Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. Neonatal morbidity and mortality is concentrated among very low-birthweight and extremely premature infants, particularly those delivered prior to 30 weeks' gestational age. In addition to the contribution of preterm birth to neonatal morbidity and mortality, the economic costs associated with this pregnancy complication are staggering. Efforts to reduce the preterm birth rate have been largely focused on prevention and early intervention with treatment for preterm labor. Mixed results regarding the success of prematurity prevention programs have been reported, and controversy continues to surround the efficacy of tocolytic therapy in the treatment of preterm labor. Although neonatal survival for infants born at early gestational ages has steadily improved in recent years, survival of infants delivered prior to 24 weeks' gestation remains very poor. Additionally, despite this decline in neonatal mortality, the United States still lags behind most industrialized nations in infant mortality, and no change in the rate of low birthweight has occurred in recent decades. Multiple lines of evidence support a role for infection as an etiologic factor in preterm labor. Although this association has been well known for many years, a wealth of new data is emerging, linking subclinical genital tract infection with spontaneous preterm birth, particularly among pregnancies that result in birth prior to 30 weeks' gestational age as a result of spontaneous preterm labor or preterm, premature rupture of membranes. Conversely, preterm birth that occurs closer to term is less likely to be associated with genital tract infection. Improved understanding of the link between genital tract infection and preterm birth now provides an exciting potential for the development of sensitive new markers to identify women at risk and effective interventions to prevent preterm birth. A review and comment on this growing literature is provided.
PCOSOpioid Tone DerangementHyperinsulinemia and LH SecretionOpioid System
Recent data indicate that an altered opioid tone could be involved in the LH hypersecretion and metabolic alterations seen in polycystic ovary syndrome (PCOS). The aim of the present study was to investigate the presence of a common mechanism of action of opioids on altered insulin and gonadotropin release in patients suffering from PCOS. Twenty-eight women affected by PCOS and 8 normal ovulatory women were studied; an oral glucose tolerance test (OGTT) and GnRH tests were performed during the follicular phase before and after 6 weeks of naltrexone treatment (50 mg/day, orally). Plasma levels of sex hormone-binding globulin and steroids were assayed in the basal samples, whereas FSH and LH were analyzed during the GnRH stimulus. Insulin and glucose were assayed by the OGTT. Based on the insulinemic response to OGTT, 17 women were classified as hyperinsulinemic and 11 as normoinsulinemic. No difference in glucose and hormone plasma concentrations was observed before and after naltrexone treatment in both groups. Only basal sex hormone-binding globulin values were higher in normoinsulinemic compared to hyperinsulinemic subjects. Administration of the opioid antagonist significantly reduced the insulin response to OGTT only in the hyperinsulinemic group. No difference were found in the LH increment after the GnRH stimulus in both group of patients before treatment; on the contrary, naltrexone administration reduced the LH response to GnRH in hyperinsulinemic women but failed to be effective in normoinsulinemic subjects. Only 5 patients showed no concordance of drug-induced changes in insulin and LH secretion. In control subjects, naltrexone failed to have any effect on insulin or LH secretion. These data support the involvement of endogenous opioids in the regulation of insulin and LH secretion in a specific group of PCOS patients exhibiting an exaggerated insulin response to OGTT.
Fertility AwarenessSymptothermal MethodBillings Ovulation MethodNFP vs Contraceptive Methods
The scientific foundations and most notable features of modern natural family planning (NFP) methods are described. NFP techniques require observation of the signs and symptoms occurring during the fertile and infertile phases of the menstrual cycle. Abstinence during the fertile period is implied when NFP is used to avoid pregnancy. Modern NFP methods are associated with success rates similar to those of oral contraceptives, the IUD, and condoms. NFP methods are based on such phenomena as the limited survival time of the ovum and sperm, the occurrence of ovulation only once per cycle, the ability to diagnose ovulation using simple means, and the ability of human beings to delay sexual satisfaction. Among the advantages of NFP methods are low cost, brevity of the required training time, increased knowledge of the body and capacity for self control, shared responsibility by both partners, and moral and religious acceptability. The Billings and symptothermal methods have shown average use-effectiveness rates ranging from 71.5 to 89.5% and from 83.4 to 97.8%, respectively. All studies of symptothermal methods conducted since 1985 have shown Pearl indexes under 5. The symptothermal method is based on observation of the duration of previous cycles, cervical mucus, basal body temperature, and optionally on palpation of the cervix and other symptoms such as breast swelling, acne, intermenstrual bleeding, and mood changes. Use of the symptothermal method requires special graph paper for recording the temperature and other symptoms. The beginning of the fertile phase is recognized by subtracting 19 from the shortest cycle in the past year, or by the appearance of cervical changes or changes in the mucus.
Rossi AM et al., 1995·Eur J Obstet Gynecol Reprod Biol
The outcome of 103 pregnancies in 64 women with constant hyperprolactinemia was evaluated. Seventy-eight pregnancies had been induced with bromocriptine and 25 occurred without any treatment. In all, 66% of the pregnancies ended in delivery, 17% in miscarriage, 10% in tubal pregnancy and 7% in induced abortion. The pregnancy of women with untreated hyperprolactinemia was more frequently ectopic when compared to those in women treated by bromocriptine. Obstetric complications as well as signs of tumoral enlargement during pregnancy were rare in hyperprolactinemic women treated or untreated with bromocriptine. Untreated hyperprolactinemia as a risk factor in tubal pregnancy is proposed.
To evaluate the effectiveness of the oxidized regenerated cellulose absorbable barrier (Interceed, TC7) in the prevention of de-novo adhesion formation after laparoscopic myomectomy, a prospective and randomized study was performed at the Department of Obstetrics and Gynaecology of the University of Cagliari, Cagliari, Italy. A total of 50 pre-menopausal non-pregnant women, aged 23-42 years, who submitted to laparoscopic myomectomy from January 1993 to June 1994, were randomized to surgery alone (control group, n = 25) or surgery and oxidized regenerated cellulose barrier (Interceed group, n = 25). Neither group received any other treatment for adhesion prevention. A second-look laparoscopy was performed 12-14 weeks after laparoscopic myomectomy. The incidence of adhesion-free patients was assessed at second-look laparoscopy by an investigator not informed of the treatment. The numbers of adhesion-free patients were three out of 25 (12%) in the control group and 15 out of 25 (60%) in the treatment group (P < 0.05). In conclusion, the oxidized regenerated cellulose absorbable barrier significantly reduced de-novo adhesion formation after laparoscopic myomectomy.
Menstrual CycleHypothalamic Amenorrhea TreatmentOpioid Antagonist TherapyNaltrexone for Amenorrhea
To evaluate whether the efficacy of naltrexone administration in patients with hypothalamic amenorrhea correlates to the response to an acute naloxone test.
Thirty patients with hypothalamic amenorrhea associated with weight loss were studied. After naloxone test (4 mg in bolus IV) patients group A, nonresponsive (n = 15) and group B, responsive (n = 15). Group A underwent two cycles of hormonal replacement therapy with E2 patches and medroxyprogesterone acetate. Then all patients were administered naltrexone at the dosage 50 mg/d orally for 6 months. A third group of 10 amenorrheic patients were treated with oral placebo with the same schedule. Plasma gonadal steroid levels increased in all patients and in 24 of 30 patients the menstrual bleeding occurred within 90 days from the beginning of treatment. After 6 months from naltrexone discontinuation, 18 of 24 patients still showed the occurrence of menstrual cycles. Luteinizing hormone plasma levels and LH pulse amplitude increased after 3 months of treatment and remained unchanged 6 months after naltrexone suspension. Plasma FSH levels did not show any change in any patient. The body mass index increased after 3 months in all patients who menstruated. Patients treated with placebo did not show any significant change in gonadotropins and gonadal steroid plasma levels. The present study supports the efficacy of naltrexone therapy for patients with hypothalamic amenorrhea either responsive or nonresponsive to naloxone test.
Sahmay S et al., 1995·Int J Fertil Menopausal Stud
Endometrial biopsy has been an important way of assessing infertile couples for several years. In this review of a wide-ranging series of endometrial biopsies of infertile couples in the Turkish population it was our aim to find the distribution of results according to the years 1956-1966, 1967-1980, 1981-1992. University hospital. 12,949 endometrial biopsies, referred to our gynecological pathology laboratory for infertility investigation between 1956 and 1992. Patient report files from pathology laboratory data, analyzed retrospectively. The assessment of the biopsies is made by the same pathologist. 78.8% of cases had primary infertility, 21.2% secondary. Most of them were in the age group 26-35 years (48.8%). 37.58% of cases were found to show normal secretory endometrium, 20.95% proliferative endometrial changes, and 28.22% signs of luteal phase defect (LPD). Other local endometrial factors were also encountered, but in 1.79% the sample was considered insufficient for diagnosis. Moreover, in nine cases, malignancy was diagnosed with the help of endometrial biopsy. During the study period, cases of normal secretory endometrium and tuberculous endometritis were observed to decrease and LPD to increase significantly. It is worthy to note that in only 28 (0.21%) cases had endometrial biopsies been performed during a pregnancy cycle. We conclude that endometrial biopsy not only shows the hormonal response of endometrium but gives additional information about the local factors of endometrium concerning atrophy, specific and non-specific infections, and malignancy.
To describe the relationship between pregnancy complications and fetal outcome in first and second pregnancies, focusing on idiopathic and indicated preterm birth of singleton infants in either pregnancy. Included in the study were 13,967 women in Denmark who gave birth to their first singleton infant in 1982 and a second infant in 1982-1987. Information on pregnancy and birth was obtained by linking the National Medical Birth Register and the National Register of Hospital Discharges, based on personal identification numbers. The risk of a preterm second birth in women with idiopathic and indicated preterm first birth did not differ significantly (15.2 and 12.8%, respectively). However, women with idiopathic preterm birth in the first pregnancy tended to repeat idiopathic preterm birth twice as often as women with indicated preterm birth repeated indicated preterm birth (11.3 versus 6.4%). Adjustment by logistic regression analysis for other risk factors for preterm birth did not influence the relative risk (6.0 before 32 weeks and 4.8 for 32-36 weeks) of a second preterm birth after a first preterm birth. Women with idiopathic preterm delivery in their first and second pregnancies gave birth to infants with lower birth weight than in previous or subsequent pregnancies. Emergency cesarean delivery in a first term pregnancy was a risk factor for subsequent idiopathic preterm birth. Idiopathic preterm birth is associated with emergency cesarean delivery at term in previous pregnancies and infants with lower birth weight in previous and subsequent pregnancies.
Fertility AwarenessNFP Knowledge and AttitudesProvider Promotion and BarriersHealthcare Provider Surveys
Perinatal health professionals are in key positions to either promote or dissuade the use of Natural Family Planning (NFP). The purpose of this article is to describe a survey conducted with perinatal physicians and nurses on their knowledge and professional use of NFP. Four hundred and fifty physicians and nurses (150 MDs and 300 RNs) were sent a questionnaire on the use of and knowledge of NFP. One hundred sixty-six (or 37%) returned the completed questionnaires. Fifty-two percent of the nurses who returned the questionnaires and 48% of the physicians indicated they were taught about NFP in basic (generic) medical or nursing school. The average lecture time spent on the subject in either nursing or medical school was less than one hour. The majority learned about NFP through self-education or on-the-job training. Only four (1 RN and 3 MDs) are certified to teach NFP. Fifty-three percent of the nurses and 44% of physicians would not advise the use of NFP to avoid pregnancy. The most frequent reasons given for not promoting the use of NFP to either avoid or achieve pregnancy were that it is not effective, not natural, too difficult to learn, better methods are available, and it only works for highly motivated educated women.
SurgerySalpingoneostomy and Salpingo-ovariolysisSalpingoscopic AssessmentSalpingoscopy Prognostic Value
To compare the prognostic value of salpingoscopy with a current classification system of adnexal adhesions and distal tubal occlusion in patients with tubal infertility undergoing reconstructive tubal surgery. Prospective clinical study. Department of Obstetrics and Gynecology of the Catholic University, a tertiary care University Center in Rome, Italy. Fifty-five infertile patients with either adnexal adhesions (29 patients) or hydrosalpinx (26 patients) undergoing reconstructive tubal surgery. Salpingoscopy performed concomitantly to salpingo-ovariolysis or salpingoneostomy at the time of either operative laparoscopy or laparotomy using microsurgical techniques. Salpingoscopic findings were compared with a current classification system of adnexal adhesions and distal tubal occlusion. The patients were followed for a mean follow-up of 49 months; the pregnancy rates achieved were correlated with the salpingoscopic findings and the classification system used. There was a significant correlation between the salpingoscopic grade and the occurrence of a term pregnancy for both the salpingo-ovariolysis and salpingoneostomy groups of patients. There was no significant correlation between the classification system used and the occurrence of a term pregnancy for both groups of patients. Salpingoscopy plays an important role in selecting the patients who may benefit the most from reconstructive tubal surgery.
Numerous epidemiological studies have been performed to determine factors that might contribute to the development of inflammatory bowel disease. Although the role of oral contraceptive agents in Crohn's disease (CD) and ulcerative colitis (UC) have been assessed, most studies were of small sample size and characterised by low statistical precision. A meta-analysis was performed to increase the statistical power and to investigate the association between the use of oral contraceptives and the development of CD and UC. The study was based on a search of a Medline database from 1975 to October 1993 and a review of reference lists from published articles, reviews, symposia proceedings, and abstracts from major gastrointestinal meetings. All studies specifically designed to evaluate this association were selected. The combined results of nine studies--two cohort studies (30,379 unexposed and 30,673 exposed patients) and seven case-control studies (482 CD, 237 UC, and 3198 controls)--which satisfied our selection criteria were evaluated. The pooled relative risk (adjusted for smoking) associated with oral contraceptive use was 1.44 (1.12, 1.86) for CD and 1.29 (0.94, 1.77) for UC. These results suggest modest associations between the use of oral contraceptives and the development of CD and UC. As these associations are weak, non-causal explanations for the findings cannot be eliminated.
Fertility AwarenessOvulation and Symptothermal MethodsPerfect Use vs Typical UseNatural Contraception
A better understanding of reproductive anatomy and physiology has led to newer methods of natural family planning, including the ovulation method and the symptothermal method. Studies have shown that 1 percent of couples who consistently and correctly use either of these methods conceives during one year of use. However, in the absence of standardized interpretation of study results, use-effectiveness data of these methods vary widely. The lactational amenorrhea method may be used in selected patients during the first six months postpartum, and its effectiveness in avoiding pregnancy is reported to be as high as 98 percent. Advocates of natural family planning promote these methods as inexpensive and safe ways to determine periods of peak fertility and point to the potential benefit of increased communication in a relationship.
InfertilityCancer Risk After Fertility TreatmentLong-term Health OutcomesCancer Registry Linkage
Concern has been expressed that exposure to fertility drugs might be associated with a risk of ovarian cancer. We have examined the incidence of breast and ovarian cancer in a cohort of 10,358 women referred for in-vitro fertilisation (IVF) treatment in Victoria, Australia, between 1978 and 1992. The "exposed" group (n = 5564) had had ovarian stimulation to induce multiple folliculogenesis and the "unexposed" group (n = 4794) had been referred for IVF but were untreated or had had "natural cycle" treatment without ovarian stimulation. Duration of follow-up ranged from 1 to 15 years. Cases of cancer were determined by record linkage with data from population-based cancer registries. 34 cases of invasive breast cancer and 6 of invasive ovarian cancer were observed. A comparison with the expected numbers, derived by applying age-standardised general population rates to the cohort gave standardised incidence ratios (SIR) for breast cancer of 0.89 (95% CI 0.55-1.46) in the exposed group and 0.98 (0.62-1.56) in the unexposed group, and for ovarian cancer SIRs were 1.70 (0.55-5.27) and 1.62 (0.52-5.02), respectively. Rates of all cancers were not significantly different from general population rates. The relative risk (RR) of cancer, adjusted for age and infertility type, was, in the treated group compared with the untreated group, 1.11 (95% CI 0.56-2.20) for breast cancer and 1.45 (0.28-7.55) for ovarian cancer. The risk of body of uterus cancer was increased in the exposed and unexposed groups combined (SIR 2.84 [1.18-6.81]). Women with unexplained infertility, independent of IVF exposure, had significantly increased risks of ovarian cancer (RR = 19.19 [2.23-165.0]) and body of uterus cancer (RR = 6.34 [1.06-38.0]) compared with women with known causes of infertility. This relatively short-term follow-up suggests that ovarian stimulation with IVF is not associated with an increased risk of breast cancer. Although there was no significantly increased risk of ovarian cancer after ovarian stimulation with IVF the small number of cases limits the conclusions that can be drawn. Longer-term follow-up of large cohorts of women who have been in IVF programmes will be necessary.
To evaluate whether preterm-birth prevention educational programs are effective at reducing neonatal mortality, low birth weight (LBW), and preterm delivery. A MEDLINE literature search of English-language studies was performed, supplemented by a bibliography search of original research and review articles to locate studies assessing preterm-birth prevention programs. We identified 31 studies that reported results from trials evaluating preterm-birth prevention programs. From this group, only the six randomized controlled trials evaluating preterm-birth prevention education programs satisfied criteria of homogeneity to be included in a meta-analysis. One of these six studies was a subset of another study and was excluded except when reporting outcomes that were not included in the larger report. Two independent reviewers assessed LBW frequency, preterm birth frequency, neonatal survival, birth weight, gestational age at delivery, and preterm labor diagnosis rates. When data were combined using meta-analytic techniques, no significant benefits were found for preterm-birth education programs in preventing neonatal death (cumulative relative risk [RR] 1.00, 95% confidence interval [CI] 0.99-1.01), LBW rates (RR 0.99, 95% CI 0.88-1.11), or preterm delivery rates (RR 1.08, 95% CI 0.92-1.27). The only statistically significant effect of preterm birth education programs appears to be an increase in the frequency at which preterm labor is diagnosed (RR 1.71, 95% CI 1.41-2.08). Preterm-birth prevention educational programs appear to have little benefit in reducing preterm birth and may result in an increased rate of diagnosis of preterm labor.
InfertilityPregnancy and Birth ComplicationsMultiple Pregnancy RiskIVF-Related Prematurity
To describe the characteristics of pregnancies and children at birth resulting from IVF-ET and to assess whether they differ from those after natural conception. Prospective multicenter survey. A national registry, representing 80% of all French IVF-ET activity for the period 1986 to 1990. Data on 7,024 pregnancies, 5,371 deliveries, and 6,879 newborn infants. A form is completed for every clinical pregnancy. Spontaneous abortion, ectopic pregnancy, multiple pregnancy, prematurity, hypotrophy, perinatal and neonatal mortality, and congenital malformations rates. The spontaneous abortion and ectopic pregnancy rates were, respectively, 17.6% and 5.8%. More than a quarter (26.8%) of the deliveries were multiple births. The preterm birth rate (29.3%), the low birth weight rate (36.2%), and the perinatal and neonatal mortality rates were higher than the national average. The rate of malformations (2.8%) was comparable with the general population (2.1%). Assisted conception frequently results in multiple pregnancy, and this is the main determinant of pregnancy outcome. Nevertheless, it is not the only risk factor for prematurity, which is also more frequent among IVF singleton newborn. The prevalence of congenital malformations is not higher than after natural conception.
Reproductive EndocrinologyNeurological ApplicationsEpilepsy and SeizuresProgesterone Clinical Trials
This open trial assessed the effects of adjunctive progesterone therapy on seizure frequency in 25 women with catamenial exacerbation of complex partial (CPS) and secondary generalized motor (SGMS) seizures. Progesterone was well tolerated by 23 of the 25 women and had readily reversible dose-related side effects of asthenia and emotional depression in two. Eighteen women (72%) experienced a decline in seizure frequency during a 3-month treatment period compared with the 3 months prior to therapy (p < 0.01). Average daily CPS frequency declined by 54% (p < 0.01), SGMS by 58% (p < 0.02).
PCOSHyperinsulinism and Opioid SystemNaltrexone Opioid Antagonist TherapyHepatic Extraction
A total of 17 women affected by polycystic ovarian disease (PCOD) were studied to evaluate the involvement of endogenous opioids in the pathophysiology of the hyperinsulinism in PCOD by administering naltrexone, an oral opioid antagonist. An oral glucose tolerance test (OGTT) was performed at baseline (on day 5 of the cycle) and repeated after 6 weeks of naltrexone administration. Plasma glucose, insulin and connecting peptide (c-peptide) concentrations were evaluated in all samples. Based on their insulinaemic response to OGTT, patients were classified as hyperinsulinaemic or normoinsulinaemic. Naltrexone treatment significantly (P < 0.007) reduced the insulin response to OGTT in the hyperinsulinaemic group without affecting the c-peptide incremental area; in the normoinsulinaemic group there was a slight, but not significant, increase in both c-peptide and insulin incremental areas. The two groups showed similar c-peptide incremental areas after naltrexone treatment. There was no significant insulin incremental areas molar ratio between the two groups; after treatment, a significant increase in this ratio was observed in both groups. When we considered the data as an expression of the fractional hepatic extraction of insulin, we found a lower value for hyperinsulinaemic in comparison with normoinsulinaemic patients (not significant), and a significant (P < 0.01) improvement of this parameter in the hyperinsulinaemic group after naltrexone administration. In conclusion, we suggest that the contribution to hyperinsulinaemia in PCOD patients may be at least in part due to both increased pancreatic secretion and reduced hepatic removal of insulin. Chronic pharmacological inhibition of opioid tone could improve the insulin plasma concentration by acting chiefly on the liver metabolism of insulin in hyperinsulinaemic patients.
DiagnosticsDoppler Assessment of Corpus LuteumNoninvasive DiagnosisBlood Flow Assessment
To determine whether color flow pulsed Doppler analysis of corpus luteum blood flow in normal cycles differs from cycles with a luteal phase defect. A prospective study of natural ovarian cycles. The University of Vermont Reproductive Endocrinology and Infertility Service. Ten women with regular menstrual cycles and at risk for luteal phase defect (LPD) four with unexplained infertility, two with recurrent abortion, and four with age > 35 years. All women were examined by transvaginal color flow pulsed Doppler during the early follicular, late follicular, early luteal, midluteal, and late luteal phase of the menstrual cycle. Venous blood for P concentration was drawn on each day of Doppler exam. Urine testing for LH surge and endometrial biopsy during the late luteal phase were performed on each patient. Lowest resistance index associated with the highest amplitude signal from intraovarian vessels of each ovary, dated endometrial biopsies, serum P. Mean resistance indexes in LPD patients (n = 3) were significantly higher compared with normal women (n = 6) throughout the follicular and luteal phases. One patient remained anovulatory and was excluded from statistical analysis. Although systolic and diastolic velocities generally were observed to be lower in LPD patients compared with normal women, these differences were not statistically significant. High correlations were observed between P and resistance index within each luteal time point, achieving its highest value during the midluteal phase. This initial study provides evidence that color flow pulsed Doppler analysis of blood flow impedance to the corpus luteum may aid in assessing luteal phase adequacy.
Valle RF, 1995·Obstetrics and Gynecology Clinics of North America
While uterotubal chromopertubations were performed early in the 1970s with the introduction of hysteroscopy, cornual cannulation was extended and adapted to fluoroscopy. The disadvantages of fluoroscopy include the difficulty in ruling out tubal spasm, inability to evaluate distal tubal disease, and other pelvic abnormalities. Tubal cannulation has emerged as an excellent alternative to treat patients with cornual obstruction. Only those patients in whom cannulation fails should be subjected to microsurgical reconstruction. While cannulation with coaxial catheters began under fluoroscopy, the use of the hysteroscope simplifies the technique. With laparoscopy the hysteroscopic approach enables tubal cannulation and evaluation of the entire pelvis. Treatment of additional problems affecting the fallopian tubes, particularly adhesions and endometriosis, is possible. Laparoscopy helps in monitoring the procedure and visual assessment of tubal patency. The ability to observe the uterotubal junctions directly by hysteroscopy provides an excellent approach for tubal cannulation. There are two techniques to cannulate the fallopian tubes, either with coaxial catheters or catheters with distal balloons, but the result obtained with these two techniques is similar. The simplicity of coaxial catheters makes this approach more appealing, and with the hysteroscope one can avoid exposure to radiation. The results obtained with tubal cannulation are encouraging and this procedure should be offered as the initial method to attempt treatment of tubal cornual obstruction. Often it can represent an excellent alternative to microsurgical tubal anastomosis, avoiding a laparotomy and extended disability.
InfertilityClomiphene Citrate EffectsEndometrial Thickness and Echo PatternClomiphene Impact
To determine whether successive cycles of clomiphene citrate affect endometrial thickness. Thirty-four women presenting for treatment of anovulation, oligoovulation, or follicle maturation defects were given the smallest dose of clomiphene citrate necessary to attain a mature follicle. If no pregnancy ensued, the same dose was continued if a follicle 18-24 mm in diameter and a serum estradiol (E2) level greater than 200 pg/mL were achieved. Ethinyl E2 was supplemented for poor cervical mucus only. Endometrial thickness and echo patterns were measured each cycle at peak follicular maturation. There was no difference in mean endometrial thickness during the first six cycles of therapy, nor was there a trend for thickness to increase or decrease with successive cycles with or without the addition of ethinyl E2. There was no change in the distribution of echo patterns with successive cycles of clomiphene citrate. Post-treatment measures of thickness and echo pattern did not differ from baseline pre-treatment values. The homogeneous hyperechogenic pattern was the rarest. Mean serum E2 and progesterone levels at mid-cycle did not change with successive cycles. One proposed mechanism for the dichotomy between ovulation and pregnancy rates after clomiphene citrate therapy is that the drug adversely affects the endometrium. If clomiphene citrate does affect implantation adversely, the mechanism does not seem to be related to thinning the endometrium or causing an echo pattern that indicates a poor prognosis. The data also suggest that estrogen supplementation does not influence endometrial thickness and would best be used exclusively for hostile cervical mucus.
To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters, as well as on the androgen receptor status, in hirsute women. Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide, three times per day for 12 months. Barrier or intrauterine contraception was used during the study in sexually active women. Safety parameters were assessed throughout the study. Hirsutism, graded by the modified Ferriman-Gallwey score, and hormonal parameters were evaluated basally and at 4-month intervals during treatment. Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy. In addition, the concentration of androgen receptors in mononuclear leukocytes was measured, in both the follicular and luteal phases of the menstrual cycle, basally and after 4 months of flutamide treatment. Flutamide was well tolerated in all women, with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy. Hirsutism markedly improved in all women during the treatment (Ferriman-Gallwey score after 1 4.1 +/- 0.5 versus 14.1 +/- 0.9). A reduction of serum androgens was found, whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH. Cycles remained ovulatory. Before treatment, the number of androgen receptors was higher in the luteal than in the follicular phase. This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug. Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function. Androgen receptor blockade might be potentiated by a reduction of serum androgens. Flutamide affects androgen receptor behavior during the menstrual cycle. The meaning of this finding remains to be elucidated.
To evaluate the efficacy of Interceed (TC7) Absorbable Adhesion Barrier, an oxidized regenerated cellulose fabric, as a barrier to the development of postsurgical ovarian adhesions after surgery involving the ovaries. In a multicenter randomized study, 55 patients with bilateral ovarian disease were treated at initial laparotomy. At the end of the procedure, one ovary was assigned randomly to be wrapped with Interceed and the other was left uncovered. A second-look laparoscopy was performed 10-98 days later to evaluate the occurrence and severity of adhesions and the raw ovarian surface area exposed after lysis of adhesions. At second-look laparoscopy, 26 of 55 Interceed-treated ovaries were free of adhesions, compared with 14 of 55 untreated control ovaries, a statistically significant difference (P = .028, Fisher exact test). At second-look laparoscopy, ovaries treated with Interceed formed adhesions less extensively (1.66 +/- 0.34 cm2) than did untreated ovaries (2.75 +/- 0.60 cm2) and with a greater reduction of raw ovarian surface area (difference in area differential -1.89 +/- 0.96 cm2; P = .055, paired t test). Adhesion scores at second-look laparoscopy were reduced significantly for ovaries treated with Interceed compared with untreated ovaries (P = .02, Wilcoxon signed-rank test). No adverse events were recorded during the course of the study. Treatment of ovaries with Interceed significantly reduced the occurrence and severity of postsurgical ovarian adhesions.
General OB/GYNObesity and Cancer RiskCancer RiskMetabolic Disease and Cancer
Large-scale studies have demonstrated that obesity increases the risk of developing some forms of cancer. The association between obesity and cancer may result from factors such as fat distribution or sex hormone levels. Studies have also shown a relationship between a high-fat, low-fiber diet and cancer risk. High estrogen levels and low progesterone levels are associated with an increased risk of endometrial cancer. Obesity is known to raise estrogen levels and may lower progesterone levels. Obesity may increase the risk of breast cancer, but the evidence is less clear, since factors, such as age, country of origin, body-fat distribution, and family history, also play a major role in determining breast cancer risk. Sex hormones, insulin, and nutritional factors are also involved in the etiology of breast cancer. The incidence of lung cancer is inversely related to body weight.
To compare ampicillin with and without sulbactam with respect to the effect on the latency period after preterm premature rupture of membranes (PROM). Patients with PROM at 25-35 weeks' gestation were offered participation in a randomized blinded trial comparing ampicillin-sulbactam with ampicillin. Evaluations for cervical pathogens were performed on admission and patients were followed-up with daily maternal and fetal evaluation. Maternal and neonatal outcomes were analyzed using indicated techniques. Fifty-three women were studied, with 25 receiving ampicillin-sulbactam and 28 receiving ampicillin. The ampicillin-sulbactam group had a significantly longer latency period (433 +/- 625 versus 143 +/- 165 hours, P = .03) and significantly fewer neonatal complications (five versus 20, P < .001). Although no neonatal infectious complications were observed in sulbactam-treated cases, there were four cases of neonatal sepsis and two of neonatal pneumonia in the ampicillin group. Also, significantly more neonates in the ampicillin group required prolonged oxygen and ventilatory support. There was no significant difference in maternal morbidity. In our population with preterm PROM, a broad-spectrum antibiotic that provides anaerobic coverage appears to extend latency and decrease neonatal morbidity without increasing adverse maternal outcome.
PCOSInsulin Resistance and CancerBreast Cancer Risk FactorsCancer Pathogenesis
Consideration of existing data regarding clinical and biochemical risk factors for the development of breast cancer leads to the hypothesis that enhanced insulin-like growth factor I (IGF-I) activity plays a significant role in the development of this disease. Abnormal IGF-I activity may be related to events occurring prenatally, during puberty, or during adult life. Insulin resistance, a common feature in populations characterized by high caloric intake, may result in the amplification of IGF-I action at the tissue level by altering serum concentrations of IGF-I binding proteins. Several approaches toward testing the hypothesis are proposed, and potential opportunities for clinical application are described.
There is considerable evidence that the childbearing years represent a time when women are highly vulnerable to developing mood disorders. Prospective, cross-sectional, and retrospective studies have demonstrated that more than 10% of new adult mothers will experience a major depressive episode during the first postpartum year. Changes in the health care delivery system will result in increased pressure on the obstetrician/gynecologist to identify and treat women with postpartum-onset depression. Despite shortcomings in the available literature, prospective studies have identified risk factors for developing postpartum depression. Furthermore, the clear overlap between the normal sequelae of childbirth and the symptoms of major depression, including alterations in sleep, energy, libido, appetite, and body weight, underscores the need to develop guidelines for early identification. We furnish a brief overview of postpartum mood disorders with a primary focus on the antenatal and postnatal risk factors for developing postpartum depression. Based on the extent literature and our clinical experience, a set of recommendations for early identification and treatment is provided.
To explore the pulsatile-release characteristics of LH and P in women with premenstrual syndrome (PMS) compared with age-matched phase-matched controls. Prospective, repeated measures, two-group study. Human volunteers in an academic research environment. Six women with rigorously defined prospectively determined PMS; six age-matched phase-matched controls. Frequency, amplitude, concentration, and coincident pulsatile release characteristics of LH and P at three symptom-related points of the luteal phase. No significant between-group differences in frequency, amplitude, or concentration were found. In pooled data, significant coincident pulsing between LH and P was demonstrated. The length of time between LH and P pulses systematically increased across the luteal phase, a finding not previously reported. In the PMS group only, significant coincident pulsing occurred at an unexpected zero time lag on the symptom-onset sampling day. A progressively increasing coupling interval may reflect the gradual decline of the corpus luteum. Presence of a zero time lag between LH and P at symptom onset in women with PMS may indicate an aberrance in corpus luteum response to LH stimulation.
To evaluate the effects of long-term administration of finasteride on hirsutism score, basal gonadotropin, and androgen secretion in women with idiopathic hirsutism. Randomized single-blinded study. Eighteen patients with moderate-severe hirsutism were recruited for the study. Nine hirsute patients received 7.5 mg/d oral finasteride for a period of 9 months whereas the other nine were treated with placebo. Hirsutism score, serum basal gonadotropin, androgens, estrogen, and sex hormone-binding globulin (SHBG) levels were evaluated in all patients before treatment and every 3 months during treatment. After 6 and 9 months of treatment, the hirsutism score improved significantly in the patients receiving finasteride, whereas no significant modifications were observed in patients treated with placebo. The side effects observed were headache and depression of modest entity during the 1st month of treatments, whereas libido did not change. Serum levels of LH, FSH, androstenedione, unbound T, DHEAS, E2, 17 alpha-hydroxyprogesterone, and SHBG did not change during therapy. Hirsute patients treated with finasteride exhibited a marked decrease of dihydrotestosterone and a significant increase of T serum levels from the 3rd and 6th months of treatment, respectively. Finasteride decreased the hirsutism score of patients affected by idiopathic hirsutism with few side effects during treatment. No modification of libido was observed.
One of the major postoperative complications of reproductive surgery is the formation of adhesions. 1, 2 Over the past several decades a number of methods have been explored to solve this problem, g, 4 Recently there has been renewed interest in covering the damaged peritoneal surface with an absorbable or nonabsorbable barrier as a means of preventing adhesions after fertility-enhancing surgery. Currently, two barriers are commercially Interceed Absorbable Adhesion Barrier (Ethicon, Somerville, NJ), which is composed of oxidized regenerated cellulose, and the Gore-Tex Surgical Membrane (W. L. Gore & Associates, Inc., Flagstaff, AZ), constructed of expanded polytetrafluoroethylene (e-PTFE). Interceed has been investigated both experimentally and clinically and has proved effective in some circumstances. 5,6 Studies also report on the laparoscopic application of Interceed in fertility-enhancement procedures.7, 8 Recent reports, however, have questioned the product's degree of effectiveness and raised concern about possible residual effects it may have on peritoneal tissue? 11 Gore-Tex Surgical Membrane has been indicated for use in peritoneal reconstruction since 1983, and experimental and clinical reports describe its effectiveness in preventing adhesion formation. 12-14
Interceed is an absorbable material that is phagocytized by macrophages within 1 month. Gore-Tex Surgical Membrane is nonabsorbable and is intended to be a permanent implant. Since all published reports on the clinical application of the Gore-Tex membrane discuss implantation by laparotomy, ~g, 14 the ease of use of this product in laparoscopic surgery is of particular interest. Moreover, because of its permanence, its long-term safety and effectiveness merit examination. A prospective, multicenter clinical study was undertaken to evaluate the ease of using Gore-Tex Surgical Membrane laparoscopically.
PregnancyUltrasound AssessmentFirst Trimester ViabilityGestational Sac and CRL Dynamics
To compile, for the first time, serial ultrasonographic findings during the first trimester of pregnancy in women with a history of primary recurrent spontaneous abortion so as to define the dynamics of early normal and abnormal gestations in this category of gravidas. Transvaginal ultrasonograms were obtained weekly from 5 to 12 weeks' gestational age in 40 women, 10 recurrent spontaneous aborters and primiparas (controls), with both successful and failed gestations. Embryonic heart motion was detected in 40-50% of successful pregnancies during the fifth week of gestation and in the balance by the sixth week, while heart motion was detected in no more than 50% of pregnancies that later failed. Of the failed pregnancies, all were evident by the eighth week of gestation, including those with previously documented viability. The gestational sac size and crown-rump length were smaller than expected in both failed groups, with the sac size difference evident as early as week 5 and the crown-rump length difference apparent by week 7. Appropriate timing of the initial ultrasonogram in recurrent aborters (i.e., 8 weeks' gestational age) can identify, by means of heart motion and gestational sac features, all pregnancies that will ultimately fail.
To test the acute effect of estrogen on peripheral blood flow and vascular resistance in postmenopausal women. Eleven normotensive, post-menopausal female volunteers (mean age 53 +/- 6 years) were studied. Six women were in natural menopause and 5 had had a hysterectomy (mean age of the menopause 49 +/- 3 years). We used a double-blind, randomized protocol to assess the acute response to sublingual estradiol-17 beta (1 mg) on the forearm resistance vessels, compared with sublingual placebo. Blood flow was measured by strain-gauge plethysmography, and mean peripheral vascular resistance was then calculated. Mean blood pressure was also measured. The mean blood flow induced by estradiol-17 beta after 40 minutes was significantly greater than that induced by placebo (3.9 +/- 0.5 mL/100 mL per minute versus 2.4 +/- 0.4 mL/100 mL per minute, respectively, P < 0.05). The forearm resistance was significantly reduced at 40 minutes after estradiol-17 beta compared with placebo (25.7 +/- 4.4 resistance units (RU) to 44.4 +/- 6.4 RU, respectively, P < 0.05). Mean blood pressure 40 minutes after the administration of estradiol-17 beta was no different when compared with placebo (91 +/- 1.5 mm Hg versus 90 +/- 2.5 mm Hg, respectively, P = NS). These results indicate that the acute administration of estradiol-17 beta affects blood flow in the peripheral vasculature in human subjects. The mechanism of this effect has not been determined, but it may explain some of the beneficial effects of estrogen on the vascular system and have future therapeutic potential in postmenopausal women.
InfertilityFecundabilityIVF OutcomesFertility Probability Models
The last decade has transformed the physician's approach to infertility. The development of IVF for its treatment has so improved our capacity to overcome this most distressing of disabilities that we now need to revise many of our working ideas on how it can come about. This is not because new causes have been discovered. Rather, an appreciation has been gained of how apparently minor disturbances can combine to cause a major disruption in the expectation of pregnancy.
At the best of times-and sometimes, no doubt, at the worst of times getting pregnant is a matter of chance. The parameter that describes this chance is the monthly probability of conception, known among epidemiologists as fecundability (f) (probability of achieving pregnancy in one menstrual cycle), and is similar to "monthly fecundity" (monthly probability of a live birth in one cycle exposed to the risk of pregnancy) (1). Like every statistic in biology, fecundability has a wide distribution of values in the population (modeled in Fig. 1). Figure 1 also illustrates a group of couples with a fecundability value of zero-meaning complete infertility, or sterility, which affects perhaps 5% of couples attempting to achieve a pregnancy.
To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses. Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group. University hospital PMS medical treatment outpatient program in obstetrics/gynecology department. Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events. A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits. Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors. Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables. Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS.
Vaginal progesterone suppositories are an accepted treatment for infertility attributed to luteal phase defects. Although oral micronized progesterone may be preferable to suppositories for many patients, there are no studies on its use for patients with luteal phase defects. This study evaluated the efficacy of oral micronized progesterone for the treatment of luteal phase defects. Seven women with luteal phase defects previously corrected by vaginal suppositories were administered oral micronized progesterone (200 mg by mouth three times a day). Endometrial biopsies were performed to evaluate treatment efficacy. Questionnaires were used to assess side effects, including sedation. On oral micronized progesterone, all patients had in-phase endometrial biopsies. Despite complaints of drowsiness, the majority of patients preferred the oral formulation over the vaginal route of administration. We conclude that oral micronized progesterone is efficacious in the treatment of luteal phase defects.
General OB/GYNEpidemiologyPredictive Risk FactorsThyroid Disease
The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort. DESIGN, Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction. Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women. This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.
Premenstrual dysphoria shares certain features with depression and anxiety states, which have been linked to serotonergic dysregulation. We evaluated the efficacy and safety of fluoxetine (which selectively inhibits the reuptake of serotonin) in the treatment of premenstrual dysphoria. The trial consisted of a single-blind, placebo washout period lasting two menstrual cycles, followed by a randomized, double-blind, placebo-controlled trial of fluoxetine at a dose of either 20 mg or 60 mg per day or placebo for six menstrual cycles. Healthy women meeting criteria for what was then called late-luteal-phase dysphoric disorder were recruited at seven university-affiliated women's health clinics in Canada. The primary outcome measure consisted of visual-analogue scales for tension, irritability, and dysphoria during the late luteal phase of each cycle. Of 405 women enrolled in the placebo washout period, 313 subsequently entered the randomized phase of the study, which lasted six menstrual cycles, and 180 completed it. Fluoxetine at a dose of 20 or 60 mg per day was significantly superior to placebo in reducing symptoms of tension, irritability, and dysphoria, as measured by the visual-analogue scales (P < 0.001). The women who received 60 mg of fluoxetine per day reported significantly more side effects than those who received 20 mg per day or placebo (P < 0.001). Fluoxetine is useful in the treatment of premenstrual dysphoria. Treatment with fluoxetine at a dose of 20 mg per day reduces the potential for side effects while maximizing therapeutic efficacy.
InfertilityDiagnostic AssessmentAccuracy and LimitationsTubal Patency Testing
To determine whether the diagnostic accuracy and prognostic value of hysterosalpingography (HSG) could be improved if routine spot films were replaced by an on-line recorded gynecoradiologic study.
Medical school-affiliated private infertility center.
In 1992, a review of 152 infertile women with infertility who demonstrated a normal HSG, by standard criteria of spot film evaluation, in 117 (77%). They were further investigated by gynecoradiologic study if the HSG revealed asymmetrical tubal filling, an increased perfusion pressure, and/or evidence for abnormal tubal spill. In 1993, 47 women with normal HSG by spot film criteria underwent bilateral selective salpingography and were subdivided into those with normal (group I, n = 23) and abnormal (group II, n = 24) tubal perfusion pressures. Patients in both study groups then were treated for their infertility independently of pressure perfusion measurements.
Clinical pregnancy rates (PRs) over the ensuing 6 to 10 months. Among 117 women with apparently normal spot film HSG, 64 (55%) demonstrated asymmetrical tubal filling, 32 (27%) demonstrated abnormal spillage into the peritoneal cavity, and 55 (47%) demonstrated abnormally elevated injection pressures. Among 98 women who underwent bilateral selective salpingography, 43 (44%) demonstrated bilaterally normal tubal perfusion pressures and 55 (56%) showed an abnormally elevated pressure in at least one oviduct. Of 47 women that were followed prospectively in 1993, patients with normal perfusion pressure (group I) demonstrated a significantly higher PR than women with elevated tubal pressure (group II) from 2 months and on after the procedure. Routine spot film HSG is of limited value in assessing tubal status beyond the determination of tubal patency. Especially with regard to fertility potential, HSG should be replaced by gynecoradiologic study.
Reproductive EndocrinologyEstradiol and Pregnancy OutcomeGIFT OutcomesHormonal Predictors
To correlate luteal estradiol (E2) levels with pregnancy outcome, 36 consecutive conceptions resulting from gamete intrafallopian transfer in gonadotropin releasing hormone agonist/human menopausal gonadotropin (GnRH-a/hMG) cycles were analyzed. GnRH-a was initiated during the preceding luteal phase. HMG was adjusted individually. Human chorionic gonadotropin (hCG), 5,000 IU, was administered when E2 was > 500 pg/mL and the leading follicle > 17 mm (day 0). The luteal phase was supported by (1) hCG, 1,500 IU in three doses from day 5 and (2) progesterone (P) from day 7. E2 and P levels were analyzed normally progressing pregnancy (NPP), abortion (AB) and preclinical abortion (PAB). No significant differences in mean E2 levels were seen between the groups from day 0 through day 5 after hCG. Midluteal E2 levels were significantly different between the groups (P < .05). Late luteal E2 values were significantly higher for NPP than for either AB or PAB (P < .05). There were no significant differences in luteal P values between the NPP, AB and PAB groups. Decreased luteal E2 appears to be associated with early pregnancy wastage; this may be due to inadequate endometrial support.
Fertility AwarenessSexual Activity PatternsEffectiveness and ComplianceNFP Behavioral Analysis
For 10 years, a prospective study has been taking place in Germany to examine the use of natural family planning (NFP). As natural methods are behavioral methods, use-effectiveness, acceptability and continuation rates are very much influenced by patterns of sexual behavior. Therefore we performed an analysis of the sexual behavior of NFP users. Out of the data base of 1211 clients and 12,591 cycles we could identify a group of 300 women, all NFP beginners, with 5900 contraceptive cycles, who contributed at least 12 cycles with reliable recording of their sexual activity. Different groups were analyzed with methods of analysis of variance and regression models to find out significant differences in their sexual behavior with respect to sociodemographic structure and time of use. Nearly half of all the women systematically combine the fertility awareness part of NFP with other family planning methods. They use barriers in more than 60% of their cycles. The other half never or only in about 7% of their cycles use additional barrier methods. The latter show a clear decrease in barrier use in the course of time, whereas the frequent barrier users constantly combine the advantages of two family planning methods. Regarding the frequency of intercourse they are the sexually more active ones and show distinct sociodemographic characteristics. We could confirm the existence of three groups of NFP users, which differ significantly in their use of NFP as a family planning method. Despite these differences the low pregnancy rates indicate the conscious and risk-related sexual behavior of the group members.
During lactational amenorrhea a special type of cervical mucus, similar to that found during the luteal phase, is produced. This mucus, however, is able to support sperm migration. In the study described, the ability of spermatozoa to bind to the human zona pellucida (hZP) after migration through periovulatory and post-partum mucus was studied. Mucus was obtained from exclusively breastfeeding women in amenorrhea at 30, 60, 120 and 180 days post-partum. Periovulatory mucus samples from normally cycling women were used as a control. Flat capillary tubes were filled with BWW culture medium at the top and cervical mucus at the bottom. The tubes were immersed in a semen reservoir and the spermatozoa allowed to migrate through the mucus for 3 h into the culture media. Then the spermatozoa were coincubated with 3-4 hZP for 30 min and the number of bound spermatozoa per zona was counted. Periovulatory cervical mucus had an average Insler score of 14 +/- 0.5 as compared to 4.6 +/- 0.4 for post-partum mucus. Spermatozoa recovered from periovulatory mucus were always able to bind to the hZP in only 68 +/- 7% of the cases. Moreover, spermatozoa recovered from post-partum mucus bound to the ZP in lower numbers than did spermatozoa recovered fro periovulatory mucus (p < 0.03). These results suggest a greater ability of sperm-hZP binding after migration through periovulatory mucus and they also indicate that sperm binding to the ZP is possible even after sperm migration through a low quality mucus.
To assess whether temperature is increased by medroxyprogesterone (MPA) and thus whether basal temperature records could be used to determine ovulation during cyclic MPA therapy.
A 2-month double-blind placebo-controlled crossover trial in which oral basal temperature was measured daily.
Normal human volunteers in an academic medical environment. Eleven postmenopausal women not taking gonadal hormones. Medroxyprogesterone acetate (10 mg/d) or placebo, calendar days 16 to 25, with crossover. Comparison of mean temperature days 17 to 26 during MPA versus placebo; comparison of differences between temperatures days 7 to 16 and 17 to 26 in MPA versus placebo months; and analysis for a significant monthly thermal shift. The mean temperatures during MPA treatment averaged 0.27 degrees C higher than during the placebo phase and showed a significant change from pretreatment to "treatment" phases during MPA but not during placebo cycles. Eight of the MPA and one of the placebo cycles showed a shift from lower to higher temperatures days 16 to 25. Medroxyprogesterone acetate has a physiological progesterone-like thermal effect. Therefore basal temperature data cannot reliably indicate ovulation during cyclic MPA administration.
To evaluate catalase activity as a rapid predictor of microbial invasion of amniotic fluid (AF). The study population consisted of 74 patients before 36 weeks' gestation with preterm labor or premature rupture of membranes (PROM). Subjects were excluded if there was evidence of clinical chorioamnionitis or fetal distress at admission. Amniocentesis was done within 24 hours of admission, and the AF was cultured for aerobic and anaerobic bacteria and for Mycoplasma species. All AF samples were Gram stained, and slides were examined by microbiology technologists. Amniotic fluid catalase activity was measured immediately after amniocentesis using a commercially available kit. The sensitivity of the Gram stain and catalase activity were compared using McNemar exact test. Amniotic fluid cultures were positive in 12 of 37 (32%) patients presenting with preterm labor and in 21 of 37 (56%) patients with PROM. Catalase activity was significantly more sensitive than Gram stain in detecting positive AF cultures in cases of PROM (P < .001) and preterm labor (P < .04). Catalase activity is a simple, rapid test that is useful in identifying subclinical intra-amniotic infection in patients with preterm labor or PROM.
To examine the role of steroid hormone receptor compartmentalization in infertile women with "in-phase" or "out-of-phase" endometrium. Nonrandomized prospective clinical study. A university clinic. Twenty-nine infertile patients without evidence of endometriosis, tubal factor, male factor, galactorrhea, or hyperandrogenism were enrolled. Sixteen patients had in-phase endometrium and a P level > or = 10 ng/mL (conversion factor to SI unit, 3.18) (group A). Four patients had out-of-phase endometrium and a P level > 10 ng/mL (group B). Four patients had in-phase endometrium and a P level < 10 ng/mL (group C), and five patients had out-of-phase endometrium and a P level < 10 ng/mL (group D). Each patient underwent determination of serum P and endometrial sampling on postovulatory days 6 to 9 based on serum LH measurement. Dating according to endometrial histology and biochemical assessment of estrogen receptor (ER) and P receptor (PR) were performed on each sample. The level of cytosol ER was significantly lower in out-of-phase endometrium regardless of serum P level. There were no significant differences in the levels of cytosol PR and nuclear ER and PR among groups. In a long-term follow-up study, 6 of 29 patients became pregnant. PR ratio in these patients was found to fit a single straight regression line (y = 0.34x - 2.2). Out-of-phase endometrium probably depends on inadequate cytosol ER. PR ratio may be important to become pregnant.
In this study we evaluated different markers of infection and their relationship to preterm delivery. Forty-four consecutive women with singleton pregnancies in uncomplicated preterm labor were investigated. C-reactive protein (CRP) in peripheral maternal blood, amniotic fluid cytokines, amniotic fluid leukocyte count, and amniotic fluid culture were performed in all patients. Thirty-six patients responded to standard tocolytic therapy and delivered after 34 weeks' gestation. In eight patients treatment failed and they delivered before 34 weeks' gestation. Two of these eight patients had a positive amniotic fluid culture for Ureaplasma urealyticum. The positive culture was accompanied by an elevated neutrophil count in the amniotic fluid. Elevated amniotic fluid levels of tumor necrosis factor (TNF) (more than 23 pg/mL), interleukin-6 (IL-6) (more than 2292 pg/mL) and interleukin-8 (more than 164 pg/mL) correlated with early preterm delivery. CRP levels in serum had a low sensitivity (38%) but a high specificity (94%) in predicting preterm delivery. This study indicates that preterm labor can be initiated by infection. Markers of infection obtained by amniocentesis have a better sensitivity and positive predictive value than noninvasive markers. Elevated IL-6 (more than 2292 pg/mL) seems to be the best predictor for preterm delivery, with a sensitivity of 75% and a specificity of 97%.
We describe the epidemiologic characteristics of conception, including subclinical early pregnancy loss, in a population of healthy women volunteers who had heterogeneous fertility experiences, and we describe the conception experience of women within this group who had evidence of impaired fertility. This was a prospective observational study of a cohort of women employed in two semiconductor manufacturing facilities. A total of 148 volunteers completed interviews and daily diaries and collected daily urine specimens for an average of 7 months. Conception, including subclinical losses and clinical pregnancies, was determined with a highly sensitive and specific assay for urinary human chorionic gonadotropin, and ovulation was determined with assays of urinary ovarian steroid hormones. There were 679 menstrual cycles at risk for pregnancy contributed by 124 (84%) of the 148 women. Women with evidence of subfertility before or during the study period had a rate of early pregnancy loss of 70% compared with 21% in women without fertility problems (relative risk 2.6, 95% confidence interval 1.8 to 3.8). The risk of pregnancy loss associated with subfertility increased with age and remained the same in women treated with clomiphene citrate. These results suggest that subfertile women have increased subclinical pregnancy losses regardless of fertility treatment and that the association between reduced fertility and advancing age may be related, in part, to early subclinical pregnancy loss.
To compare the impact of expanded polytetrafluoroethylene (PTFE; Gore-Tex Surgical Membrane; W. L. Gore & Associates, Inc., Flagstaff, AZ) and oxidized regenerated cellulose (Interceed TC7, Johnson & Johnson Medical, Inc., Arlington, TX) on the development of postsurgical adhesions. A multicenter, nonblinded, randomized clinical trial. University medical centers. Each barrier was allocated randomly to the left or right sidewall of every patient. Thirty-two women with bilateral pelvic sidewall adhesions undergoing reconstructive surgery and second-look laparoscopy. Adhesion score (on a 0- to 11-point scale), the area of adhesion (cm2), and the likelihood of no adhesions. The use of both barriers was associated with a lower adhesion score and area of adhesion postoperatively. However, those sidewalls covered with PTFE had a significantly lower adhesion score (0.97 +/- 0.30 versus 4.76 +/- 0.61 points, mean +/- SEM) and area of adhesion (0.95 +/- 0.35 versus 3.25 +/- 0.62 cm2). Overall, more sidewalls covered with PTFE had no adhesions (21 versus 7) and, when adhesions were present on the contralateral sidewall, the number of sidewalls covered with PTFE without adhesions was greater than those covered with oxidized regenerated cellulose (16 versus 2). Expanded polytetrafluoroethylene was associated with fewer postsurgical adhesions to the pelvic sidewall than oxidized regenerated cellulose.
We report the existence of a 'placental clock', which is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women we have demonstrated that placental secretion of corticotropin-releasing hormone (CRH) is a marker of this process and that measurement of the maternal plasma CRH concentration as early as 16-20 weeks of gestation identifies groups of women who are destined to experience normal term, preterm or post-term delivery. Further, we report that the exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH binding protein in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at a time that coincides with the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans.
We investigated the impact of pregestationally elevated insulin plasma levels on glycemic control in pregnant women with polycystic ovary disease (PCOD). Twelve patients with PCOD who became pregnant within six months following evaluation of their metabolic status were the study subjects. Four were obese and six (two obese) had a hyperinsulinemic response to the oral glucose tolerance test (OGTT). They were tested with the OGTT at 28-30 weeks of gestation. We also tested 12 normal patients and 10 consecutive patients with gestational diabetes; all were at the same gestational age. Plasma levels of insulin and glucose were determined in the samples collected for a period of four hours after glucose load (100 g). All PCOD patients significantly increased their insulin secretion in pregnancy. The hyperinsulinemic PCOD patients developed gestational diabetes (two patients) and impaired gestational glucose tolerance (three patients). The area under the insulin curve was greater in PCOD patients than in control and gestational diabetes patients (P < .01). In spite of their large increase in insulin secretion observed during pregnancy, patients with PCOD may develop a derangement of glycemic control, probably related to their pregestational insulinemic status.