To determine the number of embryos stored at assisted reproductive technology (ART) clinics in the United States and their current disposition. A targeted survey instrument sent by the SART-RAND team to all medical practices providing in vitro fertilization services in the United States. The SART-RAND team surveyed all 430 ART practices in the United States. Of these practices, 340 returned surveys for analysis. The data from these surveys were merged with data taken from the 1999 SART dataset, which contains information about practice size and success rates. Responding clinics reported a total of 396,526 embryos in storage as of April 11, 2002. The vast majority of the embryos (88.2%) were targeted for patient use. Small numbers of embryos were available for research, donation, destruction, quality assurance, or other uses. Nearly 400,000 embryos are stored in the United States, the majority of which (88.2%) are targeted for patient use. Few are available for research (2.8%), limiting possible conversion into embryonic stem cell lines.
Laparoscopy is the standard method to visually identify endometriotic lesions under magnification within and outside the minor pelvis. The aim of this study was to analyze the accuracy of laparoscopic visualization in diagnosing the various endometriotic sites as confirmed histologically. Presumed endometriotic sites were observed in 164 patients operated on under the clinical suspicion of endometriosis. Targeted biopsies were performed for histologic corroboration, comparing the laparoscopic findings and diagnosis to the histological results. The histological reports of the biopsies confirmed the presence of endometriosis in 138 patients (84.1%), but in 26 patients (15.9%), no evidence of endometriosis was observed. 100% of "red" lesions, 92% of "black" lesions, and 31% of "white" lesions turned out to be endometriosis. Of the 264 various suspected endometriotic sites observed, 142 (53.8%) were confirmed histologically. The most accurate diagnosis was in lesions on the parietal peritoneum of the pelvis, confirmed in 9/9 cases (100%); the ovarian fossa, confirmed in 8/12 cases (66.7%); and the uterosacral ligaments and posterior surface of the broad ligament, confirmed in 83/138 cases (60.1%). As for the other sites, the histologic confirmation rates in the ovarian surface, bowel serosa, and vesicouterine fold of the peritoneum were 48%, 40%, and 13%, respectively. Endometriosis has a multiple appearance, and the lesions may be confused with nonendometriotic lesions. It is clear that a nonhistology-based diagnosis may lead to unnecessary prolonged medical treatment and operations and may delay the proper treatment measures from being applied. Therefore, a meticulous histological confirmation should still be the first step in the laparoscopic diagnosis and treatment of suspected endometriosis.
A discrepancy exists between the interest in modern methods of natural family planning (NFP) and their actual use in developed countries. To explore reasons for this discrepancy, we analyzed data from a questionnaire administered to postpartum women in Berlin (n = 223) and Cracow (n = 233). Knowledge of NFP, past use of NFP and expected effects of abstinence on the partnership were independently associated with interest in using NFP, but not the choice to do so among those interested. Desire for future pregnancies, importance of religious belief and location in Cracow were independently associated with the choice to use NFP among those interested. Perceived accuracy of observation to identify the fertile time and acceptance of own body were independently associated with both interest in and choice to use NFP. Frequency of intercourse had no effect on interest. These results suggest that increased access and cultural support would likely lead to a higher prevalence of NFP use in developed countries.
The median age at menopause in Western populations of women is approximately 51 years. While very late (i.e., after 54 years) menopause is exceedingly uncommon, a sizeable minority of women experience cessation of ovarian function at or prior to age 45. By convention, menopause that occurs at ages 40-45 is considered "early" and occurs in about 5% of women. Premature ovarian failure (POF) is reserved for the approximately 1% of women who experience hypergonadotropic amenorrhea prior to age 40 years. POF represents the end stage of a variety of disorders that result in the loss of ovarian follicles. Depending upon the age at diagnosis, the probability of a genetic, autoimmune, or idiopathic cause will be more or less likely. Two functioning X chromosomes appear necessary for normal ovarian function. The most obvious genetic cause of POF is Turner Syndrome, in which a complete or near-complete loss of the second X chromosome occurs. Turner Syndrome typically results in the most severe and irreversible POF, often clinically evident prior to menarche. Typically, in Turner Syndrome, menopause precedes menarche, and there is no evidence of ovarian function. However, cases with multiple tissues diagnosed as 45, X have been reported to result in ovarian function and even pregnancy. It is likely that mitigating factors, perhaps autosomal, can modify this most severe and irreversible cause of ovarian failure. Lesser degrees of ovarian failure have also been attributed to partial X chromosome deletions and milder degrees of X chromosome mosaicism. Fragile X syndrome is another example of mild POF that can be linked to disorders of the X chromosome. Other genetic defects are believed to cause POF, yet their prevalence has been difficult to determine. The localization of the gene for the blepharophimosis/ptosis/POF Syndrome has been recently reported, yet this finding has not been seen commonly in POF. Other genetic syndromes including POF await elucidation. Many transgenic "knock-out" animals have been created with deficient ovarian function. Most interesting along these lines is the heterozygous FSH receptor knock-out, which exhibits a reduced follicle reserve and early ovarian depletion. Application of this knowledge and translation of these transgenic experiments into elucidation of clinical disease has been difficult, but represents an area of tremendous potential progress in the understanding of the pathogenesis of POF. Another approach to the genetics of POF has been to examine the genome of affected and unaffected individuals. The genetics appear to differ greatly depending upon the timing of the expression of the POF. For example, women with early menopause are more likely to possess the PVUII polymorphic allele for estrogen receptor alpha. Whether or not this polymorph is more common in women with earlier menopause, i.e., POF, is unclear. Pedigree data indicate that early menopause and premature menopause sort similarly within families. The only difference between women with true POF and those with early menopause may be in the timing of the expression of the syndrome, and not in the genetics. Population genetic approaches analyzing affected and unaffected individuals are underway in several research centers and represent another area of progress. Immune and other, idiopathic causes of POF await further clarification. It is clear that this is an area of great research potential. Understanding how ovaries fail may assist women with this disorder by facilitating the development of novel therapies. Additionally, such information will provide important clues about optimizing ovarian function in individuals without POF who are seeking extension of their reproductive life spans or fertility enhancement by other means.
This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.
In women suffering from polycystic ovary syndrome (PCOS), correction of hyperinsulinemia results enhances spontaneous ovulation or alternatively, the responsiveness to ovulation induction agents such as clomiphene citrate (CC). We investigated the effect of rosiglitazone maleate on ovulation induction in overweight and obese, CC-resistant women with PCOS. Double-blind, randomized, placebo-controlled trial. Academic reproductive endocrinology clinic. PATIENT(S): Overweight and obese women with clinical and laboratory manifestations of PCOS who desired pregnancy and were resistant to CC. INTERVENTION(S): Twenty-five women were randomized into two treatment groups. Subjects in Group I (n = 12) were randomized to receive rosiglitazone 4 mg b.i.d. with a placebo on cycle days 5-9. Group II (n = 13) was randomized to receive rosiglitazone 4 mg b.i.d. with CC on cycle days 5-9. The duration of the study was 2 months. MAIN OUTCOME MEASURE(S): The primary outcome was ovulation as defined by luteal serum progesterone greater than 5 ng/dL assessed on days 21, 24, and 28 of the cycle. Secondary outcomes were pregnancy and changes in insulin sensitivity, serum lipoproteins, and androgens. RESULT(S): Overall, 14 of 25 (56%) women, who were previously resistant to CC, successfully ovulated. In subjects taking rosiglitazone alone (Group I), 4 of 12 (33%) subjects ovulated compared with 10 of 13 (77%) women randomized to rosiglitazone with CC (Group II) (P=.04, Fisher's exact). One subject in Group I became pregnant, resulting in one uncomplicated live birth; two subjects in Group II conceived, with one successful live birth and one first trimester, spontaneous abortion. For all subjects, fasting insulin declined from 29.4 +/- 13.8 microU/mL to 17.3 +/- 7.8 microU/mL after rosiglitazone (P=.003, paired t-test). Although mean levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) did not decline significantly, sex hormone-binding globulin (SHBG) did increase from 0.7 +/- 0.3 microg/dL to 1.0 +/- 0.3 microg/dL after rosiglitazone therapy (P=.001, paired t test). There was also a decrease in luteinizing hormone (LH) from 9.4 +/- 6.3 mU/mL to 7.2 +/- 3.7 mU/mL (P=.01). Lipoproteins including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides did not change. Short-term rosiglitazone therapy enhances both spontaneous and clomiphene-induced ovulation in overweight and obese women with PCOS. Rosiglitazone therapy improves insulin sensitivity and decreases hyperandrogenemia primarily through increases in SHBG.
General OB/GYNUS Birth DataNational Birth TrendsPopulation-Level Trends
This report presents 2001 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal demographic characteristics including age, live-birth order, race, Hispanic origin, marital status, and educational attainment; maternal characteristics (medical risk factors, weight gain, tobacco, and alcohol use); medical care utilization by pregnant women (prenatal care, obstetric procedures, complications of labor and/or delivery, attendant at birth, and method of delivery); and infant characteristics (period of gestation, birthweight, Apgar score, abnormal conditions, congenital anomalies, and multiple births). Also presented are birth and fertility rates by age, live-birth order, race, Hispanic origin, and marital status. Selected data by mother's State of residence are shown, as well as data on month and day of birth, sex ratio, and age of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Descriptive tabulations of data reported on the birth certificates of the 4.026 million births that occurred in 2001 are presented. Denominators for population-based rates are derived from the 1990 U.S. census. As a result, rates are generally larger than would be the case if 2000-based estimates were used. The magnitude of the overestimate will vary by population subgroup; overestimates are likely greatest for those of Hispanic origin. The number of births, the birth rate, fertility rate, and total fertility rates all declined 1 percent in 2001. The teenage birth rate reached another historic low. Birth rates for women in their twenties declined slightly, whereas rates for women aged 30 to 44 years continued to rise. Births to unmarried women changed very little. Smoking by pregnant women was down again. Women were more likely to begin care in the first trimester of pregnancy (83.4 percent). The cesarean delivery rate rose for the fifth consecutive year to 24.4 percent; the primary cesarean rate was up 5 percent and the rate of vaginal births after a previous cesarean fell 20 percent. Preterm and low birthweight levels both rose for 2001. The twin birth rate continued to climb, and following 2 years of decline, the rate of triplet/+ births also increased.
Yildirim M et al., 2003·Eur J Obstet Gynecol Reprod Biol
To determine the effects of ovarian wedge resection by minilaparotomy in infertile patients with polycystic ovarian syndrome (PCOS). One hundred and thirty-four anovulatory patients with PCOS, who were previously treated with clomiphene citrate and gonadotropins and did not conceive were operated via minilaparotomy with microsurgical principles and ovarian wedge resection was performed on each subject. Pregnancy rates and adhesion formation were investigated retrospectively. A total of 121 pregnancies were achieved in 2 years (90%). One hundred and four patients conceived within the first 6 months (78%) and the remaining 17 patients conceived within 2 years (13%) following the operation. Sixty-eight patients had a second pregnancy later. In the post-operative period, 24 patients had cesarean delivery and 20 had diagnostic laparoscopy. Out of these 44 patients, only 5 of them were found to have minimal adhesions. This technique offers high pregnancy rates and minimal adhesion formation. Ovarian wedge resection by minilaparotomy might be an alternative treatment approach in patients with PCOS who did not conceive with standard ovulation induction protocols.
The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population. A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test. The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05). Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity.
To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility.
Placebo-controlled, double-blind, crossover trial.
University tertiary referral center. One hundred infertile patients (ages 20-40 years) with the following baseline concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study. Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy. Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL. Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.
Adrenomedullin (AM) gains its bioactivity by amidation at its C-terminal, forming "mature AM." The mature AM and the expression of AM receptor component mRNAs, receptor activity-modifying protein 2 and calcitonin receptor-like receptor, from feto-maternal tissues of normal pregnant women and women with histologic chorioamnionitis were examined to clarify the pathophysiological features of this intrauterine infection. Samples of the placenta and fetal membranes were obtained from 10 normal pregnant women and eight women with histologic chorioamnionitis under informed consent. Mature AM in the fetal membranes was significantly lower in patients with chorioamnionitis than in normal pregnant women. On the other hand, there were no differences in mature AM levels in the placenta between the two groups. The total AM levels as a sum of mature and immature AM were not significantly different between the two groups in either area. The ratio of mature AM/total AM was significantly decreased in the fetal membranes of the patients with chorioamnionitis compared with normal pregnancies, but not in the placenta. Also, levels of mature AM were negatively correlated with C-reactive protein concentrations. The present results thus suggested that mature AM may have some role in chorioamnionitis.
EndometriosisLaparoscopic IdentificationMinimal and Mild DiseaseHistologic Confirmation
Buchweitz O et al., 2003·J Am Assoc Gynecol Laparosc
To evaluate the reliability of diagnosing minimal and mild endometriosis under routine conditions, and to determine to what extent disease activity is taken into account. Retrospective analysis (Canadian Task Force classification II-2). University teaching hospital. Laparoscopy. One hundred eighteen consecutive women with minimal and mild endometriosis undergoing routine surgery between 1994 and 1999. MAIN Analytic parameters were the total number of endometriotic lesions; intraoperative description of pigmented, nonpigmented, and nondefined lesions; and number of extirpated lesions and histologic detection rate. In 118 patients, 311 suspected endometriotic lesions were documented. Nonpigmented lesions were reported in only 27% of women. In 51% of surgical reports no importance was attached to disease morphology or activity. Only 1.2 biopsies/patient were taken. The histologic detection rate was 56%. In 49 patients the assumed intraoperative diagnosis was confirmed by histologic examination. Intraoperative description of endometriotic lesions is inadequate. Little attention is paid to the activity of the illness. There is room for improvement in the number of excisions and histologic detection, and an attempt should be made to find a way out of this diagnostic dilemma.
Hormonal contraceptives have been associated with increased risk of HIV acquisition. The association between hormonal contraception use and HIV acquisition was assessed in a rural community-based cohort in Rakai District, Uganda. A group of 5117 sexually active HIV-negative women were surveyed at 10 month intervals between 1994 and 1999. Information on demographic and sociobehavioral characteristics, use of hormonal contraception (pill and injectable methods), condoms and the number of sexual partners was obtained by home-based interview. HIV incidence rate ratios (IRR) and 95% confidence intervals (CI) associated with hormonal contraception were estimated by multivariate Poisson regression after adjustment for age, condom use, number of sexual partners, marital status, education and history of genital ulcer disease. At one or more interviews, 16.6% of women reported use of hormonal contraceptives and 23.0% reported condom use. HIV incidence was 2.3/100 person-years in hormonal contraceptive users compared with 1.5/100 person-years in non-hormonal contraceptive users (unadjusted IRR, 1.56; 95% CI, 1.00-2.33). After multivariate adjustment, the IRR associated with hormonal contraceptives was reduced to 0.94 (95% CI, 0.53-1.64). The adjusted IRR was 1.12 (95% CI, 0.48-2.56) with oral contraceptive use and 0.84 (95%CI, 0.41-1.72) with injectable methods. Use of hormonal contraception is not associated with HIV acquisition after adjustment for behavioral confounding.
PCOSNeuroendocrine DysfunctionGnRH PulsatilityHyperandrogenism and Anovulation
Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism and chronic anovulation. Although the etiology of PCOS is unknown, perturbations of gonadotropin secretion are one of the hallmarks of this disorder. In normal menstrual physiology, the monotropic rise of plasma follicle-stimulating hormone (FSH) during the luteal-follicular transition is critical for follicular development and subsequent ovulation. One of the mechanisms by which FSH is differentially synthesized involves the luteal slowing of gonadotropin-releasing hormone (GnRH) pulse frequency by ovarian steroids. In PCOS, plasma leutinizing hormone (LH) is commonly increased, FSH is typically in the lower follicular range, and LH (and by inference GnRH) pulse frequency is persistently rapid at approximately one LH pulse per hour. The etiology of the neuroendocrine abnormalities in PCOS remain unclear; however, recent studies have revealed decreased sensitivity of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone. This abnormality is reversed by the androgen receptor antagonist flutamide, suggesting that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse generator to steroid inhibition and lead to enhanced LH secretion. As such, women with PCOS require higher levels of progesterone to slow the frequency of GnRH pulse secretion, resulting in inadequate FSH synthesis and persistent LH stimulation of ovarian androgens. The decreased sensitivity of the GnRH pulse generator may help to explain the genesis of PCOS during puberty. In normal early puberty, sleep-entrained increases in LH stimulate ovarian steroids, which subsequently suppress LH frequency and amplitude during the subsequent day. In hyperandrogenemic girls destined to develop PCOS, this nocturnal increase in ovarian steroids may not be adequate to suppress the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, impaired FSH production, and inadequate follicular development.
To review the effectiveness of metformin in restoring regular menstrual cycles and ovulation and achieving pregnancy in women with polycystic ovary syndrome (PCOS). Systematic review of pertinent studies identified using the bibliographic databases MEDLINE and EMBASE. References of selected articles identified were hand-searched for additional relevant citations. PATIENT(S): Women with PCOS undergoing treatment with metformin alone, metformin combined with other methods of ovulation induction such as clomiphene citrate (CC) or gonadotropin injections, or metformin combined with in vitro fertilization (IVF). RESULT(S): Thirty published studies were included in the overall review. Studies consisted of 12 randomized controlled trials, two cohort studies, and 16 uncontrolled descriptive studies. Due to a strong variability in the use of metformin according to study population, exposure, and outcome of interest, it was not possible to combine the data of the 12 randomized controlled trials to perform a meta-analysis. Limited data on predominately obese PCOS patients demonstrate that metformin alone improves both restoration of regular menses and spontaneous ovulation, but there are no data supporting an improvement in pregnancy rate. The addition of metformin to CC results in an improved ovulation and pregnancy rate in both unselected and CC-resistant PCOS women. There are insufficient data to make any conclusions on the effect of metformin on FSH ovulation induction or IVF. CONCLUSION(S): The effectiveness and role of metformin in the treatment of PCOS anovulatory infertility in clinical practice is difficult to assess from currently available research. Further well-designed prospective, perhaps multicenter, randomized controlled trials with the primary end point of pregnancy or live-birth rate are required.
To compare the levels of total homocysteine (tHcy), folate, vitamin B6 and B12, in women not using oral contraceptives (OC) vs. those using OC. 219 healthy women were enrolled in the study; 159 of them had not been using OC for at least 12 months prior to their enrollment, while 60 were on regular OC treatment. The median levels of vitamin B6 and B12 were significantly lower in OC users than in non-users (24.2 vs. 32.9 nmol/l, p=0.029; 278 vs. 429 ng/ml, p<0.001). There were no statistically significant differences in the levels of tHcy (fasting and post-methionine loading) and folate. In our cross-sectional study, OC use was associated with low vitamin B6 and B12 levels. Since low vitamin B6 levels are independently associated with heightened risks for arterial and venous thromboembolism (TE), they could partly account for the increased TE risk of OC users.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2002. 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).
Yong PY et al., 2003·Human reproduction (Oxford, England)
Analyses of the follicular reserve and activity of the ovary are central to our understanding of the regulation of follicular development. We have carried out a prospective analysis of endocrine and biophysical assessments under three the early follicular and mid-luteal phases, and following GnRH analogue down-regulation. Hormonal analyses were carried out before and after a single dose of FSH on spontaneously ovulating women (n = 58). Ovarian volume and antral follicle count (AFC) were also determined. Inhibin B and estradiol concentrations were increased by FSH under all three conditions, and inhibin A in the follicular phase and after down-regulation. Basal hormone concentrations, except inhibin A and B after down-regulation, did not generally correlate with AFC. A close relationship between inhibin B and AFC was evident at all stages after FSH administration (r = 0.70-0.77). AFC and inhibin B after FSH stimulation were well correlated with the number of oocytes recovered after superovulation. Multivariate analysis demonstrated that inhibin B after FSH administration in the down-regulated state showed the closest correlation with oocyte number. In the more clinically useful early follicular and luteal phases, basal FSH was the most significant contributor to the number of oocytes, with a significant contribution from luteal phase AFC. These data extend our understanding of the relationships between follicular number, follicular functional activity, and the recruitable follicular population. Down-regulation and subsequent FSH stimulation was required to clearly demonstrate the close relationship between inhibin B and the ovarian reserve. Without such complex manipulation, early follicular phase FSH (supplemented by AFC in the relatively hypogonadotrophic luteal phase) remains of greater value in predicting the ovarian reserve than the currently known direct products of the ovary.
NaProTECHNOLOGYCore CurriculumCreighton Model SystemPractitioner Training
Wright VC et al., 2003·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
MMWR 2003 Oct 3; 52(39):942. In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States to determine medical center-specific pregnancy success rates, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). 2000. CDC contracts with a professional society, the Society for Assisted Reproductive Technology (SART), to obtain data from fertility medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. The Assisted Reproductive Technology Surveillance System was initiated by CDC in collaboration with the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology, The National Infertility Association. In 2000, a total of 25,228 live-birth deliveries and 35,025 infants resulting from 99,629 ART procedures were reported to CDC from 383 medical centers that performed ART in the United States and U.S. territories. Nationally, 75,516 (76%) of ART treatments were freshly fertilized embryos using the patient's eggs; 13,312 (13%) were thawed embryos using the patient's eggs; 7,919 (8%) were freshly fertilized embryos from donor eggs; and 2,882 (3%) were thawed embryos from donor eggs. The national live-birth delivery per transfer rate was 30.8%. The five states that reported the highest number of ART procedures were California (13,194), New York (11,239), Massachusetts (8,041), Illinois (7,323), and New Jersey (5,506). These five states also reported the highest number of live-birth deliveries and infants born as a result of ART. Overall, 47% of women undergoing ART-transfer procedures using freshly fertilized embryos from their own eggs were aged <35 years; 23% were aged 35-37 years; 19% were aged 38-40 years; 7% were aged 41-42 years; and 4% were aged >42 years. Among ART treatments in which freshly fertilized embryos from the patient's eggs were used, substantial variation in patient age, infertility diagnoses, history of past infertility treatment, and past births was observed. Nationally, live-birth rates were highest for women aged <35 years (38%). The risk for a multiple-birth delivery was highest for women who underwent ART-transfer procedures using freshly fertilized embryos from either donor eggs (40%) or from their own eggs (35%). Among women who underwent ART-transfer procedures using freshly fertilized embryos from their own eggs, further variation by patient age and number of embryos transferred was observed. Of the 35,025 infants born, 44% were twins, and 9% were triplet and higher order multiples, for a total multiple-infant birth rate of 53%. Patient's residing in states with the highest number of live-birth deliveries also reported the highest number of infants born in multiple-birth deliveries. Whether an ART procedure was successful (defined as resulting in a pregnancy and live-birth delivery) varied according to different patient and treatment factors. Patient factors included the age of the woman undergoing ART, whether she had previously given birth, whether she had previously undergone ART, and the infertility diagnosis of both the female and male partners. Treatment factors included whether eggs were from the patient or a woman serving as an egg donor, whether the embryos were freshly fertilized or previously frozen and thawed, how long the embryos were kept in culture, how many embryos were transferred, and whether various specialized treatment procedures were used in conjunction with ART. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, and the number of embryos transferred. In addition, the increased risk for multiple births has a notable population impact in certain states. As use of ART and ART success rates continue to increase, ART-related multiple births are an increasingly important public health problem nationally and in many states. The proportion of infants born through ART in 2000 that were multiple births (53%) was substantially higher than in the general U.S. population during the same period. Data in this report indicate a need to reduce multiple births associated with ART. Efforts should be made to limit the number of embryos transferred for patients undergoing ART. In addition, continued research and survei
Contraception/ComparisonMechanisms of ActionPostfertilization EffectsAbortifacient Mechanisms
There are many potential mechanisms of action for the intrauterine device (IUD), which vary by type of IUD (inert, copper, or hormonal). This paper reviews the evidence for each potential mechanism of action. On the basis of available data for fertilization rates and clinical pregnancy rates, the relative contribution of mechanisms acting before or after fertilization were quantitatively estimated. These estimates indicate that, although prefertilization effects are more prominent for the copper IUD, both prefertilization and postfertilization mechanisms of action contribute significantly to the effectiveness of all types of intrauterine devices.
Reproductive EndocrinologyMicronutrient DeficienciesThyroid Hormone MetabolismTrace Element Deficiency
Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.
PCOSMetforminInsulin Resistance and HyperandrogenismAromatase Activity
To investigate the effects of reduction of insulin resistance and hyperinsulinemia associated with the polycystic ovary syndrome (PCOS) on FSH-stimulated ovarian aromatase activity. Prospective study. Academic health center, Siena, Italy. PATIENT(S): Twenty women 18 to 26 years of age in whom PCOS was diagnosed on the basis of oligomenorrhea or amenorrhea and hyperandrogenemia. INTERVENTION(S): Recombinant FSH was administered. The next day, therapy with metformin (500 mg t.i.d.) was begun. After 35 to 40 days of treatment, the pretreatment protocol was repeated. MAIN OUTCOME MEASURE(S): Plasma levels of estradiol (E(2)), androstenedione (A), and testosterone (T). The ratios of basal levels and areas under the curve (AUCs) of products and substrates were compared before and after metformin administration to detect differences in aromatase activity. RESULT(S): Metformin treatment was associated with significant reduction in basal free testosterone plasma levels, insulin plasma levels, and insulin response to oral glucose tolerance testing. Administration of FSH was followed by a significantly lesser E(2) response after metformin therapy than before this therapy. The ratios of AUC(E2) to AUC(A) and to AUC(T), indicative of aromatase activity in response to FSH, were significantly lower after metformin therapy than before. CONCLUSION(S): Metformin therapy in women with PCOS is associated with a reduction in aromatase activity in response to FSH. Insulin affects production of both androgen and estrogen. Insulin therefore plays a central role in regulating the activity of thecal and granulosa cells.
Hirsutism is a very common clinical problem encountered in daily practice, and, unfortunately, its treatment is far from satisfactory. In several studies, antiandrogens were given in combination with oral contraceptives (1–3), however, there are not enough data about the effects of combination therapy of antiandrogens in women with hirsutism.
Thirty-four patients were recruited into the study from the Endocrinology Outpatient Clinic of Erciyes University Hospital. Each patient gave informed consent, and the study was approved by the ethics committee and Institutional Review Board of Erciyes University. Cushing’s syndrome, nonclassic adrenal hyperplasia, androgen-secreting tumors, and prolactinoma were excluded by appropriate tests and radiological investigations. Twelve patients were oligomenorrheic, and these patients had polycystic ovary syndrome. Twenty-two patients had idiopathic hirsutism.
The incidence of Chlamydia trachomatis (Ct) infection and the possible correlation between couples presenting with first-trimester spontaneous abortions and active Ct infection was assessed. Additionally, the ability of Ct to infect zona-free hamster oocytes was explored by incubating the oocytes with spermatozoa from infected patients. A total of 961 women and 750 men consulting our reproductive medicine centre were screened for Ct using direct immunofluorescence. The general incidence of Ct infection was 9.4% in females (90 of 961) and 13.9% in males (104 of 750). In women with spontaneous abortions the incidence of Ct was 21.0% (14 of 66) compared with 8.9% (23 of 59) for women without spontaneous abortions and term pregnancies (chi-square, P < 0.05). When both partners of the couples were considered (one or both partners infected), the incidence rose to 68.8% (22 of 32) (chi-square, P < 0.001). In vitro studies using electron microscopy demonstrated the presence of Ct on the surface of and inside the oocyte. These results indicate a correlation between an active Ct infection and spontaneous abortion. Electron microscopy studies suggested the possibility of direct oocyte infection by Ct. Two models are proposed for the pathogenesis (i) direct zygote infection, and (ii) immune response to heat shock proteins expressed by the zygote and triggered by previous Ct infections.
Physicians who counsel women for preconception concerns are in an excellent position to give advice to couples regarding the optimal timing of intercourse to achieve pregnancy. The currently available evidence suggests that methods that prospectively identify the window of fertility are likely to be more effective for optimally timing intercourse than calendar calculations or basal body temperature. There are several promising methods with good scientific bases to identify the fertile window prospectively. These include fertility charting of vaginal discharge and a commercially available fertility monitor. These methods identify the occurrence of ovulation clinically and also identify a longer window of fertility than urinary luteinizing hormone kits. Prospectively identifying the full window of fertility may lead to higher rates of conception. Proper information given early in the course of trying to achieve pregnancy is likely to reduce time to conception for many couples, and also to reduce unnecessary intervention and cost.
PregnancyAdvanced Maternal AgePreeclampsia and Gestational DiabetesOocyte Donation Outcomes
As a result of oocyte donation, women in their sixth decade of life are now able to conceive and carry pregnancies to term. However, little is known about pregnancy outcomes in this population. To describe pregnancy outcomes in women aged 50 years or older who conceived after in vitro fertilization with donor oocytes. Retrospective analysis of cycles conducted at a US university assisted reproduction program during calendar years 1991-2001. Seventy-seven postmenopausal women with no chronic medical conditions (mean [SD] age, 52.8 [2.9] years; range, 50-63 years) who underwent 121 embryo transfer procedures (89 fresh and 32 frozen). Pregnancy outcomes were ascertained by chart review and telephone follow-up. Maternal and neonatal outcomes. There were 55 clinical pregnancies for a total pregnancy rate of 45.5%. The live birth rate was 37.2%. Of the 45 live births, 31 were singletons, 12 were twins, and 2 were triplets, for which the mean (SD) gestational ages at delivery were 38.4 (2.1) weeks, 35.8 (2.8) weeks, and 32.2 weeks, respectively. Mean (SD) birth weights were 3039 g (703 g), 2254 g (581 g), and 1913 g, respectively. Apgar scores at 1 and 5 minutes were 8.2 (0.9) and 9.1 (0.5), respectively. Of singletons, 68% were delivered by cesarean, and all multiples were delivered by cesarean. Mild preeclampsia was noted in 25% of patients and severe preeclampsia in 10%. Gestational diabetes required diet modification in 17.5%, and 2.5% required insulin. Appropriately screened women aged 50 years or older can successfully conceive via oocyte donation and experience similar pregnancy rates, multiple gestation rates, and spontaneous abortion rates as younger recipients. During pregnancy, they appear at increased risk of preeclampsia and gestational diabetes. A majority can expect to deliver via cesarean. However, there does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone.
To revise and expand the 1996 Osteoporosis Society of Canada clinical practice guidelines for the management of osteoporosis, incorporating recent advances in diagnosis, prevention and management of osteoporosis, and to identify and assess the evidence supporting the recommendations. All aspects of osteoporosis care and its fracture complications - including classification, diagnosis, management and methods for screening, as well as prevention and reducing fracture risk - were reviewed, revised as required and expressed as a set of recommendations. Strategies for identifying and evaluating those at high risk; the use of bone mineral density and biochemical markers in diagnosis and assessing response to management; recommendations regarding nutrition and physical activity; and the selection of pharmacologic therapy for the prevention and management of osteoporosis in men and women and for osteoporosis resulting from glucocorticoid treatment. All recommendations were developed using a justifiable and reproducible process involving an explicit method for the evaluation and citation of supporting evidence. All recommendations were reviewed by members of the Scientific Advisory Council of the Osteoporosis Society of Canada, an expert steering committee and others, including family physicians, dietitians, therapists and representatives of various medical specialties involved in osteoporosis care (geriatric medicine, rheumatology, endocrinology, obstetrics and gynecology, nephrology, radiology) as well as methodologists from across Canada. BENEFITS, Earlier diagnosis and prevention of fractures should decrease the medical, social and economic burdens of this disease. This document outlines detailed recommendations pertaining to all aspects of osteoporosis. Strategies for identifying those at increased risk (i.e., those with at least one major or 2 minor risk factors) and screening with central dual-energy x-ray absorptiometry at age 65 years are recommended. Bisphosphonates and raloxifene are first-line therapies in the prevention and treatment of postmenopausal osteoporosis. Estrogen and progestin/progesterone is a first-line therapy in the prevention and a second-line therapy in the treatment of postmenopausal osteoporosis. Nasal calcitonin is a second-line therapy in the treatment of postmenopausal osteoporosis. Although not yet approved for use in Canada, hPTH(1-34) is expected to be a first-line treatment for postmenopausal women with severe osteoporosis. Ipriflavone, vitamin K and fluoride are not recommended. Bisphosphonates are the first-line therapy for the prevention and treatment of osteoporosis in patients requiring prolonged glucocorticoid therapy and for men with osteoporosis. Nasal or parenteral calcitonin is a first-line treatment for pain associated with acute vertebral fractures. Impact-type exercise and age-appropriate calcium and vitamin D intake are recommended for the prevention of osteoporosis. All recommendations were graded according to the strength of the evidence; where the evidence was insufficient and recommendations were based on consensus opinion alone, this is indicated. These guidelines are viewed as a work in progress and will be updated periodically in response to advances in this field.
The (PD) peak day of cervical mucus is an important biologic marker for the self-determination of the optimal time of fertility in a woman's menstrual cycle. The purpose of this article is to provide evidence (literature and empiric) for the accuracy of the PD of cervical mucus as a biologic marker of peak fertility and the estimated day of ovulation. An analysis of data from four published studies that compared the self-determination of the PD of cervical mucus with the urinary luteinizing hormone (LH) surge was conducted. The four studies yielded 108 menstrual cycle charts from 53 women participants. The 108 cycles ranged in length from 22 to 75 days (mean 29.4 SD 6.0). Ninety-three of the 108 cycles had both an identified PD and LH surge. Data charts showed that 97.8% of the PD fell within +/-4 days of the estimated day of ovulation. Use of a standardized mucus cycle scoring system indicated that the peak in cervical mucus ratings was highest on the day of the LH surge. Self-determination of the PD of cervical mucus is a very accurate means of determining peak fertility and a fairly accurate means of determining the day of ovulation and the beginning of the end of the fertile time.
Bone HealthExercise InterventionsNon-Pharmacological Management
Exercise programs improve balance, strength and agility in elderly people and thus may prevent falls. However, specific exercise programs that might be widely used in the community and that might be "prescribed" by physicians, especially for patients with osteoporosis, have not been evaluated. We conducted a randomized controlled trial of such a program designed specifically for women with osteoporosis. We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise. Women who agreed to participate were randomly assigned to participate in a twice-weekly exercise class or to not participate in the class. We measured baseline data and, 20 weeks later, changes in static balance (by dynamic posturography), dynamic balance (by a timed figure-eight run) and knee extension strength (by dynamometry). Of 93 women who began the trial, 80 completed it. Before adjustment for covariates, the intervention group tended to have greater, although nonsignificant, improvements in static balance (mean difference 4.8%, 95% confidence interval [CI] -1.3% to 11.0%), dynamic balance (mean difference 3.3%, 95% CI -1.7% to 8.4%) and knee extension strength (mean difference 7.8%, 95% CI -5.4% to 21.0%). Mean crude changes in the static balance score were -0.85 (95% CI -2.91 to 1.21) for the control group and 1.40 (95% CI -0.66 to 3.46) for the intervention group. Mean crude changes in figure-eight velocity (dynamic balance) were 0.08 (95% CI 0.02 to 0.14) m/s for the control group and 0.14 (95% CI 0.08 to 0.20) m/s for the intervention group. For knee extension strength, mean changes were -0.58 (95% CI -3.02 to 1.81) kg/m for the control group and 1.03 (95% CI -1.31 to 3.34) kg/m for the intervention group. After adjustment for age, physical activity and years of estrogen use, the improvement in dynamic balance was 4.9% greater for the intervention group than for the control group (p = 0.044). After adjustment for physical activity, cognitive status and number of fractures ever, the improvement in knee extension strength was 12.8% greater for the intervention group than for the control group (p = 0.047). The intervention group also had a 6.3% greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis, but this difference was not significant (p = 0.06). Relative to controls, participants in the exercise program experienced improvements in dynamic balance and strength, both important determinants of risk for falls, particularly in older women with osteoporosis.
C-reactive protein (CRP) is the prototype acute-phase protein, which can increase up to 1000-fold after the onset of a stimulus. Aside from its disputed role as a marker of infection and/or inflammation in daily clinical practice, the protein has a wide variety of biological properties and functions. Due to its opsonizing abilities and its capability to activate human complement, CRP plays an important role in the innate host defense against different microorganisms, such as bacteria and fungi. The same opsonophagocyting properties can lead to clearance of host cell material, including nuclear constituents. Inflammation is one of the cornerstones in the etiology and pathogenesis of atherosclerosis, which led to worldwide attention being focused on CRP and its role in the process of atherosclerosis. This role may have a dual character. First, CRP levels reflect the 'burden' of inflammation within atherosclerotic lesions, thus reflecting the grade of vulnerability and instability of the plaques. For this reason, an increased level of the protein may be a prelude to rupture of the plaque and, thus, to occlusive arterial disease. Secondly, CRP may play an active role in the atherosclerotic process. CRP plays a role in the expression of different adhesion molecules on endothelial cells and the protein is able to activate human complement within the plaque. Furthermore, the recent discovery of local production of CRP and complement proteins within the plaque suggests an active role for the protein in the inflammatory cascade. Whatever the role for CRP in the atherosclerotic process, it has been proven that an elevated CRP level, with a cut-off point of approximately 3 mg/l, is associated with an increased risk of occlusive arterial disease, especially acute coronary syndromes.
EndometriosisVascular ErosionEmergency Conversion to LaparotomyAcute Hemoperitoneum
To report a case of acute hemoperitoneum due to erosion of the uterine artery by an endometriotic lesion of the left ovary. Case report and review of literature. University medical center. PATIENT(S): A 39-year-old nulliparous woman with stage 3 endometriosis. INTERVENTION(S): Operative laparoscopy followed by laparotomy, oophorectomy, and ligation of the bleeding uterine artery. RESULT(S): Patient is fully recovered and is attempting to conceive. CONCLUSION(S): An endometriotic lesion eroded the wall of the uterine artery, causing massive, acute hemoperitoneum. Such an event may be overlooked during laparotomy and attributed to the trauma of surgery.
SurgeryTiming and OutcomesSurgical RecurrenceSurgical Implications
In vitro studies demonstrated that implantation on membranes (peritoneum, amniotic membranes) can take place if there are defects on the surface of the membranes. If these mechanisms play a role for the development of endometriosis in vivo, then patients with surgical treatment of peritoneal endometriosis in the luteal phase must have a high recurrence rate. Retrospective analysis of operation charts and follow-up data. Department of gynecology, in a hospital-based endometriosis treatment center. PATIENT(S): Two hundred twenty premenopausal women. INTERVENTION(S): Laparoscopic treatment for peritoneal endometriosis, stage I and II by revised American Society for Reproductive Medicine guidelines. MAIN OUTCOME MEASURE(S): During the follow-up period of 2 years, symptoms and gynecological and sonographic findings were documented. In case of suspected recurrence a repeat laparoscopy with biopsy was performed to prove the recurrent endometriosis macroscopically and histologically. RESULT(S): The total recurrence rate after 2 years was 9.6%. The recurrence rate of group III (15%) was twice as high as those of group I (7%) and group II (8%), as indicated by subjective complaints, clinical findings, macroscopy, and histology; no differences were found between groups I and II. CONCLUSION(S): Endoscopic surgery for the treatment of peritoneal endometriosis should not be performed in the luteal phase.
To compare the efficacy of low-dose aspirin alone versus low-dose aspirin plus low molecular weight heparin in pregnant women with antiphospholipid syndrome and recurrent miscarriage as prophylaxis against pregnancy loss. From a regional miscarriage clinic, 119 consecutive women with persistently positive tests for lupus anticoagulant and/or anticardiolipin immunoglobulin G and M antibody were invited to participate in a randomized, controlled trial between 1997 and 2000. After ethical approval and adherence to a written protocol, 12 women were unwilling to participate, five failed exclusion/inclusion criteria, and four were nonpregnant. Laboratory analysis was performed by Sheffield University Coagulation Department, electronically generated randomization by Manchester University Centre for Cancer Epidemiology, and data collection and analysis by a research officer at Leeds University. Viability ultrasound every 2 weeks was provided until 12 weeks' gestation before transfer to the pregnancy support antenatal clinic. Ninety-eight women were randomized before 12 weeks' gestation. Forty-seven received low-dose aspirin 75 mg daily (group A), and 51 received low-dose aspirin plus low molecular weight heparin 5000 U subcutaneously daily (group B) throughout pregnancy. There were 13 pregnancy losses and 34 live births in group A and 11 losses and 40 live births in group B. The live-birth rate was 72% in group A and 78% in group B (odds ratio 1.39, 95% confidence interval 0.55, 3.47). There were no cases of maternal thrombosis in either group. A high success rate is achieved when low-dose aspirin is used for antiphospholipid syndrome in pregnancy. The addition of low molecular weight heparin does not significantly improve pregnancy outcome.
To review the evidence that polycystic ovary syndrome is a genetic disease. Review of published literature. The existing literature provides a strong basis for arguing that PCOS clusters in families. However, the mode of inheritance of the disorder is still uncertain, although the majority of studies are consistent with an autosomal dominant pattern, modified perhaps by environmental factors. In addition, studies on PCOS cells (theca, muscle, and adipocytes) in culture have documented a persistent biochemical and molecular phenotype that distinguishes them from normal cells. Although several loci have been proposed as PCOS genes including CYP11A, the insulin gene, and a region near the insulin receptor, the evidence supporting linkage is not overwhelming. The strongest case can be made for the region near the insulin receptor gene, as it has been identified in two separate studies. However, the responsible gene at chromosome 19p13.3 remains to be identified. Association studies have provided a number of potential loci with genetic variants that may create or add to a PCOS phenotype, including Calpain 10, IRS-1 and -2, and SHBG. Collectively, these findings are consistent with the concept that a gene or several genes are linked to PCOS susceptibility. Because the mutations/genotypes associated with PCOS are rare, and their full impact on the phenotype incompletely understood, routine screening of women with PCOS or stigmata of PCOS for these genetic variants is not indicated at this time. Currently the treatment implications for individually identified genetic variants is uncertain and must be addressed on a case by case basis.
InfertilityInsulin ResistanceInsulin Resistance and PregnancyFasting Insulin and Glucose
To determine whether insulin resistance is associated with recurrent pregnancy loss (RPL). Single center, case-controlled, prospective study. University-associated reproductive endocrinology clinical practice. PATIENT(S): Seventy-four nonpregnant, nondiabetic women with RPL. Controls were 74 fertile, nonpregnant, nondiabetic women without RPL who had at least one live infant, and were matched by age, race, and body mass index (BMI). INTERVENTION(S): Both groups consented to obtaining fasting insulin and glucose levels. MAIN OUTCOME MEASURE(S): Insulin resistance was defined as a fasting insulin level >20 microU/mL or a fasting glucose to insulin ratio of <4.5. RESULT(S): Among the 74 women with RPL, 20 (27.0%) demonstrated insulin resistance, whereas only 7 of 74 (9.5%) of the matched controls were insulin resistant (odds ratio 3.55; 95% confidence interval 1.40-9.01). The RPL and control groups were similar with respect to age, ethnicity, and BMI. The RPL and control groups had similar fasting glucose levels and glucose-to-insulin ratios. However, fasting insulin levels > or =20 microU/mL were statistically different between the two groups (odds ratio 3.92). CONCLUSION(S): Women with RPL have a significantly increased prevalence of insulin resistance when compared with matched fertile controls.
Fertility AwarenessDaily Conception ProbabilityDuration and TimingFecundability Estimation
This multicenter study has produced a database of 7017 menstrual cycles contributed by 881 women. It provides improved knowledge on length and location of the "fertile window" (identified as of up to 12 days duration) and the patterns and level of daily conception probability. The day of ovulation was identified in each cycle from records of basal body temperature and mucus symptoms. By referencing days of intercourse to the surrogate ovulation markers, estimates of daily fecundability were computed either directly or by the Scwartz model, both for single and multiple acts of intercourse in the fertile window. The relationship between coital pattern and fecundability has been explored. Univariate analysis underlines the significant link with fecundability only of the woman's reproductive history.
PCOSMetforminInsulin Resistance and Diabetes RiskMetabolic Effects in PCOS
Insulin resistance is a prominent feature of polycystic ovarian syndrome (PCOS), and women with the disorder are at increased risk for the development of other diseases that have been linked to insulin resistance-namely, type 2 diabetes and cardiovascular disease. This association between insulin resistance and PCOS must guide the chronic management of the disorder, and accumulating evidence suggests that administration of insulin-sensitizing drugs to individuals at high risk for type 2 diabetes decreases the rate of conversion to overt disease. In contrast, limited evidence exists to suggest that oral contraceptive pills-the currently standard therapy for PCOS-may actually decrease insulin sensitivity and induce impaired glucose tolerance in women with PCOS. Hence, PCOS should be regarded as a general health issue and the use of insulin-sensitizing drugs such as metformin should be considered for the prevention of type 2 diabetes.
To prove that several days of low-dose hCG alone can be used to stimulate folliculogenesis, complete FSH-initiated follicle/oocyte maturation, and achieve pregnancy in assisted reproduction technology. Case report. Reproductive endocrinology center at an academic institution. PATIENT(S): A 35-year-old female patient and her partner with male-related infertility. INTERVENTION(S): After an 8-day priming with hMG (225 IU/d), we administered low-dose hCG (200 IU/d) alone for 5 days in one GnRH-agonist suppressed patient until proper follicle development was obtained and intracytoplasmic sperm injection was performed. MAIN OUTCOME MEASURE(S): Daily serum levels of LH, FSH, hCG, E(2), P, and T; measurements of follicle number and size; oocytes retrieved and fertilized; pregnancy. RESULT(S): Although FSH levels rapidly declined after hMG discontinuation, E(2) and large follicles increased during hCG-only administration. Several good quality oocytes were retrieved and fertilized by intracytoplasmic sperm injection; three embryos were transferred and a twin pregnancy ensued. CONCLUSION(S): Replacement of FSH with low-dose hCG for several days in the late ovulation induction stages of assisted reproduction [1] continued growth of large ovarian follicles and E(2); [2] an optimal preovulatory follicle pattern consisting of many large and few medium and small follicles; and [3] reproductively competent oocytes and pregnancy.
General OB/GYNSystemic Lupus ErythematosusAutoimmune Disease RiskRisk Factor Analysis
Open Access
To assess risk factors associated with systemic lupus erythematosus (SLE) in the Mexican population. A case-control study was conducted on June 1996, at the Reumathology Clinic of Hospital de Especialidades del Centro Médico Nacional Siglo XXI (HE CMN), Instituto Mexicano del Seguro Social, in Mexico City. Cases were one hundred thirty subjects with four or more SLE criteria and disease evolution of +/- 5 years. Controls were hospitalized patients with acute diseases but without autoimmune diseases. Cases and controls were matched 1:1 by age and gender; both groups were evaluated by direct interview through a structured questionnaire. The following genetic family history of SLE and connective tissue disease; socioedemographic (ethnicity, geographic distribution, education, monthly income); hormonal (use of oral contraceptives, replacement therapy and gynecoobstetric background); environmental (use of hair products, living with dogs, bacterial/viral infections, and allergies). Statistical analysis consisted of odd ratios (OR) with 95% confidence intervals (CI) and multivariate analysis using logistic regression. The multivariate model showed association with family history of SLE (OR 4.2, CI 95% 1.17-15.2), family history of connective tissue disorder (OR 2.6, CI 95% 1.15-4.5), use of oral contraceptives for more than one year (OR 2.1, CI 95% 1.13-4.3), repetitive pharyngitis (OR 2.1, CI 95% 1.18-3.6), and use of medications (OR 5.0 IC 95% 1.62-21.6). No association was found with socieconomic status, hair dye products, asthma, or allergies. Genetic factors, such as family history of SLE and connective tissue disease in first-degree relatives, persist as important factors in the development of SLE. Other factors, such as use of some drugs, oral contraceptives, and repetitive pharyngitis, may also favor the onset of disease in genetically susceptible hosts. //www.insp.mx/salud/index.html.
Reproductive EndocrinologyAutoimmune Disease RiskLupus and Reproductive HistoryAutoimmune Disease Association
Estrogen and prolactin may accelerate the progression of murine systemic lupus erythematosus (SLE). In humans, 85% of lupus patients are women, which also suggests the importance of hormonal factors in disease pathogenesis. The purpose of this study was to examine hormonal and reproductive risk factors for lupus among women. This population-based, case-control study included 240 female SLE patients diagnosed between January 1, 1995 and July 31, 1999 who fulfilled the American College of Rheumatology classification criteria. Female controls (n = 321) were identified through driver's license records. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) as measures of association, adjusting for age, state, race, and education. Analyses were limited to exposures before diagnosis. Breast-feeding was associated with a decreased risk of developing SLE (OR 0.6, 95% CI 0.4-0.9), with a statistically significant trend for number of babies breast-fed and total weeks of breast-feeding. There were no associations with number of pregnancies or live births. Natural menopause occurred earlier in women with subsequent development of SLE compared with controls (P < 0.001). There was little association between SLE and current use or duration of use of hormone replacement therapy or oral contraceptives, and no association with previous use of fertility drugs. We found little evidence that estrogenor prolactin-related exposures are associated with an increased risk of lupus. The reduced risk observed among women who had breast-fed one or more babies should be examined in other studies. Early natural menopause, rather than decreasing risk of SLE because of reduced estrogen exposure, may be a marker of susceptibility to development of SLE.
Writing Group for the Women's Health Initiative Investigators, 2002·JAMA: The Journal of the American Medical Association
Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).Main outcomes measuresThe primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
To determine whether self-selected women with polycystic ovary syndrome (PCOS) are abnormal compared with a control population. Case-control. Support group meeting organized and initiated by patients. PATIENT(S): Forty-five self-selected women with PCOS and 80 control women. INTERVENTION(S): Self-selected women with PCOS at a peer support conference completed a questionnaire, had a brief physical, and gave a fasting blood sample. MAIN OUTCOME MEASURE(S): Historical, biometric, and assay results. RESULT(S): Sixty percent of the women attending the conference participated in the study. Most had been diagnosed with PCOS on the basis of ovarian morphology (35%). They were more likely to be nulliparous and have a history of oligomenorrhea (96%). They were hyperandrogenemic (significantly elevated testosterone and DHEAS levels) compared with control women. Self-selected women with PCOS displayed multiple metabolic abnormalities compared with control women, including elevations in blood pressure, waist-hip ratio, fasting insulin, fasting total cholesterol, and fasting low-density lipoprotein cholesterol levels, as well as a significant decrease in fasting glucose-insulin ratio and high-density lipoprotein cholesterol levels. CONCLUSION(S): Self-selected women with PCOS have reproductive and metabolic abnormalities. The majority of these women received inadequate treatment despite having risk factors for endometrial cancer, diabetes, and/or heart disease. Our study also suggests that women attending or participating in a PCOS support group are willing and likely to participate in clinical studies.