Ninety pregnancies conceived by infertile couples using assisted reproductive technologies and 86 pregnancies conceived by infertile couples with routine infertility treatment were analyzed to determine the outcome of and the complications experienced during the pregnancies. Pregnancies ending after 24 weeks' gestation were evaluated for pregnancy-induced hypertension, diabetes mellitus, preterm labor, premature rupture of membranes, placenta previa, and fetal growth retardation. A matched control group of normal fertile patients admitted to the obstetric service at Vanderbilt University Medical Center was used to compare the incidence of pregnancy complications among the groups. In the group treated by assisted reproduction, 81 pregnancies were singleton and nine were multiple gestations, whereas in the routine group, 84 were singleton and two were multiple gestations. In the group treated by assisted reproduction, 29 of 90 gestations (32%) ended before 24 weeks, compared with 18 of 86 (21%) in the routine group, a nonsignificant difference. Mean birth weight and gestational age were similar among the three groups for singleton gestations. Among multiple gestations, the mean (+/- standard error of the mean [SEM]) birth weights were 2513 +/- 115, 724 +/- 57, and 2282 +/- 132 g in the group treated by assisted reproduction, the group receiving routine methods, and the control group, respectively (P less than .001 when those treated by routine methods were compared with the other two groups). The mean (+/- SEM) gestational ages were 36 +/- 1.2, 26.5 +/- 2.0, and 35.5 +/- 1.2 weeks, respectively (P less than .01 comparing those treated by routine methods and the other two groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Fertility AwarenessOvulation Prediction AccuracyLH Surge vs Cervical MucusComparative Validation
Time of ovulation as detected by a self-test of luteinizing hormone (LH) in the urine was compared with time of ovulation as detected by self-observation of cervical mucus. Twenty regularly cycling women monitored their cervical mucus and urine LH for two complete menstrual cycles. Of the cycles that had an LH surge, 100% were on the peak day of cervical mucus or within three days before the peak day. Self-observation of cervical mucus, therefore, can be an accurate method of determining optimal fertility.
Menstrual CycleGlucose and Insulin DynamicsMetabolic EvaluationCarbohydrate Metabolism
Three-hour oral glucose tolerance tests were performed on days 5 and 25 of ovulatory menstrual cycles in 26 women. The women were divided into normal (n = 9) and premenstrual syndrome (PMS) (n = 17) categories. Ovulation was confirmed by basal body temperature records and plasma progesterone levels. There were no statistically significant changes in the plasma glucose or insulin levels between the two tests in either group. Except for a higher two-hour plasma insulin concentration on the day 5 test in normal women, no statistically significant carbohydrate differences were noted between the groups. The data suggest that alterations in carbohydrate metabolism are not important in PMS.
PregnancySigns and SymptomsPatient Education and AwarenessPreterm Labor Symptom Recognition
Patient and staff education concerning the subtle signs and symptoms that precede a clinical diagnosis of preterm labor have not been well established. Therefore we interviewed 100 patients for the presence or absence of various symptoms and signs during the 7 days preceding diagnosis of preterm labor. An additional 100 patients without preterm labor matched for gestation were chosen at random as control subjects. A history of increased uterine contractions, menstrual cramps, constant backache, constant pelvic pressure, increased amount and consistency and color change of vaginal discharge, and increased frequency of urination were present with a statistically significant higher frequency in patients with preterm labor compared with controls. Twenty-nine percent of patients did not report any uterine contractions and only half described them as painful. Fewer than 50% of the women reported contractions as frequently as every 10 minutes or more.
Bone HealthProgesterone Bone EffectsProgesterone PhysiologyOvulatory Cycle Bone Impact
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."
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.
Perimenopause/MenopauseEstrogen PharmacokineticsRoutes of AdministrationEstrogen Replacement Options
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.
InfertilityDiagnosis and TreatmentTransvaginal Catheter DilatationSelective Salpingography
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.
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.
PregnancyInfection DetectionC-Reactive Protein ChorioamnionitisChorioamnionitis Prediction
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.
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.
General OB/GYNPsychosocial Risk FactorsMultidisciplinary ManagementDemographics and History
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.
Fertility AwarenessContraceptive EfficacyPerfect vs Typical UseContraceptive Failure Calculation
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.
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.
Reproductive EndocrinologyLH and FSH RegulationGnRH Antagonist EffectsHormonal Dynamics
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)
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.
PCOSInsulin ResistanceGnRH Agonist TherapyHyperandrogenism and Metabolism
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.
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.
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.
PregnancyPremature Rupture of MembranesC-Reactive Protein in PregnancyChorioamnionitis Diagnosis
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.
Audebert A, 1990·J Gynecol Obstet Biol Reprod (Paris)
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 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.
InfertilityOvarian Function EvaluationSalivary ProgesteroneLuteal Phase Insufficiency
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.
Menstrual CycleLuteal Phase Defect EtiologyNormal Follicular DevelopmentLuteal Phase Dating
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 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.
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 odds ratio (OR) 0.73, 95% confidence interval (CI) 0.34-1.59; OR 1.80, CI 0.61-5.29; 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.
General OB/GYNSurgical TreatmentLaser Ablation OutcomesEndometrial Ablation
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.
InfertilityEmotional CopingPsychological Support Services
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.
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 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)
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.
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 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.
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 (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 (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.
InfertilityClomiphene Citrate DosingPharmacological StimulationWHO Group II Treatment
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 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.
InfertilityDepression and Mood DisordersPsychiatric Symptoms in InfertilityInfertility Psychology
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.
General OB/GYNToxicologyAbdominal Radiograph Findings
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.
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.
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.
PCOSEvolving Diagnostic CriteriaEndocrine Features and HeterogeneityPolycystic Ovary Syndrome
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 tions (Givens et al., 1976; Rebar er al., 1976).
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.