Despite the widespread use of clomiphene citrate (CC) for ovulation induction, the pregnancy rates (PRs) in women who take CC are less than expected based on ovulation rates. The causes of this discrepancy between the PRs and ovulation rates have been explained by the antiestrogenic effects on cervical mucus and endometrial differentiation (1). Despite these adverse effects, CC therapy is so simple and safe that it is widely administered even to normally ovulatory women in the expectation of inducing multiple ovulation and increasing the chances of conception.
On the other hand, cyclofenil, which has been reported to exert less antiestrogenic activity than CC (2), is also used to treat infertile women with not only anovulatory cycles but normal ovulatory cycles. The purpose of this study was to assess whether administration of CC or cyclofenil to women with normal ovulatory cycles is beneficial.
One hundred fifty-five normally ovulatory women who received treatment for infertility at Shiga University of Medical Science from June 1998 to June 1999 were recruited for this study. Patients with ovulatory disorders, such as irregular cycles, hypothalamic or pituitary amenorrhea, polycystic ovary syndrome, premature ovarian failure, and hyperprolactinemia, were excluded from the study. Patients with bilateral tubal obstruction or azoospermia were also excluded.
Administration of CC or cyclofenil was withheld for a period of 3 months after the first visit while the timing of coitus was advised. Patients were advised to have sexual intercourse within 24 hours after confirmation of a positive urinary LH with a urinary LH surge detection kit (Gold-sign LH, Morinaga Nyugyo, Tokyo, Japan).
Then the patients who did not conceive were sequentially a CC-treated group, a cyclofenil-treated group, and a group with no administration. Briefly, the first patient enrolled in the study was assigned to a CC-treated group, the second patient was assigned to a cyclofenil-treated group, and the third patient was assigned to a group with no administration. Then the fourth patient was assigned to the CC-treated group, and so forth.
To evaluate whether some ultrasound parameters of ovarian morphology can discriminate between control women and patients with polycystic ovary syndrome (PCOS). Retrospective data analysis. Volunteers women in an academic research environment. PATIENT(S): Eighty amenorrheic or oligomenorrheic women and 30 normal ovulatory control participants. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We evaluated ovarian volume, area, stroma, and the stroma/total area (S/A) ratio by use of transvaginal pelvic ultrasound; and we assayed serum levels of gonadotropin, androgen, and estradiol during the early follicular phase (days 2 to 5) of the menstrual cycle in regularly cycling controls and on a random day in amenorrheic patients. RESULT(S): Patients with PCOS showed significantly higher ovarian volume, area, stroma, and mean S/A ratio when compared to multifollicular and control groups. Cut-off values have been defined for ovarian volume (13.21 mL), area (7.00 cm2), stroma (1.95 cm2), and S/A ratio (0.34). The sensitivity for PCOS diagnosis was 21%, 4%, 62%, and 100%, respectively. The S/A ratio showed the most significant correlation with the androgen levels. CONCLUSION(S): The evaluation of the S/A ratio can differentiate between PCOS and control or multifollicular women with both a sensitivity and a specificity of 100%. Furthermore, this ultrasound parameter is strictly related to hormonal milieu and to anthropometric characteristics.
To compare the karyotype of babies conceived through ICSI with that of naturally conceived babies. Prospective controlled study. The Egyptian IVF-ET Center, Cairo, Egypt. PATIENT(S): Four hundred and thirty babies conceived through ICSI and 430 babies conceived naturally. INTERVENTION(S): ICSI and karyotyping. MAIN OUTCOME MEASURE(S): Abnormal karyotype. RESULT(S): Four hundred and thirty consecutive babies conceived through ICSI who were delivered in one hospital had 15 abnormal karyotypes (3.5%). Of the 15 babies, 7 were of female phenotype and 8 of male phenotype. Six babies had sex chromosome anomalies, 8 had autosomal anomalies, and 1 had combined sex chromosome and autosomal anomalies. A control group of 430 consecutive babies conceived naturally who were delivered in one hospital had no abnormal karyotype. The difference between the two groups was significant (P<.001). CONCLUSION(S): ICSI carries a small but significant increased risk of abnormal karyotyping to the offspring. This risk appears to be equally distributed between autosomal and sex chromosome anomalies.
To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea. Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women. Clinical research center in an academic medical institution. PATIENT(S): Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement. INTERVENTION(S): Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires. MAIN OUTCOME MEASURE(S): Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders. RESULT(S): Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women. CONCLUSION(S): The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.
Bone HealthDietary RestraintSubclinical AnovulationMetabolic Factors
Women with high scores for dietary restraint have been found to have higher 24-h urinary cortisol excretion and a higher prevalence of subclinical ovulatory disturbances, both of which may be risk factors for bone loss. The purpose of this study was to explore relationships between dietary restraint and bone health in regularly menstruating young women. 62 women (age: 21.7 +/- 2.5 yr) had body composition and total body and lumbar spine bone mineral density (BMD) and content (BMC) assessed using dual-energy x-ray absorptiometry. Dietary restraint was assessed using the restraint subscale from the Three-Factor 29 women had low restraint (LR; restraint score 0--5), 33 had high restraint (HR; restraint score 13--21). Exercise (h x wk(-1)) was assessed by questionnaire on two occasions. LR and HR women were similar in age and body composition (fat mass = 15.0 +/- 4.7 kg, lean mass = 40.9 +/- 4.9 kg), but HR women exercised more (3.4 +/- 1.7 vs 2.2 +/- 1.8 h x wk(-1), P < 0.05). Exercise was correlated with BMD and BMC, and when it was included as a covariate, total body BMC was significantly lower in HR than LR women. In multiple regression analysis, weekly hours of exercise and restraint score were significant predictors of total body BMD and BMC. The observations of this cross-sectional study suggest that high levels of cognitive dietary restraint, or associated factors such as higher cortisol, may attenuate the positive effects of exercise on bone in young women.
NaProTECHNOLOGYPractitioner TrainingNFP Instruction MethodsNFP Practitioner Role
Barron ML et al., 2001·J Obstet Gynecol Neonatal Nurs
The Creighton Model system of natural family planning (NFP) is useful in achieving pregnancy, avoiding pregnancy, and detecting some gynecologic disorders. NFP practitioners support the client in using NFP. Because the effectiveness of NFP is related to the teaching process and to teacher expertise, clients choosing NFP may be best served by referral to a certified NFP practitioner for instruction.
There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue. We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children. A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children. This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.
Transvaginal ultrasonic follicle puncture has now become the method of choice for oocyte retrieval among most in vitro fertilization (IVF) units. The procedure, which involves puncture then aspiration of ovarian follicles, inevitably results in damage to the fine vascular network of blood vessels on the ovarian surface and theca interna layer, and tends to produce varying degrees of blood loss. The transvaginal ultrasonically guided retrieval of oocytes can be considered noncomplicated when the procedure does not result in injury to iliac vessels, trauma to pelvic viscera, or iatrogenic pelvic infections (1, 2), which would necessitate laparoscopy and or laparotomy. The aim of our study was to quantify the amount of blood loss that should be considered “normal” after noncomplicated transvaginal ultrasonically guided retrieval of oocytes, to characterize the factors that are related to the amount of blood loss, and to identify the patients who have the highest risk of hemorrhage.
Before beginning our study, we performed a power analysis of potential participants. We established the sample size after evaluating the number of women of fertile age in our area, and we used the previous years’ data to calculate the prevalence of sterility problems and the percentage of women who had undergone in vitro fertilization. Thus, our prospective study was based on a sample of 220 women, 25 to 42 years old, who underwent assisted reproduction from January 1998 to May 1999. We excluded the women who had mild or severe ovarian hyperstimulation syndrome or thrombocytopenia, those who were taking anticoagulant drugs, and those who were overweight (body mass index 25 to 30) or obese (body mass index greater than 30). The study was approved by the local hospital ethics committee and all of the participants gave written informed consent.
General OB/GYNVaginal Medication DistributionMRI Pelvic AssessmentTopical Vaginal Therapies
To assess the use of magnetic resonance imaging (MRI) to determine the varying distribution of a vaginally placed gel over time and with different levels of patient activity. Prospectives interventional trial. University medical center. PATIENT(S): One nulliparous volunteer with normal menstrual cycles and no gynecologic disease who underwent seven MRI scans of the pelvis. INTERVENTION(S): Five mL of a commercially available topical spermicide was mixed with gadolinium-chelate magnetic resonance contrast material and introduced with a standard applicator. T1-weighted three-dimensional MRI was done to assess the distribution of the gel. MAIN OUTCOME MEASURE(S): Gel thickness and distribution. RESULT(S): The initial bolus of gel was delivered into the upper portion of the vagina, above the urogenital diaphragm. Thereafter, it spread into the vaginal fornices and "flattened" to cover the lateral aspects of the vagina. Without ambulation, the majority of spread was confined to the upper vagina. With ambulation and longer elapsed time, the gel spread further in the upper vagina and into the lower vagina, and significant vaginal surface coverage increased significantly. CONCLUSION(S): Magnetic resonance imaging can be used to monitor the spread of vaginally placed products and to evaluate coverage of topical drugs used for prevention and treatment, including those used for HIV prophylaxis.
Bone HealthOsteoporosis Risk Assessment ToolsBone Densitometry DXAFracture Risk Prediction
Identification of women with low bone mineral density (BMD) is an important strategy in reducing the incidence of osteoporotic fractures. However, screening all women is not recommended. To assess the diagnostic properties of 4 decision rules--Simple Calculated Osteoporosis Risk Estimation (SCORE), Osteoporosis Risk Assessment Instrument (ORAI), Age, Body Size, No Estrogen (ABONE), and body weight less than 70 kg (weight criterion)--for selecting women for dual-energy x-ray absorptiometry (DXA) testing and to compare results with recommendations made in the National Osteoporosis Foundation (NOF) practice guidelines. Analysis of data from the Canadian Multicentre Osteoporosis Study, a population-based community sample, collected from 9 study centers across Canada between February 1996 and September 1997. Postmenopausal women aged 45 years or older (N = 2365) without bone disease who had DXA data for the femoral neck, data to apply selection criteria, and who were not currently taking estrogens or who had been taking hormone replacement therapy for 5 or more years. Sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve of each of the 4 decision rules and the NOF guidelines for identifying women with a BMD T score of less than -1.0 SD, less than -2.0 SD, and no more than -2.5 SD at the femoral neck, and percentages of women recommended for testing, stratified by BMD level and age. The percent of women with a BMD T score less than -1, less than -2, and no more than -2.5 were 68.3%, 25.4%, and 10.0%, respectively. The AUROC curves were greatest using SCORE and ORAI. The sensitivity for identifying women with a BMD T score of less than -2.0 was 93.7% (95% confidence interval [CI], 91.8%-95.6%) using the NOF guidelines and was 97.5% (95% CI, 96.3%-98.8%), 94.2% (95% CI, 92.3%-96.1%), 79.1% (95% CI, 75.9%-82.3%), and 79.6% (95% CI, 76.4%-82.8%), respectively, using the SCORE, ORAI, ABONE, and weight criterion. However, the NOF guidelines also resulted in 74.4% (95% CI, 71.3%-77.6%) of women with a normal BMD (T score of -1.0 or higher) being tested compared with 69.2% (95% CI, 65.9%-72.5%), 56.3% (95% CI, 52.7%-59.8%), 35.8% (95% CI, 32.4%-39.2%), and 38.1% (95% CI, 34.6%-41.6%), respectively, using the 4 decision rules. Assessments suggest that ABONE and weight criterion are not useful case-finding approaches. The SCORE and ORAI decision rules are better than the NOF guidelines at targeting BMD testing in high-risk patients. The acceptability of these rules in clinical practice merits further investigation given their potential effect on the use of densitometry services.
PostpartumPostpartum Depression TreatmentEstradiol Deficiency and MoodPostpartum Depression Hormonal Therapy
The postpartum period is a time when women are vulnerable to depressive disorders, which can be severe and have long-lasting adverse sequelae. In spite of multiple contacts with health care providers, women with postpartum depression often remain unrecognized and untreated. To evaluate the association between estradiol and postpartum depression, we measured serum estradiol concentration and performed an open-label study of physiologic 17beta-estradiol. Twenty-three women fulfilling ICD-10 criteria for major depression with postpartum onset were consecutively recruited from a psychiatric emergency unit. Serum estradiol concentrations were measured at baseline and weekly during sublingual 17beta-estradiol treatment for 8 weeks. The treatment effect was assessed using a clinician-rated depression symptom scale, the Montgomery-Asberg Depression Rating Scale (MADRS). At baseline, all patients were severely depressed (mean MADRS total score = 40.7; range, 35-45) and had a low serum estradiol concentration (mean = 79.8 pmol/L; range, 23-140 pmol/L); in 16/23 patients, the concentration was even lower than the threshold value for gonadal failure. During the first week of estradiol treatment, depressive symptoms diminished significantly, resulting in a mean MADRS score of 11.0 (Z = -4.20, p < .001), and serum estradiol concentrations approached those of the follicular phase (mean +/- SD = 342 +/- 141 pmol/L). At the end of the second week of treatment, the MADRS scores were compatible with clinical recovery in 19/23 patients. This preliminary study shows that depression symptoms may be rapidly reduced in patients with postpartum depression who have documented estradiol deficiency by treatment with 17beta-estradiol and suggests that estradiol can have significance in the pathophysiology of this condition and may be an option in the treatment of women vulnerable to postpartum depression.
Bone HealthParity and Lactation EffectsLong-term Bone Health OutcomesOral Contraceptives and Bone
Several studies indicate that parity and lactation are associated with modest, short-term bone loss, but the long-term effect on osteoporotic fracture risk is uncertain. The authors therefore analyzed data from a population-based case-control study among Swedish postmenopausal women aged 50-81 years between October 1993 and February 1995. Mailed questionnaires and telephone interviews were used to collect data on 1,328 incident cases with hip fracture and 3,312 randomly selected controls. In age-adjusted analyses, the risk of hip fracture among all women was reduced by 10% per child (95% confidence interval (CI): 5, 14). After multivariate adjustment including body mass index as a covariate, the risk reduction was 5% per child (95% CI: 0, 10). Oral contraceptive use modified the association of parity with hip fracture risk. Among never users of oral contraceptives, the risk of hip fracture was reduced by 8% per child (95% CI: 2, 13), whereas among ever users of oral contraceptives, the risk was in the opposite direction, with an increase in risk by 19% per child (95% CI: 0, 41). After parity was considered, there was no association of duration of lactation period with fracture risk. The authors conclude that parity is modestly associated with a reduced hip fracture risk among women who had not used oral contraceptives previously.
The role of human chorionic gonadatropin (hCG) in the maintenance of early pregnancy is well known. Recent data suggests that hCG may play a role in the maintenance of the later stages of pregnancy as well, by directly and indirectly promoting uterine quiescence. If hCG acts as an endogenous tocolytic in normal pregnancy, then it may be an ideal candidate for therapy of preterm labor as well. We present compelling in vitro as well as in vivo data, which support the role of hCG in the maintenance of normal uterine quiescence. Additionally, we will present in vivo and in vitro data that confirms the ability of hCG to directly promote relaxation of uterine contractions. This review provides a basis for future study of the use of hCG in clinical obstetrics. Given the limited effectiveness of tocolytic therapies available at the time, hCG may provide a promising pharmacological approach to the pervasive problem of preterm labor in human pregnancy. While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics.
Reproductive EndocrinologyPharmacokinetics and RoutesFormulations and DeliveryProgesterone Administration
Progestogens, which include the natural hormone, progesterone, and synthetic steroid derivatives, are used to treat a variety of reproductive disorders. Since synthetic progestogens are often associated with undesirable side effects, improved formulations and modes of administration of progesterone have been sought. In order to find an optimal therapeutic agent, different progesterone formulations and routes of administration have been studied. This paper explains several methods of measuring progesterone levels and summarizes clinical data on the pharmacokinetic profiles of natural progesterone administered by the oral, intramuscular, vaginal, intranasal, percutaneous, sublingual and rectal routes.
Reproductive EndocrinologyEmbryo-Endometrial SignalinghCG Role in Endometrial ReceptivityGrowth and Differentiation Factor
Recent evidence suggests that human chorionic gonadotropin (hCG), in addition to its well-known endocrine effects on the corpus luteum, may act as a growth and differentiation factor during pregnancy. According to experimental results, its mode of action may be divided into three sequential phases. During the first phase, which begins at the blastocyst stage and lasts until the occurrence in the serum, hCG acts preferentially in a juxtacrine manner. We have used an intrauterine microdialysis system developed in our laboratory to administer low concentrations of hCG to the endometrium of women in the luteal phase of the menstrual cycle. HCG administration provoked profound effects on paracrine parameters of differentiation (IGFBP-1, prolactin) and implantation (LIF, M-CSF). VEGF, a cytokine important for neoangiogenesis, was significantly stimulated by hCG (P < .01), suggesting a role for hCG in the control of endometrial vascularization and placentation. The investigation of endometrial parameters of tissue remodeling revealed a significant increase of MMP-9 (P < .05) but not of TIMP-1 following hCG infusion. The second, endocrine, phase of hCG action is marked by the appearance of hCG in the maternal serum. Rising systemic hCG levels cause a very rapid elevation of serum progesterone reflecting the rescue of the corpus luteum. Other endocrine functions of hCG include its intrinsic thyrotropic activity as well as modulation of fetal testicular, ovarian, and adrenal function. The third phase may be characterized by the expression of full-length hCG/LH receptors on the trophoblasts themselves. Before the ninth week of gestation, human villous trophoblasts express a truncated hCG/LH receptor isoform (50 kDa) and are probably not responsive to hCG. Later, the expression pattern is switched to the full-length receptor (80 kDa), allowing hCG also to modulate the differentiation of the trophoblasts themselves. A special feature is the self-regulation of hCG biosynthesis that may in part explain the unique secretion profile of the hormone with peak levels during the first trimester followed by a rapid decline after the tenth week of gestation. In summary, hCG seems to have a variety of local and systemic functions in and outside the embryo-endometrial microenvironment.
Reproductive EndocrinologyEndometrial EffectshCG and Endometrial ReceptivityGonadotropin Direct Effects
Human chorionic gonadotropin (hCG) is widely used as a surrogate to luteinizing hormone (LH) to trigger ovulation in controlled ovarian hyperstimulation (COH). Yet this molecule may exert direct effects on the endometrium. These effects, not mediated by ovarian hormones, are probably a consequence of stimulation of endometrial hCG/LH receptors. Because the half-life of hCG differs markedly from that of LH, possible pharmacological effects of hCG on the endometrium could alter endometrial receptivity in COH. Arguments supporting a clinical action of gonadotropins, and hCG in particular, on the endometrium abound. Notably, evidence has been reported of decidualization of stromal cells of the human endometrium in vitro as a result of exposure to gonadotropins, including hCG. The present article discusses, from a clinical standpoint, the main basis supporting the hypothesis that hCG administration as commonly used in infertility treatments may exert direct effects in vivo on endometrial histology and partake in endometrial transformations of the luteal phase. Preliminary results suggest that endometrial effects of hCG exist in vivo and should be taken into account when assessing the endometrial effects of hormones.
InfertilityProgesterone SupplementationClinical Use in FertilityLuteal Phase Support
Progesterone, supplied in a variety of formulations, is commonly used in assisted reproduction. However, even the commonly accepted uses of progesterone in fertility care are believed to be largely empirical, as are the current available treatment options. While a critical balance of estrogen and progesterone is necessary for successful embryo implantation, achieving that balance is subject to differences in prescribing practice. In evaluating recommendations for the use of progesterone, discussion of its role in assisted-reproduction procedures must distinguish between known therapeutic benefits and empirical benefits.
To determine the association between indomethacin tocolysis and neonatal intraventricular hemorrhage. Fifty-six preterm neonates with intraventricular hemorrhage were matched by gestational age with neonates (n = 224) without this morbidity. Maternal and neonatal charts were reviewed to ascertain the type of tocolytic exposure experienced by the neonate. Other maternal and neonatal demographic and outcome data were also abstracted. Results were analyzed using the Student t test, chi(2) analysis, and multivariable logistic regression. The number of studied subjects provided 80% power to determine if antenatal exposure to indomethacin was twice as likely among infants with intraventricular hemorrhage. Univariate analysis revealed that there were no significant differences between the study and control groups with respect to maternal age, parity, or betamethasone exposure. Infants with intraventricular hemorrhage were significantly more likely to be born at an earlier gestational age, a lower birth weight, after maternal chorioamnionitis, after vaginal delivery, and after exposure to either indomethacin alone or a combination of indomethacin and magnesium. Additionally, their neonatal course was significantly more likely to be complicated by sepsis and respiratory distress syndrome. In a multivariable logistic model, only gestational age, chorioamnionitis, vaginal delivery, and respiratory distress syndrome continued to be significantly associated with intraventricular hemorrhage. Indomethacin exposure, either as single-agent (adjusted odds ratio 1.3, 95% confidence interval 0.5, 3.3) or combination tocolytic therapy (adjusted odds ratio 2.0, 95% confidence interval 0.8, 4.8), was not significantly associated with intraventricular hemorrhage. Indomethacin tocolysis is not associated with an increased risk of intraventricular hemorrhage.
General OB/GYNPsychological Impact of IVFMarital RelationshipsAnxiety in Reproductive Medicine
To compare the psychopathology, personality features, and marital relationships of women undergoing in vitro fertilization (IVF) with those of control patients, and to compare IVF inductees with program veterans. Cross-sectional clinical study. A university hospital. PATIENT(S): One hundred and one women undergoing IVF treatment. INTERVENTION(S): Psychometric tests were administered at first visit (baseline) of index treatment cycle. MAIN OUTCOME MEASURE(S): Achievement of pregnancy. RESULT(S): Women undergoing IVF show higher levels of anxiety and emotional tension than do controls. Although the infertile women showed no abnormal personality dimensions, the IVF group did have a particular psychological profile and a different marital relationship pattern when compared with the control participants. Between IVF veterans and inductees, there are significant differences with respect to psychopathology, psychological dimensions, and couple dynamics. The achievement of pregnancy is not associated with any special psychopathological, personality, or marital characteristics among the IVF women. CONCLUSION(S): The most crucial period in IVF procedures may immediately follow the end of the first cycle because of the high risk of patients dropping out of the program. To determine the most effective supporting therapies for women undergoing fertilization procedures it could be useful to consider the psychological and relational differences between veterans and inductees.
InfertilityEmbryo Transfer OptimizationUterine ContractilityLuteal Phase Support
To investigate whether uterine contractility at the time of embryo transfer (ET) can be reduced by early onset of luteal support with progesterone administered vaginally. Prospective analysis. Assisted reproduction unit. PATIENT(S): Eighty-four women undergoing 84 GnRH-a and FSH/hCG cycles for IVF-ET were studied. INTERVENTION(S): Vaginal progesterone was randomly started on the day of oocyte retrieval (group A, n = 43) or on the evening of ET (group B, n = 41). On the day of hCG administration and just before ET, 2-minute sagittal uterine scans were obtained by ultrasound and digitized with an image analysis system for assessing uterine contraction frequency. MAIN OUTCOME MEASURE(S): Uterine contraction frequency. RESULT(S): Whereas uterine contraction frequency was similar in both groups on the day of hCG (4.6 +/- 0.3 and 4.5 +/- 0.3 contractions per minute, respectively), only women in group A showed decreased uterine contraction frequency on the day of ET (2.8 +/- 0.2 vs. 4.2 +/- 0.3 contractions per minute). CONCLUSION(S): Vaginal progesterone administration starting on the day of oocyte retrieval induced a decrease in uterine contraction frequency on the day of ET as compared with preovulatory values. Uterine relaxation before ET is likely to improve IVF-ET outcome by avoiding the displacement of embryos from the uterine cavity.
Body LiteracyHealthcare Provider KnowledgeProvider Promotion of NFPChild Spacing Methods
The purpose of this study was to describe and assess certified nurse-midwives' (CNMs) knowledge and promotion of two modalities for child spacing, natural family-planning (NFP) and the lactational amenorrhea method (LAM). One thousand two hundred CNMs were randomly selected from a national membership list and mailed a 24-item questionnaire on NFP and LAM. Of the 514 respondents (42.8% return rate), 450 (87.5%) were currently practicing as CNMs. Respondents had an average age of 46 years, with an average of 10 years of practice. CNMs ranked NFP as the ninth most used and the eighth most effective family-planning method in their practice, with an average perceived method-effectiveness of 88% and use-effectiveness of 70%. Although most respondents felt somewhat prepared during their education program to provide NFP, only 22% would offer NFP as a family-planning option for child spacing.
EndometriosisMalignant TransformationAssociation with Ovarian CancerEndometriosis-Related Carcinoma
To analyse the relationship between endometriosis and epithelial ovarian cancer. We analyzed retrospectively the 20 cases associated with endometriosis in 371 cases of epithelial ovarian cancer, and these 20 cases were also compared with the left 351 cases not associated with endometriosis(including endomtriod carcinoma 38 cases and clear cell carcinoma 39 cases). Among 20 cases, endomtriod carcinoma and clear cell carcinoma were most frequently associated with endometriosis, with 11 cases and 7 cases respectively, there was also 1 case of gland carcinoma and 1 case of serous papillary carcinoma. Cases of carcinomas associated with endometriosis had higher pathological grade and 5-year survival probability (Kaplan-Meier method) than those cases not associated with endometriosis. There is a close relationship between endometriosis and ovarian endomtriod carcinoma and clear cell carcinoma, the malignant transformation of endometriosis foci may be an important origin of them. Drug therapy is recommended for endomtriosis after the operation. In the treatment of endomtriod carcinoma and clear cell carcinoma, progestin can be used as an accessory method.
PregnancyBirth Defect RiskCongenital AnomaliesPopulation-Based Cohort Study
To investigate the relationship between prematurity and birth defects. In a population-based cohort study, infants with birth defects were ascertained through the Metropolitan Atlanta Congenital Defects Program, a surveillance system with active methods of ascertainment. Gestational age data were obtained from birth certificates of liveborn, singleton infants with and without birth defects born in the 5-county metropolitan Atlanta area. Among 264,392 infants with known gestational ages born between 1989 and 1995, 7738 were identified as having birth defects (2.93%). Premature infants (<37 weeks' gestation) were more than two times as likely to have birth defects than term infants (37-41 weeks) (risk ratio = 2.43; 95% CI 2.30-2.56). This relationship was evident for several categories of birth defects. The rate of birth defects varied by gestational age categories, with the highest risk in the 29- to 32-week gestational age category (risk ratio = 3.37). The risk for birth defects is increased in premature infants. Awareness of this relationship is important for clinicians caring for premature infants. The morbidity and mortality associated with a particular defect may be significantly altered by the presence of prematurity. Further study of this association may provide insight into the etiology of these relatively common problems.
Bone HealthPubertal Bone Mineral AcquisitionGrowth and DevelopmentCalcium Intake and Bone Density
This 2-year prospective study examined associations among bone mineral acquisition and physical, maturational, and lifestyle variables during the pubertal transition in healthy girls. Forty-five girls, initially 10.5+/-0.6 years, participated. Body composition and bone mineral content (BMC) at the spine and total body (TB) were assessed at baseline and annually thereafter using dual-energy X-ray absorptiometry (DXA). Nutrient intakes were assessed using 3-day diet records and a calcium food frequency questionnaire (FFQ), physical activity by questionnaire, sexual maturation using Tanner's stages of breast and pubic hair maturation, growth by height and weight, and eating attitudes using the children's Eating Attitudes Test (Children's EAT). Mean children's EAT subscale scores (dieting, oral control [OC], and bulimia) were stable over time. Median split of OC subscale scores was used to form high and low OC groups. Groups had similar body composition, dietary intake, activity, and Tanner stage at baseline and 2 years. Using height, weight, and Tanner breast stage as covariates, girls with low OC scores had greater TB BMC at baseline (1452+/-221 g vs. 1387+/-197 g; p = 0.030) and 2 years (2003+/-323 g vs. 1909+/-299 g; p = 0.049) and greater lumbar spine (LS) BMC at 2 years (45.2+/-8.8 g vs. 41.2+/-9.6 g; p = 0.042). In multiple regression analysis, OC score predicted baseline, 2 years, and 2-year change in TB and spinal BMC, contributing 0.9-7.6% to explained variance. Calcium intake predicted baseline, 2 years, and 2-year change in TB BMC, explaining 1.6-5.3% of variance. We conclude that both OC and habitual calcium intake may influence bone mineral acquisition.
To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. Prospective randomized trial. Infertility clinic in a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. INTERVENTION(S): The women were assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities. RESULTS(S): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group. CONCLUSION(S): The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.
This study was designed to examine basal and stress-induced levels of the neuroactive progesterone metabolite, allopregnanolone, in women with premenstrual dysphoric disorder (PMDD) and healthy control subjects. Also, because evidence suggests that allopregnanolone negatively modulates the hypothalamic-pituitary-adrenal axis, plasma cortisol levels were examined. An additional goal was to investigate the relationship between premenstrual symptom severity and luteal phase allopregnanolone levels. Twenty-four women meeting prospective criteria for PMDD were compared with 12 controls during both the follicular and luteal phases of confirmed ovulatory cycles, counterbalancing phase at first testing. Plasma allopregnanolone and cortisol were sampled after an extended baseline period and again 17 min following the onset of mental stress. Owing to low follicular phase allopregnanolone levels, only luteal phase allopregnanolone and cortisol were analyzed. During the luteal phase, PMDD women had significantly greater allopregnanolone levels, coupled with significantly lower cortisol levels, during both baseline and mental stress. Moreover, significantly more controls (83%) showed the expected stress-induced increases in allopregnanolone compared with PMDD women (42%). Premenstrual dysphoric disorder women also exhibited a significantly greater allopregnanolone/progesterone ratio than control subjects, suggesting alterations in the metabolic pathways involved in the conversion of progesterone to allopregnanolone. Finally, PMDD women with greater levels of premenstrual anxiety and irritability had significantly reduced allopregnanolone levels in the luteal phase relative to less symptomatic PMDD women. No relationship between symptom severity and allopregnanolone was observed in controls. These results suggest dysregulation of allopregnanolone mechanisms in PMDD and that continued investigations into a potential pathophysiologic role of allopregnanolone in PMDD are warranted.
Studies in animal models of spontaneous Hashimoto's autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT. The aim of the present study was to clarify whether there is a benefit of prophylactic treatment with LT4 in patients with euthyroid HT with respect to the progression of the autoimmune process. Twenty-one patients with euthyroid HT were checked for thyroid function (thyrotropin [TSH], free triiodothyronine [FT3], free thyroxine [FT4]), thyroid volume, antibodies (thyroglobulin [Tg-Ab], thyroid peroxidase [TPO-Ab]), and lymphocyte subsets. Peripheral (PBL) and thyroid-derived lymphocytes (TL) were analyzed by triple color flow cytometry. One-half of the patients with euthyroid HT were treated with LT4 for 1 year (n = 10). The other half (n = 11) were never treated with LT4. TL were obtained by fine-needle aspiration biopsy (FNAB). Thirteen healthy subjects (C) without medical history of thyroid disease served as controls concerning PBL, and patients with non-toxic nodular goiter (NG; n = 10) served as controls concerning TL. Thyroid-derived T-helper cells were found more frequently in euthyroid patients with HT compared to patients with NG (p < 0.01). After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05). In contrast, TPO-Abs levels did not change or even increased in untreated euthyroid patients with HT. Thyroid volume did not differ before and after therapy. Prophylactic treatment of euthyroid patients with HT reduced both serological and cellular markers of autoimmune thyroiditis. Therefore, prophylactic LT4 treatment might be useful to stop the progression or even manifestation of the disease. However, the long-term clinical benefit of prophylactic LT4 therapy in euthyroid patients with HT is yet to be established.
PregnancyInflammatory BiomarkersTNF-Alpha PredictionCytokine Levels in Pregnancy
To evaluate maternal serum tumor necrosis factor-alpha (TNF alpha) levels in patients with preterm labor without clinical signs of chorioamnionitis and to compare these with levels in nonlaboring controls. The study group consisted of 44 patients with a singleton pregnancy admitted to our department with the diagnosis of preterm labor between 26 and 36 weeks' gestation. The control group consisted of 25 healthy consecutive patients with a singleton pregnancy without preterm contractions who were seen for routine antenatal visits. Maternal serum TNF alpha was measured using a solid-phase, two-site chemiluminescent enzyme immunometric assay method, and levels were compared in patients with preterm labor and nonlaboring controls. The median maternal serum TNF alpha level for patients with preterm labor was 29.4 pg/mL (range, 12.3-173) as compared with 23 pg/mL (range, 11.9-62.7) in the control group (P = .031). Among 44 patients with preterm labor, 14 (32%) delivered within one week of admission. The median maternal serum TNF alpha level was significantly higher in patients who delivered within one week than in those who delivered after one week and controls (71.3 pg/mL [range, 28-173]) versus 22 pg/mL (range, 12.3-86) versus 23 pg/mL (range, 11.9-62.7) (P < .0001). TNF alpha was elevated in patients with preterm labor, suggesting a role for maternal serum TNF alpha in its initiation.
PCOSNeuroendocrine MechanismsInsulin SensitizersPulse Frequency
Kalro BN et al., 2001·Obstet Gynecol Clin North Am
Although central and peripheral factors have been implicated in the neuromodulation of GnRH in PCOS, there are no definitive or conclusive data to establish a primary causal role for any one factor. Because increased GnRH pulse frequency is at least a contributor to the secretion of excess LH and insufficient FSH that are the proximate cause of chronic anovulation in PCOS, strategies to slow the GnRH pulse generator are likely to promote ovulation in women with PCOS. Several pharmacologic agents, such as dopamine agonists and antagonists, have been tried, but the lack of consistent effects in women with PCOS limits their clinical utility. Current treatment strategies include the use of the combined oral contraceptive pills, antiandrogens or androgen receptor blockers, and insulin sensitizers. Oral contraceptive preparations are effective in suppressing ovarian hyperandrogenemia, regulating menstrual cycles, and reducing the risk of endometrial hyperplasia. Androgen blockade and antiandrogens provide symptomatic relief from androgen-induced acne and hirsutism and have been reported to restore ovulation in women with PCOS. Whether this effect is mediated peripherally or centrally remains to be clarified. The most recent class of pharmacologic agents to gain popularity are the "insulin modifiers." With increasing evidence that insulin resistance constitutes a key metabolic element, it seems logical that improving insulin sensitivity and glucose disposal might wholly, or partially, reverse certain features of PCOS, including anovulation. To date, insulin modifiers have proved most promising in improving the clinical features and promoting fertility, but whether this effect is centrally mediated is yet to be elucidated.
To compare subcutaneous (SC) and intramuscular (IM) hCG administration and their association with body mass index (BMI) in women undergoing IVF-ET using hMG and ICSI. Prospective, randomized controlled trial. Private infertility clinic. PATIENT(S): Twenty-one ovulatory women, 29-39 years, were enrolled. Treatment of one patient who failed to respond to hMG was canceled. INTERVENTION(S): A standard IVF-ET treatment plan using an initial dose of 300 U of hMG was followed. Patients were randomly assigned to receive 10,000 IU hCG, either IM in the gluteal region or SC in the lower abdomen. Exactly 12 hours later, serum for hCG determination was obtained. All oocytes were fertilized using ICSI technology. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin levels 12 hours after injection, BMI, and oocyte maturity. RESULT(S): No significant differences in hCG levels were found, with mean levels of 225 +/- 24 mIU/mL for SC injection versus 213 +/- 26 mIU/mL for IM injection. No differences were observed in the percentage of mature oocytes. A significant negative correlation was found between BMI and hCG levels in all patients, regardless of route of administration. CONCLUSION(S): The highest levels of hCG were measured in women with the lowest BMI. Patients' body size, rather than route of hCG delivery, appears to determine circulating levels of hCG.
This paper considers the concept of consumer acceptance of medical products and its importance to successful healthcare provision. The critical dimensions ('domains') of acceptance for a product designed to assist family planning, and the importance of using high-quality psychometric scales to assess these domains, are discussed. Qualitative and quantitative data from acceptance studies with a personal contraceptive monitor, PERSONA, are presented. These data indicate that the monitor is user-friendly and acceptable to couples, and underline the importance of user acceptability for home monitors designed to assist family planning--including those used for conception purposes.
Zuppa AA et al., 2001·Eur J Obstet Gynecol Reprod Biol
Over the last 10 years, diffusion of assisted reproduction techniques (ovarian stimulation, IVF, GIFT) has led to an increased incidence of multiple pregnancies and consequently, of the related obstetric-neonatal problems. In this study, multiple births have been studied, with particular reference to the twin births occurring in the Gemelli hospital, Rome. The hospital is also a reference centre for obstetric pathologies and infertility treatment. In particular, attention has been focused on neonatal outcome, comparing twins born from spontaneous and assisted pregnancies. 228 neonates from spontaneous twin pregnancies and 32 from assisted twin pregnancies were taken into premature birth, low birth-weight, intrauterine growth retardation, weight discordance, Apgar score, major neonatal diseases, and mortality. Results showed a significant higher incidence of prematurity and low birth-weight, as well as a significant lower gestational age, occurring more frequently in twins resulting from assisted pregnancies than in twins from spontaneous pregnancies. Furthermore, the incidence of severe depression at birth and respiratory disease was significantly higher in twins from assisted pregnancies than in those from spontaneous pregnancies, despite similar gestational age and birth-weight.
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. New treatment approaches resulting from a refined understanding of the pathophysiology are evolving. The literature shows that PCOS is an endocrinopathy resulting from insulin resistance and the compensatory hyperinsulinemia. This results in adverse effects on multiple organ systems and may result in alteration in serum lipids, anovulation, abnormal uterine bleeding, and infertility. In addition, PCOS may place the patient at long-term risk for the development of type 2 diabetes, hypertension, endometrial cancer, and cardiovascular disease. Oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies. However, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies. Early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.
S B Roberts et al., 2001·J Gerontol A Biol Sci Med Sci
Caloric restriction (CR) reduces the rate of aging and increases life span in all small animal species studied to date, but the effects of CR in humans remain uncertain. This review summarizes current knowledge of the effects of CR in nonhuman primates and humans. The results suggest that CR has a range of beneficial effects in nonhuman primates studied under laboratory conditions, and short-term markers of CR seen in animal models appear to occur in humans subject to CR also. However, the overall benefit of CR in human populations remains to be established, and studies in human populations are needed.
MacLennan A et al., 2001·Climacteric : the journal of the International Menopause Society
To examine the effectiveness of oral hormone replacement therapy (HRT) with regard to hot flushes and night sweats, which are vasomotor symptoms commonly experienced by menopausal women. Double-blind, randomized, placebo-controlled trials of oral HRT for at least 3 months' duration and reporting vasomotor outcomes were identified using a search strategy developed by the Menstrual Disorders Group and Subfertility Group of the Cochrane Collaboration. Twenty-one trials meeting the selection criteria were included in the review. Study participants totalled 2511. Trial duration ranged from 3 months to 3 years. There was a significant reduction in the weekly hot flush frequency for HRT compared with placebo (weighted mean difference -17.46, 95% confidence interval (CI) -24.72 to -10.21). This was equivalent to a 77% reduction in frequency (95% CI 58.2-87.5) for HRT relative to placebo. Symptom severity was also significantly reduced compared with placebo (odds ratio (OR) 0.13, 95% CI 0.08-0.22). Withdrawal for lack of efficacy occurred significantly more often with placebo therapy (OR 17.25, 95% CI 8.23-36.15). Withdrawal for adverse events, commonly breast tenderness, edema, joint pain and psychological symptoms, was not significantly increased for HRT (OR 1.38, 95% CI 0.87-2.21). In women who were randomized to placebo treatment, a 50.8% (95% CI 41.7-58.5) reduction in hot flushes was observed between baseline and the end of the study. Oral HRT is highly effective in alleviating hot flushes and night sweats. Owing to the marked effect seen with placebo treatment, it is important to compare therapies purported to alleviate vasomotor symptoms with a placebo or an established therapy.
Josefsson A et al., 2001·Acta Obstet Gynecol Scand
Postnatal depression refers to a non-psychotic depressive episode that begins in or extends into the postpartum period. The aims of this study were to examine the prevalence of depressive symptoms in a pregnant and later postnatal population, to determine the natural course of these symptoms and whether there is an association between antenatal and postnatal depressive symptomatology. A longitudinal study with a total population of 1,558 consecutively registered pregnant women in the southeast region of Sweden. Presence of depressive symptoms was measured with the Edinburgh Postnatal Depression Scale on four occasions namely in gestational week 35-36, in the maternity ward, 6-8 weeks and 6 months postpartum. The prevalence of depressive symptoms during late pregnancy was 17%; in the maternity ward 18%; 6-8 weeks postnatally 13%; and 6 months postnatally, 13%. A correlation between antenatal and postnatal depressive symptoms was found (r=0.50, p<0.0001). Detection of women at risk for developing postnatal depressive symptoms can be done during late pregnancy. Antenatal care clinics constitute a natural and useful environment for recognition of women with depressive symptoms.
Bone HealthOsteoporosis PrevalenceDXA Reference StandardsBone Mineral Density
The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10,061 women and men aged > or = 25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged > or = 50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 +/- 0.121 g/cm2 for women and 1.058 +/- 0.127 g/cm2 for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 +/- 0.125 g/cm2 for women and 0.910 +/- 0.125 g/cm2 for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged > or = 50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%.
To use aromatase inhibition for induction of ovulation in women in whom clomiphene citrate (CC) treatment was unsuccessful. Prospective trial in infertility patients treated with CC. Two tertiary-referral infertility clinics associated with the Division of Reproductive Sciences, University of Toronto. PATIENT(S): Twelve patients with anovulatory polycystic ovary syndrome (PCOS) and 10 patients with ovulatory infertility, all of whom had previously received CC with an inadequate outcome (no ovulation and/or endometrial thickness of < or =0.5 cm). INTERVENTION(S): The aromatase inhibitor letrozole was given orally in a dose of 2.5 mg on days 3-7 after menses. MAIN OUTCOME MEASURE(S): Occurrence of ovulation, endometrial thickness, and pregnancy rates. RESULT(S): With CC treatment in patients with PCOS, ovulation occurred in 8 of 18 cycles (44.4%), and all ovulatory cycles for the women included in this study had endometrial thickness of < or =0.5 cm. In 10 ovulatory patients, 15 CC cycles resulted in a mean number of 2.5 mature follicles, but all cycles had endometrial thickness of < or =0.5 cm on the day of hCG administration. With letrozole treatment in the same patients with PCOS, ovulation occurred in 9 of 12 cycles (75%) and pregnancy was achieved in 3 patients (25%). In the 10 patients with ovulatory infertility, letrozole treatment resulted in a mean number of 2.3 mature follicles and mean endometrial thickness of 0.8 cm. Pregnancy was achieved in 1 patient (10%). CONCLUSION(S): Oral administration of the aromatase inhibitor letrozole is effective for ovulation induction in anovulatory infertility and for increased follicle recruitment in ovulatory infertility. Letrozole appears to avoid the unfavorable effects on the endometrium frequently seen with antiestrogen use for ovulation induction.
PCOSMetforminClomiphene CitrateCombined Medical Therapy
To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. Randomized, double-blind, placebo-controlled trial. Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.
Dmowski WP et al., 2001·J Am Assoc Gynecol Laparosc
Small bowel involvement by endometriosis occurs in about 0.5% of patients, but nodular endometriosis involving the entire wall of the terminal ileum is extremely rare. Endometriotic nodules protruding into the intestinal lumen may lead to chronic, partial, or acute complete small bowel obstruction and associated clinical changes. If obstruction is partial, preoperative diagnosis is difficult and seldom suspected, and no reliable diagnostic tests are available. At laparoscopic surgery, performed typically for associated pelvic endometriosis, bowel lesions may easily be overlooked, especially in women with abdominal adhesions from earlier surgery. Surgical injury, tension tears, or postoperative edema may contribute in such cases to the development of acute, complete small bowel obstruction, which may be difficult to differentiate from postoperative ileus. The patient may deteriorate rapidly and develop abdominal sepsis and multiple organ failure with high risk of mortality. Because of increased production of tumor necrosis factor-alpha by autologous monocytes, endometriosis may predispose to development of severe sepsis and septic shock. (J Am Assoc Gynecol Laparosc 8(1):161-166, 2001)
The objective of this effort was to assess the use and efficacy of the Lactational Amenorrhea Method (LAM) with reduced numbers of client-provider contacts. A co-sponsored multicenter study of LAM was performed to test the efficacy and acceptability of the method under "post-marketing" conditions, with investigator-initiated at the time of intake and then again at month 7 of postpartum. These data are assumed to provide an assessment of LAM's use, efficacy, and performance that more closely reflects the prevailing conditions of these populations during normal use. Three hundred and sixty-two subjects were recruited through centers that had participated in the previous, more contact-intensive studies. Using a cooperatively developed protocol, data were gathered prospectively on at least 10 and up to 50 LAM acceptors at nine sites, and entered and cleaned on site. Data were further cleaned and analyzed at the Georgetown University Institute for Reproductive Health (IRH) and the Department of Nutrition at the University of Connecticut. Using country-level and pooled data, descriptive statistics and life tables were produced. LAM efficacy in this sample is 100% because there were no pregnancies at any of the participating sites. Satisfaction with the method was high, and the rate of continuation on to another method after LAM was 66.7% at 7 months postpartum. Of the women who had never used family planning prior to LAM, 63.0% went on to use another method of family planning in a timely manner. LAM can be highly effective as an introductory postpartum family planning method when offered in a variety of cultures, health care settings, and industrial and developing country locales. Under conditions of limited client-provider contact, LAM remains effective and leads to acceptance of another method by about two-thirds of the acceptors. Women are able to use LAM effectively without extensive counseling or follow-up, with a high level of user satisfaction.
EndometriosisSusceptibility AllelesMalignant TransformationOvarian Cancer Genetics
It is likely that heritable genetic factors contribute to the development of endometriosis, which is a putative precursor of the endometrioid and clear cell histological subtypes of ovarian cancer. The phase II glutathione S-transferases (GSTs) are a family of enzymes responsible for metabolism of a broad range of xenobiotics and carcinogens. Allelic variants of GSTs that have impaired detoxification function may increase the rate of genetic damage and thereby increase the susceptibility to cancer. The null genetic polymorphism in the gene encoding the GST class mu (GSTM1) enzyme has been reported to be significantly elevated in endometriosis patients and may represent an endometriosis susceptibility allele. In this study the frequency of the GSTM1 null genotype was investigated in 84 cases of endometriosis, 293 cases of ovarian cancer and 219 controls. All cases and controls were derived from women resident in the south east of England. The frequency of the GSTM1 null allele was not over-represented in the endometriosis patients (47.6%) compared with the controls (48.9%) (P = 0.898). In the ovarian cancer group the GSTM1 null genotype was significantly elevated compared with controls (59.0 versus 48.9%, P = 0.025). When stratified according to histological subtype a significantly increased GSTM1 null genotype was only observed for the endometrioid (65.4%, P = 0.013) and the combined endometrioid/clear cell ovarian cancers (67.0%, P = 0.004). We conclude that the GSTM1 null allele is not an endometriosis susceptibility allele, however, it may predispose endometriotic lesions to malignant transformation to endometrioid and clear cell ovarian cancer.
Over the past 20 years, it has been clearly documented that the polycystic ovary syndrome (PCOS) has major metabolic sequelae related to insulin resistance and that insulin resistance plays an important role in the pathogenesis of the reproductive disturbances of the disorder. Family studies have indicated a genetic susceptibility to PCOS. Polycystic ovaries and hyperandrogenemia are present in approximately 50% of sisters of affected women. Increased androgen secretion and insulin resistance persist in cultured theca cells and skin fibroblasts, respectively, from women with PCOS; this finding suggests that these are intrinsic, presumably genetic, defects. Insulin resistance and elevated low-density lipoprotein (LDL) levels also cluster in the sisters of women with PCOS, consistent with genetic traits. Moreover, the brothers of women with PCOS have insulin resistance and elevated dehydroepiandrosterone sulfate (DHEAS) levels, which supports a genetic basis for these findings. Family-based studies of linkage and association have implicated several genes in the pathogenesis of PCOS. The strongest evidence to date points to a gene in the region of the insulin receptor. Insulin-sensitizing therapy mitigates the reproductive disturbances of PCOS.
To compare the efficacy and tolerability of agnus castus fruit (Vitex agnus castus L extract Ze 440) with placebo for women with the premenstrual syndrome. Randomised, double blind, placebo controlled, parallel group comparison over three menstrual cycles. General medicine community clinics. 178 women were screened and 170 were evaluated (active 86; placebo 84). Mean age was 36 years, mean cycle length was 28 days, mean duration of menses was 4.5 days. Agnus castus (dry extract tablets) one tablet daily or matching placebo, given for three consecutive cycles. Main change from baseline to end point (end of third cycle) in women's self assessment of irritability, mood alteration, anger, headache, breast fullness, and other menstrual symptoms including bloating. changes in clinical global impression (severity of condition, global improvement, and risk or benefit) and responder rate (50% reduction in symptoms). Improvement in the main variable was greater in the active group compared with placebo group (P<0.001). Analysis of the secondary variables showed significant (P<0.001) superiority of active treatment in each of the three global impression items. Responder rates were 52% and 24% for active and placebo, respectively. Seven women reported mild adverse events (four active; three placebo), none of which caused discontinuation of treatment. Dry extract of agnus castus fruit is an effective and well tolerated treatment for the relief of symptoms of the premenstrual syndrome.
InfertilityMultiple PregnanciesMaternal and Neonatal MorbidityMultiple Gestation
To investigate the contributions of ovulation-inducing drugs and assisted reproductive technologies to multiple birth. This historic prospective study was conducted in a cohort of 13,151 women who delivered after 20 weeks' gestation between October 1996 and December 1999. The study setting was a Colorado health maintenance organization. Cases were women who were pregnant as a result of exposure to treatment with either assisted reproductive technologies or ovulation induction in the absence of assisted reproductive technologies. The main outcome measure was multiple birth. There was a significant association between assisted conception and multiple birth. Compared with women with naturally conceived pregnancies, there was a 25-fold likelihood (95% confidence interval 18, 35, P <.001) of multiple birth among women exposed to any of those treatments. In the total cohort the proportion of multiple births attributable to those treatments was 33%. After adjusting for the use of assisted conception and other covariates, we found no association between advanced maternal age and multiple birth. In this cohort, assisted reproductive interventions were strongly associated with multiple birth. Although a higher proportion of older women sought assisted reproductive technologies, we did not find an independent relationship between advanced maternal age and multiple birth. The increasing number of multiple births attributable to assisted conception raises public health concerns regarding multiple gestation-related maternal and infant morbidities.
To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS). Prospective pilot study. Outpatient. PATIENT(S): Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin. INTERVENTION(S): Metformin, 1.5-2.55 g/day, throughout pregnancy. MAIN OUTCOME MEASURE(S): Rates of first-trimester spontaneous abortion and teratogenicity. RESULT(S): Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (all > or = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P<.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04). CONCLUSION(S): Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.
To determine the rate of clinically evident polycystic ovary syndrome (PCOS) among first-degree female relatives within families with a proband affected by PCOS. Clinical and biochemical evaluation of the mothers and sisters of 93 patients with PCOS. The diagnosis [1] a history of oligomenorrhea, [2] clinical evidence (i.e., hirsutism) or biochemical evidence (i.e., elevated total or free T) of hyperandrogenism, and [3] the exclusion of related disorders. Tertiary care university. PATIENT(S): Patients with PCOS and their mothers and sisters. INTERVENTION(S): Interview, physical examination, and hormonal testing on blood samples were performed for all subjects. MAIN OUTCOME MEASURE(S): The presence of hirsutism and hyperandrogenemia was determined in the mothers and sisters of the patients with PCOS. RESULT(S): Of the 78 mothers and 50 sisters evaluated clinically, 19 (24%) and 16 (32%) were affected with PCOS, respectively. A higher rate of PCOS was observed when only premenopausal women not taking hormones (i.e., untreated) were considered (i.e., 35% of mothers and 40% of sisters), consistent with amelioration of symptoms with hormonal therapy or aging. These rates of PCOS are significantly higher than that observed in our general population (approximately 4%) and suggest the involvement of a major genetic component in the disorder. CONCLUSION(S): The rates of PCOS in mothers and sisters of patients with PCOS were 24% and 32%, respectively, although the risk was higher when considering untreated premenopausal women only.
To assess the reliability of the most widely used clinical methods for predicting or confirming ovulation. We monitored spontaneous cycles in 101 infertile women using basal body temperature (BBT), transvaginal ultrasound, a urinary stick system for LH surge, and three serum progesterone measurements in the midluteal phase. Transvaginal ultrasound monitoring was standard for ovulation detection and sensitivity. We calculated specificity and accuracy of each method compared with that standard. Follicular development and ultrasound evidence of ovulation were confirmed in 97 of 101 cycles (96%). Urinary LH surge preceded follicular rupture assessed by ultrasonography in all cycles and showed concordance with ultrasound-evidenced ovulation in 98 of 101 cases. The timing of BBT nadir had wide variability, and BBT and ultrasonography agreed in a similar percentage of cases (74%). Midluteal serum progesterone assessments showed ovulatory values in 93 subjects, and ovulation was concordant with ultrasonography in 90 subjects. Urinary LH was accurate in predicting ovulation with ultrasonography as the standard for detection, but time varied widely. The nadir of BBT predicted ovulation poorly. The BBT chart was less accurate for confirming ovulation, whereas a single serum progesterone assessment in midluteal phase seemed as effective as repeated serum progesterone measures.