Local mononuclear cell infiltrates in infertile patients with endometrial macropolyps versus micropolyps

Abstract:
STUDY QUESTION: Is the endometrial mononuclear cell population in infertile patients altered in subjects with classical endometrial polyps (macropolyps) versus endometrial micropolyps that are hysteroscopically recognized as small uterine cavity protrusions?

SUMMARY ANSWER: Macropolypoid endometrium had a low density of pan-leukocytes, pan-T cells and natural killer (NK) cells, whereas micropolypoid endometrium was characterized by high density of B cells and plasmacytes, along with a low density of NK cells.

WHAT IS KNOWN ALREADY: Endometrial micropolyps co-exist at a high rate with chronic endometritis, which is an unusual plasmacyte infiltration within the endometrial stromal compartment.

STUDY DESIGN: Prospective cross-sectional study. From July 2009 to June 2011, hysteroscopy was performed for infertile women who had been suspected for endometrial macropolyps and who had repeated in vitro fertilization-embryo transfer failure over three or more cycles. Endometrial biopsy samples were obtained from the patients with macropolyps or micropolyps during the proliferative phase. Of 137 patients assessed, 30 were diagnosed with endometrial macropolyps and 34 were diagnosed with endometrial micropolyps. After the exclusion of the cases with heavy uterine bleeding, potential neoplasms, submucosal uterine fibroids, uterine septa, and/or intrauterine adhesion, 23 patients with macropolypoid endometrium; 25 patients with micropolypoid endometrium and 27 patients with non-polypoid endometrium were enrolled in the study. Endometrial macropolyps were surgically removed, whereas chronic endometritis was treated with antibiotics. The patients were followed up until December 2011.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The paraformaldehyde-fixed paraffin-embedded endometrial sections were immunostained with monoclonal antibodies against the specific markers of pan-leukocytes (CD45), pan-T cells (CD3), Th cells (CD4), Tc cells (CD8), B cells (CD20), plasmacytes (CD138), NK cells (CD56) and macrophages (CD68). The immunoreactive cells were enumerated in at least 20 non-overlapping stromal areas.

MAIN RESULTS AND THE ROLE OF CHANCE: Compared with the non-polypoid endometrium, macropolypoid endometrium contained a lower density of pan-leukocytes, pan-T cells and NK cells, whereas micropolypoid endometrium had a higher density of pan-leukocytes and B cells, along with a lower density of NK cells. Following the treatments, 10 patients with macropolypoid endometrium, 11 patients with micropolypoid endometrium and 10 patients with non-polypoid endometrium conceived.

LIMITATIONS, REASONS FOR CAUTION: One potential bias is immunohistochemical enumeration for leukocyte density was conducted by one examiner. The limitation of this study is that the results relied on endometrial biopsy specimens, of which immunological conditions may not always represent those in the whole endometrium.

WIDER IMPLICATIONS OF THE FINDINGS: There may be some ethnic or racial variances in the composition of the endometrial mononuclear cell subsets of infertile women.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Grand-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (22591840). There were no conflicts of interest to declare.


Progesterone use to reverse the effects of mifepristone

Abstract:
OBJECTIVE: To present a series of cases demonstrating successful reversal of mifepristone effects in women who chose to reverse the medical abortion process.

CASE REPORTS: Four of 6 women who took mifepristone were able to carry their pregnancies to term after receiving intramuscular progesterone 200 mg.

DISCUSSION: Mifepristone has been available in the US since 2000. By 2008, approximately 25% of abortions prior to 9 weeks were accomplished with mifepristone. Some women who take mifepristone wish to reverse the medical abortion process. Progesterone competes with mifepristone for the progesterone receptor and may reverse the effects of mifepristone. A PubMed literature search from 1996 to May 2012 did not reveal any trials or case studies evaluating the efficacy of progesterone use to reverse the effects of mifepristone.

CONCLUSIONS: Health care professionals should be aware of the possible use of progesterone to reverse mifepristone in women who have begun the medical abortion process by taking mifepristone and then change their minds.


The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation

Abstract:
Study question: Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)?Study answerARTs, and particularly intracytoplasmic sperm injection (ICSI), are specifically associated with a higher risk of TOF.What is already knownARTs are associated with an increase in the overall risk of birth defects. The risk for congenital heart defects (CHDs) associated with ARTs has been evaluated as a whole but there is limited information on the risks for specific CHDs. STUDY DESIGN, MATERIAL AND METHODS: We conducted a case-control study using population-based data from the Paris registry of congenital malformations for the period 1987-2009 and a cohort study of CHD (EPICARD) on 1583 cases of CHDs and 4104 malformed controls with no known associations with ARTs. ARTs included ovulation induction only, IVF and ICSI.

Results: Exposure to ARTs was significantly higher for TOF than controls (6.6 versus 3.5%, P = 0.002); this was not the case for the other three CHDs. ARTs (all methods combined) were associated with a 2.4-fold higher odds of TOF after adjustment for maternal characteristics, paternal age and year of birth [adjusted odds ratios (OR): 2.4, 95% confidence interval (CI): 1.5-3.7] with the highest risk associated with ICSI (adjusted OR: 3.0, 95% CI: 1.0-8.9). No statistically significant associations were found for the other CHDs.

Limitations: Our study cannot disentangle to what extent the observed associations between the risk of TOF and ARTs are due to causal effects of ARTs and/or the underlying infertility problems of couples who conceive following ART.

Implications: The developmental basis of the specific association between the risk of TOF and ARTs need to be further investigated.


Effects of metformin use in pregnant patients with polycystic ovary syndrome

Abstract: Use of metformin throughout pregnancy in women with polycystic ovary syndrome (PCOS) has shown to reduce the rates of early pregnancy loss, preterm labor, and prevention of fetal growth restriction. Metformin has been shown to have encouraging effects on several metabolic aspects of polycystic ovarian syndrome, such as insulin sensitivity, plasma glucose concentration and lipid profile and since women with PCOS are more likely than healthy women to suffer from pregnancy-related problems like early pregnancy loss, gestational diabetes mellitus and hypertensive states in pregnancy, the use of metformin therapy in these patients throughout pregnancy may have beneficial effects on early pregnancy loss and development of gestational diabetes.


Natural family planning

Natural family planning

Abstract: Natural family planning methods provide a unique option for committed couples. Advantages include the lack of medical adverse effects and the opportunity for participants to learn about reproduction. Modern methods of natural family planning involve observation of biologic markers to identify fertile days in a woman's reproductive cycle. The timing of intercourse can be planned to achieve or avoid pregnancy based on the identified fertile period. The current evidence for effectiveness of natural family planning methods is limited to lower-quality clinical trials without control groups. Nevertheless, perfect use of these methods is reported to be at least 95 percent effective in preventing pregnancy. The effectiveness of typical use is 76 percent, which demonstrates that motivation and commitment to the method are essential for success. Depending on the method, couples can learn about natural family planning methods in a single office visit, through online instruction, or from certified instructors.


Randomized comparison of two Internet-supported fertility-awareness-based methods  of family planning

Abstract:
Background: The aim was to compare the efficacy and acceptability of two Internet-supported fertility-awareness-based methods of family planning.

STUDY Design: Six hundred and sixty-seven women and their male partners were randomized into either an electronic hormonal fertility monitor (EHFM) group or a cervical mucus monitoring (CMM) group. Both groups utilized a Web site with instructions, charts and support. Acceptability was assessed online at 1, 3 and 6 months. Pregnancy rates were determined by survival analysis.

Results: The EHFM participants (N=197) had a total pregnancy rate of 7 per 100 users over 12 months of use compared with 18.5 for the CMM group (N=164). The log rank survival test showed a significant difference (p<.01) in survival functions. Mean acceptability for both groups increased significantly over time (p<.0001). Continuation rates at 12 months were 40.6% for the monitor group and 36.6% for the mucus group.

Conclusion: In comparison with the CMM, the EHFM method of family planning was more effective. All users had an increase in acceptability over time. Results are tempered by the high dropout rate.


Engaging men in family planning services delivery: experiences introducing the  Standard Days Method® in four countries

Abstract: Family planning is often regarded as the woman's responsibility, but there is growing recognition of the need to involve men in family planning programs. Since 2001, the fertility-awareness-based Standard Days Method® (SDM) has been introduced in more than 30 countries, providing a natural, effective birth control option. SDM requires the cooperation of the male partner, and its introduction created an opportunity to test innovative strategies to engage couples in family planning. Such strategies included couple counselling, outreach activities that encouraged men to participate in family planning and integration of family planning into traditionally male programs. Due to the SDM's intrinsic characteristics as a couple method, SDM providers are sensitized to the importance of exploring other critical sexual and reproductive health topics, including intimate partner violence, HIV, sexuality and partner communication. This paper presents several case studies describing how men were engaged in SDM introduction activities in four countries.


The Influence of BMI Levels on Phases of the Menstrual Cycle and Presumed Ovulation

Abstract: Obesity and high body mass index (BMI) are known to be risks for anovulation and infertility. Little is known about how BMI levels affect parameters of the menstrual cycle. The purpose of this study was to determine the influence of BMI on parameters of the menstrual cycle and the likelihood for ovulation. The participants in this study were 244 women between the ages of twenty and fifty-four (mean thirty years) who charted from one to thirty-six menstrual cycles (mean seven cycles) for a total of 2,035 cycles. Urinary luteinizing hormone (LH) threshold tests were used to estimate the day of ovulation and the lengths of the follicular and luteal phases. The 244 participants were classified as normal weight with a BMI of 18.5-24.9 kg/m2 (N = 141), overweight with a BMI of 25-29.9 kg/m2 (N = 67), and obese with a BMI of 30 kg/m2 or greater (N = 36). One-way ANOVA indicated that there was a significant difference between groups in length of the luteal phase (F = 4.62, p < 0.01) and length of menses (F = 3.03, p < 0.05). Odds ratio indicated that the combined obese and overweight group was 34 percent less likely to have a positive detected urinary LH surge. We concluded that obesity might contribute to infertility by shortening the luteal phase and decreasing the probability of ovulatory menstrual cycles.


The Evaluation and Treatment of Cervical Factor Infertility a Medical-Moral  Analysis

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family

Abstract: The current approach to infertility of assisted reproductive technology (ART) completely misses and then bypasses the evaluation and treatment of cervical factor infertility. In contrast, the Creighton Model Fertility Care System (CrMS), a method of fertility awareness that has the unique ability to quantify cervical mucus observations, and natural procreative technology (NaProTECHNOLOGY or NPT) directly evaluate and treat cervical factor infertility. The ART treatment of choice for cervical factor infertility--intrauterine insemination (IUI)--is also morally disparate from the NPT treatment protocol: while the latter genuinely assists the infertile couple's act of sexual union to achieve its natural end of pregnancy, IUI replaces the natural act, depriving human conception of the one context worthy of the dignity of human life and procreation, a reciprocal self-gifting act of love between husband and wife. A renewed interest and focus on the direct evaluation and treatment of cervical factor infertility is needed.


The Linacre Quarterly, Rhythm, NFP, and Human Fertility from Popes Pius XI  through Benedict XVI


Is Fibromyalgia An Endocrine/Endorphin Deficit Disorder? Is Low Dose Naltrexone a New Treatment Option?


Descriptive Statistical Evaluation of the Standard Days Method of Family  Planning

Abstract: The Standard Days Method (SDM) is a method of family planning that assumes ovulation to be close to the midpoint of the menstrual cycle; fertility falls between days 8 and 19; and is most effective for cycle lengths between twenty-six and thirty-two days. The purpose of this study was to evaluate the assumptions of the SDM with a new data set of 714 menstrual cycles produced by 131 women (mean age twenty-nine) who tracked their fertility with an electronic fertility monitor that measured urinary estrogen and luteinizing hormone (LH). The LH peak was used to estimate the day of ovulation (EDO) and the six-day fertile window. Results indicated the majority (80 percent) of menstrual cycles had EDOs within three days of the midpoint of the cycle (86 percent with cycle lengths between twenty-six and thirty-two days). Approximately 22.5 percent (172) of the cycles had fertile window days outside of days 8 to 19, 10.2 percent (78) before, and 12.1 percent (92) after. However, there is a low probability of pregnancy when women experience short cycles and the early days of the fertile window are outside of days 8 through 19. We concluded assumptions of the SDM outside of the fertile window with long cycles could be problematic. However, the SDM is valid for women who have most cycles within the twenty-six to thirty-two day range.


Perfluorochemicals and endometriosis: the ENDO study

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Background: Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues.

Methods: We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity.

Results: Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively).

Conclusions: Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.


The role of anti-Müllerian hormone in female fertility and infertility - an overview

Abstract: Anti-Müllerian hormone (AMH) plasma levels reflect the continuous non-cyclic growth of small follicles, thereby mirroring the size of the resting primordial follicle pool and thus acting as a useful marker of ovarian reserve. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women; thus, it has a potential ability to predict future reproductive lifespan. The most established role for AMH measurements is before in vitro fertilization is initiated, because AMH can be predictive of the ovarian response, namely poor and hyper-responses. However, recent research has also highlighted the use of AMH in a variety of ovarian pathological conditions, including polycystic ovary syndrome, granulosa cell tumors and premature ovarian failure. A new commercial enzyme-linked immunosorbent assay for measuring AMH levels has been developed, making results from different studies more comparable. Nevertheless, widespread clinical application awaits an international standard for AMH, so that results using future assays can be reliably compared.

Acta obstetricia et gynecologica Scandinavica


Natural Family Planning Instruction as a Marriage Requirement a Retrospective  Analysis of the First Two Years' Experience in the Diocese of Covington()

Abstract: Beginning January 1, 2009, the Roman Catholic Diocese of Covington mandated that all engaged couples take a full course of NFP instruction as part of preparation for marriage within the Church. Using data from the Couple to Couple League and its Covington-based instructors, overall NFP instruction and characteristics of the couples attending classes before and after the mandate were examined. In the first two years, 66 percent and 77 percent of couples who married in the diocese, respectively, attended an NFP class. The mandate shifted the reasons for couples taking NFP instruction; prior to the mandate, 40 percent of engaged couples attended classes solely due to a pastor's requirement while 74 percent of engaged couples did so afterward (p < 0.001). Hormonal contraceptive use was common; 54 percent reported current use while another 23 percent reported former use. Current hormonal contraceptive use was significantly more common among those attending solely due to the mandate compared to those attending for multiple reasons (59 percent vs. 41 percent respectively, p = 0.004) and was significantly more common among engaged compared to married couples (53 percent vs. 8 percent respectively, p < 0.001). Cohabiting engaged couples were significantly more likely to have ever used hormonal contraceptives (91 percent vs. 71 percent, p < 0.0001), compared to engaged couples who were not cohabiting at the time of NFP instruction, and were significantly less likely to both be Catholic (55 percent vs. 70 percent, p = 0.002). Overall, implementation of mandatory NFP instruction as part of marriage preparation was successful; in post-class surveys, over 90 percent of couples acknowledged they had a better understanding of their fertility, and 83 percent would recommend the classes to a friend. Longer-term prospective follow-up is needed to evaluate the long-term impacts to couples exposed to such a requirement.


The Importance of Fertility Awareness in the Assessment of a Woman's Health a  Review

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: Fertility awareness constitutes fundamental knowledge for every woman and is an important tool for health professionals. The objective of this review is to show how fertility awareness can be useful in the assessment of a woman's health. The main techniques for detecting ovulation are explained, and then the events that characterize a normal menstrual cycle are discussed. The relevance of cervical mucus from the perspective of female fertility is highlighted. Finally, the usefulness of fertility awareness 1) to identify fertile and infertile periods, 2) to help to detect several pathologies, and 3) in regards to how it exerts an important role in the success of programs in education for affectivity and sexuality are discussed.


Childhood thyroid radioiodine exposure and subsequent infertility in the intermountain fallout cohort

Abstract:
Background: Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951-1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility.

Objectives: We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility.

Methods: Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease.

Results: Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility.

Conclusion: Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this.


Menarche, menopause, and breast cancer risk: individual participant  meta-analysis, including 118 964 women with breast cancer from 117  epidemiological studies

Collaborative Group on Hormonal Factors in Breast Cancer

Cancer Epidemiology Unit, Richard Doll Building, Oxford OX3 7LF, UK. collaborations@ceu.ox.ac.uk

Abstract:
Background: Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.

Methods: Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.

Findings: Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).

Interpretation: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.

Funding: Cancer Research UK.


Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users

Deborah Davis

University of Canberra, 11 Kirinari St, Bruce ACT, 2617, Australia. Deborah.davis@canberra.edu.au.

Abstract:
Background: Combined hormonal contraceptives (CHCs) place women at increased risk of venous thromboembolic events (VTEs) and arterial thrombotic events (ATEs), including acute myocardial infarction and ischemic stroke. There is concern that three recent CHC preparations [drospirenone-containing pills (DRSPs), the norelgestromin-containing transdermal patch (NGMN) and the etonogestrel vaginal ring (ETON)] may place women at even higher risk of thrombosis than other older low-dose CHCs with a known safety profile.

Study design: All VTEs and all hospitalized ATEs were identified in women, ages 10-55 years, from two integrated health care programs and two state Medicaid programs during the time period covering their new use of DRSP, NGMN, ETON or one of four low-dose estrogen comparator CHCs. The relative risk of thrombotic and thromboembolic outcomes associated with the newer CHCs in relation to the comparators was assessed with Cox proportional hazards regression models adjusting for age, site and year of entry into the study.

Results: The hazards ratio for DRSP in relation to low-dose estrogen comparators among new users was 1.77 (95% confidence interval 1.33-2.35) for VTE and 2.01 (1.06-3.81) for ATE. The increased risk of DRSP was limited to the 10-34-year age group for VTE and the 35-55-year group for ATE. Use of the NGMN patch and ETON vaginal ring was not associated with increased risk of either thromboembolic or thrombotic outcomes.

Conclusions: In new users, DRSP was associated with higher risk of thrombotic events (VTE and ATE) relative to low-dose estrogen comparator CHCs, while the use of the NGMN patch and ETON vaginal ring was not.


Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated  with bone mineral density in premenopausal women

Daniel L Koller, Hou-Feng Zheng, David Karasik, Laura Yerges-Armstrong, Ching-Ti Liu, Fiona McGuigan, John P Kemp, Sylvie Giroux, Dongbing Lai, Howard J Edenberg, Munro Peacock, Stefan A Czerwinski, Audrey C Choh, George McMahon, Beate St Pourcain, Nicholas J Timpson, Debbie A Lawlor, David M Evans, Bradford Towne, John Blangero, Melanie A Carless, Candace Kammerer, David Goltzman, Christopher S Kovacs, Jerilynn C Prior, Tim D Spector, Francois Rousseau, Jon H Tobias, Kristina Akesson, Michael J Econs, Braxton D Mitchell, J Brent Richards, Douglas P Kiel, Tatiana Foroud

Abstract: Previous genome-wide association studies (GWAS) have identified common variants in genes associated with variation in bone mineral density (BMD), although most have been carried out in combined samples of older women and men. Meta-analyses of these results have identified numerous single-nucleotide polymorphisms (SNPs) of modest effect at genome-wide significance levels in genes involved in both bone formation and resorption, as well as other pathways. We performed a meta-analysis restricted to premenopausal white women from four cohorts (n = 4061 women, aged 20 to 45 years) to identify genes influencing peak bone mass at the lumbar spine and femoral neck. After imputation, ageand weight-adjusted bone-mineral density (BMD) values were tested for association with each SNP. Association of an SNP in the WNT16 gene (rs3801387; p = 1.7 × 10(-9) ) and multiple SNPs in the ESR1/C6orf97 region (rs4870044; p = 1.3 × 10(-8) ) achieved genome-wide significance levels for lumbar spine BMD. These SNPs, along with others demonstrating suggestive evidence of association, were then tested for association in seven replication cohorts that included premenopausal women of European, Hispanic-American, and African-American descent (combined n = 5597 for femoral neck; n = 4744 for lumbar spine). When the data from the discovery and replication cohorts were analyzed jointly, the evidence was more significant (WNT16 joint p = 1.3 × 10(-11) ; ESR1/C6orf97 joint p = 1.4 × 10(-10) ). Multiple independent association signals were observed with spine BMD at the ESR1 region after conditioning on the primary signal. Analyses of femoral neck BMD also supported association with SNPs in WNT16 and ESR1/C6orf97 (p < 1 × 10(-5) ). Our results confirm that several of the genes contributing to BMD variation across a broad age range in both sexes have effects of similar magnitude on BMD of the spine in premenopausal women. These data support the hypothesis that variants in these genes of known skeletal function also affect BMD during the premenopausal period.

Journal of Bone and Mineral Research : the Official Journal of the American  Society for Bone and Mineral Research


Marital fertility and income: moderating effects of the Church of Jesus Christ of Latter-day Saints religion in Utah

Abstract: Utah has the highest total fertility of any state in the United States and also the highest proportion of population affiliated with the Church of Jesus Christ of Latter-day Saints (the LDS or Mormon Church). Data were used from the 1996 Utah Health Status Survey to investigate how annual household income, education and affiliation with the LDS Church affect fertility (children ever born) for married women in Utah. Younger age and higher education were negatively correlated with fertility in the sample as a whole and among non-LDS respondents. Income was negatively associated with fertility among non-LDS respondents. However, income was positively correlated with fertility among LDS respondents. This association persisted when instrumental variables were used to address the potential simultaneous equations bias arising from the potential endogeneity of income and fertility. The LDS religion's pronatalist stance probably encourages childbearing among those with higher income.


Oral contraceptive use and risk of breast cancer: a meta-analysis of prospective  cohort studies

Abstract:
BACKGROUND AND Objectives: It has been suggested that taking oral contraceptives (OCs) may increase breast cancer incidence. However, data in this regard are inconsistent. We performed this meta-analysis to estimate the association between OC use and breast cancer risk.

Methods: Prospective cohort studies on OC use and breast cancer risk were identified by searching databases from the period 1960 to 2012. Results from individual studies were synthetically combined using STATA 11 software.

Results: A total of 13 prospective cohort studies were included in our meta-analysis, involving 11,722 cases and 859,894 participants. The combined relative risk (RR) of breast cancer for evercompared with never-OC users was 1.08 (95% confidence interval [CI]: 0.99-1.17). Dose-response analysis based on five eligible studies showed that every ten-years' increment of OC use was associated with a significant 14% (95% CI: 1.05-1.23) rise in breast cancer risk. Little evidence of publication bias was found.

Conclusions: This meta-analysis provides evidence of a non-significant increase in breast cancer risk associated with ever OC use, but the risk for long-term OC users is significantly greater. However, the latter finding is based on only a limited number of studies.

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


[The prognosis for children born after assisted reproduction]

Abstract: Children who are born after assisted reproduction (ART) have a slightly increased risk of being born preterm, of having low birthweight and a higher perinatal mortality than spontaneously conceived children. The higher rate of multiple births among women having had ART can to some extent explain this. However, adverse outcomes persist even in ART singletons. The characteristics of the infertile parents have negative effects on the outcome, but also the hormone stimulation and the in vitro techniques are thought to play a role. A milder hormone stimulation and elective single embryo transfer, which reduces the number of multiples after ART, have improved the overall health of children born as a result of ART.


Walnuts improve semen quality in men consuming a Western-style diet: randomized control dietary intervention trial

Abstract: We tested the hypothesis that 75 g of whole-shelled walnuts/day added to the Western-style diet of healthy young men would beneficially affect semen quality. A randomized, parallel two-group dietary intervention trial with single-blind masking of outcome assessors was conducted with 117 healthy men, age 21-35 yr old, who routinely consumed a Western-style diet. The primary outcome was improvement in conventional semen parameters and sperm aneuploidy from baseline to 12 wk. Secondary endpoints included blood serum and sperm fatty acid (FA) profiles, sex hormones, and serum folate. The group consuming walnuts (n = 59) experienced improvement in sperm vitality, motility, and morphology, but no change was seen in the group continuing their usual diet but avoiding tree nuts (n = 58). Comparing differences between the groups from baseline, significance was found for vitality (P = 0.003), motility (P = 0.009), and morphology (normal forms; P = 0.04). Serum FA profiles improved in the walnut group with increases in omega-6 (P = 0.0004) and omega-3 (P = 0.0007) but not in the control group. The plant source of omega-3, alpha-linolenic acid (ALA) increased (P = 0.0001). Sperm aneuploidy was inversely correlated with sperm ALA, particularly sex chromosome nullisomy (Spearman correlation, -0.41, P = 0.002). Findings demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology.


Dietary patterns and semen quality in young men

Audrey J Gaskins

Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia. Electronic address: Audrey.jane.gaskins@emory.edu.

Abstract:
STUDY QUESTION: Are different dietary patterns associated with semen parameters in young men?

STUDY ANSWER: The consumption of a Prudent dietary pattern was significantly associated with higher progressive sperm motility and unrelated to sperm concentration and morphology. The consumption of a Western dietary pattern was unrelated to conventional semen quality parameters.

WHAT IS KNOWN ALREADY: Over the past decades there has been evidence of a concomitant decline in sperm and diet quality. Yet whether diet composition influences semen quality remains largely unexplored.

STUDY DESIGN, SIZE, DURATION: The Rochester Young Men's Study (n= 188) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester.

PARTICIPANTS, SETTING, METHODS: Men aged 18-22 years were included in this analysis. Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns and conventional semen quality parameters (sperm concentration, progressive motility and morphology) adjusting for abstinence time, multivitamin use, race, smoking status, BMI, recruitment period, moderate-to-intense exercise and total calorie intake.

RESULTS: Two dietary patterns were identified by factor analysis. The 'Western' pattern was characterized by high intake of red and processed meat, refined grains, pizza, snacks, high-energy drinks and sweets. The 'Prudent' pattern was characterized by high intake of fish, chicken, fruit, vegetables, legumes and whole grains. The Prudent pattern was positively associated with percent progressively motile sperm in multivariate models (P-trend = 0.04). Men in the highest quartile of the Prudent diet had 11.3% (95% CI 1.3, 21.3) higher % progressively motile sperm compared with men in the lowest quartile. The Prudent pattern was unrelated to sperm concentration and morphology. The Western pattern was not associated with any semen parameter.

LIMITATIONS: This was a cross-sectional and observational study, which limited our ability to determine causality of diet on semen quality parameters.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the suggestion that a diet rich in fruits, vegetables, chicken, fish and whole grains may be an inexpensive and safe way to improve at least one measure of semen quality.

STUDY FUNDING/COMPETING INTERESTS: The authors are supported by NIH grant T32DK007703-16 and P30DK46200 and European Union DEER Grant 212844. The authors have no competing interests to declare.


The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

Lynne Robinson

Birmingham Women’s and Children’s NHS Foundation Trust

Ioannis Gallos

Nottingham University Hospitals NHS Trust

Abstract:
STUDY QUESTION: Is there an association between high levels of sperm DNA damage and miscarriage?

SUMMARY ANSWER: Miscarriage rates are positively correlated with sperm DNA damage levels.

WHAT IS KNOWN ALREADY: Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.

STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.

MAIN RESULTS AND THE ROLE OF CHANCE: We identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P < 0.00001).

LIMITATIONS, REASONS FOR CAUTION: There is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.

WIDER IMPLICATIONS OF THE FINDINGS: The use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.

STUDY FUNDING/COMPETING INTEREST(S): None.


Fertility awareness-based methods of family planning: A review of effectiveness for avoiding pregnancy using SORT

Abstract: Each year, over three-fourths of the women of reproductive age in the United States seek family planning services from primary care clinicians. Women and their doctors should be informed of all effective family planning options and their respective effects on a woman's reproductive health. Family physicians are well-trained to support the behavior choices necessary for the successful adoption of any reversible family planning method. However, many are unfamiliar with fertility awareness-based methods (FABM) of family planning or have misconceptions about their effectiveness, complexity, or suitability for their patients. FABM teach women to observe the physical signs and symptoms that follow hormonal fluctuations throughout the menstrual cycle to identify a couple's fertile window, which can be used to avoid or achieve pregnancy. One in 5 women in the United States expressed interest in using FABM when informed about such options. When correctly used to avoid pregnancy, modern FABM have unintended pregnancy rates<5 (per 100 women years). Studies of modern FABM show that their typical unintended pregnancy rates are comparable to those of commonly used contraceptives. This article presents a review of the FABM literature to (1) familiarize the reader with the physiological basis and features of modern FABM, (2) present and utilize a framework to evaluate clinical evidence using the Strength of Recommendation Taxonomy (SORT), which supports the effectiveness of modern FABM for avoiding pregnancy, and (3) serve as a resource for health care professionals offering FABM options to their patients.


Effects of paternal obesity on in vitro fertilization (IVF) pregnancy and live birth rates


Vitamin D in the aetiology and management of polycystic ovary syndrome

Abstract: Vitamin D deficiency is common in women with polycystic ovary syndrome (PCOS), with the 67-85% of women with PCOS having serum concentrations of 25-hydroxy vitamin D (25OHD) <20 ng/ml. Vitamin D deficiency may exacerbate symptoms of PCOS, with observational studies showing lower 25OHD levels were associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity and elevated cardiovascular disease risk factors. There is some, but limited, evidence for beneficial effects of vitamin D supplementation on menstrual dysfunction and insulin resistance in women with PCOS. Vitamin D deficiency may play a role in exacerbating PCOS, and there may be a place for vitamin D supplementation in the management of this syndrome, but current evidence is limited and additional randomized controlled trials are required to confirm the potential benefits of vitamin D supplementation in this population.


Luteal phase deficiency in normal cycling women

Sunni L Mumford

Eunice Kennedy Shriver National Institute of Child Health and Human Development


Assisted reproductive techniques and NaProTechnology

Abstract: Infertility is a significant and constantly increasing individual and social problem. It is estimated that at present it affects approx. 15 to 20 percent of couples. Inability to conceive a child elicits a range of unfavourable implications in the scope of emotional experiences, in the partner’s relationship and in a broader social perspective. Making a decision on undergoing diagnostics and infertility treatment is a difficult and often postponed moment for many couples. This is an expression of the escape model of dealing with a situation that threatens with a fall of self-esteem. However, if a couple reacts in a task-oriented way and participates in the diagnostic and therapeutic procedure, new doubts appear connected with the medical, psychological, social and ethical sphere. Infertility treatment sometimes prompts fear connected with the stripping of intimacy, loss of control over one’s body, possible complications and unsuccessful therapy. This article is an analysis of the medical and the other aspects of struggling with infertility with reference to two extremely different methods of solving this problem: NaProTechnology as a process of assisting natural procreation and assisted reproductive techniques with a special consideration of in vitro fertilization.


Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in  reproductive-aged women

Committee on Practice Bulletins—Gynecology

Abstract: Obstetrics & Gynecology: July 2012 - Volume 120 - Issue 1 - p 197-206 doi: 10.1097/AOG.0b013e318262e320


Inflammation, leukocytes and menstruation

Abstract: Menstruation has many of the features of an inflammatory process. The complexity and sequence of inflammatory-type events leading to the final tissue breakdown and bleeding are slowly being unravelled. Progesterone has anti-inflammatory properties, and its rapidly declining levels (along with those of estrogen) in the late secretory phase of each non-conception cycle, initiates a sequence of interdependent events of an inflammatory nature involving local inter-cellular interactions within the endometrium. Intracellular responses to loss of progesterone (in decidualized stromal, vascular and epithelial cells) lead to decreased prostaglandin metabolism and loss of protection from reactive oxygen species (ROS). Increased ROS results in release of NFκB from suppression with activation of target gene transcription and increased synthesis of pro-inflammatory prostaglandins, cytokines, chemokines and matrix metalloproteinases (MMP). The resultant leukocyte recruitment, with changing phenotypes and activation, provide further degradative enzymes and MMP activators, which together with a hypoxic environment induced by prostaglandin actions, lead to the tissue breakdown and bleeding characteristic of menstruation. In parallel, at sites where shedding is complete, microenvironmentally-induced changes in phenotypes of neutrophils and macrophages from proto anti-inflammatory, in addition to induction of growth factors, contribute to the very rapid re-epithelialization and restoration of tissue integrity.

Reviews in Endocrine & Metabolic Disorders


Progesterone for hot flush and night sweat treatment--effectiveness for severe  vasomotor symptoms and lack of withdrawal rebound

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christine L Hitchcock

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

Abstract: A controlled trial recently showed that oral micronized progesterone (Progesterone, 300 mg at h.s. daily) was effective for vasomotor symptoms (VMS) in 133 healthy early postmenopausal women. Here, we present subgroup data in women with severe VMS (50 VMS of moderate-severe intensity/wk) and also 1-mo withdrawal study outcomes. Women with severe VMS (n = 46) resembled the full cohort but experienced 10 VMS/d of 3 of 4 intensity. On therapy, the progesterone VMS number (#) decreased significantly more than placebo # to 5.5/day (d) versus 8/d (ANCOVA -2.0 95% CI: -3.5 to -0.4). Just after trial mid-point, a withdrawal substudy (D/C) was added--56 women were invited and 34 (61%) took part (progesterone 17; placebo 17). Those in the D/C cohort resembled the whole cohort. On stopping, VMS gradually increased--at D/C week 4, on progesterone, VMS daily # reached 78% and significantly less than baseline (-3.0 to -0.8) but placebo VMS # did not differ from run-in. In summary, progesterone is effective for severe VMS and does not cause a rebound increase in VMS when stopped. That progesterone may be used alone for severe VMS and unlike estrogen does not appear to cause a withdrawal rebound increases VMS treatment options.

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


Does hyperandrogenism have an effect on hearing loss in patients with polycystic ovary syndrome?

Abstract:
OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by chronic anovulation and hyperandrogenism. Hormonal changes can affect hearing loss and inner ear functions. We evaluated hearing loss with audiometric tests in young patients with PCOS.

METHODS: Twenty-six women having PCOS and 25 normal individuals were enrolled in the study. Age ranges for PCOS and control groups were 20-35 years. Hormonal and biochemical values including LH, LH/FSH, E2, testosterone, fasting glucose and fasting insulin were calculated. Each subject was tested with low- (250-2000Hz) and high-frequency audiometry (4000-8000Hz). For each set of tests, mean values of air conduction at each frequency were measured for the PCOS and control groups and compared.

RESULTS: No difference was observed in speech frequencies on audiologic tests between the groups, however high-frequency hearing loss were significantly higher (p<0.05) in PCOS patients than in control women. Also, hearing thresholds were normal range in all of frequencies in PCOS and control subjects. PCOS patients showed high levels of LH, LH/FSH, testosterone and fasting insulin.

CONCLUSION: Our findings suggest that patients diagnosed with PCOS should be advised audiologic evaluation especially in the high frequency.


Effect of long-term combined oral contraceptive pill use on endometrial thickness

Navid Esfandiari

Toronto Centre for Advanced Reproductive Technology, Toronto, Ontario, Canada. ; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Toron...

Abstract:
OBJECTIVE: To estimate whether there is any association of long-term use of combined oral contraceptive pills (OCP) with adverse endometrial growth.

METHODS: We reviewed the charts of 137 patients with history of OCP use undergoing endometrial preparation with estrogen for frozen embryo transfer. Endometrial thickness was measured by transvaginal ultrasonography on day 10 after menses and patients were divided into two groups (less than 7 mm and 7 mm or more).

RESULTS: Thirty patients had endometrial thickness less than 7 mm and 107 had thickness of 7 mm or more. Mean years of combined OCP use in each group were 9.8±4.54 and 5.8±4.52, respectively (P<.001). With 10 years of combined OCP use as the threshold, the difference between the two groups (63.35% users in less than 7 mm group compared with 28.04% in the 7 mm or more thickness group) was highly significant (P<.001 by Fisher exact test), with an odds ratio of 4.43 (95% confidence interval 1.89-10.41). Past use of 5 years of OCPs was also associated with a significant (P=.002) difference in endometrial thickness. The mean endometrial thicknesses on cycle day 10 in patients using combined OCP for less than 10 years and 10 years or more were 9.54±1.88 mm and 8.48±2.33 mm, respectively, with P=.007. The mean endometrial thickness was 9.72±1.69 mm in less than 5 years and 8.81±2.23 mm in 5 or more years of use, respectively (P=.008). Cycle cancellation rates in the less than 7 mm group and 7 mm or greater endometrial thickness group were 23% and 4%, respectively (P=.002), but there was no difference in the clinical pregnancy rates between the two groups (13% compared with 27%, respectively; P=.15).

CONCLUSION: Long-term combined OCP use (5 years or more) can potentially affect optimal endometrial growth, leading to a higher cancellation rate and longer stimulation in frozen embryo transfer cycles. These findings suggest a previously unidentified adverse effect of long-term combined OCP use in women who are anticipating future fertility.

LEVEL OF EVIDENCE: II.


Evaluation and treatment of recurrent pregnancy loss: a committee opinion

Practice Committee of the American Society for Reproductive Medicine

American Society for Reproductive Medicine, Birmingham, Alabama, USA.

Abstract: The majority of miscarriages are sporadic and most result from genetic causes that are greatly influenced by maternal age. Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies, and up to 50% of cases of RPL will not have a clearly defined etiology.


Hot flushes and night sweats differ in associations with cardiovascular markers  in healthy early postmenopausal women

Abstract:
Objective: The aim of this study was to evaluate the associations between vasomotor symptoms ([VMS] hot flushes or flashes and night sweats) and markers of cardiovascular risk.

Methods: Healthy postmenopausal women in a randomized controlled trial of progesterone for VMS recorded VMS frequency in the Daily Menopause Diary for 28 days at baseline. Accepted risks for cardiovascular disease were measured: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), blood pressure (BP), endothelial function by venous occlusion plethysmography, fasting lipids, glucose, high-sensitivity C-reactive protein, albumin, and D-dimer. Relationships between risk variables and VMS frequency (24 h, day and night) were assessed by univariate and multivariate robust regressions with adjustment for age and WHtR.

Results: Data were available for 145 healthy, nonsmoking women without heart disease, hypertension, or diabetes who were 1 to 11 years past their final menstruation and were aged 43 to 65 years, with a mean (SD) BMI of 25.0 (2.9) kg/m and WC of 79.1 (7.1) cm. Anthropometric variables (BMI, WC, and WHtR) were significantly negatively associated with total (24-h day) VMS frequency and with day VMS but not with night VMS frequency. Systolic BP decreased with greater 24-hour VMS frequency, and both systolic and diastolic BPs were inversely related to day but not night VMS frequency. Albumin was positively associated with night VMS frequency but not with day or 24-hour VMS frequency. Other variables showed little association with VMS frequency.

Conclusions: Hot flushes, but not night sweats, were associated with lower cardiovascular risk factors in these healthy postmenopausal women. Future research should differentiate night sweats from hot flushes.


The relationship between proton pump inhibitor use and longitudinal change in  bone mineral density: a population-based study [corrected] from the Canadian  Multicentre Osteoporosis Study (CaMos)

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Abstract:
Objectives: Proton pump inhibitor (PPI) use has been identified as a risk factor for hip and vertebral fractures. Evidence supporting a relationship between PPI use and osteoporosis remains scant. Demonstrating that PPIs are associated with accelerated bone mineral density (BMD) loss would provide supportive evidence for a mechanism through which PPIs could increase fracture risk.

Methods: We used the Canadian Multicentre Osteoporosis Study data set, which enrolled a population-based sample of Canadians who underwent BMD testing of the femoral neck, total hip, and lumbar spine (L1-L4) at baseline, and then again at 5 and 10 years. Participants also reported drug use and exposure to risk factors for osteoporosis and fracture. Multivariate linear regression was used to determine the independent association of PPI exposure and baseline BMD, and on change in BMD at 5 and 10 years.

Results: In all, 8,340 subjects were included in the baseline analysis, with 4,512 (55%) undergoing year 10 BMD testing. After adjusting for potential confounders, PPI use was associated with significantly lower baseline BMD at the femoral neck and total hip. PPI use was not associated with a significant acceleration in covariate-adjusted BMD loss at any measurement site after 5 and 10 years of follow-up.

Conclusions: PPI users had lower BMD at baseline than PPI non-users, but PPI use over 10 years did not appear to be associated with accelerated BMD loss. The reasons for discordant findings between PPI use at baseline and during follow-up require further study.

The American Journal of Gastroenterology


Interrater and intrarater reliability in the diagnosis and staging of endometriosis

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

J K Dorais

Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah, USA.

Abstract:
Objective: To estimate the interrater and intrarater reliability of endometriosis diagnosis and severity of disease among gynecologic surgeons viewing operative digital images.

Methods: The study population comprised a random sample (n=148 [36%]) of women who participated in the Endometriosis: Natural History, Diagnosis and Outcomes study. Four academic expert and four local, specialized expert surgeons reviewed the images, diagnosed the presence or absence of endometriosis for each woman, and rated severity using the revised American Society for Reproductive Medicine (ASRM) criteria. Interrater-level and intrarater-level agreement were calculated for both endometriosis diagnosis and staging.

Results: The interrater reliability for endometriosis diagnosis among the eight surgeons was substantial: Fleiss κ=0.69 (95% confidence interval [CI] 0.64-0.74). Surgeons agreed on revised ASRM endometriosis staging criteria after experienced assessment in a majority of cases (mean 61%, range 52-75%) with moderate interrater reliability: Fleiss κ=0.44 (95% CI 0.41-0.47). The intrarater reliability for experienced assessment compared with computer-assisted revised ASRM staging was almost perfect (mean weighted κ=0.95, range 0.89-0.99).

Conclusion: Substantial reliability was found for revised ASRM endometriosis diagnosis, whereas moderate reliability was observed for staging. Almost perfect reliability was observed for surgeons' rating of disease severity compared with computerized-assisted, checklist-based staging. Findings suggest that reliability in endometriosis diagnosis is not greatly altered by location or composition of surgeons, supporting the conduct of multisite studies or compilation of endometriosis data across clinical centers. Although surgeons appear to be skilled at assessing endometriosis stage intuitively, how staging of disease burden correlates with clinical outcomes remains to be developed.


What every gynecologist should know about male infertility: an update

Sandro C Esteves

Universidade Estadual de Campinas (UNICAMP)

Abstract:
PURPOSE: Our article reviews the evolving concepts in the field of male infertility for gynecologists and other health professionals involved in the care of men and women experiencing difficulty in having a child. The increased knowledge will help in the better management and treatment of infertile couples.

METHODS: Review of literature through Pubmed, Science Direct, Online Library.

RESULTS: Gynecologists are often the first healthcare providers to assess an infertile couple. Because half of all infertility problems stem from male factors, it is crucial for the gynecologist to remain updated on the main conditions that cause male infertility as well as current diagnostic tools and treatment options, including conventional strategies and assisted reproductive techniques.

CONCLUSIONS: Extraordinary advances have been achieved in the field of male infertility over the past several years and many old concepts are now challenged. Therefore, it is imperative that male infertility physicians should update the gynecologists about the recent advances in the work-up of infertile men in terms of diagnosis and management. Such convention will help improve the standards of care for the infertile couple and enhance the cooperation between male and female reproductive endocrinologists.


The female athlete triad

The female athlete triad

Abstract:
CONTEXT: The female athlete triad (the triad) is an interrelationship of menstrual dysfunction, low energy availability (with or without an eating disorder), and decreased bone mineral density; it is relatively common among young women participating in sports. Diagnosis and treatment of this potentially serious condition is complicated and often requires an interdisciplinary team.

EVIDENCE ACQUISITION: Articles from 1981 to present found on PubMed were selected for review of major components of the female athlete triad as well as strategies for diagnosis and treatment of the conditions.

RESULTS: The main goal in treatment of young female athletes with the triad is a natural return of menses as well as enhancement of bone mineral density. While no specific drug intervention has been shown to consistently improve bone mineral density in this patient population, maximizing energy availability and optimizing vitamin D and calcium intake are recommended.

CONCLUSIONS: Treatment requires a multidisciplinary approach involving health care professionals as well as coaches and family members. Prevention of this condition is important to minimize complications of the female athlete triad.


Natural procreative technology for infertility and recurrent miscarriage: outcomes in a Canadian family practice

Thomas W Hilgers

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

Abstract:
OBJECTIVE: To study the outcomes of women with infertility or miscarriage treated with natural procreative technology (NaProTechnology or NPT), a systematic medical approach to promoting conception in vivo; and to compare the outcomes with those previously published from a general practice in Ireland.

DESIGN: Retrospective cohort study.

SETTING: An urban Canadian primary care practice in which the physician had a part-time practice in NPT.

PARTICIPANTS: Couples with infertility or recurrent miscarriage who received treatment in the practice between August 2000 and July 2006.

INTERVENTION: All couples were taught to identify the fertile time of their menstrual cycles using the Creighton Model FertilityCare System (CrMS) and completed a standard NPT evaluation. Many also received additional medical treatment to enhance conception in vivo.

MAIN OUTCOME MEASURES: Live birth was the primary outcome; secondary outcomes included conceptions, multiple births, low birth weight, and prematurity.

RESULTS: A total of 108 couples received NPT and were included in the analysis, of which 19 (18%) reported having 2 or more previously unexplained miscarriages. The average female age was 35.4 years. Couples had been attempting to conceive for a mean of 3.2 years. Twentytwo participants (20%) had previously given birth; 24 (22%) had previous intrauterine insemination; and 9 (8%) had previous assisted reproductive technology. The cumulative adjusted proportion of first live births for those completing up to 24 months of NPT treatment was 66 per 100 couples, and the crude proportion was 38%. The cumulative adjusted proportion of first conceptions was 73 per 100 couples, and the crude proportion was 47%. Of the 51 couples who conceived, 12 couples (24%) conceived with CrMS instruction alone, 35 (69%) conceived with CrMS and NPT medical treatment, and 4 (8%) conceived after additional surgical treatment. All births were singleton births; 54% were born at 37 weeks' gestation or later; and 78% had birth weights of 2500 g or greater.

CONCLUSION: Natural procreative technology in a family physician's office was effective in treating infertility and miscarriage with outcomes that were comparable to those in an NPT general practice in Ireland. Larger multicentre prospective studies to compare NPT directly to other forms of infertility treatment are warranted.

Canadian Family Physician Medecin De Famille Canadien


Cumulative birth rates with linked assisted reproductive technology cycles

Abstract:
BACKGROUND: Live-birth rates after treatment with assisted reproductive technology have traditionally been reported on a per-cycle basis. For women receiving continued treatment, cumulative success rates are a more important measure.

METHODS: We linked data from cycles of assisted reproductive technology in the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for the period from 2004 through 2009 to individual women in order to estimate cumulative live-birth rates. Conservative estimates assumed that women who did not return for treatment would not have a live birth; optimal estimates assumed that these women would have live-birth rates similar to those for women continuing treatment.

RESULTS: The data were from 246,740 women, with 471,208 cycles and 140,859 live births. Live-birth rates declined with increasing maternal age and increasing cycle number with autologous, but not donor, oocytes. By the third cycle, the conservative and optimal estimates of live-birth rates with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3). At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used.

CONCLUSIONS: Our results indicate that live-birth rates approaching natural fecundity can be achieved by means of assisted reproductive technology when there are favorable patient and embryo characteristics. Live-birth rates among older women are lower than those among younger women when autologous oocytes are used but are similar to the rates among young women when donor oocytes are used. (Funded by the National Institutes of Health and the Society for Assisted Reproductive Technology.).


Low-level laser in the treatment of patients with hypothyroidism induced by  chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial

Danilo B. Höfling

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Abstract: Chronic autoimmune thyroiditis (CAT) is the most common cause of acquired hypothyroidism, which requires lifelong levothyroxine replacement therapy. Currently, no effective therapy is available for CAT. Thus, the objective of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in patients with CAT-induced hypothyroidism by testing thyroid function, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and ultrasonographic echogenicity. A randomized, placebo-controlled trial with a 9-month follow-up was conducted from 2006 to 2009. Forty-three patients with a history of levothyroxine therapy for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (830 nm, output power of 50 mW, and fluence of 707 J/cm(2); L group, n=23) or 10 sessions of a placebo treatment (P group, n=20). The levothyroxine was suspended 30 days after the LLLT or placebo procedures. Thyroid function was estimated by the levothyroxine dose required to achieve normal concentrations of T3, T4, free-T4 (fT4), and thyrotropin after 9 months of postlevothyroxine withdrawal. Autoimmunity was assessed by measuring the TPOAb and TgAb levels. A quantitative computerized echogenicity analysis was performed preand 30 days postintervention. The results showed a significant difference in the mean levothyroxine dose required to treat the hypothyroidism between the L group (38.59 ± 20.22 μg/day) and the P group (106.88 ± 22.90 μg/day, P<0.001). Lower TPOAb (P=0.043) and greater echogenicity (P<0.001) were also noted in the L group. No TgAb difference was observed. These findings suggest that LLLT was effective at improving thyroid function, promoting reduced TPOAb-mediated autoimmunity and increasing thyroid echogenicity in patients with CAT hypothyroidism.


Thrombotic stroke and myocardial infarction with hormonal contraception

Abstract:
Background: Although several studies have assessed the risk of venous thromboembolism with newer hormonal contraception, few have examined thrombotic stroke and myocardial infarction, and results have been conflicting.

Methods: In this 15-year Danish historical cohort study, we followed nonpregnant women, 15 to 49 years old, with no history of cardiovascular disease or cancer. Data on use of hormonal contraception, clinical end points, and potential confounders were obtained from four national registries.

Results: A total of 1,626,158 women contributed 14,251,063 person-years of observation, during which 3311 thrombotic strokes (21.4 per 100,000 person-years) and 1725 myocardial infarctions (10.1 per 100,000 person-years) occurred. As compared with nonuse, current use of oral contraceptives that included ethinyl estradiol at a dose of 30 to 40 μg was associated with the following relative risks (and 95% confidence intervals) for thrombotic stroke and myocardial infarction, according to progestin type: norethindrone, 2.2 (1.5 to 3.2) and 2.3 (1.3 to 3.9); levonorgestrel, 1.7 (1.4 to 2.0) and 2.0 (1.6 to 2.5); norgestimate, 1.5 (1.2 to 1.9) and 1.3 (0.9 to 1.9); desogestrel, 2.2 (1.8 to 2.7) and 2.1 (1.5 to 2.8); gestodene, 1.8 (1.6 to 2.0) and 1.9 (1.6 to 2.3); and drospirenone, 1.6 (1.2 to 2.2) and 1.7 (1.0 to 2.6), respectively. With ethinyl estradiol at a dose of 20 μg, the corresponding relative risks according to progestin type were as follows: desogestrel, 1.5 (1.3 to 1.9) and 1.6 (1.1 to 2.1); gestodene, 1.7 (1.4 to 2.1) and 1.2 (0.8 to 1.9); and drospirenone, 0.9 (0.2 to 3.5) and 0.0. For transdermal patches, the corresponding relative risks were 3.2 (0.8 to 12.6) and 0.0, and for a vaginal ring, 2.5 (1.4 to 4.4) and 2.1 (0.7 to 6.5).

Conclusions: Although the absolute risks of thrombotic stroke and myocardial infarction associated with the use of hormonal contraception were low, the risk was increased by a factor of 0.9 to 1.7 with oral contraceptives that included ethinyl estradiol at a dose of 20 μg and by a factor of 1.3 to 2.3 with those that included ethinyl estradiol at a dose of 30 to 40 μg, with relatively small differences in risk according to progestin type. (Funded by the Danish Heart Association.).


Reassured or fobbed off? Perspectives on infertility consultations in primary  care: a qualitative study

Abstract:
Background: Infertility affects 9% of couples in the UK. Most couples who visit their GP because they are worried about their fertility will ultimately conceive, but a few will not. Treatment usually happens in secondary care, but GPs can have an invaluable role in starting investigations, referring, and giving support throughout treatment and beyond.

Aim: To inform clinical practice by exploring primary care experiences of infertility treatment among females and males, and discussing findings with a reference group of GPs to explore practice experience. DESIGN AND Setting: A qualitative patient interview and GP focus group study. Interviews were conducted in patients homes in England and Scotland; the focus group was held at a national conference. METHOD: An in-depth interview study was conducted with 27 females and 11 males. A maximum variation sample was sought and interviews were transcribed for thematic analysis. Results were discussed with a focus group of GPs to elicit their views.

Results: Feeling that they were being taken seriously was very important to patients. Some felt that their concerns were not taken seriously, or that their GP did not appear to be well informed about infertility. The focus group of GPs highlighted the role of protocols in their management of patients who are infertile, as well as the difficulty GPs faced in communicating both reassurance and engagement.

Conclusion: Simple things that GPs say and do, such as describing the 'action plan' at the first consultation, could make a real difference to demonstrating that they are taking the fertility problem seriously.

The British Journal of General Practice : the Journal of the Royal College of  General Practitioners


Characterization of DNA methylation errors in patients with imprinting disorders conceived by assisted reproduction technologies

Abstract:
Background: There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The identification of epigenetic changes at imprinted loci in ART infants has led to the suggestion that the techniques themselves may predispose embryos to acquire imprinting errors and diseases. However, it is still unknown at what point(s) these imprinting errors arise, or the risk factors.

Methods: In 2009 we conducted a Japanese nationwide epidemiological study of four well-known imprinting diseases to determine any association with ART. Using bisulfite sequencing, we examine the DNA methylation status of 22 gametic differentially methylated regions (gDMRs) located within the known imprinted loci in patients with Beckwith-Wiedemann syndrome (BWS, n=1) and also Silver-Russell syndrome (SRS, n= 5) born after ART, and compared these with patients conceived naturally.

Results: We found a 10-fold increased frequency of BWS and SRS associated with ART. The majority of ART cases showed aberrant DNA methylation patterns at multiple imprinted loci both maternal and paternal gDMRs (5/6), with both hyper- and hypomethylation events (5/6) and also mosaic methylation errors (5/6). Although our study may have been limited by a small sample number, the fact that many of the changes were mosaic suggested that they occurred after fertilization. In contrast, few of the patients who were conceived naturally exhibited a similar pattern of mosaic alterations. The differences in methylation patterns between the patients who were conceived naturally or after ART did not manifest due to the differences in the disease phenotypes in these imprinting disorders.

Conclusion: A possible association between ART and BWS/SRS was found, and we observed a more widespread disruption of genomic imprints after ART. The increased frequency of imprinting disorders after ART is perhaps not surprising given the major epigenetic events that take place during early development at a time when the epigenome is most vulnerable.


Chemotherapy and fertility

Chemotherapy and fertility

Z Blumenfeld

Technion – Israel Institute of Technology

Abstract: The overall increase in cancer prevalence and the significant increase in long-term survival have generated worldwide interest in preserving fertility in young women exposed to gonadotoxic chemo- and radiotherapy. Infertility represents one of the main long-term consequences of combination chemotherapy given for lymphoma, leukaemia and other malignancies in young women. The gonadotoxic effect of various chemotherapeutic agents is diverse, may involve a variety of pathophysiologic mechanisms, and is not unequivocally understood. Proliferating cells, such as in tissues with high turnover (i.e. bone marrow, gastrointestinal tract and growing ovarian follicles) are more vulnerable to the toxic effect of alkylating agents. These agents may also be cytotoxic to cells at rest, as they are not cell-cycle specific. Alkylating agents, the most gonadotoxic chemotherapeutic medications, cause dose-dependent, direct destruction of oocytes and follicular depletion, and may bring about cortical fibrosis and ovarian blood-vessel damage. The reported rate of premature ovarian failure after various diseases and chemotherapeutic protocols differ enormously, and depend mainly on the chemotherapeutic protocol used and age range of the woman. Several options have been proposed for preserving female fertility, despite gonadotoxic chemotherapy: ovarian transposition, cryopreservation of embryos, unfertilised metaphase-II oocytes and ovarian tissue, and administration of gonadotropin-releasing hormone agonistic analogs in an attempt to decrease the gonadotoxic effects of chemotherapy by simulating a prepubertal hormonal milieu. None of these methods is ideal and none guarantees future fertility in all survivors; therefore, a combination of methods is recommended for maximising women's chances of future fertility.

Best practice & research. Clinical obstetrics & gynaecology


The effect of coenzyme Q₁₀ supplementation on partner pregnancy rate in infertile men with idiopathic oligoasthenoteratozoospermia: an open-label prospective study

Abstract:
OBJECTIVE: It has been shown that coenzyme Q(10) (CoQ(10)) supplementation in men with idiopathic oligoasthenoteratozoospermia (OAT) results in improved semen parameters. In present study, we evaluated the effects of coenzyme CoQ(10) supplementation on semen parameters and pregnancy rates in infertile men with idiopathic OAT.

PATIENTS AND METHODS: Two hundred and eighty-seven infertile men with idiopathic OAT were recruited in this study. These patients were treated with CoQ(10) 300 mg orally twice daily for 12 months. Two semen analyses and determination of resting levels of sex hormones were done in all participants. Patients were followed up for another 12 months after CoQ(10) discontinuation.

RESULTS: Mean sperm concentration, sperm progressive motility, and sperm with normal morphology improved significantly after 12-month CoQ(10) therapy by 113.7, 104.8, and 78.9%, respectively (all Ps < 0.05). The overall pregnancy rate was 34.1% within a mean of 8.4 ± 4.7 months.

CONCLUSIONS: CoQ(10) supplementation improves semen quality with beneficial effect on pregnancy rate.


Temporal trends and determinants of longitudinal change in 25-hydroxyvitamin D and parathyroid hormone levels

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Vitamin D is essential for facilitating calcium absorption and preventing increases in parathyroid hormone (PTH), which can augment bone resorption. Our objectives were to examine serum levels of 25-hydroxyvitamin D [25(OH)D] and PTH, and factors related to longitudinal change in a population-based cohort. This is the first longitudinal population-based study looking at PTH and 25(OH)D levels. We analyzed 3896 blood samples from 1896 women and 829 men in the Canadian Multicentre Osteoporosis Study over a 10-year period starting in 1995 to 1997. We fit hierarchical models with all available data and adjusted for season. Over 10 years, vitamin D supplement intake increased by 317 (95% confidence interval [CI] 277 to 359) IU/day in women and by 193 (135 to 252) IU/day in men. Serum 25(OH)D (without adjustment) increased by 9.3 (7.3 to 11.4) nmol/L in women and by 3.5 (0.6 to 6.4) nmol/L in men but increased by 4.7 (2.4 to 7.0) nmol/L in women and by 2.7 (-0.6 to 6.2) nmol/L in men after adjustment for vitamin D supplements. The percentage of participants with 25(OH)D levels <50 nmol/L was 29.7% (26.2 to 33.2) at baseline and 19.8% (18.0 to 21.6) at year 10 follow-up. PTH decreased over 10 years by 7.9 (5.4 to 11.3) pg/mL in women and by 4.6 (0.2 to 9.0) pg/mL in men. Higher 25(OH)D levels were associated with summer, younger age, lower body mass index (BMI), regular physical activity, sun exposure, and higher total calcium intake. Lower PTH levels were associated with younger age and higher 25(OH)D levels in both women and men and with lower BMI and participation in regular physical activity in women only. We have observed concurrent increasing 25(OH)D levels and decreasing PTH levels over 10 years. Secular increases in supplemental vitamin D intake influenced both changes in serum 25(OH)D and PTH levels.


Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence

Abstract:
BACKGROUND: The aim was to evaluate changes of bone mineral density (BMD) and markers of bone turnover in healthy adolescents, and in adolescent users of combined oral contraceptives (COCs) with different ethinylestradiol (EE) contents.

METHODS: In this prospective crossover study, 56 healthy females (15-19.5 years) with desire to use hormonal contraception were randomized to COC with either 30 or 15 μg of EE in crossover design of 9-month intervention each in reverse order. Nonusers of the same age (n=28) served as controls. BMD at lumbar spine (LS), total femur, femoral neck, distal radius, and total body, and serum markers (N-propeptide of type I procollagen, and type I collagen C-telopeptide) were measured at baseline and after 9 and 18 months.

RESULTS: In COC nonusers, BMD significantly increased at LS and radius, while markers decreased. In COC users, BMD did not increase, with the exception of LS BMD in the 30 μg COC group (P<0.05). In the crossover design, a difference between the low- and very low-dose COC users was found in LS BMD changes (P<0.05), where increase in BMD was more impaired in the 15 μg COC users. The skeletal effects of COC remained significant after adjustments for age and smoking status. Markers declined faster in COC users during the first period, while they remained stable or even increased during the second 9 months.

CONCLUSION: Physiological acquisition of LS BMD during adolescent age may be prevented by use of COC, especially those containing very low dose of EE.


Oral contraceptives, reproductive factors and risk of inflammatory bowel disease

Abstract:
Background: Oral contraceptive use has been associated with risk of Crohn's disease (CD) and ulcerative colitis (UC).

Objective: To determine whether this association is confounded or modified by other important lifestyle and reproductive factors.
Design: A prospective cohort study was carried out of 117,375 US women enrolled since 1976 in the Nurses Health Study I (NHS I) and 115,077 women enrolled since 1989 in the Nurses' Health Study II (NHS II) with no prior history of UC or CD. These women had provided information every 2 years, on age at menarche, oral contraceptive use, parity, menopause status and other risk factors. Diagnoses of CD and UC were confirmed by review of medical records. Cox proportional hazards models were used to calculate HRs and 95% CIs.

Results: Among 232,452 women with over 5,030,196 person-years of follow-up, 315 cases of CD and 392 cases of UC were recorded through 2007 in NHS II and 2008 in NHS I. Compared with never users of oral contraceptives, the multivariate-adjusted HRs for CD were 2.82 (95% CI 1.65 to 4.82) among current users and 1.39 (95% CI 1.05 to 1.85) among past users. The association between oral contraceptives and UC differed according to smoking history (pheterogeneity=0.04). Age at menarche, age at first birth and parity were not associated with risk of UC or CD.

Conclusion: In two large prospective cohorts of US women, oral contraceptive use was associated with risk of CD. The association between oral contraceptive use and UC was limited to women with a history of smoking.


Rising incidence of multiple sclerosis in females associated with urbanization

Abstract:
Objective: To design and perform a case-control study of multiple sclerosis (MS) in Crete, an island of 0.6 million people, that has experienced profound socioeconomic changes in recent decades.

Methods: All MS cases occurring on Crete from 1980 to 2008 were ascertained. To search for putative risk factors, a structured questionnaire of 71 variables was employed, with patients with MS (n = 657) being compared to random controls (n = 593) matched for age, gender, and current place of residence.

Results: MS incidence rose markedly on Crete over the past 3 decades. This increase was associated with a major shift in MS distribution among genders (1980: F/M = 0.9; 2008: F/M = 2.1), with females living in towns or having relocated at a young age from the countryside to urban centers being mainly affected. In rural Crete, MS showed lesser increases and gender preference. Of the major changes that accompanied urbanization, smoking among women with MS increased dramatically, while imported pasteurized cow milk virtually replaced fresh goat milk produced locally. Compared to controls, female patients with MS more often used contraceptives and were older at first childbirth. Besides smoking, alcohol drinking and vitamin intake was more common among female patients with MS. Also, the distribution of childhood diseases and chronic medical conditions differed significantly between patients with MS and controls.

Conclusions: MS incidence rose markedly over 3 decades in a genetically stable population in tandem with a transition from rural to urban living, thus possibly implicating environmental factors introduced by urbanization.


Adhesion prevention in endometriosis: a neglected critical challenge

Edgardo Somigliana

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Abstract: Prevention of adhesions, whether de novo or by re-formation, is one of the most important and surprisingly neglected aspect of the treatment of endometriosis. Adhesions may cause infertility, dyspareunia, chronic pelvic pain but also intestinal obstruction and complications at subsequent surgery. They may play a role in the development of some forms of the disease such as ovarian endometriomas and possibly also deep invasive nodules. Three randomized controlled trials have been published documenting some partial success with Interceed, Oxiplex/AP gel or Adept solution in reducing adhesions extent at second look laparoscopy performed a few weeks after initial surgery. However, data on relevant long-term outcomes such as fertility, pelvic pain or disease recurrences or other adhesions-related complications is lacking. Noteworthy, endometriosis is a chronic inflammatory disorder and the insult causing adhesions is expected to persist after surgery. Therefore preventing adhesion formation with exclusively agents at the time of surgery may be insufficient. Future studies should focus on a 2-step strategy that includes measures applied at the time of surgery and subsequent administration of agents able to prevent the development of new adhesions.

Journal of Minimally Invasive Gynecology


Venous thrombosis in users of non-oral hormonal contraception: follow-up study,  Denmark 2001-10

Abstract:
Objective: To assess the risk of venous thrombosis in current users of non-oral hormonal contraception.
Design: Historical national registry based cohort study.
Setting: Four national registries in Denmark.

Participants: All Danish non-pregnant women aged 15-49 (n=1,626,158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010.

Main Outcome Measures: Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis.

Results: Within 9,429,128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10,000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10,000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7).

Conclusion: Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10,000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.


Family Planning, Natural Family Planning, and Abortion Use among U.S. Hispanic Women: Analysis of Data from Cycle 7 of the National Survey of Family Growth

Abstract: Hispanics are the largest minority group in the U.S. and they contribute to over 50 percent of Catholics under the age of 25. The purpose of this study was to determine the patterns of contraceptive use (current and ever), natural family planning (NFP), and abortion among U.S. Hispanic women between the ages of 15 and 44 years and to compare their patterns of use to non-Hispanic women of the same age range. A particular interest was to determine the influence of faith on the choice of family-planning methods among the sexually active U.S. Catholic Hispanic women. Data for this study came from the National Survey of Family Growth 2006-2008, which included 1,613 Hispanic and 5,743 non-Hispanic women between the ages of 15 and 44. Approximately 57 percent of the Hispanic women are Catholic. In general, U.S. Hispanic women had significantly less frequent use of the hormonal pill, male condom, withdrawal, and vasectomy (of male partner) but more frequent use of the IUD and Depo-Provera compared to non-Hispanic women. There was little use of NFP and no difference in the frequency of reported abortion. Catholic Hispanic women had significantly less frequent use of the male condom, the Pill, vasectomy, and abortion and more use of NFP compared to non-Catholic Hispanic women. Although there is some positive influence of faith among the sexually active Hispanic women of reproductive age, overall, the amount of ever use of sterilization (21 percent), condom use (80 percent), Pill use (66 percent), and Depo-Provera (30 percent) is remarkable. The more frequent use of Depo-Provera and the IUD might reflect the economic level of the participants and the use of federally funded family-planning services.


Infertility treatment in a population-based sample: 2004-2005

Abstract: To describe the characteristics of women seeking infertility treatment and the types of fertility treatment sought within a population-based sample. We analyzed data from the cross-sectional Pregnancy Risk Assessment Monitoring System (PRAMS) of women with a live birth using data from seven states. Logistic regression was used to determine factors associated with infertility treatment utilization. Infertility treatment was reported by 10.5% of women who were trying to become pregnant. The most common treatment reported was fertility enhancing drugs (29%), followed by assisted reproductive technology including in vitro fertilization (21%), and artificial insemination together with fertility enhancing drugs (15%). Some women reported using other types of treatment (23%). The PRAMS data provide insights into the use of infertility treatment among women giving birth in the United States. Further research is needed to understand the true prevalence of infertility, factors that influence treatment choices, and the longitudinal impact of infertility treatment on outcomes.


The use of hormonal contraceptive agents and mood disorders in women

Abstract:
Background: Mood disorders are a major cause of disability in developed countries, and contraceptive agents among the most widely used medications. The relationship between contraceptive agents and mood is unclear. The aim of this study was therefore to investigate the association between current contraception use and mood disorders in a random population-based sample of women.

Methods: This study examined epidemiological data obtained from 498 women aged 20-50year participating in the Geelong Osteoporosis Study (GOS). Mood disorders were diagnosed using a clinical interview (SCID-I/NP) and information on medication use and other lifestyle factors were documented.

Results: After adjusting for age and socioeconomic status (SES), women taking progestin-only contraceptive agents had an increased likelihood of a current mood disorder (OR 3.0 95%CI: 1.1-7.8, p=0.03). In contrast, women taking combined contraceptive agents had a decreased likelihood of a current mood disorder, adjusting this for age and SES (OR 0.3 95%CI: 0.1, 0.9 p=0.03). These findings were not explained by weight, physical activity level, past depression, number of medical conditions or cigarette smoking.

Limitations: This study is cross-sectional, which precludes any determination regarding the direction of the relationships.

Conclusions: These data suggest a protective effect of the combined contraceptive pill, and a deleterious effect of progestin only agents in regards to mood disorders.


Osteoporosis-related fracture case definitions for population-based  administrative data

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Abstract:
Background: Population-based administrative data have been used to study osteoporosis-related fracture risk factors and outcomes, but there has been limited research about the validity of these data for ascertaining fracture cases. The objectives of this study were to: (a) compare fracture incidence estimates from administrative data with estimates from population-based clinically-validated data, and (b) test for differences in incidence estimates from multiple administrative data case definitions.

Methods: Thirty-five case definitions for incident fractures of the hip, wrist, humerus, and clinical vertebrae were constructed using diagnosis codes in hospital data and diagnosis and service codes in physician billing data from Manitoba, Canada. Clinically-validated fractures were identified from the Canadian Multicentre Osteoporosis Study (CaMos). Generalized linear models were used to test for differences in incidence estimates.

Results: For hip fracture, sex-specific differences were observed in the magnitude of underand over-ascertainment of administrative data case definitions when compared with CaMos data. The length of the fracture-free period to ascertain incident cases had a variable effect on over-ascertainment across fracture sites, as did the use of imaging, fixation, or repair service codes. Case definitions based on hospital data resulted in under-ascertainment of incident clinical vertebral fractures. There were no significant differences in trend estimates for wrist, humerus, and clinical vertebral case definitions.

Conclusions: The validity of administrative data for estimating fracture incidence depends on the site and features of the case definition.


Effects of hormonal contraception on vaginal flora

Stefano Restaino

Ospedale Santa Maria della Misericordia di Udine

Davide De Santo

Universidad Católica Tecnológica de Barahona

Abstract:
Background: The sector of the market that deals with contraception offers a long list of different contraceptive methods. Within the estroprogestinic choice, the routes of administration are oral, transdermic and vaginal one. Even though efficacy is comparable with these methods, secondary and adverse effects are directly involved in the acceptability of the method.

Study Design: This was a prospective comparative study. During 1 year, we enrolled 60 asymptomatic women who voluntarily requested combined oral contraception (COC) or combined contraceptive vaginal ring (CCVR group). After a baseline study of vaginal milieu prior to starting hormonal contraception, we performed a follow-up. For each woman, we examined vaginal pH; quantification of leukocytes, lactobacilli, Candida and cocci on saline microscopy fluid; Gram stain with Nugent score and the presence of vaginal infection [culture for Trichomonas vaginalis, albicans and nonalbicans Candida, Group B Streptococcus (GBS)].

Results: At the end of follow-up, there was a little change of vaginal milieu in both groups. We noted an increase of lactobacilli in the CCVR users and an increase of GBS in COC users.

Conclusion: CCVR compared to COC users showed an increase of the number of lactobacilli in vaginal flora. It means that an increase of leukorrhea in that group could be protective in terms of prevention of vaginal imbalance/infection.