Some randomized studies have suggested a significant beneficial effect of 17-hydroxyprogesterone caproate in the prevention of preterm labor [1, 2], The therapy in both studies was initiated at approximately 12-16 weeks and continued until labor.
We considered the possibility that a deficient proges terone effect during the first trimester may lead to a higher rate of preterm deliveries. A retrospective study was thus performed comparing the incidence of preterm versus full-term pregnancies in women with luteal phase defects who were either treated or not treated with proges terone supplementation during the first trimester.
Cyclofenil is a triphenylethylene derivative, similar in structure to clomiphene citrate, which is used to induce ovulation in anovulatory women. The effects of cyclofenil on a group of 10 normal cyclic and 10 oligomenorrhoeic subjects were examined in a double blind controlled cross-over study. Both groups of women were administered either cyclofenil or, following a washout cycle, a placebo in two treatment cycles. Urinary oestrone and pregnanediol excretion were measured daily and ultrasound scans performed to assess follicular development. Frequent sampling of blood was performed on day 6 to study luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile release. Cervical mucus changes and sperm-cervical mucus interaction were studied after identification of the LH peak. There were no significant differences between cyclofenil and placebo ovulation rates, daily urinary oestrone and pregnanediol excretion, the number or size of developing follicles, LH pulsatility (parameters number of peaks, pulse interval, pulse amplitude, pulse area and mean nadir LH), mean FSH level on day 6, cervical mucus and sperm-cervical mucus interaction. In view of our inability to demonstrate an effect on any parameter of endocrine function in normal and oligomenorrhoeic women, these results throw doubt on the therapeutic value of cyclofenil in its present dosage and formulation.
Home uterine activity monitoring has been proposed as an effective technique for reducing the incidence of preterm birth by early recognition of incipient labor. Five randomized controlled trials evaluating this technique have been published in peer review journals. As judged by accepted criteria for such trials, all have serious methodologic deficiencies. Four of the five trials demonstrated no significant benefit from this monitoring. Two other trials not published in peer review journals support the hypothesis that home uterine activity monitoring is no more effective than daily nursing contact. Until the efficacy of this technology has been established, home uterine activity monitoring should not be used clinically.
To assess the deleterious effect of clomiphene citrate (CC) on the development of the endometrium and its improvement by the addition of ethinyl estradiol (E2). Infertility-treated patients, monitored for induction of ovulation or timing of insemination (control group). We studied four groups of women during an ovulatory cycle with various treatment schedules. Group 1: untreated patients; group 2: patients treated by CC; group 3: patients treated by CC + ethinyl E2; group 4: patients treated by human menopausal gonadotropin. Follow-up of the patients was done by vaginal ultrasonography and measurements of blood E2. In the group treated by CC, both endometrial thickness and uterine volume growth during the follicular phase were lower as compared with untreated controls and menotropin-treated patients. The addition of ethinyl E2 to these patients reversed this deleterious effect of CC without interfering with ovulation. Ethinyl E2 may reverse the deleterious effect of CC on endometrial development during the follicular phase.
Davis MS, 1992·NAACOGS Clin Issu Perinat Womens Health Nurs
Natural family planning includes the calendar (rhythm), basal body temperature, ovulation (mucus), and sympto-thermal methods. Reliability of such methods often is underestimated, but effectiveness of various methods has been reported. Correct understanding and use of proper techniques, primarily abstinence during fertile periods, is imperative for effectiveness. New methods being studied may heighten awareness of fertile times and shorten required periods of abstinence or use of back-up methods.
EndometriosisLaparoscopyTechniqueClassification Systems
In order to clarify the relationship between endometrial histology and progesterone (P4), plasma P4 and estradiol levels in the luteal phase were measured in 126 cases of unexplained infertility. Endometrial biopsies were performed in the midluteal period of menstrual cycles. Forty-three of the 126 cases showed retarded endometrium. Of these 43 cases, 23 exhibited three different types of abnormal P4 secretion. Type A showed low P4 levels throughout the luteal period. Type B showed low P4 levels only in the early luteal period. Type C showed normal P4 levels in the early luteal period followed by a prompt decline. These findings indicated that P4 determination during the early, mid- and late luteal phases is necessary to assess P4 secretion. However, 20 of the 43 cases had normal P4 levels through the entire luteal phase, demonstrating an insufficient response of the endometrium to P4. Consequently, histological examination of the endometrium is required to investigate the luteal phase defect.
Clomiphene citrate therapy has been found to improve the infertility rate in women suffering from polycystic ovarian disease (PCOD). However, there still exists a group of women with PCOD who fail to respond to clomiphene citrate or human menopausal gonadotropin/human chorionic gonadotropin or urofollitropin/chorionic gonadotropin treatment, an ovarian wedge resection by laparotomy approach which has been known for 50 years. Within the last decade, translaparoscopic electrocautery and laser drilling techniques have been utilized. In 1986, a translaparoscopic carbon dioxide laser ovarian wedge resection was introduced for resistant PCOD. This paper describes the surgical principle of a translaparoscopic carbon dioxide laser ovarian wedge resection. This type of treatment results in a 75% crude conception rate, with a 67% rate of healthy live birth. There was an 8% postsurgical adhesion rate among 12 cases that were incorporated into the study. This mode of therapy may prove to be very useful, safe, easy to perform, and cost effective as a second-line therapy for resistant PCOD in cases where medical inductions fail to achieve ovulation.
To evaluate the effects of Ringer's lactate instillation, Interceed(TC7) (Johnson and Johnson Medical, Inc., New Brunswick NJ), and Gore-Tex Surgical Membrane (W. L. Gore and Associates, Inc., Flagstaff, AZ) in a rat uterine horn model. Rats were in a conventional laboratory setting. Sprague-Dawley white rats, weighing 225 to 250 g. The left uterine horn was subjected to a standardized lesion by serosal denudation and devascularization. The rats were randomly assigned into control group, Interceed(TC7) group, Gore-Tex group, and Ringer's lactate group. Degree of adhesions was evaluated 2 weeks after the initial surgery. Adhesion score after Ringer's lactate instillation was significantly lower than those of control, Interceed(TC7), and Gore-Tex groups. Gore-Tex was associated with less adhesion formation than control. No difference was found in the adhesion formation between the Interceed(TC7) group and the control group. Confirming our previous observations, Ringer's lactate instillation is effective in decreasing adhesion formation. Gore-Tex reduces adhesion formation, but its efficacy is inferior to those of Ringer's lactate. Contrary to previous reports, Interceed(TC7) is ineffective in our animal model.
To evaluate the impact of the materials contained in the available adhesion prevention barriers on the peritoneum. STUDY DESIGN, SETTING, A murine paradigm was used, placing oxidized-regenerated cellulose (Interceed [TC7]) and expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane) in the peritoneal cavity for intervals up to 14 days. MAIN The appearance of the peritoneum on scanning and transmission electron microscopy and the presence of de novo adhesions were the end-points used. Oxidized-regenerated cellulose caused localized sloughing of the mesothelial cell layer and leukocyte infiltration of the deeper tissue leading to the formation of adhesions to the bowel and liver in 58% of the animals. The surface of the oxidized-regenerated cellulose-injured peritoneum healed in 5 to 7 days. Neither peritoneal injury nor adhesions were noted in sham-operated animals or animals with PTFE. Oxidized-regenerated cellulose but not PTFE has a localized injurious effect on the peritoneum of the mouse, resulting in de novo adhesions. The impact of the barrier material itself on normal peritoneum may be an important consideration in designing surgical barriers for the prevention of postoperative adhesions.
A study was initiated to evaluate the prevalence of the luteinized unruptured follicle (LUF) syndrome in a group of 355 women with infertility. The diagnosis was established by carefully observing daily sonograms along with measuring estradiol, progesterone, and luteinizing hormone (LH) levels. Two distinct types of mature follicle LUF, in which release of an ovum was not demonstrated after a follicle attained maturity (serum estradiol reached 200 pg/mL while serum progesterone remained less than 2.5 ng/mL), versus premature luteinization LUF, where the serum progesterone increased above 2.5 ng/mL before follicular maturation was attained. The use of either hCG alone or hCG in combination with hMG in a single injection at the time of follicular maturation successfully corrected mature follicle LUF in 21 of 46 patients (46%), whereas ovulation-inducing drugs plus hCG or hCG and hMG corrected LUF in 24 of 25 patients (96%). Clomiphene citrate proved inferior to hMG in that it corrected LUF in 3 of 25 patients (12%) versus 12 of 22 patients (95%) who had undergone hMG therapy. Thus, hMG-hCG therapy is the most efficacious for mature follicle LUF, but because release can occur spontaneously on occasion by an appropriately timed single gonadotropin injection, one could offer the less costly options first. For premature luteinization, speeding up follicular maturation with gonadotropin therapy is effective. Upon failure of this technique, the more costly endogenous gonadotropin suppression followed by hMG can be employed.
Excised tubal segments from 94 infertile women with tubal obstruction, with a mean infertility duration of 5.3 years, and 40 women with ectopic tubal pregnancy were studied histopathologically to evaluate the association with salpingitis isthmica nodosa (SIN). The mean age of the 94 infertile women with tubal obstruction was 24.5 years. Hysterosalpingographies and laparoscopy were performed on all of them. Only the women with ectopic pregnancies we performed salpingectomy on were included in the present study. The incidence of SIN in women with tubal obstruction was 7.4%, in women with ectopic tubal pregnancy 10%, and in the control group the incidence was 0.2%. In 60% of the cases, SIN was present in both of the tubes. Based on this study, we conclude that SIN is significantly associated with infertility and ectopic tubal pregnancy.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1991. DIR is the German national IVF/ICSI registry, founded 1982. Phase B historical-archive source.
PregnancyAdvanced Maternal AgeHypertension and DiabetesMaternal Age
Infertility, spontaneous abortions and trisomic anomalies increase with maternal age, as do ectopic pregnancy, low birth weight, macrosomia, abruptio placentae and labor dysfunction. However, those phenomena are multifactorial in origin and cannot be ascribed solely to advancing age. Older pregnant women are also at increased risk for diabetes and hypertension. Whereas the older gravida is at increased risk for maternal mortality and morbidity and for fetal and infant mortality, those problems are explainable in large part by coexisting medical complications. The healthy older pregnant woman who receives appropriate prepregnancy counseling and up-to-date perinatal care can achieve results comparable to those achieved by younger ones.
We report an interesting case of above-normal serum estradiol concentration of unknown origin. A 30-year-old white woman was seen for infertility problems. Hormonal evaluation revealed the following results. Postovulatory progesterone concentrations and profile (a plot of hormone concentration vs time of cycle) were within the normal range for our laboratory (Table 1). However, the post-ovulatory estradiol concentrations were extremely high, although the curve appeared normal in profile (Table 1).
The incidence and fertility effects of postoperative adhesion formation after laparoscopic ovarian electrocautery or laser photocoagulation of polycystic ovaries has not been adequately analyzed. Short-interval second-look laparoscopy appears to be a useful method for addressing this issue. Employing short-interval second-look laparoscopy 3 to 4 weeks after the initial laparoscopic intervention, we were able to demonstrate adhesions in 6 of 7 patients (85%) treated with ovarian electrocautery and 8 of 10 patients (80%) submitted to laser therapy. The adhesions were amenable to laparoscopic lysis in 12 of 14 patients (85%). The subsequent conception rates within 6 months of second-look laparoscopy that were 57% and 40% in YAG laser groups, respectively, may in part be attributed to the restoration of normal pelvic anatomy during this procedure.
An improved delivery method to achieve sustained physiological P levels would be useful. Based on this single-dose pharmacokinetic study, micronized P prepared in a nonliquefying vaginal cream holds promise as a convenient method to achieve this goal with a single daily application.
Fifty-one consecutive twin pregnancies studied prospectively were compared with 153 consecutive control twin gestations that were concurrently delivered, but chosen retrospectively. Study patients were managed by a protocol that used weekly ultrasound surveillance combined with clinical assessment. Control subjects were not managed by protocol or ultrasound surveillance. Seven of 51 study patients (13.7%) were diagnosed as having cervical incompetency before 30 weeks' gestation (range 18-28 weeks, mean 24). In comparison, 14 of 153 controls (9.2%) delivered before 30 weeks' gestation (range 18-29 weeks, mean 25). The mean cervical length, dilatation, and membrane herniation (funneling) at diagnosis were 1.9, 2.2, and 3.6 cm, respectively, for patients with cervical incompetency. There was a significant difference in perinatal mortality. All study twins survived, whereas nine control subjects delivered at a mean gestational age of 22.7 weeks, with a loss of 17 infants. Life table analysis demonstrated that a significantly greater proportion of controls delivered very low birth weight, premature twins. The use of ultrasound and clinical criteria to select patients for cerclage placement helped prevent birth of the youngest and smallest twins and significantly decreased perinatal mortality in the study group. Routine cerclage placement is not recommended for twin gestations, but multifetal gestations may benefit from ultrasound surveillance for cervical incompetency.
To determine possible etiologies of unsuccessful fluoroscopically guided tubal canalization, we studied the histology of tubal segments in cases of failed canalization for proximal tubal obstruction. Factors contributing to cases of unsuccessful fluoroscopically guided tubal canalization remain unclear. Prospective. Reproductive Endocrinology Clinic. Twenty-seven cornual and/or isthmic tubal segments from 15 patients who underwent proximal tubal surgery after fluoroscopically guided tubal canalization were studied. Specimens were prepared with hemotoxylin-eosin and Masson trichrome stains. Histologic examination of excised cornual and isthmic tubal segments revealed abnormalities in 93% of specimens. Obliterative fibrosis (61%), chronic salpingitis (57%), and salpingitis isthmica nodosa (42%) were the most commonly found histologic tubal abnormalities. One case of complete tubal occlusion and tubal schistosomiasis was also detected. These data suggest that cases of failed fluoroscopically guided tubal canalization may be secondary to severe intrinsic tubal disease and tubal occlusion and not to the technique. Fluoroscopically guided tubal canalization may provide a means of differentiating a functional obstruction amenable to conservative management from true occlusion requiring management by microsurgical techniques or in vitro fertilization.
PCOSCancer RiskCancer Risk FactorsCase-Control Study
Data from a case-control study that was conducted between 1980 and 1982 were analyzed to investigate the possible association between polycystic ovaries and the risk of breast cancer. The multicenter, population-based study included in-home interviews with 4,730 women with breast cancer and 4,688 control women aged 20-54 years. The age-adjusted odds ratio for breast cancer among women with a self-reported history of physician-diagnosed polycystic ovaries was 0.52 (95% confidence interval 0.32-0.87). The inverse association was not an artifact of infertility, age at first birth, or surgical menopause. Because women with this syndrome have abnormal levels of certain endogenous hormones, the observation of a low risk of breast cancer in this group may provide new insights into hormonal influences on breast cancer.
To determine the long-term outcome after laparoscopic excision of endometriosis. This longitudinal unmatched study evaluated surgical outcome using follow-up questionnaires and evaluation of reoperations with results presented in life table format. Surgery was performed by a private practitioner at a referral center. All 359 patients undergoing laparoscopic excision of endometriosis between December 12, 1980, and March 31, 1990, were studied. Endometriosis, including deeply invasive disease, was completely excised laparoscopically using 3-mm scissors and graspers. Adjunctive medical therapy was not used. Extent of disease present at reoperation and quarterly rates of reoperation and recurrent/persistent disease are used as indicators of efficacy of surgery. Interval rates of reoperation and recurrence/persistence of disease and extent or invasiveness of disease when found at reoperation did not increase with the passage of time after surgery. The maximum cumulative rate of recurrent or persistent disease was 19%, achieved in the 5th postoperative year. Laparoscopic excision of endometriosis results in a low rate of minimal persistent/recurrent disease. The natural history of endometriosis after surgery suggests a rather static nature of the disease.
Home uterine activity monitoring has been described as an effective means of detecting uterine contractions, but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor. In this study 377 women at risk for preterm labor from three centers were prospectively, randomly assigned to high-risk prenatal care alone (not monitored) or to the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). The two groups were medically and demographically similar at entry into the study. Routine visits, nonroutine visits, and gestational age at diagnosis of preterm labor were similar in both groups. Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients. Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored (p = 0.0006); 73.1% of monitored and 27.5% of not monitored had preterm labor detected before 2 cm dilatation (p = 0.00009). Neonatal outcome of singleton pregnancies showed greater birth weight, fewer days in the neonatal intensive care unit, and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group. The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring, thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome.
InfertilityPregnancy ComplicationsLow Birth WeightCross-Sectional Study
We evaluated the association between subfertility and low birth weight infants. Women in this analysis participated in a cross-sectional investigation of maternal risk factors for adverse pregnancy outcomes. Medical and obstetric history and life style information were obtained from women who delivered at the Boston Hospital for Women, 1977 to 1980. PATIENTS, Our analysis was restricted to nondiabetic married women who planned their pregnancies and subsequently delivered viable singletons (3,622). The 644 "subfertile" women (no conception during a year of unprotected intercourse) were compared with 2,978 "fertile" women (conception within 1 year). MAIN OUTCOME MEASURE(S): The relative risk of low birth weight was estimated using the cumulative incidence risk ratio. After adjusting for confounding, the relative risk of delivering a low birth weight infant (less than 2,500 g) for subfertile women versus fertile women was 1.9 (95% confidence interval [CI], 1.3 to 2.8). The adjusted relative risk of delivering a term low birth weight (intrauterine growth retarded) infant was 2.3 (95% CI, 1.2 to 4.4). In these data, subfertility is a predictor for low birth weight. The association may result from endocrinological, immunological, cervical, or other factors that interfere with optimal fetal growth.
PCOSMultifactorial MechanismsLong-term Health Risks
The incidence of polycystic ovarian disease (PCOD) varies from 0.6 to 92%, depending on the parameters analysed, PCOD has been reported to appear in association with Cushing's Syndrome, adrenal hyperplasia, hypothyroidism, adrenal and ovarian tumours and some genetic abnormalities. The controversy regarding the pathophysiological mechanism underlying the disease still persists. Critical evaluation of old data, assessment of new findings concerning the possible role of insulin, growth factors and their binding proteins, and extrapolation of neuroendocrinological experiments enabled the construction of a concise hypothesis of the pathophysiology of PCOD. According to this hypothesis, PCOD is a multifactorial disease. The sequence of events finally leading to clinical manifestation of the disease (hyperandrogenism, abnormal luteinizing hormone pulsatility pattern and ovulation disturbances) may originate in different organs or be triggered by different mechanisms. It may stem from the adrenals, the hypothalamus or higher central nervous system centres, or from the ovary itself; it may originate from excess of fat tissue usually combined with hyperinsulinism; or may be the result of a net increase in active growth factors. Each of the above disturbances probably appears early in life, much before the clinical signs of the disease are evident. Predisposing factors such as gestational diabetes of the mother, childhood obesity, borderline adrenal hyperplasia and late menarche have to be looked for as early as possible in order to prevent the late consequences of the disease, such as increased risk of infertility, endometrial and breast cancer and cardiovascular disease.
PCOSHyperinsulinemiaOpioid System InvolvementOpioid Receptors
In order to test the hypothesis that endogenous opiates are at least partially responsible for hyperinsulinaemia in patients with polycystic ovarian disease (PCOD), the effect of naloxone (an opiate receptor blocker) on the insulin response to oral glucose load (OGTT) was studied in 20 women with PCOD and 17 control subjects at days 5-8 of their follicular phase. After fasting overnight for 10-12 h, each woman received an i.v. bolus injection (2 mg) of naloxone or an equal volume of saline infusion followed by a constant infusion of naloxone or saline solution at a rate of 8 ml/h (1 mg/h of naloxone) for 5 h. OGTT (75 g) was performed 1 h after the bolus injection. The naloxone study was performed 48 h after the saline study. Naloxone did not modify the insulin response to OGTT in either group. When the data were related to the insulin response, in PCOD hyperinsulinaemic patients, naloxone significantly reduced (P less than 0.02) the insulin response to OGTT without any change in glycaemic response curves. In control and PCOD normoinsulinaemic patients, naloxone did not change significantly either the glycaemia or the insulin levels after OGTT. No change of gonadotrophin and steroid secretion was found in any patient receiving naloxone. In conclusion, endogenous opiates may play a significant role in hyperinsulinaemia in PCOD.
To test a sonoscopic technique developed for transvaginal catheterization and recanalization of the fallopian tube. In a feasibility study, catheterization was performed with the use of laparoscopic control. Patients with bilateral proximal tubal obstruction underwent fallopian tube recanalization under ultrasonic observation. This study represents patients evaluated for primary or secondary infertility at Humboldt University Hospital. PATIENTS, Proximal tubal obstruction had been diagnosed on previous hysterosalpingogram and with laparoscopy. None. Tubal patency was assessed by hydrotubation under ultrasonic observation. Transvaginal catheterization was successful in 31 (91.2%) of the 34 tubes. In 19 patients with proximal tubal obstruction, patency of both or at least one tube was achieved in 16 (84.2%) women. Five (31.6%) of 16 patients successfully recanalized were found to have an intrauterine pregnancy at a 6-month follow-up interval. This catheterization technique should be investigated for possible use in diagnostic schedule early in the evaluation of the infertile patient. Also, the transvaginal recanalization of proximally obstructed tubes calls into question the application of microsurgical treatment of a selected group of patients.
To characterize the extent and sources of imprecision in histologic dating of the endometrial biopsy. Duplicate endometrial biopsies from 25 women were dated by five evaluators on two separate occasions to evaluate the overall precision of the measure. Using variance component analysis, estimates of intrauterine, intraevaluator, and interevaluator variability were determined. Samples were obtained during outpatient fertility testing. Evaluators were colleagues at the same institution. PATIENTS, Women presenting with infertility undergoing routine evaluation. None. Variability in histologic dating of the endometrium. Inconsistencies between evaluators accounted for 65% of the observed variability, whereas 27% was because of inconsistencies in duplicate readings by the same evaluator. Regional differences in the uterus accounted for only 8% of the total variability. The overall error from these sources have the potential to result in a substantial false-positive rate for diagnosis of luteal phase defect.
Endovaginal sonography of the endometrium demonstrates characteristic findings throughout the menstrual cycle. To correlate these findings with histologic criteria for normal endometrial development, we compared endometrial biopsies with ultrasonographic findings. Nineteen cycles were monitored in 18 women with ovarian failure whose endometrial cycles were induced exogenously by sequential transdermal 17 beta-estradiol (E2) and intramuscular progesterone. These subjects underwent ultrasonography of the endometrium prior to the day of progesterone initiation (luteal day +1) and continuing throughout the mid-secretory phase. On luteal day +1, ultrasonography characteristically demonstrated a multilayered endometrium consisting of a hyperechoic perimeter (endometrial-myometrial interface), a hypoechoic inner layer, and a hyperechoic midline (luminal interface). By luteal day +7, a gradual increase in echogenicity of the inner layer was detected, while the inner myometrium remained hypoechoic. Eleven of 19 cycles demonstrated a completely hyperechoic endometrium on luteal day +7 and also demonstrated normal stromal development on endometrial biopsies. Three patients who had endometrial biopsies consistent with their chronological development failed to demonstrate a hyperechoic endometrium by luteal day +7. All five biopsies that were histologically out of phase were detected by ultrasonography. Thus, ultrasonography demonstrated a sensitivity of 100% and a specificity of 62% for the detection of histologically normal endometrial development. Endometrial thickness could not be used to discriminate between biopsies that were normal (13 +/- 1.0 mm) and those out of phase (13.8 +/- 1.8 mm). Endometrial histology demonstrated asynchrony of glands and stroma in nine cases in which ultrasonography correlated with stromal, but not with glandular dating, suggesting that the increased echogenicity may reflect stromal edema.(ABSTRACT TRUNCATED AT 250 WORDS)
Noblot G et al., 1991·Eur J Obstet Gynecol Reprod Biol
The results of a study concerning the treatment of acute menace beta-mimetics were administered intravenously in all cases (44) and micronized progesterone or placebo was administered orally after classical double-blind randomization (22 cases in each group). The mean index of pregnancy prolongation was the same in both groups. However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group (P less than 0.01). The mean duration of hospital stay was also significantly reduced (P less than 0.05). Cost and risks are finally significantly lessened.
The bioavailability and the clinical usefulness of the P administered by nasal spray were investigated. Ten healthy menopausal women received an IN spray administration (4 doses of an oleic P solution 20 mg/mL, corresponding to nearly 11.2 mg of P) and the circulating P levels were calculated. Sixty minutes after administration, the maximum concentration (CMax, 3.75 +/- 0.214 ng/mL) was reached. High P levels (greater than 2 ng/mL) lasted until 360 minutes, and the AUC 0 to 720 was 1,481.6 +/- 343 ng.h/mL. Progesterone administration by spray formulation has proven to be effective in reaching therapeutic levels and to be acceptable to patients and, probably, clinically safe.
The role of natural killer (NK) cells in the decreased cellular immunity of women with endometriosis was investigated. DESIGN, SETTING, Thirty-four women were investigated prospectively before a CO2-laser laparoscopy for infertility and/or pain at the University Hospital Gasthuisberg. Endometriosis was scored blindly. The cytotoxicity, directed against the endometrium, was mediated by NK cells because this cytotoxicity could be removed by treating the effector cells with the NK-specific anti-Leu-11b monoclonal antibody. Consequently, we evaluated prospectively in those women the lymphocyte-mediated cytotoxicity toward NK sensitive (K562-assay) and autologous endometrial target cells. The NK activity (K562-assay) and the cytotoxicity against autologous endometrial cells were similarly decreased in women with endometriosis and correlated with the severity of the disease. Using heterologous effector cells, the decreased chromium release in women with endometriosis was less pronounced but still present. The decreased cytotoxicity to endometrial cells in women with endometriosis is mainly because of a defect in NK activity but is also partially because of a resistance of the endometrium to NK cytotoxicity.
A study was conducted to determine if the increased recognition of various forms of endometriosis might have increased the ability to correlate focal tenderness with lesions. The prospective study of 82 patients revealed a strong correlation between focal tenderness on examination with the presence of deep fibrotic endometriosis and other fibrotic pathology. The data suggested that focal tenderness and depth of infiltration may direct further study in women with endometriosis.
At an interdisciplinary workshop on home monitoring of uterine activity, participants reviewed the basis of this technology and its use in the identification of women at high risk of preterm delivery and in the prevention of preterm birth. Although the guard-ring devices in current use appear capable of detecting uterine activity, they do not clearly distinguish between Braxton Hicks contractions and the contractions of early labor. There was agreement that women destined for preterm delivery have more uterine activity on average than do other women of comparable gestational age but that there is substantial overlap between the two groups. Thus it is uncertain whether this difference can be used effectively for screening purposes. Conferees agreed that there is considerable evidence that twice-daily monitoring of very-high-risk women, in conjunction with daily nursing support and high-quality obstetric care, may prevent preterm births. Available evidence does not clearly distinguish the contribution of tocodynamometry from that of nursing support. A number of areas were identified in which further research is needed.
Fertility AwarenessEfficacy EvaluationPearl Index AnalysisFamily Planning Regulation
5 major criteria are used to evaluate efficacy, both theoretical and practical; acceptability as measured by continuation of use; safety; reversibility; and cost, including the cost of treatment, follow-up, and screening for contraindications. Traditional family planning methods are mostly based on periodic abstinence during the presumed fertile period. The calendar, temperature, Billings or cervical mucus, and symptothermal methods are based on observation of different symptoms of ovulation and fertility. Their advantages are that they do not require intervention by health personnel, their costs of use are nil, and they are morally acceptable to some couples. Their efficacy is lower than that of other methods and they should be viewed as methods to space rather than limit births. The withdrawal method, also less effective, requires active cooperation by the male partner. Among mechanical methods, the use of condoms has increased recently because of the protection they offer against HIV infection and other sexually transmitted diseases. Their efficacy depends on correct use, regular use, and the quality of the condom. The Pearl index varies from 93099 per 100 woman-years. The diaphragm must be individually measured and should be used with spermicides. The Pearl index ranges from 85095 per 100 woman-years. Spermicides, generally either nonoxynol-9 or benzalkonium chloride, are surfactants that have a Pearl index of 83-97 per 100 woman-years. They are available as creams, jellies, foams, suppositories, tablets, or impregnated sponges. Most failures appear due to errors of utilization. The mechanism of action of the IUD is imperfectly understood, but it is known to prevent nidation of the fertilized egg. Copper devised have higher rates of efficacy and tolerance. Pearl indices range from 95-99.5. Contraindications include genital infection, uterine anomalies, valvular cardiopathy, and coagulation problems. The IUD is relatively contraindicated if there is history of ectopic pregnancy or upper genital tract infections. The combined oral contraceptive is the most widely utilized method in France. The Pearl index is nearly 100 in the absence of forgetting, vomiting, or drug interactions. The contraindications are history of thrombosis, prolonged bedrest, hypertension, hyperlipidemia, hepatic disorders, hormonodependent cancers, or smoking after age 35. Progestin-only methods are available in 3 low-dose pills which must be taken at the same time each day, higher-dosed progestins taken for 20 days each month, and injectable progestins providing contraception for 8-12 weeks. Postcoital contraception using OCs or IUDs is possible but not well known among women or physicians. The Neuwirth law authorizing use of contraception in France was passed in 1967. Amendments in 1974 improved access and provided for reimbursement for some methods, but some newer forms are not reimbursed.
To examine the clinical efficacy of low dose spironolactone in hirsute women. Retrospective. Outpatient endocrinology clinic. One hundred nine consecutive women prescribed 75 to 100 mg/d spironolactone for at least 4 months in whom adequate follow-up data were available. Hirsutism improved in 72% of the women. Women with regular menses, whether or not they used oral contraceptives (OCs), had the highest response rate to spironolactone (78%), whereas women with irregular menses who did not use an OC had the lowest response rate (55%). Favorable responses were associated with increased severity of hirsutism (P = 0.04) and lower serum dehydroepiandrosterone sulfate levels (P = 0.05). Responders and nonresponders did not differ significantly in age (P = 0.10), duration of hirsutism (P = 0.14), pretreatment serum testosterone (T) (P = 0.48), or body mass index (P = 0.11). However, when each parameter was divided into subsets, trends toward decreasing response were observed with increasing age, duration of hirsutism over 15 years, and increasing serum T level. Low-dose spironolactone improves hirsutism in a majority of hirsute women, irrespective of age, severity or duration of hirsutism, menstrual status, or serum hormone levels.
Luteal phase abnormalities are known to complicate ovulation induction with gonadotropins. This study was performed to test the effect of a modified human chorionic gonadotropin (hCG) regimen on the luteal phase during gonadotropin treatment. Fifteen women from a private practice setting volunteered to be studied during each of two nonconception, gonadotropin-stimulated cycles. After ovarian stimulation with human menopausal gonadotropins (hMG), hCG was administered either as a single dose of 10,000 IU (single dose) or in two divided doses of 5,000 IU given 1 week apart (split dose). Early, midluteal, and late luteal estradiol (E2) and progesterone (P) levels and luteal phase lengths were measured, and their median values and intraquartile ranges (IQR) compared using nonparametric analysis. Early and midluteal E2 and P levels were similar regardless of which hCG regimen was administered. The median late luteal E2 level was 1,146.0 pg/mL (the IQR ranged from 633 to 1,650, IQR = 1,017) with the split-dose regimen and 240.0 pg/mL (the IQR ranged from 150 to 460, IQR = 310) with the single-dose regimen. The median late luteal P level was 108.0 ng/mL (the IQR ranged from 58.5 to 129, IQR = 70.5) with the split-dose regimen and 4.2 ng/mL (the IQR ranged from 1.9 to 11.7, IQR = 9.8) with the single-dose regimen. Median luteal phase lengths were 16 days (the IQR ranged from 15 to 17, IQR = 2) for the split-dose regimen and 11 days (the IQR ranged from 10 to 12, IQR = 2) for the single-dose regimen. In hMG-stimulated cycles, a second dose of hCG given during the midluteal phase significantly increases late luteal E2 and P levels and consistently lengthens the luteal phase.
The rate of adhesion formation after ovarian electrocauterization has been described in two selective and unselective groups of patients with PCOS. The rate of this complication in the selective group was 0 from 16 ovaries and in the unselective group (5/25). However, the rate of major adnexal adhesion in the unselective group was 1 from 25 ovaries.
Evaluation of selective salpingography for diagnosis and treatment of tubal injection failure during hysterosalpingography (HSG). Prospective study. Obstetrics and Gynecology Department, University of Genoa (Italy)--tertiary care. One hundred eighty infertile women with unilateral or bilateral proximal tubal injection failure during HSG were submitted to the procedure. Under fluoroscopy, a 4.5-F nylon catheter (3-F tip) was inserted into the ostium with or without the aid of a J-shaped, coaxial, angiographic guide wire, and 2 to 3 mL of contrast medium were injected. The procedure lasts 20 to 30 sec/tube. Of 155 tubal ostia, 145 (94.2%) were catheterized. Of the 146 catheterized tubes, 110 (75%) were rendered patent. Of the others, 21 (14.3%) presented hydrosalpinx or distal obstructions, and isthmic obstruction was present in 5 (3.4%). Patency of at least one tube was achieved in 82 (81.2%) of the 101 catheterized women; 8 conceived spontaneously and 11 after gamete intrafallopian transfer to the recanalized tube. During HSG, selective salpinography can be performed when proximal injection failure is observed to determine its cause or to restore patency.
The relative contributions of home tokodynamometry and daily nursing telephone contact to the success of preterm birth prevention programs remains a subject of debate. Because investigators have obtained conflicting data, a reinterpretation of published results was undertaken by proposing a dynamic interface between the nurse and the machine. Experience gained from the technology and the development of nursing expertise with assessment of patient symptoms are presented as interdependent factors, both of which are critical to a therapeutic nurse-patient relationship. It is proposed that this combined interactive expertise increases sensitivity to the early recognition of preterm labor. The nurse's role in providing social support to high-risk pregnant women is then identified as a potential additional independent contributing factor to reported observed reductions in preterm births. Discussion focuses on future research, public policy issues, and the need for expanding nurse-patient interactions into the home.
Fertility AwarenessElectronic Fertility MonitorsOvulation Detection DevicesTechnological Aids
In recent years, several new devices have been developed to help women achieve or avoid pregnancy. These devices include computerized basal body temperature thermometers, electronic fertility monitors, and chemical and hormonal ovulation detection kits. This article describes these new fertility devices and discusses their effectiveness and impact on helping women understand and control their fertility.
Rabbit uterine cervical fibroblasts produced a large amount of matrix metalloproteinases (MMPs) such as collagenase (MMP-1) and stromelysin (MMP-3) and a small relatively amount of tissue inhibitor of metalloproteinases (TIMP). When cells were treated with progesterone or oestradiol-17 beta, both steroids concurrently decreased the level of procollagenase and prostromelysin in the culture media and the steady-state levels of the respective mRNAs. On the other hand, the level of TIMP in the culture media and the steady-state level of its mRNA were simultaneously increased by these steroids. Similarly, the suppression of production of MMPs and the augmentation of TIMP production by both steroids were observed with interleukin 1 (IL-1)-treated cells, but the action of progesterone was more effective than that of oestradiol-17 beta in the IL-1-untreated and -treated cells. These results suggest that collagenolysis in uterine cervical fibroblasts is negatively regulated by steroid hormones via the acceleration of TIMP production and the suppression of synthesis of MMPs at the pretranslational level.
In this study we have evaluated the score, sperm migration and ultrastructural characteristics of cervical mucus present in amenorrhoeic women under exclusive breastfeeding at 30, 60, 90, 120, 150 and 180 days post-partum. Periovulatory mucus samples from seven normally cycling women were used as a control. The average scores of post-partum and periovulatory mucus were 4.6 +/- 0.4 and 14.1 +/- 0.5 respectively. Twenty-one (39%) of the 54 post-partum cervical mucus samples and all (100%) periovulatory mucus samples allowed sperm migration. Positive sperm migration into post-partum mucus was observed at all time intervals studied. The only parameter that correlated with sperm migration into post-partum mucus was ferning formation. Sperm migration was obtained in all post-partum mucus samples with a score greater than 8, but samples with scores between 2 and 7 also showed sperm penetration. Scanning electron microscopic studies showed the characteristic spongy appearance of periovulatory mucus. Post-partum mucus was formed by a dense mesh (rocky appearance), when samples were generally unable to sustain sperm migration, but samples where sperm migration occurred showed small areas of spongy mucus mixed with areas in which a dense mesh and high cellularity was observed.
EndometriosisDeep Infiltrating EndometriosisStaging SystemsPelvic Pain Association
In a 3-year prospective study of 643 consecutive laparoscopies for infertility, pelvic pain, or infertility and pain, the pelvic area, the depth of infiltration, and the volume of endometriotic lesions were evaluated. The incidence, area, and volume of subtle lesions decreased with age, whereas for typical lesions these parameters and the depth of infiltration increased with age. Deeply infiltrating endometriosis was strongly associated with pelvic pain, women with pain having larger and deeper lesions. Because deep endometriosis has little emphasis in the revised American Fertility Society classification and after analyzing the diagnoses made in each class, considerations for a simplifying revision with inclusion of deep lesions are suggested. In conclusion, suggestive evidence is presented to support the concept that endometriosis is a progressive disorder, and it is demonstrated that deep endometriosis is strongly associated with pelvic pain.
Bhavnani BR et al., 1991·J Steroid Biochem Mol Biol
One of the main components of conjugated equine estrogens is equilin sulfate and this estrogen in postmenopausal women is metabolized to 17 beta-dihydroequilin, 17 beta-dihydroequilenin and equilenin. To investigate the possibility that some of these estrogens may be formed directly in the target tissues, we studied the in vitro metabolism of [3H]equilin in various types of normal and malignant human endometrium, including adenocarcinoma grown in athymic nude mice. The results indicate that normal and neoplastic human endometrium can form the above three metabolites. The highest level of 17 beta-reduced products were isolated from the normal secretory endometrium. Equilenin was the most abundant metabolite isolated from both the normal and malignant endometrium. The formation of [3H]equilenin indicates the presence of a 6,8(9) steroid dehydrogenase-isomerase in the human endometrium. The formation of 17 beta-dihydroequilin in the endometrium may be of importance as this estrogen is 8 times more potent as a uterotrophic agent than equilin and estrone.
Women with luteal phase deficiency have been shown to have an increased frequency of luteinizing hormone pulses in the early follicular phase of the menstrual cycle. Because progesterone is known to modulate luteinizing hormone secretion, it has been hypothesized that the decreased progesterone secretion in a previous luteal phase deficiency cycle could lead to the abnormal luteinizing hormone secretory pattern in the ensuing early follicular phase. With the possibility that the higher luteinizing hormone pulse frequency might lead to another deficient luteal phase, it becomes conceivable that luteal phase deficiency could be self-perpetuating. To test this hypothesis, luteal phase deficiency was induced in six normal women by decreasing luteinizing hormone support of the corpus luteum with a gonadotropin-releasing hormone antagonist Nal-Glu, administered twice daily beginning in the midluteal phase after a control cycle. During the antagonist-treated luteal phase, each subject met the predetermined criteria for induced a 33% or greater decrease in integrated progesterone from the control cycle and an integrated progesterone level less than 100 ng/ml per day. Luteinizing hormone secretion patterns were determined by frequent blood sampling performed every 10 minutes for 12 hours in the early follicular phase of the control cycle and the cycle after antagonist administration. Daily luteal progesterone levels were measured in the control, treatment, and posttreatment cycles. Each volunteer served as her own control. Standard parameters were compared between the control and posttreatment pulse studies (1) luteinizing hormone pulse frequency was 9.5 +/- 1.0 vs 10.0 +/- 0.9 pulses/12 hours, control vs posttreatment, respectively, p = 0.5; (2) luteinizing hormone pulse amplitude was 11.0 +/- 1.3 vs 12.0 +/- 2.2 ng/ml, p = 0.6; and (3) luteinizing hormone mean level was 19.4 +/- 2.3 vs 22.2 +/- 3.3 ng/ml, p = 0.1. Corpus luteum function was also compared between the control and posttreatment cycles. Luteal phase length was 13.7 +/- 0.6 vs 12.7 +/- 0.6 days, p = 0.08. Integrated progesterone values were 136.9 +/- 12.9 vs 130.5 +/- 11.3 ng/ml per day, p = 0.5. Therefore no discernible abnormalities in early follicular luteinizing hormone secretions or corpus luteum secretion of progesterone occurred after an induced luteal phase deficiency cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy.
A pregnant woman may become anxious if she has not delivered by the date given to her by her physician. Much anxiety would be alleviated if a range of dates (38-42 weeks) was substituted for a specific date of delivery.