Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome

Practice Committe of the American Society for Reproductive Medicine

The Practice Committee of the American Society for Reproductive Medicine


Use of clomiphene citrate in women

Use of clomiphene citrate in women

Practice Committee of the American Society for Reproductive Medicine


21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender

Carlos Moran

Health Research Council, Mexican Institute of Social Security, Mexico City, Mexico.

Abstract: Polycystic ovary syndrome (PCOS) affects about 4 to 6% of women of reproductive age and accounts for at least 75% of hyperandrogenic patients. PCOS is diagnosed by the presence of oligo-ovulation and hyperandrogenism after the exclusion of related disorders, such as 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH). In turn, NCAH is a homozygous recessive disorder, diagnosed by a corticotropin-stimulated 17-hydroxyprogesterone (17-HP) level greater than10 ng/mL (30.3 nmol/L) and confirmed by genotyping of the CYP21 gene. The prevalence of NCAH is approximately 50 times less than that of PCOS, affecting between 1 and 10% of hyperandrogenic women, depending on ethnicity. However, it is generally difficult to distinguish NCAH from PCOS solely on clinical grounds, as both demonstrate varying degrees of hyperandrogenism and ovulatory dysfunction. Most PCOS patients have insulin resistance, in contrast to those with NCAH. Likewise, polycystic ovaries are observed in up to 40% of NCAH patients. Both disorders have a strong familial component. The only method that allows the separation of NCAH from PCOS patients is the measurement of 17-HP levels. In conclusion, PCOS and NCAH have differences in prevalence and pathophysiology. However, because the disorders have significant clinical and hormonal similarities, the measurement of 17-HP, preferably basally as a screening method, should be incorporated into the evaluation of all hyperandrogenic patients.


Metformin in polycystic ovary syndrome: systematic review and meta-analysis

Abstract:
OBJECTIVE: To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent.

SELECTION OF STUDIES: 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence.

MAIN OUTCOME MEASURE: Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome.

RESULTS: Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect on body mass index or waist:hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance.

CONCLUSIONS: Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.


Pregnancy created using egg nucleus of infertile woman


Iatrogenic multiple pregnancies. Do they complicate perinatal care?

Emmanuel Nowak

Laboratoire des Sciences et Techniques de l’Information de la Communication et de la Connaissance

Abstract: This review addresses questions related to medicosocial concerns surrounding the care of women with multiple births and their infants. Relevant articles and texts on twin and triplet pregnancies were reviewed. Population-based data were selected for inclusion whenever possible. Relevant tables were simplified from original sources. The review clarifies obstetric and perinatal questions in a manner that is helpful to clinicians and their patients.


Excess mortality and morbidity among small-for-gestational-age premature infants: a population-based study

Abstract:
OBJECTIVE: We examined the effect of intrauterine growth restriction on mortality and morbidity in the Israel cohort of very low birth weight premature infants.

METHODS: The study population included 2764 singleton very low birth weight infants without congenital malformations born from 24 to 31 weeks of gestation during 1995 to 1999. Four hundred six (15%) were born small for gestational age (SGA). The effect of SGA on death, bronchopulmonary dysplasia, and retinopathy of prematurity was assessed using multiple logistic regression analysis.

RESULTS: After adjustment for perinatal risk factors, SGA infants had a 4.52-fold risk for death (95% CI, 3.24-6.33), a 3.42-fold risk for bronchopulmonary dysplasia (95% CI, 2.29-5.13), and a 2.06-fold risk for grade 3 to 4 retinopathy of prematurity (95% CI, 1.15-3.66).

CONCLUSIONS: SGA premature infants had an increased risk for death, and major morbidity among survivors was increased.


Preventing low birth weight: is prenatal care the answer?

Abstract:
OBJECTIVES: To review the evidence of effectiveness of prenatal care for preventing low birth weight (LBW).

METHODS: We reviewed original research, systematic reviews, meta-analyses and commentaries for evidence of effectiveness of the three core components of prenatal care--risk assessment, health promotion and medical and psychosocial interventions--for preventing the two constituents of LBW: preterm birth and intrauterine growth restriction (IUGR).

RESULTS: Clinical risk assessment will fail to identify the majority of pregnancies at risk for preterm delivery or IUGR. While biophysical and biochemical modalities appear promising, their cost-effectiveness has not been demonstrated, nor can their routine use be recommended in the absence of effective interventions. Smoking cessation programs appear to be modestly effective. There is insufficient evidence to conclude a benefit for nutrition interventions, work counseling or preterm birth education. Only antenatal corticosteroid therapy has demonstrated a clear benefit in the tertiary prevention of preterm delivery. Interventions for which there is insufficient evidence to conclude a benefit include bed rest, hydration, sedation, cerclage, progesterone supplementation, antibiotic treatment, tocolysis without concomitant use of corticosteroids, thyrotropin-releasing hormone, psychosocial support and home visitation. Additionally, there is a paucity of evidence supporting the effectiveness of prenatal interventions, such as low-dose aspirin, bed rest, maternal hyperoxygenation, plasma volume expansion and antenatal fetal assessment, in preventing IUGR or its associated morbidity and mortality.

CONCLUSIONS: Neither preterm birth nor IUGR can be effectively prevented by prenatal care in its present form. Preventing LBW will require reconceptualization of prenatal care as part of a longitudinally and contextually integrated strategy to promote optimal development of women's reproductive health not only during pregnancy, but over the life course.

The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the  European Association of Perinatal Medicine, the Federation of Asia and Oceania  Perinatal Societies, the International Society of Perinatal Obstetricians


Morphological characterization of different human cervical mucus types using light and scanning electron microscopy

Abstract:
BACKGROUND: This study was conducted on human cervical mucus using light microscopy (LM) and scanning electron microscopy (SEM). The objective was the morphological characterization of the different mucus types, with samples taken from the lumen of the cervix and from the different secretory zones of the cervical mucosa.

METHODS: A total of 230 samples from 195 women were spread out on slides and air dried. The phenomenon of 'ferning' was observed and assessed in these samples using both LM and SEM. Further samples from the lumen of the cervix and the different secretory crypts were spread out on cover slips and fixed with glutaraldehyde (2.5%) to be studied by SEM.

RESULTS: The results show the presence of four different morphological mucus types, namely L, S, P and G, in both types of sample using dried and fixed techniques.

CONCLUSIONS: Mucus from the lumen of the cervix appears to be a morphologically heterogeneous entity. It contains different types of secretions, the proportions of which vary throughout the menstrual cycle. The different mucosal types show different types of crystallization, different patterns of ultrastructure (probably related to the arrangement of the glycoprotein network) and are produced in different secretory zones of the crypts in the cervix.


The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up

Abstract:
Background: This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis.

Methods: In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded.

Results: Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%.

Conclusions: Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.


Osteoporosis: What a clinician expects to learn from a patient's bone density examination

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Brian C Lentle

Department of RadiologyUniversity of British ColumbiaVancouverBCCanada

Abstract: Osteoporosis has lately become recognized as an important disease on two accounts. On one hand, demographic change has resulted in a greatly increased and increasing burden of morbidity and mortality due to osteoporotic fracturing. On the other hand, lifestyle changes and preventive measures have become recognized as important factors in prevention of both osteoporosis and osteoporotic fractures, while several effective drug treatments have recently become available to treat osteoporosis by increasing bone density and reducing fracture incidence. Because bone density is, with age, the best predictor of fracture risk, its measurement has become central to the care of those potentially at risk. When a clinician refers a person for a bone density examination, the clinician should be concerned less with an "imaging diagnosis" than with the requirement that the laboratory has procedures in place for rigorous quality assurance and precision measurements, as well as for education of the staff involved. Implementation of these measures and an understanding of their clinical relevance in diagnosis and follow-up, as well as communication with clinicians in this context, are more important than any diagnostic insight that might be provided by "interpreting" a bone density study.


Time to pregnancy: results of the German prospective study and impact on the  management of infertility

Petra Frank-Herrmann

Department of Gynaecological Endocrinology and Fertility Disorders, University of Heidelberg, Vossstrasse 9, 69115 Heidelberg, Germany. petra.frank-herrmann@med.uni-heidelberg.de

Abstract:
Background: The likelihood of spontaneous conception in subsequent cycles is important for a balanced management of infertility. Previous studies on time to pregnancy are mostly retrospective and biased because of exclusion of truly infertile couples. The study aim was to present a non-parametric estimation of cumulative probabilities of conception (CPC) in natural family planning (NFP) users illustrating an ideal of human fertility potential.

Methods: A total of 346 women was observed who used NFP methods to conceive from their first cycle onwards. The couples practising NFP make optimal use of their fertility potential by timed intercourse. The CPC were estimated for the total group and for couples who finally conceived by calculating Kaplan-Meier survival rates.

Results: A total of 310 pregnancies occurred among the 346 women; the remaining 36 women (10.4%) did not conceive. Estimated CPC for the total group (n = 340 women) at one, three, six and 12 cycle(s) were 38, 68, 81 and 92% respectively. For those who finally conceived (truly fertile couples, n = 304 women), the respective pregnancy rates were 42, 75, 88 and 98% respectively. Although the numbers of couples in both groups were similar, the impact of age on time to conception, as judged by the Wilcoxon test, was less in the truly fertile than in the total group.

Conclusions: Most couples conceive within six cycles with timed intercourse. Thereafter, every second couple is probably either subfertile or infertile. CPC decline with age because heterogeneity in fecundity increases. In the subgroup of truly fertile couples, an age-dependent decline in CPC is statistically less obvious because of high homogeneity, even with advancing age.


Uterine and ovarian function in endometriosis

Abstract: Although numerous studies have attempted to elucidate the implication of endometriosis for infertility, this matter still remains unexplained. Diverse clinical approaches based on assisted reproduction techniques have produced conflicting results on this issue. Nevertheless, impairment of implantation and pregnancy rates seems to affect women who suffer from endometriosis. Whether this effect is due to alteration of the oocyte/embryo or the endometrium still remains to be elucidated, although actual data allude to deficiencies in both. Infertility due to poor quality embryos derived from impaired oocytes obtained from malfunctioning ovaries have been described by some groups. Endometrial defects have been argued by others. Adding more confusion to this topic, the influence of peritoneal fluid in women with endometriosis and/or mixed causes also needs to be considered. The aim of this review is to describe the current situation in the endometriosis-related infertility literature.


Future directions in endometriosis research

Abstract: Endometriosis is an estrogen-dependent condition that affects 5 million American women; however, its etiology is not fully understood. The development of the baboon model of endometriosis provides an extremely powerful tool to investigate the development and progression of endometriosis from the early invasive phase to the advanced established disease. The inflammatory reaction that occurs in the peritoneal cavity at the site of endometriotic lesions does not clear the refluxed endometrial fragments. Moreover, this reaction appears to promote the survival of the tissue and the development of the disease. Exploration of the interactions between peritoneal macrophages and cytotoxic T cells and endometrial cells will determine whether their ability to scavenge and induce apoptosis is altered. Determining the mechanism(s) that induces the expression of estrogen and its receptor (ERbeta) is crucial to our understanding of the progression of the disease. The effects of ERbeta activation in endometriotic lesions should be investigated. It is important to determine the effects of estrogen on the function of the immune cells, either directly or indirectly. Finally, determining the effect of events at sites of ectopic endometrium on the eutopic endometrium may elucidate the mechanism(s) of infertility associated with endometriosis.


Endometriosis and subfertility: is the relationship resolved?

Abstract: There are many arguments to support the hypothesis that there is a causal relationship between the presence of endometriosis and subfertility. These arguments are reviewed in this article and include: (1) an increased prevalence of endometriosis in subfertile women compared with women of proven fertility; (2) a reduced monthly fecundity rate (MFR) in baboons with mild to severe (spontaneous or induced) endometriosis compared with those with minimal endometriosis or a normal pelvis; (3) a trend toward a reduced MFR in infertile women with minimal to mild endometriosis compared with women with unexplained infertility; (4) a dose-effect relationship: a negative correlation between the r-AFS stage of endometriosis and the monthly fecundity rate and crude pregnancy rate; (5) a reduced monthly fecundity rate and cumulative pregnancy rate after donor sperm insemination in women with minimal-mild endometriosis compared with those with a normal pelvis; (6) a reduced MFR after husband sperm insemination in women with minimal to mild endometriosis compared with those with a normal pelvis; (7) a reduced implantation rate per embryo after IVF in women with moderate to severe endometriosis compared with women with a normal pelvis; and (8) an increased monthly fecundity rate and cumulative pregnancy rate after surgical removal of minimal to mild endometriosis.


The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos)

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract: Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.


Mortality and neurologic, mental, and psychomotor development at 2 years in infants born less than 27 weeks' gestation: the Leiden follow-up project on prematurity

Abstract:
OBJECTIVE: To determine the outcome of infants with a gestational age (GA) <27 weeks, born in the mid-1990s.

DESIGN: Regional, prospective study; part of the Leiden Follow-Up Project on Prematurity.

SETTING: Three health regions in The Netherlands.

PATIENTS: A total of 266 live born infants (1996/1997) with GA <32 weeks; 46 infants were <27 weeks.

MAIN OUTCOME MEASURES: Neurologic examination (according to Hempel) and assessment of mental and psychomotor development using the Bayley Scales of Infant Development I, at the corrected age of 2 years.

RESULTS: Mortality was 35% (16 of 46) <27 weeks, compared with 6% (14 of 220) in infants with GA 27 to 32 weeks; withdrawal of treatment in 60% and 43%, respectively. Below 27 weeks mortality was higher after extra-uterine transport and pregnancy induction. Neonatal morbidity was higher in infants <27 weeks compared with infants 27 to 32 weeks. Below 27 weeks postnatal use of dexamethasone and being hospitalized at term were associated with abnormal neurologic outcome; there was a higher incidence in (mild) mental developmental delay compared with the older infants. Adverse outcome (dead or abnormal neurologic, psychomotor, or mental development) in infants 23 to 24, 25, 26, and 27 to 32 weeks GA was, respectively, 92% (11 of 12), 64% (7 of 11), 35% (8 of 23), and 18% (40 of 220).

CONCLUSIONS: Mortality and neonatal morbidity were higher in infants with GA <27 weeks compared with infants born between 27 and 32 weeks. The high adverse outcome of infants <25 weeks suggests that one should carefully weigh whether or not to aggressively resuscitate and treat these extremely premature infants.


Decreased maximal aerobic capacity with use of a triphasic oral contraceptive in highly active women: a randomised controlled trial

C M Lebrun

Fowler Kennedy Sport Medicine Clinic 3M Centre, University of Western Ontario, London, ON N6A 3K7, Canada. clebrun@uwo.ca

Abstract:
Background: Oral contraceptives are commonly used by women athletes. However, their effect on athletic performance is unclear.

Objectives: To examine the effects of a moderate dose, triphasic oral contraceptive on measures of athletic performance in highly trained women athletes.

Methods: This is a double blind, placebo controlled trial in 14 women with ovulatory menstrual cycles and maximal aerobic capacity (VO(2)MAX) >/==" BORDER="0">50 ml/kg/min. Four measures of athletic performance were tested: VO(2)MAX, anaerobic capacity (anaerobic speed test), aerobic endurance (time to fatigue at 90% of VO(2)MAX), and isokinetic strength (Cybex II dynamometer). Height, weight, and six skinfold measurements were also recorded. All these observational tests were completed during both the follicular and mid-luteal phases of an ovulatory menstrual cycle. Cycle phases were confirmed by assaying plasma oestradiol and progesterone. Participants were subsequently randomly assigned to either a tricyclic oral contraceptive or placebo and retested in identical fashion (oral contraceptive phase).

Results: Absolute and relative changes in VO(2)MAX from follicular to oral contraceptive phase decreased in the oral contraceptive group by 4.7%, whereas the placebo group showed a slight increase (+1.5%) over the same time period. Two of the women taking oral contraceptive had decreases of 4 and 9 ml/kg/min. In contrast, most women in the placebo group improved or maintained VO(2)MAX. There was also a significant increase in the sum of skinfolds in women taking oral contraceptive compared with those taking placebo (p<0.01). There were no significant changes in other physiological variables (maximum ventilation, heart rate, respiratory exchange ratio, packed cell volume) or measures of performance (anaerobic speed test, aerobic endurance, isokinetic strength) as a function of oral contraceptive treatment.

Conclusions: The decrease in VO(2)MAX that occurs when oral contraceptive is taken may influence elite sporting performance in some women. Further studies are required to determine the mechanisms of this change.


Endometrial abnormalities in infertile women

Abstract:
OBJECTIVE: To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy.

STUDY DESIGN: From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality.

RESULTS: Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma.

CONCLUSION: Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.


Couples' views of the effects of natural family planning on marital dynamics

Leona Vande Vusse

Nurse-Midwifery Program, College of Nursing, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA.

Abstract:
Purpose: Natural Family Planning (NFP) requires periodic abstinence and partner cooperation to prevent pregnancy. The aim of this study was to learn about the effects of modern NFP methods on marital relationships.
Design: Descriptive survey.

Methods: Questionnaires were mailed to 1,400 randomly selected couples known to use NFP and residing in the United States of America; 334 couples (24%) responded. Content analysis was used to identify meanings and themes. Numeric analyses were used to determine frequencies.

Findings: Nearly two-thirds of the qualitative comments were positive. Four themes were identified in the positive responses: relationship enhancements, knowledge improvements, spirituality enrichments, and method successes. Three negative themes were identified: strained sexual interactions, worsened relationships, and method problems. Although about one-fourth of the comments indicated that NFP presented challenges, the majority (74%) found it beneficial, often resulting in stronger bonds, better communication, and improved knowledge.

Conclusions: NFP had more positive than negative effects and its use warrants further consideration.

Journal of Nursing Scholarship : an Official Publication of Sigma Theta Tau  International Honor Society of Nursing


Estrogen in the adult male reproductive tract: a review

Abstract: Testosterone and estrogen are no longer considered male only and female only hormones. Both hormones are important in both sexes. It was known as early as the 1930's that developmental exposure to a high dose of estrogen causes malformation of the male reproductive tract, but the early formative years of reproductive biology as a discipline did not recognize the importance of estrogen in regulating the normal function of the adult male reproductive tract. In the adult testis, estrogen is synthesized by Leydig cells and the germ cells, producing a relatively high concentration in rete testis fluid. Estrogen receptors are present in the testis, efferent ductules and epididymis of most species. However, estrogen receptor-alpha is reported absent in the testis of a few species, including man. Estrogen receptors are abundant in the efferent ductule epithelium, where their primary function is to regulate the expression of proteins involved in fluid reabsorption. Disruption of the alpha-receptor, either in the knockout (alphaERKO) or by treatment with a pure antiestrogen, results in dilution of cauda epididymal sperm, disruption of sperm morphology, inhibition of sodium transport and subsequent water reabsorption, increased secretion of Cl-, and eventual decreased fertility. In addition to this primary regulation of luminal fluid and ion transport, estrogen is also responsible for maintaining a differentiated epithelial morphology. Thus, we conclude that estrogen or its alpha-receptor is an absolute necessity for fertility in the male.

Reproductive biology and endocrinology : RB&E


Cyclicity of breast tenderness and night-time vasomotor symptoms in mid-life  women: information collected using the Daily Perimenopause Diary

Christine L Hitchcock

Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Objective: The purpose was to explore cyclicity of breast tenderness and vasomotor symptoms in menstruating mid-life women using the Daily Perimenopause Diary.

Methods: Untreated mid-life women from a convenience sample completed the Daily Perimenopause Diary for clinical (n = 14) or research (n = 10) assessments. Breast tenderness, sleep disturbance and day and night vasomotor intensity were rated on a 0-4 scale with vasomotor number as a count. Daily oral temperature data were analyzed using the Quantitative Basal Temperature algorithm to assess ovulation and estimate luteal phase length. Analysis of variance tested cyclicity using the mean of three 3-day windows (during flow, at mid-cycle and premenstrually).

Results: Ninety-eight complete flow-to-flow diaries (from 24 women, mean age 47 years, cycle length 27 +/- 6.4 (standard deviation) days) were available, with quantitative temperature data for 60 cycles in 16 women. Of assessed cycles, 90% were ovulatory; 25% had luteal phases < 10 days. Breast tenderness was maximal in the premenstrual window overall (p < 0.0001) and in the ovulatory subset. Night sweats were maximal premenstrually (p = 0.0035) except in anovulatory cycles. Daytime flushes were not cyclic (p = 0.1333) except in ovulatory cycles (p = 0.031).

Conclusion: Daily Perimenopause Diaries from mid-life women show premenstrual increases in breast tenderness and night sweats.

Climacteric : the Journal of the International Menopause Society


Uncertainty in estimating the day of ovulation causes overestimation of the role of ovulation disturbance on the effectiveness of the Yuzpe method of emergency contraception


Reproductive medicine and violation of the "free exercise" clause of the United States Constitution

Abstract: Over the years of my involvement in obstetrics and gynecology, and reproductive medicine and surgery I have had the opportunity to see, first hand, how the religious liberties of individual physicians, medical students, nurses, patients, etc., have been violated by the contemporary trends in reproductive medicine. Since the advent of oral contraceptives, the practice of obstetrics and gynecology as it relates to procreative medicine has dramatically changed. Contraception, sterilization, abortion and in vitro fertilization are the foundation upon which reproductive medicine decision making is made. These decisions are often made with a "steam roller effect" which is completely devoid of any consent from those who are impacted by the implementation of those decisions. It has been an interesting series of events to watch over these years as the profession has become less and less diagnostically attuned and more and more "band aid" oriented. The birth control pill is used for the treatment of almost every gynecologic malady known, even though it cures none of them. Family physicians, internists, pediatricians and others tend to follow the same approach as their OB-GYN colleagues. With in vitro fertilization, instead of finding out what the underlying cause of one's infertility or reproductive problem might be, there is a "jumping over" of the underlying causes (the diseases) and a pursuit directly to a solution which first of all is very expensive, second, is not very effective and third, is considered to be highly immoral and unethical by many people in our society.


Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S

Abstract:
BACKGROUND: Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery.

METHODS: We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle.

RESULTS: Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.

CONCLUSIONS: Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.


Progesterone and preterm delivery--deja vu all over again

Abstract: It has become almost a platitude to lament the complexity and intractability of the problem of preterm delivery, the poor predictive value of screening tests for its occurrence, its resistance to attempted interventions, and its increasing rate.1 Preterm delivery is more common among blacks, the poor, the unmarried, cigarette smokers, underweight women, women with multiple gestations, women with uterine anomalies, women with a history of previous preterm delivery, and women without prenatal care. Although the perinatal mortality rate due to prematurity has decreased dramatically during the past three decades, this reduction has resulted from improvements in perinatal and pediatric care . . .


Hormonal monitoring of ovarian activity using the Ovarian Monitor, part I.  Validation of home and laboratory results obtained during ovulatory cycles by  comparison with radioimmunoassay

Pilar Vigil

Pontificia Universidad Católica de Chile

Catherine d'Arcangues

Special Programme of Research, Development, and Research Training in Human Reproduction, Geneva, Switzerland. darcanguesc@who.ch

Abstract: A study was conducted to determine the accuracy and reliability of the Home Ovarian Monitor for measuring estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during ovulatory cycles as a means of monitoring ovarian activity. Approximately 60 ovulating women in three centres collected timed specimens of urine (3h or more) for a total of six cycles each. The women measured the E1G and PdG excretion per 24h in their urine specimens using the Monitor. A local laboratory using the Monitor also measured the excretion. Urine specimens from 18 to 19 cycles were sent frozen to the WHO Reference Laboratory in London where they were analysed for E1G and PdG by the Monitor and by radioimmunoassay (RIA). The correlation coefficients between the Monitor and radioimmunoassay results obtained in London were better than 0.84 in 80% of the cycles. A urine bias caused the Monitor E1G results to be higher than those obtained by radioimmunoassay but the daily patterns were the same. In 50% of the cycles, this bias caused a delay of up to 3 days in identifying the beginning of the E1G rise compared with radioimmunoassay. Timing of the preovulatory E1G peak and the postovulatory PdG rise agreed within the experimental errors of the two systems. The study confirmed that women using the Monitor at home obtained results that were as accurate as those obtained by laboratory procedures. Careful supervision was required to maintain laboratory levels of quality control and interpretation of results.


Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome

Basak Yildirim

Department of Obstetrics and Gynecology, Faculty of Medicine, Pamukkale University, Denizli, Turkey. basakyildirim@hotmail.com

Abstract:
OBJECTIVE: To investigate the relation between intra-abdominal fat distribution and metabolic disorders in nonobese patients with the polycystic ovary syndrome (PCOS).

DESIGN: Prospective case-control study.

SETTING: University-based hospital.

PATIENT(S): Thirty nonobese patients with PCOS and 30 lean women with regular menstrual cycles (controls). All participants had a body mass index < 25kg/m(2).

MAIN OUTCOME MEASURES: Subcutaneous and intra-abdominal visceral and preperitoneal fat thicknesses were assessed by ultrasonography. Glucose tolerance and insulin sensitivity were evaluated by standard 75-g oral glucose tolerance test and area-under-the-curve analysis. Serum hormones and lipid profile were measured.

RESULT(S): The mean preperitoneal and visceral fat thicknesses were significantly greater in nonobese patients with PCOS. Subcutaneous fat mass was similar between the PCOS and control groups. Nonobese patients with PCOS had glucose intolerance, hyperinsulinemia, and dyslipidemia, manifested by high serum levels of triglyceride, total cholesterol, and high-density lipoprotein (HDL) levels and low serum low-density lipoprotein (LDL) levels. No correlation existed between subcutaneous fat thickness and the metabolic variables in nonobese patients with PCOS. However, serum triglyceride levels correlated with visceral fat and preperitoneal fat thickness. The mean HDL level correlated negatively with visceral fat and preperitoneal fat thickness. The area under the curve for insulin and mean fasting insulin levels correlated positively with visceral fat thickness. In multiple regression analysis, visceral fat thickness contributed significantly to high serum triglyceride and fasting insulin levels.

CONCLUSION(S): Intra-abdominal preperitoneal and visceral fat accumulation may contribute to the development of glucose and lipid metabolism disorders in nonobese patients with PCOS.


Do assisted reproductive technologies cause adverse fetal outcomes?

Christos Coutifaris

University of Pennsylvania Health System

Abstract:
Treatment for infertility using assisted reproductive technologies (ART) is highly successful and has been used to help a steadily growing number of couples worldwide. In 1999, in the United States, more than 86,000 treatment cycles were performed resulting in the birth of more than 30,000 babies. Despite this widespread application, few follow-up studies of children conceived through ART have been performed, and more rigorous investigation of this important issue has clearly been needed. In recent months, three studies linking ART with several complications have been published in high profile and widely read general medical journals: Schieve et al. (1) reported that singletons conceived using ART were at an increased risk for low birth weight, whereas Hansen et al. (2) suggested an increased risk of major birth defects. Finally, Stromberg et al. (3) concluded that children conceived through IVF have an increased risk of neurological problems, especially cerebral palsy.
The importance of these studies is obvious as they provide clues of possible risks associated with ART. However, they are all retrospective analyses of data collected through registries and therefore are vulnerable to biases inherent to such study design. We must be careful not to overinterpret the data by concluding that the use of ART, whether from gamete or embryo manipulation or use of medications, is the direct cause of the complications—the observed associations may simply be explained by one or more confounders, such as an underlying infertility-related condition in the treated women. This short communication is an attempt to place these three articles in proper perspective for the clinician and to provide the impetus for conducting further studies to determine the true nature of the described associations.
At the outset, it should be stated that a major weakness of all three studies is the lack of proper controls. If the aim of a study is to determine whether a cause and effect relationship exists between the process of IVF and a specific outcome (i.e., low birth weight, major birth defects, neurological problems), the appropriate control population is that of babies born to infertile women achieving pregnancies by methods other than IVF. None of the three studies specifically included such a control population.


Vulvar mucus observations and the probability of pregnancy

David B Dunson

National Institute of Environmental Health Sciences

Abstract:
OBJECTIVE: To assess the day-specific and cycle-specific probabilities of conception leading to clinical pregnancy, in relation to the timing of intercourse and vulvar mucus observations.

METHODS: This was a retrospective cohort study of women beginning use of the Creighton Model Fertility Care System in Missouri, Nebraska, Kansas, and California. Data were abstracted from Creighton Model Fertility Care System records, including women's daily standardized vulvar observations of cervical mucus discharge, days of intercourse, and clinically evident pregnancy (conception). Established statistical models were used to estimate day-specific probabilities of conception.

RESULTS: Data were analyzed from 1681 cycles with 81 conceptions from 309 normally fertile couples (initially seeking to avoid pregnancy) and from 373 cycles with 30 conceptions from 117 subfertile couples (who were initially trying to achieve pregnancy). The highest probability of pregnancy occurred on the peak day of vulvar mucus observation (.38 for normally fertile couples and.14 for subfertile couples). The probability of pregnancy was greater than.05 for normally fertile couples from 3 days before to 2 days after the peak, and for subfertile couples from 1 day before to 1 day after the peak. The cycle-specific probability of conception correlated with the quality of mucus discharge in normally fertile couples but not in subfertile couples.

CONCLUSION: Standardized vulvar observations of vaginal mucus discharge identify the days with the greatest likelihood of conception from intercourse in normal fertility and subfertility and provide an indicator of the overall potential for conception in a given menstrual cycle in normal fertility.


Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle

Abstract:
OBJECTIVE: To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG.

DESIGN: In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval.

SETTING: This study was carried out in a university-affiliated IVF program.

PATIENT(S): Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration.

INTERVENTION(S): S.c. or i.m. injection of hCG.

MAIN OUTCOME MEASURE(S): Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval.

RESULT(S): There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L).

CONCLUSION(S): After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.


Success of laparoscopic ovarian wedge resection is related to obesity, lipid  profile, and insulin levels

Abstract:
Objective: To evaluate the effects of laparoscopic ovarian wedge resection on hormonal and metabolic parameters of polycystic ovary syndrome (PCOS) and to compare profiles of women who achieved pregnancy with those who did not.
Design: Prospective study.
Setting: University hospital. PATIENT(S): Thirty-three women with PCOS. INTERVENTION(S): Laparoscopic ovarian wedge resection using harmonic scalpel. MAIN OUTCOME MEASURE(S): Pregnancy; levels of testosterone, DHEAS, gonadotropins, sex hormone-binding globulin (SHBG), and glucose and insulin during 2-hour glucose tolerance test; lipid profile; body mass index; and waist-to-hip ratio. RESULT(S): Twenty-two women (67%) achieved clinical pregnancy within the mean of 4.9 months after surgery. Baseline parameters of women who became pregnant differed from those who did not: those who became pregnant were less obese, had lower levels of total cholesterol, low-density lipoprotein, and triglycerides; higher levels of SHBG; lower levels of fasting insulin; lower insulin area under the curve; and higher insulin sensitivity index. Subjects not pregnant by 12 weeks after surgery underwent repeat endocrine and metabolic evaluations. In these women, wedge resection was followed by declines in testosterone, LH, and insulin sensitivity index. Wedge resection had no significant effect on SHBG, DHEAS, or lipid profile. CONCLUSION(S): Laparoscopic wedge resections are associated with the highest pregnancy rates among less obese subjects with favorable lipid profiles and lower insulin. In this study, the postoperative decline of serum testosterone and LH is not attributable to improvement of insulin sensitivity.


Metformin has direct effects on human ovarian steroidogenesis

Abstract:
OBJECTIVE: To investigate the possibility of direct effects of metformin on ovarian steroidogenesis.

DESIGN: Cultured ovarian cells.

SETTING: Academic research environment.

PATIENT(S): Women undergoing bilateral salpingoophorectomy for benign gynecological disease.

MAIN OUTCOME MEASURE(S): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium.

RESULT(S): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude.

CONCLUSION(S): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).


Use of recombinant human chorionic gonadotropin in ovulation induction

Abstract: To review the use of hCG and to describe the clinical benefit of recombinant hCG (r-hCG) based on the published results of prospective, randomized studies. Review of published articles. Tertiary infertility care center.None.None. Oocyte number and quality, luteal phase progesterone, pregnancy and OHSS rate, and local tolerability. The published data consistently show that single doses of 250 microg r-hCG and 5,000 IU urinary (u)-hCG produce similar clinical outcomes when used in infertility treatment cycles for timed intercourse, IUI, and IVF in terms of the number of oocytes retrieved, number of mature oocytes harvested, and fertilization and pregnancy rates attained. Single doses of 10,000 IU u-hCG also gave results comparable to single doses of 250 microg r-hCG. P levels in the midluteal phase were significantly higher with the use of r-hCG compared with u-hCG, and local injection site adverse effects were significantly less frequent, demonstrating the higher purity of the recombinant product. A single 500-microg dose of r-hCG led to a higher rate of ovarian hyperstimulation syndrome compared with a 250-microg dose, with no significant improvement in pregnancy rates.A single dose of 250 microg r-hCG was at least as effective as single doses of 5,000 or 10,000 IU u-hCG but offered the advantages associated with use of a recombinant product: local injection site adverse effects were significantly less frequent with r-hCG than with u-hCG.


Cryopreserved embryos in the United States and their availability for research

Society for Assisted Reproduction Technology (SART) and RAND

Abstract:
OBJECTIVE: To determine the number of embryos stored at assisted reproductive technology (ART) clinics in the United States and their current disposition.

DESIGN: A targeted survey instrument sent by the SART-RAND team to all medical practices providing in vitro fertilization services in the United States.

RESULTS: The SART-RAND team surveyed all 430 ART practices in the United States. Of these practices, 340 returned surveys for analysis. The data from these surveys were merged with data taken from the 1999 SART dataset, which contains information about practice size and success rates. Responding clinics reported a total of 396,526 embryos in storage as of April 11, 2002. The vast majority of the embryos (88.2%) were targeted for patient use. Small numbers of embryos were available for research, donation, destruction, quality assurance, or other uses.

CONCLUSIONS: Nearly 400,000 embryos are stored in the United States, the majority of which (88.2%) are targeted for patient use. Few are available for research (2.8%), limiting possible conversion into embryonic stem cell lines.


ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologist. Number 43, May 2003. Management of preterm labor

ACOG Committee on Practice Bulletins. American College of Obstetricians and Gynecologist


Accuracy of laparoscopic diagnosis of endometriosis

Abstract:
BACKGROUND AND OBJECTIVE: Laparoscopy is the standard method to visually identify endometriotic lesions under magnification within and outside the minor pelvis. The aim of this study was to analyze the accuracy of laparoscopic visualization in diagnosing the various endometriotic sites as confirmed histologically.

METHOD: Presumed endometriotic sites were observed in 164 patients operated on under the clinical suspicion of endometriosis. Targeted biopsies were performed for histologic corroboration, comparing the laparoscopic findings and diagnosis to the histological results.

RESULT: The histological reports of the biopsies confirmed the presence of endometriosis in 138 patients (84.1%), but in 26 patients (15.9%), no evidence of endometriosis was observed. 100% of "red" lesions, 92% of "black" lesions, and 31% of "white" lesions turned out to be endometriosis. Of the 264 various suspected endometriotic sites observed, 142 (53.8%) were confirmed histologically. The most accurate diagnosis was in lesions on the parietal peritoneum of the pelvis, confirmed in 9/9 cases (100%); the ovarian fossa, confirmed in 8/12 cases (66.7%); and the uterosacral ligaments and posterior surface of the broad ligament, confirmed in 83/138 cases (60.1%). As for the other sites, the histologic confirmation rates in the ovarian surface, bowel serosa, and vesicouterine fold of the peritoneum were 48%, 40%, and 13%, respectively.

CONCLUSION: Endometriosis has a multiple appearance, and the lesions may be confused with nonendometriotic lesions. It is clear that a nonhistology-based diagnosis may lead to unnecessary prolonged medical treatment and operations and may delay the proper treatment measures from being applied. Therefore, a meticulous histological confirmation should still be the first step in the laparoscopic diagnosis and treatment of suspected endometriosis.

JSLS : Journal of the Society of Laparoendoscopic Surgeons


Factors influencing the choice to use modern natural family planning

Martina Rauchfuss

Department of Psychosomatics, Charité University Hospital Berlin, Berlin, Germany.

Abstract: A discrepancy exists between the interest in modern methods of natural family planning (NFP) and their actual use in developed countries. To explore reasons for this discrepancy, we analyzed data from a questionnaire administered to postpartum women in Berlin (n = 223) and Cracow (n = 233). Knowledge of NFP, past use of NFP and expected effects of abstinence on the partnership were independently associated with interest in using NFP, but not the choice to do so among those interested. Desire for future pregnancies, importance of religious belief and location in Cracow were independently associated with the choice to use NFP among those interested. Perceived accuracy of observation to identify the fertile time and acceptance of own body were independently associated with both interest in and choice to use NFP. Frequency of intercourse had no effect on interest. These results suggest that increased access and cultural support would likely lead to a higher prevalence of NFP use in developed countries.


Mechanisms of premature ovarian failure

Mechanisms of premature ovarian failure

Abstract: The median age at menopause in Western populations of women is approximately 51 years. While very late (i.e., after 54 years) menopause is exceedingly uncommon, a sizeable minority of women experience cessation of ovarian function at or prior to age 45. By convention, menopause that occurs at ages 40-45 is considered "early" and occurs in about 5% of women. Premature ovarian failure (POF) is reserved for the approximately 1% of women who experience hypergonadotropic amenorrhea prior to age 40 years. POF represents the end stage of a variety of disorders that result in the loss of ovarian follicles. Depending upon the age at diagnosis, the probability of a genetic, autoimmune, or idiopathic cause will be more or less likely. Two functioning X chromosomes appear necessary for normal ovarian function. The most obvious genetic cause of POF is Turner Syndrome, in which a complete or near-complete loss of the second X chromosome occurs. Turner Syndrome typically results in the most severe and irreversible POF, often clinically evident prior to menarche. Typically, in Turner Syndrome, menopause precedes menarche, and there is no evidence of ovarian function. However, cases with multiple tissues diagnosed as 45, X have been reported to result in ovarian function and even pregnancy. It is likely that mitigating factors, perhaps autosomal, can modify this most severe and irreversible cause of ovarian failure. Lesser degrees of ovarian failure have also been attributed to partial X chromosome deletions and milder degrees of X chromosome mosaicism. Fragile X syndrome is another example of mild POF that can be linked to disorders of the X chromosome. Other genetic defects are believed to cause POF, yet their prevalence has been difficult to determine. The localization of the gene for the blepharophimosis/ptosis/POF Syndrome has been recently reported, yet this finding has not been seen commonly in POF. Other genetic syndromes including POF await elucidation. Many transgenic "knock-out" animals have been created with deficient ovarian function. Most interesting along these lines is the heterozygous FSH receptor knock-out, which exhibits a reduced follicle reserve and early ovarian depletion. Application of this knowledge and translation of these transgenic experiments into elucidation of clinical disease has been difficult, but represents an area of tremendous potential progress in the understanding of the pathogenesis of POF. Another approach to the genetics of POF has been to examine the genome of affected and unaffected individuals. The genetics appear to differ greatly depending upon the timing of the expression of the POF. For example, women with early menopause are more likely to possess the PVUII polymorphic allele for estrogen receptor alpha. Whether or not this polymorph is more common in women with earlier menopause, i.e., POF, is unclear. Pedigree data indicate that early menopause and premature menopause sort similarly within families. The only difference between women with true POF and those with early menopause may be in the timing of the expression of the syndrome, and not in the genetics. Population genetic approaches analyzing affected and unaffected individuals are underway in several research centers and represent another area of progress. Immune and other, idiopathic causes of POF await further clarification. It is clear that this is an area of great research potential. Understanding how ovaries fail may assist women with this disorder by facilitating the development of novel therapies. Additionally, such information will provide important clues about optimizing ovarian function in individuals without POF who are seeking extension of their reproductive life spans or fertility enhancement by other means.


Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian Multicentre Osteoporosis Study

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Alexandra Papaioannou

McMaster University, Hamilton, ON, Canada

Canadian Multicentre Osteoporosis Study Research Group

Abstract: This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.


False risk attribution results in misleading assessment of the relationship between suppression of ovulation and the effectiveness of the Yuzpe regimen for emergency contraception


Effect of rosiglitazone on spontaneous and clomiphene citrate-induced ovulation in women with polycystic ovary syndrome

Ghina Ghazeeri

University of Tennessee Health Science Center

Abstract:
OBJECTIVE: In women suffering from polycystic ovary syndrome (PCOS), correction of hyperinsulinemia results enhances spontaneous ovulation or alternatively, the responsiveness to ovulation induction agents such as clomiphene citrate (CC). We investigated the effect of rosiglitazone maleate on ovulation induction in overweight and obese, CC-resistant women with PCOS.

DESIGN: Double-blind, randomized, placebo-controlled trial.

SETTING: Academic reproductive endocrinology clinic.

PATIENT(S): Overweight and obese women with clinical and laboratory manifestations of PCOS who desired pregnancy and were resistant to CC.

INTERVENTION(S): Twenty-five women were randomized into two treatment groups. Subjects in Group I (n = 12) were randomized to receive rosiglitazone 4 mg b.i.d. with a placebo on cycle days 5-9. Group II (n = 13) was randomized to receive rosiglitazone 4 mg b.i.d. with CC on cycle days 5-9. The duration of the study was 2 months.

MAIN OUTCOME MEASURE(S): The primary outcome was ovulation as defined by luteal serum progesterone greater than 5 ng/dL assessed on days 21, 24, and 28 of the cycle. Secondary outcomes were pregnancy and changes in insulin sensitivity, serum lipoproteins, and androgens.

RESULT(S): Overall, 14 of 25 (56%) women, who were previously resistant to CC, successfully ovulated. In subjects taking rosiglitazone alone (Group I), 4 of 12 (33%) subjects ovulated compared with 10 of 13 (77%) women randomized to rosiglitazone with CC (Group II) (P=.04, Fisher's exact). One subject in Group I became pregnant, resulting in one uncomplicated live birth; two subjects in Group II conceived, with one successful live birth and one first trimester, spontaneous abortion. For all subjects, fasting insulin declined from 29.4 +/- 13.8 microU/mL to 17.3 +/- 7.8 microU/mL after rosiglitazone (P=.003, paired t-test). Although mean levels of total testosterone (T) and dehydroepiandrosterone sulfate (DHEAS) did not decline significantly, sex hormone-binding globulin (SHBG) did increase from 0.7 +/- 0.3 microg/dL to 1.0 +/- 0.3 microg/dL after rosiglitazone therapy (P=.001, paired t test). There was also a decrease in luteinizing hormone (LH) from 9.4 +/- 6.3 mU/mL to 7.2 +/- 3.7 mU/mL (P=.01). Lipoproteins including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides did not change.

CONCLUSIONS: Short-term rosiglitazone therapy enhances both spontaneous and clomiphene-induced ovulation in overweight and obese women with PCOS. Rosiglitazone therapy improves insulin sensitivity and decreases hyperandrogenemia primarily through increases in SHBG.


Births: final data for 2001

Births: final data for 2001

Abstract:
OBJECTIVES: This report presents 2001 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal demographic characteristics including age, live-birth order, race, Hispanic origin, marital status, and educational attainment; maternal characteristics (medical risk factors, weight gain, tobacco, and alcohol use); medical care utilization by pregnant women (prenatal care, obstetric procedures, complications of labor and/or delivery, attendant at birth, and method of delivery); and infant characteristics (period of gestation, birthweight, Apgar score, abnormal conditions, congenital anomalies, and multiple births). Also presented are birth and fertility rates by age, live-birth order, race, Hispanic origin, and marital status. Selected data by mother's State of residence are shown, as well as data on month and day of birth, sex ratio, and age of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.

METHODS: Descriptive tabulations of data reported on the birth certificates of the 4.026 million births that occurred in 2001 are presented. Denominators for population-based rates are derived from the 1990 U.S. census. As a result, rates are generally larger than would be the case if 2000-based estimates were used. The magnitude of the overestimate will vary by population subgroup; overestimates are likely greatest for those of Hispanic origin.

RESULTS: The number of births, the birth rate, fertility rate, and total fertility rates all declined 1 percent in 2001. The teenage birth rate reached another historic low. Birth rates for women in their twenties declined slightly, whereas rates for women aged 30 to 44 years continued to rise. Births to unmarried women changed very little. Smoking by pregnant women was down again. Women were more likely to begin care in the first trimester of pregnancy (83.4 percent). The cesarean delivery rate rose for the fifth consecutive year to 24.4 percent; the primary cesarean rate was up 5 percent and the rate of vaginal births after a previous cesarean fell 20 percent. Preterm and low birthweight levels both rose for 2001. The twin birth rate continued to climb, and following 2 years of decline, the rate of triplet/+ births also increased.

National Vital Statistics Reports : From the Centers for Disease Control and  Prevention, National Center for Health Statistics, National Vital Statistics  System


Ovarian wedge resection by minilaparatomy in infertile patients with polycystic ovarian syndrome: a new technique

Abstract:
OBJECTIVE: To determine the effects of ovarian wedge resection by minilaparotomy in infertile patients with polycystic ovarian syndrome (PCOS).

STUDY DESIGN: One hundred and thirty-four anovulatory patients with PCOS, who were previously treated with clomiphene citrate and gonadotropins and did not conceive were operated via minilaparotomy with microsurgical principles and ovarian wedge resection was performed on each subject. Pregnancy rates and adhesion formation were investigated retrospectively.

RESULTS: A total of 121 pregnancies were achieved in 2 years (90%). One hundred and four patients conceived within the first 6 months (78%) and the remaining 17 patients conceived within 2 years (13%) following the operation. Sixty-eight patients had a second pregnancy later. In the post-operative period, 24 patients had cesarean delivery and 20 had diagnostic laparoscopy. Out of these 44 patients, only 5 of them were found to have minimal adhesions.

CONCLUSION: This technique offers high pregnancy rates and minimal adhesion formation. Ovarian wedge resection by minilaparotomy might be an alternative treatment approach in patients with PCOS who did not conceive with standard ovulation induction protocols.

European Journal of Obstetrics, Gynecology, and Reproductive Biology


Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study

Abstract:
OBJECTIVE: The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population.

STUDY DESIGN: A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test.

RESULTS: The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05).

CONCLUSION: Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity.

American Journal of Obstetrics and Gynecology


Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial

Abstract:
Objective: To determine the efficacy of L-carnitine therapy in selected cases of male factor infertility.
Design: Placebo-controlled, double-blind, crossover trial.
Setting: University tertiary referral center.

Patients: One hundred infertile patients (ages 20-40 years) with the following baseline sperm selection criteria: concentration, 10-20 x 10(6)/mL; total motility, 10%-30%; forward motility, <15%; atypical forms, <70%; velocity, 10-30 micro/s; linearity, <4. Eighty-six patients completed the study.

Interventions: Patients underwent L-carnitine therapy 2 g/day or placebo; the study design was 2 months of washout, 2 months of therapy/placebo, 2 months of washout, and 2 months placebo/therapy.

Main Outcome Measures: Variation in sperm parameters used in the patients selection criteria, in particular, sperm motility. Excluding outliers, a statistically significant improvement in semen quality, greater than after the placebo cycle, was seen after the L-carnitine therapy for sperm concentration and total and forward sperm motility. The increase in forward sperm motility was more significant in those patients with lower initial values, i.e., <5 x 10(6) or <2 x 10(6) of forward motile sperm/ejaculate or sperm/mL.

Conclusions: Based on a controlled study of efficacy, L-carnitine therapy was effective in increasing semen quality, especially in groups with lower baseline levels. However, these results need to be confirmed by larger clinical trials and in vitro studies.


Decreased mature adrenomedullin levels in feto-maternal tissues of pregnant women with histologic chorioamnionitis

Fumiki Yoshihara

National Cerebral and Cardiovascular Center

Ikuko Makino

Mawatari Ladies Clinic, Fukuoka 819-1113, Japan.

Abstract: Adrenomedullin (AM) gains its bioactivity by amidation at its C-terminal, forming "mature AM." The mature AM and the expression of AM receptor component mRNAs, receptor activity-modifying protein 2 and calcitonin receptor-like receptor, from feto-maternal tissues of normal pregnant women and women with histologic chorioamnionitis were examined to clarify the pathophysiological features of this intrauterine infection. Samples of the placenta and fetal membranes were obtained from 10 normal pregnant women and eight women with histologic chorioamnionitis under informed consent. Mature AM in the fetal membranes was significantly lower in patients with chorioamnionitis than in normal pregnant women. On the other hand, there were no differences in mature AM levels in the placenta between the two groups. The total AM levels as a sum of mature and immature AM were not significantly different between the two groups in either area. The ratio of mature AM/total AM was significantly decreased in the fetal membranes of the patients with chorioamnionitis compared with normal pregnancies, but not in the placenta. Also, levels of mature AM were negatively correlated with C-reactive protein concentrations. The present results thus suggested that mature AM may have some role in chorioamnionitis.

Biochemical and Biophysical Research Communications


The diagnostic dilemma of minimal and mild endometriosis under routine conditions

Abstract:
STUDY OBJECTIVE: To evaluate the reliability of diagnosing minimal and mild endometriosis under routine conditions, and to determine to what extent disease activity is taken into account.

DESIGN: Retrospective analysis (Canadian Task Force classification II-2).

SETTING: University teaching hospital.

INTERVENTION: Laparoscopy.

PATIENTS: One hundred eighteen consecutive women with minimal and mild endometriosis undergoing routine surgery between 1994 and 1999.

MEASUREMENTS AND

MAIN RESULTS: Analytic parameters were the total number of endometriotic lesions; intraoperative description of pigmented, nonpigmented, and nondefined lesions; and number of extirpated lesions and histologic detection rate. In 118 patients, 311 suspected endometriotic lesions were documented. Nonpigmented lesions were reported in only 27% of women. In 51% of surgical reports no importance was attached to disease morphology or activity. Only 1.2 biopsies/patient were taken. The histologic detection rate was 56%. In 49 patients the assumed intraoperative diagnosis was confirmed by histologic examination.

CONCLUSIONS: Intraoperative description of endometriotic lesions is inadequate. Little attention is paid to the activity of the illness. There is room for improvement in the number of excisions and histologic detection, and an attempt should be made to find a way out of this diagnostic dilemma.

The Journal of the American Association of Gynecologic Laparoscopists


Hormonal contraceptive use and HIV-1 infection in a population-based cohort in Rakai, Uganda

Abstract:
Background: Hormonal contraceptives have been associated with increased risk of HIV acquisition.

Methods: The association between hormonal contraception use and HIV acquisition was assessed in a rural community-based cohort in Rakai District, Uganda. A group of 5117 sexually active HIV-negative women were surveyed at 10 month intervals between 1994 and 1999. Information on demographic and sociobehavioral characteristics, use of hormonal contraception (pill and injectable methods), condoms and the number of sexual partners was obtained by home-based interview. HIV incidence rate ratios (IRR) and 95% confidence intervals (CI) associated with hormonal contraception were estimated by multivariate Poisson regression after adjustment for age, condom use, number of sexual partners, marital status, education and history of genital ulcer disease.

Results: At one or more interviews, 16.6% of women reported use of hormonal contraceptives and 23.0% reported condom use. HIV incidence was 2.3/100 person-years in hormonal contraceptive users compared with 1.5/100 person-years in non-hormonal contraceptive users (unadjusted IRR, 1.56; 95% CI, 1.00-2.33). After multivariate adjustment, the IRR associated with hormonal contraceptives was reduced to 0.94 (95% CI, 0.53-1.64). The adjusted IRR was 1.12 (95% CI, 0.48-2.56) with oral contraceptive use and 0.84 (95%CI, 0.41-1.72) with injectable methods.

Conclusion: Use of hormonal contraception is not associated with HIV acquisition after adjustment for behavioral confounding.


Regulation of gonadotropin secretion: implications for polycystic ovary syndrome

Abstract: Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism and chronic anovulation. Although the etiology of PCOS is unknown, perturbations of gonadotropin secretion are one of the hallmarks of this disorder. In normal menstrual physiology, the monotropic rise of plasma follicle-stimulating hormone (FSH) during the luteal-follicular transition is critical for follicular development and subsequent ovulation. One of the mechanisms by which FSH is differentially synthesized involves the luteal slowing of gonadotropin-releasing hormone (GnRH) pulse frequency by ovarian steroids. In PCOS, plasma leutinizing hormone (LH) is commonly increased, FSH is typically in the lower follicular range, and LH (and by inference GnRH) pulse frequency is persistently rapid at approximately one LH pulse per hour. The etiology of the neuroendocrine abnormalities in PCOS remain unclear; however, recent studies have revealed decreased sensitivity of the GnRH pulse generator to inhibition by ovarian steroids, particularly progesterone. This abnormality is reversed by the androgen receptor antagonist flutamide, suggesting that elevated androgen levels may alter the sensitivity of the hypothalamic GnRH pulse generator to steroid inhibition and lead to enhanced LH secretion. As such, women with PCOS require higher levels of progesterone to slow the frequency of GnRH pulse secretion, resulting in inadequate FSH synthesis and persistent LH stimulation of ovarian androgens. The decreased sensitivity of the GnRH pulse generator may help to explain the genesis of PCOS during puberty. In normal early puberty, sleep-entrained increases in LH stimulate ovarian steroids, which subsequently suppress LH frequency and amplitude during the subsequent day. In hyperandrogenemic girls destined to develop PCOS, this nocturnal increase in ovarian steroids may not be adequate to suppress the GnRH pulse generator, leading to a persistently rapid LH pulse frequency, impaired FSH production, and inadequate follicular development.


A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome

Abstract:
OBJECTIVE: To review the effectiveness of metformin in restoring regular menstrual cycles and ovulation and achieving pregnancy in women with polycystic ovary syndrome (PCOS).

DESIGN: Systematic review of pertinent studies identified using the bibliographic databases MEDLINE and EMBASE. References of selected articles identified were hand-searched for additional relevant citations.

PATIENT(S): Women with PCOS undergoing treatment with metformin alone, metformin combined with other methods of ovulation induction such as clomiphene citrate (CC) or gonadotropin injections, or metformin combined with in vitro fertilization (IVF).

RESULT(S): Thirty published studies were included in the overall review. Studies consisted of 12 randomized controlled trials, two cohort studies, and 16 uncontrolled descriptive studies. Due to a strong variability in the use of metformin according to study population, exposure, and outcome of interest, it was not possible to combine the data of the 12 randomized controlled trials to perform a meta-analysis. Limited data on predominately obese PCOS patients demonstrate that metformin alone improves both restoration of regular menses and spontaneous ovulation, but there are no data supporting an improvement in pregnancy rate. The addition of metformin to CC results in an improved ovulation and pregnancy rate in both unselected and CC-resistant PCOS women. There are insufficient data to make any conclusions on the effect of metformin on FSH ovulation induction or IVF.

CONCLUSION(S): The effectiveness and role of metformin in the treatment of PCOS anovulatory infertility in clinical practice is difficult to assess from currently available research. Further well-designed prospective, perhaps multicenter, randomized controlled trials with the primary end point of pregnancy or live-birth rate are required.


Blood levels of homocysteine, folate, vitamin B6 and B12 in women using oral contraceptives compared to non-users

Abstract:
BACKGROUND AND OBJECTIVES: To compare the levels of total homocysteine (tHcy), folate, vitamin B6 and B12, in women not using oral contraceptives (OC) vs. those using OC.

MATERIALS AND METHODS: 219 healthy women were enrolled in the study; 159 of them had not been using OC for at least 12 months prior to their enrollment, while 60 were on regular OC treatment.

RESULTS: The median levels of vitamin B6 and B12 were significantly lower in OC users than in non-users (24.2 vs. 32.9 nmol/l, p=0.029; 278 vs. 429 ng/ml, p<0.001). There were no statistically significant differences in the levels of tHcy (fasting and post-methionine loading) and folate.

CONCLUSIONS: In our cross-sectional study, OC use was associated with low vitamin B6 and B12 levels. Since low vitamin B6 levels are independently associated with heightened risks for arterial and venous thromboembolism (TE), they could partly account for the increased TE risk of OC users.


The Creighton Model FertilityCare™ System: A Standardized Case Management Approach to Teaching. Book II — Advanced Teaching Skills

Thomas W Hilgers

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


2001 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports

National Center for Chronic Disease Prevention and Health Promotion


March of Dimes Updates: Multiple Births and the Rising Rate of Preterm Delivery


Too Soon to Adopt Progesterone for the Prevention of Preterm Delivery


DIR Jahrbuch 2002 (Deutsches IVF-Register Annual Report 2002)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2002. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation

Abstract:
BACKGROUND: Analyses of the follicular reserve and activity of the ovary are central to our understanding of the regulation of follicular development. We have carried out a prospective analysis of endocrine and biophysical assessments under three differing basal conditions: the early follicular and mid-luteal phases, and following GnRH analogue down-regulation.

METHODS: Hormonal analyses were carried out before and after a single dose of FSH on spontaneously ovulating women (n = 58). Ovarian volume and antral follicle count (AFC) were also determined.

RESULTS: Inhibin B and estradiol concentrations were increased by FSH under all three conditions, and inhibin A in the follicular phase and after down-regulation. Basal hormone concentrations, except inhibin A and B after down-regulation, did not generally correlate with AFC. A close relationship between inhibin B and AFC was evident at all stages after FSH administration (r = 0.70-0.77). AFC and inhibin B after FSH stimulation were well correlated with the number of oocytes recovered after superovulation. Multivariate analysis demonstrated that inhibin B after FSH administration in the down-regulated state showed the closest correlation with oocyte number. In the more clinically useful early follicular and luteal phases, basal FSH was the most significant contributor to the number of oocytes, with a significant contribution from luteal phase AFC.

CONCLUSIONS: These data extend our understanding of the relationships between follicular number, follicular functional activity, and the recruitable follicular population. Down-regulation and subsequent FSH stimulation was required to clearly demonstrate the close relationship between inhibin B and the ovarian reserve. Without such complex manipulation, early follicular phase FSH (supplemented by AFC in the relatively hypogonadotrophic luteal phase) remains of greater value in predicting the ovarian reserve than the currently known direct products of the ovary.


The Creighton Model FertilityCare™ System: Core Curriculum, 2nd Edition


Gauging Preterm Delivery Risk in Asymptomatic Gravidas


Assisted reproductive technology surveillance--United States, 2000

Laura A Schieve

Centers for Disease Control and Prevention

Abstract: MMWR 2003 Oct 3; 52(39):942. PROBLEM/CONDITION: In 1996, CDC initiated data collection regarding assisted reproductive technology (ART) procedures performed in the United States to determine medical center-specific pregnancy success rates, as mandated by the Fertility Clinic Success Rate and Certification Act (FCSRCA) (Public Law 102-493, October 24, 1992). ART includes fertility treatments in which both eggs and sperm are handled in the laboratory (i.e., in vitro fertilization and related procedures). Patients who undergo ART treatments are more likely to deliver multiple-birth infants than women who conceive naturally. Multiple births are associated with increased risk for mothers and infants (e.g., pregnancy complications, premature delivery, low-birthweight infants, and long-term disability among infants). REPORTING PERIOD COVERED: 2000. DESCRIPTION OF SYSTEM: CDC contracts with a professional society, the Society for Assisted Reproductive Technology (SART), to obtain data from fertility medical centers located in the United States. Since 1997, CDC has compiled data related to ART procedures. The Assisted Reproductive Technology Surveillance System was initiated by CDC in collaboration with the American Society for Reproductive Medicine, the Society for Assisted Reproductive Technology, and RESOLVE: The National Infertility Association. RESULTS: In 2000, a total of 25,228 live-birth deliveries and 35,025 infants resulting from 99,629 ART procedures were reported to CDC from 383 medical centers that performed ART in the United States and U.S. territories. Nationally, 75,516 (76%) of ART treatments were freshly fertilized embryos using the patient's eggs; 13,312 (13%) were thawed embryos using the patient's eggs; 7,919 (8%) were freshly fertilized embryos from donor eggs; and 2,882 (3%) were thawed embryos from donor eggs. The national live-birth delivery per transfer rate was 30.8%. The five states that reported the highest number of ART procedures were California (13,194), New York (11,239), Massachusetts (8,041), Illinois (7,323), and New Jersey (5,506). These five states also reported the highest number of live-birth deliveries and infants born as a result of ART. Overall, 47% of women undergoing ART-transfer procedures using freshly fertilized embryos from their own eggs were aged <35 years; 23% were aged 35-37 years; 19% were aged 38-40 years; 7% were aged 41-42 years; and 4% were aged >42 years. Among ART treatments in which freshly fertilized embryos from the patient's eggs were used, substantial variation in patient age, infertility diagnoses, history of past infertility treatment, and past births was observed. Nationally, live-birth rates were highest for women aged <35 years (38%). The risk for a multiple-birth delivery was highest for women who underwent ART-transfer procedures using freshly fertilized embryos from either donor eggs (40%) or from their own eggs (35%). Among women who underwent ART-transfer procedures using freshly fertilized embryos from their own eggs, further variation by patient age and number of embryos transferred was observed. Of the 35,025 infants born, 44% were twins, and 9% were triplet and higher order multiples, for a total multiple-infant birth rate of 53%. Patient's residing in states with the highest number of live-birth deliveries also reported the highest number of infants born in multiple-birth deliveries. INTERPRETATION: Whether an ART procedure was successful (defined as resulting in a pregnancy and live-birth delivery) varied according to different patient and treatment factors. Patient factors included the age of the woman undergoing ART, whether she had previously given birth, whether she had previously undergone ART, and the infertility diagnosis of both the female and male partners. Treatment factors included whether eggs were from the patient or a woman serving as an egg donor, whether the embryos were freshly fertilized or previously frozen and thawed, how long the embryos were kept in culture, how many embryos were transferred, and whether various specialized treatment procedures were used in conjunction with ART. ART poses a major risk for multiple births. This risk varied according to the patient's age, the type of ART procedure performed, and the number of embryos transferred. In addition, the increased risk for multiple births has a notable population impact in certain states. PUBLIC HEALTH ACTIONS: As use of ART and ART success rates continue to increase, ART-related multiple births are an increasingly important public health problem nationally and in many states. The proportion of infants born through ART in 2000 that were multiple births (53%) was substantially higher than in the general U.S. population during the same period. Data in this report indicate a need to reduce multiple births associated with ART. Efforts should be made to limit the number of embryos transferred for patients undergoing ART. In addition, continued research and survei

Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)


Mechanisms of action of intrauterine devices: update and estimation of postfertilization effects

Abstract: There are many potential mechanisms of action for the intrauterine device (IUD), which vary by type of IUD (inert, copper, or hormonal). This paper reviews the evidence for each potential mechanism of action. On the basis of available data for fertilization rates and clinical pregnancy rates, the relative contribution of mechanisms acting before or after fertilization were quantitatively estimated. These estimates indicate that, although prefertilization effects are more prominent for the copper IUD, both prefertilization and postfertilization mechanisms of action contribute significantly to the effectiveness of all types of intrauterine devices.

American Journal of Obstetrics and Gynecology


The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health

Michael Zimmermann

École Polytechnique Fédérale de Lausanne

Josef Köhrle

Institut für Experimentelle EndoKrinologie, Charité, Humboldt-Universitaet zu Berlin, Germany.

Abstract: Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.

Thyroid : Official Journal of the American Thyroid Association


Insulin-lowering treatment reduces aromatase activity in response to follicle-stimulating hormone in women with polycystic ovary syndrome

Abstract:
OBJECTIVE: To investigate the effects of reduction of insulin resistance and hyperinsulinemia associated with the polycystic ovary syndrome (PCOS) on FSH-stimulated ovarian aromatase activity.

DESIGN: Prospective study.

SETTING: Academic health center, Siena, Italy.

PATIENT(S): Twenty women 18 to 26 years of age in whom PCOS was diagnosed on the basis of oligomenorrhea or amenorrhea and hyperandrogenemia.

INTERVENTION(S): Recombinant FSH was administered. The next day, therapy with metformin (500 mg t.i.d.) was begun. After 35 to 40 days of treatment, the pretreatment protocol was repeated.

MAIN OUTCOME MEASURE(S): Plasma levels of estradiol (E(2)), androstenedione (A), and testosterone (T). The ratios of basal levels and areas under the curve (AUCs) of products and substrates were compared before and after metformin administration to detect differences in aromatase activity.

RESULT(S): Metformin treatment was associated with significant reduction in basal free testosterone plasma levels, insulin plasma levels, and insulin response to oral glucose tolerance testing. Administration of FSH was followed by a significantly lesser E(2) response after metformin therapy than before this therapy. The ratios of AUC(E2) to AUC(A) and to AUC(T), indicative of aromatase activity in response to FSH, were significantly lower after metformin therapy than before.

CONCLUSION(S): Metformin therapy in women with PCOS is associated with a reduction in aromatase activity in response to FSH. Insulin affects production of both androgen and estrogen. Insulin therefore plays a central role in regulating the activity of thecal and granulosa cells.


Comparison of spironolactone and spironolactone plus finasteride in the treatment of hirsutism

Abstract:
Hirsutism is a very common clinical problem encountered in daily practice, and, unfortunately, its treatment is far from satisfactory. In several studies, antiandrogens were given in combination with oral contraceptives (1–3), however, there are not enough data about the effects of combination therapy of antiandrogens in women with hirsutism.
Thirty-four patients were recruited into the study from the Endocrinology Outpatient Clinic of Erciyes University Hospital. Each patient gave informed consent, and the study was approved by the ethics committee and Institutional Review Board of Erciyes University. Cushing’s syndrome, nonclassic adrenal hyperplasia, androgen-secreting tumors, and prolactinoma were excluded by appropriate tests and radiological investigations. Twelve patients were oligomenorrheic, and these patients had polycystic ovary syndrome. Twenty-two patients had idiopathic hirsutism.


First-trimester pregnancy loss and active Chlamydia trachomatis infection: correlation and ultrastructural evidence

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: The incidence of Chlamydia trachomatis (Ct) infection and the possible correlation between couples presenting with first-trimester spontaneous abortions and active Ct infection was assessed. Additionally, the ability of Ct to infect zona-free hamster oocytes was explored by incubating the oocytes with spermatozoa from infected patients. A total of 961 women and 750 men consulting our reproductive medicine centre were screened for Ct using direct immunofluorescence. The general incidence of Ct infection was 9.4% in females (90 of 961) and 13.9% in males (104 of 750). In women with spontaneous abortions the incidence of Ct was 21.0% (14 of 66) compared with 8.9% (23 of 59) for women without spontaneous abortions and term pregnancies (chi-square, P < 0.05). When both partners of the couples were considered (one or both partners infected), the incidence rose to 68.8% (22 of 32) (chi-square, P < 0.001). In vitro studies using electron microscopy demonstrated the presence of Ct on the surface of and inside the oocyte. These results indicate a correlation between an active Ct infection and spontaneous abortion. Electron microscopy studies suggested the possibility of direct oocyte infection by Ct. Two models are proposed for the pathogenesis of Ct-related early abortions: (i) direct zygote infection, and (ii) immune response to heat shock proteins expressed by the zygote and triggered by previous Ct infections.


Timing intercourse to achieve pregnancy: current evidence

Abstract: Physicians who counsel women for preconception concerns are in an excellent position to give advice to couples regarding the optimal timing of intercourse to achieve pregnancy. The currently available evidence suggests that methods that prospectively identify the window of fertility are likely to be more effective for optimally timing intercourse than calendar calculations or basal body temperature. There are several promising methods with good scientific bases to identify the fertile window prospectively. These include fertility charting of vaginal discharge and a commercially available fertility monitor. These methods identify the occurrence of ovulation clinically and also identify a longer window of fertility than urinary luteinizing hormone kits. Prospectively identifying the full window of fertility may lead to higher rates of conception. Proper information given early in the course of trying to achieve pregnancy is likely to reduce time to conception for many couples, and also to reduce unnecessary intervention and cost.