Recurrent urinary tract infections are a problem for many postmenopausal women. Estrogen replacement restores atrophic mucosa, lowers vaginal pH, and may prevent urinary tract infections. We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a randomized, double-blind, placebo-controlled trial of a topically applied intravaginal estriol cream. Midstream urine cultures were obtained at enrollment, monthly for eight months, and whenever urinary symptoms occurred. Vaginal cultures and pH measurements were obtained at entry and after one and eight months. The women were assigned to receive either estriol (n = 50) or placebo (n = 43), both administered intravaginally; 36 and 24, respectively, completed the eight months of follow-up. The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo (0.5 vs. 5.9 episodes per patient-year, P < 0.001). Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection (P < 0.001). Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women (61 percent) but in none of the 24 placebo recipients (P < 0.001). With estriol the mean vaginal pH declined from 5.5 to 3.8 (P < 0.001), whereas there was no significant change with placebo. The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged (from 67 to 63 percent) in the placebo recipients (P < 0.005). Side effects were minor, but caused 10 estriol recipients (28 percent) and 4 placebo recipients (17 percent) to discontinue treatment. The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women, probably by modifying the vaginal flora.
To assess the outcome of pregnancy following assisted conception. Cohort descriptive study. Unit of Reproductive Medicine, Ninewells Hospital and Medical School. One hundred and forty-eight consecutive assisted conceptions. Patient characteristics and outcome of pregnancy. Seventy-nine percent of mothers were aged between 26 and 35 years (mean 31.4). The main causes of infertility were tubal (48%), unexplained (35%), anovulatory (8%) and male factor (8%). Primary infertility accounted for 61% of cases and 82% of pregnancies occurred within 3 treatment cycles. Thirty-five (24%) pregnancies miscarried before 14 weeks and 7 (5%) between 15 and 24 weeks gestation. One hundred and three pregnancies resulted in 136 liveborn infants. There was one neonatal death. Thirty-five babies were admitted to SCBU. Antenatally, 13% of patients were admitted to hospital with hypertension and 8% with APH; 50% of multiple and 13% of singleton pregnancies were delivered prematurely, 68% following preterm labour. There were 28 sets of twins (four miscarried at less than 24 weeks) and four sets of triplets. Multiple pregnancy was not associated with cause of infertility, treatment, age or ovarian hyperstimulation syndrome. Seventy-eight per cent of singletons and 50% of multipara were delivered vaginally. Our data confirm the high incidence of pregnancy loss and preterm delivery associated with assisted conception once allowing for the high rate of multiple pregnancies. The effect of assisted conception programme on health services is discussed.
To evaluate the ability of the two currently available surgical barriers, oxidized regenerated cellulose and expanded-polytetrafluoroethylene (PTFE), to prevent postsurgical adhesions.
Murine uterine horns were approximated in the midline and the contacting uterine surfaces injured by electrocautery, cutting, and scratching, with and without barriers interposed. Sham-operated and experimental animals had adhesions assessed visually and histologically 7 days postoperatively. In another group, adhesions were created and then lysed 7 days later with barriers interposed. Readhesion formation was assessed 14 days after lysis with the PTFE being removed 7 days after lysis.
Adhesions occurred at 58.5% of the electrocautery sites without barriers, 100% of the readhesion sites with recautery for hemostasis, and 92% of the recautery sites without hemostasis. None of the sham-operated sites developed adhesions. When oxidized regenerated cellulose was interposed, adhesions were observed at 36% of uninjured uterine horn sites, 62% with single and 92% with double electrocautery injuries and 90% of the reformation sites. The PTFE did not cause adhesions in uninjured controls and completely prevented adhesion formation and reformation, regardless of the type of injury or whether hemostasis was achieved. A thin cellular membrane, continuous with the uterine serosa, enveloped the PTFE. Expanded-polytetrafluoroethylene, but not oxidized regenerated cellulose, prevents adhesion formation and reformation in this murine uterine horn model. Additionally, oxidized regenerated cellulose was adhesiogenic even without surgical injury.
The Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study examines the risk factors of osteoporosis, the relationship of risk factors to bone density and fractures, as well as the possibility to prevent bone loss by administering certain hormones. The baseline postal enquiry in 1989 was sent to all the 14,220 women aged 47-56 years residing in the Kuopio Province, Finland. The questionnaire included questions about their gynaecological history, physical exercise and smoking habits, calcium intake, body weight and height, history of bone fractures, health disorders, their current and previous use of drugs, as well as their willingness to participate in bone densitometry and in a clinical hormone trial. The response rate was 92.8%. In all, 56% reported some previous use of female hormones. Strong contraindications for oestrogen replacement therapy were found in 9.3% of the women. Almost half of the respondents reported lack of regular physical exercise, 11.9% were smokers, and 17.0% reported a calcium intake from milk products of less than 500 mg daily. The incidence of fractures increased steadily with age. The incidence of premenopausal fractures within the last 10 years was 7.65 per 1000 person/years and that of postmenopausal fractures was 17.40 per 1000 person/years (P = 0.000). The effect of menopause on fracture incidence was stronger than the effect of a 5-year age increase. Of the respondents, 84.4% were willing to participate in bone densitometry and 68.3% for long-term prevention of osteoporosis with oestrogen.
Mårtensson O et al., 1993·Acta Obstet Gynecol Scand
In 25 women with primary or secondary infertility, primary hysterosalpingography (HSG) or laparoscopy with chromopertubation indicated 33 proximal and 2 distal tubal obstructions. Four salpingectomies had been performed earlier. All patients were considered for transcervical catheter salpingoplasty (TCSP) to reconstruct tubal patency. Secondary examination with repeat HSG or selective osteal salpingography confirmed 26 proximal and 3 distal tubal occlusions while 17 tubes were patent. Selective osteal salpingography was performed successfully in 32 of 33 (97%) tubes. Sixteen of 26 (61.5%) proximally occluded tubes were successfully recanalized by coaxial catheter and guidewire technique while two of three distally occluded tubes were reopened by forceful flushing of contrast medium. So far, one ectopic and five intrauterine pregnancies were achieved in ten patients with observation time more than four months. Three patients have had normal deliveries. The favorable results, lack of complications and low costs seem to justify the recommendation to use selective salpingography and fallopian tube recanalization as the first intervention in patients with obstruction of the proximal fallopian tube.
Adhesion re-formation after a reproductive operation, particularly involving the pelvic sidewall, is a prominent cause of failure in the surgical treatment of infertility. This study was done to evaluate the impact of standard microsurgery through laparotomy and the additional benefit of an oxidized regenerated cellulose adhesion barrier (INTERCEED [TC7] Absorbable Adhesion Barrier [Ethicon Inc.]), in reducing pelvic sidewall adhesion re-formation. One hundred and thirty-four patients with bilateral pelvic sidewall adhesions undergoing adhesiolysis by standard microsurgical techniques through laparotomy were treated during a prospective randomized trial involving 13 centers. After adhesiolysis, the deperitonealized surface of one pelvic sidewall was randomly assigned to be covered with INTERCEED Barrier, the contralateral sidewall serving as control. A second-look laparoscopy was performed ten days to 14 weeks postoperatively. Microsurgical adhesiolysis alone resulted in 24 percent of the sidewalls becoming free of adhesions and a 55.6 percent reduction in the area of adherent peritoneum. With microsurgery alone, 60 and 39 percent of adhesions initially characterized as filmy or severe, respectively, were not seen at second-look laparoscopy. The use of INTERCEED Barrier increased the incidence of adhesion-free sidewalls twofold. The treatment was also associated with a statistically significant reduction in the area of peritoneum affected by adhesion re-formation, compared with the control wall. Of the adhesions originally graded as severe, 61 percent of those treated with INTERCEED Barrier did not re-form at all. When evaluated on filmy adhesions, the use of the barrier was associated with a 72 percent reduction in adhesion re-formation. A measurable reduction in adhesion re-formation was found, depending on the initial adhesion type, with microsurgery alone. The addition of INTERCEED Barrier further reduced the incidence, extent and severity of postoperative adhesion re-formation. In this study, 90 percent of the patients benefited from the use of INTERCEED Barrier.
Fulghesu AM et al., 1993·Obstetrics and gynecology
To evaluate the involvement of endogenous opiates in the pathophysiology of the hyperinsulinism in patients affected by polycystic ovary disease by administering naloxone and naltrexone. We also studied the hormonal status following long-term opioid antagonist administration. Twenty-one women affected by polycystic ovary disease participated in the study. An oral glucose tolerance test (GTT) was performed at baseline and repeated after short-term naloxone infusion and after 6 weeks of naltrexone administration. Plasma glucose and insulin levels were evaluated in all samples. Gonadotropins, sex hormone-binding globulin, and androgen levels were determined initially and after the naltrexone treatment. None of the patients showed any alteration of glucose tolerance. Based on the insulin response to the GTT, the patients were classified as normo- or hyperinsulinemic. Opioid antagonist administration significantly reduced the insulin response to the GTT in hyperinsulinemic patients, without affecting their glycemic levels. In normoinsulinemic patients, glucose plasma levels were increased whereas insulin levels were not modified by the treatments. Gonadotropin and androgen plasma concentrations were not modified after naltrexone administration. This work supports a role for the endogenous opiates in the regulation of exaggerated insulin secretion in patients with polycystic ovary disease. The reduction of insulin secretion failed to demonstrate any hormonal modification in such hyperandrogenized patients.
To evaluate the involvement of endogenous opiates in the pathophysiology of the hyperinsulinism in patients affected by polycystic ovary disease by administering naloxone and naltrexone. We also studied the hormonal status following long-term opioid antagonist administration. Twenty-one women affected by polycystic ovary disease participated in the study. An oral glucose tolerance test (GTT) was performed at baseline and repeated after short-term naloxone infusion and after 6 weeks of naltrexone administration. Plasma glucose and insulin levels were evaluated in all samples. Gonadotropins, sex hormone-binding globulin, and androgen levels were determined initially and after the naltrexone treatment. None of the patients showed any alteration of glucose tolerance. Based on the insulin response to the GTT, the patients were classified as normo- or hyperinsulinemic. Opioid antagonist administration significantly reduced the insulin response to the GTT in hyperinsulinemic patients, without affecting their glycemic levels. In normoinsulinemic patients, glucose plasma levels were increased whereas insulin levels were not modified by the treatments. Gonadotropin and androgen plasma concentrations were not modified after naltrexone administration. This work supports a role for the endogenous opiates in the regulation of exaggerated insulin secretion in patients with polycystic ovary disease. The reduction of insulin secretion failed to demonstrate any hormonal modification in such hyperandrogenized patients.
To evaluate publications that introduced novel diagnostic and therapeutic transcervical procedures on the fallopian tubes. Major studies that conceptually changed the therapeutic approach to the fallopian tubes were reviewed. Minor publications were also included if they introduced a new concept or contributed to the topic. Clinical publications were selected if they involved transcervical diagnosis and treatment of fallopian tubes. Transcervical tubal catheterization procedures for diagnosis of tubal disease, tubal obliteration, tubal recanalization, and tubal medication are minimally invasive procedures that can improve our understanding and diagnostic accuracy of tubal disease. These procedures allow transcervical treatment of proximal tubal occlusion. Further improvements in equipment and methodology are promising. Transcervical tubal occlusion, gamete and embryo deposition, and treatment of ectopic pregnancy may all be performed using the transcervical approach. Transcervical tubal catheterization can replace microsurgery and IVF in selected patients with proximal tubal occlusion, improve the diagnostic accuracy of tubal disease, and deliver medications to the fallopian tubes. Cumulative knowledge suggests that transcervical tubal catheterization should become a universally accepted, taught, and practiced approach in the diagnosis and treatment of the fallopian tubes.
General OB/GYNSex Differences in DiseasePrevention StrategiesSex-Based Research Gaps
Each year approximately 2.5 million U.S. women are hospitalized for cardiovascular illness, which also claims the lives of 500,000 women annually; half these deaths are due to coronary heart disease1. Despite the magnitude of this problem and its adverse repercussions on the national public health, we have insufficient information about preventive strategies, diagnostic testing, responses to medical and surgical therapies, and other aspects of cardiovascular illness in women. This lack of information is compounded by the less frequent participation of women in research studies; the difference has been due in part to the exclusion of women of childbearing age and in part to the exclusion of elderly women because of their frequent coexisting illnesses2-4. Characteristics of patients and physicians that limit the participation of women in clinical trials and sex-specific psychosocial or economic factors remain largely unexplored.
There is increasing evidence that women undergo intensive or invasive evaluations and treatments for cardiac diseases substantially less frequently than do men with symptoms of similar or lesser severity; this is particularly true for the evaluation of chest pain5-7. The contributions to the differences in the use of procedures of physicians' attitudes toward women patients and their symptoms, different choices made by women themselves, and cultural or social attitudes about sex differences must be assessed, but of pivotal importance is the relation between the use of procedures for women and the clinical outcomes of cardiovascular illness.
In January 1992, the National Heart, Lung, and Blood Institute convened an invitational conference, “Cardiovascular Health and Disease in Women,” to highlight new information derived from epidemiologic and clinical research that was appropriate for clinical application and that required wider dissemination and to identify gaps in contemporary knowledge that impeded the delivery of optimal cardiovascular care to women8. In addition to addressing general issues of the cardiovascular health of women, this article summarizes the recommendations of the conference.
Perimenopause/MenopauseEstrogen CardioprotectionCoronary Artery Disease in WomenRandomized Crossover Trial
Oestradiol-17 beta causes relaxation of isolated coronary arteries and increases blood flow in several vascular beds in human beings and animals. Oestrogen replacement therapy is associated with a lower incidence of cardiovascular disease, but the acute effects of oestradiol-17 beta on myocardial ischaemia are unknown. We have studied the acute effect of sublingual oestradiol-17 beta on exercise-induced myocardial ischaemia in eleven women (mean age 58 [SD 8] years) with coronary artery disease. The women did two treadmill exercise tests on separate days; 40 min before the test they took sublingual oestradiol-17 beta (1 mg) or placebo, in random order. Plasma oestradiol-17 beta concentrations were confirmed to be higher after sublingual oestradiol-17 beta than after placebo (2531 [1192] vs 155 [168] pmol/L, p < 0.001). Oestradiol-17 beta increased both time to 1 mm ST depression (456 [214] vs 579 [191] s, p < 0.004; difference of medians 92 [95% CI 46-254]) and total exercise time (569 [249] vs 658 [193] s, p < 0.01; difference 54 [10-212]). Acute administration of oestradiol-17 beta therefore has a beneficial effect on myocardial ischaemia in women with coronary artery disease. This effect may be due to a direct coronary-relaxing effect, to peripheral vasodilation, or to a combination of these mechanisms. Oestradiol-17 beta may prove to be a useful adjunct to the treatment of angina in postmenopausal women with coronary heart disease.
To evaluate the incidence and extent of periovarian adhesion formation subsequent to laparoscopic electrocoagulation of the ovarian surface in infertility patients with polycystic ovarian disease (PCOD). From a total of 199 PCOD patients treated with ovarian electrocautery, 50 cases of laparoscopy and 12 cesarean sections served as second-look investigation. A subgroup of 30 patients had abdominal lavage and artificial ascites after surgery; they underwent "early" second-look (2 to 14 days after laparoscopy). All patients were referred to our fertility outpatient clinic affiliated with the university hospital. Infertility patients with polycystic ovarian reaction to hormonal stimulation therapy underwent laparoscopic electrocoagulation of the ovarian surface. Adhesion formation was detected in 19.3%; the incidence reduced to 16.6% with the use of abdominal lavage. The adhesions found were obviously due to bleeding of the ovarian capsule caused by electrocautery. Adhesiolysis was easily possible during "early" second-look. The incidence of de novo adhesion formation caused by laparoscopic electrocoagulation of the ovarian surface seems to be lower than after ovarian wedge resection; it can be reduced by abdominal lavage and artificial ascites.
EndometriosisMalignant TransformationOvarian CancerAssociation with Neoplasm
In 556 patients undergoing surgery for ovarian cancers the frequency of endometriosis ranged from 3.6% to 5.6% in serous, mucinous, and miscellaneous neoplasms versus 26.3%, 21.1%, and 22.2%, respectively, in endometrioid, clear cell, and mixed subtypes; the differences were statistically significant (chi 2 heterogeneity 50.0, p < 0.001) and consistent in strata of age, parity, menopausal status, and disease stage.
Women diagnosed as suffering from premenstrual syndrome and symptom free controls were compared on hormonal parameters, glucose tolerance, mineralocorticoids, cholesterols, triglycerides, apolipoprotein (a), magnesium and calcium in the follicular and luteal phases of the menstrual cycle. The effect of treatment with essential fatty acids on the biochemical variables was also evaluated in a randomized, double-blind crossover design. The results showed that the hormonal and biochemical profiles of women with PMS and symptom free controls were markedly similar, except for aldosterone which was lower in the follicular and luteal phases and cholesterol which was higher in the follicular phase in women with PMS. No effects of treatment with essential fatty acids were found for any of the biochemical variables studied.
InfertilityService UtilizationSociodemographic DisparitiesNational Survey of Family Growth
To examine the characteristics of women in the 1988 National Survey of Family Growth who reported having obtained medical services for impaired fecundity. From a national sample of 8450 women between the ages of 15-44, drawn from the civilian, noninstitutionalized population of the entire United States in 1988, we estimated the use of infertility services in the United States. Multivariate statistical modeling was used to identify the characteristics associated with use of infertility services among the 770 women who reported impaired fecundity in this survey. Of all women with impaired fecundity, 43% had obtained some form of infertility service and 24% had obtained specialized infertility treatment--ovulation drugs, treatment of fallopian tubes, artificial insemination, or in vitro fertilization. Older, white, married women of higher socioeconomic status were most likely to have obtained specialized services, and a history of endometriosis was also strongly associated with having received such services. Most women with impaired fecundity had not obtained infertility services. Use of specialized services was strongly associated with certain sociodemographic variables or a history of endometriosis.
Bone HealthBone Resorption MarkersTransdermal vs OralPostmenopausal Women
To evaluate and compare the effects or oral and transdermal estrogen replacement therapy on biochemical markers of bone resorption in early postmenopausal women. Controlled, randomized group comparison. Outpatient clinic for menopausal women and research into osteoporosis. Sixty healthy women menopausal for less than 5 years and who had never received any medications interfering with bone metabolism. The 60 women were randomly allocated to 3 months therapy with either oral conjugated estrogens (0.625 mg/day) (n = 28) or transdermal estradiol (50 micrograms/day) (n = 32) in cyclical combination with medroxyprogesterone acetate (5 mg/day). Traditional (urinary calcium/creatinine and hydroxyproline/creatinine) and the new specific (urinary pyridinoline/creatinine and deoxypyridinoline/creatinine) markers of bone resorption were determined before and after 3 months of treatment. In both groups, circulating levels of estrone and estradiol were significantly (P < 0.001) increased during treatment. In women treated with oral conjugated equine estrogens, urinary calcium/creatinine and hydroxyproline/creatinine ratios were significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 69.1 (4) [mean (SEM)] to 50 (4) mumol/mumol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 10.8 (1) [mean (SEM)] to 8.3 (0.8) mumol/mumol (P < 0.01). In the group treated with transdermal estradiol, urinary hydroxyproline/creatinine ratio was significantly (P < 0.05) reduced. Pyridinoline/creatinine ratio fell from 66.3 (4) [mean (SEM)] to 46.2 (3) mumol/mumol (P < 0.01) and deoxypyridinoline/creatinine ratio fell from 11.5 (1.5) [mean (SEM)] to 7.7 (0.6) mumol/mumol (P < 0.01). There were no differences between the evolution of the biochemical variables in the two groups. These results suggest that oral conjugated equine estrogens and transdermal estradiol, in the given doses, are equally effective in reducing postmenopausal bone resorption.
Reproductive EndocrinologyPharmacokineticsRoute of AdministrationProgesterone Formulations
To examine the effects of food ingestion and administered dose on the absorption of oral micronized P (Utrogestan; Besins-Iscovesco, Paris, France) and to compare the bioavailability of intramuscular versus oral routes of administration. Prospective, randomized, open label crossover protocol with 7 days between dosages. Academic institution. Fifteen normal postmenopausal women. All subjects participated [1] micronized P (200 mg) or placebo under fasting or nonfasting conditions once daily for 5 days; [2] micronized P (100, 200, or 300 mg) once daily under fasting conditions for 5 days; and [3] micronized P (200 mg) or intramuscular P (50 mg in oil) administered once daily for 2 days. Serum P concentrations were measured in all groups. Concomitant food ingestion increased the area under the serum P concentration versus time curve (AUC0 to 24) and the maximum serum P concentration (Cmax) without affecting time to maximum serum concentration (Tmax) (P < 0.05). Micronized P absorption and elimination were first-order processes and exhibited dose-independent pharmacokinetics between 100 and 300 mg. After intramuscular P, Cmax was higher and Tmax occurred later compared with the oral P preparation. Oral P had lower relative bioavailability (8.6%) than intramuscular P. Absorption of micronized P was enhanced twofold in the presence of food. Both absorption and elimination were dose-independent, dose proportionality being confirmed. Bioavailability of the oral P was approximately 10% compared with intramuscular P.
To assess the endocrinologic and clinical outcome after laparoscopic ovarian electrocautery because of polycystic reaction to ovarian stimulation in anovulatory infertility patients. Between 1986 and 1989, 133 patients with polycystic ovarian disease underwent laparoscopic electrocoagulation of the ovarian surface in an outpatient clinic after conventional ovarian stimulation had led to polycystic reaction. All patients were referred to our outpatient clinic affiliated with the university hospital. The reduction of androgen levels and normalization of cycle length were highly significant. The overall pregnancy rate was 70% (73 of 104), ranging from 27% in smokers to 94% in nonsmoking couples. In 26 second-look operations de novo adhesions were found in 26.9% of the patients. Laparoscopic coagulation of the ovarian surface is an effective tool to reduce elevated androgen levels and to improve the intraovarian mechanism of selecting a dominant follicle. A postoperative complication may be adhesion formation.
EndometriosisPeritoneal FluidAngiogenesis and Growth FactorsPeritoneal Factor
To review and evaluate published studies that have examined the role of peritoneal fluid (PF) in the development of endometriosis. Important studies related to this topic have been identified through a computerized bibliographical search (MEDLINE), as well as by manually scanning the published literature of major reproductive journals over the last several years. Studies that examined the effect of PF or its components on the pathophysiology of endometriosis are discussed. These include reported effects on the histogenesis, maintenance and proliferation of endometriosis, as well as related actions on infertility. The majority of investigations into the role PF plays in the pathogenesis of endometriosis have evaluated how it may adversely affect fertility. Suggestive but inconclusive data in the literature indicate that degenerating endometrial tissue may release a biochemical factor(s) into the peritoneal environment that is capable of inducing ectopic endometrium formation. Peritoneal fluid itself contains growth factor that may play a role in the implantation and maintenance of the ectopic endometrium. The PF of women with endometriosis has been shown to contain angiogenic as well as other growth factors. These compounds may contribute to the proliferation of the ectopic endometrium.
General OB/GYNEndometrial CancerCancer RiskInsulin Resistance
Insulin is a major regulator of circulating insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), suppressing the hepatic production of IGFBP-1. Postmenopausal age, obesity, hypertension, and impaired glucose tolerance, which are known risk factors for endometrial cancer, are all associated with hyperinsulinemia and insulin resistance. In this study, we investigated the relationship among serum insulin, glucose, insulin-like growth factors (IGF-I and IGF-II), and IGFBP-, -2, and -3 in 32 nondiabetic postmenopausal women with endometrial cancer and in 18 healthy controls. The mean fasting levels of glucose and insulin were higher, whereas the mean basal IGF-I, IGF-II, and IGFBP-3 levels were lower in the endometrial cancer patients than in the healthy control subjects. The mean fasting IGFBP-1 and IGFBP-2 levels did not differ between the groups, and no correlation was found between fasting insulin and IGFBP-1 concentrations or between insulin and IGFBP-2 concentrations in either of the study groups. During an oral glucose tolerance test, the mean glucose levels at 1 and 3 h as well as the mean insulin level at 3 h were significantly higher in the endometrial cancer patients than in the controls, and the area under the glucose curve was larger in the first group. An oral glucose load resulted in a similar fall in serum IGFBP-1 levels in endometrial cancer patients and controls (51% and 55% at 3 h). When the cancer patients were divided into two subgroups according to the body mass index (kilograms per m2), the obese group had higher glucose and insulin indices than the nonobese group. No difference was found by the same measures in healthy controls. The fasting serum IGFBP-1 levels tended to be lower in the obese than in the normal weight subjects, but the difference did not reach statistical significance. In summary, these results provide preliminary evidence that the inverse relation between fasting insulin and IGFBP-1, well established in children and young adults, disappears in elderly women, although short term suppression by insulin still occurs. Further, our data indicate that in addition to carbohydrate metabolism, postmenopausal women with endometrial cancer have alterations in their circulating IGF system compared to controls.
Published studies relating to the usefulness of diagnostic and operative laparoscopy in women with chronic pelvic pain (CPP) were reviewed. This revealed that approximately 40 per cent of all laparoscopies were done for CPP. However, the definition of CPP was found to be nebulous and inconsistent, and that muddled definitive conclusions about patient diagnoses and treatments. The following nonmenstrual pain of 3 or more months duration that localizes to the anatomic pelvis and is severe enough to cause functional disability and require medical or surgical treatment. A survey of published reports showed laparoscopically diagnosable abnormalities in 61 per cent of patients, compared with abnormalities in 28 per cent of women without CPP. Studies in adolescents were also reviewed and showed that adolescents with CPP also had significant laparoscopically diagnosed abnormalities, with 78 per cent showing some pathology, especially endometriosis (40 per cent). Endometriosis, pelvic adhesions, chronic pelvic inflammatory disease, and ovarian cysts were the diagnoses most commonly made via laparoscopy in CPP patients. The potential roles of each of these abnormalities in CPP were discussed, as well as the results of laparoscopic treatment of each disease. Laparoscopy was also found to have a limited role in women with CPP after hysterectomy or bilateral salpingo-oophorectomy, with usefulness in diagnosing and treating adhesions and residual ovary syndrome, although its role in ovarian remnant syndrome was uncertain. Overall, the data showed that less than 50 per cent of women with CPP were helped by diagnostic and operative laparoscopy, stressing the need for both physicians and patients to recognize that laparoscopy is neither the ultimate evaluation nor the panacea for CPP.
MRC/RCOG Working Party on Cervical Cerclage, 1993·Br J Obstet Gynaecol
To assess whether cervical cerclage in women deemed to be at increased risk of cervical incompetence prolongs pregnancy and thereby improves fetal and neonatal outcome. Multicentre randomised controlled trial. Hospitals in the United Kingdom, France, Hungary, Norway, Italy, Belgium, Zimbabwe, South Africa, Iceland, Ireland, the Netherlands and Canada. One thousand two hundred and ninety-two pregnant women whose obstetricians were uncertain whether to recommend cervical cerclage, most of whom had a history of early delivery or cervical surgery. Cervical cerclage was compared with a policy of withholding the operation unless it was considered to be clearly indicated. Delivery before 33 completed weeks, preterm delivery (< 37 weeks), and vital status of the baby after completion of the pregnancy. The overall preterm delivery rate was 28%. There were fewer deliveries before 33 weeks in the cerclage group (83 (13%) compared with 110 (17%), P = 0.03) and this difference reflected deliveries characterised by features of cervical incompetence (painless cervical dilatation and prelabour rupture of the membranes). There was a corresponding difference in very low birthweight deliveries (63 (10%) compared with 86 (13%), P = 0.05). The difference in the overall rate of miscarriage, stillbirth or neonatal death (55 (9%) compared with 68 (11%)) was less marked and was not statistically significant. The use of cervical cerclage was associated with increased medical intervention and a doubling of the risk of puerperal pyrexia. These results suggest that the operation had an important beneficial effect in 1 in 25 cases in the trial (95% confidence interval (CI) 1 in 12 to 1 in 300 sutures). Its use is associated with increased medical intervention and puerperal pyrexia. Nevertheless, this trial suggests that, on balance, cervical cerclage should be offered to women at high risk, such as those with a history of three or more pregnancies ending before 37 weeks gestation.
Premenstrual syndrome (PMS) is a menstrual cycle-related disorder of mood and behavior with unknown etiology and lack of evidence of endocrine imbalances. The absence of menstrual cyclicity eliminates PMS symptoms, and cyclic gonadal changes appear necessary but not sufficient cause for behavioral symptoms in predisposed women. As there are many depressive symptoms in PMS, we focused on the neuroendocrine characteristics of depression, primarily hypothalamic-pituitary-adrenal hyperactivity, and investigated plasma adrenocorticotropin (ACTH) and cortisol levels in the menstrual cycle. Blood samples were drawn daily from ten patients with PMS and eight asymptomatic control subjects who also reported symptoms daily throughout one menstrual cycle. The ACTH levels were significantly lower in patients with PMS compared to control subjects in the luteal phase. Two PMS subgroups were identified by cluster analysis applied to symptom scores. Plasma ACTH levels of PMS Cluster 1 subjects were significantly lower compared to controls. The ACTH levels of PMS Cluster 2 subjects were nearly identical to controls. These preliminary results suggest distinct hormonal subgroups in the heterogeneous PMS population and support further study of ACTH as a biological correlate of PMS.
General OB/GYNEmbryo Transfer PolicyMultiple Pregnancy PreventionEmbryo Management
To limit the high number of multiple pregnancies in an IVF program. In Vitro Fertilization Laboratory, Fertility Department, Public Hospital. The number of embryos transferred was limited to two instead of three. Limiting the number of embryos transferred to only two did not influence the take home baby rate but eliminated triplet and quadruplet gestations. Moreover, the number of patients with good quality supernumerary embryos available for cryopreservation increased. To reduce the high frequency of multiple gestations in an IVF program, the number of embryos replaced should be limited to a maximum of two.
InfertilityClomiphene Citrate Side EffectsClomiphene EffectsDrug-Induced Changes
To analyze the effects of clomiphene citrate (CC) on cervical mucus (CM) and endometrial morphology independently of hormonal changes encountered when CC is administered for ovulation induction. Volunteers whose ovarian functions were temporarily suppressed (n = 18) by a long-acting GnRH agonist and 6 women of similar age suffering from premature ovarian failure (POF) received E2 and P. Half of the women also received CC (50 mg/d, days 2 to 6). Tertiary University Institution, Hôpital A. Béclère. PATIENTS, Eighteen volunteers suffering from infertility not related to a uterine cause and 6 women of similar age suffering from POF. Plasma gonadotropins, E2, and P were measured at baseline to confirm that the ovaries were inactive and twice weekly during physiological E2 and P replacement. Cervical mucus was analyzed on day 14 and scored from 0 to 15. Endometrial biopsies were obtained on replacement days 20 and 24 for conventional histology and immunocytochemistry analysis of estrogen receptors and progesterone receptors (PR). Premature ovarian failure women whose results have been previously published served as controls for day 20 biopsies. Cervical mucus scored lower in women who received CC (5.5 +/- 3.2) than in controls (13.6 +/- 4.7, mean +/- SEM). On day 20, endometrial findings were similar in women treated with CC and in controls. On day 24, specimens showed a significant delay in endometrial maturation in women treated with CC. On day 24, only staining for PR selectively persisted in endometrial stroma, and no difference was observed between women who received CC and controls. Our results indicate that CC significantly alters CM quality and late luteal phase endometrial morphology despite physiological levels of plasma E2 and P. Hence, clinicians should monitor E2 levels when using CC, and caution should be exerted when supraphysiological levels of E2 are not present to counterbalance the effects of CC on the CM and the endometrium.
To compare the effect of hCG therapy with placebo or bed rest in women with threatened abortion. Random assignment, double-blind. Community hospitals. Sixty-one women with viable pregnancies under 8 weeks' gestation on admission to hospital were randomly allocated to receive injections of hCG or placebo, or were advised to rest in bed. Abortion vs. continuation of pregnancy at 16 weeks' gestation. Thirty-one 6/20 on hCG, 10/21 on placebo, 15/20 on bed rest. hCG vs. bed rest, P < .01; placebo vs. bed rest, hCG vs. placebo--not significant. continuing pregnancy > abortion, P < .01; continued with hCG vs. aborted on placebo, P < .001; continued with hCG vs. aborted with bed rest, P < .001. No significant differences in pregnancy/birth complications or infants' birth weight. Female/male ratio was 2:1. hCG is significantly better than bed rest.
Induction of ovulation is indicated for anovulatory and amenorrheic women as well as for women who have an inadequate luteal phase. It is also indicated as a strategy for recruiting multiple follicles for women with unexplained infertility and those who are undergoing assisted reproductive technologies. The use of various agents and detection of ovulation are described. This includes a discussion of clomiphene citrate, bromocriptine, human menopausal gonadotropins, urinary follicle stimulating hormone and pulsatile gonadotropin releasing hormone therapy. Regimens, success rates and potential complications of each form of therapy are reviewed. Also discussed is the use of combination therapy and partial ovarian destruction.
Body LiteracyPro-Life PerspectiveValue of LifeEthical Foundations
We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.
Studies to evaluate use-effectiveness and cost-effectiveness of natural family planning (NFP) were conducted in Liberia and Zambia. The Liberian programme provided uni-purpose NFP services to 1055 clients mainly in rural areas; the Zambian programme provided NFP services integrated with MCH to 2709 clients predominantly in urban areas. The one-year life table continuation and unplanned pregnancy rates were 78.9 and 4.3 per 100 woman-years in Liberia, compared to 71.2 and 8.9 in Zambia. However, high rates of loss to follow-up mandate caution in interpretation of these results, especially in Zambia. More women progressed to autonomous NFP use in Liberia (58%) than in Zambia (35.3%). However, programme costs per couple-year protection were lower in Zambia (US$25.7) than in Liberia (US$47.1). Costs per couple-year protection were higher during learning than autonomy, and declined over time. These studies suggest that NFP programmes can achieve acceptable useand cost-effectiveness in Africa.
Serum progesterone (P) levels were determined at the time of routine prenatal registration (227 patients) or upon presentation for evaluation of vaginal bleeding and/or abdominopelvic cramping/pain (135 patients). P associated with a normal intrauterine gestation was 24.63 +/- 4.19 (SD) ng/mL as compared with 6.29 +/- 2.43 ng/mL and 6.02 +/- 2.39 ng/mL for spontaneous abortions and ectopic gestations, respectively. Further, P differed between asymptomatic (11.92 +/- 9.61 ng/mL) and symptomatic patients (4.81 +/- 3.92 ng/mL) who were subsequently shown to have an abnormal gestation. By establishing a P cutoff point of < or = 14.2 ng/mL and < or = 10.5 ng/mL in asymptomatic and symptomatic patients, respectively, 100% screening sensitivity was reached, and therefore no abnormal gestations would escape detection in our study population. P was either in the normal or abnormal range as early as four weeks' estimated gestational age and persisted as such through the luteal-to-placental shift and up to the time of pregnancy loss or 12 weeks' estimated gestational age. Although there was no significant correlation between P and chorionic gonadotropin levels and pregnancy outcome, the binding constant for native chorionic gonadotropin was 15-52 times lower in 12 of 41 cases of spontaneous abortion but not ectopic gestation, suggesting a possible molecular basis for suboptimal P production. P is therefore an excellent adjunctive marker for prediction of early pregnancy outcome, and in some cases qualitative abnormalities in chorionic gonadotropin may dictate its production.
Our aim was to determine the efficacy and safety of tocolytic agents currently used to treat premature labor. We carried out a comprehensive review of tocolytic agents in the treatment of premature labor. Three hundred twenty-eight studies published between 1933 and 1992 were analyzed. An analysis of randomized, placebo-controlled, clinical trials showed that magnesium sulfate is not better than placebo in the treatment of premature labor. beta-Adrenergic receptor agonists effectively stop premature labor for only 24 to 48 hours. Calcium channel blockers and oxytocin antagonists inhibit uterine contractions, but their role in stopping labor is undefined. Prostaglandin inhibitors appear to be effective in treating premature labor and have few adverse side effects. The only tocolytic drugs that might be effective are the prostaglandin inhibitors. Tocolytic agents should be used only between 24 and 32 completed weeks of gestation. Magnesium sulfate should not be used to treat premature labor. Oxytocin antagonists should be used only in experimental clinical trials. Calcium channel blockers and beta-adrenergic receptor agonists inhibit uterine contractions but do not prolong gestation for longer than 48 hours.
Ovarian laparoscopic resection was applied to 23 sterile patients affected with polycystic ovarian disease (PCOD) resistant to different pharmacological treatments, in order to induce ovulation. After resection, 56% of the patients had spontaneous ovulatory cycles and 13 pregnancies arose. Ten of the pregnancies were spontaneous and three followed treatment with clomiphene. Hormone changes were assessed in 15 patients, including five with spontaneous menstruation but without ovulation and five with persistent amenorrhoea for 3 months after resection. A significant decrease in both androstenedione and testosterone levels occurred in all patients. These decreases were not related to the clinical results of resection. Luteinizing hormone (LH) did not vary greatly in any group after resection. Mean values and mean pulsatility of follicle stimulating hormone (FSH) increased significantly only in pregnant patients or those with spontaneous ovulatory cycles. The results of gonadotrophin-releasing hormone (GnRH) assays did not change after resection. The mechanisms involved in the resumption of cyclic function of the hypophyseal-ovarian axis after resection are discussed briefly.
InfertilityPsychosocial FactorsStress and ReproductionInfertility Risk Factors
An adaptive model for the evolution of reproductive failure predicted psychosocial stress to increase as anatomic causes of infertility decrease. The nonanatomic infertility group in our study reported greater psychosocial stress than intermediate (P < 0.008) or anatomic groups (P < 0.0005). Controls, women with nonanatomic etiologies who were not attempting pregnancy, also reported higher psychosocial stress than the anatomic group (P < 0.007). Results are consistent with the hypothesis that psychosocial distress contributes significantly to the etiology of some forms of infertility.
In a case-control study the effects of smoking and the use of oral contraceptives were examined in 83 patients with Crohn's disease and 37 patients with ulcerative colitis in comparison with members of the general population who served as controls. After controlling for oral contraceptives, smokers were found to have a significantly elevated relative risk of contracting Crohn's disease of 3.0 (1.3 to 6.8). Patients on oral contraceptives for more than three years had an elevated risk for Crohn's disease of 4.3 (1.3 to 14.4); this elevated risk was, however, found only in the non-smoking group. In the case of ulcerative colitis, the relative risk in smokers was significantly lower (0.21 [0.04 to 0.91]) than in non-smokers. The use of oral contraceptives does not represent a risk factor for ulcerative colitis. While smoking has been established as a risk factor in the development of inflammatory bowel disease, the role of oral contraceptives in the aetiology of this condition remains unclear.
More than half of new mothers may be affected by mood disorders after childbirth. Possible causes and recommended management depend on the type of disorder and its severity. In this article, Dr Knops discusses recognition, prevention, and management of three types of postpartum mood disorders as well as the need for support for a woman and her family at this vulnerable time.
Delangue AF, 1993·Soins Gynecol Obstet Pueric Pediatr
The Billings method, or cervical mucus method, is a natural family planning method developed during the 1970s by the Australian physicians John and Evelyn Billings. The method requires periodic abstinence during the periods recognized as fertile according to the characteristics of the mucus. The method can be used to avoid pregnancy or to favor it through identification of the day of maximum fecundity. The method does not alter the natural rhythms of the body or entail unpleasant side effects. At the beginning of the menstrual cycle, the cervix is closed by a mucus plug and the sperm survive less than two hours in the acidic environment of the vagina. Several days before ovulation, the cervix begins to secrete mucus that will protect the sperm from the acidity of the vagina and permit their passage to the uterus. Thus protected, the sperm can survive up to four days. Mucus at this stage has an elastic quality. After ovulation, the mucus thickens and becomes increasingly impenetrable to sperm. It feels sticky and gelatinous. The Billings method requires observation of the sensation of wetness or dryness and the characteristics of the mucus. Each evening the woman should note that day's observations on a chart. The "peak day" is the last day of elastic mucus that gives a sensation of wetness. The peak day is the most visible sign of ovulation and can be recognized only on the next day. The three days following the peak day are considered fertile, because ovulation can occur up to 48 hours after the peak and the ovum can survive up to 24 hours. If the Billings method is used to avoid pregnancy, intercourse should be avoided during menstruation as the appearance of mucus may be masked in a short cycle. Intercourse is permissible in the evening of every second day until the appearance of the mucus.
Data from the Oxford.FPA prospective study show that oral contraceptive use and pregnancy have no discernible effect on the risk of developing multiple sclerosis (MS). Women of parity 0-2 developed MS twice as often as women of parity 3 or more but the difference did not reach statistical significance. Smoking may be a risk factor for developing MS. A nested case-control analysis did not identify any associations between MS onset and preceding illnesses.
In clinical programs of assisted reproduction involving infertile males, it is essential to obtain semen of maximum quality. To evaluate ways of achieving this objective, and to assess the fertilizing capacity of the sperm, six semen samples were collected from each of 38 infertile men via masturbation. Six more samples were then collected from each man at sexual intercourse using a semen collection device (SCD). We confirmed that the volume of seminal plasma, total sperm count, sperm motility, and percentage of morphologically normal spermatozoa were significantly higher in samples collected at intercourse than masturbation, as reported previously. In addition, the markers of the secretory function of the prostate and the outcome of sperm function tests (hypoosmotic swelling test, acrosin assay, and sperm penetration assay) were significantly higher for the samples collected at intercourse. There were no significant differences in markers of the secretory function of the seminal vesicles and epididymis between the samples. The improved spermatozoal parameters in the samples collected at intercourse may reflect a higher prostatic secretory function at that time. There were no significant differences in the serum concentrations of gonadotropins, or in the serum or seminal plasma concentrations of testosterone, before or after masturbation or sexual intercourse. Therefore, the differences in prostatic secretory function and semen parameters may not be attributed to differences in hormonal levels. Semen collection during intercourse using an SCD appears to be the method of choice for selecting semen samples for artificial insemination.
EndometriosisFamilial and Genetic RiskReproductive Disease Heritability
Cervical mucus is produced throughout the menstrual cycle. Sperm migration, however, is possible only during the periovulatory period of the cycle. Cervical mucus is also produced during the amenorrhoeic post-partum period. Post-partum mucus is very similar to luteal phase mucus except that it can allow sperm migration. In this study, mucus samples obtained from all these periods were classified according to their capacity to allow sperm migration. The biochemical characteristics of mucus samples that did (peri-ovulatory and 40% of post-partum samples) and did not (luteal and 60% of post-partum samples) allow sperm migration were then compared. Mucus samples with positive sperm migration showed the highest percentage of water and lowest protein and glycoprotein concentration (per ml of mucus). In addition, post-partum mucus samples with positive sperm migration showed lower concentrations of proteins and glycoproteins than post-partum mucus samples that did not allow sperm migration. However, the amount of glycoproteins per mg of protein was similar between post-partum samples that were positive and negative for sperm migration. These data suggest that the carbohydrate composition of the glycoproteins is playing a key role in the ability of cervical mucus to accept spermatozoa.
Contraception/ComparisonBone Health OutcomesHormonal Contraception EffectsFracture Outcomes
It has been suggested that use of the oral contraceptive pill by women confers protection against osteoporosis later in life. However, cross-sectional studies of bone density among pill users have yielded discrepant results. We therefore investigated the relationship between pill use and subsequent occurrence of fracture in a cohort of 46,000 women enrolled in the Royal College of General Practitioners Oral Contraception Study during 482,083 person-years of follow-up. Fracture risk was lower among multiparous women, non-smokers, and those of lower socio-economic class. The risk of subsequent fractures among the women who had ever used the oral contraceptive pill was significantly greater than that among women who had never used it (relative risk 1.20, 95% confidence intervals 1.08-1.34) after adjustment for these variables. When the analysis was confined to forearm fractures, no significant effect of pill use on fracture risk was detected. Although the study only includes limited observation of older women to date, these data do not support the hypothesis that pill use protects women against the occurrence of osteoporotic fractures in later life.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1992. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
Preterm labor is defined as the onset of uterine contractions in a woman who has completed less than 37 weeks of pregnancy. It may be due to maternal, placental, fetal, or idiopathic causes, and it is associated with a number of risk factors. Nondrug measures such as bedrest and hydration have been used alone or in combination with drug therapy to treat the disorder. Pharmacologic (tocolytic) agents include ethanol, progesterone, indomethacin, nifedipine, beta-adrenergic agonists, and magnesium salts. The three most commonly used drugs are ritodrine, terbutaline, and magnesium.