (Daya 1989; Goldstein et al. 1989), prompted this third meta-analysis of placebo-controlled trials involving the prophylactic use of a single agent, 17 alpha-hydroxyprogesterone caproate. Of seven relevant published reports of controlled trials, six had involved women considered to be a high risk of miscarriage or preterm birth. This analysis provides no support for the view that 17 alpha-hydroxyprogesterone caproate protects against miscarriage, but suggests that it does reduce the occurrence of preterm birth. The latter effect was reflected in a reduced rate of low birthweight babies, but not in a statistically significant reduction in perinatal mortality and morbidity. The difference between this meta-analysis and the two earlier meta-analyses illustrates the problems both of selective sub-grouping and of comprehensive pooling of data from small trials.

British Journal of Obstetrics and Gynaecology


Laparoscopic Appearance of Endometriosis: Color Atlas (Second Edition)


Living Proof: A Visual Encounter with the Unborn

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.


Expanding our Human Sexual Horizons

Expanding our Human Sexual Horizons


Prevention of postoperative intra-abdominal adhesions

Jiong Zhou

Second Affiliated Hospital of Zhejiang University

Shan Lin

Fujian Agriculture and Forestry University

Li Huang

Guangdong Province Women and Children Hospital

Current Opinion in Obstetrics & Gynecology


Recent Advances in Infertility Evaluation and Treatment


Ultrasonic Visualization of Human Ovulation


Stress and Reproduction: The Role of Cortisol: In: Yen SSC, Vale WW (Eds). Neuroendocrine Regulation of Reproduction


Changes in circulating hormone levels after ovarian wedge resection in patients with polycystic ovary syndrome

Abstract: Serum gonadotropin, prolactin, estradiol, sex hormone binding globulin (SHBG) and androgen levels were measured before, 5 days and 6 weeks following ovarian wedge resection in 9 patients with polycystic ovary syndrome. Elevated levels of LH, androstenedione, testosterone and dehydroepiandrosterone-sulphate (DHEA-S) were found before surgery. There was a marked decrease in androstenedione and DHEA-S levels 5 days following wedge resection, but a rebound effect could be observed 6 weeks later. Serum gonadotropin, prolactin, testosterone and SHBG concentrations were practically unaffected by surgery. At 6-12 months follow up patients showed regular, mainly ovulatory cycles, but pregnancy occurred only in two cases.


C-reactive protein in preterm premature rupture of the membranes

Abstract: The usefulness of maternal C-reactive protein (CRP) measurements in the diagnosis of chorioamnionitis and puerperal and neonatal infectious morbidity was studied among 147 patients with preterm rupture of the membranes (PROM). Thirty-three patients developed chorioamnionitis, 10 patients developed puerperal endometritis, and 21 newborn infants developed neonatal infections. There was no difference in the highest antepartum CRP between patients with or without chorioamnionitis. The overall test performance for CRP was poor suggesting that elevated antepartum CRP may be misleading in the diagnosis of chorioamnionitis. However, use of serial CRP measurements increases the test performance. The high negative predictive value suggests that CRP is useful in predicting the absence of chorioamnionitis.


Stress and Reproduction: The Role of Cortisol


The Gift of Life: The Proceedings of a Conference on the Vatican Instruction on the Respect for Human Life

Wallace M

Robert Gordon University Aberdeen Business School


LUF-syndrome: recent findings

LUF-syndrome: recent findings

Abstract: Luteinization of a follicle without its rupture and without the oocyte being expelled which is also called the LUF-syndrome by English speaking authors is one of a number of functional abnormalities that can occur to the follicle in the ovary and is diagnosed by ultrasound methods. It is one that has been known for quite a long time. Many publications have appeared since 1978 to describe this syndrome, which all the same is still very controversial. One has learnt how to diagnose it fairly well. One knows more about its physiopathogenesis and how often it occurs. This seems to be more often when there is pelvic endometriosis or so-called unexplained infertility. What is more difficult however is to find out how important it is as a cause of lowered fertility, and it is also difficult to decide whether: it just happens occasionally or is a true syndrome? It is still not possible today to give a definite answer to this question because of reasons of methodology. Finally, as far as treatment goes, even if the facts about its pathogeneiity have been found out and should be able to help decide on a logical treatment there have been no controlled studies to find out whether the treatment works.

Journal De Gynecologie, Obstetrique Et Biologie De La Reproduction


Follicular growth and corpus luteum function in women with unexplained infertility, monitored by ultrasonography and measurement of daily salivary progesterone

F. P. Median

Ollscoil na Gaillimhe – University of Galway

Abstract: Ovarian function was evaluated over a minimum of 3 consecutive menstrual cycles from each of 41 women with unexplained infertility. Follicular development and ovulation were monitored using real time ultrasonography and luteal function was evaluated by daily salivary progesterone measurement. In 129 spontaneous cycles, normal single ovulations were detected in 121 (93.8%). Luteal phase insufficiency was identified in 21 (17.4%) of these 121 cycles and this was a recurrent phenomenon in the cycles of 5 of the 41 women (12.2%). A successful pregnancy was seen only in association with consistently normal salivary progesterone profiles or where the empirical use of clomiphene citrate therapy had corrected previously diagnosed luteal phase insufficiency. Basal body temperature records or mid-luteal serum progesterone measurements were less satisfactory indices of luteal function than a salivary progesterone profile.

Gynecological Endocrinology : the Official Journal of the International Society  of Gynecological Endocrinology


Luteal phase deficiency after completely normal follicular and periovulatory phases

Abstract: Luteal phase defect (LPD) accounts for a significant proportion of reproductive disorders, however its etiology is still debated. A prospective study was performed on 37 ovulatory women to determine whether LPD can occur in cycles characterized by completely normal folliculogenesis. Criteria for normal folliculogenesis included: a gradual rise of serum estradiol, a luteinizing hormone (LH) surge, the presence of a dominant follicle that disappeared, an increase of serum progesterone, and normal serum levels of prolactin, testosterone, dehydroepiandrosterone sulfate, follicle-stimulating hormone, and LH. Thirty of 37 women fulfilled the above mentioned strict criteria and underwent endometrial biopsy in the late luteal phase. Seven of 30 (23%) demonstrated a delay in endometrial development and all had normal hormonal and ultrasonographic parameters of folliculogenesis and ovulation. Women with delayed endometrial development demonstrated slightly longer follicular phases (17.0 +/- 1.1 versus 14.5 +/- 0.3 days). Perfectly normal follicular and periovulatory events may be followed by deficient luteal phases.


Lack of association between oral contraceptive use and Crohn's disease: a  community-based matched case-control study

Abstract: Previous epidemiologic studies have suggested a weak association between oral contraceptive use and Crohn's disease, specifically Crohn's colitis. To measure a possible etiologic association, 51 women with Crohn's disease who were 18-50 yr old were studied and compared with peer-nominated ageand sex-matched controls. There were no differences between cases and controls with respect to race, religion, marital status, and number of pregnancies. There was no association between oral contraceptive use and Crohn's disease incidence [current use: odds ratio (OR) 0.73, 95% confidence interval (CI) 0.34-1.59; former use: OR 1.80, CI 0.61-5.29; current or former use: OR 1.00, CI 0.46-2.16]. Stratifying by disease location also failed to identify an association. Cigarette smoking was significantly associated with Crohn's disease incidence. Controlling for possible confounding effects of cigarette smoking did not alter the lack of association between oral contraceptive use and Crohn's disease. Similarly, testing for interaction failed to demonstrate any effect modification. Analyzing for duration of current oral contraceptive use or time interval since last use failed to demonstrate a "dose-response" effect. The study was of sufficient size to detect statistical significance for oral contraceptive use for odds ratios of greater than or equal to 2.76. From this community-based matched case-control study, there was no association between oral contraceptive use and Crohn's disease, and women need not be advised to discontinue oral contraceptive use when a diagnosis of Crohn's disease is made.


Premenstrual syndrome improvement after laser ablation of the endometrium for menorrhagia

Abstract: Laser ablation of the endometrium was performed on 18 patients for menorrhagia. The patients were evaluated for the premenstrual syndrome (PMS) preoperatively and again at three and six months postoperatively. An improvement in both the severity and duration of PMS symptoms was noted postoperatively, and the reduction in menstrual bleeding was correlated with the reduction in PMS symptoms.


Psychologic aspects of providing infertility services

Abstract: Psychologic issues enter into all aspects of providing infertility services. At the onset the infertile are faced with decisions regarding treatment options. Treatment involves uncertainty and lack of control and exposes the couple to the possibility of failure. The introduction of in vitro fertilization and gamete intrafallopian transfer exposes a proportion of couples to successive experiences of failure. These treatments have implications for emotional processing; some factors can increase the likelihood of impaired coping. Specific ways of dealing with the psychologic needs of infertile couples at all stages of their treatment can be helpful.


Luteal phase deficiency: characterization of reproductive hormones over the menstrual cycle

W J Bremner

United States Department of Veterans Affairs

Abstract: The recurrent deficiency of progesterone (P) secretion by the corpus luteum has been associated with infertility and habitual abortion and given the clinical diagnosis of luteal phase deficiency (LPD). There is evidence that both follicular and luteal phase abnormalities can result in LPD cycles. In this study we have examined reproductive hormone levels and preovulatory follicular size in women with LPD (n = 10). For the purposes of this study, LPD was determined by an endometrial biopsy in the studied cycle that was more than 2 days out of phase. These biopsies were performed in women with infertility or habitual abortion who exhibited an out of phase biopsy in a prior cycle. The control group consisted of 28 normal women. Daily serum levels of the following hormones were determined in each subject: LH and FSH [immuno- and bioactive (LH-immuno and LH-bio)], P, estradiol (E2), and inhibin. The LPD women exhibited significant decreases in integrated luteal phase levels of inhibin [10,615 +/- 898 vs. 13,560 +/- 662 (U/L).days; P less than 0.02] and E2 [5,015 +/- 275 vs. 6,435 +/- 393 (pmol/L).days (1366 vs. 1753 (pg/mL).days); P less than 0.05] in addition to the expected decrease in P [280 +/- 23 vs. 420 +/- 23 (nmol/L).days (88 vs. 132 (ng/mL).days); P less than 0.01]. On days 6-11 after the LH surge (day 0), there was a significant (P less than 0.05) decrease in mean LH-bio levels in LPD compared with those in normal women (146 +/- 26 vs. 212 +/- 24 micrograms/L). The midcycle LH surge was deficient in LPD when both LH-immuno [482 +/- 30 vs. 672 +/- 43 (micrograms/L).days; P less than 0.01] and LH-bio [1711 +/- 179 vs. 2248 +/- 226 (micrograms/L).days; P less than 0.05] levels were compared with normal values. When comparing the follicular phase in LPD with that in normal women, similar follicle size, peak and integrated E2 levels, and mean LH and FSH (immuno and bio) levels were found. The only follicular phase abnormality noted in this study was decreased mean levels of serum inhibin in the early and midfollicular phases (221 +/- 19 vs. 308 +/- 25 U/L; P less than 0.01). In this group of women with LPD, low levels of inhibin in the follicular phase were consistent with the concept of a defect in function of the preovulatory follicle, possibly as a result of previously described defects in gonadotropin secretion in this condition.(ABSTRACT TRUNCATED AT 400 WORDS)

The Journal of Clinical Endocrinology and Metabolism


A short course of menotropin after clomiphene failure in infertile women with luteal phase defects

C H Wu

Department of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.

Abstract: Twenty-four women with luteal phase defects who were ovulatory on clomiphene therapy with or without human chorionic gonadotropin (hCG) at midcycle for three to eight cycles yet failed to produce a live birth were treated with a short course of menotropin (hMG-S), one to two ampules for five days in the early follicular phase followed or not followed by hCG at midcycle for three to eight cycles. The luteal phase defect was diagnosed with repeat endometrial biopsies with a lag time of three or more days prior to clomiphene therapy. A complete infertility workup revealed only eight patients (33%) with a purely endocrine factor (luteal phase defect). The rest (16 patients, or 67%) had one or two additional infertility factors. Two abortions occurred in this group during clomiphene therapy, while five pregnancies (four live births and one spontaneous abortion) occurred during hMG-S therapy. The ovulation rates were similar for hMG-S (89%) and clomiphene (91%) therapy, but the frequency of a normal ovulatory cycle was significantly greater (P = .026) for hMG-S therapy (71%) than for clomiphene therapy (57%). The midluteal mean serum progesterone level was lower and the mean luteal length shorter in the cycles with less than 130 ng/mL/d of total integrated luteal progesterone. The postcoital test results showed better cervical mucus, with increased mucus volume and better fluidity and spinnbarkeit, in hMG-S cycles than in clomiphene cycles. It appears that hMG-S treatment can improve ovarian function and achieve successful pregnancy in patients with luteal phase defects who fail to produce a live birth during clomiphene treatment.


Absorption of oral progesterone is influenced by vehicle and particle size

Abstract: The oral route of progesterone administration has long been considered impractical because of poor absorption and short biologic half-life. Recent reports suggest that micronization of progesterone enhances absorption and increases serum and tissue levels of progesterone. This study checks serum progesterone levels before and 0.5, 1, 2, 3, 4, and 6 hours after oral administration of 200 mg of progesterone in seven subjects. Progesterone was plain milled, micronized, plain milled in oil, micronized in oil, or micronized in enteric-coated capsules. All patients exhibited a significant increase in serum progesterone levels after oral progesterone administration. Mean peak progesterone levels (30.3 +/- 7.0 ng/ml) (p less than 0.005) were achieved with micronized progesterone in oil at 2.0 +/- 0.3 (p less than 0.05) hours after administration. Four types of oral progesterone had equivalent mean peak elevations and mean times to peak: plain milled, 9.6 +/- 2.5 ng/ml at 4.0 +/- 0.5 hours; micronized 13.2 +/- 2.4 ng/ml at 3.2 +/- 0.4 hours; plain milled in oil, 11.3 +/- 3.0 ng/ml at 4.0 +/- 0.5 hours; and micronized in enteric-coated capsules, 11.2 +/- 3.0 ng/ml at 4.1 +/- 0.7 hours. Contrary to traditional teaching, these data show that significant serum progesterone levels can be achieved by oral administration. Absorption can be significantly improved by the physical characteristics of the progesterone and the vehicle used with oral administration.

American Journal of Obstetrics and Gynecology


Optimal time in the menstrual cycle for serum progesterone measurement to diagnose luteal phase defects

Abstract: Inadequate production of progesterone by the corpus luteum results in luteal phase deficiency, which is a frequent cause of recurrent spontaneous abortion. The diagnosis is made by assessment of endometrial biopsy specimens. Measurement of serum progesterone offers a less invasive alternative, but its utility as a diagnostic test is limited since there is no agreement on the level that will accurately differentiate between normal and luteal phase deficiency cycles. The purpose of this study was to determine whether there was an optimal time in the menstrual cycle when serum progesterone measurement could improve the diagnostic accuracy of the test. The results demonstrate that this time period is day 25 to day 26 and not the midluteal phase as has previously been suggested. The discriminatory level was found to be 21 nmol/L and provided a test with sensitivity of 81% and specificity of 73%.


Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns

Abstract: Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.


Endovaginal and transabdominal sonography of ovarian follicles

R F Andreotti

Department of Diagnostic Radiology, Mount Sinai Medical Center, Miami Beach, Florida 33140.

Abstract: Endovaginal and transabdominal sonography (EVS and TAS, respectively) are effective methods for monitoring ovarian follicular development. Our study evaluates both modalities by subjective comparisons and objective correlations with serum estradiol levels. In 21 of 41 studies, TVS showed more follicles over 1 cm than did TAS. The same number was seen by both in 17 studies and more by TAS in only 3 studies. Margins of the follicles were sharply defined in 37 of 41 EVS studies (90%) but only in 18 of 41 TAS studies (41%). In each of the 4 cases in which follicles were not sharply defined by EVS the ovaries were located high in the pelvis. In 29 sonographic studies, there were corresponding estradiol levels. The number and size of dominant follicles correlated well with estradiol levels (r = .9074) for EVS but less so (r = .3816) for TAS. EVS has several advantages when monitoring follicular development.

Journal of Ultrasound in Medicine : Official Journal of the American Institute of  Ultrasound in Medicine


Comparison of five clomiphene citrate dosage regimens: follicular recruitment and distribution in the human ovary

Abstract: One hundred fifty-six women with cycle disorders presenting as absence or infrequency of ovulation and with luteal phase deficiency (group II, according to the World Health Organization classification) received clomiphene citrate (CC) for ovulation induction. The administered dosage ranged from 50 to 250 mg/d. The follicular development in terms of numbers of small (less than 8 mm), intermediate (9 to 15 mm), and large (greater than 15 mm) follicles and their distribution in either one or both ovaries on the day of assumed ovulation was related to the dosage of CC. A statistically significant increase was found in the total number of follicles in relation to the dosage of CC (P less than 0.003). In view of the development of the mature follicles, the gradual increase in CC daily dosage was thought to be associated with additional mature follicles before ovulation. However, this increased follicular recruitment was not regarded as statistically significant. Treatment with low doses of CC resulted in follicular development in only one ovary, whereas increased follicular recruitment after high CC dosage was found in association with follicular development in both ovaries.


Selective reduction in multiple gestations: pregnancy outcome after transvaginal and transabdominal needle-guided procedures

Abstract: Selective fetal reduction was performed in the first trimester of pregnancy in 20 women with multifetal gestations after ovulation induction with human menopausal gonadotropin (hMG). In 10 women (group A) reduction was performed transabdominally, and in 10 women (group B) the transvaginal approach was used. The transvaginal technique achieved penetration of several gestational sacs without withdrawing the needle from the uterus. Fetal termination using either procedure occurred with intrafetal injection of potassium chloride. Six (60%, group A) and eight (80%, group B) patients delivered healthy newborns. One patient (group B) is at 30 weeks' gestation. Four (40%, group A) and one (10%, group B) aborted 1 day to 8 weeks after the procedure (1 septic abortion, each group). Our results suggest that transvaginal fetal reduction offers a better outcome, with minimal complications, to patients referred for selective continuation of pregnancy.


Mood disorders, psychiatric symptoms, and distress in women presenting for infertility evaluation

Jennifer I. Downey

New York Psychoanalytic Society and Institute

Abstract: Women who undergo treatment for infertility frequently report depression, but it is crucial to distinguish between subjective distress, symptoms, and clinical depressive disorders. In the initial assessment of a prospective, longitudinal study, 59 women presenting for infertility treatment were compared with 35 women presenting for routine gynecological care. Infertility patients and controls were not significantly different on self-report measures of partner satisfaction, sexual functioning, or self-esteem. There was also no difference in psychiatric symptomatology, or in the percentage of subjects who were currently experiencing or had ever experienced a major depressive episode. However, the infertility patients perceived themselves to have been already quite affected by their inability to conceive. For instance, 49.2% reported changes in their sexual functioning and 74.6% reported changes in their mood.


Acute arsenic toxicity--an opaque poison

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: We report a patient with fatal acute arsenic poisoning presenting as vomiting and diarrhea with the finding of intra-abdominal radiopacities on radiographs. These represent the classic features of acute arsenic toxicity and are detailed here as a reminder to others facing a similar puzzling patient with this potentially treatable poisoning.


Sonographic definition of the empty follicle syndrome

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.

Abstract: The sonographic definition of the empty follicle syndrome is presented in a group of 89 consecutive, unmedicated menstrual cycles in women with primary or secondary infertility. The incidence of the empty follicle syndrome was found to be 50%. The incidence increased with age and was independent of gravidity or the type of follicular rupture (or lack of rupture). These data suggest that the empty follicle syndrome may represent a significant etiologic factor in infertility or other reproductive abnormalities.


Safety of intraperitoneal 32% dextran 70 as an antiadhesion adjuvant

Abstract: The records of 139 consecutive patients who underwent major gynecologic abdominal surgery in which 32% dextran 70 was used as an antiadhesion adjuvant were carefully reviewed for the presence or absence of dextran-related complications. Eleven patients (8.0%) were thought to have dextran-related complications, including postoperative ileus (2.9%), pleural effusion (2.2%), allergic reactions (1.4%), wound infection (1.4%) and labial swelling (0.7%). The mean amount of dextran used was 183 mL. The study indicated that dextran can be used in moderate amounts when instilled intraperitoneally and has an acceptably low rate of complications. Since dextran is used often in spite of scanty evidence of its effectiveness as an antiadhesion adjuvant, understanding its safety and potential complications is especially important.


Polycystic ovary syndrome: a changing perspective

Abstract:
Few subjects have provoked such controversy in the field of reproductive endocrinology as polycystic ovary syndrome (PCOS). It is characterized by heterogeneous clinical and endocrine features and this has led to considerable debate about its definition. The controversy has been fuelled by uncertainty about the aetiology of the syndrome. It seems probable that there are several causes of the typical ovarian appearance although, as will be discussed later, a familial basis for the disorder appears to be the most common of these. Traditionally, since the classic description of the syndrome by Stein and Leventhal in 1935, the diagnosis has rested primarily on the typical appearance of bilateral sclerocystic ovaries in women presenting with anovulation or hirsutism (or both). But the results from subsequent publications indicated that there could be a wide variety of clinical presentations in women who had evidence of polycystic ovaries (PCO) at ovarian biopsy (Goldzieher & Axelrod, 1963; Goldzicher & Green, 1962; Jeffcoate, 1963; Smith et al.. 1965; Givens, 1977, 1984; Yen, 1980). Although most of the women had menstrual disorders or hirsutism, there were also those who had evidence of ovulatory cycles and others who were non-hirsute. McArthur, Ingersoll and Worcester (1958) made the important observation that women with bilateral PCO characteristically had elevated urinary excretion of luteinizing hormone (LH). When radioimmunoassay became widely available in the early 1970s the emphasis changed from diagnosis by histology to use of biochemical markers of the syndrome. The typical endocrine abnormalities in PCS were raised serum concentrations of LH and testosterone (and/or androstenedione) to which could be added, in later studies, evidence of hypersecretion of adrenal androgens and abnormalities of estrogen secretion, particularly estrone (Yen et al., 1970; Gambrell et al., 1973; Rebar et al., 1976; Baird et al.. 1977; Kandeel et al.. 1978; Yen, 1980). So great was the reliance on biochemical diagnosis that, in some studies, the appearance of the ovaries was considered to be of secondary importance. One problem has been that there has seldom been total agreement as to the biochemical definition of PCOS. Some groups, for example, have taken a raised serum LH to be important for the diagnosis (Lobo, 1985; Waldstreicher et al.. 1988). However, it was clear from early biochemical studies that some women with all the other clinical and biochemical features of PCOS had normal serum LH concentra-
tions (Givens et al., 1976; Rebar er al., 1976).


Perspectives of physicians in Sri Lanka on periodic abstinence

Abstract: Since physicians strongly influence both national family planning policy and individuals' contraceptive choice, a survey was conducted to learn about the perspectives of Sri Lankan physicians (n-100) regarding periodic abstinence methods of family planning (PA). Female doctors (28% of the sample) were twice as likely to have ever provided PA advice to their clients as their male counterparts. Providers of PA were more likely to have ever personally used this form of contraception than PA non-providers. Regardless of PA provider status, all physicians most frequently recommended pills, injectables and IUDs to their clients. They had very good knowledge of the temperature method. The scientific foundation of this method is studied in medical school, suggesting that if the other modern methods (Billings and sympto-thermal) were incorporated into medical school curricula, physicians might be more willing to discuss, refer or provide other modern, scientific forms of PA to their clients.


Spontaneous Abortions in Women With Endometriosis

D L Olive

University of Arkansas for Medical Sciences


Prevention of postsurgical adhesions by INTERCEED(TC7), an absorbable adhesion barrier: a prospective randomized multicenter clinical study. INTERCEED(TC7) Adhesion Barrier Study Group

Abstract: INTERCEED(TC7) (Johnson & Johnson Patient Care Inc., New Brunswick, NJ) is an absorbable fabric specially designed to reduce postsurgical adhesions. The authors report on a prospective, randomized, multicenter, clinical trial that evaluated the efficacy of Interceed in reducing adhesions in humans. Infertility patients (n = 74) with bilateral pelvic sidewall adhesions were studied at treatment laparotomy and "second-look" laparoscopy to determine Interceed's effectiveness. After removal of adhesions at laparotomy, the deperitonealized area of one pelvic sidewall was covered with Interceed. The contralateral untreated sidewall served as the control. Pelvic sidewalls covered with Interceed had a 90% improvement over control sidewalls in preventing adhesion formation. Additionally, Interceed treatment was associated with a 57% reduction of the extent of adhesion formation over that obtained by microsurgical techniques alone. Interceed also provided a significant benefit in reducing the severity of those adhesions that did form, and significantly reduced the number of adhesions between the ovary and pelvic sidewall. In conclusion, Interceed significantly reduced the incidence, extent, and severity of postsurgical pelvic adhesions.


Diagnosis and management of out-of-phase endometrial biopsies among patients receiving clomiphene citrate for ovulation induction

Abstract: Eighty-seven patients who underwent a late secretory phase endometrial biopsy while taking clomiphene citrate (CC) for ovulation induction were studied. Of the endometrial biopsies, 21 (24%) showed an endometrium greater than 2 days out of phase (OOP) with respect to the subsequent menstrual cycle. All 87 patients were categorized by age, weight, CC dosage, and underlying disease entity. The patients then were evaluated by these categories in relation to the incidence of an OOP biopsy while taking CC. Patients with a diagnosis of hypothalamic amenorrhea were statistically more likely to have an OOP endometrium. No other subgroup showed an increased or decreased incidence of OOP biopsies. Conception and spontaneous abortion rates were similar among patients with in-phase biopsies and those with out-of-phase biopsies, which subsequently were corrected with further medical therapy. An aggressive approach to the diagnosis and treatment of luteal phase insufficiency in patients who receive CC for ovulation induction is recommended.


Gamete membrane fusion in hamster spermatozoa with reacted equatorial segment

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: Mammalian spermatozoa must undergo many changes to be able to fertilize the oocyte. One of these changes, the acrosome reaction, has been established as a requisite for gamete membrane fusion to occur; it consists of the fusion and vesiculation of the sperm plasma membrane with the outer acrosomal membrane of the principal segment of the acrosome. Reaction of the equatorial segment has occasionally been observed. The objective of the present work was to determine whether the presence of the sperm plasma membrane over the equatorial segment is necessary for gamete membrane fusion to occur. Golden hamster spermatozoa were capacitated in vitro in TAPL 10K, and the maximum possible percentage of acrosome reaction was determined at 82.79% + 1.69% SD (P = 0.27; r = 0.21). Ultrastructural studies showed that 93.6% of the reacted spermatozoa in this population had their principal and equatorial segments reacted. The fertilizing ability of these spermatozoa was assayed using zona-free hamster oocytes. The percentage of fertilized ova obtained was 98.8% (308/312). Ultrastructural studies showed the presence of spermatozoa with reacted equatorial segment inside the cytoplasm of immature oocytes. The evidence presented in this work demonstrates that the plasma membrane of spermatozoa with reacted equatorial segment retains its ability to fuse with the oocyte.


Potential use of C-reactive protein determinations in obstetrics and gynecology

Abstract: C-reactive protein (CRP) is an acute-phase protein synthesized by the liver during the course of a large number of diseases. During gestation and parturition, progressively increasing numbers of gravida develop elevated levels up to 32, 48 to 80 per cent, respectively). These elevations in pregnancy, the nonspecificity of the test, and the inability to function as a reliable marker of fetal and/or maternal infectious morbidity have obscured the pragmatic utility of CRP determinations in both obstetrics and gynecology. Because of its biophysical kinetics, C-reactive protein determinations are best used as a monitoring parameter after the documentation of infection rather than as a diagnostic indicator of infection. They can provide valuable end titration points for termination of parenteral antibiotic therapy.


Tamoxifen treatment in women with failure of clomiphene citrate therapy

R Borenstein

Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel.

Abstract: Fourteen pregnancies were achieved with tamoxifen therapy in 12 women who failed to conceive with clomiphene citrate. There were no side-effects and fewer treatment cycles were required than with clomiphene citrate treatment. Ovulation and cervical score with tamoxifen therapy were significantly higher (p less than 0.005).

The Australian & New Zealand Journal of Obstetrics & Gynaecology


How precise is histologic dating of endometrium using the standard dating criteria?

Tin-Chiu Li

University of Sheffield, United Kingdom.

Abstract: Sixty-three endometrial biopsies were dated histologically by using the standard criteria on two separate occasions by the same observer. Overall, it was found that exact agreement occurred in 15 (24%), but disagreement of more than 2 days occurred in 6 (10%). The proportion of exact agreement in the first half of the luteal phase (32%) was found to be significantly higher (P less than 0.05) than that in the second half of the luteal phase (9%). In a separate part of the study, 27 women had two endometrial biopsies, each performed in a separate cycle. The within-subject between-cycle variation of the results of endometrial dating (exact agreement: 4%, disagreement of more than 2 days: 41%) was found to be significantly different from intraobserver variation (P less than 0.01 for both). The amount of intraobserver variation suggests that the traditional dating criteria are not precise enough to quantify corpus luteum function in the second half of the luteal phase, whereas the amount of within-subject between-cycle variation implies that the result of endometrial dating in one cycle cannot be used reliably to predict that of another cycle.


Decreased follicular phase gonadotropin secretion is associated with impaired estradiol and progesterone secretion during the follicular and luteal phases in normally menstruating women

Abstract: We tested the hypothesis that disturbed follicular development and disturbed luteal progesterone (P4) secretion are associated with reduced gonadotropin secretion in the early follicular phase by measuring pulsatile LH and FSH secretion at that time in 53 normally menstruating women. Three groups of women were identified on the basis of serum sex steroid concentrations (measured daily throughout the cycle) and luteal phase length. Group A (n = 27) had normal ovarian hormone secretion with peak serum estradiol (E2) concentrations of 440 pmol/L or more, peak serum P4 concentrations of 19 nmol/L or more, and luteal phase length of 9 days or more. Group B (n = 16) had normal peak serum E2 values, but peak serum P4 values less than 19 nmol/L and/or luteal phase length less than 9 days. Group C (n = 10) had peak serum E2 values below 440 pmol/L. Risk factors for the disturbances found in groups B and C were exercise and/or intermittent dieting. Compared to group A, both groups B and C had reduced mean serum LH concentrations (3.1 +/- 1.5 vs. 2.3 +/- 1.4 and 2.0 +/- 1.0 IU/L; P less than 0.05) and reduced LH pulse frequencies (5.2 +/- 2.1 vs. 3.5 +/- 1.8 and 3.3 +/- 2.3 pulses/12 h; P less than 0.02). LH amplitude was similar in all 3 groups. Mean serum FSH concentrations were slightly but not significantly lower in group C. We conclude that reduced gonadotropin secretion during the follicular phase may indeed affect E2 and P4 secretion at later stages of the menstrual cycle. The patterns of alteration associated with disturbed E2 and P4 secretion in normally menstruating women are similar to those that occur in women with hypothalamic amenorrhea.

The Journal of Clinical Endocrinology and Metabolism


Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight

Roberto Romero

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract: The relationship between asymptomatic bacteriuria and prematurity/low birth weight (LBW) is still a controversial issue, despite many studies. Meta-analysis, a research tool designed to analyze and combine the results of previous studies, may resolve this discrepancy among contradictory results of clinical trials. The purpose of this study was to examine the relationship between asymptomatic bacteriuria and preterm delivery/LBW using meta-analysis. Reports from the literature were classified according to study design into cohort or randomized-treatment control trials. Meta-analysis of cohort studies showed that untreated asymptomatic bacteriuria during pregnancy significantly increased rates of LBW and preterm delivery. Nonbacteriuric patients had only about two-thirds the risk (typical relative risk = 0.65; 95% confidence interval 0.57, 0.74) of LBW and half the risk (typical relative risk = 0.50; 95% confidence interval 0.36, 0.70) of preterm delivery of those with untreated asymptomatic bacteriuria. These reduced risks correspond to a 3.4 (confidence interval 1.8, 5.0) percentage-point difference in LBW and a 3.8 (1.1, 6.4) percentage-point difference in preterm delivery. The analysis of randomized clinical trials showed that antibiotic treatment significantly reduced the risk of LBW (typical relative risk = 0.56; 95% confidence interval 0.43, 0.73), with a substantial reduction of 6.4 (confidence interval 3.3, 9.5) percentage points in the rate of LBW. We conclude that clinical and epidemiologic evidence indicates a strong association between untreated asymptomatic bacteriuria and LBW/preterm delivery and that antibiotic treatment is effective in reducing the occurrence of LBW.


Follicle size by ultrasound versus cervical mucus quality: normal and abnormal patterns in spontaneous cycles

Karen L. Reuter

University of Massachusetts Chan Medical School

Abstract: Ultrasound (US) has been demonstrated to be the method of choice for diagnosing luteinized unruptured follicle syndrome and to be a valuable adjuvant in the assessment of luteal phase defect. In this prospective study, the use of US with postcoital testing (PCT) is evaluated. Fifty control infertility patients were examined with serial US for follicle dynamics in conjunction with PCT. Standard curves for follicle dynamics versus cervical mucus quality (Insler score) were calculated. Eighteen patients referred for abnormal mucus underwent similar evaluation. Their follicle dynamics versus mucus quality were compared with those of the controls. The findings were: (1) there is a predictable relationship between follicle size and mucus quality, (2) the majority of patients with abnormal mucus have normal follicular dynamics, and (3) a minority of patients with abnormal mucus have either a narrow mucus window or abnormal follicular dynamics. In addition, US was found to be cost-effective in the overall fertility evaluation.


Twenty-four-hour progesterone and luteinizing hormone profiles in the midluteal phase of the infertile patient: correlation with other indicators of luteal phase insufficiency

D L Olive

University of Arkansas for Medical Sciences

Abstract: The authors have further analyzed women diagnosed as having luteal phase insufficiency in hope of determining the value of specific screening tests as well as determining the degree of heterogeneity of pathophysiologic mechanisms involved in the disorder. Twelve women with the disorder were identified, 6 with two consecutive midluteal serum progesterone (P) levels less than 10 ng/ml (group 1) and 6 with two consecutive late luteal phase endometrial biopsies out of phase (group 2); 4 infertile women with normal serum P and late luteal biopsies also were studied (group 3). All underwent serum sampling for P and luteinizing hormone (LH) at 20-minute intervals for 24 hours, beginning at 9:00 A.M. of day 7 post-LH surge. No significant differences were noted among the three groups for LH area under the curve, pulse frequency, or pulse amplitude. Furthermore, no differences were ascertained for P area under the curve. However, individuals were identified who had one or more hormonal abnormalities but no abnormal biopsy, as well as patients with normal hormonal profiles but having abnormal endometrial development. Receiver Operating Characteristic curves demonstrated that pooled morning serum P levels provided optimal predictive ability of biopsy results. The authors conclude that luteal phase insufficiency is a heterogeneous disorder, and that neither endometrial biopsy nor serum hormonal analysis obviates the need for the other.


The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies

Abstract: Five regularly menstruating women of proven fertility, with normal prolactin and thyroid function studies, underwent a total of 39 endometrial biopsies (EMBs). The slides were dated in blinded fashion, and the cycle date determined by considering the date of the next menstrual period as day 28 and counting backward. Using a 2-day or greater lag in endometrial maturity to define a luteal phase defect (LPD), the incidence of single and sequential out-of-phase EMBs was 51.4% and 26.7%, respectively. Using a 3-day or greater lag to define a LPD, the incidence of single and sequential out-of-phase EMBs was 31.4% and 6.6%, respectively. These incidences in normal, fertile women are as high as the rates quoted for infertile populations, and call into question the standard criteria for defining this condition and evaluating therapies to correct it.


Origin of luteinizing hormone-releasing hormone neurons

M Schwanzel-Fukuda

Rockefeller University, New York, New York 10021.

Abstract: Neurons expressing luteinizing hormone-releasing hormone (LHRH), found in the septal-preoptic nuclei and hypothalamus, control the release of gonadotropic hormones from the anterior pituitary gland and facilitate reproductive behaviour. LHRH-expressing neurons are also found in the nervus terminalis, a cranial nerve that is a part of the accessory olfactory system and which projects directly from the nose to the septal-preoptic nuclei in the brain. During development, LHRH-immunoreactivity is detected in the peripheral parts of the nervus terminalis before it is found in the brain. Using a combination of LHRH immunocytochemistry and tritiated thymidine autoradiography in fetal mice, we show that LHRH neurons originate in the medial olfactory placode of the developing nose, migrate across the nasal septum and enter the forebrain with the nervus terminalis, arching into the septal-preoptic area and hypothalamus. Clinically, this migratory route for LHRH-expressing neurons could explain the deficiency of gonadotropins seen in 'Kallmann's syndrome' (hypogonadotropic hypogonadism with anosmia).


C-reactive protein in preterm labour: association with outcome of tocolysis and placental histology

Abstract: Tocolytics were administered in 66 consecutive women in uncomplicated preterm labour with intact fetal membranes (53 singleton and 13 twin pregnancies). C-reactive protein (CRP), a marker of infection, was determined daily and used retrospectively to investigate the role of subclinical infection in preterm labour and to predict the efficacy of tocolysis and the development of a clinical perinatal infection. CRP was also determined in 66 women in uncomplicated labour at term (53 singleton and 13 twin pregnancies). The placenta was examined for histological evidence of infection in all patients who were delivered before 36 weeks (n = 21) and in all women in the control group (n = 66). Elevated CRP levels were more often found in patients who were refractory to tocolysis, suggesting an underlying infectious morbidity. Placental infection was found in 62% of the preterm delivery group and in 12% of the control group. There was an association between elevated CRP levels and histological evidence of placental infection. However, confounding factors such as urinary tract infections limit the usefulness of the CRP test. Because CRP cannot predict clinical perinatal infection accurately, its clinical relevance is very limited.

British Journal of Obstetrics and Gynaecology


Oral contraception, smoking and inflammatory bowel disease--findings in the Royal  College of General Practitioners Oral Contraception Study

Abstract: Data from the Royal College of General Practitioners Oral Contraception Study have been examined to determine whether oral contraceptive use was associated with the development of Crohn's disease or ulcerative colitis. Over a 17 year period Crohn's disease developed in 42 women and ulcerative colitis in 78. The incidence of both diseases was greater in oral contraceptive users compared to non-users with the rate ratio for Crohn's disease being 1.7 (95% confidence limits, 0.88, 3.2) and for ulcerative colitis being 1.3 (95% confidence limits 0.82, 2.0). For both diseases incidence was unrelated to parity or social class, but women smoking at recruitment had a greater incidence of Crohn's disease (rate ratio 1.8, 95% confidence limits 0.93, 3.3) and a reduced incidence of ulcerative colitis (rate ratio 0.68, 95% confidence limits 0.41, 1.1). Although these results are based on small numbers and could be chance findings, they are consistent with other studies showing associations between oral contraceptive use, smoking and the development of Crohn's disease and ulcerative colitis.


The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume

Abstract: Fifteen ovulating women had serial ultrasound scans to measure follicular, endometrial, and uterine growth, as well as biochemical indices including estradiol (E2) and the free androgen index, throughout a natural and a clomiphene-citrate-induced cycle. Despite higher E2 levels in the 5 days preceding ovulation, the clomiphene cycles were characterized by absence of the normal increase in uterine volume and an inhibition of endometrial thickening. It is proposed that the anti-estrogen effect of clomiphene inhibits the normal cyclical growth of the uterus and endometrium.


Spironolactone with physiological female steroids for presurgical therapy of male-to-female transsexualism

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: The clinical and hormonal response to 12-month therapy with the antiandrogen, spironolactone, in conjunction with near-physiologic doses of female gonadal steroids in 50 transsexual males, is presented. An unselected referred series of 61 men with the psychiatric diagnosis of transsexualism was treated; 10 subjects who had received previous gonadal surgery and 1 man with Klinefelter's syndrome were excluded. Twenty-seven conventionally treated (CT; high-dose estrogen), age 34.4 +/- 10.5 years, mean +/- SD, and 23 untreated patients (SPS), age 30.7 +/- 6.2 years, were studied. Following the initial visit, all 50 were begun on spironolactone and low-dose female hormone therapy. Despite high-dose estrogen treatment for more than 2 years, the mean testosterone (T) level for the CT group was not in the female range (169 +/- 193 ng/dl; normal 20-80). Spironolactone, in doses of 200-600 mg/day, lowered T to the female range in both groups after 12 months (CT 87 +/- 111 and SPS 49 +/- 41 ng/dl). This was achieved in the CT group despite decreases in estrogen dose and discontinuation of parenteral therapy. SPS subjects experienced significant decreases in plasma T (642 +/- 236 to 49 +/- 41 ng/dl, p less than 0.001). Systolic blood pressure dropped (128 +/- 14 to 121 +/- 14 mm Hg, p less than 0.05). The clinical response, including decreased male pattern hair, breast development, feminization, and lack of erections was excellent in most subjects.


Alterations in the hypothalamic-pituitary-ovarian and the hypothalamic-pituitary-adrenal axes in athletic women

A B Loucks

Department of Reproductive Medicine, School of Medicine (T-002), University of California-San Diego, La Jolla 92093.

Abstract: The functional integrity of the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axes was assessed by determining pulsatile LH, ACTH, and cortisol secretion during the early follicular phase in athletic women with regular menstrual cycles (CA; n = 9), athletic women with amenorrhea (AA; n = 9), and regularly cyclic sedentary women (CS; n = 8). The CA and AA women were not significantly different in body composition, exercise training, psychometric tests, or dietary consumption. The CA women had shorter luteal phases (P less than 0.05) and lower urinary excretion of pregnanediol glucuronide than the CS women. In the AA women, urinary estrone glucuronide, pregnanediol glucuronide, and LH excretion were low throughout a 30-day period. The CA women had a 24-h pattern of pulsatile LH secretion characterized by reduced frequency (P less than 0.05) and increased amplitude (P less than 0.05), yielding an overall increased 24-h mean level (P less than 0.05), but interpulse intervals similar to those in the CS women. During sleep, LH pulse frequency slowed in the CS and CA women, while pulse amplitude increased and the mean serum LH level decreased in both groups. The AA women had even fewer pulses (P less than 0.05) of normal amplitude occurring at much more variable (P less than 0.01) interpulse intervals. Sleep-associated changes in LH pulsatility were absent. Responses to a 10-microgram bolus GnRH dose revealed blunted (P less than 0.05) FSH release in CA and augmented (P less than 0.05) LH release in AA women. The groups did not differ in any 24-h ACTH pulse pattern parameter or in cortisol pulse frequencies. Yet, early morning (0200-0800 h) serum cortisol levels were higher (P less than 0.05) in both groups of athletes, and this elevation was extended through the day (0800-2000 h; P less than 0.001) and evening (2000-0200 h; P less than 0.05) in the AA women. The plasma ACTH and serum cortisol responses to bolus human CRH administration were blunted in the CA and AA women [change from baseline (delta) in ACTH, P less than 0.05 and P less than 0.01; delta cortisol, P less than 0.01 and P less than 0.01, respectively], but adrenal sensitivity (delta cortisol/delta ACTH ratio) was increased (P less than 0.05). The plasma ACTH and serum cortisol responses to meals also were blunted in the athletic groups (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

The Journal of Clinical Endocrinology and Metabolism


Hormonal Regulation of the Menstrual Cycle: The Evolution of Concepts


Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study

Abstract: Oral clomiphene citrate (CC) and vaginal progesterone suppositories (PS) are common treatment modalities in luteal phase dysfunction (LPD). Little is known regarding the relative efficacy of these agents. To study the use of CC and PS in the management of LPD, a retrospective cohort study of patients presenting with infertility was undertaken. Sixty-five patients in whom LPD was diagnosed and corrected, as judged by endometrial biopsies, were studied; 35 were treated with PS and 30 with CC. Using Student's t-tests and chi-square analyses, the two treatment groups were demographically comparable. Using life-table analysis, no one therapeutic approach proved superior. Clomiphene citrate and PS are comparable treatment modalities in the setting of LPD given correction of endometrial lag.


Correlation of endometrial maturation with four methods of estimating day of ovulation

Abstract: Dating of maturity of the endometrium by histologic examination was correlated with four methods of ovulation detection in 13 cycling parous women. Histologic dating was assessed independently by two pathologists and correlated with the postovulatory duration as determined by daily transvaginal ultrasound scanning, serum LH measurements, basal body temperature (BBT), and subtraction of 14 days from the onset of menses. In addition, progesterone and estradiol (E2) were measured in daily serum samples. Dating of the endometrial biopsy was highly correlated (P less than .002) with the day of ovulation as determined by ultrasound, and was found to be within 2 days of the correct postovulatory day on evaluation of 25 of 26 (96.1%) of the interpretations. The accuracy of dating using the LH surge was 84.6% (22 of 26 interpretations), and with the BBT thermogenic shift was 76.9% (20 of 26 interpretations). However, dating of the endometrium was within 2 days of the correct day in only 17 of the 26 interpretations as determined by subtracting 14 days from the onset of the subsequent menses. The accuracy of dating was significantly better correlated (P less than .025) with days from ovulation as determined by ultrasound than as calculated from the onset of menses. There was a significant correlation between endometrial dating and the amount of progesterone (P less than .01) and E2 (P less than .01) secreted from the day of ovulation, as determined by transvaginal ultrasound, to the day of biopsy. These data confirm a strong correlation between endometrial dating and ovarian hormone secretion during the postovulatory phase.(ABSTRACT TRUNCATED AT 250 WORDS)


Bone mineral density in women with endometriosis before and during ovarian suppression with gonadotropin-releasing hormone agonists or danazol

W P Dmowski

University of Arkansas for Medical Sciences

Abstract: Lumbar bone mineral density (BMD) was evaluated by dual photon absorptiometry (DPA) in 38 women with laparoscopically diagnosed and staged endometriosis. DPA was performed before and at the completion of 26 weeks of treatment with either gonadotropin releasing hormone agonist (GnRHa) or danazol. Twenty-five women received GnRHa either nasally or subcutaneously and 13 women received danazol 200 mg four times daily by mouth. During treatment amenorrhea and suppressed estradiol levels were observed in all patients. Each patient took a supplement of oral calcium 1 gm daily. DPA (reproducibility +/- 1.5%) was read by a single observer unaware of the treatment assignment of the patient. The mean (+/- standard error) of the entire group prior to treatment was 98.8% +/- 0.03% of a control population of women from the same geographic area matched for race, age, and weight. At the completion of treatment, BMD was slightly decreased in the GnRHa group and marginally increased in the danazol group but neither change was significant. Women with endometriosis have lumbar BMD in the normal range and ovarian suppression with either GnRHa or danazol produces no significant change in BMD.


Inability of sonography to detect imminent ovulation

WD Middleton

Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226.

Abstract: Sonographic visualization of the cumulus oophorus or of morphologic alterations in the wall of the dominant follicle have been reported to be reliable signs of imminent ovulation when conventional transabdominal sonography is used. To determine if transvaginal sonography could allow a more frequent and confident prediction of imminent ovulation, we prospectively monitored 22 ovulatory menstrual cycles in four women undergoing artificial insemination and in 13 normally menstruating volunteers. Scanning was done on alternate days in the periovulatory period; a 7.5-MHz transvaginal transducer was used. Despite the improved resolution obtained with transvaginal sonography, confident identification of the cumulus oophorus or of mural changes in the follicle was not possible in any of the cycles followed. No other consistent follicular characteristic predicted imminent ovulation. We conclude that confident prediction of imminent ovulation is not possible with sonographic analysis.


Intense Exercise During the First Two Trimesters of Unapparent Pregnancy

Abstract: In brief: Two runners who were not aware they had conceived continued their intense running regimens during the first and second trimesters of pregnancy. Both women assumed that their amenorrhea was due to endurance training. When their pregnancies were diagnosed, both women markedly reduced their training mileage during the third trimester because they feared that intense exercise might harm the fetus. Retrospective data were collected on their antenatal and intrapartum courses. Both women delivered healthy infants of normal weight. Although these two cases suggest that strenuous anaerobic exercise during pregnancy is not harmful, more studies are needed to determine if these cases are isolated.


Cobalt in the Environment and Its Toxicological Implications

Abstract: Cobalt is an essential trace element which is widely distributed in nature. Most of cobalt consumed is used in the manufacture of alloys, and although not released extensively in the environment, it may represent a hazard to human health. In addition, excess dietary cobalt produces toxic effects in animals. Polycythemia and hyperglycemia with transitory damage to pancreatic alpha-cells have been widely reported after cobalt administration. Cobalt salts induce respiratory deficiency in yeast. CoCl2 increased sister chromatid exchange (SCE) in P388D1 cells and in lymphocytes from two donors. So far it has not been possible to induce cancer in experimental animals using cobalt by any other route than by injection. Ingestion of cobalt may lead to reproductive changes in the male rat such as loss of testicular volume and darkening of testicle color. On the other hand, oral administration of cobalt did not produce teratogenicity or significant fetotoxicity in the rat at daily doses as high as 100 mg CoCl2/kg. However, cobalt affected the period of late gestation as well as the postnatal development of the pups. Occupational toxicology of cobalt, hygienic and epidemiologic aspects, and treatment of cobalt poisoning are also topics of special interest. Cobalt is a metal with marked allergenic potential. Asthma, interstitial lung disease and combined asthma and alveolitis have been described as occupational health hazards. EDTA, DTPA, and N-acetyl-L-cysteine have been suggested as possible antidotes in cobalt intoxication.

Reviews of Environmental Contamination and Toxicology


Hormone Regulation of the Menstrual Cycle: The Evolution of Concepts


Encountering Human Ecology: Natural Family Planning

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.


Theologians and Authority

Theologians and Authority


Cervical Mucus Anomalies in Patients with Endometriosis


Efficacy of human menopausal gonadotropins as therapy for abnormal cervical mucus

C Soto-Albors

University of Connecticut Health Center, Farmington.

Ying Ying

The First Affiliated Hospital, Sun Yat-sen University

Abstract: Traditional therapies for abnormal cervical mucus, other than timed intrauterine insemination, are noteworthy for being ineffectual. Patients (n = 27) with documented abnormal Insler scores in repetitive cycles and failure to conceive with traditional treatments were screened with conjugated equine estrogens (CEE) for estrogen responsiveness of the cervix. Only 5 patients were found unresponsive. Seventeen patients with CEE-responsive cervices then were treated with human gonadotropins (hMG), initially 1 ampule days 5 to 11. If the mucus failed to improve, the hMG was increased to standard doses. Eight patients responded to 1 ampule hMG with improved mucus and conception. The remainder required 2 ampules hMG. In patient cycles with corrected cervical mucus, the viable fecundibility (fv) was 0.35. This is significantly higher than predicted for this population (fv = 0.09; P less than 0.01). In all, 14 of 17 patients conceived viable pregnancies during hMG treatment. It is concluded that graduated hMG is efficacious in treating patients with abnormal cervical mucus responsive to CEE. It is preferable to either in vitro fertilization or gamete intrafallopian transfer, based on both cost and efficacy for most patients.


The validity of gestational age estimation by menstrual dating in term, preterm, and postterm gestations

Michael S Kramer

Department of Pediatrics, McGill University Faculty of Medicine, Montreal, Quebec, Canada.

Abstract: Despite recognition that estimation of gestational age (GA) based on maternal recollection of the last normal menstrual period (LNMP) is fraught with error, it is not generally appreciated that the magnitude and direction of this error vary as a function of the LNMP estimate. Early second-trimester (16 to 18 weeks) ultrasound determinations of the fetal biparietal diameter were used as the "gold standard" to test the validity of LNMP-based GA estimates in 11,045 women. The large majority of deliveries occurring at or near term showed LNMP estimates that were valid within plus or minus seven days of the ultrasound estimate. As the LNMP GA deviated progressively toward earlier or later GAs, however, the discrepancies became quite marked, especially for postterm dates. The positive predictive values of the LNMP GA estimates decreased dramatically from term (.949) to preterm (.775) to postterm (.119) deliveries. These systematic errors in menstrual GA estimates have profound implications for unnecessary induction, dysfunctional labor and cesarean section, and resultant neonatal and maternal morbidity.


The effect of interobserver variation in dating endometrial histology on the diagnosis of luteal phase defects

Abstract: Endometrial biopsy specimens (n = 62) were evaluated by five pathologists to assess the effect of interobserver variation on histologic dating of the endometrium. The potential effect of this variation on the diagnosis of luteal phase defects (LPDs) and resulting clinical management was also determined. Mean (+/- standard error) interobserver variation was 0.96 +/- 0.08 days, comparable to results reported by other investigators. The magnitude of the variation was not affected by whether the biopsy specimen was obtained in the mid or late luteal phase, the degree of lag between the dating and subsequent menses, or the presence of an LPD. Redating of a specimen by another pathologist would have resulted in a change in the determination of "in" or "out" of phase in 22% of cases. The subsequent probability of changing patient management altered ranged from 22% to 39% depending on the clinical setting.


The luteinized unruptured follicle and other ovulatory dysfunctions

Abstract: DlJ. ring the last stage of puberty, the hypothalamic-pituitary-ovarian axis acquires the ability to respond to high levels of estradiol; this results in a sharp increase in the pituitary output of luteinizing hormone (LH). It is believed that within a mature follicle, the LH surge triggers a complex set of events that results in two apparently independent phenomena: ovulation and luteinization. The term ovulation will imply rupture of the follicular wall and release of an oocyte, whereas luteinization will imply the morphologic and biochemical shift in the …


Spontaneous abortions in women with endometriosis

Abstract: Pregnancy outcomes were evaluated retrospectively in 350 women to investigate the relationship between endometriosis and spontaneous abortions. The frequency of spontaneous abortions in women with endometriosis was significantly higher than in both a fertile nonendometriosis group and an infertile group with tubal disease. There was no correlation between the severity of the endometriosis and the frequency of spontaneous abortions. After treatment, the frequency of spontaneous abortions was significantly decreased in both the endometriosis and the tubal disease group, but these values were not significantly different from each other. We conclude that high spontaneous abortion rates are a characteristic of other subgroups of women with secondary infertility and not just in women with endometriosis, and that the majority of spontaneous abortions associated with endometriosis are not caused by the condition.


A comparison of the psychological and hormonal factors in women with and without premenstrual syndrome


Use of the subcutaneous terbutaline pump for long-term tocolysis

M Katz

Rutgers, The State University of New Jersey

Miranda Smith

Department of Pathology, Southern Regional Area Health Education Center, Fayetteville, North Carolina, USA.

Abstract: Nine patients in preterm labor requiring long-term tocolysis were managed with subcutaneous terbutaline administered via a portable infusion pump. All had failed oral tocolytic therapy and were therefore faced with prolonged hospitalization. In this feasibility study, the patients were treated at home and monitored with portable tocodynamometers and home nursing visits. Uterine activity data were transmitted via telephone to the study center and terbutaline pump infusion rates were adjusted accordingly. Terbutaline pump therapy consisted of a combination of low-dose continuous basal infusion supplemented with intermittent high-dose boluses. Total daily drug dosage remained exceptionally low (less than 3 mg/24 hours). The mean gestational age at initiation of therapy was 29.6 +/- 3.7 weeks, and pregnancy was prolonged an average of 9.2 +/- 4.3 weeks. The minimum gestational age at delivery was 37.3 weeks. Patient tolerance was excellent and, in a total 394 patient-days of therapy, there were no significant complications. We conclude that the portable subcutaneous terbutaline pump may be a promising new method for long-term outpatient tocolysis in patients who cannot be maintained on oral therapy.


Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites

R Andersen

Norwegian Labour and Welfare Administration

Abstract: Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry, respectively, after ingestion of micronized progesterone by eight postmenopausal women. One subject received 400 mg of micronized progesterone orally that induced a hypnotic state that lasted for approximately 2 hours. Blood samples were drawn periodically from all subjects for measurement of progesterone and its metabolites in serum. Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progesterone administration. Significant quantities of five compounds (progesterone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha,20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione) that have been reported to possess anesthetic qualities were identified. The sedative and hypnotic effects of oral administration of progesterone may be mediated through those compounds.

American Journal of Obstetrics and Gynecology


The Billings Ovulation Method. An update

Abstract: Women can accurately predict the day of ovulation by examining vaginal mucus using the Billings Ovulation Method (BOM). they then can choose to either have sexual intercourse if they wish to conceive or to refrain if they do not want to become pregnant by being able to identify the peak day of fertility and the 3 following days of diminishing fertility. A preovulatory phase of the ovulatory cycle follows menstruation which generally includes a sensation of dryness around the genital area but sometimes no dry days occur. At this point progesterone activates the secretion of a thick sticky mucus into the cervical canal which sperms cannot penetrate. This mucus also serves to guard against infection in the reproductive tract and abdominal cavity. When circulating estrogen increases due to follicular development a fluid clear and stringy mucus replaces the thick mucus. this mucus is like a raw egg white. Under the microscope it has a distinctive fern pattern. Sexual intercourse during this time period may result in pregnancy because this mucus sustains sperm cells in cervical crypts for 48-72 hours. Not all women notice the changes in the mucus however but they can sense the vulva as soft swollen and moist. The final day of this sensation identifies the peak day (day 1) in which ovulation customarily occurs. Even though fertility decreases in the next 3 days conception may occur in days 1-3. Infertility sets in on day 4 and last on average 2 weeks. any mucus now seems sticky and opaque. WHO field trials in El Salvador and 4 other countries confirmed that BOM is >99% effective when couples adhere to the guidelines. Research demonstrated that illiterate couples from low socioeconomic status understand it and apply it successfully.


Endometriosis. Obtaining relief via 'near-contact' laparoscopy

Abstract: Since 1979, Dr Redwine has performed the near-contact laparoscopy for the removal of endometriosis on nearly 400 women. Data collected from Dr Redwine's follow-up studies indicate that 75% of his patients have experienced complete relief of symptoms, and 20% have experienced an improvement in their symptoms from disabling pain to minimal pain. The individualized perioperative care and the high success rate realized with the near-contact technique has attracted women seeking relief from the painful and sometimes debilitating effects of endometriosis.


Characteristics of ovulation method acceptors: a cross-cultural assessment

Abstract: Five programs of instruction in the ovulation method (OM) in diverse geographic and cultural settings are described, and characteristics of approximately 200 consecutive OM acceptors in each program are examined. Major findings include: the religious background and family size of acceptors are variable, as is the level of previous contraceptive use. Acceptors are drawn from a wide range of socioeconomic and religious backgrounds; however, family planning intention was similarly distributed in all five countries. In sum, the ovulation method is accepted by persons from a variety of backgrounds within and between cultural setting.


Clinical trial of naltrexone in premenstrual syndrome

Abstract: Twenty women with the diagnosis of premenstrual syndrome (PMS) participated in a double-blind, placebo-controlled, crossover study to evaluate the efficacy of naltrexone, an oral opiate antagonist. This study was designed to test the hypothesis that inhibition of opiate withdrawal would aid in the treatment of PMS. The subjects received either placebo or naltrexone from days 9-18 of the cycle for three consecutive cycles. The mean scores of the three day-25 Menstrual Distress Questionnaires of 16 patients on naltrexone were compared with the mean scores of the same patients on placebo. Scores were at least ten points lower on naltrexone in 11 patients and at least ten points higher on naltrexone in two patients. Score changes of less than ten points were noted in the other three patients. The mean scores dropped 28 points on naltrexone (P = .016). The general acceptability of naltrexone was good, with side effects including nausea, decreased appetite, and dizziness. These results suggest that naltrexone alleviates many PMS symptoms and may be an effective treatment for this syndrome.


Primary structure of human insulin-like growth factor-binding protein/placental protein 12 and tissue-specific expression of its mRNA

Abstract: The low-molecular-mass insulin-like growth factor-binding protein (IGF-BP) and placental protein 12 (PP12) are identical proteins that are present in human serum, amniotic fluid, secretory endometrium and decidua. IGF-BP/PP12 is believed to act as an autocrine or paracrine regulator of cell growth. A cDNA clone encompassing the entire protein coding region of this protein was isolated from a human decidual cDNA library. The authenticity of the cDNA was verified by in vitro transcription/translation experiments and by the identity of the 10 N-terminal amino acids deduced for the mature peptide with those obtained by direct protein sequencing. The amino acid sequence indicates that pre-IGF-BP/PP12 consists of 259 amino acid residues. The putative signal peptide is 25 residues long, and the mature protein thus contains 234 amino acids and has a molecular mass of 25293 Da. The sequence is very cysteine-rich at the N-terminus after which there are regions of clustered Pro, Glu, Ser and Thr residues (so-called PEST regions), which exist in proteins with short half-lives. The amino acid sequence also includes an Arg-Gly-Asp tripeptide that may function as a cell recognition signal. The IGF-BP/PP12 gene encodes a single 1.6 kb mRNA species that is expressed in decidua, secretory endometrium, liver and a human hepatoma cell line (HepG2). Southern blot analysis suggests that there is a single IGF-BP/PP12 gene in the human genome.


Medroxyprogesterone acetate therapy in early pregnancy has no apparent fetal effects

Abstract: Medroxyprogesterone acetate (MPA; Provera) was given orally to 449 women from the 5th to 7th week of pregnancy until at least the 18th week. Data are recorded from two treatment groups (recurrent abortion and threatened abortion) and are compared to a matched series. A total of 1,016 pregnancies are included in the study, and all patients were recruited from a subfertile population conceiving from a range of infertility treatments. Early pregnancy wastage was high throughout the groups and was significantly elevated (43%; P less than .001) in those women who had vaginal bleeding in early pregnancy. The study focuses on the question of potential teratogenicity of progestagens administered in the first trimester. There were 15/366 (4.1%) infants with congenital abnormalities in the MPA-treated group and 15/428 in the untreated group (3.5%). The difference was not significant, and MPA is considered to have no embryopathic risk, nor is it likely to retain an abnormal fetus that might otherwise abort. It appears that MPA is a safe drug to use in pregnancy although the question of efficacy has not been addressed in this report. Considering other recent negative epidemiologic studies with regard to teratogenicity, we add to the conclusion that MPA cannot be demonstrated to have a measurable teratogenic risk and certainly does not present a risk for congenital heart disease and limb reduction defects.


The diagnosis of luteal phase deficiency: a critical review

Abstract: Luteal phase deficiency is an ovulatory dysfunction problem that is subtle but real. It may be the most common ovulatory problem in women. Luteal phase deficiency has been clearly demonstrated in the research setting (1) in spontaneous cycles, (2) when follicular maturation has been impeded, and (3) when luteotrophic influences have been suppressed. The diagnosis of LPD in the clinical setting remains problematic and controversial primarily because there is no practical diagnostic method that has been validated. This article has reviewed the methods that have been used to diagnose LPD. BBT charts are insensitive; these charts reliably diagnose LPD only when there are persistent short luteal phases. There is disagreement whether ovarian follicular size, as determined by ultrasonography, is decreased in LPD; however, ultrasonographic diagnosis of LPD would require daily scans through ovulation, which makes this approach impractical. Mild hyperprolactinemia is a probable cause of LPD in a minority of patients; a physician should obtain a PRL level in LPD women with the realization that there is considerable sampling variability. Determination of serum gonadotropin levels (LH or FSH or both) is not practical for the clinical diagnosis of LPD. Random serum P levels, whether single or multiple, are not helpful in the diagnosis of LPD in individual patients. The secretory pattern of P results in such wide confidence limits that P samples from individuals cannot be compared to normal in a useful manner. Most of the controversy about the diagnosis of LPD has centered around the use of individual serum P levels. The timed endometrial biopsy relies on the endometrium as a bioassay of P over time. The endometrial biopsy has not been carefully validated in terms of its sensitivity or accuracy for the diagnosis of LPD. However, it remains the best current method for the diagnosis of LPD when the standard guidelines for its use are followed. As opposed to the other tests for LPD, awareness of the usefulness of the biopsy has increased as we have learned more about CL physiology. No current research method for the diagnosis of LPD appears to be a practical method that could be applied in the clinical setting. Specific secretory proteins from the endometrium and methods to measure hormone secretion that circumvent the secretory pattern hold promise for improved methods to diagnose LPD in the future.