Abstract: 20. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010. Dyer S(1), Chambers GM(2), de Mouzon J(3), Nygren KG(4), Zegers-Hochschild F(5), Mansour R(6), Ishihara O(7), Banker M(8), Adamson GD(9). (1)Department of Obstetrics & Gynaecology, Groote Schuur Hospital and Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa silke.dyer@uct.ac.za. (2)National Perinatal Epidemiology and Statistics Unit, University of New South Wales, Sydney, Australia. (3)Institut National de la Santé et de la Recherche Médicale Service de Gynécologie Obstétrique II et de Médecine de la Reproduction, Groupe Hospitalier Cochin-Saint Vincet de Paul, Paris, France. (4)Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. (5)Clinica las Condes and Program of Ethics and Public Policies in Human Reproduction, University Diego Portales, Santiago, Chile. (6)Egyptian IVF-ET Center, Cairo, Egypt. (7)Department of Obstetrics and Gynaecology, Saitama Medical University, Moroyama, Japan. (8)Nova IVI Fertility, Chennai, India. (9)Palo Alto Medical Foundation Fertility Physicians of North California, San Jose, CA, USA. Comment in Hum Reprod. 2016 Jul;31(7):1381-2. doi: 10.1093/humrep/dew092. STUDY QUESTION: What were utilization, outcomes and practices in assisted reproductive technology (ART) globally in 2008, 2009 and 2010? SUMMARY ANSWER: Global utilization and effectiveness remained relatively constant despite marked variations among countries, while the rate of single and frozen embryo transfers (FETs) increased with a concomitant slight reduction in multiple birth rates. WHAT IS KNOWN ALREADY: ART is widely practised in all regions of the world. Monitoring utilization, an approximation of availability and access, as well as effectiveness and safety is an important component of universal access to reproductive health. STUDY DESIGN, SIZE, DURATION: This is a retrospective, cross-sectional survey on utilization, effectiveness and safety of ART procedures performed globally from 2008 to 2010. PARTICIPANTS, SETTING, METHODS: Between 58 and 61 countries submitted data from a total of nearly 2500 ART clinics each year. Aggregate country data were processed and analyzed based on forms and methods developed by the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). Results are presented at country, regional and global level. MAIN RESULTS AND THE ROLE OF CHANCE: For the years 2008, 2009 and 2010, >4 461 309 ART cycles were initiated, resulting in an estimated 1 144 858 babies born. The number of aspirations increased by 6.4% between 2008 and 2010, while FET cycles increased by 27.6%. Globally, ART utilization remained relatively constant at 436 cycles/million in 2008 and 474 cycles/million population in 2010, but with a wide country range of 8-4775 cycles/million population. ICSI remained constant at around 66% of non-donor aspiration cycles. The IVF/ICSI combined delivery rate (DR) per fresh aspiration was 19.8% in 2008; 19.7% in 2009 and 20.0% in 2010, with corresponding DRs for FET of 18.8, 19.7 and 20.7%. In fresh non-donor cycles, single embryo transfer increased from 25.7% in 2008 to 30.0% in 2010, while the average number of embryos transferred fell from 2.1 to 1.9, again with wide regional variation. The rates of twin deliveries following fresh non-donor transfers were, in 2008, 2009 and 2010, 21.8, 20.5 and 20.4%, respectively, with a corresponding triplet rate of 1.3, 1.0 and 1.1%. Fresh IVF and ICSI carried a perinatal mortality rate per 1000 births of 22.8 (2008), 19.2 (2009) and 21.0 (2010), compared with 15.1, 12.8 and 14.6/1000 births following FET in the same periods of observation. The proportion of women aged 40 years or older undergoing non-donor ART increased from 20.8 to 23.2% from 2008 to 2010. LIMITATIONS, REASON FOR CAUTION: The data presented are reliant on the quality and completeness of data submitted by individual countries. This report covers approximately two-thirds of the world ART activity. WIDER IMPLICATIONS OF FINDINGS: The ICMART World Reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment continues to increase globally, the wide disparities in access to treatment and embryo transfer practices warrant attention by clinicians and policy makers. STUDY FUNDING/COMPETING INTERESTS: The authors declare no conflict of interest and no specific support from any organizations in relation to this manuscript. ICMART acknowledges financial support from the following organizations: American Society for Reproductive Medicine; European Society for Human Reproduction and Embryology; Fertility Society of Australia; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproduccion Asistida; Society for Assisted Re


Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A  Systematic Review and Meta-analysis

Abstract:
Objective: As the HIV/AIDS epidemic continues to spread in Africa and Asia, use of the injectable contraceptive steroid DMPA is widespread and has been increasing. Since studies dating back to 1992 have suggested that DMPA may increase the transmission of HIV to women, we endeavored to determine if the extant epidemiological and biological evidence is sufficient to conclude that DMPA use constitutes a definite hazard to women's health.

Methods: We searched Medline using the search terms: contraceptives or contraception AND HIV and searched bibliographies of articles thus identified. We included in the meta-analysis all studies examining the association between use of DMPA (or injectable contraceptives comprising mostly DMPA) and the presence (cross-sectional studies, n = 8) or acquisition (longitudinal studies, n = 16) of HIV+ status in women, using a random effects models to estimate odds ratios (ORs; cross-sectional studies) and hazard ratios (HRs; longitudinal studies). Studies were excluded if the comparison group included women using any form of steroidal contraception.

Results: Statistically significant positive associations between DMPA use and HIV positivity were observed both in cross-sectional (OR = 1.41, 95% CI 1.15 - 1.73) and longitudinal studies (HR = 1.49, 95% CI 1.28 - 1.73). The biological plausibility of increased vulnerability to HIV infection due to progestational action (via thinning of the vaginal epithelial barrier and immunosuppression) as well as glucocorticoid agonistic immunosuppression, are discussed.

Conclusion: The epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission.


The Use of Isomolecular Progesterone in the Support of Pregnancy and Fetal Safety

Thomas W Hilgers

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

Abstract: Progesterone support in pregnancy has been in use for over 60 years, having received its start in the 1940s. Its initial use was in patients who had habitual spontaneous abortion caused by luteal phase deficiency. More recently, the administration of progesterone later in pregnancy has been considered to be justified because of an observed decrease in circulating progesterone with the onset of labor, an association of premature labor with decreased progesterone concentrations, and the observation that progesterone has a tocolytic effect. A considerable boost to the use of progestational agents to reduce preterm delivery was received with the publication of two papers which showed a significant reduction in preterm delivery rates with the prophylactic administration of either progesterone or 17-a hydroxyprogesterone caproate. Recently it has been shown, however, that its use is not universal. This may be related to the significant late sequelae that were documented following the in utero exposure of the fetus to the potent steroid diethylstilbestrol (DES) and that this bad experience cast “a long shadow,” In spite of this, the use of progesterone, at least in early pregnancy, is widespread in the various artificial reproductive programs and is growing in its use as an agent to reduce prematurity. Over the years, there has been an extraordinary amount of confusion related to the use of progesterone support in pregnancy. The Food & Drug Administration (FDA) created some of this confusion. In various labeling of progesterone products by the FDA, one of the contraindications to the use of oral progesterone is listed as “known or suspected pregnancy.” And, yet, no such contraindication is identified for the use of progesterone gel. In fact, progesterone gel is indicated for progesterone supplementation or replacement as a part of an assisted reproductive technology (ART) treatment program for infertile women with a progesterone deficiency. To make this even more confusing, oral progesterone, while it was contraindicated in “known or suspected pregnancy,” its official labeling stated that it “should be used during pregnancy only if indicated (see contraindications).” Also, up until very recently, there was a dire “warning” contained in the labeling for USP progesterone injection in sesame seed oil regarding an increased possibility of birth defects. An analysis of the fetal safety of isomolecular progesterone (Pregn-4-ene-3,20-dione) administration during the course of 1,310 pregnancies over a 35-year period of time (1979-2014) was undertaken to address this confusion.


Myo-inositol may prevent gestational diabetes onset in overweight women: a  randomized, controlled trial

Rosario D'Anna

Department of Obstetrics and Gynecology, University of Messina, Italy.

Abstract:
Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women.

Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m(2)). The primary outcome was the incidence of GDM.

Results: From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15-0.70).

Conclusions: Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.

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


Dietary patterns in men and women are simultaneously determinants of altered glucose metabolism and bone metabolism

Christopher S Kovacs

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

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: We hypothesized that diet would have direct effects on glucose metabolism with direct and indirect effects on bone metabolism in a cohort of Canadian adults. We assessed dietary patterns (Prudent [fruit, vegetables, whole grains, fish, and legumes] and Western [soft drinks, potato chips, French fries, meats, and desserts]) from a semiquantitative food frequency questionnaire. We used fasting blood samples to measure glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR), 25-hydroxyvitamin D (25OHD), parathyroid hormone, bone-specific alkaline phosphatase (a bone formation marker), and serum C-terminal telopeptide (CTX; a bone resorption marker). We used multivariate regression models adjusted for confounders and including/excluding body mass index. In a secondary analysis, we examined relationships through structural equations models. The Prudent diet was associated with favorable effects on glucose metabolism (lower insulin and HOMA-IR) and bone metabolism (lower CTX in women; higher 25OHD and lower parathyroid hormone in men). The Western diet was associated with deleterious effects on glucose metabolism (higher glucose, insulin, and HOMA-IR) and bone metabolism (higher bone-specific alkaline phosphatase and lower 25OHD in women; higher CTX in men). Body mass index adjustment moved point estimates toward the null, indicating partial mediation. The structural equation model confirmed the hypothesized linkage with strong effects of Prudent and Western diet on metabolic risk, and both direct and indirect effects of a Prudent diet on bone turnover. In summary, a Prudent diet was associated with lower metabolic risk with both primary and mediated effects on bone turnover, suggesting that it is a potential target for reducing fracture risk.


Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles

Abstract:
Comment in BMJ. 2015 Dec 23;351:h6913. doi: 10.1136/bmj.h6913. JAMA. 2015 Dec 22-29;314(24):2627-9. doi: 10.1001/jama.2015.17297.
 IMPORTANCE: The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. OBJECTIVE: To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. EXPOSURES: In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. MAIN OUTCOMES AND MEASURES: Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. RESULTS: Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. CONCLUSIONS AND RELEVANCE: Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.


Monitoring of ovarian activity by measurement of urinary excretion rates using  the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide  threshold to basal body temperature and cervical mucus as markers for the  beginning of the post-ovulatory infertile period

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract:
STUDY Question: Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value?

SUMMARY ANSWER: Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles.

WHAT IS KNOWN ALREADY: The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account.

STUDY DESIGN, SIZE, DURATION: Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years.

PARTICIPANTS/MATERIALS, SETTING, Methods: A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound.

MAIN RESULTS AND THE ROLE OF CHANCE: The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators.

LIMITATIONS, REASONS FOR CAUTION: The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested.

WIDER IMPLICATIONS OF THE Findings: The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested.

STUDY FUNDING/COMPETING INTERESTS: This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare.


Use of exogenous hormones and the risk of breast cancer: results from  self-reported survey data with validity assessment

Eero Pukkala

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Unioninkatu 22, 00130, Helsinki, Finland.

Abstract:
Purpose: Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data.

Methods: The survey 'Women's Health and Use of Hormones' was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys.

Results: We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10-1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (≥2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12-1.68) for premenopausal and 1.11 (95 % CI 1.03-1.20) for postmenopausal women, when compared to never-users of other HC.

Conclusions: Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant.


Epigenetic effects of casein-derived opioid peptides in SH-SY5Y human neuroblastoma cells

Abstract:
Background: Casein-free, gluten-free diets have been reported to mitigate some of the inflammatory gastrointestinal
and behavioral traits associated with autism, but the mechanism for this palliative effect has not been elucidated. We
recently showed that the opioid peptide beta-casomorphin-7, derived from bovine (bBCM7) milk, decreases cysteine
uptake, lowers levels of the antioxidant glutathione (GSH) and decreases the methyl donor S-adenosylmethionine
(SAM) in both Caco-2 human GI epithelial cells and SH-SY5Y human neuroblastoma cells. While human breast milk
can also release a similar peptide (hBCM-7), the bBCM7 and hBCM-7 vary greatly in potency; as the bBCM-7 is highly
potent and similar to morphine in it's effects. Since SAM is required for DNA methylation, we wanted to further
investigate the epigenetic effects of these food-derived opioid peptides. In the current study the main objective was
to characterize functional pathways and key genes responding to DNA methylation effects of food-derived opioid
peptides.

Methods: SH-SY5Y neuroblastoma cells were treated with 1 μM hBCM7 and bBCM7 and RNA and DNA were isolated
after 4 h with or without treatment. Transcriptional changes were assessed using a microarray approach and CpG
methylation status was analyzed at 450,000 CpG sites. Functional implications from both endpoints were evaluated via
Ingenuity Pathway Analysis 4.0 and KEGG pathway analysis was performed to identify biological interactions between
transcripts that were significantly altered at DNA methylation or transcriptional levels (p < 0.05, FDR <0.1).

Results: Here we show that hBCM7 and bBCM7, as well as morphine, cause epigenetic changes affecting gene
pathways related to gastrointestinal disease and inflammation. These epigenetic consequences exhibited the same
potency order as opiate inhibition of cysteine uptake insofar as hBCM7 was less potent than bBCM7, which was less
potent than morphine.

Conclusion: Our findings indicate that epigenetic effects of milk-derived opiate peptides may contribute to GI
dysfunction and inflammation in sensitive individuals. While the current study was performed using SH-SY5Y
neuronal cellular models, similar actions on other cells types might combine to cause symptoms of intolerance. These
actions may provide a potential contributing mechanism for the beneficial effects of a casein-free diet in alleviating
gastrointestinal symptoms in neurological conditions including autism and other conditions. Lastly, our study also
contributes to the evolving awareness of a “gut-brain connection”.
Keywords: Epigenetics, Gluten free casein free diet, Autism, Glutathione, Gastrointestinal, Inflammation


Evaluating Endocrine Disruption Activity of Deposits on Firefighting Gear Using a  Sensitive and High Throughput Screening Method

Abstract:
Objective: Adverse health outcomes related to exposure to endocrine disrupting chemicals, including increased incidences of coronary heart disease, prostate and testicular cancers, and congenital disabilities, have been reported in firefighters or their offspring. We, therefore, measured the estrogenic and antiestrogenic activity of extracts of used firefighter gear to assess exposure to these agents.

Methods: Extracts and known chemical contaminants were examined for estrogenicity and antiestrogenicity in yeast cells expressing the estrogen receptor.

Results: Most extracts of used gear and phthalate diesters detectable on this gear displayed strong antiestrogenic effects. Notably, new glove and hood extracts showed significant estrogenic activity.

Conclusions: Overall, our data suggest that firefighters are exposed to both estrogenic and antiestrogenic agents, possibly phthalates that may lead to health risks observed in this occupation as a result of perturbation of hormone homeostasis.

Journal of Occupational and Environmental Medicine


Cumulative live birth rate: time for a consensus?

Abstract: Traditionally, IVF success rates have been reported in terms of live birth per fresh cycle or embryo transfer. With the increasing use of embryo freezing and thawing it is essential that we report not only outcomes following fresh but also those after frozen embryo transfer as a complete measure of success of an IVF treatment. Most people agree that an individual's chance of having a baby following fresh and frozen embryo transfer should be described as cumulative live birth rate. However, views on the most appropriate parameters required to calculate such an outcome have been inconsistent. There is an additional dimension - time for all frozen embryos to be used up by a couple, which can influence the outcome. Given that cumulative live birth rate is generally perceived to be the preferred reporting system in IVF, it is time to have an international consensus on how this statistic is calculated, reported and interpreted by stakeholders across the world.


Efficacy of Ginger for Alleviating the Symptoms of Primary Dysmenorrhea: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Xiqian Zhang

Guangdong Province Women and Children Hospital

Abstract:
OBJECTIVE: There has been no attempt to date to synthesize the available evidence for the efficacy of ginger for treating primary dysmenorrhea. This systematic review evaluates the current evidence for the effectiveness of ginger for treating primary dysmenorrhea.

METHODS: Literature searches were conducted using 12 electronic databases including PubMed, EMBASE, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were: "ginger" or "Zingiber officinale" and "dysmenorrhea" and "pain." Studies using ginger as a treatment of primary dysmenorrhea were considered for inclusion. The major outcome of primary dysmenorrhea was assessed using a pain visual analogue score (PVAS).

RESULTS: Initial searches yielded 29 articles. Of these original results, seven met specific selection criteria. Four of the RCTs compared the therapeutic efficacy of ginger with a placebo during the first 3-4 days of the menstrual cycle and were included in the meta analysis. The meta-analysis of these data showed a significant effect of ginger in reducing PVAS in subjects having primary dysmenorrhea (risk ratio, -1.85; 95% CI of -2.87, -0.84, P = 0.0003). Six RCTs out of 7 exhibited low to moderate of risk of bias.

CONCLUSION: Collectively these RCTs provide suggestive evidence for the effectiveness of 750-2000 mg ginger powder during the first 3-4 days of menstrual cycle for primary dysmenorrhea.


A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

Coomarasamy A, Williams H, Truchanowicz E, Seed PT, Small R, Quenby S, Gupta P, Dawood F, Koot YE, Bender Atik R, Bloemenkamp KW, Brady R, Briley AL, Cavallaro R, Cheong YC, Chu JJ, Eapen A, Ewies A, Hoek A, Kaaijk EM, Koks CA, Li TC, MacLean M, Mol BW, Moore J, Ross JA, Sharpe L, Stewart J, Vaithilingam N, Farquharson RG, Kilby MD, Khalaf Y, Goddijn M, Regan L, Rai R

Abstract:
BACKGROUND: Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain.

METHODS: We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice-daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation.

RESULTS: A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, -4.0 to 9.0). There were no significant between-group differences in the rate of adverse events.

CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.).


ACOG Committee Opinion No. 651: Menstruation in Girls and Adolescents: Using the Menstrual Cycle as a Vital Sign

Abstract: Despite variations worldwide and within the U.S. population, median age at menarche has remained relatively stable-between 12 years and 13 years-across well-nourished populations in developed countries. Environmental factors, including socioeconomic conditions, nutrition, and access to preventive health care, may influence the timing and progression of puberty. A number of medical conditions can cause abnormal uterine bleeding, characterized by unpredictable timing and variable amount of flow. Clinicians should educate girls and their caretakers (eg, parents or guardians) about what to expect of a first menstrual period and the range for normal cycle length of subsequent menses. Identification of abnormal menstrual patterns in adolescence may improve early identification of potential health concerns for adulthood. It is important for clinicians to have an understanding of the menstrual patterns of adolescent girls, the ability to differentiate between normal and abnormal menstruation, and the skill to know how to evaluate the adolescent girl patient. By including an evaluation of the menstrual cycle as an additional vital sign, clinicians reinforce its importance in assessing overall health status for patients and caretakers.


Serum Antioxidants Are Associated with Serum Reproductive Hormones and Ovulation among Healthy Women

Richard W Browne

University at Buffalo, State University of New York

Torie Comeaux Plowden

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract:
Background: Evidence is growing that the equilibrium between reactive oxygen species and antioxidants plays a vital role in women's reproductive health.

Objective: The objective of this study was to evaluate variations in serum antioxidant concentrations across the menstrual cycle and associations between antioxidants and reproductive hormones and anovulation among healthy women.

Methods: The BioCycle Study, a prospective cohort, followed 259 women aged 18-44 y for up to 2 menstrual cycles. Serum fat-soluble vitamin and micronutrient (α-tocopherol, γ-tocopherol, retinol, lutein, lycopene, and β-carotene), ascorbic acid, and reproductive hormone concentrations were measured 5-8 times/cycle. We used weighted linear mixed models to assess associations between antioxidants and hormone concentrations, after adjustment for age, race, body mass index, parity, sleep, pain medication use, total energy intake, concurrent hormones, serum cholesterol, F2-isoprostanes, and other antioxidants. Generalized linear models were used to identify associations with anovulation.

Results: Serum antioxidant concentrations varied across the menstrual cycle. Retinol and α-tocopherol were associated with higher estradiol [RR: 1.00 pg/mL (95% CI: 0.67, 1.34 pg/mL); RR: 0.02 pg/mL (95% CI: 0.003, 0.03 pg/mL), respectively] and testosterone [RR: 0.61 ng/dL (95% CI: 0.44, 0.78 ng/dL); RR: 0.01 ng/dL (95% CI: 0.001, 0.01 ng/dL), respectively]. Ascorbic acid was associated with higher progesterone (RR: 0.15 ng/mL; 95% CI: 0.05, 0.25 ng/mL) and with lower follicle-stimulating hormone (RR: -0.06 mIU/mL; 95% CI: -0.09, -0.03 mIU/mL). The ratio of αto γ-tocopherol was associated with an increased risk of anovulation (RR: 1.03; 95% CI: 1.01, 1.06).

Conclusions: These findings shed new light on the intricate associations between serum antioxidants and endogenous hormones in healthy premenopausal women and support the hypothesis that concentrations of serum vitamins affect steroidogenesis even after adjustment for oxidative stress.


Effects of Letrozole-HMG and Clomiphene-HMG on Incidence of Luteinized Unruptured  Follicle Syndrome in Infertile Women Undergoing Induction Ovulation and  Intrauterine Insemination: A Randomised Trial

Zeinab Hamzehgardeshi

Mazandaran University of Medical Sciences

Azra Azmoodeh

Department of Reproduction & Infertility, Mirza-kouchak Khan women Hospital, Tehran University of Medical Sciences, Tehran, Iran. Azmoodeh@yahoo.com.

Abstract:
Background: Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes.

Methods: The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18-23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38-40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome.

Results: There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF cycles (p = 0.039) and (p < 0.001). The results of our multivariate logistic regression indicate that size 18-19.9 mm leads to the complete LUF less than ≥22 mm [AOR: 0.25, P = 0.005], and in size 20- 21.9 mm as well [AOR: 0.17, P = 0.002].

Conclusion: Letrozole, with lower incidences of LUF, is more effective than clomiphene citrate for the induction of ovulation in IUI cycles. In our study, we illustrated that larger follicles of ≥22 mm diameter were associated with higher incidences of LUF. We recommend that further studies investigate and focus on the relationship between follicular size and/or full hormonal profiles and LUF.


Obesity and reproduction: a committee opinion

Ethics Committee of the American Society for Reproductive Medicine

Abstract: The purpose of this ASRM Practice Committee report is to provide clinicians with principles and strategies for the evaluation and treatment of couples with infertility associated with obesity. This revised document replaces the Practice Committee document titled, "Obesity and reproduction: an educational bulletin," last published in 2008 (Fertil Steril 2008;90:S21-9).


Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility

Abstract: Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.

Journal of assisted reproduction and genetics


The Association between Stress Level in Daily Life and Age at Natural Menopause in Korean Women: Outcomes of the Korean National Health and Nutrition Examination Survey in 2010-2012

Abstract:
BACKGROUND: Although several risk factors associated with reduced age at natural menopause (ANM) have been investigated, the results are inconsistent. Excessive stress, which leads to elevation of stress hormones, can also negatively affect reproductive ability, including by accelerating menopause. However, a direct association between stress level and ANM has not yet been demonstrated. Therefore, the object of this study was to investigate the association between stress level and ANM in Korean women.

METHODS: Study participants were Korean women between 40 and 70 years old who were in natural menopause during the 5th Korean National Health and Nutrition Examination Survey (n=3,176). The level of stress in daily life was estimated based on data from the mental health topics of the survey. We used the t-test and one-way analysis of variance to analyze the correlation between stress level and ANM. Regression (β) coefficients calculated by multiple regression analysis were used to estimate various factors affecting ANM.

RESULTS: Women who experienced a high level of stress in daily life had a lower mean ANM than women with a low stress level (50.17±3.7 and 50.58±3.5 years, respectively), with a statistically significant correlation (P<0.05). This correlation was still observed after adjusting for age, body mass index, menstrual regularity, and personal income (P<0.05 for variables).

CONCLUSION: In Korean women between 40 and 70 years of age who are in natural menopause, there is a statistically significant correlation between stress level and ANM. In particular, women who experience a high level of stress in daily life have reduced ANM.


Is Anti-Müllerian Hormone Associated With Fecundability? Findings From the EAGeR Trial

Abstract:
Objective: The objective of the study was to evaluate whether anti-Müllerian hormone (AMH) is associated with fecundability among women with proven fecundity and a history of pregnancy loss.
Design: This was a prospective cohort study within a multicenter, block-randomized, double-blind, placebo-controlled clinical trial ( clinicaltrials.gov , number NCT00467363).
Setting: The study was conducted at four US medical centers (2006-2012).

Participants: Participating women were aged 18-40 years, with a history of one to two pregnancy losses who were actively attempting pregnancy.

Main Outcome Measures: Time to human chorionic gonadotropin detected and clinical pregnancy were assessed using Cox proportional hazard regression models to estimate fecundability odds ratios (fecundability odds ratios with 95% confidence interval [CI]) adjusted for age, race, body mass index, income, low-dose aspirin treatment, parity, number of previous losses, and time since most recent loss. Analyses examined by preconception AMH levels: low (<1.00 ng/mL, n = 124); normal (referent 1.00-3.5 ng/mL, n = 595); and high (>3.5 ng/mL, n = 483).

Results: Of the 1202 women with baseline AMH levels, 82 women with low AMH (66.1%) achieved an human chorionic gonadotropin detected pregnancy, compared with 383 with normal AMH (65.2%) and 315 with high AMH level (65.2%). Low or high AMH levels relative to normal AMH (referent) were not associated with fecundability (low AMH: fecundability odds ratios 1.13, 95% CI 0.85-1.49; high AMH: FOR 1.04, 95% CI 0.87-1.24).

Conclusions: Lower and higher AMH values were not associated with fecundability in unassisted conceptions in a cohort of fecund women with a history of one or two prior losses. Our data do not support routine AMH testing for preconception counseling in young, fecund women.

The Journal of clinical endocrinology and metabolism


Progesterone or progestin as menopausal ovarian hormone therapy: recent  physiology-based clinical evidence

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
PURPOSE OF Review: Provide evidence-based recent data on oral micronized progesterone (OMP) and progestins in menopausal hormonal therapy (MHT). RECENT Findings: Medroxyprogesterone acetate (MPA) increases breast cancer acting through the glucocorticoid receptor; progestins in MHT increase thrombosis more than oral estrogens; MPA, but not OMP or other progestins, increase monocyte cell endothelium adhesion; MPA and estradiol (E2)/MPA have negative brain effects, whereas E2/progesterone (P4) has neuroregenerative brain effects. The 'window of opportunity' cardiovascular disease hypothesis is not supported by a randomized controlled trial showing that transdermal estradiol with sequential OMP in early menopause does not prevent increased carotid intimal media thickness; P4 in the cardiac electrical system opposes E2 effects and prevents sudden death/long QT syndrome; transdermal estradiol/OMP does not increase venous thromboembolism in observational data. P4 decreases breast cell proliferation and improves prognosis through P4 receptor alteration of estrogen receptor α genetic effects; OMP with conjugated equine estrogen (CEE)/estrogen (E)/E2 does not increase breast cancer in two prospective cohorts, one population-based. Endometrial cancer is increased in MHT of CEE/E/E2+cyclic OMP at 200 mg/day.
Summary: New data show CEE/E/E2+MPA/P mechanisms for negative breast cancer, venous thromboembolism, cardiovascular system, and brain effects. OMP/P4 counterbalances CEE/E/E2-related negative effects on breast cancer and long QT syndrome. OMP effectively treats vasomotor symptoms and sleep disturbances, and could safely be used alone for symptomatic menopause.

Current Opinion in Endocrinology, Diabetes, and Obesity


Using pilot data to size a two-arm randomized trial to find a nearly optimal personalized treatment strategy

Anastasios Tsiatis

John Wiley & Sons, Ltd The Atrium  Southern Gate, Chichester West Sussex PO19 8SQ U.K.

Abstract: A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness.


A rare presentation of aplasia cutis congenita after feto-reduction in a trichorionic-triamniotic pregnancy

Abstract: Aplasia cutis congenita (ACC) is rare skin disorder of newborns that has been linked to both assisted reproductive technology (ART) and feto-reduction procedures. ACC is characterized by well-demarcated lesions that are devoid of all skin layers. Group-V ACC presents with a distinctive and symmetrical distribution pattern. It is thought to result from an insult to the fetus after concomitant twin demise and is almost exclusively reported in monochorionic gestations.A 41-year-old female with an in vitro fertilization (IVF) assisted tri-chorionic gestation subsequently underwent selective feto-reduction of Fetus C. The patient delivered two pre-term neonates secondary to pre-eclampsia. The initial exam of Twin B showed extensive, well-demarcated, symmetrical areas devoid of any skin over the anterior and lateral trunk, extending up the lateral thoracic walls. Chest and abdominal viscera were visible through a thin fibrous membrane. The skin defects were managed conservatively with twice-daily dressings of Aquaphor, and Vaseline gauze. The areas of aplasia slowly contracted, though residual scarring was noted. After four weeks in the NICU, most of the areas were healed.ACC in multi-fetal pregnancies is a rare, but well-described complication. This is, to our knowledge, the first reported case in a tri-chorionic IVF gestation after feto-reduction. With increased incidence of ART-associated pregnancies and the use of feto-reduction for higher order gestations, this may become more common. Neonates often require specialized intensive care. Conservative management usually will suffice, although surgical grafting may be required. Physicians should be aware of this condition and counsel their feto-reduction patients of the risk.


Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal  Complications

Tadahiro Yasuo

Kyoto Prefectural University of Medicine

Abstract: Chronic endometritis (CE) is a local inflammatory disease characterized by unusual plasmacyte infiltration in the endometrial stromal areas. CE has been neglected in gynecologic practice, as it is a less symptomatic benign disease that requires demanding and time-consuming histopathologic examinations for the definite diagnosis. Recent studies, however, suggest the association of CE with infertility and obstetric and neonatal complications. In this review article, we aimed to update the knowledge on epidemiology, etiology, and pathogenesis of CE as well as discuss its clinical management from diagnosis to treatment.

American Journal of Reproductive Immunology (New York, N.Y. : 1989)


Endocrine abnormalities in HIV-infected women are associated with peak viral load - the Children and Women: AntiRetrovirals and Markers of Aging (CARMA) Cohort

Arianne Y.K. Albert

Women's Health Research Institute Vancouver BC Canada

Hélène C F Côté

Women's Health Research Institute, H214-4500 Oak St, Vancouver, British Columbia V6H 3N1, Canada; Department of Pathology & Laboratory Medicine, University of British Columbia, Rm. G227 - 2211 Wesb...

Melanie C M Murray

Oak Tree Clinic, BC Women's Hospital and Health Centre, 4500 Oak St, Vancouver, British Columbia V5Z 0A7, Canada; Women's Health Research Institute, H214-4500 Oak St, Vancouver, British Columbia V6...

the CIHR team grant on HIV therapy and aging: CARMA

Abstract:
Objectives: To investigate the prevalence of endocrine disturbances in a group of HIV-positive (HIV+) women and to identify factors affecting presence of these disorders. To examine specifically whether cellular ageing, as measured by leukocyte telomere length (LTL), is correlated with the presence of endocrine disturbance.
Design: A cross-sectional retrospective substudy of an ongoing prospective cohort study.

Patients: Adult HIV+ (≥19 years) women enrolled in the CARMA (Children and Women: AntiRetrovirals and Markers of Aging) cohort study (N = 192). Prevalences of T2DM, glucose intolerance, dyslipidaemia, thyroid disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline LTL, combined antiRetroviral therapy (cART) and substance exposures were collected. Statistical analysis included univariable followed by multivariable Poisson regression and step-wise reduction to refine the multivariable model.

Results: Prevalence of any endocrine abnormality was 58% (dyslipidaemia 43%, glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis, age was associated with number and type (any, glucose, lipid) of abnormality, while increasing body mass index (BMI) was associated with number of diagnoses and with glucose metabolism disorders. Interestingly, peak HIV pVL ≥100 000 copies/ml was associated with any abnormality, total number of disorders and presence of a thyroid disorder, while any disorder, glucose abnormalities and dyslipidaemia were negatively associated with alcohol use. LTL was not associated with number or type of endocrine abnormalities in this study.

Conclusion: Further studies examining the relationship between duration and extent of exposure to HIV viraemia in relation to developing abnormal endocrine function are warranted.


Fluctuations of Hyperglycemia and Insulin Sensitivity Are Linked to Menstrual Cycle Phases in Women With T1D

Abstract:
BACKGROUND: Factors influencing glycemic variability in type 1 diabetes (T1D) may play a significant role in the refinement of closed loop insulin administration. Phase of menstrual cycle is one such factor that has been inadequately investigated. We propose that unique individual patterns can be constructed and used as parameters of closed loop systems.

METHOD: Women with T1D on continuous subcutaneous insulin infusion and continuous glucose monitoring were studied for 3 consecutive menstrual cycles. Ovulation prediction kits and labs were used to confirm phase of menstrual cycle. Glycemic risks were assessed using the low- and high blood glucose indices (LBGI and HBGI). Insulin sensitivity (SI) was estimated using a Kalman filtering method from meal and insulin data. Overall change significance for glycemic risks was assessed by repeated measures ANOVA, with specific phases emphasized using contrasts.

RESULTS: Ovulation was confirmed in 33/36 cycles studied in 12 subjects (age = 33.1 ± 7.0 years, BMI = 25.7 ± 2.9 kg/m(2), A1c = 6.8 ± 0.7%). Risk for hyperglycemia changed significantly during the cycle (P = .023), with HBGI increasing until early luteal phase and returning to initial levels thereafter. LBGI was steady in the follicular phase, decreasing thereafter but not significantly. SI was depressed during the luteal phase when compared to the early follicular phase (P ≤ .05). Total daily insulin, carbohydrates, or calories did not show any significant fluctuations.

CONCLUSIONS: Women with T1D have glycemic variability changes that are specific to the individual and are linked to phase of cycle. An increased risk of hyperglycemia was observed during periovulation and early luteal phases compared to the early follicular phase; these changes appear to be associated with decreased insulin sensitivity during the luteal phase.

Journal of diabetes science and technology


Women with minor menstrual irregularities have increased risk of preeclampsia and  low birthweight in spontaneous pregnancies

Barbara Bonnesen

Department of Gynecology and Obstetrics Copenhagen University Hospital Hvidovre Hvidovre Denmark

Abstract:
Introduction: Very few studies describe the obstetric and neonatal outcome of spontaneous pregnancies in women with irregular menstrual cycles. However, menstrual cycle irregularities are common and may be associated with increased risk, and women who develop pregnancy complications more frequently recollect irregular menstrual cycles before the time of conception in case-control studies.

MATERIAL AND Methods: This retrospective cohort study compares obstetric and neonatal outcomes in spontaneous singleton pregnancies in 3440 primiparous Danish women stratified according to menstrual cycle regularity. All pregnancies delivered after 22 weeks of gestation and had a nuchal translucency examination at Copenhagen University Hospital Hvidovre between 1 January 2009 and 31 December 2010. Menstrual cycle irregularity was defined as more than 7 days' deviation between self-reported and ultrasound examination-based gestational age. Outcome measures were gestational diabetes, hypertension, preeclampsia, preterm premature rupture of membranes, preterm birth, prolonged pregnancy, birthweight, umbilical artery pH <7.1, APGAR <7 after 5 min, admission to neonatal intensive care unit and stillbirth. Women with more than 7 days' deviation between self-reported and ultrasound examination-based gestational age were compared with women with a deviation of 7 days or less.

Results: Irregular menstrual cycle before conception increases the risk of preeclampsia (7.9% vs. 5.2%, p < 0.05) and low birthweight (6.0% vs. 3.6%, p < 0.05) in spontaneous pregnancies, but reduces the risk of prolonged pregnancy (1.4% vs. 4.7%, p < 0.001).

Conclusion: Irregular menstrual cycle before conception is associated with increased risk of adverse obstetric and neonatal outcome.

Acta Obstetricia Et Gynecologica Scandinavica


Decreased fecundity and sperm DNA methylation patterns

Abstract:
Objective: To evaluate the relationship between epigenetic patterns in sperm and fecundity.
Design: Prospective study.
Setting: Academic andrology and in vitro fertilization laboratory. PATIENT(S): Twenty-seven semen samples from couples who conceived within 2 months of attempting a pregnancy and 29 semen samples from couples unable to achieve a pregnancy within 12 months. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genomewide assessment of differential sperm DNA methylation and standard semen analysis. RESULT(S): We analyzed DNA methylation alterations associated with fecundity in 124 semen samples, and identified regions of interest in 27 semen samples from couples who conceived within 2 months of attempting a pregnancy and a total of 29 semen samples from couples who were unable to achieve a pregnancy within 12 months. No differences in sperm count, sperm morphology, or semen volume were observed between the patients achieving a pregnancy within 2 months of study time and those not obtaining a pregnancy within 12 months. However, using data from the human methylation 450k array analysis we did identify two genomic regions with statistically significantly decreased (false discovery rate <0.01) methylation and three genomic regions with statistically significantly increased methylation in the failure-to-conceive group. The only two sites where decreased methylation was associated with reduced fecundity are at closely related genes known to be expressed in sperm, HSPA1L and HSPA1B. CONCLUSION(S): Our data suggest that there are genomic loci where DNA methylation alterations are associated with decreased fecundity. We have thus identified candidate loci for future study to verify these results and investigate the causative or contributory relationship between altered sperm methylation and decreased fecundity.


Endometriosis diagnosis and staging by operating surgeon and expert review using multiple diagnostic tools: an inter-rater agreement study

Y Xie

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Objective: To determine agreement on endometriosis diagnosis between real-time laparoscopy and subsequent expert review of digital images, operative reports, magnetic resonance imaging (MRI), and histopathology, viewed sequentially.
Design: Inter-rater agreement study.
Setting: Five urban surgical centres.

Population: Women, aged 18-44 years, who underwent a laparoscopy regardless of clinical indication. A random sample of 105 women with and 43 women without a postoperative endometriosis diagnosis was obtained from the ENDO study.

Methods: Laparoscopies were diagnosed, digitally recorded, and reassessed.

Main Outcome Measures: Inter-observer agreement of endometriosis diagnosis and staging according to the revised American Society for Reproductive Medicine criteria. Prevalence and bias-adjusted kappa values (κ) were calculated for diagnosis, and weighted κ values were calculated for staging.

Results: Surgeons and expert reviewers had substantial agreement on diagnosis and staging after viewing digital images (n = 148; mean κ = 0.67, range 0.61-0.69; mean κ = 0.64, range 0.53-0.78, respectively) and after additionally viewing operative reports (n = 148; mean κ = 0.88, range 0.85-0.89; mean κ = 0.85, range 0.84-0.86, respectively). Although additionally viewing MRI findings (n = 36) did not greatly impact agreement, agreement substantially decreased after viewing histological findings (n = 67), with expert reviewers changing their assessment from a positive to a negative diagnosis in up to 20% of cases.

Conclusion: Although these findings suggest that misclassification bias in the diagnosis or staging of endometriosis via visualised disease is minimal, they should alert gynaecologists who review operative images in order to make decisions on endometriosis treatment that operative reports/drawings and histopathology, but not necessarily MRI, will improve their ability to make sound judgments. Tweetable Abstract: Endometriosis diagnosis and staging agreement between expert reviewers and operating surgeons was substantial.

BJOG : an international journal of obstetrics and gynaecology


Live-birth rate in euthyroid women with recurrent miscarriage and thyroid peroxidase antibodies

Rosa Vissenberg

Academic Medical Centre, Centre for Reproductive Medicine, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands. Electronic address: r.vissenberg@amc.uva.nl.

Joris A M van der Post

Academic Medical Centre, Department of Obstetrics and Gynaecology, Amsterdam, The Netherlands.

Abstract: Thyroid autoimmunity with normal thyroid function is associated with recurrent miscarriage (RM), but the association with live birth is less clear. Therefore, we determined the association between thyroid peroxidase antibodies (TPO-Ab) and live-birth rate (LBR) in a retrospective cohort of euthyroid women with unexplained RM. We included 202 women of which 28 were TPO-Ab positive (13.9%) and 174 were TPO-Ab negative. TPO-Ab positive women (n = 10) without levothyroxine treatment had a lower LBR (29%) compared to TPO-Ab negative women (51%) (HR 0.23, 0.07-0.72, p = 0.012). The LBR in women with TPO-Ab receiving levothyroxine was not different compared women without TPO-Ab (60% versus 51%, p = 0.50). In conclusion, TPO-Ab are associated with a lower LBR in euthyroid women with unexplained RM and these women may benefit from treatment with levothyroxine.

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


The placenta is the center of the chronic disease universe

Abstract: Over the past quarter century it has become clear that adult onset chronic diseases like heart disease and type 2 diabetes have their roots in early development. The report by David Barker and colleagues showing an inverse relationship between birthweight and mortality from ischemic heart disease was the first clear-cut demonstration of fetal programming. Because fetal growth depends upon the placental capacity to transport nutrients from maternal blood, it has been a suspected causative agent since the original Barker reports. Epidemiological studies have shown that placental size and shape have powerful associations with offspring disease. More recent studies have shown that maternal phenotypic characteristics, such as body mass index and height, interact with placental size and shape to predict disease with much more precision than does birthweight alone. For example, among people in the Helsinki Birth Cohort, who were born during 1924–1944, the risk for acquiring colorectal cancer increased as the placental surface became longer and more oval. Among people in whom the difference between the length and breadth of the surface exceeded 6 cm, the hazard ratio for the cancer was 2.3 (95% CI 1.2–4.7, p=0.003) compared with those in whom there was no difference. Among Finnish men, the hazard ratio for coronary heart disease was 1.07 (1.02–1.13, P =0.01) per 1% increase in the placental weight/birthweight ratio. Thus, it appears that the ratio of birthweight to placental weight, known as placental efficiency, predicts cardiovascular risk as well. Babies born with placentas at the extremes of efficiency are more vulnerable for adult onset chronic diseases. Recent evidence suggests that placental growth patterns are sex specific. Boys’ placentas are, in general, more efficient than those made by girls. Another recent discovery is that the size, shape and efficiencies of the placenta can change over years of time with very narrow confidence limits. This suggests that the growth of the placenta within a population of women is strongly affected by their nutritional environment. Even though it is known that an individual placenta can expand to improve its nutrient acquisition capacity in the first 2/3(rd) of gestation, the mechanisms by which placentas grow in response to a specific nutritional environment are not known. Discovering those mechanisms is the task of the current generation of scientists. While it may seem obvious that good nutrition is highly important for women who are pregnant because it supports optimal placentation and fetal development, more research is needed to determine the mechanisms by which maternal nutrition, placenta growth and fetal health are related.

American Journal of Obstetrics and Gynecology


Alcohol intake, reproductive hormones, and menstrual cycle function: a prospective cohort study

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract:
Background: Although habitual low-to-moderate alcohol intake has been linked with reduced all-cause mortality and morbidity, the effect of recent alcohol intake on female reproductive function has not been clearly established.

Objective: We assessed the relation between acute alcohol consumption, reproductive hormones, and markers of menstrual cycle dysfunction including sporadic anovulation, irregular cycle length, luteal phase deficiency, long menses, and heavy blood loss.
Design: A total of 259 healthy, premenopausal women from Western New York were followed for ≤2 menstrual cycles (2005-2007) and provided fasting blood specimens during ≤8 visits/cycle and four 24-h dietary recalls/cycle. Linear mixed models were used to estimate associations between previous day's alcohol intake and hormone concentrations, whereas Poisson regression was used to assess RR of cycle-average alcohol intake and menstrual cycle function.

Results: For every alcoholic drink consumed, the geometric mean total and free estradiol, total and free testosterone, and luteinizing hormone were higher by 5.26% (95% CI: 1.27%, 9.41%), 5.82% (95% CI: 1.81%, 9.99%), 1.56% (95% CI: 0.23%, 2.90%), 1.42% (95% CI: 0.02%, 2.84%), and 6.18% (95% CI: 2.02%, 10.52%), respectively, after adjustment for age, race, percentage of body fat, perceived stress, pain-medication use, sexual activity, caffeine, and sleep. Binge compared with nonbinge drinking (defined as reporting ≥4 compared with <4 drinks/d, respectively) was associated with 64.35% (95% CI: 18.09%, 128.71%) and 63.53% (95% CI: 17.41%, 127.73%) higher total and free estradiol. No statistically significant associations were shown between cycle-average alcohol intake and menstrual cycle function.

Conclusion: Although recent moderate alcohol intake does not appear to have adverse short-term effects on menstrual cycle function, including sporadic anovulation, potential protective and deleterious long-term effects of alterations in reproductive hormones on other chronic diseases warrant additional investigation.

The American journal of clinical nutrition


Perimenopause and menopause as oestrogen deficiency while ignoring progesterone

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre


Od eugeniki do procedury zapłodnienia in vitro

Gruszka Marta Joanna

Cardinal Stefan Wyszynski University in Warsaw

Abstract: In vitro fertilization (IVF) is a method known almost all over the world, by which modern man is trying to cope with the problem of infertility. The aim of this article is to show the eugenic roots of in vitro and to attempt to reconciliate the supporters and opponents of this controversial procedure at a NaProTechnological plane. In order to achieve this, the author characterizes IVF from the technical, medical and legal point of view. Then, the article shows the relationship between the in vitro procedure and eugenic thought. The third section contextualizes the problem of artificial insemination in the contemporary, human uncritical faith in technological progress. The last part of this article directs the reader's attention towards NaProTechnology – a method of infertility treatement which can engage both the supporters and the opponents of IVF.


Associations of Protein Intake and Protein Source with Bone Mineral Density and  Fracture Risk: A Population-Based Cohort Study

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Christopher S Kovacs

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

Abstract:
High dietary protein has been hypothesized to cause lower bone mineral density (BMD) and greater fracture risk. Previous results are conflicting and few studies have assessed potential differences related to differing protein sources.
Objective: To determine associations between total protein intake, and protein intake by source (dairy, non-dairy animal, plant) with BMD, BMD change, and incident osteoporotic fracture. DESIGN/Setting: Prospective cohort study (Canadian Multicentre Osteoporosis Study). Participants/Measures: Protein intake was assessed as percent of total energy intake (TEI) at Year 2 (1997-99) using a food frequency questionnaire (N=6510). Participants were contacted annually to ascertain incident fracture. Total hip and lumbar spine BMD was measured at baseline and Year 5. Analyses were stratified by group (men 25-49 y, men 50+ y, premenopausal women 25-49 y, and postmenopausal women 50+ y) and adjusted for major confounders. Fracture analyses were limited to those 50+ y.

Results: Intakes of dairy protein (with adjustment for BMI) were positively associated with total hip BMD among men and women aged 50+ y, and in men aged 25-49. Among adults aged 50+ y, those with protein intakes of <12% TEI (women) and <11% TEI (men) had increased fracture risk compared to those with intakes of 15% TEI. Fracture risk did not significantly change as intake increased above 15% TEI, and was not significantly associated with protein source.

Conclusions: In contrast to hypothesized risk of high protein, we found that for adults 50+ y, low protein intake (below 15% TEI) may lead to increased fracture risk. Source of protein was a determinant of BMD, but not fracture risk.

The Journal of Nutrition, Health & Aging


Hormonal contraception and pelvic floor function: a systematic review

Abstract:
INTRODUCTION AND HYPOTHESIS: Hormonal contraceptive use is common practice worldwide. Although the effects of hormone treatments in the pelvic region are well established, there is no clear evidence regarding their effects on incontinence, bladder, bowel, vaginal and sexual symptoms in premenopausal women. We hypothesized that hormonal contraceptives affect pelvic floor function. We therefore performed a comprehensive systematic review of published studies to determine the influence of hormonal contraception on pelvic floor functions.
Methods: Electronic literature databases were searched from database inception to March 2015. Keywords and medical subject headings searched for included terms and word variations for 'contraception', and 'bowel', 'vaginal', 'sexual' and 'urinary' symptoms. Studies were eligible if they looked at these symptoms in women taking hormonal contraception. Two reviewers independently screened studies for inclusion, and extracted data on study characteristics, quality and results. Data were combined where possible.

Results: Of the 429 citations identified, 13 studies were included in the review. Data were meta-analysed where possible and presented as prevalence. The results indicate statistically significant links between interstitial cystitis and oral contraceptive use at any point (ever) (OR 2.31, 95 % CI 1.03 - 5.16; p = 0.04) and vulvar vestibulitis and current oral contraceptive use (OR 2.10, 95 % CI 1.26 - 3.49; p = 0.004). The evidence is unclear in other areas.

Conclusions: Our results indicate that oral contraceptives may have an effect on pelvic floor function. They could increase the risk of painful bladder and vulvar vestibulitis, but their effect on dyspareunia is inconsistent. However, robustly collected prospective data to establish causal associations are needed.


Prevalence of hyperprolactinemia and thyroid disorders among patients with  abnormal uterine bleeding

Abstract:
Objective: To evaluate the prevalence of hyperprolactinemia and thyroid disorders among patients with abnormal uterine bleeding (AUB) compared with matched controls.

Methods: In 2013-2014, an observational study of women with AUB (group A) and women with regular menstruation (group B) was undertaken at one center in Egypt and one in the United Arab Emirates. Eligible women were aged 20-35 years and were not obese. Participants underwent clinical examinations, vaginal ultrasonography, office hysteroscopy (in selected cases), and measurement of hormone levels.

Results: Hyperprolactinemia was present in 17 (16.2%) of 105 patients in group A and 4 (3.2%) of 125 patients in group B (P=0.009). In group A, a high thyroid-stimulating hormone (TSH) level was observed in 8 (7.6%) patients and low levels of free triiodothyronine/thyroxine were found in 5 (4.8%) patients, compared with 2 (1.6%) patients and 1 (0.8%) patient in group B (P=0.012 and P=0.008, respectively). Polymenorrhea was the most frequent presentation of AUB (n=60 [57.1%]). Five (29.4%) patients with hyperprolactinemia had galactorrhea. In group A, 8 (47.1%) patients with a high TSH had hyperprolactinemia, whereas 1 (1.1%) patient with a high TSH had a normal prolactin value (P=0.008).

Conclusion: Screening by evaluating prolactin and thyroid hormone levels is recommended for all patients with AUB, even in the absence of galactorrhea.

International Journal of Gynaecology and Obstetrics: the Official Organ of the  International Federation of Gynaecology and Obstetrics


Invited Commentary: The Association Between Marijuana Use and Male Reproductive Health

Abstract: Approximately 15% of all couples are unable to conceive after a year and are labeled infertile. In recent years, increasing attention has been given to lifestyle factors that may impact fertility. In the United States, it is estimated that there are more than 17 million current users of marijuana with 4.6 million using marijuana almost daily. Although common, to date, little data exist on the impact of marijuana use on male fertility. In the current issue of the Journal, Gundersen et al. (Am J Epidemiol. 2015;182(6):473-481) provide data examining the relationship between marijuana use and semen quality from young men recruited out of the general Danish population. Men who reported daily marijuana use displayed significant lower sperm concentration and sperm counts compared with nonusers, while testosterone levels were higher. The current report provides important information for patients and providers regarding the negative association of marijuana use on semen quality. Although the benefit of marijuana cessation on recovery is uncertain, further study on the impact of marijuana use on male reproductive health is warranted as more states explore marijuana legalization.


Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss

Laurie L Lesher

Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Room 2B200 SOM, 50 North Medical Drive, Salt Lake City, UT 84132, USA.

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract:
Background: Several lines of evidence suggest that male embryos may have greater vulnerability than female embryos to disordered inflammation; therefore, antiinflammatory drugs, such as low-dose aspirin (LDA), may alter the sex ratio. Here, we assessed the effect of LDA on male live birth and male offspring, incorporating pregnancy losses (n = 56) via genetic assessment, as part of a parallel-design, block-randomized, placebo-controlled trial of preconception LDA.

Methods: Participants (615 treated with LDA, 613 treated with placebo) ranged in age from 18 to 40 years of age, with 1 to 2 prior pregnancy losses. We estimated the intention-to-treat (ITT) risk ratio (RR) and 95% CI and assessed interaction with baseline high-sensitivity C-reactive protein (hsCRP) serum concentration - a marker of systemic inflammation.

Results: Among the 1,078 women who completed follow-up (535 treated with LDA, 543 treated with placebo), the male live birth ITT RR equaled 1.31 (95% CI: 1.07-1.59). With increasing tertile of hsCRP, the proportion of males at birth decreased in the placebo group, and the effect of LDA on male live birth increased (first tertile: 48% male in LDA vs. 52% in placebo, ITT RR = 0.97, 95% CI: 0.70-1.35; second tertile: 57% male in LDA vs. 43% in placebo, ITT RR = 1.36, 95% CI: 0.98-1.90; third tertile: 53% male in LDA vs. 35% in placebo, ITT RR = 1.70, 95% CI: 1.13-2.57; P interaction = 0.03). Analysis of pregnancy with male offspring yielded similar results.

Conclusion: Initiation of LDA prior to conception restored numbers of male live births and pregnancy with male offspring among women with 1 to 2 prior pregnancy losses. Moreover, our data suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos.

Trial Registration: ClinicalTrials.gov NCT00467363.

Funding: Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health.


Trying to conceive after a pregnancy loss: how long should couples wait?


Single-Use Energy Sources and Operating Room Time for Laparoscopic Hysterectomy:  A Randomized Controlled Trial

Mary B Holloran-Schwartz

St. Louis University School of Medicine, Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics, Gynecology, and Women's Health, St. Louis, MO, USA.

Abstract:
STUDY Objectives: To compare the intraoperative direct costs of a single-use energy device with reusable energy devices during laparoscopic hysterectomy.
Design: A randomized controlled trial (Canadian Task Force Classification I).
Setting: An academic hospital.

Patients: Forty-six women who underwent laparoscopic hysterectomy from March 2013 to September 2013.

Interventions: Each patient served as her own control. One side of the uterine attachments was desiccated and transected with the single-use device (Ligasure 5-mm Blunt Tip LF1537 with the Force Triad generator). The other side was desiccated and transected with reusable bipolar forceps (RoBi 5 mm), and transected with monopolar scissors using the same Covidien Force Triad generator. The instrument approach used was randomized to the attending physician who was always on the patient's left side. Resident physicians always operated on the patient's right side and used the converse instruments of the attending physician. MEASUREMENTS AND

MAIN Results: Start time was recorded at the utero-ovarian pedicle and end time was recorded after transection of the uterine artery on the same side. Costs included the single-use device; amortized costs of the generator, reusable instruments, and cords; cleaning and packaging of reusable instruments; and disposal of the single-use device. Operating room time was $94.14/min. We estimated that our single use-device cost $630.14 and had a total time savings of 6.7 min per case, or 3.35 min per side, which could justify the expense of the device. The single-use energy device had significant median time savings (-4.7 min per side, p < .001) and total intraoperative direct cost savings ($254.16 per case).

Conclusions: A single-use energy device that both desiccates and cuts significantly reduced operating room time to justify its own cost, and it also reduced total intraoperative direct costs during laparoscopic hysterectomy in our institution. Operating room cost per minute varies between institutions and must be considered before generalizing our results.

Journal of Minimally Invasive Gynecology


Ovarian reserve assessment in users of oral contraception seeking fertility  advice on their reproductive lifespan

Abstract:
STUDY Question: To what extent does oral contraception (OC) impair ovarian reserve parameters in women who seek fertility assessment and counselling to get advice on whether their remaining reproductive lifespan is reduced?

SUMMARY ANSWER: Ovarian reserve parameters defined by anti-Müllerian hormone (AMH), antral follicle count (AFC) and ovarian volume were found to be significantly decreased by 19% (95% CI 9.1-29.3%), 18% (95% CI 11.2-24.8%) and 50% (95% CI 45.1-53.7%) among OC users compared with non-users.

WHAT IS KNOWN ALREADY: AMH and AFC have proved to be reliable predictors of ovarian ageing. In women, AMH declines with age and data suggest a relationship with remaining reproductive lifespan and age at menopause. OC may alter parameters related to ovarian reserve assessment but the extent of the reduction is uncertain.

STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 887 women aged 19-46 attending the Fertility Assessment and Counselling Clinic (FACC) from 2011 to 2014 comparing ovarian reserve parameters in OC users with non-OC users.

PARTICIPANTS/MATERIALS, SETTING, Methods: The FAC Clinic was initiated to provide individual fertility assessment and counselling. All women were examined on a random cycle day by a fertility specialist. Consultation included; transvaginal ultrasound (AFC, ovarian volume, pathology), a full reproductive history and AMH measurement. Women were grouped into non-users and users of OC (all combinations of estrogen-progestin products and the contraceptive vaginal ring). Non-users included women with an intrauterine device (IUD) or no hormonal contraception.

MAIN RESULTS AND THE ROLE OF CHANCE: Of the 887 women, 244 (27.5%) used OC. In a linear regression analyses adjusted for age, ovarian volume was 50% lower (95% CI 45.1-53.7%), AMH was 19% lower (95% CI 9.1-29.3%), and AFC was 18% lower (95% CI 11.2-24.8%) in OC users compared with non-users. Comparison of AMH at values of <10 pmol/l OC was found to have a significant negative influence on AMH (OR 1.6, 95% CI 1.1; 2.4, P = 0.03). Furthermore, we found a significant decrease in antral follicles sized 5-7 mm (P < 0.001) and antral follicles sized 8-10 mm (P < 0.001) but an increase in antral follicles sized 2-4 mm (P = 0.008) among OC users. The two groups (OC users versus non-users) were comparable regarding age, BMI, smoking and maternal age at menopause. LIMITATIONS, REASON FOR CAUTION: The study population comprised women attending the FAC Clinic. Recruitment was based on self-referral, which could imply a potential selection bias. Ovarian reserve was examined at a random cycle day. However, both AMH and AFC can be assessed independently of the menstrual cycle. The accuracy in predicting residual reproductive lifespan is still needed in both users and non-users of OC.

WIDER IMPLICATIONS OF THE Findings: OC has a major impact on the ovarian volume, and a moderate impact on AFC and AMH with a shift towards the smaller sized antral follicle subclasses. The most evident reduction occurs in the antral follicles of 5-7 and 8-10 mm with the highest number of AMH secreting granulosa cells. It is essential to be aware of the impact of OC use on ovarian reserve parameters when guiding OC users on their fertility status and reproductive lifespan.

STUDY FUNDING/COMPETING INTERESTS: The FAC Clinic was established in 2011 as part of the ReproHigh collaboration. This study received funding through the Capital Region Research Fund and by EU-regional funding. There are no competing interests.

TRIAL REGISTRATION NUMBER: The biobank connected to FAC Clinic is approved by the Scientific Ethical Committee (H-1-2011-081).


Body composition and resting metabolic rate of perimenopausal women using  continuous progestogen contraception

Abstract:
Objective: The effect on body composition and in particular on fat mass (FM) of 12 months' use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause.

Methods: An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months.

Results: FM did not change in the control group (- 0.5 ± 1.6%) but significantly increased in the LNG-IUS group (+ 1.1 ± 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8 ± 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG or the LNG-IUS showed a non-significant increase in body weight, body mass index and waist circumference. RMR did not significantly vary in the control group (- 3.8 ± 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG-IUS (115.5 ± 531.8 kJ/ 24 h) and DSG groups (305.9 ± 556.9 kJ/24 h).

Conclusions: The results of this preliminary study seem to indicate that in perimenopausal women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may favour FM accumulation.

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


Ovulation Prevalence in Women with Spontaneous Normal-Length Menstrual Cycles - A  Population-Based Cohort from HUNT3, Norway

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Marit Naess

HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.

Arnulf Langhammer

Abstract:
Background: Ovulatory menstrual cycles are essential for women's fertility and needed to prevent bone loss. There is a medical/cultural expectation that clinically normal menstrual cycles are inevitably ovulatory. Currently within the general population it is unknown the proportion of regular, normal-length menstrual cycles that are ovulatory. Thus, the objective of this study was to determine the population point prevalence of ovulation in premenopausal, normally menstruating women. The null hypothesis was that such cycles are ovulatory.

Methods: This is a single-cycle, cross-sectional, population-based study-a sub-study of the HUNT3 health study in the semi-rural county (Nord Trøndelag) in mid-Norway. Participants included >3,700 spontaneously (no hormonal contraception) menstruating women, primarily Caucasian, ages 20-49.9 from that county. Participation rate was 51.9%. All reported the date previous flow started. A single, random serum progesterone level was considered ovulatory if ≥9.54 nmol/L on cycle days 14 to -3 days before usual cycle length (CL).

Results: Ovulation was assessed in 3,168 women mean age 41.7 (interquartile range, [IQR] 36.8 to 45.5), cycle length 28 days (d) (IQR 28 to 28) and body mass index (BMI) 26.3 kg/m2 (95% CI 26.1 to 26.4). Parity was 95.6%, 30% smoked, 61.3% exercised regularly and 18% were obese. 1,545 women with a serum progesterone level on cycle days 14 to -3 were presumed to be in the luteal phase. Of these, 63.3% of women had an ovulatory cycle (n = 978) and 37% (n = 567) were anovulatory. Women with/ without ovulation did not differ in age, BMI, cycle day, menarche age, cigarette use, physical activity, % obesity or self-reported health. There were minimal differences in parity (96.7% vs. 94.5%, P = 0.04) and major differences in progesterone level (24.5 vs. 3.8 nmol/L, P = 0.001).

Conclusion: Anovulation in a random population occurs in over a third of clinically normal menstrual cycles.


Practice Bulletin Summary No. 152: Emergency Contraception

Abstract: Emergency contraception, also known as postcoital contraception, is therapy used to prevent pregnancy after an unprotected or inadequately protected act of sexual intercourse. Common indications for emergency contraception include contraceptive failure (eg, condom breakage or missed doses of oral contraceptives) and failure to use any form of contraception (1-3). Although oral emergency contraception was first described in the medical literature in the 1960s, the U.S. Food and Drug Administration (FDA) approved the first dedicated product for emergency contraception in 1998. Since then, several new products have been introduced. Methods of emergency contraception include oral administration of combined estrogen-progestin, progestin only, or selective progesterone receptor modulators and insertion of a copper intrauterine device (IUD). Many women are unaware of the existence of emergency contraception, misunderstand its use and safety, or do not use it when a need arises (4-6). The purpose of this Practice Bulletin is to review the evidence for the efficacy and safety of available methods of emergency contraception and to increase awareness of these methods among obstetrician-gynecologists and other gynecologic providers.


Pain typology and incident endometriosis

Abstract:
STUDY QUESTION: What are the pain characteristics among women, with no prior endometriosis diagnosis, undergoing laparoscopy or laparotomy regardless of clinical indication?

SUMMARY ANSWER: Women with surgically visualized endometriosis reported the highest chronic/cyclic pain and significantly greater dyspareunia, dysmenorrhea, and dyschezia compared with women with other gynecologic pathology (including uterine fibroids, pelvic adhesions, benign ovarian cysts, neoplasms and congenital Müllerian anomalies) or a normal pelvis.

WHAT IS KNOWN ALREADY: Prior research has shown that various treatments for pain associated with endometriosis can be effective, making identification of specific pain characteristics in relation to endometriosis necessary for informing disease diagnosis and management.

STUDY DESIGN, SIZE, DURATION: The study population for these analyses includes the ENDO Study (2007-2009) operative cohort: 473 women, ages 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at one of 14 surgical centers located in Salt Lake City, UT or San Francisco, CA. Women with a history of surgically confirmed endometriosis were excluded.

PARTICIPANTS/MATERIALS, SETTING AND

METHODS: Endometriosis was defined as surgically visualized disease; staging was based on revised American Society for Reproductive Medicine (rASRM) criteria. All women completed a computer-assisted personal interview at baseline specifying 17 types of pain (rating severity via 11-point visual analog scale) and identifying any of 35 perineal and 60 full-body front and 60 full-body back sites for which they experienced pain in the last 6 months.

MAIN RESULTS AND THE ROLE OF CHANCE: There was a high prevalence (≥30%) of chronic and cyclic pelvic pain reported by the entire study cohort regardless of post-operative diagnosis. However, women with a post-operative endometriosis diagnosis, compared with women diagnosed with other gynecologic disorders or a normal pelvis, reported more cyclic pelvic pain (49.5% versus 31.0% and 33.1%, P < 0.001). Additionally, women with endometriosis compared with women with a normal pelvis experienced more chronic pain (44.2 versus 30.2%, P = 0.04). Deep pain with intercourse, cramping with periods, and pain with bowel elimination were much more likely reported in women with versus without endometriosis (all P < 0.002). A higher percentage of women diagnosed with endometriosis compared with women with a normal pelvis reported vaginal (22.6 versus 10.3%, P < 0.01), right labial (18.4 versus 8.1%, P < 0.05) and left labial pain (15.3 versus 3.7%, P < 0.01) along with pain in the right/left hypogastric and umbilical abdominopelvic regions (P < 0.05 for all). Among women with endometriosis, no clear and consistent patterns emerged regarding pain characteristics and endometriosis staging or anatomic location.

LIMITATIONS, REASONS FOR CAUTION: Interpretation of our findings requires caution given that we were limited in our assessment of pain characteristics by endometriosis staging and anatomic location due to the majority of women having minimal (stage I) disease (56%) and lesions in peritoneum-only location (51%). Significance tests for pain topology related to gynecologic pathology were not corrected for multiple comparisons.

WIDER IMPLICATIONS OF THE FINDINGS: Results of our research suggest that while women with endometriosis appear to have higher pelvic pain, particularly dyspareunia, dysmenorrhea, dyschezia and pain in the vaginal and abdominopelvic area than women with other gynecologic disorders or a normal pelvis, pelvic pain is commonly reported among women undergoing laparoscopy, even among women with no identified gynecologic pathology. Future research should explore causes of pelvic pain among women who seek out gynecologic care but with no apparent gynecologic pathology. Given our and other's research showing little correlation between pelvic pain and rASRM staging among women with endometriosis, further development and use of a classification system that can better predict outcomes for endometriosis patients with pelvic pain for both surgical and nonsurgical treatment is needed.

STUDY FUNDING/COMPETING INTERESTS: Supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001406-02). The authors have no potential competing interests.


Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese  Pregnant Women: A Randomized Controlled Trial

Rosario D'Anna

Department of Obstetrics and Gynecology, University of Messina, Italy.

Abstract:
Objective: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women.

Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (α=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test.

Results: From January 2011 to April 2014, 220 pregnant women at 12-13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17-0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, -1.0±3.1 compared with 0.1±1.8 (P=.048).

Conclusion: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance.

CLINICAL Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.


The Role of Kisspeptin in the Onset of Puberty and in the Ovulatory Mechanism: A  Mini-review

Hernán Rioseco

Pontificia Universidad Católica de Chile

BÁrbara Carrera

Reproductive Health Research Institute, Biomedical Division, Santiago, Chile.

Abstract: The onset of puberty has been a fascinating topic for reproductive endocrinologists for decades; however, its underlying physiological mechanisms have remained elusive until recently. The discovery and understanding of the effects exerted by the peptide hormone kisspeptin have shed light on this research area. This review is aimed to discuss the functions of kisspeptin, with special focus on its role in the onset of puberty and in the ovulatory mechanism. The points under discussion are (1) the characteristics of kisspeptin and its receptor, (2) the relevance of this hormone and its interaction with leptin in the onset of puberty, (3) the role of kisspeptin in the ovulatory mechanism based on its differential expression at hypothalamic nuclei, which is modulated by sex steroid hormones, and (4) the clinical relevance of kisspeptin and its antagonists in new therapeutic strategies for the treatment of various reproductive pathologies. All of this explains the revolution that kisspeptin has caused among researchers working in the field of gynecological endocrinology and reproductive biology.

Journal of Pediatric and Adolescent Gynecology


The influence of contraception, abortion, and natural family planning on divorce rates as found in the 2006-2010 National Survey of Family Growth

Abstract: The purpose of this study was to determine the influence of contraception, abortion, and natural family planning (NFP) on divorce rates of US women of reproductive age. The variables of importance of religion and frequency of church attendance were also included in the analysis. The study involved 5,530 reproductive age women in the (2006-2010) National Survey of Family Growth who indicate that they were ever married. Among the women who ever used NFP only 9.6 percent were currently divorced compared with the 14.4 percent who were currently divorced among the women who never used NFP (x (2) = 5.34, P < 0.21). Odds ratio analysis indicated that ever having an abortion, sterilization, and/or methods of contraception increased the likelihood of divorce - up to two times. Frequency of church attendance decreased the risk of divorce. Although there is less divorce among NFP users the reason might be due to their religiosity. Lay summary: Providers of natural family planning (NFP) frequently mention that couples who practice NFP have fewer divorces compared to couples who use contraception. Evidence for this comment is weak. This study utilized a large data set of 5,530 reproductive age women to determine the influence that contraception, sterilization, abortion, and NFP has on divorce rates. Among the women participants who ever used NFP only 9.6 percent were currently divorced compared with the 14.4 percent who used methods of contraception, sterilization or abortion as a family planning method. Frequency of church attendance also reduced the likelihood of divorce.