Serum caffeine and paraxanthine concentrations and menstrual cycle function: correlations with beverage intakes and associations with race, reproductive hormones, and anovulation in the BioCycle Study

Enrique F Schisterman

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Jean Wactawski-Wende

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

Abstract:
Background: Clinicians often recommend limiting caffeine intake while attempting to conceive; however, few studies have evaluated the associations between caffeine exposure and menstrual cycle function, and we are aware of no previous studies assessing biological dose via well-timed serum measurements.

Objectives: We assessed the relation between caffeine and its metabolites and reproductive hormones in a healthy premenopausal cohort and evaluated potential effect modification by race.

Design: Participants (n = 259) were followed for ≤2 menstrual cycles and provided fasting blood specimens ≤8 times/cycle. Linear mixed models were used to estimate associations between serum caffeine biomarkers and geometric mean reproductive hormones, whereas Poisson regression was used to assess risk of sporadic anovulation.

Results: The highest compared with the lowest serum caffeine tertile was associated with lower total testosterone [27.9 ng/dL (95% CI: 26.7, 29.0 ng/dL) compared with 29.1 ng/dL (95% CI: 27.9, 30.3 ng/dL), respectively] and free testosterone [0.178 ng/mL (95% CI: 0.171, 0.185 ng/dL) compared with 0.186 ng/mL (95% CI: 0.179, 0.194 ng/dL), respectively] after adjustment for age, race, percentage of body fat, daily vigorous exercise, perceived stress, depression, dietary factors, and alcohol intake. The highest tertiles compared with the lowest tertiles of caffeine and paraxanthine were also associated with reduced risk of anovulation [adjusted RRs (aRRs): 0.39 (95% CI: 0.18, 0.87) and 0.40 (95% CI: 0.18, 0.87), respectively]. Additional adjustment for self-reported coffee intake did not alter the reproductive hormone findings and only slightly attenuated the results for serum caffeine and paraxanthine and anovulation. Although reductions in the concentrations of total testosterone and free testosterone and decreased risk of anovulation were greatest in Asian women, there was no indication of effect modification by race.

Conclusion: Caffeine intake, irrespective of the beverage source, may be associated with reduced testosterone and improved menstrual cycle function in healthy premenopausal women.

The American journal of clinical nutrition


Uterine fibroids

Uterine fibroids

Abstract: Uterine fibroids (also known as leiomyomas or myomas) are common clonal neoplasms of the uterus. Fibroids have both smooth muscle and fibroblast components, in addition to a substantial amount of fibrous extracellular matrix, which all contribute to the pathogenetic process. Fibroids are extremely heterogeneous in their pathophysiology, size, location and clinical symptomatology. They are also a part of a range of disease in which some variants have facets of malignant behaviour but overall are benign. Risk for fibroids is associated with race; black women have a higher risk of developing fibroids earlier in life than their white counterparts and also develop more-severe forms of the disease. Clinically, fibroids account for one-third to half of all hysterectomies and are associated with substantial morbidity and health care costs for women of reproductive age. Indeed, current treatments are primarily surgical and interventional; approximately three-quarters of all fibroid treatments are hysterectomies. However, clinical innovations are emerging in the use of progesterone receptor modulators as a medical therapy. New information is rapidly accumulating about the genetic subgroups that lead to fibroid formation, which might aid further understanding of the clinical heterogeneity of this disease and lead to individualized treatments. This information is a crucial development given the current lack of high-quality evidence on which to base therapeutic decisions.


Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease

Hyslop LA, Blakeley P, Craven L, Richardson J, Fogarty NM, Fragouli E, Lamb M, Wamaitha SE, Prathalingam N, Zhang Q, O'Keefe H, Takeda Y, Arizzi L, Alfarawati S, Tuppen HA, Irving L, Kalleas D, Choudhary M, Wells D, Murdoch AP, Turnbull DM, Niakan KK, Herbert M

Abstract: Of the 237 women, 92 (38.8%) had experienced both a normal and a toxaemic pregnancy, and 72 (78%) contrasted the sense of well-being associated with a normal pregnancy with the malaise and minor symptoms characteristic of the toxaemic condition. The striking feature of these early minor symptoms of toxaemia was their close resemblance to those of premenstrual syndrome noted in an earlier investigation (Greene and Dalton, 1953), most patients confirming that the minor symptoms during their toxaemic pregnancy were similar, though of increased severity, to those experienced in the premenstruum, irrespective of whether the onset of premenstrual syndrome had preceded or followed the toxaemic pregnancy.


The Home Observation of Periconceptional Exposures (HOPE) study, a prospective cohort: aims, design, recruitment and compliance

Abstract:
BACKGROUND: To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid.

RESULTS: Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected ≥97.2 % of requested saliva samples, and men collected ≥89.9 % of requested semen samples. Within the periovulatory days (±3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was ≥88 % for questionnaire completion at specified time points.

CONCLUSIONS: Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data.

Environmental Health : a Global Access Science Source


Patterns and prevalence of medication use across the menstrual cycle among healthy, reproductive aged women

Abstract:
Purpose: The purpose of this study is to characterize the patterns of medication intake in healthy, reproductive-age women not using hormonal contraception.

Methods: Two hundered fifty-nine healthy, premenopausal women (18-44 years of age) enrolled in the BioCycle Study (2005-2007) were followed over two menstrual cycles. Women were excluded if they were currently using oral contraceptives or other chronic medications. Over-the-counter and prescription medication use among participants was evaluated daily throughout the study via a diary assessing type of medication, dosage, units, and frequency. Medications were categorized as allergy, antibiotics, central nervous system (CNS), cold and cough, gastrointestinal, musculoskeletal, and pain medication based on primary active ingredient. Medication use within each category was assessed across standardized 28-day cycles to evaluate differences in use across cycle phases (i.e., early, middle, and late).

Results: Medication use was reported by 73% of participants. The most and least frequently used medications, respectively, were pain (69%) and musculoskeletal medications (1%). Pain, CNS, and antibiotic medication use varied significantly across the cycle, with pain and CNS medication more frequently reported during menses and antibiotics more frequently during the luteal phase. Allergy, cold and cough, gastrointestinal, and musculoskeletal medication use did not vary across the cycle.

Conclusions: Patterns of medication use among reproductive age women vary across the menstrual cycle for certain types of medications, particularly in pain (e.g., Ibuprofen), antibiotics (e,g, Amoxicillin), and CNS (e.g., Adderall) medications. Future studies involving use of these types of medication in premenopausal women may need to consider the relationship of their use to the menstrual cycle.


Marijuana, the Endocannabinoid System and the Female Reproductive System

Abstract: Marijuana use among women is highly prevalent, but the societal conversation on marijuana rarely focuses on how marijuana affects female reproduction and endocrinology. This article reviews the current scientific literature regarding marijuana use and hypothalamic-pituitary-ovarian (HPO) axis regulation, ovarian hormone production, the menstrual cycle, and fertility. Evidence suggests that marijuana can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles. Tolerance to these effects has been shown in rhesus monkeys, but the effects of chronic marijuana use on human female reproduction are largely unknown. Marijuana-induced analgesia, drug reinforcement properties, tolerance, and dependence are influenced by ovarian hormones, with estrogen generally increasing and progesterone decreasing sensitivity to marijuana. Carefully controlled regulation of the Endocannabinoid System (ECS) is required for successful reproduction, and the exogenous cannabinoids in marijuana may disrupt the delicate balance of the ECS in the female reproductive system.

The Yale journal of biology and medicine


Stress-induced increases in progesterone and cortisol in naturally cycling women

Abstract: Studies with animals of both sexes show that the adrenal glands release progesterone in addition to cortisol in response to stress. However, little is known about the progesterone response to stress in naturally cycling women. We investigated the effect of stress on estradiol, progesterone, and cortisol levels in women during the follicular phase of the menstrual cycle. We found that physical stress (the cold pressor test) had no effect on estradiol levels, but increased progesterone and cortisol. We also found positive correlations between baseline progesterone and cortisol levels, as well as between the change in progesterone and cortisol before and after water exposure in both the stress and control sessions. Mediation analyses revealed during the stress session, the change in progesterone from baseline to 42-min post-stress onset was mediated by the magnitude of change in cortisol levels across the same time span. Overall, these findings reveal that progesterone released in response to stress as observed in animals and men extends to women during the low ovarian output follicular phase of the menstrual cycle, and that the mechanism of release may be similar to the mechanism of cortisol release.


Deep Retraction Pockets, Endometriosis, and Quality of Life

Abstract:
Objective: The purpose of this study was to examine if deep retraction pockets (DRPs) in the posterior cul-de-sac and uterosacral ligaments could be a manifestation of endometriosis and if excision of these pockets improves pain symptoms and quality of life.

Study Design: Prospective cohort study Canadian Task Force Classification, II-3.

Materials and Methods: Preoperative data, operative data, and follow-up data were collected prospectively at the Center for Endometriosis at Saint Louis University, a referral center for the surgical management of endometriosis.

Results: The 107 consecutive patients who presented with preoperative deep dyspareunia were included in the study, and the median postoperative follow-up was 13 months. Endometriosis was confirmed histologically in any location excised in 88/107 (82.2%) of the women, and 31 DRPs were excised from 25 women with DRPs in the posterior cul-de-sac or uterosacral ligaments, of which 15/31 (48.4%) had endometriosis. Of the 10 DRPs without visible surface lesions, 3 (30.0%) had endometriosis on histology. Pain symptoms and quality of life significantly improved after excision surgery, whether or not DRPs were present. Women who had endometriosis in their DRP also had significant improvement in deep dyspareunia and chronic pelvic pain and quality of life. Results did not differ when patients who took postoperative hormonal suppression were removed from the analyses.

Conclusion: Patients had significantly improved pain symptoms and quality of life after excision surgery, whether or not DRPs were present. This study demonstrated that a DRP may be a manifestation of endometriosis (even with a clear surface of the pocket), so that DRPs should be excised to achieve optimal excision of endometriosis.


A randomized trial of Boswellia in association with betaine and myo-inositol in the management of breast fibroadenomas

Abstract:
Objective: Breast fibroadenoma is a common finding in young women and actually accounts for the majority of benign breast lumps. Fibroadenoma does not require any treatment unless clinical symptoms (mostly mastalgia) or histological markers of cancer risk (atypia) impose specific medical or surgical intervention. In symptomatic fibroadenoma, anti-estrogenic treatments provided evidence of success. Yet, these therapies are often associated with relevant side effects that lead to drug treatment discontinuation. Additionally, in such cases, relapse is a frequent issue. Therefore, an optimal strategy is still warranted. Boswellia, betaine and myo-inositol have already been proved to modulate different pathways - inflammatory, metabolic, oxidative and endocrine processes - in a wide array of human tissues. Based on that background, we hypothesized that these substances can effectively synergize in inducing the regression of fibroadenoma.
Patients and

Methods: We included 64 patients ≤ 30 years of age with fibroadenoma. The patients were randomized into two groups. The experimental group was treated with an association of Boswellia, betaine, myo-inositol, B-group vitamins and N-acetylcysteine for 6 months; otherwise, the placebo group was treated only with B-group vitamins and N-acetylcysteine. Patients were monitored at the enrollment and the end of the study for evaluating the clinical response.

Results: A significant clinical improvement was observed in the experimental arm. Fibroadenoma median volume reduction averaged 17.86% in the experimental group and 5.96% in the placebo group. Moreover, 14 out of 36 (38.88%) patients showed a reduction of fibroadenoma volume compared to 5/28 (17.85%) observed in the placebo group (p = 0.005).

Conclusions: A supplementation with Boswellia, betaine and myo-inositol reduces fibroadenoma dimension in young women. No relevant side effects have been recorded.

European Review for Medical and Pharmacological Sciences


The State of Sex Education in the United States

The Journal of Adolescent Health : Official Publication of the Society for  Adolescent Medicine


Ovarian Cancer: The Fallopian Tube as the Site of Origin and Opportunities for  Prevention

Abstract: High-grade serous carcinoma (HGSC) is the most common and aggressive histotype of epithelial ovarian cancer (EOC), and it is the predominant histotype associated with hereditary breast and ovarian cancer syndrome (HBOC). Mutations in BRCA1 and BRCA2 are responsible for most of the known causes of HBOC, while mutations in mismatch repair genes and several genes of moderate penetrance are responsible for the remaining known hereditary risk. Women with a history of familial ovarian cancer or with known germline mutations in highly penetrant genes are offered the option of risk-reducing surgery that involves the removal of the ovaries and fallopian tubes (salpingo-oophorectomy). Growing evidence now supports the fallopian tube epithelia as an etiological site for the development of HGSC and consequently, salpingectomy alone is emerging as a prophylactic option. This review discusses the site of origin of EOC, the rationale for risk-reducing salpingectomy in the high-risk population, and opportunities for salpingectomy in the low-risk population.


Laparoscopic Fimbrioplasty and Neosalpingostomy in Female Infertility: A Review  of 402 Cases at the Gynecological Endoscopic Surgery and Human Reproductive  Teaching Hospital in Yaoundé-Cameroon

Etienne Belinga

Department of Obstetrics and Gynaecology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; Gynecological Endoscopic Surgery and Human Reproductive Teaching H...

Alexis Medou

Anesthesia Unit, Gynecological Endoscopic Surgery and Human Reproductive Teaching Hospital, Yaoundé, Cameroon.

Yolande Salome Mimboe

Department of Obstetrics and Gynaecology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon.

Michel Toukam

Laboratory of Clinical Biology, Gynecological Endoscopic Surgery and Human Reproductive Teaching Hospital, Yaoundé, Cameroon.

Abstract:
Background: More than 70 million couples suffer from infertility worldwide. The aim of this study was to evaluate the fertility outcomes after laparoscopic fimbrioplasty and neosalpingostomy in female infertility.

Methods: Laparoscopic distal tuboplasty was carried out for 402 cases at the Gynecological Endoscopic Surgery and Human Reproductive Teaching Hospital in Yaoundé-Cameroon in Central Africa from December 2002 to December 2007. Laparoscopic fimbrioplasty and neosalpingostomy were done using bipolar electrocoagulation and conventional endoscopic instruments. Log-rank test was used to compare cumulative rate curves of intrauterine pregnancy with respect to the tubal stages. P<0.05 was considered statistically significant.

Results: The mean age of the patients was 31.6±5.45 years. Secondary infertility was the most frequent type of infertility (70.14%). The laparoscopic tubal surgery done consisted of fimbrioplasty in 185(46%) cases and neosalpingostomy in 217 (54%) cases. Of 260 women followed up after tuboplasty, there were overall 74 (28.48%) pregnancies; 68(26.1%) intrauterine pregnancies and 6(2.3%) ectopic pregnancies. Pregnancy rates were significantly associated to the tubal stage (63% in stage 1, 15% in stage 3 and 00% in stage 4; p<0.001) and the adnexal adhesion scores (73.91% in the absence of adnexal adhesions and 8.8% in the case of a severe adnexal adhesion score). Of the 68 intrauterine pregnancies, there were 60(88%) live births and 8(12%) spontaneous abortions.

Conclusion: It is believed that laparoscopic fimbrioplasty and neosalpingostomy should be the preferred choice when faced with tubal distal occlusion in a context of female infertility. This implies that training in endoscopic surgery should be regarded as an important issue in developing countries.


Adolescents’ use of combined hormonal contraceptives for menstrual cycle–related problem treatment and contraception: evidence of potential lifelong negative reproductive and bone effects

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Non-sexually active adolescents are currently treated with combined hormonal contraception (CHC) for common experiences (e.g., cramps, acne) and serious problems (e.g., hypothalamic amenorrhea, heavy menstrual flow) for which it is not indicated, is ineffective, and is likely to cause negative long-term reproductive and bone effects. The importance to a woman's health of adolescent reproductive/bone maturation is described. Evidence is also provided to show the association of CHC use by adolescents with subfertility and inadequate bone growth. Ibuprofen is safer and more effective for cramps and heavy flow; cyclic progesterone builds bone in amenorrhea. In summary, a common, unscientific medical "habit" is compromising long-term reproductive and bone health in adolescents.


Apply the Precautionary Principle Concerning Combined Hormonal Contraception Use in Adolescents

Abstract: Here I respond to Akers, Dhar, and Shah's (2016), Stubbs's (2016), Olshansky's (2016), and Kissling's (2016) commentaries on the article (Prior, 2016) in which I expressed concerns about the potential adverse long-term reproductive and bone health effects on normal adolescents’ maturation related to use of combined hormonal contraceptives (CHC) for contraception and/or treatment. Although Akers et al. (2016) take exception, the precautionary principle on which medical/pharmaceutical ethics is based challenges us to show that CHC is officially indicated and effective in randomized, double-blind, placebo-controlled trials with adolescents. Those who support current practices are obligated to provide young patients and their parents with evidence from large, population-based, prospective studies (or meta-analyses of longitudinal data) that adolescents who have used CHC develop the same menstrual cycle/ovulatory function, fertility, and reproductive lifespan and similar bone density and strength as peers who did not use CHC. Without this information there can be neither reproductive justice (Kissing, 2016), nor true choice. Why is this minimal, expected scientific data not available? It is likely that authors of practice guidelines for adolescent CHC contraceptive use and who advocate its “non-contraceptive benefits” have pro-estrogen cultural biases or conflicts of interests due to pharmaceutical industry connections. I agree with Olshansky (2016) that we should listen to adolescents’ concerns and use evidence-based and safe treatments for milder heavy bleeding and cramps. For heterosexual adolescents seeking contraception, we can suggest and explain the use of safer, yet effective, nonhormonal strategies, such as the copper IUD or a barrier plus full-dose vaginal spermicide.


Endometriosis and Risk of Coronary Heart Disease

Abstract:
BACKGROUND: Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women's risk for coronary heart disease (CHD).

METHODS AND RESULTS: We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses' Health Study II (1989-2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98), angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these CHD end points combined (1.62; 1.39-1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02-4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35-2.02; 50< age ≤55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis.

CONCLUSIONS: In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD.

Circulation. Cardiovascular quality and outcomes


Zika Virus and Birth Defects--Reviewing the Evidence for Causality

Sonja A Rasmussen

Center for Surveillance, Epidemiology, and Laboratory Services

Denise J Jamieson

National Center for Chronic Disease Prevention and Health Promotion

Margaret A Honein

National Center on Birth Defects and Developmental Disabilities

Lyle R Petersen

Centers for Disease Control and Prevention

Abstract: The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and birth outcomes, most notably microcephaly and other serious brain anomalies. To determine whether Zika virus infection during pregnancy causes these adverse outcomes, we evaluated available data using criteria that have been proposed for the assessment of potential teratogens. On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this causal relationship included Zika virus infection at times during prenatal development that were consistent with the defects observed; a specific, rare phenotype involving microcephaly and associated brain anomalies in fetuses or infants with presumed or confirmed congenital Zika virus infection; and data that strongly support biologic plausibility, including the identification of Zika virus in the brain tissue of affected fetuses and infants. Given the recognition of this causal relationship, we need to intensify our efforts toward the prevention of adverse outcomes caused by congenital Zika virus infection. However, many questions that are critical to our prevention efforts remain, including the spectrum of defects caused by prenatal Zika virus infection, the degree of relative and absolute risks of adverse outcomes among fetuses whose mothers were infected at different times during pregnancy, and factors that might affect a woman’s risk of adverse pregnancy or birth outcomes. Addressing these questions will improve our ability to reduce the burden of the effects of Zika virus infection during pregnancy.


Metabolic syndrome and metabolic risk profile according to polycystic ovary  syndrome phenotype

Derya Akdag Cirik

Department of Reproductive Medicine and Infertility Ankara Etlik Zubeyde Hanım Women's Health Training and Research Hospital  Ankara Turkey

Abstract:
Aim: It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes.

Methods: A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups.

Results: Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P < 0.001). Although the prevalence of obesity was similar, the number of patients with homeostatic model assessment insulin resistance index (HOMA-IR) >3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P < 0.01).

Conclusion: Phenotypes A and B had the highest risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women.

The Journal of Obstetrics and Gynaecology Research


Oral Contraceptive Use and Prevalence of Self-Reported Glaucoma or Ocular Hypertension in the United States

Yuhua Li

Third Affiliated Hospital of Guangzhou Medical University

Abstract:
PURPOSE: To investigate the association between oral contraceptive (OC) use and glaucoma prevalence in the United States.

DESIGN: Cross-sectional study.

PARTICIPANTS: A total of 3406 female participants, aged 40 years or older, from the 2005 to 2008 National Health and Nutrition Examination Survey, who reported a presence or absence of glaucoma or ocular hypertension completed both the vision and the reproductive health questionnaires and underwent eye examinations.

METHODS: Multivariate regression analysis was used to assess the correlation between OC use and self-reported glaucoma or ocular hypertension (n = 231 cases), controlling for potential confounders, including age, ethnicity, systemic comorbidities such as hypertension and stroke, ocular diseases such as cataract and diabetic retinopathy, and reproductive health factors, including age at menopause, age at menarche, history of hormone replacement therapy, and gynecological surgical history.

MAIN OUTCOME MEASURES: The outcome variable was self-reported glaucoma or ocular hypertension.

RESULTS: After adjusting for confounders, those with ≥3 years of OC use had greater odds (odds ratio, 1.94; 95% confidence interval, 1.22-3.07) of self-reported glaucoma or ocular hypertension. Other factors associated with higher glaucoma or ocular hypertension prevalence included older age, African American race, and later age at menarche.

CONCLUSIONS: Oral contraceptive use may be associated with increased risk of self-reported glaucoma or ocular hypertension.


Phthalate metabolite levels and menopausal hot flashes in midlife women

Abstract: During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women.

Reproductive toxicology (Elmsford, N.Y.)


The effect of depot medroxyprogesterone acetate on postnatal depression: a  randomised controlled trial

Mandisa Singata-Madliki

Deputy Director, Effective Care Research Unit (ECRU), Eastern Cape Department of Health, East London Hospital Complex, Universities of the Witwatersrand and Fort Hare, East London, South Africa

Abstract:
Background: Depot medroxyprogesterone acetate (DMPA) is the most commonly used hormonal contraceptive method in South Africa. It is frequently administered in the immediate postnatal period, yet it is unclear whether it affects the risk of postnatal depression (PND).

Aim: To determine whether DMPA increases the risk of PND compared with the copper-containing intrauterine device (IUD) when administered after delivery. DESIGN AND Setting: A single-blind randomised controlled trial conducted at two teaching hospitals in East London, South Africa.

Methods: Eligible, consenting women (N=242) requiring postnatal contraception were randomised to receive DMPA or an IUD within 48 hours of childbirth and interviewed at 1 and 3 months postpartum. Depression was measured using the Beck Depression Inventory (BDI-II) and the Edinburgh Postnatal Depression Scale (EPDS). Resumption of sexual intercourse, menstrual symptoms and breastfeeding rates were also assessed.

Results: One-month EPDS depression scores were statistically significantly higher in the DMPA arm compared with IUD arm (p=0.04). Three-month BDI-II scores were significantly higher in the DMPA arm than in the IUD arm (p=0.002) and, according to the BDI-II but not the EPDS, more women in the DMPA arm had major depression at this time-point (8 vs 2; p=0.05). There were no statistically significant differences in other outcome measures except that fewer women had resumed sexual activity by 1 month postpartum in the DMPA arm (13% vs 26%; p=0.02).

Conclusions: The possibility that immediate postnatal DMPA use is associated with depression cannot be excluded. These findings justify further research with longer follow-up. CLINICAL TRIAL NUMBER: PACTR201209000419241.

The Journal of Family Planning and Reproductive Health Care


Effects of Zinc Supplementation on Endocrine Outcomes in Women with Polycystic Ovary Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: The current study was conducted to evaluate the effects of zinc supplementation on endocrine outcomes, biomarkers of inflammation, and oxidative stress in patients with polycystic ovary syndrome (PCOS). This study was a randomized double-blind, placebo-controlled trial. Forty-eight women (18-40 years) with PCOS diagnosed according to Rotterdam criteria were randomly assigned to receive either 220 mg zinc sulfate (containing 50 mg zinc) (group 1; n = 24) and/or placebo (group 2; n = 24) for 8 weeks. Hormonal profiles, biomarkers of inflammation, and oxidative stress were measured at study baseline and after 8-week intervention. After 8 weeks of intervention, alopecia (41.7 vs. 12.5%, P = 0.02) decreased compared with the placebo. Additionally, patients who received zinc supplements had significantly decreased hirsutism (modified Ferriman-Gallwey scores) (-1.71 ± 0.99 vs. -0.29 ± 0.95, P < 0.001) and plasma malondialdehyde (MDA) levels (-0.09 ± 1.31 vs. +2.34 ± 5.53 μmol/L, P = 0.04) compared with the placebo. A trend toward a significant effect of zinc intake on reducing high-sensitivity C-reactive protein (hs-CRP) levels (P = 0.06) was also observed. We did observe no significant changes of zinc supplementation on hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative stress. In conclusion, using 50 mg/day elemental zinc for 8 weeks among PCOS women had beneficial effects on alopecia, hirsutism, and plasma MDA levels; however, it did not affect hormonal profiles, inflammatory cytokines, and other biomarkers of oxidative stress.


Vitamin D and Ovarian Reserve and Fecundability among Women with Proven Fecundity

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.

Rebecca A. Garbose

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
Vitamin D is associated with markers of ovarian reserve in women of advanced reproductive age and
in vitro
studies suggest that vitamin D may influence anti‐mullerian hormone (AMH). Higher vitamin D levels are also associated with improved IVF outcomes in some studies. However, less is understood regarding associations with ovarian reserve or time to pregnancy among younger women or women without a history of infertility. Our purpose was to assess the relationships between vitamin D and AMH and fecundability among women with proven fecundity.
Design
Secondary analysis of the EAGeR Trial, a multicenter, block‐randomized, double‐blind, placebo‐controlled clinical trial to evaluate the effect of preconception‐initiated daily low dose aspirin on reproductive outcomes in women with a history of pregnancy loss and normal fecundity.

Methods

Participants were attempting pregnancy, aged 18–40 years, with 1–2 prior pregnancy losses and no history of infertility. We assessed 25‐OH vitamin D and AMH in serum at baseline (not pregnant) among 1185 women. AMH levels were log‐transformed for normality. Linear regression was used to estimate associations between vitamin D and AMH concentrations adjusting for age, body mass index, race, season, physical activity, and number of prior losses. Time to hCG detected pregnancy was assessed using Cox proportional hazard regression models for discrete survival time, accounting for left truncation and right censoring, to estimate fecundability odds ratios (FOR), adjusting for the same factors.

Results
A total of 163 women (13.8%) had deficient vitamin D levels (<20 ng/mL). Overall, vitamin D levels were not associated with AMH (percent change −1.6, 95% confidence interval [CI] −5.3%, 2.3% per 10 ng/mL). Vitamin D deficiency was also not associated with AMH (deficient: adjusted geometric mean AMH 2.51, 95% CI 2.20, 2.85 vs. inadequate/sufficient: 2.74, 95% CI 2.60, 2.89). There also were no significant associations observed between overall vitamin D levels or deficiency and fecundability (FOR 1.09, 95% CI 0.84, 1.42 comparing deficient vs. inadequate/sufficient) after adjustment.

Conclusions
Vitamin D was not associated with AMH, time to pregnancy, or fecundability among women with proven fecundity. These results suggest that vitamin D is not associated with ovarian reserve or fecundability and that vitamin D supplementation may offer little clinical benefit for improving markers of ovarian reserve and fecundity.
Support or Funding Information
Intramural Research Program, DIPHR, NICHD, NIH


Antimüllerian hormone and pregnancy loss from the Effects of Aspirin in Gestation and Reproduction trial

Abstract:
Objective: To evaluate if antimüllerian hormone (AMH) is associated with pregnancy loss.
Design: Prospective cohort study within a block-randomized, double-blind, placebo-controlled trial of low-dose aspirin.
Setting: Not applicable. PATIENT(S): Women (n = 1,228) were of ages 18-40 years with a history of one to two pregnancy losses and were actively attempting pregnancy without fertility treatment. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Pregnancy loss. RESULT(S): Relative risks (and 95% confidence interval [CIs]) of human chorionic gonadotropin (hCG)-detected and clinical pregnancy loss were assessed with the use of log binomial models with robust variance and inverse probability weights adjusted for age, race, body mass index, income, trial treatment assignment, parity, number of previous losses, and time since most recent loss. AMH levels were defined as: low (<1.00 ng/mL; n = 124), normal (referent; 1.00-3.5 ng/mL; n = 595), and high (>3.5 ng/mL; n = 483). Of the 1,202 women with baseline AMH data, 19 (17.3%) with low AMH experienced a clinical loss, compared with 61 (11.4%) with normal AMH and 50 (11.8%) with high AMH levels. Low or high AMH levels, compared with normal AMH, were not associated with clinical loss. Results for hCG-detected pregnancy loss mirrored those of clinical loss. CONCLUSION(S): AMH values were not associated with hCG-detected or clinical pregnancy loss in unassisted conceptions in women with a history of one to two previous losses. Our data do not support routine AMH testing for prediction of pregnancy loss. Clinical

Trial Registration Number: NCT00467363.


Population, Reproductive, and Sexual Health: Data Are Essential Where Disciplines Meet and Ideologies Conflict

Abstract: The flourishing of the individual human person, the health of human society, and the ecological well being of planet earth are inextricably connected with the issues of human population, sexuality, and reproduction. Many academic disciplines have strong interests in these issues, approaching them from different perspectives and with different emphases. However, these areas of study are also infused with controversy and strong ideological positions arising from cultural, religious, political, and social traditions that sometimes clash with each other. To address these issues, two things are needed: (1) data that address questions from different underlying assumptions; (2) open and respectful discussion among scientists, clinicians, and policy makers who have different backgrounds, narrative frameworks, and conceptual perspectives (1). The new Section on Population, Reproductive and Sexual Health, Frontiers in Public Health will contribute constructively to these critical needs.


Methods for a Retrospective Population-based and Clinic-based Subfertility Cohort Study: the Fertility Experiences Study

Abstract:
BACKGROUND: Most cohort-based research for subfertility has been conducted in clinic-based cohorts, which may differ from population-based cohorts.

METHODS: We retrospectively recruited parallel cohorts of subfertile women: one by sampling two specialty fertility clinics in Utah, and one by population-based sampling based on marriage and birth records. The index date (of first clinic visit or subfertility status) was between 2000 and 2009, and we linked the women recruited to subsequent birth certificate records through December 2010.

RESULTS: We enrolled 459 women through clinic-based sampling and 501 women through population-based sampling. Clinic-based women were older, had higher annual household income and more likely to have had a most intensive treatment of intrauterine insemination (31%) or in vitro fertilisation (46%) than women from population recruitment (19% and 14% respectively). Conversely, they were less likely to have received no medical treatment (9%) compared to women from population recruitment (41%). For both types of sampling, prior to eligibility screening, non-responders were less likely to link to a live birth than responders: 51% vs. 58% for clinic-based, and 69% vs. 76% for the population-based with an index date in 2004.

CONCLUSIONS: Population-based sampling for subfertility cohort research identifies women who were more likely to have had less intensive treatment or no treatment. However, in both clinic-based and population-based sampling, women who have had a live birth are more likely to respond to retrospective recruitment.


Differential Item Functioning in the SF-36 Physical Functioning and Mental Health Sub-Scales: A Population-Based Investigation in the Canadian Multicentre Osteoporosis Study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Richard Sawatzky

School of Nursing, Trinity Western University & Centre for Health Evaluation and Outcomes Sciences, Providence Health Care, Langley, BC, Canada.

Alexandra Papaioannou

McMaster University, Hamilton, ON, Canada

Abstract:
Background: Self-reported health status measures, like the Short Form 36-item Health Survey (SF-36), can provide rich information about the overall health of a population and its components, such as physical, mental, and social health. However, differential item functioning (DIF), which arises when population sub-groups with the same underlying (i.e., latent) level of health have different measured item response probabilities, may compromise the comparability of these measures. The purpose of this study was to test for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scale items in a Canadian population-based sample.

Methods: Study data were from the prospective Canadian Multicentre Osteoporosis Study (CaMos), which collected baseline data in 1996-1997. DIF was tested using a multiple indicators multiple causes (MIMIC) method. Confirmatory factor analysis defined the latent variable measurement model for the item responses and latent variable regression with demographic and health status covariates (i.e., sex, age group, body weight, self-perceived general health) produced estimates of the magnitude of DIF effects.

Results: The CaMos cohort consisted of 9423 respondents; 69.4% were female and 51.7% were less than 65 years. Eight of 10 items on the PF sub-scale and four of five items on the MH sub-scale exhibited DIF. Large DIF effects were observed on PF sub-scale items about vigorous and moderate activities, lifting and carrying groceries, walking one block, and bathing or dressing. On the MH sub-scale items, all DIF effects were small or moderate in size.

Conclusions: SF-36 PF and MH sub-scale scores were not comparable across population sub-groups defined by demographic and health status variables due to the effects of DIF, although the magnitude of this bias was not large for most items. We recommend testing and adjusting for DIF to ensure comparability of the SF-36 in population-based investigations.


Effectiveness of bilateral tubotubal anastomosis in a large outpatient  population

Gary S Berger

University of North Carolina at Chapel Hill

Abstract:
STUDY Question: Is bilateral tubotubal anastomosis a successful treatment in an outpatient patient population?

SUMMARY ANSWER: For women wanting children after tubal sterilization, bilateral tubotubal anastomosis is an effective outpatient treatment.

WHAT IS KNOWN ALREADY: With the current emphasis in reproductive medicine on high technology procedures, the effectiveness of female surgical sterilization reversal is often overlooked. Previous clinical studies of tubal sterilization reversal have been mostly retrospective analyses of small patient populations.

STUDY DESIGN, SIZE, DURATION: A cohort of women who underwent outpatient bilateral tubotubal anastomosis from January 2000 to June 2013 was followed prospectively until December 2014 to determine the proportions of women undergoing the procedure who became pregnant and who had live births. Data were collected at the time of pregnancy. Differences in pregnancy rates and live birth rates associated with age, race and sterilization method were evaluated.

PARTICIPANTS/MATERIALS, SETTING, Methods: A total of 6692 women, aged 20-51 years, underwent outpatient bilateral tubotubal anastomosis.

MAIN RESULTS AND THE ROLE OF CHANCE: The crude overall pregnancy rate was 69%. The crude overall birth rate was 35%. Results varied according to age at sterilization reversal and the method of sterilization. Women under 30 years of age at reversal of ring/clip sterilizations had an 88% pregnancy rate and 62% birth rate. Pregnancy and birth rates declined as age increased at sterilization reversal. Coagulation sterilization reversals resulted in the lowest rates of pregnancies and births. Ligation/resection reversals had intermediate success rates.

LIMITATIONS, REASONS FOR CAUTION: Limitations of our study include probable underreporting of pregnancies based on patient-initiated reports; possible errors in the reporting of pregnancies or early miscarriages that may have been based solely on home pregnancy tests; and probable over-reporting of the diagnosis of ectopic pregnancies. We identified age and sterilization method as being associated with subsequent pregnancy, however, in order to be considered predictive, the associations would need to be validated in an independent second prospectively studied group of representative patients. Finally, we also included patients in the study population who had additional surgical procedures performed at the time of tubotubal anastomosis (e.g. uterine myomectomy, fimbrioplasty, ovarian cystectomy and adhesiolysis), factors that could result in differences in pregnancy statistics in our study versus other patient populations.

WIDER IMPLICATIONS OF THE Findings: The results of this study can help inform patients and clinicians about this low technology alternative to IVF.

STUDY FUNDING/COMPETING INTERESTS: None.

TRIAL REGISTRATION NUMBER: N/A.


Increased rate of spontaneous miscarriages in endometriosis-affected women

Abstract:
STUDY Question: Were spontaneous miscarriages more frequent in women with histologically proven endometriosis when compared with endometriosis-free controls?

SUMMARY ANSWER: Endometriosis-affected women display a significantly higher rate of previous spontaneous miscarriages than endometriosis-free controls.

WHAT IS KNOWN ALREADY: The association between endometriosis and miscarriages has long been debated without reaching a consensus.

STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study comparing exposed women (endometriosis) and control (without endometriosis) regarding the incidence of miscarriages. All study participants underwent surgery for benign gynaecological conditions in a tertiary-care university hospital between January 2004 and March 2013. After thorough surgical examination of the abdominopelvic cavity, 870 women with histologically proven endometriosis were allocated to the endometriosis group and 981 unaffected women to the control group. Only previously pregnant women were finally included for the study analysis: 284 women in the endometriosis group and 466 in the control group.

PARTICIPANTS/MATERIALS, SETTING, Methods: Data were collected preoperatively using a structured questionnaire. Among women with at least one pregnancy before the surgery, the type and number of the different previous first trimester pregnancies outcomes were studied. Previous history of miscarriage was studied according to the existence of previous infertility history and the disease severity (revised American Fertility Society and surgical classification).

MAIN RESULTS AND THE ROLE OF CHANCE: Four hundred and seventy-eight pregnancies in endometriosis-affected women and 964 pregnancies in controls were analysed. The previous miscarriage rate was significantly higher in women with endometriosis compared with the controls (139/478 [29] versus 187/964 [19%], respectively; ITALIC! P < 0.001). After a subgroup analysis, the miscarriage rates of women with endometriosis and the controls were, respectively: 20 versus 12% ( ITALIC! P = 0.003) among women without a previous history of infertility and 53 versus 30% ( ITALIC! P < 0.001) for women with a previous history of infertility. After using a random-effects Poisson regression and adjusting for confounding factors, we found a significantly increased incidence rate ratio (IRR) for miscarriages in women with endometriosis (adjusted IRR: 1.70, 95% confidence interval: 1.34-2.16).

LIMITATIONS, REASONS FOR CAUTION: There is a possible selection bias due to the specificity of the study design which included only surgical patients. In the control group, certain of the surgical gynaecological conditions, such as fibroids, ovarian cysts or tubal pathologies, might be associated with higher spontaneous miscarriage rates. In the endometriosis group, asymptomatic women were less likely to be referred for surgery and might therefore be underrepresented.

WIDER IMPLICATIONS OF THE Findings: This study opens the doors to future, more mechanistic studies to establish the exact link between endometriosis and spontaneous miscarriage rates.

STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. The authors have no conflicts of interest to declare.


Progesterone in Women with Recurrent Miscarriages

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.


Oral Contraceptives and Multiple Sclerosis/Clinically Isolated Syndrome  Susceptibility

Annette M Langer-Gould

Kaiser Permanente Southern California, Department of Research & Evaluation, Pasadena, California, United States of America.

Abstract:
Background: The incidence of multiple sclerosis (MS) is rising in women.

Objective: To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content.

Methods: We conducted a nested case-control study of females ages 14-48 years with incident MS or clinically isolated syndrome (CIS) 2008-2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record.

Results: We identified 400 women with incident MS/CIS and 3904 matched controls. Fortypercent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21-1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29-2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16-2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95).

Conclusions: Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman's lifestyle is a more likely explanation for this weak association.


Expression of progesterone receptors is significantly impaired in the endometrium of infertile women during the implantation window: a prospective observational study

Chrysoula Margioula-Siarkou

rd Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece,

Abstract:
OBJECTIVE: To compare the expression of progesterone receptors (A + B) and type-B progesterone receptors in the epithelial and stromal cells of fertile and infertile women.

METHODS: Women were divided into two groups, the group of fertile controls (group 1) and the group of infertile women (group 2) and were set on regular ultrasound imaging in order to detect ovulation. An endometrial biopsy was obtained on the seventh or eighth post-ovulatory day. Immunohistochemistry was performed to measure percentage of positive nuclei, intensity of staining and h-score for progesterone receptors (PgR) (A + B) as well as type-B progesterone receptors in epithelial and stromal cells. Secondary outcomes included endometrial tissue dating, the rate of tissues being out-of-phase and endometrial thickness.

RESULTS: Endometrial issue was obtained from 15 fertile and 30 infertile women. Expression of PgR (A + B) and PgR type-B was significantly lower in the epithelial cells of infertile women. PgR (A + B) h-score was 220.0 ± 18.5 for fertile versus 147.3 ± 18.0 for infertile women (p = 0.02). PgR type-B h-score in epithelial cells was 166.8 ± 30.7 for fertile versus 90.8 ± 20.6 for infertile (p = 0.04). No significant difference was observed in stromal cells.

CONCLUSIONS: Expression levels of PgR (A + B) as well as type-B receptors are significantly lower in the epithelial cells of infertile women during implantation window.

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


Abnormal thyroid function parameters in the second trimester of pregnancy are associated with breech presentation at term: a nested cohort study

Tanja G M Vrijkotte

Academic Medical Centre, Department of Public Health, Amsterdam, The Netherlands.

Joris A M van der Post

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

Rosa Vissenberg

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

Abstract:
OBJECTIVE: Thyroid dysfunction has been described as a possible risk factor for having an abnormal fetal position at birth. In this study we aim to determine the association between thyroid function in early pregnancy and breech presentation at term.

STUDY DESIGN: We used data from the Amsterdam Born Children and their Development (ABCD) cohort. 3347 pregnant women were included between January 2003 and March 2004 in Amsterdam, the Netherlands. Thyroid function tests were performed between 5 and 37 weeks gestational age (median 12.9 weeks). The main outcome measure was the association between thyroid function in early pregnancy and breech presentation at term. Univariate and multivariate analysis were performed to determine the association between thyroid function and breech presentation.

RESULTS: Increased TSH in pregnancy, defined as thyroid stimulating hormone (TSH) >97.5th percentile (>3.53mIU/L), was associated with a higher risk for breech presentation at term (aOR 2.32, CI 1.1-4.8, p=0.02) compared to euthyroidism (TSH between 2.5th and 97.5th percentile). After exclusion of overt hypothyroidism and hyperthyroidism the aOR was 2.34 (CI 1.1-5.0, p=0.03). Trimester specific analysis showed a significant association of increased TSH levels (>3.68mIU/L) in the second trimester with breech presentation (aOR 3.7, CI 1.7-7.8, p=0.001). In the second trimester low free thyroxine (FT4) <2.5th percentile (<6.7pmol/L) was also associated with breech presentation (aOR 2.5, CI 1.0-6.3, p=0.04).

CONCLUSIONS: Increased TSH and decreased FT4 in the second trimester of pregnancy are associated with an increased risk for breech presentation at term. The association of abnormal thyroid parameters in the first of third trimester is still unclear.

European Journal of Obstetrics, Gynecology, and Reproductive Biology


Oocyte donation pregnancies and the risk of preeclampsia or gestational hypertension: a systematic review and metaanalysis

A Nasr

Women's Health Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Assiut University, P.O. Box 1, 71516 Assiut, Egypt. a_nasr02@lycos.com

Abstract: The purpose of this study was to determine whether pregnancies that were achieved via oocyte donation, compared with pregnancies achieved via other assisted reproductive technology methods or natural conception, demonstrate increased risk of preeclampsia or gestational hypertension. Comparative studies of pregnancies that were achieved with oocyte donation vs other methods of assisted reproductive technology or natural conception with preeclampsia or gestational hypertension were included as 1 of the measured outcomes. Abstracts and unpublished studies were excluded. Two reviewers independently selected studies, which were assessed for quality with the use of methodological index for non-randomized studies, and extracted the data. Statistical analysis was conducted. Of the 523 studies that were reviewed initially, 19 comparative studies met the predefined inclusion and exclusion criteria and were included in the metaanalysis, which allowed for analysis of a total of 86,515 pregnancies. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte-donation pregnancies compared with other methods of assisted reproductive technology (odds ratio, 2.54; 95% confidence interval, 1.98-3.24; P < .0001) or natural conception (odds ratio, 4.34; 95% confidence interval, 3.10-6.06; P < .0001). The risk of gestational hypertension was also increased significantly in oocyte donation pregnancies in comparison with other methods of assisted reproductive technology (odds ratio, 3.00; 95% confidence interval, 2.44-3.70; P < .0001) or natural conception (odds ratio, 7.94; 95% confidence interval, 1.73-36.36; P = .008). Subgroup analysis that was conducted for singleton and multiple gestations demonstrated a similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations. This metaanalysis provides further evidence that supports that egg donation increases the risk of preeclampsia and gestational hypertension compared with other assisted reproductive technology methods or natural conception.

American journal of obstetrics and gynecology


Depression and Posttraumatic Stress Symptoms After Perinatal Loss in a Population-Based Sample

Abstract:
INTRODUCTION: Perinatal loss is often a traumatic outcome for families. While there are limited data about depressive outcomes in small populations, information about depression and posttraumatic stress disorder among large racially and economically diverse populations is sparse.

METHODS: We collaborated with the Michigan Department of Community Health to conduct a longitudinal survey of bereaved mothers with stillbirth or infant death under 28 days of life and live-birth (control) mothers in Michigan. The study assessed 9-month mental health outcomes including self-reported symptoms of depression and posttraumatic stress disorder along with information about demographics, pregnancy and loss experience, social support, and past and present mental health and treatment.

RESULTS: Of 1400 women contacted by the State of Michigan, 609 completed surveys and were eligible to participate for a 44% response rate (377 bereaved mothers and 232 control mothers with live births). In multivariable analysis, bereaved women had nearly 4-fold higher odds of having a positive screen for depression and 7-fold higher odds of a positive screen for post-traumatic stress disorder after controlling for demographic and personal risk variables. A minority of screen-positive women were receiving any type of psychiatric treatment.

CONCLUSION: This is the largest epidemiologically based study to date to measure the psychological impact of perinatal loss. Nine months after a loss, bereaved women showed high levels of distress with limited rates of treatment. Symptoms need to be monitored over time for persisting disorder and further research should identify women at highest risk for poor outcomes.


Expanded findings from a randomized controlled trial of preconception low-dose aspirin and pregnancy loss

Laurie L Lesher

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

Jean Wactawski-Wende

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

Abstract:
Study Question: What is the association between daily preconception-initiated low-dose aspirin (LDA) treatment and very early pregnancy losses or euploid (chromosomally normal) losses among women with one to two prior losses?

Summary Answer: Daily LDA initiated preconception was not associated with the rate or type of pregnancy loss among women with a history of one to two prior pregnancy losses.

What Is Known Already: LDA is often used to treat recurrent pregnancy loss with reductions in pregnancy loss generally only observed among women with antiphospholipid antibodies, and null associations observed among women without antiphospholipid antibodies. We previously evaluated the association between LDA and pregnancy loss overall among women with one to two prior losses in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial and found no association, though did not distinguish between potential effects at different stages of pregnancy loss, including implantation failure, or between euploid and aneuploid losses.

STUDY DESIGN, SIZE, Duration: The EAGeR trial was a multi-site prospective block-randomized double-blind placebo-controlled trial. In total, 1228 women were randomized to daily LDA (81 mg/day) plus folic acid (400 mcg/day), or placebo plus folic acid. Participants were assigned study drug for less than or equal to six menstrual cycles or if they conceived, throughout pregnancy with study drug discontinued at 36 weeks gestation. This analysis includes additional outcome information obtained from chart abstractions after the completion of the trial, as well as testing of stored urine for measurement of hCG and detection of very early pregnancy losses, and karyotyping of the products of conception for assessment of aneuploidy of the losses. PARTICIPANTS, SETTING,

Methods: Women aged 18-40 with a history of one to two prior losses and actively trying to conceive were randomized (n = 615 LDA and n = 613 placebo) at four clinical centers in the USA (2007-2011). Log-binomial regression was used to estimate risk ratios under the intent-to-treat approach.

Main Results and the Role of Chance: Daily LDA initiated preconception was not associated with clinically recognized pregnancy losses or implantation failures among women with proved fecundity and a history of one to two prior losses. Specifically, 1088 (88.6%) women completed the trial with 797 having an hCG detected pregnancy (64.9%). Overall there were 133 clinical losses (12.7% LDA versus 11.8% placebo, P = 0.71) and 55 implantation failures (5.2% LDA versus 4.9% placebo, P = 0.89). No differences were found in rate of euploid losses (RR 1.11, 95% confidence interval: 0.99, 1.26).

LIMITATIONS, Reasons for Caution: Generalizability of these findings is limited to women with a history of one to two prior losses, and may further be limited to women of white race with higher socioeconomic status as given the rigors of the study protocol participants tended to be white and have higher incomes and more education. We were also missing karyotype information on approximately one-third of the clinically recognized pregnancy losses, which may limit our power to detect effects on euploid losses, though detailed sensitivity analysis showed similar results. WIDER IMPLICATIONS OF THE FINDINGS: Our data do not support the general use of LDA to decrease pregnancy loss and further demonstrate no increased risk of loss for women on LDA treatment.

Study Funding/competing Interests: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426). The authors have no conflicts of interest.

Trial Registration Number: The trial was registered at ClinicalTrials.gov #NCT00467363. Trial Registration Date: 27 April 2007. DATE OF FIRST PATIENT'S Enrollment: 15 June 2007.


Epidemiology of Uterine Fibroids: From Menarche to Menopause

Lauren A Wise

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Abstract: Uterine leiomyomata (UL) have a substantial impact on women's health, but relatively few studies have identified opportunities for primary prevention of these neoplasms. Most established risk factors are not modifiable, including premenopausal age, African ancestry, age at menarche, and childbearing history. The main challenge in studying UL is that a large proportion of tumors are asymptomatic. Herein, we review the epidemiology of UL from published studies to date. We highlight the advantages of ultrasound screening studies and the ways in which their innovative methods have helped clarify the etiology of disease. We conclude with a discussion of promising new hypotheses.


Menses resumption after cancer treatment-induced amenorrhea occurs early or not at all

Abstract:
OBJECTIVE: To identify factors associated with cancer treatment-induced amenorrhea and time to return of menses.

DESIGN: Population-based cohort study.

SETTING: Not applicable.

PATIENT(S): Female cancer survivors who were diagnosed with cancer between the ages of 20 and 35 and were at least 2 years postdiagnosis at the time of recruitment (median = 7 years; interquartile range, 5-11).

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Amenorrhea (≥6 months without menses) and resumption of menses.

RESULT(S): After excluding women with hysterectomies before cancer diagnosis, 1,043 women were eligible for analysis. Amenorrhea occurred in 31.6% of women. Among women treated with chemotherapy (n = 596), older age at diagnosis (30-35 vs. 20-24 years: adjusted odds ratio [aOR] = 2.37; 95% confidence interval [CI], 1.30, 4.30) and nulligravidity (vs. gravid: aOR = 1.50; 95% CI, 1.02, 2.21) were risk factors for amenorrhea. Among amenorrheic women, menses resumed in most (70.0%), and resumption occurred within 2 years of treatment for 90.0% of women. Survivors of breast cancer were more likely to resume menses at times greater than 1 year compared with lymphoma and pelvic-area cancers. Women diagnosed at older ages, those exposed to chemotherapy, and those exposed to any radiation experienced longer times to return of menses. Women who were older at diagnosis were more likely to have irregular cycles when menses returned.

CONCLUSION(S): Treatment-induced amenorrhea is common in cancer survivors, although most women resume menses within 2 years. However, once resumed, older women are more likely to have irregular cycles. Age at diagnosis and pregnancy history affect the risk of amenorrhea.


Long-acting contraceptives for adolescents

Abstract: In 2014, the American Academy of Pediatrics published its policy statement on contraception for adolescents, which provides, in effect, a mandate to temporarily sterilize all adolescents with long-acting reversible contraceptives for five to ten years. The author reviews the AAP guidelines and their effects on Catholic adolescents, their families, and adolescent health care providers. He then discusses medicolegal issues raised by the policy, outlines Catholic strategies for combating it, and proposes a diocese-based physician-led program for teaching and counseling elementary and high school students.

The national Catholic bioethics quarterly


Trying to Conceive After an Early Pregnancy Loss: An Assessment on How Long Couples Should Wait

Abstract: Our study supports the hypothesis that there is no physiologic evidence for delaying pregnancy attempt after an early loss.


Influence of race and ethnicity on in vitro fertilization outcomes: systematic review

Leigh Ann Humphries

National Confidential Enquiry into Patient Outcome and Death

Abstract:
Objective: We conducted a systematic review to evaluate the influence of race and ethnicity on clinical pregnancy and live birth outcomes after in vitro fertilization (IVF).StudyWe searched PubMed, EMBASE, Web of Science, CINAHL, POPLINE, and Cochrane Central, and hand-searched relevant articles published through July 22, 2015.Study appraisal and synthesis methodsTwo reviewers independently evaluated abstracts to identify studies that compared clinical pregnancy rates and live birth rates for ≥2 racial and/or ethnic groups after nondonor IVF cycles.

Results: Twenty-four studies were included. All 5 US registry-based studies showed that black, Hispanic, and Asian women had lower clinical pregnancy rates and/or live birth rates after IVF, compared with white women. Similarly, most clinic-specific studies reported significant disparities in these primary outcomes, potentially attributable to differences in infertility diagnosis, spontaneous abortion, and obesity. Studies varied with respect to definitions of race/ethnicity, inclusion of first cycles vs multiple cycles for individual women, and collected covariates. Most studies were limited by sample size, inadequate adjustment for confounding, selection bias, and extensive missing data.

Conclusions: Although current evidence points to race and ethnicity, especially black race, as strong predictors of poorer outcomes after IVF, the utility of results is constrained by the limitations described.

American Journal of Obstetrics and Gynecology


The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

Roura E, Travier N, Waterboer T, de Sanjosé S, Bosch FX, Pawlita M, Pala V, Weiderpass E, Margall N, Dillner J, Gram IT, Tjønneland A, Munk C, Palli D, Khaw KT, Overvad K, Clavel-Chapelon F, Mesrine S, Fournier A, Fortner RT, Ose J, Steffen A, Trichopoulou A, Lagiou P, Orfanos P, Masala G, Tumino R, Sacerdote C, Polidoro S, Mattiello A, Lund E, Peeters PH, Bueno-de-Mesquita HB, Quirós JR, Sánchez MJ, Navarro C, Barricarte A, Larrañaga N, Ekström J, Lindquist D, Idahl A, Travis RC, Merritt MA, Gunter MJ, Rinaldi S, Tommasino M, Franceschi S, Riboli E, Castellsagué X

Abstract:
Background: In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC).

Methods and findingsWe followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥ 15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4-0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7).

Conclusions: Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors.


Reconstructive tubal microsurgery and assisted reproductive technology


Health Care Provider Hormonal Recommendations for Treatment of Menstrual Cycle-related Problems - A Vignette-Based Study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Journal of Pharmaceutical Research International (Issn: 2456-9119) is dedicated to publish high quality papers in all areas of pharmaceutical Science including pharmaceutical drugs, community pharmacy, hospital pharmacy, clinical pharmacy, compounding pharmacy, consultant pharmacy, internet pharmacy, veterinary pharmacy, nuclear pharmacy, military pharmacy, pharmacy informatics, pharmaceutics, medicinal chemistry, pharmacognosy, pharmacotherapy, pharmacodynamics, pharmacokinetics, clinical pharmacology, neuropharmacology, psychopharmacology, pharmacogenetics, pharmacogenomics, pharmacoepidemiology, toxicology, theoretical pharmacology, posology, pharmacognosy, behavioral pharmacology, environmental pharmacology, medicine development and safety testing, drug legislation and safety, pharmaceutical microbiology, pharmaceutical molecular biology, pharmaceutical biotechnology. The journal also encourages the submission of useful reports of negative results. This is a quality controlled, OPEN peer reviewed, open access INTERNATIONAL journal.

British journal of pharmaceutical research


Epigenetic imprinting during assisted reproductive technologies: The effect of temporal and cumulative fluctuations in methionine cycling on the DNA methylation state

Abstract: SUMMARYAssisted reproductive technology (ART) exposes gametes and embryos to an artificial environment that does not resemble the conditions of natural conception, and therefore might change epigenetic regulation of genes that are imprinted during development. In the present review, we discuss the relationship between susceptibility of specific genes to receive an altered epigenetic composition during ART processes, possibly via alterations in the biochemical folate and methionine cycle. We provide a comprehensive view of the current state of epigenetic patterning in ART‐conceived healthy children and in Angelman syndrome (AS) and Beckwith–Wiedemann syndrome (BWS) patients. We illustrate that similar genes—that is, MEST, KCNQ1OT1, and IGF2—possess an altered DNA methylation profile in animal models, ART‐conceived healthy children, and AS and BWS patients. The developmental stage at which these genes receive their epigenetic imprint appears to coincide with the specific moment that ART takes place. We highlight that ART procedures affect physiological levels of enzymes and substrates involved in the folate and methionine cycle thereby altering the DNA methylation state. Moreover, although the DNA methylation rate appears to be robust: (i) temporal imbalances coinciding with defined moments of epigenetic imprinting of specific genes affect the eventual DNA methylation state of those genes and (ii) cumulative ART effects on methionine and folate cycling can alter DNA methylation rates. These observations underscore the necessity to further investigate consequences of ART treatments on the epigenetic profile. Mol. Reprod. Dev. 83: 94–107, 2016. © 2015 Wiley Periodicals, Inc.


Recurrent varicocele

Recurrent varicocele

Abstract: Varicocele recurrence is one of the most common complications associated with varicocele repair. A systematic review was performed to evaluate varicocele recurrence rates, anatomic causes of recurrence, and methods of management of recurrent varicoceles. The PubMed database was evaluated using keywords "recurrent" and "varicocele" as well as MESH criteria "recurrent" and "varicocele." Articles were not included that were not in English, represented single case reports, focused solely on subclinical varicocele, or focused solely on a pediatric population (age <18). Rates of recurrence vary with the technique of varicocele repair from 0% to 35%. Anatomy of recurrence can be defined by venography. Management of varicocele recurrence can be surgical or via embolization.


Changes in macronutrient, micronutrient, and food group intakes throughout the menstrual cycle in healthy, premenopausal women

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.


[Occupational, educational and residential factors are associated with the outcomes of in vitro fertilization-embryo transfer]

Bingbing Wu

Second Affiliated Hospital of Zhejiang University

Abstract:
OBJECTIVE: To investigate the associations of occupational, educational and residential factors with the outcomes of in vitro fertilization -embryo transfer (IVF-ET).

METHODS: A retrospective analysis was conducted among 3998 patients undergoing the first treatment with IVF-ET and 3064 perinatal infants in our center between January, 2010 and June, 2014. The relation of the patients' occupation, educational background, and residence registry with IVF-ET outcomes was analyzed.

RESULTS: The risk of abortion in the first trimester was significantly higher in female patients engaged in agriculture (OR=4.319, P=0.047). Occupation and educational background of the patients and their spouse were related with the incidence of ectopic pregnancy following IVF-ET. The total incidence rate of perinatal birth defects was 2.1% in this cohort, and was the highest in Shenzhen (5.5%) but this difference was not statistically significant (P>0.05).

CONCLUSION: The patients' occupation and educational background are related with the outcomes of IVF-ET, suggesting the importance of health education and prenatal examination.

Nan fang yi ke da xue xue bao = Journal of Southern Medical University


THE EVALUATION OF INFERTILITY TREATMENT AND APPLICATION OF ASSISTED REPRODUCTION IN THE ASPECT OF HUMAN DIGNITY

Abstract: The article raises the issue of today’s application of assisted (artificial) reproduction methods, which are incom-patible with human dignity. The authors articulate the principles of human dignity, which are formulated as an evaluation tool of criteria and them revealing system of indicators in the assessed object. The article compares Naprotechnology as a contemporary holistic method of diagnosis and treatment of infertility, which comprises therapeutic, surgical and fertility awareness method, with methods of assisted reproduction and identifies their medical and ethical differences. The project of the Assisted Reproduction Law of the Republic of Lithuania is evaluated in the aspect of human dignity as well.


DIR Jahrbuch 2015 (Deutsches IVF-Register Annual Report 2015)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2015. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).


Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation

Abstract: OBJECTIVE: Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. METHODS: We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. RESULTS: On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. CONCLUSIONS: There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.


Fertility Treatment 2014: Trends and Figures

Human Fertilisation and Embryology Authority


Epidemiology of Uterine Myomas: A Review

Antonio Malvasi

Obstetrics and Gynecology Unit, Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy

Abstract: Myomas are the most common benign tumors of the genital organs in women of childbearing age, causing significant morbidity and impairing their quality of life. In our investigation, we have reviewed the epidemiological data related to the development of myomas in order to homogenize the current data. Therefore, a MEDLINE and PubMed search, for the years 1990-2013, was conducted using a combination of keywords, such as "myoma," "leiomyoma," "fibroids," "myomectomy," "lifestyle," "cigarette," "alcohol," "vitamins," "diet," and "hysterectomy". Randomized controlled studies were selected based upon the authors' estimation. Peer-reviewed articles examining myomas were sorted by their relevance and included in this research. Additional articles were also identified from the references of the retrieved papers and included according to authors' estimation. Many epidemiologic factors are linked to the development of myomas; however, many are not yet fully understood. These factors include age, race, heritage, reproductive factors, sex hormones, obesity, lifestyle (diet, caffeine and alcohol consumption, smoking, physical activity and stress), environmental and other influences, such as hypertension and infection. Some of the epidemiological data is conflicting. Thus, more research is needed to understand all the risk factors that contribute to myoma formation and how they exactly influence their onset and growth.

International journal of fertility & sterility


Evidence that the endometrial microbiota has an effect on implantation success or failure

American Journal of Obstetrics and Gynecology


CARTR Plus 2016 Annual Report (2015 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.


Thyroid dysfunction in metabolic syndrome patients and its relationship with components of metabolic syndrome

Abstract:
BACKGROUND: A growing body of evidence suggests that metabolic syndrome is associated with endocrine disorders including thyroid dysfunction. Thyroid dysfunction in metabolic syndrome patients may further add to cardiovascular disease risk thereby increasing mortality. This study was done to assess thyroid function in metabolic syndrome patients and evaluate its relationship with the components of metabolic syndrome.

METHODS: A cross sectional study was carried out among 169 metabolic syndrome patients at B P Koirala Institute of Health Sciences, Dharan, Nepal. Anthropometric measurements (height, weight, waist circumference) and blood pressure were taken. Fasting blood samples were analysed to measure glucose, triglyceride, high density lipoprotein (HDL) cholesterol and thyroid hormones (triiodothyronine, thyroxine and thyroid stimulating hormone).

RESULTS: Thyroid dysfunction was seen in 31.9 % (n = 54) metabolic syndrome patients. Subclinical hypothyroidism (26.6 %) was the major thyroid dysfunction followed by overt hypothyroidism (3.5 %) and subclinical hyperthyroidism (1.7 %). Thyroid dysfunction was much common in females (39.7 %, n = 29) than males (26 %, n = 25) but not statistically significant (p = 0.068). The relative risk of having thyroid dysfunction in females was 1.525 (CI: 0.983-2.368) as compared to males. Significant differences (p = 0.001) were observed in waist circumference between patients with and without thyroid dysfunction and HDL cholesterol which had significant negative correlation with thyroid stimulating hormone.

CONCLUSIONS: Thyroid dysfunction, particularly subclinical hypothyroidism is common among metabolic syndrome patients, and is associated with some components of metabolic syndrome (waist circumference and HDL cholesterol).


Perinatal risks associated with assisted reproductive technology: committee opinion no. 671

American College of Obstetricians and Gynecologists


Pathophysiology of heavy menstrual bleeding

Abstract: Heavy menstrual bleeding (HMB) is a common gynecological complaint with multiple etiologies and diverse pathophysiological origins. This review discusses HMB with reference to the recently proposed PALM-COEIN classification system for abnormal uterine bleeding, initially describing the endometrial events in normal menstruation followed by discussion of the perturbations of normal endometrial shedding that can result in HMB. Our present understanding of the mechanisms of menstrual bleeding as well as many of the pathological aberrations of HMB is incomplete. Further research into the pathophysiology of HMB is urgently needed, as clear knowledge of the mechanisms of this disorder will provide new therapeutic targets to formulate more effective treatments.


Infertility in The Philippines and Natural Procreative (Napro) Technology: A Commentary

Flores R

University of Texas MD Anderson Cancer Center

Abstract: The latest retrievable data about infertility in the Philippines was made available to the public by Merck Serono, a private pharmaceutical company who commissioned the survey in 2011. The survey was conducted by Synovate in 100 participating households in the Philippines, particularly in key cities located in Luzon, Visayas and Mindanao. The survey results revealed that one out of ten Filipino couples are suffering from infertility. And these couples are not seeking treatment due to the following reasons: (1) financial constraints; (2) time constraints; and (3) the patient’s belief. Of all these, financial constraints, at 86%, is the primary reason why infertile couples are not seeking treatment. In addition to this data, the Chief of The Medical City’s Reproductive Medicine, Infertility and Gynecologic Endoscopy, Dr. Marc Anthony Ancheta, further reveals that “some 35 to 40% of a couple’s inablity to conceive a child are due to female factors; while the other 35 to 40% could be attributed to male factors.” While male factor infertility is also deserving of proper attention, it is the female factor infertility that should receive greater attention and focus in terms of treatment. Why? Because, primarily, the female’s reproductive cycle is very complex and would need months and/or years to partially identify the underlying reason/s of infertility; and second, the female’s ability to conceive naturally will fall by 50% when she reached the age of 35. Therefore, there should be urgency in treating female factor infertility in an efficient, ethical and affordable way. And these conditions can be achieved by the use of NaPro Technology.

Scholars Academic Journal of Biosciences


The Principle of Double Effect in Ethics: A Review

Abstract:
Introduction
- A pregnant woman is diagnosed with uterine cancer. Is it permissible to operate to remove the cancer, even though doing so will result in the loss of the baby?
- A dying man is in extreme pain. Is it permissible to administer large doses of morphine to reduce the pain, even though doing so will shorten the amount of time the man has left to live?
- A country has been attacked by another. Is it morally permissible for the country that has been attacked to respond by, among other things, bombing its attacker’s industrial centers, even though doing so will also bring about the deaths of some civilian workers?
Cases
- A pregnant woman is diagnosed with uterine cancer. Is it permissible to operate to remove the cancer, even though doing so will result in the loss of the baby? Supporters of the principle of double effect will argue that it is permissible to remove the cancerous uterus (thus also terminating the pregnancy) if this is the only way to stop the spread of the cancer and if the physician does not intend to end the pregnancy, only to remove the cancer. The good effect (removal of the cancer) does not follow from the bad effect (termination of the pregnancy).
- A dying man is in extreme pain. Is it permissible to administer large doses of morphine to reduce the pain, even though doing so will shorten the amount of time the man has left to live? Again, defenders of the principle of double effect will argue that, since the genuine intent is only to relieve the pain and since there is no other way to accomplish this goal, large doses of pain killers may be permitted even though they will hasten the inevitable end of the patient's life.
- A country has been attacked by another. Is it morally permissible for the country that has been attacked to respond by, among other things, bombing its attacker’s industrial centers, even though doing so will also bring about the deaths of some civilian workers? The principle of double effect has been a cornerstone of the wartime policy of many countries, including the United States. Indeed, long range strategic bombers (such as the B-52) are essentially weapons for the mass destruction of civilian populations. Both the atomic bombs dropped on Japan were dropped on civilian centers.
The Arguments
The principle of double effect finds its natural home in deontological, non-consequentialist moral theories, since it turns very specifically on the intention of the moral agent.
Utilitarianism and other consequentialist doctrines give little or no weight to the agent’s intentions, and as a result the principle of double effect makes little sense within such theories.
We will see a similar issue arise when we discuss the difference between killing and letting die, a distinction that is much more meaningful within deontological theories than consequentialist ones.
Typically, for an act to qualify as morally permissible under the principle of the double effect, a number of conditions must be met:
- The act must be morally good or at least morally neutral;
- The agent must intend only the good effect, nor the bad effect;
- The good effect cannot be the causal result of the bad effect;
- There must be a proportionately serious reason for permitting the evil effect;
- There must not be any other, less morally troubling way of accomplishing the good effect.


Adverse Incidents in Fertility Clinics: Lessons to Learn 2015

Human Fertilisation and Embryology Authority


Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies

Xiyao Liu

First Affiliated Hospital of Chongqing Medical University

Abstract:
OBJECTIVE: To determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally.

DESIGN: Meta-analysis.

SETTING: University-affiliated teaching hospital.

PATIENT(S): Singleton pregnancies conceived with ART and naturally.

INTERVENTION(S): PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated 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): Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I(2) = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I(2) = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I(2) = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I(2) = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I(2) = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I(2) = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I(2) = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I(2) = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I(2) = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I(2)=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I(2) = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I(2) = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I(2) = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I(2) = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I(2)=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I(2)=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed.

CONCLUSION(S): The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk.


Dietary fat intake and reproductive hormone concentrations and ovulation in regularly menstruating women

Kara A Michels

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.

The American Journal of Clinical Nutrition


Nurse-Midwifery and NaProTECHNOLOGY: Healthcare women really need

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family