Polycystic ovary syndrome: it's not just infertility

Abstract: Recent diagnostic and pharmacologic developments have focused renewed attention on polycystic ovary syndrome. Clinical features of the syndrome include anovulation, hyperandrogenism and menstrual dysfunction, but several other abnormalities, including hyperinsulinemia, luteinizing hormone hypersecretion, elevated testosterone levels and acyclic estrogen production, have been documented. Accompanying obesity and lipid abnormalities compound the risk of developing diabetes mellitus or cardiovascular disease, and chronic anovulation increases the risk for endometrial cancer. A careful history and physical examination should guide diagnostic testing. Slowly progressive hyperandrogenic symptoms with anovulation of peripubertal onset often represent polycystic ovary syndrome. Treatment goals include symptom management and the identification and prevention of potential cardiovascular risks. Treatment should take into account the patient's desire for fertility. Advances in transvaginal ultrasonography and infertility treatments, including newer medications, have facilitated assisted reproduction in patients with polycystic ovary syndrome. Ongoing pharmacologic research focusing on the treatment of insulin resistance appears promising in reversing the longterm complications of the syndrome.


Oral contraceptives and the incidence of multiple sclerosis

Abstract:
Background: Experimental and clinical data suggest a protective effect of estrogens on the development and progression of MS.

Methods: We assessed whether MS incidence was associated with oral contraceptive use or parity in two cohort studies of U.S. women, the Nurses' Health Study (NHS; 121,700 women aged 30 to 55 years at baseline in 1976) and the Nurses' Health Study II (NHS II; 116,671 women aged 25 to 42 years at baseline in 1989). Participants with a diagnosis of MS before baseline were excluded. Oral contraceptive history and parity were assessed at baseline and updated biennially. During follow-ups of 18 years (NHS) and 8 years (NHS II) we documented a total of 315 definite or probable cases of MS.

Results: Neither use of oral contraceptives nor parity were significantly associated with the risk of MS. As compared with women who never used oral contraceptives, the age-adjusted relative risk (95% CI) was 1.2 (0.9, 1.5) for past users, and 1.0 (0.6, 1.7) for current users. Similar results were obtained after adjustment for latitude, ancestry, and other potential confounding factors. There was no clear trend of MS risk with either increasing duration of use or time elapsed since last use. Age at first birth was also not associated with the risk of MS.

Conclusions: These prospective results do not support a lasting protective effect of oral contraceptive use or pregnancy on the risk of MS. The decision to use hormonal contraception should not be affected by its effects on the risk of MS.


Menstrual cycle symptom variation in a community sample of women using and not using oral contraceptives

Abstract:
BACKGROUND: The prevalence of significant symptom change (symptom cyclicity) prospectively rated over multiple menstrual cycles has not been established in a non-clinical population.

METHODS: Seventy-three women charted 57 symptoms over 2-6 menstrual cycles each. Symptoms, and summarized symptom scores within seven symptom groups, were tested for changes between the follicular phase and the luteal phase of each cycle. Recurrent symptom cyclicity over multiple cycles within individuals was ascertained and the stability between cycles of mean symptom scores for both the follicular phase and the luteal phase.

RESULTS: Forty-five percent of the participants experienced cyclicity over multiple cycles in at least one symptom and 23% in at least one symptom group. Eighteen percent of the participants consistently reported a higher symptom score during the luteal phase compared to the follicular phase (a PMS-like pattern) in all symptoms in which they experienced a change. The remaining 27% experienced a varying direction of change in the same symptom between cycles, or consistently experienced a lower symptom score during the luteal phase (a reverse PMS-like pattern) of the cycles they charted. Recurrent cyclicity was experienced by 16% of the participants in one symptom; in two symptoms by 15%; in 3 8 symptoms by 14%; in one symptom group by 19% and in two symptom groups by only 4% of participants. Average symptom severity did not vary significantly between cycles.

CONCLUSION: Due to the varied direction of symptom severity change over multiple cycles, prospective daily ratings are necessary to achieve a true picture of menstrual related symptom cyclicity in the general population.

Acta Obstetricia Et Gynecologica Scandinavica


Subfertility and risk of spontaneous abortion

Lin Wu

First Affiliated Hospital of Xiamen University

Abstract:
OBJECTIVES: The purpose of this study was to assess the association between subfertility and spontaneous abortion.

METHODS: A total of 1572 women in New York and Vermont reported 3269 pregnancies between 1980 and 1990 and were able to provide an estimate of the waiting time to conception for 2967. Subfertility was defined as a delay of 1 year or more before a recognized conception was achieved. Rates of spontaneous abortion were determined among women with and without subfertility, and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via multiple logistic regression.

RESULTS: Spontaneous abortion rates were 23.0% in pregnancies preceded by subfertility and 14.0% in pregnancies without impaired fertility (adjusted OR = 1.71, 95% CI = 1.26, 2.94). The attributable risk of spontaneous abortion associated with subfertility was 6.2%.

CONCLUSIONS: Subfertile women evidence an increased number of spontaneous abortions.


Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos)

Abstract: The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality', the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50-59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies.


Effectiveness of a Standard-Rule Method of Calendar Rhythm among Mayan Couples in Guatemala

Abstract: Mayan couples in Guatemala have very low rates of contraceptive use but have long expressed an interest in natural family planning methods. A simple calendar rhythm method of family planning was tested among 301 couples living in two departments in the Guatemalan highlands. The method requires couples to keep track of the womans menstrual cycle using a calendar and a necklace as a reminder and to abstain from intercourse on days 9-19 of each cycle. Participants--most of whom were Mayan had had fewer than 7 years of schooling and had never used a contraceptive method--received instruction in how to use the method and were followed up for 1 year. Data were analyzed using life tables. 79% of couples successfully completed 1 year of use. Any difficulties they encountered with the method (i.e. with using the calendar or necklace or abstaining from intercourse for 11 days each month) occurred early in the study and after 1 year couples were highly satisfied with the method. 11% of couples conceived during the study and one-third of this group said that they had not had relations during the womans fertile period. Among the 31 couples who discontinued method use for reasons other than pregnancy the principal reason was personal factors. The only demographic characteristic that was significantly associated with continuation and pregnancy rates was age. A fairly simple natural method is potentially effective and highly acceptable among the Mayan population of Guatemala. (authors)

International family planning perspectives


Change in cervical length after cerclage as a predictor of preterm delivery

K Dijkstra

Department of Obstetrics and Gynecology, University Medical Center, Utrecht, The Netherlands. k.dijkstra@azu.nl

Abstract:
OBJECTIVE: To determine whether the degree of cervical lengthening after cerclage and whether serial follow-up measurements of cervical length after cerclage are predictive of pregnancy outcome.

METHODS: Eighty women whose primary physician determined that a prophylactic (n = 50) or urgent cerclage (n = 30) was indicated had transvaginal ultrasonographic evaluation before and after cerclage. Thereafter, most women had three additional transvaginal ultrasound examinations until 32 weeks' gestation. At each examination, the mean of three measurements was calculated. Statistical analyses were done by t test, analysis of variance, and logistic regression, with significance set at P <.05.

RESULTS: The mean +/- standard deviation precerclage cervical length was 27.2 +/- 10.3 mm and after cerclage was 34.1 +/- 9.9 mm (n = 80, P <.001, paired t test). No significant association was found (r = -0.26) between the difference in cervical length (postcerclage - precerclage lengths) and pregnancy outcome. Patients with a prophylactic cerclage had a mean cervical length that was consistently longer in patients delivering at term compared with those who delivered preterm at 20 to 32 weeks' gestation. In the urgent cerclage group a significant difference in cervical length between those who delivered at term compared with preterm was evident only at 28 to 32 weeks.

CONCLUSION: The increase in cervical length after cerclage is not predictive of term delivery. Serial cervical length measurements in the late second or early third trimester predict preterm birth but could provide earlier warning in patients with a prophylactic cerclage than in patients with urgent cerclage.


Effects of estrogen replacement on the progression of coronary-artery atherosclerosis

Abstract:
BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects.

METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography.

RESULTS: Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups.

CONCLUSIONS: Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit.


Peripheral metabolism of thyroid hormones: a review

Abstract: Peripheral metabolism of thyroid hormones is a critical component of the impact these hormones have on intracellular function. Thyroid hormones can be metabolized in peripheral tissue by deiodination, conjugation, deamination, and decarboxylation enzyme reactions. Therefore, alterations in these metabolic pathways might significantly impact the quantity of specific thyroid hormone metabolites influencing function at the cellular level. Available evidence also suggests that, under some circumstances, the activity of hepatic antioxidant enzyme systems and lipid peroxidation might influence the peripheral metabolism of thyroid hormones. Several syndromes, such as "euthyroid sick syndrome" and "low T3 syndrome," have been classified within the medical literature. The common feature of these disorders is a low level of circulating T3, with generally normal to slightly elevated blood T4 levels and either normal or slightly suppressed TSH levels. This pattern of altered thyroid hormone levels is generally agreed to be a result of impairment in extra-thyroidal peripheral metabolism. Hepatic and renal pathology, as well as catabolic states such as those induced subsequent to severe injury, illness, or trauma result in consistent shifts in the thyroid hormone profile, secondary to their impact on peripheral enzyme pathways. Lifestyle factors, such as stress, caloric restriction, and exercise, influence peripheral metabolism of thyroid hormones. Exposure to toxic metals, chemical poisons, and several drugs can also influence the peripheral fate of thyroid hormones. While the role of vitamins, minerals, and botanical extracts in thyroid hormone metabolism requires further elucidation, current evidence supports a role for selenium in the hepatic 5'-deiodination enzyme.

Alternative Medicine Review : a Journal of Clinical Therapeutic


Canadian normative data for the SF-36 health survey. Canadian Multicentre  Osteoporosis Study Research Group

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Jonathan Adachi

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada.

EA Papadimitropoulos and the CaMos Research Group.

Abstract:
Background: The Medical Outcomes Study 36-item Short Form (SF-36) is a widely used measure of health-related quality of life. Normative data are the key to determining whether a group or an individual scores above or below the average for their country, age or sex. Published norms for the SF-36 exist for other countries but have not been previously published for Canada.

Methods: The Canadian Multicentre Osteoporosis Study is a prospective cohort study involving 9423 randomly selected Canadian men and women aged 25 years or more living in the community. The sample was drawn within a 50-km radius of 9 Canadian cities, and the information collected included the SF-36 as a measure of health-related quality of life. This provided a unique opportunity to develop ageand sex-adjusted normative data for the Canadian population.

Results: Canadian men scored substantially higher than women on all 8 domains and the 2 summary component scales of the SF-36. Canadians scored higher than their US counterparts on all SF-36 domains and both summary component scales and scored higher than their UK counterparts on 4 domains, although many of the differences are not large.

Interpretation: The differences in the SF-36 scores between age groups, sexes and countries confirm that these Canadian norms are necessary for comparative purposes. The data will be useful for assessing the health status of the general population and of patient populations, and the effect of interventions on health-related quality of life.

CMAJ : Canadian Medical Association Journal = Journal De l'Association Medicale  Canadienne


Non-steroidal anti-inflammatory drugs as a possible cause for reversible infertility

L L Mendonça

Lupus in Pregnancy Clinic, St Thomas' Hospital, London, UK.

Abstract:
OBJECTIVE: To highlight the possible association between infertility and treatment with long-term non-steroidal anti-inflammatory drug (NSAIDs). NSAIDs act mainly through the inhibition of cyclooxygenase, the enzyme that catalyses the synthesis of prostaglandins, which are essential mediators of ovulation, implantation and placentation of the conceptus.

METHODS: Case reports of four women suffering from severe arthritis, on long-term NSAIDs and undergoing extensive investigation and treatment for infertility.

RESULTS: During the last 2 yr, four out of five women with severe arthritis and difficulty conceiving were counselled to stop NSAIDs, and they successfully conceived shortly after the withdrawal of NSAIDs.

CONCLUSION: NSAIDs, used largely for the treatment of rheumatological conditions, may be responsible for some cases of infertility.


Perineal endometriosis with anal sphincter involvement: report of a case

Abstract:
INTRODUCTION: Perineal endometriosis with anal sphincter involvement is an infrequent occurrence. Wide excision is the best chance of cure of perineal endometriosis but may cause incontinence when the anal sphincter is involved. Conversely, narrow excision may result in incomplete removal, with increased recurrence rates and need of additional therapy. Wide excision with primary sphincteroplasty and narrow excision surgical techniques are reviewed.

METHODS: One case report of perineal endometriosis with anal sphincter involvement and previously reported cases were reviewed. Patients were compared based on type of resection (wide or narrow excision) and outcome.

RESULTS: Since 1957 there have been seven reported cases of perineal endometriosis with anal sphincter involvement, with the present authors adding one additional case for a total of eight. The mean age was 33 (range, 22-47) years. Surgical treatment included wide excision with primary sphincteroplasty (2 cases), narrow excision (4 cases), and incomplete excision (1 case). One case spontaneously regressed after a subsequent pregnancy. There were two recurrences in the narrow excision group and no recurrences in the wide excision group. There were no complications reported for any of the procedures.

CONCLUSIONS: Although follow-up time was variable and the numbers small, wide excision with primary sphincteroplasty for patients with perineal endometriosis with anal sphincter involvement seems to be the best chance of cure with good functional results. It should be considered particularly in younger patients to obviate the need of long-term subsequent hormonal therapy or re-excision for symptomatic recurrences. In contrast, patients closer to menopause (when endometriosis tends to regress) may be treated optimally by narrow excision to avoid the risks of significant anal sphincter resection.


Profile and opinions of the female Persona user in The Netherlands

C J Janssen

Department of Sexology and Psychosomatic Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, The Netherlands.

Abstract:
Objectives: The primary objective of this study was to investigate the profile of the Dutch Persona user and her opinion about this relatively new way of natural birth control. The results of the study were used to draw conclusions for the suitability for Persona as a contraceptive method. METHOD: Data from 137 users of the device were obtained from structured questionnaires.

Results: The 'Persona woman' is typically in a steady relationship, highly educated and has an above-average income. She wants to have a contraceptive method with no side-effects and desires children in the future. She is therefore looking for information about her own cycle. It is remarkable that one in four women uses the system to help in planning a pregnancy instead of avoiding one.

Conclusions: Persona seems to be a welcome alternative for natural family planning and for couples who have no absolute negative attitude towards a(nother) child, but want to postpone their first pregnancy or to space pregnancies. The method is not reliable enough to be used as the only contraceptive method when a couple absolutely wants to prevent a pregnancy. Another conclusion that can be drawn is that the method improves fertility awareness.

The European Journal of Contraception & Reproductive Health Care : the Official  Journal of the European Society of Contraception


The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System

Michael S Kramer

Department of Pediatrics, McGill University Faculty of Medicine, Montreal, Quebec, Canada.

Abstract:
CONTEXT: The World Health Organization defines preterm birth as birth at less than 37 completed gestational weeks, but most studies have focused on very preterm infants (birth at <32 weeks) because of their high risk of mortality and serious morbidity. However, infants born at 32 through 36 weeks are more common and their public health impact has not been well studied.

OBJECTIVE: To assess the quantitative contribution of mild (birth at 34-36 gestational weeks) and moderate (birth at 32-33 gestational weeks) preterm birth to infant mortality.

DESIGN, SETTING, AND

PARTICIPANTS: Population-based cohort study using linked singleton live birth-infant death cohort files for US birth cohorts for 1985 and 1995 and Canadian birth cohorts (excluding Ontario) for 1985-1987 and 1992-1994.

MAIN OUTCOME MEASURES: Relative risks (RRs) and etiologic fractions (EFs) for overall and cause-specific early neonatal (age 0-6 days), late neonatal (age 7-27 days), postneonatal (age 28-364 days), and total infant death among mild and moderate preterm births vs term births (at >/=37 gestational weeks).

RESULTS: Relative risks for infant death from all causes among singletons born at 32 through 33 gestational weeks were 6.6 (95% confidence interval [CI], 6.1-7.0) in the United States in 1995 and 15.2 (95% CI, 13.2-17.5) in Canada in 1992-1994; among singletons born at 34 through 36 gestational weeks, the RRs were 2.9 (95% CI, 2.8-3.0) and 4.5 (95% CI, 4.0-5.0), respectively. Corresponding EFs were 3.2% and 4.8%, respectively, at 32 through 33 gestational weeks and 6.3% and 8.0%, respectively, at 34 through 36 gestational weeks; the sum of the EFs for births at 32 through 33 and 34 through 36 gestational weeks exceeded those for births at 28 through 31 gestational weeks. Substantial RRs were observed overall for the neonatal (eg, for early neonatal deaths, 14.6 and 33.0 for US and Canadian infants, respectively, born at 32-33 gestational weeks; EFs, 3.6% and and 6. 2% for US and Canadian infants, respectively) and postneonatal (RRs, 2.1-3.8 and 3.0-7.0 for US and Canadian infants, respectively, born at 32-36 gestational weeks; EFs, 2.7%-5.8% and 3.0%-7.0% for the same groups, respectively) periods and for death due to asphyxia, infection, sudden infant death syndrome, and external causes. Except for a reduction in the RR and EF for neonatal mortality due to infection, the patterns have changed little since 1985 in either country.

CONCLUSIONS: Mild- and moderate-preterm birth infants are at high RR for death during infancy and are responsible for an important fraction of infant deaths. JAMA. 2000;284:843-849


Multiple gestation: reflections on epidemiology, causes, and consequences

Abstract: Multiple births (of all orders) increased in epidemic proportions in the years 1971-1997. Twins increased 53%, 32%, 31%, and 83% in white, Afro-American, Native American and Mexican American women, respectively. Triplet, quadruplet, and quintuplet+ births increased >400%, >1,100%, and >500%, respectively, in the same years. The principal causes of these changes are related to the increasing age of the maternal cohort and an increasing incidence of fertility-inhibiting diseases and conditions in association with advancing maternal age. Major immediate consequences of these changes include disproportionately large numbers of infants born at <33 weeks' gestation (1.7% for singletons vs. 41.2% for triplets) and at <1,500 g birth weight (1.1% for singletons vs. 31.9% for triplets). Additional short-term consequences include an almost 2,000% increase in infant deaths (per 1,000 live births) among triplets compared with singletons (190.4 vs. 11.2). Long-term risks include a 300% increase in the relative risk of handicap in triplets compared with singletons (2.9 vs. 1.0), and a 650% increase in the rate of cerebral palsy per 1,000 live births in triplets compared with singletons (26.6 vs. 1.6). Peripartum costs relate to prematurity rather than plurality, as do lifetime survivorship costs, which relate to morbidities and subsequent health-related problems.

International Journal of Fertility and Women's Medicine


Disposition of extra embryos

Disposition of extra embryos

S A Beyler

University of North Carolina at Chapel Hill

M A Fritz

Uniformed Services University of the Health Sciences

Abstract:
Contemporary practice in assisted reproductive technologies (ART) compensates for the attrition that occurs at each phase of the cycle. Every follicle does not yield an egg, nor does every egg fertilize. Of those that do, many fail to properly develop, and even fewer implant. Nevertheless, ART cycles usually result in more embryos than are needed for transfer. With clinical and laboratory advances in the field and the undeniable need to reduce the incidence of multiple gestation, we must focus increased attention on these “spare” or “extra” embryos and their fate.
The relative quality of extra embryos clearly influences their disposition. Although the pregnancy potential of any single embryo is always uncertain, a fragmented embryo from a patient over the age of 40 generally has less potential than a morphologically normal one from an egg donor. Data from 1996 SART registry (1) suggests that only 4% of transferred embryos from patients 39 years and older result in a child, whereas this number is approximately 12% in women under 35. Because most programs choose the highest quality embryos for transfer, potential implantation rates for spare embryos would be lower.
Registry data are invaluable to track progress in the field, but they do little to guide decisions concerning individual patients, because the implantation rate of any given embryo of reasonable morphology is either zero or 100%. In the absence of more reliable markers of implantation potential, we must assume that all transferred embryos can implant. . .


Infertility is a symptom, not a disease

Infertility is a symptom, not a disease

R P Dickey

Louisiana State University Health Sciences Center New Orleans

Abstract:
In an otherwise excellent editorial that appeared in this journal concerning the problems created by failure of the Health Insurance Industry to provide coverage for infertility, the author, a noted academician and clinician, repeatedly referred to infertility as a disease (1). The mistaken idea that infertility is a disease is commonplace among not only academicians and clinicians but also among third-party payers and the general public and is one of the reasons that infertility is not covered by most insurance plans.
The facts are that infertility and its frequent companion, anovulation, are not diseases; they are symptoms of underlying, sometimes serious disease in one or both marital partners. One result of considering infertility and anovulation as diseases rather than as symptoms is that unnecessarily powerful and expensive treatments may be used to obtain an immediate pregnancy, whereas chronic disease that may affect lifelong health is overlooked.
Just as the symptoms chronic headache, chronic stomach pain, and chronic chest pain may be caused by underlying disease, so may infertility be caused by underlying disease. Endometriosis, uterine fibroids, benign ovarian tumors, and pelvic adhesive disease are causes of infertility that can be treated by laparoscopy, if detected early, but may require more extensive surgery later if they remain undiagnosed. Anovulation may be due to insulin resistance that can result in diabetes or cardiovascular disease later in life (2) or any of a number of other endocrine disorders with lifelong effects.
A 1991 study from the Centers for Disease Control and prevention (CDC) found that the lifetime risk of developing endometrial cancer was increased not only in patients with polycystic ovary syndrome but also in infertile patients with hypothyroidism, uterine fibroids, and endometriosis (3). Infertile women with any of these conditions who conceived a term pregnancy did not have an increased risk of endometrial cancer.
A major obstacle to the treatment of infertility as a symptom by the Health Insurance Industry is the way it is characterized in the International Classification of Diseases, Volume 9 (ICD). In the ICD, female infertility (Code 628.0) and male infertility (606.0) are classified as diseases but are clearly treated as symptoms. Female infertility is listed as “associated with,” “due to,” or “having its origin in” 30 other conditions. Similarly, male infertility is listed as “due to” 12 other conditions. Anovulation is given the same diagnostic code number as female infertility (628.0) and is not classified further as to its underlying causes. Health insurers have taken advantage of this to deny coverage for endocrine evaluation of patients with anovulation on the basis that it is synonymous with infertility.
The ICD needs to be revised according to modern understanding of anovulation and the causes of female and male infertility, as was done in the 1999 edition for complications of pregnancy and childbirth. Health insurers must acknowledge that anovulation is a symptom separate from infertility that requires diagnosis and treatment irrespective of a desire to become pregnant. All of us, practicing physicians and academicians, should make establishment of an accurate and complete diagnosis our first goal when presented with an infertile couple.


Laparoscopy in the "normal" infertile patient: a question revisited

Abstract:
STUDY OBJECTIVE: To determine the prevalence of reproductive pathology in a group of infertile women thought to be at low risk for altered pelvic anatomy.

DESIGN: Retrospective chart review and follow-up (Canadian Task Force classification II-2).

SETTING: Academic-affiliated, private reproductive endocrinology practice.

PATIENTS: One hundred infertile women.

INTERVENTION: Diagnostic and/or therapeutic laparoscopy.

MEASUREMENTS AND

MAIN RESULTS: Of 100 patients with a negative reproductive work-up up to the point of laparoscopy, 68 had pathology of reproductive

significance: intrinsic tubal disease 24, peritubal adhesive disease 34, and endometriosis 43, some in combination. Laparoscopy was especially helpful in establishing treatment protocols for older women, who were referred for assisted reproductive techniques earlier than otherwise might have been the case. Women conceived after hormone therapy and after operative intervention. Although the hysterosalpingogram was read as normal in all women, tubal disease was diagnosed laparoscopically, independent of endometriosis, in 27 patients, with 2 having complete obstruction. Endometriosis stage I-II was found in 22 patients, stage III in 13, and stage IV in 6.

CONCLUSION: Even in women thought to be at low risk for significant pelvic pathology affecting reproduction, the yield was high. Although some pregnancies were achieved after operative intervention, frequently laparoscopy was helpful in making a decision to go to assisted reproductive technology, particularly when infertility had been of long duration and in older women. Frequently the degree of pathology was such that a full operating suite was necessary to provide adequate instrumentation and anesthesia for operative intervention, which would not have been the case with office laparoscopy.

The Journal of the American Association of Gynecologic Laparoscopists


Contribution of assisted reproductive technology and ovulation-inducing drugs to triplet and higher-order multiple births--United States, 1980-1997

Abstract: In the United States, pregnancies associated with assisted reproductive technology (ART) or ovulation-inducing drugs are more likely to result in multiple births than spontaneously conceived pregnancies (1). In addition, triplet and higher-order multiple births are at greater risk than singleton births to be preterm (< or = 37 completed weeks' gestation), low birthweight (LBW) (i.e., < or = 2500 g), or very low birthweight (i.e., < 1500 g), resulting in higher infant morbidity and mortality (2). Because preterm and LBW infants often require costly neonatal care and long-term developmental follow-up, the continuing increase in triplet and higher-order multiple births causes concern among health-care providers and policymakers (3). This report provides estimates of the contribution of ART and ovulation-inducing drugs to these birth outcomes for 1996 and 1997, and summarizes trends during 1980-1997, which indicate that the ratio of triplet and higher-order multiple births has more than quadrupled and that a large proportion of this increase can be attributed to ART or the use of ovulation-inducing drugs.

MMWR. Morbidity and Mortality Weekly Report


Gonadotropin-releasing hormone-stimulated sperm binding to the human zona is mediated by a calcium influx

P Morales

Pontificia Universidad Católica de Chile

Abstract: The mechanism by which GnRH increases sperm-zona pellucida binding in humans was investigated in this study. We tested whether GnRH increases sperm-zona binding in Ca(2+)-free medium and in the presence of Ca(2+) channel antagonists. We also examined the GnRH effect on the intracellular free Ca(2+) concentration ([Ca(2+)](i)). Sperm treatment with GnRH increased sperm-zona binding 300% but only when Ca(2+) was present in the medium. In Ca(2+)-free medium or in the presence of 400 nM nifedipine, 80 microM diltiazem, or 50 microM verapamil, GnRH did not influence sperm-zona binding. GnRH increased the [Ca(2+)](i) in the sperm in a dose-dependent manner. The maximum effect was reached with 75 nM GnRH. The GnRH-induced increase in [Ca(2+)](i) was fast and transient, from a basal [Ca(2+)](i) of 413 +/- 22 nM to a peak value of 797 +/- 24 nM. The GnRH-induced increase in [Ca(2+)](i) was entirely due to a Ca(2+) influx from the extracellular medium because the increase in [Ca(2+)](i) was blocked by the Ca(2+) chelator EGTA and by the Ca(2+) channel antagonists nifedipine and diltiazem. These antagonists, however, were not able to inhibit the progesterone-activated Ca(2+) influx. On the contrary, T-type calcium channel antagonists pimozide and mibefradil did not affect GnRH-activated Ca(2+) influx but inhibited the progesterone-activated Ca(2+) influx. Finally, the GnRH-induced Ca(2+) influx was blocked by two specific GnRH antagonists, Ac-D-Nal(1)-Cl-D-Phe(2)-3-Pyr-D-Ala(3)-Arg(5)-D-Glu(AA)(6)-GnRH and Ac-(3,4)-dehydro-Pro(1),-p-fluoro-D-Phe(2), D-Trp(3,6)-GnRH. These results suggest that GnRH increases sperm-zona binding via an elevation of [Ca(2+)](i) through T-type, voltage-operated calcium channels.


Population-based screening for postpartum depression

Abstract:
OBJECTIVE: To estimate the community prevalence in Olmsted County, Minnesota of elevated scores on the Edinburgh Postnatal Depression Scale, a self-report screening tool for postpartum depression.

METHODS: At the 6-week postpartum visit, the Edinburgh Postnatal Depression Scale was administered to women who gave birth in Olmsted County between July 28, 1997 and March 28, 1998. Study sites included all ambulatory clinics that provide pregnancy care in the county, and women who missed postpartum visits were contacted by mail. A threshold of 12 or more points on the scale was selected for clinical use; data for scores of ten and above were also examined.

RESULTS: Of the 909 Olmsted County women studied (response rate 83.2%), 11.4% (n = 104) had scores of 12 or greater, with a 95% confidence interval (CI) of 9.4%, 13.5%. The percentage of women with a positive screen increased to 19.8% (n = 180; 95% CI 17.2%, 22.4%) when scores of 10 or higher were included, as has been recommended for screening in primary care settings. Forty-eight or 5.3% of the subjects (95% CI 3.8%, 6.7%) indicated experiencing suicidal ideation during the previous week.

CONCLUSION: More than 11% of women had elevated scores on the Edinburgh Postnatal Depression Scale, indicating a high likelihood of postpartum depression and the need for further assessment. The screening process required little extra time and was acceptable to the subjects and clinicians. Screening for postpartum depression is appropriate and feasible for clinical practice and increases the identification of women suffering from this serious, common, and highly treatable disorder.


Oral contraceptives and fatal pulmonary embolism

Abstract: In a national case-control study of fatal pulmonary embolism in New Zealand women of childbearing age, we estimated that current users of combined oral contraceptives had a relative risk of 9.6 (95% CI 3.1-29.1). From national distribution data, the absolute risk of death from pulmonary embolism in current users was estimated to be 10.5 per million woman-years.


Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey

Abstract: A cross-sectional survey was conducted to examine quality of life (QOL) related to physiological, somatic, and vasomotor effects of changing progestogen treatment from medroxyprogesterone acetate (MPA) to micronized progesterone in postmenopausal women. Eligible women (n = 176) were currently using hormone replacement therapy (HRT) containing micronized progesterone for 1-6 months and had previously received HRT containing MPA. QOL was assessed via telephone interview using the Greene Climacteric Scale and the Women's Health Questionnaire. When compared with the MPA-containing regimen, women using micronized progesterone-containing HRT experienced significant improvement in vasomotor symptoms, somatic complaints, and anxiety and depressive symptoms. Women reported improved perceptions of their patterns of vaginal bleeding and control of menopausal symptoms while on the micronized progesterone-containing regimen. Approximately 80% of women reported overall satisfaction with the micronized progesterone-containing regimen. A micronized progesterone-containing HRT regimen offers the potential for improved QOL as measured by improvement of menopause-associated symptoms.

Journal of Women's Health & Gender-based Medicine


The importance of user compliance on the effectiveness of natural family planning  programs

G A Tommaselli

Department of Gynecology, Obstetrics and Pathophysiology of Human Reproduction, School of Medicine, University Federico II of Naples, Italy.

Abstract: Nowadays, there is an increasing interest in natural family planning methods. The biological basis for the application of natural family planning methods is the recognition of ovulation and, more extensively, of the fertile period. Several studies in the past decade have shown the efficacy of these methods and that the main cause of failure was either a conscious departure from the rules of the method or erroneous application of the method. Another problem affecting natural family planning that has been highlighted is the relatively high discontinuation rate. These features are probably due to low compliance in applying the natural family planning rules, which may be too demanding for a number of couples. In this review, there are comments on the application of natural family planning methods, the discontinuation rates and the failure of the method due to mistakes in the studies carried out in the past 15 years. Steps that can be taken to limit mistakes and discontinuity are also addressed.

Gynecological Endocrinology : the Official Journal of the International Society  of Gynecological Endocrinology


Avoiding multiple pregnancies in ART: consideration of new strategies

Abstract: To maximize pregnancy rates, physicians who perform IVF, often transfer multiple embryos, which increases the multiple birth risk. Multiple birth infants are at significant risk for a number of adverse outcomes including preterm delivery, low birth weight, congenital malformations, fetal and infant deaths and long term morbidity and disability among survivors. Since the ultimate goal for an IVF treatment is the birth of a healthy infant, an important issue for all kinds of assisted reproductive technologies (ART) must be the reduction or elimination of multiple pregnancies. In this article, different strategies to avoid multiple births in ART are discussed.


Uterine contractility during the menstrual cycle

Dominique De Ziegler

Université de Versailles Saint-Quentin-en-Yvelines

Abstract: The non-pregnant uterus shows different patterns of contractility during the menstrual cycle. A renewed interest in uterine contractility has resulted from reports of non-invasive ultrasound (US) based studies. To clarify the changes in uterine contractility occurring throughout the menstrual cycle, we prospectively studied uterine contractions (UC) at six representative stages with US and intrauterine pressure (IUP) based approaches in 30 cycling volunteers. Results showed UC frequency could be measured by either US or IUP. UC amplitude and resting pressure tone could only be assessed by IUP. Conversely, direction of UC displacement could only be assessed by US. UC frequency increased at mid-cycle and decreased throughout the luteal phase suggesting oestradiol and progesterone exert positive and negative actions on uterine contractility, respectively. UC amplitude increased throughout the menstrual cycle to maximum values in the late luteal phase. Retrograde UC were most frequent at mid-cycle and convergent ('opposing') UC predominated during the luteal phase. While the former pattern ensures sperm transport, the latter may facilitate embryo implantation. In conclusion, UC changes throughout the menstrual cycle assessed by US and IUP emphasize the hormonal dependence of uterine contractility. Although UC patterns favouring sperm transport appear regulated by oestradiol, uterine quiescence and the dominance of convergent UC prevailing at the time of implantation are linked to progesterone. These data will serve to identify and treat possible dyskinetic changes in uterine contractility, particularly in women suffering from infertility, endometriosis, and dysmenorrhea.


Polycystic Ovary Syndrome as an Autoimmune Disease: A New Concept


Increased adverse pregnancy outcomes with unreliable last menstruation

Van Thanh Nguyen

University of Medicine and Pharmacy at Ho Chi Minh City

Abstract:
OBJECTIVE: To estimate the risk of adverse outcomes in women whose first day of the last menstrual period (LMP) was unreliable.

METHODS: Among 20,244 singleton pregnancies with measurements of biparietal diameter between 12 and 22 weeks' gestation, LMP was registered as unreliable in 3775 (18.6%) and reliable in 16,469 (81.4%). Adverse outcomes were defined as spontaneous or missed abortions after 12 weeks' gestation, stillbirth or postnatal death within 1 year, preterm birth, birth weight less than 2500 g, and low birth weight (LBW) for gestation (lower than 22% below sex-specific expected weight). Logistic regression analysis and Kaplan-Meier survival analysis were used to analyze the risk of adverse outcomes.

RESULTS: The risk of death was doubled in pregnant women with unreliable LMPs compared with those with reliable LMPs (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.5, 2.6). This risk was highest with respect to stillbirth (OR 2.7; 95% CI 1.7, 4.3). The risks of preterm birth, LBW, and LBW for gestation were also significantly increased (ORs 1.5, 1.4, and 1.2; 95% CIs 1.3, 1.7; 1.2, 1.6; and 1. 0, 1.4, respectively).

CONCLUSION: An unreliable LMP is associated with increased risk of adverse outcomes, especially fetal death.


Treatment of Preterm Labor with Human Chorionic Gonadotropin: A New Modality

Abstract:
Background: Previous studies have demonstrated that human myometrium contains receptors for human chorionic gonadotropin (hCG) and that hCG can inhibit myometrial contractions in vitro.

Objective: To use for the first time hCG as a tocolytic agent in the treatment of preterm labor.

Methods: The study group included 100 women with preterm labor; 50 were assigned to receive HCC and 50 placebo. Assignment was made with stratification according to four categories of gestational age between 20–35 weeks. One half of the surviving infants were followed-up at 18 months. The protocol of the dosage consisted of one single dose of hCG 5,000 IV and 10,000 units of hCG in 500 dextrose as a drip of 20 drops per minute.

Results: The mean length of time from randomization to delivery differs significantly for the two groups: 28.8 days for the hCG group and 15 days for the placebo treatment group (highly statistically significant, P <0.001). There was statistically significant difference (P <0.05) between the two groups regarding the induction of delivery before 37 weeks and the proportion of infants weighing less than 2,500 g. Human chorionic gonadotropin treatment was associated with an improvement score on the Bayley psychomotor development index.

Conclusions: Human chorionic gonadotropin exhibits potent tocolysis with no fetal side effects. This preliminary study suggests that HCG may be a candidate for tocolytic therapy of preterm labor.


Effects of gonadal steroids in women with a history of postpartum depression

M Bloch

Behavioral Endocrinology Branch, NIMH, NIH, Bethesda, MD 20892-1276, USA.

P J Schmidt

Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1276, USA.

Merry A. Danaceau

Center for Clinical Research (United States)

L K Nieman

Health and Human Development (2HD) Research Network

Abstract:
OBJECTIVE: Endocrine factors are purported to play a role in the etiology of postpartum depression, but direct evidence for this role is lacking. The authors investigated the possible role of changes in gonadal steroid levels in postpartum depression by simulating two hormonal conditions related to pregnancy and parturition in euthymic women with and without a history of postpartum depression.

METHOD: The supraphysiologic gonadal steroid levels of pregnancy and withdrawal from these high levels to a hypogonadal state were simulated by inducing hypogonadism in euthymic women-eight with and eight without a history of postpartum depression-with the gonadotropin-releasing hormone agonist leuprolide acetate, adding back supraphysiologic doses of estradiol and progesterone for 8 weeks, and then withdrawing both steroids under double-blind conditions. Outcome measures were daily symptom self-ratings and standardized subjective and objective cross-sectional mood rating scales.

RESULTS: Five of the eight women with a history of postpartum depression (62.5%) and none of the eight women in the comparison group developed significant mood symptoms during the withdrawal period. Analysis of variance with repeated measures of daily and cross-sectional ratings of mood showed significant phase-by-group effects. These effects reflected significant increases in depressive symptoms in women with a history of postpartum depression but not in the comparison group after hormone withdrawal (and during the end of the hormone replacement phase), compared with baseline.

CONCLUSIONS: The data provide direct evidence in support of the involvement of the reproductive hormones estrogen and progesterone in the development of postpartum depression in a subgroup of women. Further, they suggest that women with a history of postpartum depression are differentially sensitive to mood-destabilizing effects of gonadal steroids.


Amniotic fluid interleukin-6 and preterm delivery: a review

Abstract:
OBJECTIVE: To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection.

DATA SOURCES: We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords "labor/infant," "premature," "cytokines/interleukin-6," and "AF." We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles.

METHODS OF STUDY SELECTION: The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery.

TABULATION, INTEGRATION, AND

RESULTS: There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33-70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered.

CONCLUSION: Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.


Effects of in vitro fertilization on low birth weight, preterm delivery, and multiple birth

Abstract:
PURPOSE: To quantify the contribution of in vitro fertilization (IVF) on changes in the rates of low birth weight (LBW), preterm delivery, very low birth weight, and multiple births during the past 3 years.

METHODS: Data on IVF pregnancies from 1994 to 1996 within Alberta were reviewed. Population data were obtained from the Provincial notice of a live or stillbirth.

RESULTS: The IVF component of increased LBW rate in the province was 17.8% for infants <2500 g and 43.5% for those born <1500 g. IVF accounted for 10.5% of the provincial rate increase in deliveries <37 weeks' gestation and 66.2% of those <30 weeks' gestation. IVF accounted for 21.4% of the twins and all of the sets of triplets in the province.

CONCLUSION: During a 3-year period IVF has affected the incidence of LBW, preterm delivery, and multiple birth. IVF is a substantial contributor to changes in very low birth weight and delivery before 30 weeks, which is partly related to multiple births.


Characteristics of women associated with continuing instruction in the Creighton Model Fertility Care System

Abstract: Effective use of natural family planning is strongly dependent upon adequate instruction. The Creighton Model Fertility Care System (CrMS) has a standardized protocol for instruction of new users that includes individual follow-up visits in the first year of use. This study evaluated the number of follow-up visits completed by new CrMS users from eight CrMS centers in the United States. Four follow-up visits were completed by 75.7% of women. Women who continued instruction were more likely to be educated, Catholic, and white, and to have a more challenging reproductive status (discontinuing oral contraceptives, or breastfeeding). These results suggest that the number of follow-up visits needed varies among new CrMS users. Future research should address the optimal length of instruction for adequate use of the CrMS by women with different characteristics and needs.


Barrier agents for preventing adhesions after surgery for subfertility

Abstract:
Background: Pelvic adhesions can be the result of inflamation, endometriosis or surgical trauma. Prevention of postoperative adhesions (either new or reoccurance) has been postulated by using barriers to prevent two surfaces being in contact. When pelvic surgery is being undertaken strategies to reduce pelvic adhesions occurring may be undertaken and these include barrier agents which are placed between the pelvic structures. Two synthetic barriers with differential characteristics are commercially available: oxidised regenerated cellulose (Interceed) and polytetrafluoroethylene (PTFC) (GoreTex).

Objectives: The objective of this review was to assess the effect of mechanical barriers (materials interposed between pelvic structures to prevent adherence of serosal surfaces) used during pelvic surgery in women of reproductive age on pregnancy rates, pelvic pain, or postoperative adhesion reformation.
Search Strategy: The Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled clinical trials was undertaken. In addition, companies were contacted for unpublished trials.
Selection Criteria: Randomised controlled trials or controlled clinical trials of barriers versus no treatment or other barriers in women undergoing fertility preserving pelvic surgery. DATA COLLECTION AND ANALYSIS: Reviewers assessed eligibility and trial quality.

MAIN Results: 15 randomised controlled trials were included. Five trials randomised patients while the remainder randomised pelvic organs. Laparoscopy was the primary surgical technique in six trials while the remaining trials were laparotomy. Indications for surgery included myomectomy (five trials), ovarian surgery (four trials), pelvic adhesions (six trials), endometriosis (two trials) and mixed (one trial). Thirteen trials assessed Interceed versus no treatment, two assessed Interceed versus Gore-Tex, one trial assessed Gore-Tex versus no treatment, and one trial assessed Seprafilm versus no treatment. No study reported pregnancy or reduction in pain as an outcome. The use of Interceed in women was associated with reduced incidence of pelvic adhesion formation, both new formation and re-formation following laparoscopic surgery and after laparotomy. Gore-Tex was more effective than no barrier or Interceed in preventing adhesion formation. There was limited evidence that Seprafilm was effective in preventing adhesion formation in women following myomectomy. REVIEWER'S

Conclusions: The absorbable adhesion barrier Interceed reduces the incidence of adhesion formation, both new formation and re-formation, at laparoscopy and laparotomy, but there are insufficient data to support its use to improve pregnancy rates. Gore-Tex may be superior to Interceed in preventing adhesion formation but its usefulness is limited by the need for suturing and later removal. There was no evidence of effectiveness of Seprafilm in preventing adhesion formation.

The Cochrane Database of Systematic Reviews


Preterm delivery for maternal or fetal indications: maternal morbidity, neonatal outcome and late sequelae in infants

M Kurkinen-Räty

Department of Obstetrics and Gynaecology, University of Oulu, Finland.

Abstract:
Objective: To assess maternal morbidity, and neonatal outcome and especially long term sequelae in infants born preterm due to maternal or fetal indications.
Design: Analysis of retrospective cohort.
Setting: Oulu University Central Hospital, Finland.

Population: One hundred and three women, who were between the 24th and the 33rd week of pregnancy, delivered by caesarean delivery because of maternal or fetal indications. They were matched with 103 women who had spontaneous preterm delivery at corresponding gestational weeks between 1990-1997.

Main Outcome Measures: Maternal morbidity, reasons for caesarean delivery, neonatal mortality and morbidity rates, and later development of the infants.

Results: Pre-eclampsia was diagnosed in 57% of the women in the indicated group and only in one woman in the control group. All infants in the indicated group and almost a third in the control group were born by caesarean birth; the main indication was threatening fetal asphyxia. There was a significant difference in neonatal mortality rates between the groups (175 vs 78 per thousand live births in the indicated vs control infants; RR 2.3, 95% CI 1.02, 4.9) and the main cause of death was respiratory insufficiency: 64% in the indicated group and 22% in the controls; RR 2.9, 95% CI 0.8, 10. Respiratory distress syndrome occurred more often (73% vs 53%, RR 1.4, 95% CI 1.1, 1.7) and it was more severe and more complicated in infants in the indicated group, compared with those in the control group. Symptomatic chronic lung disease at one year of age was more common in infants in the indicated group than in the control group (15% vs 3%; RR 4.6, 95% CI 1.4, 15.9).

Conclusions: Not only the risks of neonatal mortality and morbidity but also long term pulmonary consequences, appear to be greater in infants born preterm by indicated delivery than in preterm infants born spontaneously at corresponding weeks.

BJOG : an international journal of obstetrics and gynaecology


Obstetric outcome of pregnancies following ICSI, classified according to sperm origin and quality

Abstract: The aim of this study was to report the outcome of all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) performed during a 5 year period at two fertility clinics, with special reference to delivery outcome associated with different sperm origin and quality and the transfer of fresh or frozen-thawed pre-embryos. A total of 1293 clinical pregnancies was analysed. Deliveries occurred in 75.9% (n = 982) and early spontaneous abortion, late spontaneous abortion and ectopic pregnancy in 21.4, 1.0 and 1.2% respectively. Multiple birth occurred in 21.3% (208 sets of twins and one set of triplets) of the deliveries, with the highest incidence in the epididymal sperm group (30.2%) and lowest in the cryopreserved group (13.7%). A total of 1192 infants was born. Preterm birth occurred in 15.7% of all deliveries. Preterm birth was not related to sperm origin or quality but was related to multiple birth. The prematurity rate was 8.4%, 42.3% and 100% for singletons, twins and triplets respectively. Singleton infants born after cryopreservation as embryos had a significantly higher birthweight than the ejaculated sperm group with fresh embryo transfer. The perinatal mortality rate was 11.7 per 1000 born infants. Eighty-seven of the 1192 infants (7.3%) had a malformation, 40 of which were minor. The perinatal mortality rate and the malformation rate were similar in the different subgroups. Prenatal karyotyping was performed on 149 fetuses (12.5%) and abnormal results were found in four cases (2.7%). In conclusion, obstetric outcome of ICSI pregnancies was similar to that of conventional IVF and was not influenced by sperm origin or quality. The high incidence of multiple births is still the major concern.


Comparison between different routes of progesterone administration as luteal phase support in infertility treatments

Asimina Tavaniotou

Centre for Reproductive Medicine, Dutch-Speaking Free University of Brussels, Brussels, Belgium.

Abstract: Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.


Nausea and vomiting during pregnancy: A prospective study of its frequency, intensity, and patterns of change

Abstract:
OBJECTIVE: Our purpose was to provide a detailed description of patterns of nausea and vomiting of pregnancy.

STUDY DESIGN: A prospective study was performed with 160 women who provided daily recordings of frequency, duration, and severity of nausea and vomiting.

RESULTS: Seventy-four percent of women reported nausea lasting a mean of 34.6 days. "Morning sickness" occurred in only 1.8% of women, whereas 80% reported nausea lasting all day. Only 50% of women were relieved by 14 weeks' gestation; 90% had relief by week 22. Data based on the McGill Nausea Questionnaire indicate that the nausea experienced by pregnant women is similar in character and intensity to the nausea experienced by patients undergoing cancer chemotherapy.

CONCLUSIONS: Traditional teachings about nausea and vomiting of pregnancy are contradicted by our findings. Standardized tools for measuring the distribution, duration, and intensity of nausea are applicable to the study of nausea and vomiting of pregnancy and could be used in clinical trials to assess palliative measures.

American Journal of Obstetrics and Gynecology


Evaluation of four automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications

Abstract:
BACKGROUND: C-reactive protein (CRP) can provide prognostic information about the risk of developing atherosclerotic complications in apparently healthy patients. This new clinical application requires quantification of CRP concentrations below those traditionally measured in the clinical laboratory.

METHODS: The Dade Behring BN II, the Abbott IMx, the Diagnostic Products Corporation IMMULITE, and the Beckman Coulter IMMAGE are four automated analyzers with high-sensitivity CRP (hs-CRP) methods. We evaluated these assays for precision, linearity, and comparability with samples from 322 apparently healthy blood donors.

RESULTS: The imprecision (CV) of the BN II, IMx, IMMULITE, and IMMAGE methods was < or = 7.6%, < or = 12%, < or = 9.8%, and < or = 9.7% at 3.5 mg/L, respectively. The BN II, IMx, IMMULITE, and IMMAGE methods were linear down to < or = 0.30, < or = 0.32, < or = 0.85, and 2.26 mg/L, respectively. CRP concentrations demarcating each quartile in a healthy population were method dependent. The IMx method gave results comparable to the BN II method for values in the reference interval. The IMMULITE method had a positive intercept compared with the BN II method. The IMMAGE method demonstrated more scatter and a positive intercept compared with the BN II method, which may reflect the fact that it is a less sensitive assay.

CONCLUSIONS: The four hs-CRP methods exhibited differences in results for a healthy population. Additional standardization efforts are required to ensure that hs-CRP results can be related to large-scale epidemiologic studies.


Indomethacin for preterm labor: a randomized comparison of vaginal and rectal-oral routes

Abstract:
OBJECTIVE: To compare the efficacy of intravaginal and intrarectal plus oral indomethacin for the treatment of preterm labor.

METHODS: Between December 1996 and November 1998, 46 eligible gravidas admitted with singleton pregnancies and idiopathic preterm labor before 33 gestational weeks were randomized to receive 200 mg of intravaginal or intrarectal plus oral indomethacin.

RESULTS: Twenty-three subjects were allocated to each study group. The interval from initiation of treatment to delivery was significantly longer in the intravaginal indomethacin group (26.5 +/- 5.7 versus 12.6 +/- 3.7 days; P =.007). Delivery was delayed by more than 7 days in 18 of 23 subjects (78%) in the intravaginal indomethacin group compared with ten (43%) in the intrarectal plus oral indomethacin group (P =.03). Birth weights were significantly higher (2306 +/- 436 versus 1862 +/- 232 g; P =.002) and hospitalization in a neonatal intensive care unit (NICU) (3.1 +/- 0.8 versus 9.3 +/- 3. 7 days; P =.001) and mechanical ventilation (1.4 +/- 0.2 versus 5.3 +/- 1.6 days; P =.001) were significantly shorter in the intravaginal indomethacin group.

CONCLUSION: Intravaginal indomethacin is more effective than intrarectal plus oral application in delaying preterm labor and is associated with higher birth weights, shorter NICU stays, and shorter intervals of mechanical ventilation.


Neonatal effects of nifedipine and ritodrine for preterm labor

Abstract:
OBJECTIVE: We compared nifedipine and ritodrine for treatment of preterm labor with respect to neonatal outcome.

METHODS: We conducted an open randomized multicenter study of neonatal outcome in 185 women who received either oral nifedipine (n = 95) or intravenous (IV) ritodrine (n = 90) for treatment of preterm labor. Secondary outcome measures included neonatal mortality and morbidity, especially neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), and intracranial bleeding.

RESULTS: There were no significant differences in umbilical artery pH values and Apgar scores between groups. Nifedipine was associated with lower admission rates to the NICU (49% versus 66%; odds ratio 0. 51, confidence interval 0.28, 0.93) compared with ritodrine, and lower incidences of RDS (21% versus 37%; 0.46, 0.24, 0.89), intracranial bleeding (18% versus 31%; 0.48, 0.24, 0.96), and neonatal jaundice (52% versus 67%; 0.53, 0.29, 0.97). Logistic regression analysis showed that even after correction for gestational age at birth, newborn risk of RDS, intracranial bleeding, or neonatal jaundice was significantly lower in the nifedipine group than the ritodrine group.

CONCLUSION: Nifedipine for treatment of preterm labor was associated with a lower incidence of neonatal morbidity than ritodrine. That difference appeared to be partly because of the higher tocolytic efficacy of nifedipine and partly because of an intrinsic beneficial effect of nifedipine, or the lack of harmful effects when compared with ritodrine.


A fixed formula to define the fertile window of the menstrual cycle as the basis  of a simple method of natural family planning

Abstract: A significant number of women worldwide use periodic abstinence as their method of family planning. Many of them use some type of calendar-based approach to determine when they should abstain from unprotected intercourse to avoid pregnancy; yet they often lack correct knowledge of when during their menstrual cycle they are most likely to become pregnant. A simple method of natural family planning (NFP) based on a fixed formula to define the fertile window could be useful to these women. This article reports the results of an analysis of the application of a fixed formula to define the fertile window. A large existing data set from a World Health Organization study of the Ovulation Method was used to estimate the theoretical probability of pregnancy using this formula. Information about the variable probability of pregnancy on different cycle days relative to ovulation also was considered in the analysis. Results suggest that a fixed formula in which days 8-19 of the menstrual cycle are considered to be the fertile window would provide the appropriate basis of a simple, effective, family planning method.


Efficacy and safety of oral estriol for managing postmenopausal symptoms

Abstract:
OBJECTIVE: to assess the therapeutic efficacy and safety of oral estriol for the treatment of climacteric symptoms in postmenopausal women.

METHODS: 68 postmenopausal women with climacteric symptoms received oral estriol, 2 mg/day, daily for 12 months. We evaluated the degree of climacteric complaints with estriol therapy; serum levels of gonadotropins, estradiol (E2) and lipids; biochemical markers of bone metabolism; blood pressure; and side effects both at baseline and during treatment. Climacteric symptoms were assessed according to the menopausal index (MI), a version of the Kupperman index that had been modified for Japanese women.

RESULTS: oral estriol therapy significantly reduced total MI scores. The greatest relief was noted for hot flushes, night sweats, and insomnia. Estriol treatment significantly lowered serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations but did not affect any of the other parameters (lipids, bone, liver and blood pressure) during the study period. Slightly vaginal bleeding occurred in 14.3% of those who underwent natural menopausal women. Histologic evaluation of the endometrium and ultrasound assessment of the breasts following 12 months of estriol treatment found normal results in all women.

CONCLUSION: Estriol is a safe and effective alternative for relieving climacteric symptoms in postmenopausal Japanese women.


Ectopic pregnancy

Ectopic pregnancy

Abstract: Ectopic pregnancy occurs at a rate of 19.7 cases per 1,000 pregnancies in North America and is a leading cause of maternal mortality in the first trimester. Greater awareness of risk factors and improved technology (biochemical markers and ultrasonography) allow ectopic pregnancy to be identified before the development of life-threatening events. The evaluation may include a combination of determination of urine and serum human chorionic gonadotropin (hCG) levels, serum progesterone levels, ultrasonography, culdocentesis and laparoscopy. Key to the diagnosis is determination of the presence or absence of an intrauterine gestational sac correlated with quantitative serum beta-subunit hCG (beta-hCG) levels. An ectopic pregnancy should be suspected if transvaginal ultrasonography shows no intrauterine gestational sac when the beta-hCG level is higher than 1,500 mlU per mL (1,500 IU per L). If the beta-hCG level plateaus or fails to double in 48 hours and the ultrasound examination fails to identify an intrauterine gestational sac, uterine curettage may determine the presence or absence of chorionic villi. Although past treatment consisted of an open laparotomy and salpingectomy, current laparoscopic techniques for unruptured ectopic pregnancy emphasize tubal preservation. Other treatment options include the use of methotrexate therapy for small, unruptured ectopic pregnancies in hemodynamically stable patients. Expectant management may have a role when beta-hCG levels are low and declining.


Reproductive features in women developing ovarian granulosa cell tumour at a fertile age

L Unkila-Kallio

Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland.

Abstract: Ovarian granulosa cell tumour (GCT) is a rare malignancy, which has been linked to both infertility and infertility treatment with ovulation inducers. The reproductive features were analysed of 146 women with GCT diagnosed between 1956 and 1996. During the study period no changes were found in the mean age (53 years), menopausal status (59% postmenopausal), parity (32% nulliparous) or tumour size or stage at diagnosis. The clinical features in women with GCT at fertile age were compared with GCT diagnosed later in life and to population-based data. Nulliparity (50%) and history of infertility (22%) were more frequent if the tumour occurred at fertile age (n = 50). Of the 12 infertile cases, seven had anovulatory infertility (58%); 11 occurred during the era of ovulation inducers, but only five had used these drugs (clomiphene citrate in five patients, gonadotrophins in two, and tamoxifen in one patient) and no patient had undergone in-vitro fertilization. Endometrial hyperplasia was associated with GCT at all ages, while endometrial cancer was found solely after the age of 45 years. In conclusion, GCT at fertile age is associated with nulliparity and with a clinical presentation of anovulatory infertility, while GCT later in life is associated with a more normal average fertility pattern and with occurrence of endometrial cancer.


Augmented trochanteric bone mineral density after modified physical education  classes: a randomized school-based exercise intervention study in prepubescent  and early pubescent children

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

H A McKay

Departments of Human Kinetics, Medicine, Division of Endocrinology and Metabolism, and Human Nutrition, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract:
Background: Of the few exercise intervention studies focusing on pediatric populations, none have confined the intervention to the scheduled physical education curriculum.

Objective: To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density (aBMD), in grams per square centimeter, of healthy thirdand fourth-grade children.

Study Design: Ten elementary schools were randomized to exercise (n = 63) and control groups (n = 81). Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping, hopping, and skipping into twice weekly physical education classes. Control groups did regular physical education classes. At baseline and after 8 months of intervention, we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry (Hologic QDR-4500). Calcium intake, physical activity, and maturity were estimated by questionnaire.

Results: The exercise group showed significantly greater change in femoral trochanteric aBMD (4.4% vs 3.2%; P <.05). There were no group differences at other sites. Results were similar after controlling for covariates (baseline aBMD change in height, change in lean, calcium, physical activity, sex, and ethnicity) in hierarchical regression.

Conclusions: An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton.


Postfertilization effects of oral contraceptives and their relationship to informed consent

Abstract: The primary mechanism of oral contraceptives is to inhibit ovulation, but this mechanism is not always operative. When breakthrough ovulation occurs, then secondary mechanisms operate to prevent clinically recognized pregnancy. These secondary mechanisms may occur either before or after fertilization. Postfertilization effects would be problematic for some patients, who may desire information about this possibility. This article evaluates the available evidence for the postfertilization effects of oral contraceptives and concludes that good evidence exists to support the hypothesis that the effectiveness of oral contraceptives depends to some degree on postfertilization effects. However, there are insufficient data to quantitate the relative contribution of postfertilization effects. Despite the lack of quantitative data, the principles of informed consent suggest that patients who may object to any postfertilization loss should be made aware of this information so that they can give fully informed consent for the use of oral contraceptives.


Ureteral displacement associated with pelvic peritoneal defects and endometriosis

Abstract: Ten women had endometriosis and pelvic peritoneal defects of the posterior leaf of the broad ligament, with the consistent finding of medial displacement of the ureter toward the uterosacral ligament. Ureterolysis at the time of surgery revealed the underlying course of the ureter and its proximity to the uterosacral ligament, making it susceptible to surgical injury. It is important for surgeons to be aware of this anatomic alteration associated with these specific peritoneal defects.

The Journal of the American Association of Gynecologic Laparoscopists


Myomectomy in Gynecologic, Obstetric and Related Surgery, 2nd Ed


DIR Jahrbuch 1999 (Deutsches IVF-Register Annual Report 1999)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 1999. 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).


The Changing Face of Breast Cancer: A Clinic Bulletin on Menopause


Pregnancy Achievement and Outcome In Sonographically Observed Spontaneous Ovulation

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.


OC's Inadequate for Managing Most PMS (ACOG Guidelines)


Living Proof in 3-D: Putting a Face on the Unborn Human Person


Hormonal Correlates to Sonographically Identified Ovulatory Defects


"Natural" isomolecular hormone replacement: an evidence-based medicine approach

J A Drisko

Department of Gynecology and Obstetrics, The University of Kansas School of Medicine, Kansas City, KS.

International Journal of Pharmaceutical Compounding


Infertility Counseling: A Comprehensive Handbook for Clinicians


Cervical Cerclage: Green-top Guideline No. 75

Abstract: This is the second edition of this guideline; the first edition was published in 2011 under the same name. It supplements NICE guideline NG25 Preterm labour and birth. Cerclage remains one of the standard options for prophylactic intervention in the care of women at risk of preterm birth and second trimester fetal loss and is used by most obstetricians, despite difficulties in identifying the population of women who would most benefit. The procedure, a stitch inserted into the cervix, was first performed in 1902 in women with a history of second trimester loss or spontaneous preterm birth suggestive of cervical insufficiency, with the aim of preventing recurrent loss. Cervical insufficiency is an imprecise clinical diagnosis frequently applied to women with such a history, where it is assumed that the cervix is ‘weak’ and unable to remain closed during the pregnancy. Recent evidence suggests that, rather than being a dichotomous variable, cervical integrity is likely to be a continuum influenced by factors related not solely to the intrinsic structure of the cervix but also to processes driving premature effacement and dilatation. While cerclage may provide a degree of structural support to a ‘weak’ cervix, its role in maintaining the cervical length and the endocervical mucus plug as a mechanical barrier to ascending infection may be more important. There is lack of consensus on the optimal cerclage technique, timing of suture placement, the role of amniocentesis before emergency cerclage insertion and optimal care following insertion. Complications are not well documented and often difficult to separate from risks inherent to the underlying condition. The purpose of this guideline is to review the literature and provide evidence-based guidance on the use of cerclage in women at risk of preterm birth and second trimester loss. This guideline supplements NICE guideline [NG25] Preterm labour and birth.1 Within this document we use the terms woman and women’s health. However, it is important to acknowledge that it is not only people who identify as women for whom it is necessary to access women’s health and reproductive services in order to maintain their gynaecological health and reproductive wellbeing. Gynaecological and obstetric services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth. This Royal College of Obstetricians and Gynaecologists (RCOG) guideline was developed in accordance with the standard methodology for producing RCOG Green-top Guidelines.2 The Cochrane Library (including the Cochrane Database of Systematic Reviews), DARE, EMBASE, TRIP, Medline and PubMed (electronic databases) were searched for relevant randomized control trials, systematic reviews and meta-analyses. The search was restricted to articles published between 2011 and April 2020. The databases were searched using the relevant MeSH terms, including all subheadings and this was combined with a keyword search. Search words included ‘cervical cerclage’, ‘cervical suture’, ‘cervical stitch’, ‘midtrimester miscarriage’, ‘McDonald cerclage’, ‘Shirodkar cerclage’, ‘infection and cerclage’, ‘tocolytics and cerclage’ and ‘inflammatory mediators and cerclage’; the search was limited to humans and the English language. The National Library for Health and National Guidelines Clearing House were also searched for relevant guidelines and reviews. The full search strategy is available to view online as supporting information (Appendices S1 and S2). Previous terminology (prophylactic, as a planned procedure, emergency, urgent, rescue) of cervical sutures/cerclage can be ambiguous. More appropriate nomenclature based on indication for cervical suture is recommended. The terms below are increasingly used in the scientific literature. History-indicated cerclage Insertion of a cerclage as a result of factors in a woman’s obstetric or gynaecological history, which increase the risk of spontaneous second trimester loss or preterm birth.3 A history-indicated suture is performed as a prophylactic measure in asymptomatic women and usually inserted as a planned procedure at 11–14 weeks of gestation. Preterm Birth Birth before to 37+0 weeks’ gestation. Ultrasound-indicated cerclage Insertion of a cerclage as a therapeutic measure in cases of cervical length shortening seen on transvaginal ultrasound.3 Ultrasound-indicated cerclage is performed on asymptomatic women who do not have exposed fetal membranes in the vagina. Sonographic assessment of the cervix is usually performed between 14 and 24 weeks of gestation by transvaginal scan and with an empty maternal bladder. Emergency cerclage (also known as physical exam-indicated or emergency cerclage) Insertion of cerclage as a salvage measure in the case of premature cervical dilatation with exposed fetal membranes in the vagina.3 This may be discovered by ultrasound examination of the cervix or as a result of a speculum/physical examination performed for symptoms such as vaginal discharge, bleeding or ‘sensation of pressure’. It can be considered up to 27+6 weeks gestation.1 Transvaginal cerclage (McDonald) A transvaginal purse-string suture placed at the cervical isthmus junction, without bladder mobilization.4 High transvaginal cerclage requiring bladder mobilization (including Shirodkar) A transvaginal purse-string suture placed following bladder mobilization, to allow insertion above the level of the cardinal ligaments.5 Transabdominal cerclage A suture performed via a laparotomy or laparoscopy, placing the suture at the cervicoisthmic junction.6 Occlusion cerclage Occlusion of the external os by placement of a continuous non-absorbable suture. The theory behind the potential benefit of occlusion cerclage is retention of the mucus plug.7 Routine surveillance of women at low risk is not currently recommended by the National Screening Committee. Ultrasound surveillance of cervical length is advocated in women at high and intermediate risk in Element 5 of the Saving Babies Lives Care Bundle,21 the timing of which is dependent on the women’s history. These women are recommended to be reviewed by a preterm prevention specialist by 12 weeks where possible, or with the dating scan whichever is sooner, and offered transvaginal cervix scanning as a secondary screening test every 2–4 weeks between 16 and 24 weeks. There is, however, uncertainty as to how to care for these women if a short cervix is identified in women who have had serial screening but do not have a history of a previous preterm birth; an ultrasound indicated cerclage may be considered. STOPPIT-2 is a randomised trial of the Arabin pessary to prevent preterm birth in twin pregnancies with a short cervix. Data collection is now complete and the results are currently being analysed.26 Carers should be aware of the potential psychological sequelae associated with fetal death and miscarriage, and women and their families supported by debriefing services and the offer of counselling. Families should also be signposted to the relevant patient support groups. There is no clear evidence that the gestation at which the cerclage is inserted affects the magnitude of prolongation of the pregnancy; however, consideration should be given to the fact that, in cases presenting before 20 weeks of gestation, insertion of a emergency cerclage is highly likely to result in a preterm birth before 28 weeks of gestation. Furthermore, emergency cerclage can rarely be justified beyond 24 weeks’ gestation due to the potential risk of iatrogenic membrane rupture and subsequent preterm birth. Prior to cerclage insertion, women should be given appropriate verbal and written information; patient information can be found on the RCOG website.50 The interval between presentation and suture insertion varies between studies. Any delay must balance the risk of inserting a suture in a cervix that is inevitably going to continue dilating against the increased risk of ascending infection. There are no studies evaluating the effect of sexual intercourse on the risk of second trimester loss or preterm birth in women with cervical cerclage. Although other tests are commercially available for the prediction of preterm birth, such as Partosure and Actim Partus no studies to date have evaluted their use following cervical cerclage insertion. Multiple studies have compared different agents (cerclage, progesterone and pessaries) for the prevention of preterm birth, however these often do not control for clinician preference and many of the studies are retrospective in nature. Conde-Agudelo et al.87 also compared the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth and short cervix undertaking a meta-analysis of RCTs comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth and a sonographic cervical length less than 25 mm. Five trials comparing vaginal progesterone versus placebo and five comparing cerclage versus no cerclage were included. Both progesterone and cerclage were equally effective for preventing preterm birth and improving perinatal outcomes. However, cerclage and progesterone were not compared directly. A number of randomized controlled trials are planned comparing the efficacy of cerclage versus pessary versus progesterone.83, 88 There are no studies comparing elective removal of transvaginal cerclage with removal in labour. However, in the absence of preterm labour, elective removal at 36–37 weeks of gestation is advisable owing to the potential risk of cervical injury in labour and the minimal risk to a neonate born at this gestation. There are no studies regarding the use of anaesthesia in the removal of a cerclage inserted with bladder mobilization but, given that the technique involves burial of the suture, an anaesthetic is likely to be necessary for removal. Decisions regarding use of anaesthetic should be taken jointly with the woman. There are no published studies on long-term outcome comparing a policy of removing a transabdominal cerclage to it remaining in place. However, if further pregnancies are contemplated, it is reasonable to recommend leaving the cerclage in place. There have been anecdotal reports of suture ‘pulling through’ prior to labour, and a vaginal birth can occur safely if this is identified. The developers would like to acknowledge Miss Meekai To for their work as co-developer of the previous edition of this guideline. AHS has declared no conflicts of interest. LS has declared no conflicts of interest. Full disclosure of interests are available to view online as supporting information. All those involved in the development of the Green-top Guidelines, including the Guidelines Committee, Guidelines Committee co-chairs, guideline developers, peer reviewers and other reviewers, are unpaid volunteers and receive no direct funding for their work in producing the guideline. The exception to this are the RCOG staff involved who are salaried employees of the College and GC members who receive reimbursement for expenses for attending GC meetings. Please see more information on travel expense rules on the RCOG website. Appendix S1. Cervical cerclage literature search strategy. Appendix S2. Cervical cerclage search strategy top up. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. This guideline was produced on behalf of the Royal College of Obstetricians and Gynaecologists by: Professor Andrew H Shennan FRCOG, London; Dr Lisa Story MRCOG, London. and peer reviewed by: Miss A Gorry MRCOG, London; Dr G Kumar FRCOG, Wrexham; Mr D Fraser FRCOG, Norwich; Dr P Maouris FRCOG, Perth, Western Australia; Mr B Kumar FRCOG, Wrexham; Dr KC Dundas FRCOG, Edinburgh; Miss M To MRCOG, London; Professor JE Norman FRCOG, Bristol; RCOG Women’s Network; Imperial College Academic Health Science Centre. Committee lead reviewers were: Dr A Macleod FRCOG,1 Edinburgh, Dr B Magowan FRCOG, Melrose2 and Mr A McKelvey MRCOG, Norfolk.3 1until December 2020; 2until May 2021; 3from December 2021. The chair of the Guidelines Committee was: Dr MA Ledingham MRCOG, Glasgow; Dr B Magowan FRCOG, Melrose. All RCOG guidance developers are asked to declare any conflicts of interest. A statement summarising any conflicts of interest for this guideline is available from: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg75. The final version is the responsibility of the Guidelines Committee of the RCOG. The guideline will be considered for update 3 years after publication, with an intermediate assessment of the need to update 2 years after publication. The Royal College of Obstetricians and Gynaecologists produces guidelines as an educational aid to good clinical practice. They present recognised methods and techniques of clinical practice, based on published evidence, for consideration by obstetricians and gynaecologists and other relevant health professionals. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor or other attendant in the light of clinical data presented by the patient and the diagnostic and treatment options available. This means that RCOG Guidelines are unlike protocols or guidelines issued by employers, as they are not intended to be prescriptive directions defining a single course of management. Departure from the local prescriptive protocols or guidelines should be fully documented in the patient’s case notes at the time the relevant decision is taken.

BJOG : an international journal of obstetrics and gynaecology


Successful Pregnancies in Kallmann Syndrome using Pulsatile GnRH


Ovarian differentiation and gonadal failure

Abstract: Ovarian failure can result from several different genetic mechanisms-X chromosomal abnormalities, autosomal recessive genes causing various types of XX gonadal dysgenesis, and autosomal dominant genes. The number and precise location of loci on the X are still under investigation, but it is clear that, in aggregate, these genes are responsible for ovarian maintenance, given that monosomy X shows germ cells that undergo accelerated atresia. Despite recent hypotheses, at present there is no evidence for a gene directing primary ovarian differentiation; this process may be constitutive. Phenotypic/karyotypic correlation and limited molecular confirmation have long shown that proximal Xp and proximal Xq contain regions of the most importance to ovarian maintenance. Terminal deletions at Xp11 result in 50% primary amenorrhea and 50% premature ovarian failure or fertility. Deletions at Xq13 usually produce primary amenorrhea. Terminal deletions nearer the telomeres on either Xp of Xq bring about premature ovarian failure more often than complete ovarian failure. The X-linked zinc finger gene (ZFX) and diaphanous 2 Drosophila homologue (DIAPH2) are the only candidate genes for ovarian maintenance that map to the X chromosome. Additional, as yet unidentified, genes along the X chromosome must be involved. The search for these genes in humans is hampered by the lack of candidate genes that map to the X chromosome, the scarcity of patients with fortuitous autosomal translocations, and small pedigrees, which hinder mapping of the loci. In addition, difficulties with human germ cell research also make it challenging to dissect genes important to ovarian development. Autosomal genes also are involved in ovarian differentiation and gonadal failure. Follicle-stimulating hormone receptor and ataxia telangiectasia are examples of autosomal genes known to cause human ovarian failure. Transgenic mouse models point to many other candidate autosomal genes, and sequencing of the human homologues in affected women should lead to the discovery of new genes responsible for human ovarian failure. Identification, functional analysis, and mapping of novel genes specifically expressed in the ovary of mice and women eventually should lead to fruitful dissection of essential genes in mammalian ovarian development and maintenance.


The prognostic role of salpingoscopy in laparoscopic tubal surgery

Abstract: The present study was designed to evaluate the prognostic value of salpingoscopy in patients undergoing tubal laparoscopic surgery for infertility due to periadnexal adhesion or distal tubal occlusion. In addition, the clinical value of salpingoscopy was compared with a current classification system of adnexal adhesions and distal tubal occlusion. A total of 51 patients with either adnexal adhesions (24 patients) or hydrosalpinx (27 patients) were prospectively evaluated. Salpingoscopy was performed concomitantly with salpingo-ovariolysis or salpingoneostomy at the time of operative laparoscopy. There was no significant correlation between salpingoscopic classes and the classification system used for both the salpingo-ovariolysis and the salpingoneostomy groups of patients. The patients had a mean follow-up of 33 months. Patients with a normal tubal mucosa (salpingoscopic classes I and II) had a 71% cumulative term pregnancy rate in the salpingo-ovariolysis group and a 64% cumulative term pregnancy rate in the salpingoneostomy group. No intrauterine pregnancies were obtained in patients with intratubal damage (salpingoscopic classes III to V). There was a statistically significant correlation between the occurrence of a term pregnancy and the salpingoscopic classes, but not with the classification system used. These results suggest that patients with tubal infertility should be offered operative laparoscopy with salpingoscopy as the first step of treatment.


Clinical efficacy of an automated high-sensitivity C-reactive protein assay

Abstract:
BACKGROUND: Prospective studies have shown that C-reactive protein (CRP) can be used to predict risk of future cardiovascular events. High-sensitivity methods for CRP (hs-CRP) measurement are needed for this purpose.

METHODS: We compared the clinical efficacy of an automated and commercially available latex-enhanced assay (Latex) for hs-CRP (Dade Behring) to a validated in-house ELISA, previously shown to predict future peripheral arterial disease (PAD) in asymptomatic populations. Using a prospective, nested, case-control design, we measured baseline hs-CRP concentrations in 144 apparently healthy men who subsequently developed symptomatic PAD and 144 age- and smoking habit-matched controls who remained free of vascular disease over the follow-up period of 60 months.

RESULTS: The two hs-CRP assays correlated highly (r = 0.95; P <0.001), and all but two participants were classified into concordant quartiles or varied by only one quartile. The median hs-CRP of the case group was significantly higher than that of controls when measured by either the ELISA (1.34 vs 0.99 mg/L; P = 0.034) or the Latex method (1.80 vs 1.20 mg/L; P = 0.042). Furthermore, for both ELISA and the Latex method, the calculated relative risks of developing PAD increased significantly with each increasing quartile of hs-CRP. The calculated interquartile increase in relative risk of PAD was 31% (95% confidence interval, 5.2-62.2%; P = 0.01) for ELISA and 34% (95% confidence interval, 8.2-66.1%; P = 0.007) for the Latex method.

CONCLUSIONS: Our findings indicate that the Latex method is equally as efficacious as the validated ELISA in classifying patients into cutoff points established by prospective studies for risk stratification for coronary and cerebrovascular disease.