Influence of a Specialized Trigonella foenum-graecum Seed Extract (Libifem), on Testosterone, Estradiol and Sexual Function in Healthy Menstruating Women, a Randomised Placebo Controlled Study

Abstract: The aim of the study was to evaluate the effect of Trigonella foenum-graecum (fenugreek) seed extract on sex hormones and sexual function in healthy menstruating women who reported low sexual drive. This short term, single site, double blind, randomised, placebo-controlled study was conducted on 80 women, aged 20 to 49 years. Participants were randomised to either an oral dose of a standardised T. foenum-graecum seed extract (libifem) at a dose of 600 mg/day or placebo over two menstrual cycles. Dehydroepiandrosterone sulfate, progesterone, androstenedione, total and free testosterone, estradiol (E2), luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and cholesterol were measured at baseline and 8 weeks. The individual aspects of sexual function were measured using the Derogatis interview for sexual functioning and female sexual function index self-administered questionnaires. Stress, fatigue and quality of the relationship with partner were also measured using the PSS (Perceived Stress Scale), MFI-20 (Multidimensional Fatigue Inventory) and DAS (Dyadic Adjustment Scale) quality of life measures, respectively. There was a significant increase in free testosterone and E2 in the active group as well as sexual desire and arousal compared with the placebo group. The results indicate that this extract of T. foenum-graecum may be a useful treatment for increasing sexual arousal and desire in women.


The Recent Review of the Genitourinary Syndrome of Menopause

Abstract: The genitourinary syndrome of menopause (GSM) is a new term that describes various menopausal symptoms and signs including not only genital symptoms (dryness, burning, and irritation), and sexual symptoms (lack of lubrication, discomfort or pain, and impaired function, but also urinary symptoms (urgency, dysuria, and recurrent urinary tract infections). The terms vulvovaginal atrophy and atrophic vaginitis, which were generally used until recently, had a limitation because they did not cover the full spectrum of symptoms and did not imply that the symptoms are related to a decreased estrogen level in menopause. Since the GSM may have a profound negative impact on the quality of life of postmenopausal women, women should be made aware of these problems and treated with an appropriate effective therapy. Thus, in this review we introduce new terminology and discuss the importance of comprehension of GSM and the necessity of active treatment of this syndrome in postmenopausal women.


Nothing Boring About Boron

Nothing Boring About Boron

Abstract: The trace mineral boron is a micronutrient with diverse and vitally important roles in metabolism that render it necessary for plant, animal, and human health, and as recent research suggests, possibly for the evolution of life on Earth. As the current article shows, boron has been proven to be an important trace mineral because it (1) is essential for the growth and maintenance of bone; (2) greatly improves wound healing; (3) beneficially impacts the body's use of estrogen, testosterone, and vitamin D; (4) boosts magnesium absorption; (5) reduces levels of inflammatory biomarkers, such as high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α); (6) raises levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase; (7) protects against pesticide-induced oxidative stress and heavy-metal toxicity; (8) improves the brains electrical activity, cognitive performance, and short-term memory for elders; (9) influences the formation and activity of key biomolecules, such as S-adenosyl methionine (SAM-e) and nicotinamide adenine dinucleotide (NAD(+)); (10) has demonstrated preventive and therapeutic effects in a number of cancers, such as prostate, cervical, and lung cancers, and multiple and non-Hodgkin's lymphoma; and (11) may help ameliorate the adverse effects of traditional chemotherapeutic agents. In none of the numerous studies conducted to date, however, do boron's beneficial effects appear at intakes > 3 mg/d. No estimated average requirements (EARs) or dietary reference intakes (DRIs) have been set for boron-only an upper intake level (UL) of 20 mg/d for individuals aged ≥ 18 y. The absence of studies showing harm in conjunction with the substantial number of articles showing benefits support the consideration of boron supplementation of 3 mg/d for any individual who is consuming a diet lacking in fruits and vegetables or who is at risk for or has osteopenia; osteoporosis; osteoarthritis (OA); or breast, prostate, or lung cancer.

Integrative medicine (Encinitas, Calif.)


Recurrence of endometriosis: risk factors, mechanisms and biomarkers

Gürkan Bozdağ

Department of Obstetrics and Gynecology, Reproductive Endocrinology and Infertility Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Abstract: While the incidence of endometriosis is up to 40-60% in women with severe dysmenorrhea/chronic pelvic pain, patients with subfertility carries a risk up to 20-30%. In symptomatic patients, although medical therapy is preferred in women with endometriosis, surgery might be needed in nonresponders or patients with an endometrioma. Following the surgery, recurrence of the disease and/or symptoms might be still noticed which will progressively increase as times goes by. Nevertheless, some risk factors have been identified for the risk of recurrence that decreases the success of the procedure. Those risk factors might be classified as patient-disease related and surgery-associated variables. Herein, we will address about the management of endometriosis regarding the risk factors for relapse, mechanisms of recurrence and potential biomarkers to predict the event.


Comparison of Abstinence and Coital Frequency Between 2 Natural Methods of Family  Planning

Abstract:
Introduction: The length of periodic abstinence, due to overestimation of the fertile phase of the menstrual cycle, is often a cause for dissatisfaction, discontinuation, and user error with natural family planning (NFP) methods. The objective of this research was to compare the length of required abstinence (ie, estimated fertility) and coital frequency between 2 NFP methods.

Methods: This was an analysis of data from a 12-month prospective comparison study in which participants were randomized into either an electronic hormonal fertility monitor (EHFM) group or a cervical mucus monitoring (CMM) group-both of which included a fertility algorithm as a double check for the beginning and end of the estimated fertile window. The number of days of estimated fertility and coitus was extracted from each menstrual cycle of data, and t tests were used to compare the means of these 2 variables between the 2 NFP methods.

Results: The study involved 197 women (mean [SD] age 29.7 [5.4]) who used the EHFM to estimate the fertile window and 160 women (mean [SD] age 30.4 [5.3]) who used CMM to estimate the fertile window. They produced 1,669 menstrual cycles of data. After 12 months of use, the EHFM group had statistically fewer days of estimated fertility than the CMM group (mean [SD] days, 13.25 [2.79] vs 13.68 [2.99], respectively; t = 2.07; P = .039) and significantly more coitus (mean [SD] coital acts, 4.22 [3.16] vs 4.05 [2.88], respectively; t = 1.17; P = .026).

DISCUSSION: The use of the EHFM seems to provide more objectivity and confidence in self-estimating the fertile window and using nonfertile days for intercourse when avoiding pregnancy.


Steroidal contraceptives and bone fractures in women: evidence from observational  studies

Kathryn M Curtis

Centers for Disease Control and Prevention

Abstract:
Background: Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life.

Objectives: We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women. SEARCH

Methods: Through June 2015, we searched for observational studies. The databases included PubMed, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports.
Selection Criteria: We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture.
Data Collection and Analysis: Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis.

MAIN Results: We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use. AUTHORS'

Conclusions: Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.

The Cochrane Database of Systematic Reviews


Development and initial validation of a fertility experiences questionnaire

Shawn E Gurtcheff

Utah Fertility Center, 1446 W. Pleasant Grove Blvd, 84062, Pleasant Grove, UT, USA.

Abstract:
Background: Many women throughout the world have history of subfertility (resolved or unresolved), but much remains unknown about services and treatments chosen.

Methods: We developed a mixed-mode fertility experiences questionnaire (FEQ) in 2009 through literature review and iterative pilot work to optimize question format and mode of administration. The focus of the FEQ is to collect data retrospectively on time at risk for pregnancy, fertility treatments received and declined, pregnancy, time to pregnancy and pregnancy outcomes. We conducted a validation of key elements of the FEQ with comparison to medical records in 2009 and 2010. The validation sample was selected from women initially seen at a specialized fertility treatment center in Utah in 2004.

Results: The FEQ was optimized with two components: 1) written (paper or web-based), self-administered, followed by 2) telephoneadministered questions. In 63 patients analyzed, high levels of correlation were identified between patient self-report and medical records for the use of intrauterine insemination and assisted reproductive technology, pregnancy and live birth histories, time at risk for pregnancy and time to pregnancy. There was low correlation between medical records and self-report for the use of oral ovulation drugs and injectable ovulation drugs. Compared to the medical record, the FEQ was over 90% sensitive for all elements, except injectable ovulation drugs (70% sensitivity).

Conclusions: The FEQ accurately captured elements of fertility treatment history at 5-6 years after the first visit to a specialty clinic.


Herbal Medicines Use During Pregnancy: A Review from the Middle East

Lisha J John

Department of Pharmacology, Gulf Medical University, Ajman, United Arab Emirates.

Nisha Shantakumari

Department of Physiology, Gulf Medical University, Ajman, United Arab Emirates.

Abstract: The prevalence of the herbal medicines use is on the rise across the world, especially amongst pregnant women. The scenario in the Middle Eastern region was reviewed to explore the prevalence, usage pattern, motivation, and attitude towards use of herbal medicine by pregnant women. Literature published up to December 2012 showed the prevalence of herbal medicine use varied between 22.3-82.3%, implying a rising trend in the utilization of herbal medicine during pregnancy. The most common herbs used were peppermint, ginger, thyme, chamomile, sage, aniseed, fenugreek, and green tea. The most common reasons for use included the treatment of gastrointestinal disorders and cold and flu symptoms. The majority of women used these products during their first trimester, and did not reveal this information to their physician. Most women were advised by family and friends to use herbal medicines and believed they were more effective and had fewer side effects than modern medicine especially during pregnancy. In conclusion, the use of herbal medicine is prevalent among pregnant women in the Middle Eastern region and healthcare providers need to seek information pertaining to their use.


Fertility treatments and adverse perinatal outcomes in a population-based sampling of births in Florida, Maryland, and Utah: a cross-sectional study

Abstract:
OBJECTIVE: To investigate perinatal outcomes associated with fertility treatments, including assisted reproductive technology (ART), intrauterine insemination with ovulation stimulation (IUI), and ovulation stimulation alone (OS).

DESIGN: Population-representative cross-sectional survey of women with live births, 2004-2008.

SETTING: Florida, Maryland, and Utah, USA.

SAMPLE: 21 803 women, weighted to represent 1 022 597 women.

METHODS: Survey and birth certificate data were analysed with logistic regression models adjusted for age, education, race, income, and parity, using separate models for singletons and all births. We used two referent groups: (1) women who never used fertility treatment and (2) subfertile women conceiving without treatment.

MAIN OUTCOME MEASURES: Preterm birth (<37 weeks), very preterm birth (<34 weeks), low birthweight (<2500 g), and very low birthweight (<1500 g).

RESULTS: Referent group 1: In singletons, ART was associated with preterm birth (OR 3.28; 95% CI 1.74, 6.20) and low birthweight (OR 2.91; 95% CI 1.99, 4.26). OS was also associated with low birthweight (OR 1.62; 95% CI 1.19, 2.19). Including all births, treatment was associated with preterm birth and low birthweight: ART (OR 6.21; 95% CI 4.21, 9.16 and OR 6.51; 95% CI 4.85, 8.73); IUI (OR 2.10; 95% CI 1.24, 3.56 and OR 2.41; 95% CI 1.54, 3.76); OS (OR 1.40; 95% CI 1.01, 1.94 and OR 2.10; 95% CI 1.60, 2.75), respectively. Referent group 2: ART was associated with both outcomes in all births, but not singletons.

CONCLUSIONS: Preterm birth and low birthweight associated with fertility treatments are largely attributable to multiple gestation, but are also related to underlying subfertility.

TWEETABLE ABSTRACT: Preterm birth is associated with subfertility, and with fertility treatments through multiple gestation.

BJOG : an International Journal of Obstetrics and Gynaecology


Complementary Therapies in Nursing and Midwifery


Oral contraceptive pill use is associated with localized decreases in cortical thickness

Abstract: Oral contraceptive pills (OCs), which are used to prevent pregnancy by the majority of women in the United States, contain steroid hormones that may affect the brain's structure and function. In this investigation, we tested the hypothesis that OC use is associated with differences in brain structure using a hypothesis-driven, surface-based approach. In 90 women, (44 OC users, 46 naturally-cycling women), we compared the cortical thickness of brain regions that participate in the salience network and the default mode network, as well as the volume of subcortical regions in these networks. We found that OC use was associated with significantly lower cortical thickness measurements in the lateral orbitofrontal cortex and the posterior cingulate cortex. These regions are believed to be important for responding to rewards and evaluating internal states/incoming stimuli, respectively. Further investigations are needed to determine if cortical thinning in these regions are associated with behavioral changes, and also to identify whether OC use is causally or only indirectly related to these changes in brain morphology.


Vitamin B-12 Status Differs among Pregnant, Lactating, and Control Women with Equivalent Nutrient Intakes

Abstract:
BACKGROUND: Limited data are available from controlled studies on biomarkers of maternal vitamin B-12 status.

OBJECTIVE: We sought to quantify the effects of pregnancy and lactation on the vitamin B-12 status response to a known and highly controlled vitamin B-12 intake.

METHODS: As part of a 10-12 wk feeding trial, pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant, nonlactating; n = 21) women consumed vitamin B-12 amounts of ∼8.6 μg/d [mixed diet (∼6 μg/d) plus a prenatal multivitamin supplement (2.6 μg/d)]. Serum vitamin B-12, holotranscobalamin (bioactive form of vitamin B-12), methylmalonic acid (MMA), and homocysteine were measured at baseline and study-end.

RESULTS: All participants achieved adequate vitamin B-12 status in response to the study dose. Compared with control women, pregnant women had lower serum vitamin B-12 (-21%; P = 0.02) at study-end, whereas lactating women had higher (P = 0.04) serum vitamin B-12 throughout the study (+26% at study-end). Consumption of the study vitamin B-12 dose increased serum holotranscobalamin in all reproductive groups (+16-42%; P ≤ 0.009). At study-end, pregnant (vs. control) women had a higher holotranscobalamin-to-vitamin B-12 ratio (P = 0.04) with ∼30% (vs. 20%) of total vitamin B-12 in the bioactive form. Serum MMA increased during pregnancy (+50%; P < 0.001) but did not differ by reproductive state at study-end. Serum homocysteine increased in pregnant women (+15%; P = 0.009) but decreased in control and lactating women (-16-17%; P < 0.001). Despite these changes, pregnant women had ∼20% lower serum homocysteine than the other 2 groups at study-end (P ≤ 0.02).

CONCLUSION: Pregnancy and lactation alter vitamin B-12 status in a manner consistent with enhanced vitamin B-12 supply to the child. Consumption of the study vitamin B-12 dose (∼3 times the RDA) increased the bioactive form of vitamin B-12, suggesting that women in these reproductive states may benefit from vitamin B-12 intakes exceeding current recommendations. This trial was registered at clinicaltrials.gov as NCT01127022.


Effects of over-the-counter analgesic use on reproductive hormones and ovulation in healthy, premenopausal women

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:
Study Question: Does use of commonly used over-the-counter (OTC) pain medication affect reproductive hormones and ovulatory function in premenopausal women?

Summary Answer: Few associations were found between analgesic medication use and reproductive hormones, but use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for potential confounders.

What Is Known Already: Analgesic medications are the most commonly used OTC drugs among women, but their potential effects on reproductive function are unclear.

STUDY DESIGN, SIZE, Duration: The BioCycle Study was a prospective, observational cohort study (2005-2007) which followed 259 women for one (n = 9) or two (n = 250) menstrual cycles. PARTICIPANTS, SETTING,

Methods: Two hundred and fifty-nine healthy, premenopausal women not using hormonal contraception and living in western New York state. Study visits took place at the University at Buffalo.

Main Results and the Role of Chance: During study participation, 68% (n = 175) of women indicated OTC analgesic use. Among users, 45% used ibuprofen, 33% acetaminophen, 10% aspirin and 10% naproxen. Analgesic use during the follicular phase was associated with decreased odds of sporadic anovulation after adjusting for age, race, body mass index, perceived stress level and alcohol consumption (OR 0.36 [0.17, 0.75]). Results remained unchanged after controlling for potential confounding by indication by adjusting for 'healthy' cycle indicators such as amount of blood loss and menstrual pain during the preceding menstruation. Moreover, luteal progesterone was higher (% difference = 14.0, -1.6-32.1, P = 0.08 adjusted) in cycles with follicular phase analgesic use, but no associations were observed with estradiol, LH or FSH.

LIMITATIONS, Reasons for Caution: Self-report daily diaries are not validated measures of medication usage, which could lead to some classification error of medication use. We were also limited in our evaluation of aspirin and naproxen which were used by few women. WIDER IMPLICATIONS OF THE FINDINGS: The observed associations between follicular phase analgesic use and higher progesterone and a lower probability of sporadic anovulation indicate that OTC pain medication use is likely not harmful to reproduction function, and certain medications possibly improve ovulatory function.

Study Funding/competing Interests: This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275200403394C). The authors have no conflicts of interest to disclose.


New diagnostic criteria and operative strategy for cesarean scar syndrome:  Endoscopic repair for secondary infertility caused by cesarean scar defect

Abstract:
Aim: The aim of the present study was to assess the efficacy of endoscopic repair for secondary infertility caused by post-cesarean scar defect (PCSD). Our investigation focused on the validity of new diagnostic criteria and selection methods.

MATERIAL AND Methods: The subjects were 22 women with secondary infertility due to PCSD with retention of bloody fluid in the uterine cavity. Women with a residual myometrial thickness of ≥ 2.5 mm and an anteflexed or straight uterus underwent hysteroscopic surgery, while all others underwent laparoscopic repair. Hysteroscopic surgery involved resection and coagulation of scarred areas, whereas laparoscopic surgery involved removal of scarred areas combined with hysteroscopy, followed by resuturing.

Results: Fourteen of the 22 women (63.6%) who were followed up for ≥ 1 year after surgery achieved pregnancy. Pregnancies occurred in all four women (100%) who underwent hysteroscopic surgery and in 10 of the 18 women (55.6%) who underwent laparoscopic surgery. Three out of four women who underwent hysteroscopic surgery had term deliveries. Among the women who underwent laparoscopic surgery, five had term deliveries. No cases of uterine rupture were experienced, and the delivery method was cesarean section in all cases.

Conclusion: We propose that infertility associated with PCSD, cesarean scar syndrome, is caused by the retention of bloody fluid in the uterine cavity and scarring. Endoscopic treatment, such as hysteroscopy or laparoscopy, was effective for cesarean scar syndrome.

The Journal of Obstetrics and Gynaecology Research


Dietary factors and luteal phase deficiency in healthy eumenorrheic women

Mary A Andrews

Walter Reed National Military Medical Center

Abstract:
STUDY QUESTION: Are prospectively assessed dietary factors, including overall diet quality, macronutrients and micronutrients, associated with luteal phase deficiency (LPD) in healthy reproductive aged women with regular menstrual cycles?

SUMMARY ANSWER: Mediterranean Diet Score (MDS), fiber and isoflavone intake were positively associated with LPD while selenium was negatively associated with LPD after adjusting for age, percentage body fat and total energy intake.

WHAT IS KNOWN ALREADY: LPD may increase the risk of infertility and early miscarriage. Prior research has shown positive associations between LPD and low energy availability, either through high dietary restraint alone or in conjunction with high energy expenditure via exercise, but few studies with adequate sample sizes have been conducted investigating dietary factors and LPD among healthy, eumenorrheic women.

STUDY DESIGN, SIZE, DURATION: The BioCycle Study (2005-2007) prospectively enrolled 259 women from Western New York state, USA, and followed them for one (n = 9) or two (n = 250) menstrual cycles.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-44 years, with self-reported BMI between 18 and 35 kg/m(2) and cycle lengths between 21 and 35 days, were included in the study. Participants completed baseline questionnaires, four 24-h dietary recalls per cycle and daily diaries capturing vigorous exercise, perceived stress and sleep; they also provided up to eight fasting serum samples during clinic visits timed to specific phases of the menstrual cycle using a fertility monitor. Cycles were included for this analysis if the peak serum luteal progesterone was >1 ng/ml and a urine or serum LH surge was detected. Associations between prospectively assessed diet quality, macronutrients and micronutrients and LPD (defined as luteal duration <10 days) were evaluated using generalized linear models adjusting for age, percentage body fat and total energy intake.

MAIN RESULTS AND THE ROLE OF CHANCE: LPD occurred in 41 (8.9%) of the 463 cycles from 246 women in the final analysis. After adjusting for age, percentage body fat and total energy intake, LPD was positively associated with MDS, adjusted odds ratio (aOR): 1.70 (95% confidence interval [CI]: 1.17, 2.48), P = 0.01. In separate macro- and micronutrient adjusted models, increased fiber and isoflavone intake showed modest positive associations with LPD: fiber (per g), aOR: 1.10 (95% CI: 0.99, 1.23), P = 0.07; and isoflavones (per 10 mg), aOR: 1.38 (95% CI: 0.99, 1.92), P = 0.06. In contrast, selenium (per 10 mcg) was inversely associated with LPD, aOR: 0.80 (95% CI: 0.65, 0.97), P = 0.03. Additional adjustments for relevant lifestyle factors including vigorous exercise, perceived stress and sleep did not appreciably alter estimates.

LIMITATIONS, REASONS FOR CAUTION: The number of LPD cycles was limited, and thus these findings are exploratory. We relied on participant self-report of their medical history to apply exclusion criteria; it is possible that we admitted to the study women with a gynecologic or medical disease who were unaware of their diagnosis.

WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that diet quality may be associated with LPD among healthy eumenorrheic women. As LPD may contribute to infertility and early miscarriage, further research is warranted to elucidate how dietary factors, such as MDS, may influence LPD. The inverse association we found with selenium is supported by previous research and deserves further investigation to determine whether this finding has pathophysiologic and therapeutic implications.

STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. No competing interests declared.


Pregnancy-related complications and adverse pregnancy outcomes in multiple pregnancies resulting from assisted reproductive technology: a meta-analysis of cohort studies

Abstract:
Objective: To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception.

Design: Meta-analysis.

Setting: University-affiliated teaching hospital.Patient(s)Multiple pregnancies conceived by ART or naturally.Intervention(s)Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main outcome measure(s)Pregnancy-related complications and adverse pregnancy outcomes.Result(s)Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05-1.37; I(2) = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04-1.19; I(2) = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25-2.55; I(2) = 42%); preterm birth (RR = 1.08, 95% CI: 1.03-1.14; I(2) = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04-1.34; I(2) = 79%); low birth weight (RR = 1.04, 95% CI: 1.01-1.07; I(2) = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01-1.25; I(2) = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02-1.22; I(2) = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.Conclusion(s)Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized.


Ten-year Retrospective Study on the Efficacy of a Manual Physical Therapy to  Treat Female Infertility

Abstract:
Background: Female infertility is a complex issue encompassing a wide variety of diagnoses, many of which are caused or affected by adhesions.

Objectives: The study intended to examine the rates of successful treatment of infertile women using a protocol of manual physical therapy to address underlying adhesive disease leading to infertility. Methods • The research team designed a retrospective chart review.
Setting: The study took place in a private physical therapy clinic.

Participants: Participants were 1392 female patients who were treated at the clinic between the years of 2002 and 2011. They had varying diagnoses of infertility, including occluded fallopian tubes, hormonal dysfunction, and endometriosis, and some women were undergoing in vitro fertilization (IVF). Intervention • All patients underwent whole-body, patient-centered treatments that used a protocol of manual physical therapy, which focused on restoring mobility and motility to structures affecting reproductive function.

OUTCOME MEASURES: Improvements demonstrated in the condition(s) causing infertility were measured by improvements in tubal patency and/or improved hormone levels or by pregnancy. Results • The results included a 60.85% rate of clearing occluded fallopian tubes, with a 56.64% rate of pregnancy in those patients. Patients with endometriosis experienced a 42.81% pregnancy rate. The success rate was 49.18% for lowering elevated levels of follicle stimulating hormone (FSH), with a 39.34% pregnancy rate in that group, and 53.57% of the women with polycystic ovarian syndrome (PCOS) achieved pregnancy. The reported pregnancy rate for patients who underwent IVF after the therapy was 56.16%. The results also suggested that the treatment was effective for patients with premature ovarian failure (POF).

Conclusion: The manual physical therapy represented an effective, conservative treatment for women diagnosed as infertile due to mechanical causes, independent of the specific etiology.

Alternative Therapies in Health and Medicine


Use of combined oral contraceptives and risk of venous thromboembolism: nested  case-control studies using the QResearch and CPRD databases

Julia Hippisley-Cox

Division of Primary Care, University Park, Nottingham, NG2 7RD UK.

Abstract:
Objective: To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account.
Design: Two nested case-control studies.
Setting: General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices).

Participants: Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year.

Main Outcome Measures: Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets.

Results: 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10,000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17).

Conclusions: In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.


Median-lower normal levels of serum thyroxine are associated with low  triiodothyronine levels and body temperature in patients with central  hypothyroidism

Abstract:
Objective: Although it has been recommended that serum free thyroxine (FT4) levels should be targeted to middle-upper normal levels during levothyroxine (l-T4) replacement therapy in patients with central hypothyroidism (CeH), the rationale has not been clarified.

Methods: A retrospective single-center study enrolled 116 patients with hypothyroidism (CeH, n=32; total thyroidectomy (Tx), n=22; primary hypothyroidism (PH), n=33; and control benign thyroid nodule (C), n=29). The patients had received L-T4 therapy at the Kobe University Hospital between 2003 and 2013. They were stratified according to serum FT4 level (≥ 1.10 or <1.10 ng/dl), and body temperature (BT), serum free triiodothyronine (FT3) levels, FT3/FT4 ratio, and lipid profiles were compared. The effect of GH replacement therapy on thyroid function was also analyzed.

Results: FT3 levels and FT3/FT4 ratios were significantly lower in patients with CeH than in patients with PH (P<0.05) or C (P<0.05). In patients with FT4 <1.10 ng/dl, BT was significantly lower in patients with CeH (P=0.002) and Tx (P=0.005) than in patients with PH, whereas no differences were found in patients with FT4 ≥ 1.10 ng/dl. In patients with CeH, FT3 levels were higher in those with GH replacement therapy (P=0.018).

Conclusion: In CeH, patients with median-lower normal levels of serum FT4 exhibited lower serum FT3 levels and lower BT. These results support the target levels of serum FT4 as middle-upper normal levels during l-T4 replacement therapy in patients with CeH.


No increase in breast cancer risk in Japanese women taking oral contraceptives: a  case-control study investigating reproductive, menstrual and familial risk  factors for breast cancer

Miho Ichida

Carolina Women's Research and Wellness Center

Abstract:
Background: Low-dose oral contraceptives (OC) were approved by the Japanese Ministry of Health, Labor and Welfare in 1999, yet despite their contraceptive and non-contraceptive health benefits, only 5% of the target population use them. Fear of increased cancer risk, particularly breast cancer, is one reason for this. Due to low OC uptake and low screening participation, a paucity of data is available on the risk of OC use and breast cancer in Japanese women. The present study investigated OC use and breast cancer risk, as well as menstrual, reproductive and family factors.

Materials and Methods: This was a clinic-based case-control study of women aged 20-69yrs who had undergone breast screening between January 2007 and December 2013 in central Tokyo. In all, 28.8% of the participants had experience with OC use. Cases were 155 women with a pathologically confirmed diagnosis of breast cancer. Controls were the remaining 12,333 women.

Results: Increased age was a significant risk factor for breast cancer (p<0.001). A lower risk was found in premenopausal women presently taking OC compared to never users (OR 0.45; 95% CI 0.22-0.90) after adjusting for age, parity and breast feeding, and a family history of breast cancer.

Conclusions: Increased age rather than OC use had a greater effect on breast cancer risk. This risk may be decreased in premenopausal women with OC use, but further long-term prospective studies are necessary.

Asian Pacific Journal of Cancer Prevention : APJCP


The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis

Abstract: To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.


Role of tubal surgery in the era of assisted reproductive technology: a committee opinion

Practice Committee of the American Society for Reproductive Medicine

Abstract: This document reviews surgical options for achieving patency in obstructed fallopian tubes and the factors that must be considered when deciding between surgical repair and IVF. This document replaces the document of the same name, last published in 2012 (Fertil Steril 2012;97:539–45).


Effects of boron supplementation on the severity and duration of pain in primary dysmenorrhea

Abstract:
BACKGROUND: Primary dysmenorrhea refers to painful menstrual cramps without pelvic pathology. The condition is highly prevalent among women and exerts negative effects on their quality of life. Considering the evidence for anti-inflammatory properties of Boron, the present study aimed to determine the effects of Boron supplementation on the severity and duration of menstrual pain in female university students.

METHODS: This triple-blind randomized clinical trial study recruited 113 university students. The participants were matched for the severity and duration of dysmenorrhea and randomly allocated into the case and control groups (n = 58 and 55, respectively). The case group consumed 10 mg/day Boron from two days before the menstrual flow until its third day. The control group received placebo capsules (similar to those distributed among the cases). All subjects were asked to take the capsules for two consecutive menstrual cycles. Pain severity (measured on a visual analog scale) and duration (in hours) were measured at baseline and during the two cycles.

RESULTS: The two groups had no significant differences in the severity and duration of pain at baseline. After the intervention, however, the severity and duration of pain were significantly lower in the case group than in the control group (P < 0.05).

CONCLUSION: Based on our findings, Boron supplementation can reduce the severity and duration of menstrual pain through exerting anti-inflammatory effects. In order to clarify the effects of Boron on dysmenorrhea, future studies are required to measure the levels of hormones and inflammatory biomarkers.

Complementary therapies in clinical practice


Disease-related differences in resting-state networks: a comparison between localized provoked vulvodynia, irritable bowel syndrome, and healthy control subjects

Abstract: Localized provoked vulvodynia (LPVD) affects approximately 16% of the female population, but biological mechanisms underlying symptoms remain unknown. Like in other often comorbid chronic pain disorders, altered sensory processing and modulation of pain, including central sensitization, dysregulation of endogenous pain modulatory systems, and attentional enhancement of pain perception, have been implicated. The aim of this study was to test whether regions of interest showing differences in LPVD compared to healthy control subjects (HCs) in structural and evoked-pain neuroimaging studies, also show alterations during rest when compared with HCs and a chronic pain control group (irritable bowel syndrome [IBS]). Functional magnetic resonance imaging was performed during resting state in 87 age-matched premenopausal females (29 LPVD, 29 HCs, and 29 IBS). Group-independent component analysis and general linear models were applied to investigate group differences in the intrinsic connectivity of regions comprising sensorimotor, salience, and default mode resting-state networks. Subjects with LPVD showed substantial alterations in the intrinsic connectivity of these networks compared with HCs and IBS. The intrinsic connectivity of many of the regions showing group differences during rest were moderately associated with clinical symptom reports in LPVD. Findings were robust to controlling for affect and medication usage. The current findings indicate that subjects with LPVD have alterations in the intrinsic connectivity of regions comprising the sensorimotor, salience, and default mode networks. Although shared brain mechanisms between different chronic pain disorders have been postulated, the current findings suggest that some alterations in functional connectivity may show disease specificity.


Preconception low dose aspirin and time to pregnancy: findings from the effects of aspirin in gestation and reproduction randomized trial

Enrique F Schisterman

Eunice Kennedy Shriver National Institute of Child Health and Human Development

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:
Objective: The objective was to determine the effect of preconception-initiated daily low-dose aspirin (LDA; 81 mg/day) treatment on time to pregnancy in women with a history of pregnancy loss.
Design: This was a multicenter, block-randomized, double-blind, placebo-controlled trial. Participants were block-randomized by center and eligibility stratum.
Setting: The study was conducted at four U.S.A. medical centers (2007-2012).

Participants: Participants women aged 18-40 years actively attempting pregnancy, stratified by eligibility criteria: the "original" stratum, women with one loss <20 weeks' gestation during the previous year; and the "expanded" stratum, women with one or two previous losses of any gestational age regardless of time since loss.

Intervention: Daily LDA was compared with matching placebo for up to six menstrual cycles of attempting pregnancy. Main Outcome Measure: Time to hCG detected pregnancy and clinically confirmed pregnancy, analyzed by intention-to-treat, was measured.

Results: Of the 1228 women randomly assigned to LDA (n = 615) or placebo (n = 613), 410 (67%) women receiving LDA achieved pregnancy compared to 382 (63%) receiving placebo, corresponding to a fecundability odds ratio (FOR) of 1.14 (95% CI: 0.97, 1.33). Among women in the original stratum (n = 541), LDA was associated with increased fecundability compared to placebo (For: 1.28; 95%CI: 1.02, 1.62).

Conclusions: Preconception-initiated LDA treatment resulted in a nonsignificant increase in fecundability of 14% in women with a history of 1-2 pregnancy losses, and a significant increase of 28% in women with a history of only one pregnancy loss of <20 weeks' gestation in the preceding year. Preconception-initiated LDA may increase fecundability in certain women with a recent early pregnancy loss.

The Journal of clinical endocrinology and metabolism


Helicobacter pylori Infection Is Associated with an Increased Risk of Hyperemesis Gravidarum: A Meta-Analysis

Haike Gu

Beijing Academy of Science and Technology

Abstract:
Background. Several studies have shown a possible involvement of Helicobacter pylori (H. pylori) infection in individuals with hyperemesis gravidarum (HG), but the relationship remains controversial. This meta-analysis was performed to validate and strengthen the association between HG and H. pylori infection.

Methods. PubMed, Embase, and Web of Science databases up to March 20, 2014, were searched to select studies on the prevalence of H. pylori infection between pregnant women with HG and the normal pregnant control subjects.

Results. Of the HG cases, 1289 (69.6%) were H. pylori-positive; however, 1045 (46.2%) were H. pylori-positive in control group. Compared to the non-HG normal pregnant controls, infection rate of H. pylori was significantly higher in pregnant women with HG (OR = 3.34, 95% CI: 2.32-4.81, P < 0.001). Subgroup analysis indicated that H. pylori infection was a risk factor of HG in Asia, Africa, and Oceania, especially in Africa (OR = 12.38, 95% CI: 7.12-21.54, P < 0.001).

Conclusions. H. pylori should be considered one of the risk factors of HG, especially in the developing countries. H. pylori eradication could be considered to relieve the symptoms of HG in some intractable cases.


Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial

Abstract:
OBJECTIVE: This study was conducted to evaluate the effects of zinc supplementation on glucose homeostasis parameters and lipid concentrations in PCOS women. We are aware of no study evaluating the effects of zinc supplementation on metabolic profiles of patients with polycystic ovary syndrome (PCOS).

METHODS: This randomized, double-blind, placebo-controlled trial was conducted among 52 women diagnosed with PCOS and aged 18-40 years old. Participants were randomly divided into 2 groups to receive 220 mg zinc sulfate (containing 50 mg zinc) supplements (n=26) or placebo (n=26) per day for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks' intervention to quantify glucose, insulin and lipid concentrations.

RESULTS: After 8 weeks of intervention, subjects who received zinc supplements had significantly increased serum zinc levels (+15.6±21.8 vs. -4.1±16.7 mg/dL, P=0.001) compared with placebo. In addition, zinc-supplemented patients had reduced fasting plasma glucose (FPG) (-4.3±9.6 vs. +0.5±6.0 mg/dL, P=0.03), serum insulin levels (-3.0±2.9 vs. +1.5±8.4 µIU/mL, P=0.01), homeostasis model of assessment-insulin resistance (HOMA-IR) (-0.8±0.8 vs. +0.3±1.9, P=0.006), homeostatic model assessment-Beta cell function (HOMA-B) (-10.6±9.5 vs. +4.9±32.1, P=0.02) and increased quantitative insulin sensitivity check index (QUICKI) (+0.02±0.02 vs. -0.004±0.05, P=0.03) compared with placebo. Additionally, a significant reduction in serum triglycerides (-15.6±40.3 vs. +14.5±25.3 mg/dL, P=0.002) and VLDL-cholesterol concentrations (-3.2±8.1 vs. +2.9±5.1 mg/dL, P=0.002) was observed following the administration of zinc supplements compared with placebo.

CONCLUSION: Taken together, 220 mg zinc sulfate supplementation per day for 8 weeks among PCOS women had beneficial effects on metabolic profiles.

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association


Hormonal contraceptive use and risk of glioma among younger women: a nationwide case-control study

Abstract:
AIM: Oral contraceptive use influences the risk for certain cancers. However, few studies have examined any link with risk of central nervous system tumours. We investigated the association between hormonal contraceptive use and glioma risk among premenopausal women in a population-based setting.

METHODS: Using national administrative and health registries in Denmark to conduct a nationwide case-control study, we identified all women ages 15 to 49 years with a first time diagnosis of histologically verified glioma between 2000 and 2009. Each case was age-matched to eight population controls using risk set sampling. Based on prescription data, exposure until 2 years prior to the index date was categorized according to hormonal contraceptive type, i.e. combined oestrogen-progestagen or progestagen only, and duration of use (<1, 1 to <5, ≥5 years). We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for glioma associated with hormonal contraceptive use, adjusting for potential confounders.

RESULTS: We identified 317 cases and 2126 controls. Ever use of hormonal contraceptive was associated with an OR of 1.5 (95% CI 1.2, 2.0) and the OR increased with duration of use (long term, ≥5 years: OR 1.9; 95% CI 1.2, 2.9). The association between long term hormonal contraceptive use and glioma risk was most pronounced for progestagen only therapy (OR 2.4; 95% CI 1.1, 5.1), especially when this regimen constituted the sole hormonal contraceptive therapy (OR 4.1; 95% CI 0.8, 20.8).

CONCLUSION: Long term hormonal contraceptive use may increase the risk of glioma.

British journal of clinical pharmacology


The effects of cigarette smoking on male fertility

Abstract: Cigarette smoking, one of the main causes of preventable morbidity and mortality, has a multitude of well-known side effects. The relationship between cigarette smoking and infertility has been studied for decades; however, large-scale, population-wide prospective studies are lacking. The majority of the current literature is in the form of retrospective studies focused on the effects of smoking on semen analyses. This article discusses the results of these studies and reviews the postulated mechanisms. The effects of smoking on assisted reproduction and in vitro fertilization outcomes are noted. The consequences of smoking while pregnant on future fertility as well as the outcomes of second-hand smoke are analyzed. The current evidence suggests that men should be advised to abstain from smoking in order to improve reproductive outcomes.


The effects of diabetes on male fertility and epigenetic regulation during  spermatogenesis

Hefeng Huang

International Peace Maternity & Child Health Hospital

Abstract: The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.


A retrospective, case-control study on traditional environmental risk factors in  inflammatory bowel disease in Vukovar-Srijem County, north-eastern Croatia, 2010

Abstract:
Background: Traditional environmental risk factors in inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), were examined as part of the retrospective epidemiologic study conducted in Vukovar-Srijem County, north-eastern Croatia in 2010. The geographical variations in the frequency of IBD in Croatia have been observed, which is also the trend in the Central Eastern European region and Europe as a whole, indicating the influence of environmental and lifestyle factors. However, the data on the spread of environmental IBD risk factors are still limited. The purpose of this study was to analyse the traditional environmental risk factors in IBD on our cohort sample, including measles virus infection and vaccination (MMR vaccine-Mumps, Measles, Rubella), tonsillectomy, appendectomy, current and former cigarette smoking and use of oral contraceptives in women.

Methods: This retrospective, case-control study was performed as a part of a wider epidemiologic study aimed at assessing the incidence, prevalence and clinical expression of IBD, in Vukovar-Srijem County (

population: 204,768; 2001), which is a lesser developed part of the continental Croatia that experienced deep demographic changes in the recent past. IBD patients were identified according to the hospital's patient records. There were 119 UC patients and 31 CD patients of a total of 150 patients in the cohort. A total of 150 individuals, volunteers, not having a diagnosis of IBD, ageand sex-matched, were used as the control group. Information on examined risk factors were obtained from all subjects in a previously conducted interview. Patients were contacted personally or by phone and interviewed by a gastroenterologist.

Results: There were no differences in the number of smokers, former smokers and non-smokers, between UC and CD patients and the controls, nor in the duration of smoking (years), in current smokers and ex-smokers. Only marginally significant longer time of non-smoking, in ex-smokers was found in IBD patients, compared to the controls, more pronounced in CD patients (p = 0.05). No difference was found in relation to tonsillectomy and risk of IBD. There was no difference in the number of female IBD patients and women from the controls using oral contraceptives. Duration (years) of oral contraceptives use was longer in women from the controls than in female IBD patients (p < 0.001). Frequency of appendectomy was the lowest in UC patients, compared to the controls and CD patients (3.4, 12.0 and 38.7%, respectively) (p < 0.001). No difference was found in relation to measles virus infection and risk of IBD. MMR vaccination rates were higher in CD patients (90.3%), compared to UC patients and the controls (74.8 and 67.3%, respectively) (p = 0.026).

Conclusions: No association was found between smoking and tonsillectomy and risk of IBD. Our results do not support the idea of oral contraceptives use as a risk factor for IBD. Frequency of appendectomy was the lowest in UC patients, suggesting that appendectomy decreases the risk of UC, contributing the earlier results. MMR vaccination seemed to be associated with Crohn's disease. These results can add value to our understanding of the increasing incidence of IBD in Croatia and other Central Eastern European countries and can be introductory to future large-scale research.


Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system

C J C M Hamilton

Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.

Abstract:
STUDY QUESTION: Does the prewash total motile sperm count (TMSC) have a better predictive value for spontaneous ongoing pregnancy (SOP) than the World Health Organization (WHO) classification system?

SUMMARY ANSWER: The prewash TMSC shows a better correlation with the spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 classification system.

WHAT IS KNOWN ALREADY: According to the WHO classification system, an abnormal semen analysis can be diagnosed as oligozoospermia, astenozoospermia, teratozoospermia or combinations of these and azoospermia. This classification is based on the fifth percentile cut-off values of a cohort of 1953 men with proven fertility. Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable. The TMSC is obtained by multiplying the sample volume by the density and the percentage of A and B motility spermatozoa.

STUDY DESIGN, SIZE, DURATION: We analyzed data from a longitudinal cohort study among unselected infertile couples who were referred to three Dutch hospitals between January 2002 and December 2006. Of the total cohort of 2476 infertile couples, only the couples with either male infertility as a single diagnosis or unexplained infertility were included (n = 1177) with a follow-up period of 3 years.

PARTICIPANTS/MATERIALS, SETTING, METHODS: In all couples a semen analysis was performed. Based on the best semen analysis if more tests were performed, couples were grouped according to the WHO classification system and the TMSC range, as described in the Dutch national guidelines for male infertility. The primary outcome measure was the SOPR, which occurred before, during or after treatments, including expectant management, intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection. After adjustment for the confounding factors (female and male age, duration and type of infertility and result of the postcoital test) the odd ratios (ORs) for risk of SOP for each WHO and TMSC group were calculated. The couples with unexplained infertility were used as reference.

MAIN RESULTS AND THE ROLE OF CHANCE: A total of 514 couples did and 663 couples did not achieve a SOP. All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397). Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia [OR 0.501 (95% CI 0.311-0.809)] and teratozoospermia [OR 0.499 (95% CI: 0.252-0.988)], and oligoasthenozoospermia is compared with asthenozoospermia [OR 0.572 (95% CI: 0.373-0.877)]. All TMSC groups have a significantly lower SOPR compared with the unexplained group (ORs varying from 0.171 to 0.461). Couples with a TMSC of <1 × 10(6) and 1-5 × 10(6) have significantly lower SOPR compared with couples with a TMSC of 5-10 × 10(6) [respectively, OR 0.371 (95% CI: 0.215-0.64) and OR 0.505 (95% CI: 0.307-0.832)].

LIMITATIONS, REASON FOR CAUTION: To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment.

WIDER IMPLICATIONS OF THE FINDINGS: Roughly, three prognostic groups can be discerned: couples with a TMSC <5, couples with a TMSC between 5 and 20 and couples with a TMSC of more than 20 × 10(6) spermatozoa. We suggest using TMSC as the method of choice to express severity of male infertility.

STUDY FUNDING/COMPETING INTERESTS: None.


Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss

Abstract:
OBJECTIVE: To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL).

DESIGN: Decision analytic model comparing costs and clinical outcomes.

SETTING: Academic recurrent pregnancy loss programs.

PATIENT(S): Women with unexplained RPL.

INTERVENTION(S): IVF/PGS with 24-chromosome screening and expectant management.

MAIN OUTCOMES MEASURE(S): Cost per live birth.

RESULT(S): The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management.

CONCLUSION(S): In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.


Revisiting the fertile window

Revisiting the fertile window

Abstract: Ovulation occurs on 1 day during each menstrual cycle (even if multiple follicles are involved), and the several days preceding ovulation are when intercourse is most likely to result in pregnancy. Collectively, the potentially fertile days up to and including the day of ovulation are called the “fertile window” (1). Since the 1930s, several biomarkers of the fertile window have been investigated for the purposes of empowering women and couples seeking to use fertility-awareness based methods or natural family planning to avoid pregnancy, as well as to expand understanding of human reproductive physiology.


Endometriosis: a high-risk population for major chronic diseases?

Leslie V Farland

Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona; Department of Obstetrics and Gynecology, College of Medicine -...

Abstract:
BACKGROUND: Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities.

METHODS: We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches.

RESULTS: We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer.

CONCLUSIONS: Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If these relationships are confirmed, these findings may have important implications in screening practices and in the management and care of endometriosis patients.


The effect of a very short interpregnancy interval and pregnancy outcomes following a previous pregnancy loss

Sunni L Mumford

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:
Objective: We sought to assess the relationship between a short interpregnancy interval (IPI) following a pregnancy loss and subsequent live birth and pregnancy outcomes.

Study Design: A secondary analysis of women enrolled in the Effects of Aspirin in Gestation and Reproduction trial with a human chorionic gonadotropin-positive pregnancy test and whose last reproductive outcome was a loss were included in this analysis (n = 677). IPI was defined as the time between last pregnancy loss and last menstrual period of the current pregnancy and categorized by 3-month intervals. Pregnancy outcomes include live birth, pregnancy loss, and any pregnancy complications. These were compared between IPI groups using multivariate relative risk estimation by Poisson regression.

Results: Demographic characteristics were similar between IPI groups. The mean gestational age of prior pregnancy loss was 8.6 ± 2.8 weeks. The overall live birth rate was 76.5%, with similar live birth rates between those with IPI ≤3 months as compared to IPI >3 months (adjusted relative risk [aRR], 1.07; 95% confidence interval [CI], 0.98-1.16). Rates were also similar for periimplantation loss (aRR, 0.95; 95% CI, 0.51-1.80), clinically confirmed loss (aRR, 0.75; 95% CI, 0.51-1.10), and any pregnancy complication (aRR, 0.88; 95% CI, 0.71-1.09) for those with IPI ≤3 months as compared to IPI >3 months.

Conclusion: Live birth rates and adverse pregnancy outcomes, including pregnancy loss, were not associated with a very short IPI after a prior pregnancy loss. The traditional recommendation to wait at least 3 months after a pregnancy loss before attempting a new pregnancy may not be warranted.

American journal of obstetrics and gynecology


Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults

Abstract:
BACKGROUND: Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements.

OBJECTIVES: We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L.

METHODS: Serum samples from the cross-sectional NHANES 2007-2008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLC-tandem mass spectrometry.

RESULTS: In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (≥8 h) adults (≥20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L.

CONCLUSIONS: UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ≥1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements.


Self-identification of the clinical fertile window and the ovulation period

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract:
OBJECTIVE: To assess the sensitivity and specificity of the self-identified fertile window.

DESIGN: Observational study.

SETTING: Not applicable.

PATIENT(S): A total of 107 women.

INTERVENTION(S): Women recorded cervical mucus observation and basal body temperature daily while undergoing daily ovarian ultrasound.

MAIN OUTCOME MEASURE(S): The biological fertile window, defined as the 6 days up to and including the day of ovulation; and the 2-day ovulation window, defined as the day before and the day of ovulation.

RESULT(S): The self-identification of the biological fertile window by the observation of any type of cervical mucus provides 100% sensitivity but poor specificity, yielding a clinical fertile window of 11 days. However, the identification of the biological fertile window by peak mucus (defined as clear, slippery, or stretchy mucus related to estrogen) yielded 96% sensitivity and improved specificity. The appearance of the peak mucus preceded the biological fertile window in less than 10% of the cycles. Likewise, this type of mucus identified the ovulation window with 88% sensitivity.

CONCLUSION(S): These results suggest that, when perceived accurately, more accurate clinical self-detection of the fertile window can be obtained by identification of peak mucus. This may improve efforts to focus intercourse in the fertile phase for couples with fertility concerns.


Mechanism of action of levonorgestrel emergency contraception

Chris Kahlenborn

The Polycarp Research Institute, Enola, PA, USA

Walter B Severs

Penn State Milton S. Hershey Medical Center

Abstract: There has been much debate regarding levonorgestrel emergency contraception's (LNG-EC's) method of action since 1999 when the Food and Drug Administration first approved its use. Proponents of LNG-EC have argued that they have moral certitude that LNG-EC works via a non-abortifacient mechanism of action, and claim that all the major scientific and medical data consistently support this hypothesis. However, newer medical data serve to undermine the consistency of the non-abortifacient hypothesis and instead support the hypothesis that preovulatory administration of LNG-EC has significant potential to work via abortion. The implications of the newer data have important ramifications for medical personnel, patients, and both Catholic and non-Catholic emergency room protocols. In the future, technology such as the use of early pregnancy factor may have the potential to quantify how frequently preovulatory LNG-EC works via abortion. Lay Summary: How Plan B (levonorgestrel emergency contraception) works has been vigorously debated ever since the Food and Drug Administration approved it in 1999. Many doctors and researchers claim that it has either no-or at most-an extremely small chance of working via abortion. However, the latest scientific and medical evidence now demonstrates that levonorgestrel emergency contraception theoretically works via abortion quite often. The implications of the newer data have important ramifications for medical personnel, patients, and both Catholic and non-Catholic emergency room rape protocols.


The harmonious relationship between faith and science from the perspective of  some great saints: A brief comment

Abstract: The objective of this editorial is to show that a harmonious relationship between science and faith is possible, as exemplified by great saints of the Catholic Church. It begins with the definitions of science and faith, followed by an explanation of the apparent conflict between them. A few saints that constitute an example that a fruitful relationship between these two seemingly opposed realities has been possible are Saint Albert the Great, Saint John of the Cross, Saint Giuseppe Moscati, and Saint Edith Stein, among others, and this editorial highlights their deep contributions to the dialogue between faith and reason. This editorial ends with a brief discussion on whether it is possible to be both a scientist and a man of faith.


A case-control analysis of oral contraceptive use and breast cancer subtypes in the African American Breast Cancer Epidemiology and Risk Consortium

Melissa A Troester

University of North Carolina at Chapel Hill

Elisa V Bandera

Rutgers, The State University of New Jersey

Christine B Ambrosone

Roswell Park Comprehensive Cancer Center

Julie R Palmer

Georgetown Lombardi Comprehensive Cancer Center

Abstract:
Introduction: Recent oral contraceptive (OC) use has been consistently associated with increased risk of breast cancer, but evidence on specific breast cancer subtypes is sparse.

Methods: We investigated recency and duration of OC use in relation to molecular subtypes of breast cancer in a pooled analysis of data from the African American Breast Cancer Epidemiology and Risk Consortium. The study included 1,848 women with estrogen receptor-positive (ER+) breast cancer, 1,043 with ER-negative (ER-) breast cancer (including 494 triple negative (TN) tumors, which do not have receptors for estrogen, progesterone, and human epidermal growth factor 2), and 10,044 controls. Multivariable polytomous logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for exposure categories relative to never use, controlling for potential confounding variables.

Results: OC use within the previous 5 years was associated with increased risk of ER+ (OR 1.46, 95% CI 1.18 to 1.81), ER- (OR 1.57, 95% CI 1.22 to 1.43), and TN (OR 1.78, 95% CI 1.25 to 2.53) breast cancer. The risk declined after cessation of use but was apparent for ER+ cancer for 15 to 19 years after cessation and for ERbreast cancer for an even longer interval after cessation. Long duration of use was also associated with increased risk of each subtype, particularly ER-.

Conclusions: Our results suggest that OC use, particularly recent use of long duration, is associated with an increased risk of ER+, ER-, and TN breast cancer in African American women. Research into mechanisms that explain these findings, especially the association with ERbreast cancer, is needed.


Risk of breast cancer in relation to reproductive factors in North-West of Iran,  2013-2014

Abstract: More than one million new patients suffer from breast cancer annually in the world. In developed countries, breast cancer is the most common malignancy diagnosed among women, and in developing regions, it often ranks second to cervical cancer. This study aimed to investigate the relationship between incidence of breast cancer and reproductive factors in North-West of Iran. This retrospective analytical control-case study was conducted with 235 breast cancer patients and 235 women in the control group. Data collection tools included a set of questions with interviews and patient medical records. Data were analyzed using statistical tests: t-test, Chi-square, Fisher, and Pearson correlation coefficient. Significantly increased risks were associated between breast cancer and older age at first pregnancy, age at menopause and history of contraceptive use. A trend for decreasing risk were observed with increasing parity. Findings of this study showed no association between breast cancer and age at menarche. The study results suggested that physiological and reproductive factors may play important roles in the development breast cancer among Iranian women.

Asian Pacific Journal of Cancer Prevention : APJCP


Surveillance of congenital malformations in infants conceived through assisted reproductive technology or other fertility treatments

Abstract:
Background: As assisted reproductive technology (ART) becomes more common, it is important to understand the associated risks. The objective of this study was to determine if congenital malformations are associated with ART or other fertility treatments in New York.

Methods: In a retrospective cohort study of all live births in upstate New York from 1997 to 2005, exposure was defined using ART or other fertility treatments as noted on birth certificates. Outcomes were assessed from the New York State Congenital Malformations Registry. Specific malformations were examined to determine if there is elevated risk for exposed singleton infants compared with infants conceived naturally.

Results: The study included 7120 in the ART group, 11,890 in the other fertility treatments group and 1,118,162 in the comparison group. The relative risk for a congenital malformation was 1.43 (95% CI 1.19–1.72) for singleton infants conceived through ART compared with singleton infants conceived naturally. The specific defects associated with ART were patent ductus arteriosus, hypospadias, and obstructive defect in the renal pelvis and ureter, while spina bifida, other specific anomalies of the spinal cord, atresia or stenosis of the pulmonary valve, hypospadias, and obstructive defects of the renal pelvis and ureter were associated with other fertility treatment.

Conclusion: Assisted reproductive technology is associated with a slight excess risk of birth defects. The specific congenital malformations with elevated risks for singleton infants vary depending on the exposure. Further research is necessary to understand the mechanism related to the increase in risk. Birth Defects Research (Part A) 103:119–126, 2015 © 2015 Wiley Periodicals, Inc.

Birth Defects Research Part A: Clinical and Molecular Teratology


Effect of male and female body mass index on pregnancy and live birth success after in vitro fertilization

Sunni L Mumford

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Objective: To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.
Design: Prospective cohort study.
Setting: University fertility center. PATIENT(S): All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryologic parameters, clinical pregnancy, and live birth incidence. RESULT(S): The average male BMI among the study population was 27.5 ± 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (≥35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success. CONCLUSION(S): Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.


Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy

Ettore Cicinelli

Unit of Obstetrics and Gynecology, Department of Biomedical and Human Oncologic Science, University of Bari, 70124 Bari, Italy

Ugo Indraccolo

L'organizzazione Ospedale di Civitanova M

Pantaleo Greco

Department of Translational and for Romagna Medicine, University of Ferrara, 44121 Ferrara, Italy

Abstract:
STUDY QUESTION: What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome?

SUMMARY ANSWER: Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle.

WHAT IS KNOWN ALREADY: We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE.

STUDY DESIGN, SIZE, DURATION: A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF.

PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt.

MAIN RESULTS AND THE ROLE OF CHANCE: Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively).

LIMITATIONS, REASONS FOR CAUTION: Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases.

WIDER IMPLICATIONS OF THE FINDINGS: A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt.


Hormonal contraception and the risk of HIV acquisition: an individual participant  data meta-analysis

Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, Van Damme L, Delany-Moretlwe S, Francis SC, Friedland BA, Hayes RJ, Heffron R, Kapiga S, Karim QA, Karpoff S, Kaul R, McClelland RS, McCormack S, McGrath N, Myer L, Rees H, van der Straten A, Watson-Jones D, van de Wijgert JH, Stalter R, Low N

Abstract:
Background: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC. METHODS AND

Findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37,124 women (43,613 woman-years) and 1,830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I(2) < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (p(interaction) = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship.

Conclusions: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.


Endometriosis and infertility: how and when to treat?

Jean Bouquet de la Jolinière

Service de gynécologie obstétrique, HFR Fribourg - Hôpital Cantonal , Fribourg , Switzerland.

Abstract: Endometriosis is defined as the presence of endometrial-like tissue (glands or stroma) outside the uterus, which induces a chronic inflammatory reaction. Although endometriosis impairs fertility, it does not usually completely prevent conception. The question of evidence based-medicine guidelines in endometriosis-associated infertility is weak in many situations. Therefore, we will highlight in this issue where the challenges are.


Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies

Abstract:
Background: The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies.

Methods: We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features.

Findings: We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1·40, 95% CI 1·16-1·69). This risk was lower in the eight studies done in women in the general population (pooled HR 1·31, 95% CI 1·10-1·57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I(2) 51·1%, 95% CI 0-79·3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I(2) 54%, 0-88·7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1·00, 0·86-1·16) or five studies of norethisterone enanthate (pooled HR 1·10, 0·88-1·37).

Interpretation: Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.

Funding: None.


Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: preliminary clinical results

Abstract: OBJECTIVE: The clinic use of alpha Lipoic Acid (ALA) is linked to its capability to exert antioxidant effects and, more interestingly, to counteract the pathologic changes of complex networks of cytokines, chemokines and growth factors, restoring their physiological state. The aim of this randomized controlled clinical trial was to test the contribution of oral supplementation of ALA to the standard treatment with Progesterone vaginal suppositories, in healing subchorionic hematomas in patients with threatened miscarriage. Controls were administered only Progesterone suppositories. PATIENTS AND METHODS: Nineteen pregnant women in the first trimester of gestation, with threatened miscarriage and ultrasound evidence of subchorionic hematoma, were included in the trial and randomly divided in two groups: controls, treated with 400 mg Progesterone (200 mg 2 times per day), given by vaginal suppositories, and case study treated with the same Progesterone dosage, plus ALA, given orally at the dose of 600 mg (300 mg 2 times per day, DAV(R), Lo.Li. Pharma srl, Italy). Sixteen patients completed the trial. Treatment was performed until complete resolution of the clinical picture. RESULTS: In both groups, the subjects improved significantly but, in general, a better and faster evolution in the major signs of threatened miscarriage was observed in the subjects treated with ALA and Progesterone. In these patients, the speed of resorption of subchorionic hematoma was significantly (p <= 0.05) superior compared to controls. The ALA and Progesterone group showed a faster decrease or disappearance of all symptoms than that observed in the control group, however the difference was not significant. CONCLUSIONS: These preliminary results suggest that ALA supplementation significantly contributes to speed up the process of restoration of physiological conditions in threatened miscarriage and ameliorates the medical conditions of both the mothers and the foetus, probably modulating the networks of cytokines, growth factors and other molecules.

European review for medical and pharmacological sciences


Endometriosis in adolescents

Endometriosis in adolescents

Abstract:
BACKGROUND AND OBJECTIVES: Women with endometriosis often report onset of symptoms during adolescence; however, the diagnosis of endometriosis is often delayed. The aim of this study was to describe the experience of adolescents who underwent laparoscopy for pelvic pain and were diagnosed with endometriosis: specifically, the symptoms, time from onset of symptoms to correct diagnosis, number and type of medical professionals seen, diagnosis, treatment, and postoperative outcomes.

METHODS: We reviewed a series of 25 females ≤21 years of age with endometriosis diagnosed during laparoscopy for pelvic pain over an 8-year period. These patients were followed up for 1 year after surgery.

RESULTS: The mean age at the time of surgery was 17.2 (2.4) years (range, 10-21). The most common complaints were dysmenorrhea (64%), menorrhagia (44%), abnormal/irregular uterine bleeding (60%), ≥1 gastrointestinal symptoms (56%), and ≥1 genitourinary symptoms (52%). The mean time from the onset of symptoms until diagnosis was 22.8 (31.0) months (range, 1-132). The median number of physicians who evaluated their pain was 3 (2.3) (range, 1-12). The adolescents had stage I (68%), stage II (20%), and stage III (12%) disease. Atypical endometriosis lesions were most commonly observed during laparoscopy. At 1 year, 64% reported resolved pain, 16% improved pain, 12% continued pain, and 8% recurrent pain.

CONCLUSIONS: Timely referral to a gynecologist experienced with laparoscopic diagnosis and treatment of endometriosis is critical to expedite care for adolescents with pelvic pain. Once the disease is diagnosed and treated, these patients have favorable outcomes with hormonal and nonhormonal therapy.

JSLS : Journal of the Society of Laparoendoscopic Surgeons


Trends of male factor infertility, an important cause of infertility: A review of literature

Abstract: Infertility and problems of impaired fecundity have been a concern through ages and is also a significant clinical problem today, which affects 8-12% of couples worldwide. Of all infertility cases, approximately 40-50% is due to "male factor" infertility and as many as 2% of all men will exhibit suboptimal sperm parameters. It may be one or a combination of low sperm concentration, poor sperm motility, or abnormal morphology. The rates of infertility in less industrialized nations are markedly higher and infectious diseases are responsible for a greater proportion of infertility. The present literature will help in knowing the trends of male factor infertility in developing nations like India and to find out in future, various factors that may be responsible for male infertility.


Relationship between semen production and medical comorbidity


CARTR Plus 2015 Annual Report (2014 Data) - Canadian Assisted Reproductive Technologies Register Plus

Canadian Fertility and Andrology Society; BORN Ontario

Abstract: CARTR Plus annual report covering Canadian ART cycle outcomes. Voluntary professional society data submission via CFAS / BORN Ontario.