Environmental Contaminants Affecting Fertility and Somatic Health

Abstract: This review article summarizes the epidemiological findings published between 2011 and 2016 concerning bisphenol A (BPA), phthalates, dioxins, pesticides, air pollution, fracking chemicals, triclosan, and parabens and fertility parameters in men (i.e., semen volume, sperm concentration, sperm motility, and sperm morphology) as well as fertility parameters in women (i.e., cyclicity, fertility treatment outcomes), pregnancy outcomes (i.e., preterm birth,miscarriage), and reproductive disorders (i.e., polycystic ovary syndrome, endometriosis, and uterine fibroids). Overall, this review indicates that several environmental toxicants are significantly associated with reduced fertility parameters in men and women as well as several reproductive disorders in women. Although many studies reported that the selected exposures are associated with adverse fertility outcomes, several studies reported null associations. Thus, future studies are still needed to better elucidate the associations and potential mechanisms between these environmental chemicals and fertility outcomes in men and women.


Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia

Rolnik DL, Wright D, Poon LC, O'Gorman N, Syngelaki A, de Paco Matallana C, Akolekar R, Cicero S, Janga D, Singh M, Molina FS, Persico N, Jani JC, Plasencia W, Papaioannou G, Tenenbaum-Gavish K, Meiri H, Gizurarson S, Maclagan K, Nicolaides KH

Abstract:
BACKGROUND: Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.

METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.

RESULTS: A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.

CONCLUSIONS: Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).


Medical Students' Knowledge of Fertility Awareness-Based Methods of Family Planning

Abstract:
OBJECTIVE: Traditional medical school curricula have not addressed fertility awareness-based methods (FABMs) of family planning. The objective of this study was to assess (1) 3-year medical students' knowledge of FABMs of family planning, (2) their confidence in utilizing that knowledge in patient care, and (3) to implement focused education on FABMs to improve knowledge and confidence.

METHODS: Third-year medical students at one institution in the United States were given a 10-question assessment at the beginning of their OB-GYN rotation. Two lectures about FABMs and their clinical applications were given during the rotation. Students were given the same questions at the end of the rotation. Each questionnaire consisted of eight questions to assess a student's knowledge of FABMs and two questions to assess the student's confidence in sharing and utilizing that information in a clinical setting. McNemar's test was used to analyze the data.

RESULTS: Two hundred seventy-seven students completed a pretest questionnaire and 196 students completed the posttest questionnaire. Medical knowledge improved from an initial test score of 38.99% to final test score of 53.57% (p < 0.05). Confidence in sharing FABM information with patients (0 = very uncomfortable; 5 = very comfortable) improved from 1.51 to 3.00 (p < 0.05). Confidence in utilizing FABM to diagnose and treat gynecologic/reproductive problems (0 = not very confident and 5 = very confident) improved from 1.01 to 3.15 (p < 0.05).

CONCLUSION: Medical schools may not include FABMs in OB-GYN curriculum; however, to patients, these methods remain a sought after and valid form of family planning. This study shows that brief, focused education can increase medical students' knowledge of and confidence with FABMs of family planning.


Competing Factors Link to Bone Health in Polycystic Ovary Syndrome: Chronic  Low-Grade Inflammation Takes a Toll

Hélène C F Côté

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Chronic inflammation predisposes to poor bone health. Women with polycystic ovary syndrome (PCOS) experience androgen excess, ovulatory disturbances, insulin resistance, abdominal adiposity and chronic inflammation. Our objective was to investigate the relationships among bone health parameters, chronic subclinical inflammation and anthropometric measures in premenopausal women with and without PCOS. In 61 premenopausal women, 22 women with PCOS and 39 controls, we assessed bone parameters (total hip bone mineral density [BMD] by dual-energy X-ray absorptiometry and radius strength-strain index [SSI] by peripheral quantitative computed tomography), inflammation (C-reactive protein/albumin), oxidative stress (leukocyte telomere length, urinary 8-hydroxydeoxyguanosine); hemoglobin A1c; anthropometric measures (body mass index, waist-to-height ratio, cross-sectional muscle area). A diagnosis of PCOS negatively predicted (beta = -0.251, p = 0.022) hip BMD in a regression model including weight. In women with PCOS, inflammation, which was predicted by increased waist-to-height ratio and current use of oral contraceptives, attenuated the positive influences of increased weight and muscle mass on bone strength and was inversely associated with radial SSI (R(2) = 0.25, p = 0.018). In conclusion, chronic subclinical inflammation may negatively impact bone physiology in women with PCOS. Strategies focused on reducing abdominal adiposity and avoiding medications that increase inflammation may counter this effect.


Effectiveness of an Online Natural Family Planning Program for Breastfeeding  Women

Abstract:
Objective: To analyze the effectiveness of an online, nurse-managed natural family planning (NFP) program among breastfeeding women and subgroups of these women.
Design: Longitudinal comparative cohort study.
Setting: A university-based online NFP education program and menstrual cycle charting system.

Participants: Women (N = 816) with a mean age of 30.3 years (standard deviation = 4.5) who registered to use the online NFP system and indicated they were breastfeeding.

Methods: Participants tracked their fertile times with an electronic hormone fertility monitor (EHFM), cervical mucus monitoring, or both. All unintended pregnancies were evaluated by professional nurses.

Results: The correct use pregnancy rates were 3 per 100 users over 12 cycles of use, and typical rates were 14 per 100 at 12 cycles of use. At 12 cycles of use, total pregnancy rates were 16 per 100 for electronic hormone fertility monitor users (n = 380), 81 per 100 among mucus-only users (n = 45), and 14 per 100 for electronic hormone fertility monitor plus mucus users (n = 391).

Conclusion: Use of a nurse-managed online NFP program for women can be effective to help women avoid pregnancy while breastfeeding, especially with correct and consistent use.

Journal of Obstetric, Gynecologic, and Neonatal Nursing : JOGNN


Fertility Treatment Is Associated with Stay in the Neonatal Intensive Care Unit  and Respiratory Support in Late Preterm Infants

Lauren W Sundheimer

Cedars-Sinai Medical Center, Los Angeles, CA; UCLA David Geffen School of Medicine, Los Angeles, CA.

Abstract: Late preterm infants are at risk for short-term morbidities. We report that late preterm singletons conceived with fertility treatment have increased risk for admission to the neonatal intensive care unit and respiratory support compared with spontaneously conceived infants. Fertility treatment may be a risk factor to consider in managing late preterm infants.


Progesterone resistance in endometriosis: origins, consequences and interventions

Robert N Taylor

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility (Drs. Peterson and Taylor), University of Utah, Salt Lake City, Utah.

Abstract: Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment.

Acta obstetricia et gynecologica Scandinavica


Exposure to endocrine disruptors during adulthood: consequences for female fertility

Abstract: Endocrine disrupting chemicals are ubiquitous chemicals that exhibit endocrine disrupting properties in both humans and animals. Female reproduction is an important process, which is regulated by hormones and is susceptible to the effects of exposure to endocrine disrupting chemicals. Disruptions in female reproductive functions by endocrine disrupting chemicals may result in subfertility, infertility, improper hormone production, estrous and menstrual cycle abnormalities, anovulation, and early reproductive senescence. This review summarizes the effects of a variety of synthetic endocrine disrupting chemicals on fertility during adult life. The chemicals covered in this review are pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated biphenyls, triclosan, and parabens. This review focuses on the hypothalamus, pituitary, ovary, and uterus because together they regulate normal female fertility and the onset of reproductive senescence. The literature shows that several endocrine disrupting chemicals have endocrine disrupting abilities in females during adult life, causing fertility abnormalities in both humans and animals.


Elevated progesterone and its impact on birth weight after fresh embryo transfers

Abstract:
PURPOSE: The purpose of the study was to examine the association between serum progesterone levels on the day of hCG administration and birth weight among singleton live births after fresh embryo transfer.

METHODS: This study was conducted as a retrospective cohort database analysis on patients who underwent IVF treatment cycles from January 2004 to April 2012. The study was performed at a University affiliated private infertility practice. All cycles that had achieved a singleton live birth after fresh embryo transfer and for which progesterone was measured on the day of hCG administration were examined. Generalized linear models were used to calculate mean birth weight and z-scores.

RESULTS: We analyzed 817 fresh IVF embryo transfers in which birth weight, gestational age, and progesterone (ng/mL) level on day of hCG administration were documented. While there was a decrease in birth weight as progesterone quartile [≤0.54; >0.54 to ≤0.81; >0.81 to ≤1.17; >1.17 ng/mL] increased, the difference in mean birth weights among the four quartiles was not statistically significant (p = 0.11) after adjusting for maternal age and peak estradiol levels. When dichotomizing based on a serum progesterone considered clinically elevated, cycles with progesterone >2.0 ng/mL had a significantly lower mean singleton birth weight (2860 g (95% CI 2642 g, 3079 g)) compared to cycles with progesterone ≤2.0 ng/mL (3167 g (95% CI 3122 g, 3211 g) p = 0.007)) after adjusting for maternal age and estradiol.

CONCLUSION: We demonstrated that caution should be exercised when performing fresh embryo transfers with elevated progesterone levels and in particular with levels (>2.0 ng/mL) as this may lead to lower birth weight.

Journal of assisted reproduction and genetics


Association between formaldehyde exposure and miscarriage in Chinese women

Xiqian Zhang

Guangdong Province Women and Children Hospital

Abstract: The aim of this study was to assess whether higher plasma formaldehyde concentration existed in women diagnosed with miscarriage and whether it contributed to higher risk of miscarriage in Chinese women.A case-control study was conducted in 118 women with a diagnosed miscarriage at the first trimester and 191 healthy women who delivered at term. Plasma levels of formaldehyde were measured by gas chromatography in conjunction with mass spectrometry after derivatization of the formaldehyde to the pentafluorophenylhydrazone and characteristics of the subjects including age, education level, occupation, family income, home decoration status, and exposure to second-hand smoke were recorded. Logistic regression analyses were performed to investigate the relationship between miscarriage and levels of formaldehyde.Women with miscarriage were comparable to controls in terms of age, education level, occupation, family income, and home decoration status. They were, however, more likely to be exposed to second-hand smoke. Plasma levels of formaldehyde were significantly higher in women with miscarriage (0.0944 ± 0.0105 vs. 0.0239 ± 0.0032 μg/mL, P < .001). Multivariate logistic regression showed that higher level of formaldehyde (odds ratio [OR]: 8.06, 95% confidence interval [CI]: 4.96-13.09) and exposure to second-hand smoke (OR: 3.60, 95% CI: 1.58-8.20) were independently and significantly associated with higher risk of miscarriage.Plasma levels of formaldehyde were significantly higher in women who were diagnosed with miscarriage than those who delivered at term and higher levels of formaldehyde was an independent risk factor for miscarriage, with higher levels being associated with higher risk of miscarriage.


Dyspareunia From Large Retained Fetal Bone Diagnosed by Pelvic Ultrasound

Cara Buskmiller

Department of Obstetrics, Gynecology, and Women’s Health, St. Louis University, St. Louis, MO, USA

Journal of Ultrasound in Medicine : Official Journal of the American Institute of  Ultrasound in Medicine


Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women

Dreyer K, van Rijswijk J, Mijatovic V, Goddijn M, Verhoeve HR, van Rooij IAJ, Hoek A, Bourdrez P, Nap AW, Rijnsaardt-Lukassen HGM, Timmerman CCM, Kaplan M, Hooker AB, Gijsen AP, van Golde R, van Heteren CF, Sluijmer AV, de Bruin JP, Smeenk JMJ, de Boer JAM, Scheenjes E, Duijn AEJ, Mozes A, Pelinck MJ, Traas MAF, van Hooff MHA, van Unnik GA, de Koning CH, van Geloven N, Twisk JWR, Hompes PGA, Mol BWJ

Abstract:
BACKGROUND: Pregnancy rates among infertile women have been reported to increase after hysterosalpingography, but it is unclear whether the type of contrast medium used (oil-based or water-soluble contrast) influences this potential therapeutic effect.

METHODS: We performed a multicenter, randomized trial in 27 hospitals in the Netherlands in which infertile women who were undergoing hysterosalpingography were randomly assigned to undergo this procedure with the use of oil-based or water-based contrast. Subsequently, couples received expectant management or the women underwent intrauterine insemination. The primary outcome was ongoing pregnancy within 6 months after randomization. Outcomes were analyzed according to the intention-to-treat principle.

RESULTS: A total of 1119 women were randomly assigned to hysterosalpingography with oil contrast (557 women) or water contrast (562 women). A total of 220 of 554 women in the oil group (39.7%) and 161 of 554 women in the water group (29.1%) had an ongoing pregnancy (rate ratio, 1.37; 95% confidence interval [CI], 1.16 to 1.61; P<0.001), and 214 of 552 women in the oil group (38.8%) and 155 of 552 women in the water group (28.1%) had live births (rate ratio, 1.38; 95% CI, 1.17 to 1.64; P<0.001). Rates of adverse events were low and similar in the two groups.

CONCLUSIONS: Rates of ongoing pregnancy and live births were higher among women who underwent hysterosalpingography with oil contrast than among women who underwent this procedure with water contrast. (Netherlands Trial Register number, NTR3270 .).


Latent variable mixture models to test for differential item functioning: a population-based analysis

Richard Sawatzky

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Alexandra Papaioannou

McMaster University, Hamilton, ON, Canada

Abstract:
Background: Comparisons of population health status using self-report measures such as the SF-36 rest on the assumption that the measured items have a common interpretation across sub-groups. However, self-report measures may be sensitive to differential item functioning (DIF), which occurs when sub-groups with the same underlying health status have a different probability of item response. This study tested for DIF on the SF-36 physical functioning (PF) and mental health (MH) sub-scales in population-based data using latent variable mixture models (LVMMs).

Methods: Data were from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective national cohort study. LVMMs were applied to the ten PF and five MH SF-36 items. A standard two-parameter graded response model with one latent class was compared to multi-class LVMMs. Multivariable logistic regression models with pseudo-class random draws characterized the latent classes on demographic and health variables.

Results: The CaMos cohort consisted of 9423 respondents. A three-class LVMM fit the PF sub-scale, with class proportions of 0.59, 0.24, and 0.17. For the MH sub-scale, a two-class model fit the data, with class proportions of 0.69 and 0.31. For PF items, the probabilities of reporting greater limitations were consistently higher in classes 2 and 3 than class 1. For MH items, respondents in class 2 reported more health problems than in class 1. Differences in item thresholds and factor loadings between one-class and multi-class models were observed for both sub-scales. Demographic and health variables were associated with class membership.

Conclusions: This study revealed DIF in population-based SF-36 data; the results suggest that PF and MH sub-scale scores may not be comparable across sub-groups defined by demographic and health status variables, although effects were frequently small to moderate in size. Evaluation of DIF should be a routine step when analysing population-based self-report data to ensure valid comparisons amongst sub-groups.


Cancer-Associated Mutations in Endometriosis without Cancer

Anglesio MS, Papadopoulos N, Ayhan A, Nazeran TM, Noë M, Horlings HM, Lum A, Jones S, Senz J, Seckin T, Ho J, Wu RC, Lac V, Ogawa H, Tessier-Cloutier B, Alhassan R, Wang A, Wang Y, Cohen JD, Wong F, Hasanovic A, Orr N, Zhang M, Popoli M, McMahon W, Wood LD, Mattox A, Allaire C, Segars J, Williams C, Tomasetti C, Boyd N, Kinzler KW, Gilks CB, Diaz L, Wang TL, Vogelstein B, Yong PJ, Huntsman DG, Shih IM

Abstract:
BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis.

METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations.

RESULTS: Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions.

CONCLUSIONS: We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.


Comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in polycystic ovary syndrome: A randomized controlled clinical trial

Abstract:
OBJECTIVE: To our knowledge, data on comparison of myo-inositol and metformin on clinical, metabolic and genetic parameters in subjects with polycystic ovary syndrome (PCOS) are limited. This study was carried out to compare myo-inositol and metformin on clinical, metabolic and genetic parameters in subjects with PCOS.

DESIGN, PATIENTS AND

MEASUREMENTS: This randomized controlled trial was conducted among 60 subjects with PCOS aged 18-40 years. Subjects were randomly allocated into two groups to receive either myo-inositol (N=30) or metformin (N=30) for 12 weeks. Gene expression of inflammatory cytokines was assessed in peripheral blood mononuclear cells (PBMCs) of PCOS women by RT-PCR.

RESULTS: After the 12-week intervention, compared with metformin, myo-inositol intake significantly decreased serum total testosterone (-1.4±4.2 vs +0.7±1.4 nmol/L, P=.03), modified Ferriman-Gallwey (mF-G) scores (-1.1±0.7 vs -0.5±0.8, P=.01) and serum high-sensitivity C-reactive protein (hs-CRP) levels (-2.6±3.9 vs +0.2±1.5 mg/L, P<.001). RT-PCR demonstrated that compared with metformin, myo-inositol downregulated gene expression of interleukin-1 (IL-1) (P=.02) in PBMCs of subjects with PCOS. We did not observe any significant effect of myo-inositol intake compared with metformin on other hormonal profiles, plasma nitric oxide (NO) or gene expression of IL-8 and tumour necrosis factor alpha (TNF-α).

CONCLUSIONS: Overall, taking myo-inositol, compared with metformin, for 12 weeks in patients with PCOS with hyperinsulinism and normoinsulinism had beneficial effects on total testosterone, mFG scores, serum hs-CRP levels and gene expression of IL-1, but did not affect other hormonal profiles, NO levels or gene expression of IL-8 and TNF-α.


Pulse Rate Measurement During Sleep Using Wearable Sensors, and its Correlation with the Menstrual Cycle Phases, A Prospective Observational Study

Abstract: An affordable, user-friendly fertility-monitoring tool remains an unmet need. We examine in this study the correlation between pulse rate (PR) and the menstrual phases using wrist-worn PR sensors. 91 healthy, non-pregnant women, between 22-42 years old, were recruited for a prospective-observational clinical trial. Participants measured PR during sleep using wrist-worn bracelets with photoplethysmographic sensors. Ovulation day was estimated with "Clearblue Digital-Ovulation-urine test". Potential behavioral and nutritional confounders were collected daily. 274 ovulatory cycles were recorded from 91 eligible women, with a mean cycle length of 27.3 days (±2.7). We observed a significant increase in PR during the fertile window compared to the menstrual phase (2.1 beat-per-minute, p < 0.01). Moreover, PR during the mid-luteal phase was also significantly elevated compared to the fertile window (1.8 beat-per-minute, p < 0.01), and the menstrual phase (3.8 beat-per-minute, p < 0.01). PR increase in the ovulatory and mid-luteal phase was robust to adjustment for the collected confounders. There is a significant increase of the fertile-window PR (collected during sleep) compared to the menstrual phase. The aforementioned association was robust to the inter- and intra-person variability of menstrual-cycle length, behavioral, and nutritional profiles. Hence, PR monitoring using wearable sensors could be used as one parameter within a multi-parameter fertility awareness-based method.


Preconception maternal lipoprotein levels in relation to fecundability

Richard W Browne

University at Buffalo, State University of New York

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: Are maternal preconception lipid levels associated with fecundability?Summary answerFecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels.

What is known already: Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones. Evidence illustrating this relationship at the mechanistic level is mounting but few studies in humans have explored the role of preconception lipids in fecundity.Study design, size, durationA secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a block-randomized, double-blind, placebo-controlled trial.

Participants/materials, setting, methodsA total of 1228 women, with 1-2 prior pregnancy losses and without a diagnosis of infertility, attempting pregnancy for up to six menstrual cycles were recruited from clinical sites in Utah, New York, PA and Colorado. Time to pregnancy was the number of menstrual cycles to pregnancy as determined by positive hCG test or ultrasound. Individual preconception lipoproteins were measured at baseline, prior to treatment randomization and dichotomized based on clinically accepted cut-points as total cholesterol ≥200 mg/dl, LDL-C ≥130 mg/dl, HDL-C Main results and the role of chanceThere were 148 (12.3%) women with elevated total cholesterol, 94 (7.9%) with elevated LDL-C, 280 (23.2%) with elevated triglycerides and 606 (50.7%) with low HDL-C. The fecundability odds ratio (FOR) was reduced for all abnormal lipids before and after confounder adjustment, indicating reduced fecundability. Total cholesterol ≥200 mg/dl was associated with 24% (For: 0.76, 95% CI: 0.59, 0.97) and 29% (For: 0.71, 95% CI: 0.55, 0.93) reduced fecundability for hCG-detected and ultrasound-confirmed pregnancy, respectively, compared with total cholesterol Limitations, reasons for cautionAlthough the FOR is a measure of couple fecundability, we had only measures of female lipid levels and can therefore not confirm the findings from a previous study indicating the independent role of male lipids in fecundity. The attenuated estimates and decreased precision after adjustment for central adiposity and obesity indicate the complexity of potential causal lipid pathways, suggesting other factors related to obesity besides dyslipidemia likely contribute to reduced fecundability.

Wider implication: s of the findingsOur results are consistent with one other study relating preconception lipid concentrations to fecundity and expand these findings by adding critically important information about individual lipoproteins. As lipid levels are modifiable they may offer an inexpensive target to improve female fecundability.Study funding and competing interest(s)This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have declared that no conflicts of interest exist.Trial registration number#NCT00467363.


Preconception Low-Dose Aspirin Restores Diminished Pregnancy and Live Birth Rates in Women With Low-Grade Inflammation: A Secondary Analysis of a Randomized Trial

Abstract:
Context: Inflammation is linked to causes of infertility. Low-dose aspirin (LDA) may improve reproductive success in women with chronic, low-grade inflammation.

Objective: To investigate the effect of preconception-initiated LDA on pregnancy rate, pregnancy loss, live birth rate, and inflammation during pregnancy.
Design: Stratified secondary analysis of a multicenter, block-randomized, double-blind, placebo-controlled trial.
Setting: Four US academic medical centers, 2007 to 2012.

Participants: Healthy women aged 18 to 40 years (N = 1228) with one to two prior pregnancy losses actively attempting to conceive.

Intervention: Preconception-initiated, daily LDA (81 mg) or matching placebo taken up to six menstrual cycles attempting pregnancy and through 36 weeks' gestation in women who conceived.

Main Outcome Measures: Confirmed pregnancy, live birth, and pregnancy loss were compared between LDA and placebo, stratified by tertile of preconception, preintervention serum high-sensitivity C-reactive protein (hsCRP) (low, <0.70 mg/L; middle, 0.70 to <1.95 mg/L; high, ≥1.95 mg/L).

Results: Live birth occurred in 55% of women overall. The lowest pregnancy and live birth rates occurred among the highest hsCRP tertile receiving placebo (44% live birth). LDA increased live birth among high-hsCRP women to 59% (relative risk, 1.35; 95% confidence interval, 1.08 to 1.67), similar to rates in the lower and mid-CRP tertiles. LDA did not affect clinical pregnancy or live birth in the low (live birth: 59% LDA, 54% placebo) or midlevel hsCRP tertiles (live birth: 59% LDA, 59% placebo).

Conclusions: In women attempting conception with elevated hsCRP and prior pregnancy loss, LDA may increase clinical pregnancy and live birth rates compared with women without inflammation and reduce hsCRP elevation during pregnancy.

The Journal of clinical endocrinology and metabolism


Red light improves spermatozoa motility and does not induce oxidative DNA damage

Veronica Gomez-Godinez

Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.

Abstract: The ability to successfully fertilize ova relies upon the swimming ability of spermatozoa. Both in humans and in animals, sperm motility has been used as a metric for the viability of semen samples. Recently, several studies have examined the efficacy of low dosage red light exposure for cellular repair and increasing sperm motility. Of prime importance to the practical application of this technique is the absence of DNA damage caused by radiation exposure. In this study, we examine the effect of 633 nm coherent, red laser light on sperm motility using a novel wavelet-based algorithm that allows for direct measurement of curvilinear velocity under red light illumination. This new algorithm gives results comparable to the standard computer-assisted sperm analysis (CASA) system. We then assess the safety of red light treatment of sperm by analyzing, (1) the levels of double-strand breaks in the DNA, and (2) oxidative damage in the sperm DNA. The results demonstrate that for the parameters used there are insignificant differences in oxidative DNA damage as a result of irradiation.


Crucial role of estrogen for the mammalian female in regulating semen coagulation and liquefaction in vivo

Abstract: Semen liquefaction changes semen from a gel-like to watery consistency and is required for sperm to gain mobility and swim to the fertilization site in the Fallopian tubes. Kallikrein-related peptidases 3 (KLK3) and other kallikrein-related peptidases from male prostate glands are responsible for semen liquefaction by cleaving gel-forming proteins (semenogelin and collagen). In a physiological context, the liquefaction process occurs within the female reproductive tract. How seminal proteins interact with the female reproductive environment is still largely unexplored. We previously reported that conditional genetic ablation of Esr1 (estrogen receptor α) in the epithelial cells of the female reproductive tract (Wnt7aCre/+;Esr1f/f) causes female infertility, partly due to a drastic reduction in the number of motile sperm entering the oviduct. In this study, we found that post-ejaculated semen from fertile wild-type males was solidified and the sperm were entrapped in Wnt7aCre/+;Esr1f/f uteri, compared to the watery semen (liquefied) found in Esr1f/f controls. In addition, semenogelin and collagen were not degraded in Wnt7aCre/+;Esr1f/f uteri. Amongst multiple gene families aberrantly expressed in the absence of epithelial ESR1, we have identified that a lack of Klks in the uterus is a potential cause for the liquefaction defect. Pharmacological inhibition of KLKs in the uterus replicated the phenotype observed in Wnt7aCre/+;Esr1f/f uteri, suggesting that loss of uterine and seminal KLK function causes this liquefaction defect. In human cervical cell culture, expression of several KLKs and their inhibitors (SPINKs) was regulated by estrogen in an ESR1-dependent manner. Our study demonstrates that estrogen/ESR1 signaling in the female reproductive tract plays an indispensable role in normal semen liquefaction, providing fundamental evidence that exposure of post-ejaculated semen to the suboptimal microenvironment in the female reproductive tract leads to faulty liquefaction and subsequently causes a fertility defect.


Aristotle Anniversary Year: remembering the contributions to medicine and human  biology of this great polymath

Jorge L Rodríguez

Facultad de Salud, Universidad Bernardo O’Higgins, Chile.

Pilar Vigil

Pontificia Universidad Católica de Chile


Fertility Treatment, Use of in Vitro Fertilization, and Time to Live Birth Based on Initial Provider Type

Abstract:
PURPOSE: To explore the relationship between the type of clinician (generalist vs subspecialist) initially seen by infertile women, the treatment received, and the time to pregnancy.

METHODS: We analyzed mixed-mode questionnaire data from 867 women with primary infertility enrolled into a retrospective cohort through population- and fertility clinic-based sampling. We compared women presenting first to generalist providers with women presenting first to fertility subspecialists, with the main outcomes of receiving in vitro fertilization (IVF), time to pregnancy, and live birth.

RESULTS: The first contact for most (84%) women with infertility was a generalist provider. Only 8% of women sought care first from a fertility subspecialist, and these women were older and had been trying longer to conceive. Women who presented first to a generalist provider were less likely to receive IVF (adjusted odds ratio, 0.48; 95% confidence interval, 0.28-0.82), were equally likely to achieve pregnancy, and had similar times to pregnancy (adjusted hazard ratio, 1.11; 95% confidence interval, 0.80-1.53) compared with women who presented first to a subspecialist.

CONCLUSIONS: Generalist providers are frequently the first point of care for women with difficulty conceiving and are uniquely positioned to promote the balanced management of infertility.

Journal of the American Board of Family Medicine : JABFM


Functional Hypothalamic Amenorrhea: An Endocrine Society Clinical Practice  Guideline

Catherine M Gordon

Cincinnati Children's Hospital Medical Center

Michelle P Warren

Columbia University Irving Medical Center

Abstract:
COSPONSORING ASSOCIATIONS: The American Society for Reproductive Medicine, the European Society of Endocrinology, and the Pediatric Endocrine Society. This guideline was funded by the Endocrine Society.
Objective: To formulate clinical practice guidelines for the diagnosis and treatment of functional hypothalamic amenorrhea (FHA).

Participants: The participants include an Endocrine Society-appointed task force of eight experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Endocrine Society committees and members and cosponsoring organizations reviewed and commented on preliminary drafts of this guideline.

Conclusions: FHA is a form of chronic anovulation, not due to identifiable organic causes, but often associated with stress, weight loss, excessive exercise, or a combination thereof. Investigations should include assessment of systemic and endocrinologic etiologies, as FHA is a diagnosis of exclusion. A multidisciplinary treatment approach is necessary, including medical, dietary, and mental health support. Medical complications include, among others, bone loss and infertility, and appropriate therapies are under debate and investigation.

The Journal of Clinical Endocrinology and Metabolism


Fallopian tube catheterization in the treatment of proximal tubal obstruction: a systematic review and meta-analysis

Ioannis Gallos

Nottingham University Hospitals NHS Trust

Lynne Robinson

Birmingham Women’s and Children’s NHS Foundation Trust

Abstract:
STUDY QUESTION: What is the chance of clinical pregnancy when fallopian tube catheterization is used for proximal tubal obstruction?

SUMMARY ANSWER: The pooled clinical pregnancy rate of tubal catheterization after proximal tubal obstruction is 27% (95% CI 25-30%).

WHAT IS KNOWN ALREADY: Restoring fallopian tube patency by performing tubal catheterization has fallen out of favour since the increased availability of IVF. Our study is the first systematic review and meta-analysis to investigate reproductive outcomes following tubal catheterization for proximal tubal obstruction.

STUDY DESIGN, SIZE, DURATION: We undertook a systematic review and meta-analysis of 27 observational studies consisting of 1720 patients undergoing tubal catheterization for proximal tubal obstruction, who attempted to conceive naturally after the procedure.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Systematic literature searches were performed in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A total of 2195 titles and abstracts were reviewed. Only studies that reported outcomes when tubal catheterization was performed with no other tubal surgery were included. Twenty-seven cohort studies matched the inclusion criteria for the meta-analysis.

MAIN RESULTS AND THE ROLE OF CHANCE: The meta-analysis showed a pooled clinical pregnancy rate of 27% (95% CI 25-30%) after the use of tubal catheterization for unilateral or bilateral proximal tubal obstruction (27 studies, 1556 patients). In women with bilateral obstruction (14 studies, 617 patients), the clinical pregnancy rate was 27% (95% CI 23-32%). Our meta-analysis demonstrated that the pooled cumulative clinical pregnancy rates were 22.3% (95% CI 17.8-27.8%) at 6 months, 25.8% (95% CI 21.1-31.5%) at 9 months, 26.4% (95% CI 23.0-30.2%) at 12 months, 26.0% (95% CI 22.8-29.7%) at 18 months, 27.0% (95% CI 24.0-30.5%) at 24 months, 27.9% (95% CI 24.9-31.3%) at 36 months and 28.5% (95% CI 25.5-31.8%) at 48 months. The pooled live birth rate (14 studies, 551 patients) was 22% (95% CI 18-26%). The pooled ectopic pregnancy rate (27 studies, 1556 patients) was 4% (95% CI 3-5%). The included studies scored satisfactorily on the Newcastle-Ottawa quality assessment scale.

LIMITATIONS, REASONS FOR CAUTION: The pooled clinical pregnancy rate after tubal catheterization was found to be almost comparable to that after IVF. However, included studies were small, non-comparative series with significant clinical heterogeneity in population characteristics, follow-up and surgical equipment, technique and experience.

WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest fallopian tube catheterization as an alternative strategy to IVF in patients presenting with proximal tubal obstruction. Further research should focus on comparing different surgical techniques of fallopian tube catheterization with IVF and provide cumulative reproductive outcomes over long-term follow-up.

STUDY FUNDING/COMPETING INTEREST(S): No funding was required and the authors have no competing interests to declare.

REGISTRATION NUMBER: N/A.


Use of Natural Family Planning (NFP) and Its Effect on Couple Relationships and  Sexual Satisfaction: A Multi-Country Survey of NFP Users from US and Europe

Elisabeth Rötzer

Institute of Natural Conception Regulation , Vienna , Austria.

Abstract:
Purpose: Birth control is a persistent global health concern. Natural family planning (NFP) comprises methods to achieve or avoid pregnancy independent of mechanical or pharmacological intervention. The sympto-thermal method (STM) of NFP employs daily observation of cervical fluids and measurement of basal body temperature. This multi-country study was undertaken to describe the characteristics of STM users, understand their perceptions of NFP, and its perceived impact on relationships. METHODS AND

Results: Questionnaires for women and men were developed in German and translated to English, Polish, Italian, Czech, and Slovak by native speakers. A total of 2,560 respondents completed the online questionnaire (37.4% response). Participants were married (89%) and well educated, and their self-perceived financial status was described as "good" or "very good" by 65% of the respondents. Forty-seven percent had previously used contraceptives. Ninety-five percent of women and 55% of men said using NFP has helped them to know their body better. Large majorities of men (74%) and women (64%) felt NFP helped to improve their relationship while <10% felt use of NFP had harmed their relationship. Most women (53%) and men (63%) felt using NFP improved their sex life while 32% of women and 24% of men felt it was unchanged from before they used NFP. Seventy-five percent of women and 73% of men said they are either "satisfied" or "very satisfied" with their frequency of sexual intercourse.

Conclusion: This survey demonstrates STM of NFP is a well-accepted approach to family planning across several Western cultures. It is consistently viewed as being beneficial to couples' self-knowledge, their relationship, and satisfaction with frequency of sexual intercourse.


The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen-Thawed  Embryo Transfer

Abstract: Tamoxifen has played a vital role in endocrine therapy for the treatment of estrogen receptor-positive breast cancer. We examined the effect of tamoxifen in patients with a thin endometrium in frozen-thawed embryo transfer (FET) cycles and compared the improvement in endometrial thickness (EMT) and pregnancy outcomes stratified by different etiologies of thin endometrium. A total of 226 women were recruited for a new tamoxifen protocol; all had an EMT of less than 7.5 mm in previous cycles, including natural cycle (NC), hormone replacement treatment (HRT), and ovulation induction (OI) cycles. Compared with previous cycles, tamoxifen cycles showed a significantly increased EMT (from 6.11 ± 0.98 mm to 7.87 ± 1.48 mm in the NC group, from 6.24 ± 1.01 mm to 8.22 ± 1.67 mm in the HRT group, and from 6.34 ± 1.03 mm to 8.05 ± 1.58 mm in the OI group; all P < .001). Patients were further divided into 3 groups based on the causes of their thin endometrium: (1) history of intrauterine adhesion (n = 34), (2) history of uterine curettage (n = 141), and (3) polycystic ovary syndrome (PCOS; n = 51). Patients with PCOS obtained the thickest EMT (9.31 ± 1.55 mm), the lowest cycle cancellation rate (11.76%), and the highest rate of clinical pregnancy (60%) and live birth (55.56%) per transfer ( P < .001). Multivariable regression analysis showed that EMT was related to live birth (odds ratio: 1.487; 95% confidence interval: 1.172-1.887). A tamoxifen protocol improves EMT in patients after NC, HRT, and OI cycles during FET. Patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.

Reproductive Sciences (Thousand Oaks, Calif.)


Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Patients with Autoimmune Thyroiditis

Abstract: Clinical evidences have highlighted the efficacy of myo-inositol and selenium in the treatment of autoimmune thyroiditis. Aim of this study was to further analyze the role of myo-inositol plus selenium (Myo-Ins-Se) in restoring a normal thyroid function of Hashimoto's patients with subclinical hypothyroidism. Eighty-six patients with Hashimoto's thyroiditis having thyroid-stimulating hormone (TSH) levels between 3 and 6 mIU/L, elevated serum antithyroid peroxidase (TPOAb) and/or antithyroglobulin (TgAb), and normal free thyroxine (fT(4)) and free triiodothyronine (fT(3)) levels were enrolled in the study: one hyperthyroid subject with TSH about 0.14 μU/ml was included in this trial as a single case. Patients were assigned to receive Myo-Ins-Se. TSH, TPOAb, and TgAb levels were significantly decreased in patients treated with combined Myo-Ins-Se after 6 months of treatment. In addition, a significant fT(3) and fT(4) increase, along with an amelioration of their quality of life, was observed. Remarkably, TSH values of the hyperthyroid patient increased from 0.14 μU/ml up to 1.02 μU/ml, showing a complete restoration of TSH values at a normal range. In conclusion, the administration of Myo-Ins-Se is significantly effective in decreasing TSH, TPOAb, and TgAb levels, as well as enhancing thyroid hormones and personal wellbeing, therefore restoring euthyroidism in patients diagnosed with autoimmune thyroiditis.


Effectiveness of a video intervention on fertility knowledge among university  students: a randomised pre-test/post-test study

Mariana V Martins

a Faculty of Psychology and Education Science , University of Porto , Porto , Portugal.

Abstract:
Objectives: Recent evidence has shown that young adults have poor knowledge about reproductive health and fertility, and that interventions are needed to increase fertility awareness. The aim of this study was to assess the effectiveness of a brief video in increasing knowledge about fertility and infertility in young adults.

Methods: We carried out a two-arm, parallel-group, randomised controlled trial with a pre-test/post-test design (NCT02607761, ClinicalTrials.gov). The sample was composed of 173 undergraduates who completed a self-report questionnaire. Participants were randomly assigned to exposure or no exposure to an educational video about reproductive health and infertility (intervention group, n = 89; control group, n = 84).

Results: At baseline, participants revealed poor knowledge of infertility risk factors and fertility issues, and average knowledge of the definition of infertility. Interaction effects between group and time were found for all variables targeted in the video. Participants in the intervention group significantly increased their knowledge of fertility issues, infertility risk factors and the definition of infertility. No significant differences in post-test knowledge were observed in the control group, except for the age at which there is a marked decrease in female fertility.

Conclusions: A short video intervention is effective in increasing short-term knowledge about reproductive health and infertility. If future research using longer intervals corroborates our findings, video intervention could be a useful tool in public health prevention campaigns.

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


Population-Wide Impact of Non-Hip Non-Vertebral Fractures on Mortality

Tineke van Geel

Department of Family MedicineResearch School Care and Public Health Research Institute (CAPHRI)Maastricht UniversityMaastrichtThe Netherlands

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Christopher S Kovacs

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Jacqueline R Center

Faculty of MedicineUniversity of New South WalesSydneyAustralia

Joop van den Bergh

Department of Internal MedicineVieCuri Medical Centre of Noord-LimburgVenloThe Netherlands

Abstract: Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two-thirds of all fragility fractures, are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526 community dwelling women and 2163 men aged 50 years or older followed from July 1995 to September 2013. Population impact number was used to quantify the average number of people for whom one death would be attributable to fracture and case impact number to quantify the number of deaths out of which one would be attributable to a fracture. There were 1370 fragility fractures followed by 296 deaths in women (mortality rate: 3.49; 95% CI, 3.11 to 3.91), and 302 fractures with 92 deaths in men (5.05; 95% CI, 4.12 to 6.20). NHNV fractures accounted for three-quarters of fractures. In women, the population-wide impact of NHNV fractures on mortality was greater than that of hip and vertebral fractures because of the greater number of NHNV fractures. Out of 800 women, one death was estimated to be attributable to a NHNV fracture, compared with one death in 2000 women attributable to hip or vertebral fracture. Similarly, out of 15 deaths in women, one was estimated to be attributable to a NHNV fracture, compared with one in over 40 deaths for hip or vertebral fracture. The impact of forearm fractures (ie, one death in 2400 women and one out of 42 deaths in women attributable to forearm fracture) was similar to that of hip, vertebral, or rib fractures. Similar, albeit not significant, results were noted for men. The study highlights the important contribution of NHNV fractures on mortality because many NHNV fracture types, except for the most distal fractures, have serious adverse consequences that affect a significant proportion of the population.

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


Endometriosis: Epidemiology, Diagnosis and Clinical Management

Abstract:
PURPOSE OF REVIEW: Endometriosis is a disease of adolescents and reproductive-aged women characterized by the presence of endometrial tissue outside the uterine cavity and commonly associated with chronic pelvic pain and infertility. Here we review the epidemiology of endometriosis as well as potential biomarkers for detection and with the goal of highlighting risk factors that could be used in combination with biomarkers to identify and treat women with endometriosis earlier..

RECENT FINDINGS: Early age at menarche, shorter menstrual length, and taller height are associated with a higher risk of endometriosis while parity, higher body mass index (BMI) and smoking are associated with decreased risk. Endometriosis often presents as infertility or continued pelvic pain despite treatment with analgesics and cyclic oral contraceptive pills.

SUMMARY: Despite a range of symptoms, diagnosis of endometriosis is often delayed due to lack of non-invasive, definitive and consistent biomarkers for diagnosis of endometriosis. Hormone therapy and analgesics are used for treatment of symptomatic endometriosis. However, the efficacy of these treatments are limited as endometriosis often recurs. In this review, we describe potential diagnostic biomarkers and risk factors that may be used as early non-invasive in vitro tools for identification of endometriosis to minimize diagnostic delay and improve reproductive health of patients.

Current obstetrics and gynecology reports


Interpregnancy interval following miscarriage and adverse pregnancy outcomes: systematic review and meta-analysis

Abstract:
BACKGROUND: A short interpregnancy interval (IPI) following a delivery is believed to be associated with adverse outcomes in the next pregnancy. The optimum IPI following miscarriage is controversial. Based on a single large-scale study in Latin and South America, the World Health Organization recommends delaying pregnancy for 6 months after a miscarriage to achieve optimal outcomes in the next pregnancy.

OBJECTIVE AND RATIONALE: Our aim was to determine if a short IPI (<6 months) following miscarriage is associated with adverse outcomes in the next pregnancy.

SEARCH METHODS: Studies were retrieved from MEDLINE, Embase and Pubmed, with no time and language restrictions. The search strategy used a combination of Medical Subject Headings terms for miscarriage, IPI and adverse outcomes. Bibliographies of the retrieved articles were also searched by hand. All studies including women with at least one miscarriage, comparing subsequent adverse pregnancy outcomes for IPIs of less than and more than 6 months were included. Two independent reviewers screened titles and abstracts for inclusion. Characteristics of the studies were extracted and quality assessed using Critical Appraisal Skills Programme criteria. A systematic review and meta-analysis were conducted to compare short (<6 months) versus long (>6 months) IPI following miscarriage in terms of risk of further miscarriage, preterm birth, stillbirth, pre-eclampsia and low birthweight babies in the subsequent pregnancy. Review Manager 5.3 was used for conducting meta-analyses.

OUTCOMES: Sixteen studies including 1 043 840 women were included in the systematic review and data from 10 of these were included in one or more meta-analyses (977 972 women). With an IPI of less than 6 months, the overall risk of further miscarriage (Risk ratio (RR) 0.82 95% CI 0.78, 0.86) and preterm delivery (RR 0.79 95% CI 0.75, 0.83) were significantly reduced. The pooled risks of stillbirth (RR 0.88 95% CI 0.76, 1.02); low birthweight (RR 1.05 95% CI 0.48, 2.29) and pre-eclampsia (RR 0.95 95% CI 0.88, 1.02) were not affected by IPI. Similar findings were obtained in subgroup analyses when IPI of <6 months was compared with IPI of 6-12 months and >12 months.

WIDER IMPLICATIONS: This is the first systematic review and meta-analysis providing clear evidence that an IPI of less than 6 months following miscarriage is not associated with adverse outcomes in the next pregnancy. This information may be used to revise current guidance.


NaProTechnology: science and the person in human papillomavirus (HPV) infection among women and preadolescents

José María Murcia Lora

Unit of Restaurative Roproductive Medicine, Clinical Consulting G&E, 26002 Logroño, La Rioja, Spain

Abstract: En la actualidad hay suficiente evidencia científica que relaciona directamente adquisición, exposición y prevalencia del virus del papiloma humano (VPH) con el cáncer del cuello de uterino. Por ello, el artículo aborda el VPH en la mujer teniendo en cuenta la naprotecnología, que permite conjugar evidencia científica y planteamientos éticos. Se busca que se tengan en cuenta tanto el aspecto biológico de la sexualidad como la capacidad de hacerse persona en su núcleo sexual. De ahí que se analicen programas dirigidos a la educación sexual, basados tanto en la prevención sanitaria como en la antropología de la sexualidad, y apoyados por las instituciones familiares, que han demostrado una mejor acogida ante los riesgos de las enfermedades de transmisión sexual, y entre ellas la infección por el VPH.


Contraceptive Failure in the United States: Estimates from the 2006-2010 National Survey of Family Growth

James Trussell

Princeton University; Office of Population research; Wallaca Hall Princeton New Jersey USA NJ 08544

Abstract:
CONTEXT: Contraceptive failure rates measure a woman's probability of becoming pregnant while using a contraceptive. Information about these rates enables couples to make informed contraceptive choices. Failure rates were last estimated for 2002, and social and economic changes that have occurred since then necessitate a reestimation.

METHODS: To estimate failure rates for the most commonly used reversible methods in the United States, data from the 2006-2010 National Survey of Family Growth were used; some 15,728 contraceptive use intervals, contributed by 6,683 women, were analyzed. Data from the Guttmacher Institute's 2008 Abortion Patient Survey were used to adjust for abortion underreporting. Kaplan-Meier methods were used to estimate the associated single-decrement probability of failure by duration of use. Failure rates were compared with those from 1995 and 2002.

RESULTS: Long-acting reversible contraceptives (the IUD and the implant) had the lowest failure rates of all methods (1%), while condoms and withdrawal carried the highest probabilities of failure (13% and 20%, respectively). However, the failure rate for the condom had declined significantly since 1995 (from 18%), as had the failure rate for all hormonal methods combined (from 8% to 6%). The failure rate for all reversible methods combined declined from 12% in 2002 to 10% in 2006-2010.

CONCLUSIONS: These broad-based declines in failure rates reverse a long-term pattern of minimal change. Future research should explore what lies behind these trends, as well as possibilities for further improvements.

Perspectives on Sexual and Reproductive Health


Polycystic Ovary Syndrome (PCOS), Diagnostic Criteria, and AMH

Majid Bani Mohammad

Department of Medicine Faculty, Islamic Azad University, Ardabil Branch, Ardabil.Iran. Email: abbas.majdi@yahoo.com

Abstract: The polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and a notable proportion of women of reproductive age are affected. It may constitute a risk factor for cancer development. Different factors could result in different manifestations and many of these are related to predispositions. It is essential to establish criteria to achieve an exact diagnosis of PCOS, especially among adolescent patients because of the overlap between features of PCO syndrome and physiological findings in puberty. Day by day the technology of ultrasonography is improving and accuracy is increasing, but remains dependent on the specific equipment available. Some factors are inter-related in determining PCOS prognosis. Serum AMH is synthesized by small antral follicles, which are precisely those seen on ultrasound and could help us to diagnose PCOS but there are many aspects that still require elucidation. In this minireview we have attempted to identify some of these correlations.

Asian Pacific Journal of Cancer Prevention : APJCP


Optimizing natural fertility: a committee opinion

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinology and Infertility.

American Society for Reproductive Medicine, Birmingham, Alabama.

Samantha Pfeifer

Abstract: This Committee Opinion provides practitioners with suggestions for optimizing the likelihood of achieving pregnancy in couples/individuals attempting conception who have no evidence of infertility. This document replaces the document of the same name previously published in 2013, Fertil Steril 2013;100(3):631-7.


Endometriosis in Hydatid Cysts of Morgagni: A Retrospective Cohort Study of  Another Atypical Manifestation of Endometriosis

Abstract:
STUDY Objective: To report on the presence and rate of endometriosis in hydatid cysts of Morgagni found at the time of excision surgery for endometriosis and to describe any association of endometriosis in hydatid cysts of Morgagni with preoperative or operative factors.
Design: A retrospective cohort study (Canadian Task Force Classification II-2).
Setting: The Center for Endometriosis at Saint Louis University, a tertiary referral center for endometriosis.

Patients: Women who underwent optimal excision surgery for suspected endometriosis because of chronic pelvic pain and/or infertility and who also had hydatid cysts of Morgagni removed at the time of surgery when found.

Interventions: Preoperative and operative data were collected prospectively.

Main Outcome Measures: The rate of endometriosis in hydatid cysts of Morgagni. Secondary measures included are the rate of hydatid cysts of Morgagni in patients with pelvic pain or infertility with and without endometriosis in the cysts.

Results: The overall prevalence of endometriosis in hydatid cysts of Morgagni was 11.3%. Patients with pelvic pain had a higher rate (although not statistically significant) of hydatid cysts of Morgagni compared with those without pain (21.1% vs 12.5 %, p = .54). Patients with infertility had a higher rate of hydatid cysts of Morgagni compared with those without infertility (38.1% vs 16.7%, p < .001), and there was a higher rate of endometriosis in the hydatid cysts of Morgagni in patients with infertility compared with those without (11.1% vs 0.0%, p < .001).

Conclusions: This study is the first known report of endometriosis found within hydatid cysts of Morgagni. With a rate of 11.3% of cysts of Morgagni having endometriosis within them, this study supports a practice of removing hydatid cysts of Morgagni at the time of surgery in order to achieve optimal excision of endometriosis. The rates of hydatid cysts of Morgagni and of endometriosis found within hydatid cysts of Morgagni were higher in patients with infertility. Further studies are needed to evaluate whether excising cysts of Morgagni affects clinical outcomes.

Journal of Minimally Invasive Gynecology


Natural conception rates in subfertile couples following fertility awareness  training

Petra Frank-Herrmann

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

Abstract:
Purpose: To analyze cumulative pregnancy rates of subfertile couples after fertility awareness training.

Methods: A prospective observational cohort study followed 187 subfertile women, who had received training in self-observation of the fertile phase of the menstrual cycle with the Sensiplan method, for 8 months. The women, aged 21-47 years, had attempted to become pregnant for 3.5 years on average (range 1-8 years) before study entry. Amenorrhea, known tubal occlusion and severe male factor had been excluded. An additional seven women, who had initially been recruited, became pregnant during the cycle immediately prior to Sensiplan training: this is taken to be the spontaneous pregnancy rate per cycle in the cohort in the absence of fertility awareness training.

Results: The cumulative pregnancy rate of subfertile couples after fertility awareness training was 38% (95% CI 27-49%; 58 pregnancies) after eight observation months, which is significantly higher than the estimated basic pregnancy rate of 21.6% in untrained couples in the same cohort. For couples who had been seeking to become pregnant for 1-2 years, the pregnancy rate increased to 56% after 8 months. A female age above 35 (cumulative pregnancy rate 25%, p = 0.06), couples who had attempted to become pregnant for more than 2 years (cumulative pregnancy rate 17%, p < 0.01), all significantly reduce the chances of conceiving naturally at some point.

Conclusions: Training women to identify their fertile window in the menstrual cycle seems to be a reasonable first-line therapy in the management of subfertility.


Recommendations for practices utilizing gestational carriers: a committee opinion

Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org

Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology

Abstract: This document provides the latest recommendations for evaluation of gestational carriers and intended parents. It incorporates recent information from the US Centers for Disease Control and Prevention, the US Food and Drug Administration, and the American Association of Tissue Banks, with which all programs offering gestational carrier services must be thoroughly familiar. This document replaces the previous document of the same name, last published in 2015 (Fertil Steril® 2015; 103:e1-8).


Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year

Abstract:
BACKGROUND: Due to its potent effects on social behavior, including maternal behavior, oxytocin has been identified as a potential mediator of postpartum depression and anxiety. The objective of this study was to examine the relationship between peripartum synthetic oxytocin administration and the development of depressive and anxiety disorders within the first year postpartum. We hypothesized that women exposed to peripartum synthetic oxytocin would have a reduced risk of postpartum depressive and anxiety disorders compared with those without any exposure.

METHODS: Population-based data available through the Massachusetts Integrated Clinical Academic Research Database (MiCARD) were used to retrospectively (2005-2014) examine this relationship and calculate the relative risk of peripartum synthetic oxytocin for the development of postpartum depressive and anxiety disorders in exposed (n = 9,684) compared to unexposed (n = 37,048) deliveries.

RESULTS: Among deliveries to women with a history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 36% (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.20-1.55). In deliveries to women with no history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 32% compared to those not exposed (RR: 1.32; 95% CI: 1.23-1.42).

CONCLUSIONS: Contrary to our hypothesis, results indicate that women with peripartum exposure to synthetic oxytocin had a higher relative risk of receiving a documented depressive or anxiety disorder diagnosis or antidepressant/anxiolytic prescription within the first year postpartum than women without synthetic oxytocin exposure.


Patterns and predictors of sitting time over ten years in a large population-based Canadian sample: Findings from the Canadian Multicentre Osteoporosis Study (CaMos)

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Adrian E Bauman

Prevention Research Collaboration, Sydney School of Public Health, University of Sydney, Level 6, The Charles Perkins Centre (D17), Sydney, NSW 2006, Australia.

Abstract: Our objective was to describe patterns and predictors of sedentary behavior (sitting time) over 10 years among a large Canadian cohort. Data are from the Canadian Multicentre Osteoporosis Study, a prospective study of women and men randomly selected from the general population. Respondents reported socio-demographics, lifestyle behaviors and health outcomes in interviewer-administered questionnaires; weight and height were measured. Baseline data were collected between 1995 and 1997 (n = 9418; participation rate = 42%), and at 5- (n = 7648) and 10-year follow-ups (n = 5567). Total sitting time was summed across domain-specific questions at three time points and dichotomized into "low" (≤ 7 h/day) and "high" (> 7 h/day), based on recent meta-analytic evidence on time sitting and all-cause mortality. Ten-year sitting patterns were classified as "consistently high", "consistently low", "increased", "decreased", and "mixed". Predictors of sedentary behavior patterns were explored using chi-square tests, ANOVA and logistic regression. At baseline (mean age = 62.1 years ± 13.4) average sitting was 6.9 h/day; it was 7.0 at 5and 10-year follow-ups (p for trend = 0.12). Overall 23% reported consistently high sitting time, 22% consistently low sitting, 14% decreased sitting, 17% increased sitting with 24% mixed patterns. Consistently high sitters were more likely to be men, university educated, full-time employed, obese, and to report consistently low physical activity levels. This is one of the first population-based studies to explore patterns of sedentary behavior (multi-domain sitting) within men and women over years. Risk classification of sitting among many adults changed during follow-up. Thus, studies of sitting and health would benefit from multiple measures of sitting over time.


Chronic endometritis and infertility

Chronic endometritis and infertility

Abstract: Chronic endometritis (CE) is a condition involving the breakdown of the peaceful co-existence between microorganisms and the host immune system in the endometrium. A majority of CE cases produce no noticeable signs or mild symptoms, and the prevalence rate of CE has been found to be approximately 10%. Gynecologists and pathologists often do not focus much clinical attention on CE due to the time-consuming microscopic examinations necessary to diagnose CE, its mild clinical manifestations, and the benign nature of the disease. However, the relationship between CE and infertility-related conditions such as repeated implantation failure and recurrent miscarriage has recently emerged as an area of inquiry. In this study, we reviewed the literature on the pathophysiology of CE and how it may be associated with infertility, as well as the literature regarding the diagnosis and treatment of CE. In addition, we discuss the value of hysteroscopic procedures in the diagnosis and treatment of CE.

Clinical and Experimental Reproductive Medicine


Direct-to-consumer advertising of success rates for medically assisted reproduction: a review of national clinic websites

Abstract: OBJECTIVES: To establish how medically assisted reproduction (MAR) clinics  report success rates on their websites. SETTING: Websites of private and NHS clinics offering in vitro fertilisation  (IVF) in the UK. PARTICIPANTS: We identified clinics offering IVF using the Choose a Fertility  Clinic facility on the website of the Human Fertilisation and Embryology  Authority (HFEA). Of 81 clinics identified, a website could not be found for 2,  leaving 79 for inclusion in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Outcome measures reported by clinic  websites. The numerator and denominator included in the outcome measure were of  interest. RESULTS: 53 (67%) websites reported their performance using 51 different outcome  measures. It was most common to report pregnancy (83% of these clinics) or live  birth rates (51%). 31 different ways of reporting pregnancy and 9 different ways  of reporting live birth were identified. 11 (21%) reported multiple birth or  pregnancy rates. 1 clinic provided information on adverse events. It was usual  for clinics to present results without relevant contextual information such as  sample size, reporting period, the characteristics of patients and particular  details of treatments. CONCLUSIONS: Many combinations of numerator and denominator are available for  the purpose of reporting success rates for MAR. The range of reporting options  available to clinics is further increased by the possibility of presenting  results for subgroups of patients and for different time periods. Given the  status of these websites as advertisements to patients, the risk of selective  reporting is considerable. Binding guidance is required to ensure consistent,  informative reporting.


Per- and Polyfluoroalkyl Substances (PFASs) in Food and Human Dietary Intake: A Review of the Recent Scientific Literature

Abstract: Because of the important environmental presence and the potential human toxicity of per- and polyfluorinated alkyl substances (PFASs), in recent years the social and scientific interest in these compounds has notably increased. Special attention has been paid to perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), the most extensively investigated PFASs. Although human exposure to PFASs may occur through different pathways, dietary intake seems to be the main route of exposure to these compounds. In 2012, we published a wide revision on the state of the science regarding the concentrations of PFASs in foodstuffs, the human dietary exposure to these compounds, and their health risks. In the present review, we have updated the information recently (2011-2016) published in the scientific literature. As in our previous review, we have also observed considerable differences in the PFASs detected-and their concentrations-in the food items analyzed in samples from a number of regions and countries. However, fish and other seafood seem to be the food group in which more PFASs are detected and where the concentrations of these compounds are higher. On the basis of the recommendations of the EFSA on the maximum dietary intakes of PFOS and PFOA, human health risks would not be of concern for nonoccupationally exposed populations, at least in the very limited countries for which recent data are available.

Journal of Agricultural and Food Chemistry


The effects of tomato juice on male infertility

Kuniko Furui

Department of Pharmacy, International University of Health and Welfare Hospital, Nasushiobara, Japan.

Teruaki Iwamoto

Center for Infertility and IVF, International University of Health and Welfare Hospital, Nasushiobara, Japan.

Makiko Mieno

Center for Information, Jichi Medical University, Shimotsuke, Japan.

Ikuo Sato

Department of Obstetrics and Gynecology, International University of Health and Welfare Hospital, Nasushiobara, Japan.

Yu Yamamoto

Research and Development Division, Kagome, Nasushiobara, Japan. Email: Yu_Yamamoto@kagome.co.jp.

Kazumitsu Yamazaki

Department of Urology, International University of Health and Welfare Hospital, Nasushiobara, Japan.

Abstract:
BACKGROUND AND OBJECTIVES: This study aimed to investigate the effects of tomato juice consumption on seminal plasma lycopene levels and sperm parameters in infertile men.

METHODS AND

STUDY DESIGN: Subjects were male infertility patients with poor sperm concentration (<20×10 6/mL) and/or motility (<50%). Following a fourweek observation period, subjects were randomly assigned among three groups: a tomato juice group, an antioxidant group, and a control group. The subjects in the tomato juice group and the antioxidant group daily consumed one can of tomato juice (containing 30 mg of lycopene) or one antioxidant capsule (containing vitamin C 600 mg, vitamin E 200 mg, and glutathione 300 mg), respectively, for 12 weeks (feeding period). Seminal plasma lycopene levels and sperm parameters were measured every 6 weeks during the feeding period.

RESULTS: Forty-four patients completed the study (control group: 12, antioxidant group: 15, tomato juice group: 17). In the tomato juice group, plasma lycopene level was significantly increased at the 12th week of the feeding period. Moreover, a decrease in seminal plasma white blood cells and an increase in sperm motility in the tomato juice group were statistically significant at the 12th and 6th weeks, respectively, compared to the control group. In the antioxidant capsule group, no significant improvement was observed in semen parameters.

CONCLUSIONS: In conclusion, regular consumption of tomato juice seems to improve sperm motility in infertile patients. This is the first report to show that commercially available food, such as tomato juice, might be beneficial for male infertility.

Asia Pacific Journal of Clinical Nutrition


Tridimensional Visualization and Analysis of Early Human Development

Abstract: Generating a precise cellular and molecular cartography of the human embryo is essential to our understanding of the mechanisms of organogenesis in normal and pathological conditions. Here, we have combined whole-mount immunostaining, 3DISCO clearing, and light-sheet imaging to start building a 3D cellular map of the human development during the first trimester of gestation. We provide high-resolution 3D images of the developing peripheral nervous, muscular, vascular, cardiopulmonary, and urogenital systems. We found that the adult-like pattern of skin innervation is established before the end of the first trimester, showing important intra- and inter-individual variations in nerve branches. We also present evidence for a differential vascularization of the male and female genital tracts concomitant with sex determination. This work paves the way for a cellular and molecular reference atlas of human cells, which will be of paramount importance to understanding human development in health and disease. PAPERCLIP.


DIR Jahrbuch 2016 (Deutsches IVF-Register Annual Report 2016)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2016. 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).


Endometriosis in Adolescents: A Systematic Review

Abstract: Introduction The aim of this manuscript is to present a systematic review of characteristics and management of endometriosis in adolescents in order to gain some relevant insight into the most appropriate clinical management of the disease. Methods The literature review was done using electronic database PubMed focusing on the terms ‘adolescents’, ‘endometriosis’, ‘teenagers’, ‘pain’, ‘infertility’, ‘quality of life’, ‘medical’ and ‘surgical management’ from 1980 onward and was limited to articles in English. Articles were only included if they reported original relevant research. Results The 24 studies selected for review included 1148 adolescents with laparoscopic proven endometriosis. The diagnosis of endometriosis was histologically confirmed in 39.02% (448/1148) of cases. The results from trials have been tabulated and main results presented in a question and answer format. Conclusions The majority of adolescent girls with chronic pelvic pain not responding to conventional medical therapy have endometriosis (up to 80%). Laparoscopy with biopsy is the only way to diagnose endometriosis in the adolescent population, and depends on recognition of atypical manifestations of the disease. Surgical management (especially by an expert surgeon) has been shown to be beneficial in reducing pain, improving infertility, and preventing progression or recurrence of disease. Postoperative hormonal suppression helps reduce pain symptoms and recurrence of endometriomas, but it does not seem to prevent disease recurrence or progression of peritoneal endometriosis, and has not been shown to improve future fertility. Postoperative suppression until pregnancy is based on expert opinion only. There is a need for good quality properly randomized trials.

Journal of Endometriosis and Pelvic Pain Disorders


Oral contraceptives cause evolutionarily novel increases in hormone exposure: A risk factor for breast cancer

Abstract: Background and objectives: In the evolutionary past, women spent most of their reproductive lives either pregnant or in lactational amenorrhea, and rarely menstruated. The current pattern of frequent menses, and the associated increase in endogenous hormonal exposure, has been implicated in the current breast cancer epidemic. It is not known, however, whether oral contraceptives further increase, or actually decrease, hormonal exposure over one menstrual cycle. Here, we examined variation in hormonal exposure across seven oral contraceptive (OC) formulations, and produced the first quantitative comparison of exogenous versus endogenous hormone exposure. Methodology: Data from 12 studies of serum estradiol (E2) and progesterone (P4) were aggregated to create a composite graph of endogenous hormone levels over one menstrual cycle in European or American women (age 19-40 years). Pharmacokinetic package insert data, also from Western women, were used to calculate exposures for hormones in seven different OC formulations. Endogenous and exogenous hormone levels were compared after adjusting for the relative binding affinity (RBA) of progestin to the progesterone receptor and ethinyl estradiol (EE) to the estrogen receptor. Results: After adjusting for RBA, median ethinyl estradiol exposure across 28 days in the OCs was 11.4 nmol/l, similar to median E2 exposure. One formulation, however, was 40% higher in ethinyl estradiol exposure relative to median endogenous estradiol. Median exposure from progestins in OCs (1496 nmol/l) was 4-fold higher than the median endogenous exposure from P4 (364 nmol/l). Exposure from OC progestins ranged from one sixtieth to 8-fold median endogenous P4 over 28 days. Conclusions and implications: Given that breast cancer risk increases with hormonal exposure, our finding that four widely prescribed formulations more than quadruple progestin exposure relative to endogenous progesterone exposure is cause for concern. As not all formulations produce the same exposures, these findings are pertinent to contraceptive choice. We also identify critical gaps in the provision of relevant data on pharmacokinetics and carcinogenicity by drug manufacturers.


Systematic Review of Premenstrual, Postmenstrual and Infertility Disorders of Vitex Agnus Castus

Abstract:
INTRODUCTION: Vitex agnus-castus, also called vitex is aboriginal to the Mediterranean region, with long leaves, tender stem, flowers and ripening seeds. The aim of this study was to overview premenstrual, postmenstrual and infertility disorder of Vitex agnus-castus.

METHODS: This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified about 87 references. In this study, 43 studies were accepted for further screening, and met all our inclusion criteria (in English, full text, therapeutic effects of Vitex agnus-castus and dated mainly from the year 2009 to 2016). The search terms were Vitex agnus-castus, premenstrual, postmenstrual, infertility disorder properties and pharmacological effects.

RESULT: Vitex agnus-castus was shown to contribute to the treatment of premenstrual syndrome (PMS). Moreover, the result of the present study showed that this valuable plant is helpful in alleviation of pain resulting from postmenstrual disease. Furthermore, it was found that Vitex agnus-castus is beneficial in infertility disorder.

CONCLUSION: Vitex agnus-castus (AC) is a phytopharmaceutical compound and is shown to be widely used to treat PMS and PMDD. In addition, it was shown to be beneficial in post-menstrual cases and it can also contribute to treatment of infertility cases in both men and women. Dopaminergic compounds available in this plant help to treat premenstrual mastodynia as well as other symptoms of the premenstrual syndrome.


The sixth vital sign: what reproduction tells us about overall health. Proceedings from a NICHD/CDC workshop

Lee Warner

Abstract:
STUDY QUESTION: Does the fertility status of an individual act as a biomarker for their future health?

SUMMARY ANSWER: Data support an association between reproductive health and overall health for men and women.

WHAT IS ALREADY KNOWN: Various chronic conditions, such as diabetes, obesity and cancer, can compromise fertility, but there are limited data for the converse situation, in which fertility status can influence or act as a marker for future health. Data reveal an association between infertility and incident cardiovascular disease and cancer in both men and women.

STUDY DESIGN SIZE AND DURATION: A National Institute of Child Health and Human Development-Centers for Disease Control and Prevention workshop in April 2016 was convened that brought together experts in both somatic diseases and conditions, and reproductive health. Goals of the workshop included obtaining information about the current state of the science linking fertility status and overall health, identifying potential gaps and barriers limiting progress in the field, and outlining the highest priorities to move the field forward.

PARTICIPANTS/MATERIALS SETTING AND METHODS: Approximately 40 experts participated in the workshop.

MAIN RESULTS AND THE ROLE OF CHANCE: While the etiology remains uncertain for infertility, there is evidence for an association between male and female infertility and later health. The current body of evidence suggests four main categories for considering biological explanations: genetic factors, hormonal factors, in utero factors, and lifestyle/health factors. These categories would be key to include in future studies to develop a comprehensive and possibly standardized look at fertility status and overall health. Several themes emerged from the group discussion including strategies for maximizing use of existing resources and databases, the need for additional epidemiologic studies and public health surveillance, development of strategies to frame research so results could ultimately influence clinical practice, and the identification of short and long-term goals and the best means to achieve them.

LIMITATIONS REASONS FOR CAUTION: Further research may not indicate an association between fertility status and overall health.

WIDER IMPLICATIONS OF THE FINDINGS: Currently medical care is compartmentalized. Reproductive medicine physicians treat patients for a short period of time before they transition to others for future care. Going forward, it is critical to take an interdisciplinary patient care approach that would involve experts in a broad range of medical specialties in order to more fully understand the complex interrelationships between fertility and overall health. If infertility is confirmed as an early marker of chronic disease then screening practices could be adjusted, as they are for patients with a family history of malignancy.

STUDY FUNDING/COMPETING INTERESTS: Funding for the workshop was provided by the Fertility and Infertility Branch, National Institute of Child Health and Human Development, National Institutes of Health and the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control. There are no conflicts of interest to declare. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Institutes of Health.

TRIAL REGISTRATION NUMBER: Not applicable.


Epigenetic Influences During the Periconception Period and Assisted Reproduction

Abstract: The periconception period starts 6 months before conception and lasts until the tenth week of gestation. In this chapter, we will focus on epigenetic modifications to DNA and gene expression within this period and during assisted reproduction. There are two critical times during the periconception window when significant epigenetic 'reprogramming' occur: one during gametogenesis and another during the pre-implantation embryonic stage. Furthermore, assisted conception treatments, laboratory protocols and culture media can affect the embryo development and birth weights in laboratory animals. There is, however, an ongoing debate as to whether epigenetic changes in humans, causing embryo mal-development, placenta dysfunction and birth defects, result from assisted reproductive technologies or are consequences of pre-existing medical and/or genetic conditions in the parents. The periconception period starts from ovarian folliculogenesis, through resumption of oogenesis, fertilisation, peri-implantation embryo development, embryogenesis until the end of organogenesis. In men, it is the period from spermatogenesis to epididymal sperm storage and fertilisation. Gametes and developing embryos are sensitive to environmental factors during this period, and epigenetic modifications can occur in response to adverse lifestyles and environmental factors. We now know that lifestyle factors such as advanced parentage age, obesity or undernutrition, smoking, excessive alcohol and caffeine intake and recreational drugs used during gamete production and embryogenesis could induce epigenetic alterations, which could impact adversely on pregnancy outcomes and health of the offspring. Furthermore, these can also result in a permanent and irreversible effect in a dose-dependent manner, which can be passed on to the future generations.

Advances in experimental medicine and biology


CARTR Plus 2017 Annual Report (2016 Data) - Canadian Assisted Reproductive Technologies Register Plus

Canadian Fertility and Andrology Society; BORN Ontario

Abstract: CARTR Plus annual report presented at CFAS Annual Meeting October 2016, reporting Canadian ART cycle outcomes.


Effects of acupuncture for the treatment of endometriosis-related pain: A systematic review and meta-analysis

Yan-wen Xu

The First Affiliated Hospital, Sun Yat-sen University

Tin-Chiu Li

University of Sheffield, United Kingdom.

Abstract:
BACKGROUND: Endometriosis is a multifactorial, oestrogen-dependent, inflammatory, gynaecological condition that can result in long-lasting visceral pelvic pain and infertility. Acupuncture could be an effective treatment for endometriosis and may relieve pain. Our aim in the present study was to determine the effectiveness of acupuncture as a treatment for endometriosis-related pain.

METHODS: In December 2016, six databases were searched for randomised controlled trials that determined the effectiveness of acupuncture in the treatment of endometriosis-related pain. Ultimately, 10 studies involving 589 patients were included. The main outcomes assessed were variation in pain level, variation in peripheral blood CA-125 level, and clinical effective rate. All analyses were performed using comprehensive meta-analysis statistical software.

RESULTS: Of the 10 studies included, only one pilot study used a placebo control and assessed blinding; the rest used various controls (medications and herbs), which were impossible to blind. The sample sizes were small in all studies, ranging from 8 to 36 patients per arm. The mean difference (MD) in pain reduction (pre- minus post-interventional pain level-measured on a 0-10-point scale) between the acupuncture and control groups was 1.36 (95% confidence intervals [CI] = 1.01-1.72, P<0.0001). Acupuncture had a positive effect on peripheral blood CA-125 levels, as compared with the control groups (MD = 5.9, 95% CI = 1.56-10.25, P = 0.008). Similarly, the effect of acupuncture on clinical effective rate was positive, as compared with the control groups (odds ratio = 2.07; 95% CI = 1.24-3.44, P = 0.005).

CONCLUSIONS: Few randomised, blinded clinical trials have addressed the efficacy of acupuncture in treating endometriosis-related pain. Nonetheless, the current literature suggests that acupuncture reduces pain and serum CA-125 levels, regardless of the control intervention used. To confirm these findings, additional, blinded studies with proper controls and adequate sample sizes are needed.


Assisted reproductive technology in Japan: a summary report of 1992-2014 by the Ethics Committee, Japan Society of Obstetrics and Gynecology

Abstract: Multi-decade summary report covering assisted reproductive technology (ART) cycles performed in Japan from 1992 through 2014, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG). Provides longitudinal trends in cycle volume, treatment-type stratification, and outcomes from JSOG-registered ART facilities.


Naprotechnology for Abnormal Bleeding and PCOS in Adolescents: Vital Sign-Based Evaluation

Abstract:
The topic of how the menstrual cycle is a vital sign which could signal pathophysiologic process has received considerable attention in the past decade. The current recommendations of various academic groups will be discussed as well as the FertilityTMM Care method of charting and the Naprotechnology approach to evaluating abnormalities of the menstrual cycle. Two clinical scenarios seen in adolescent medicine, PCOS and AUB, will be analyzed looking at the pathophysiology of these clinical scenarios and their management. The approach will be one that conducts an evaluation to try to find the underlying problem and aims to restore the normal physiology of the menstrual cycle.
The American Academy of Pediatrics, the American College of Obstetrics and Gynecology and the New York Academy of Sciences have published academic statements during the past ten years emphasizing the need for providers to teach patients how to chart and the important clinical ramifications of using this charting as a vital sign. In 2006 the American Academy of Pediatrics published in the Pediatrics Journal a recommendation titled: "Menstruation in Girls and Adolescents: Using the Menstrual Sign as a Vital Sign." In 2015, the American College of Obstetrics and Gynecology published a Committee Opinion emphasizing the need to teach women the charting of their menses and the important pathophysiologic process that could be detected with the charting.


Fetal Effects of Estrogens, Progestogens, and Diethylstilbestrol

Qian-Xing Zou

Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi 330031, PR China.

Qiuhong Zhao

University of Tennessee Health Science Center

Tao Luo

Institute of Life Science and School of Life Science, Nanchang University, Nanchang, Jiangxi 330031, PR China luotao@ncu.edu.cn.


Maternal Morbidity After Previable Prelabor Rupture of Membranes

Catherine J. Vladutiu

University of North Carolina at Chapel Hill

Abstract:
OBJECTIVE: To identify risk factors for maternal morbidity after previable prelabor rupture of membranes (PROM).

METHODS: We conducted a case-control study of singleton and twin pregnancies complicated by previable PROM (14.0-22.9 weeks of gestation) at a single tertiary care referral institution, 2000-2015. Pregnancies complicated by fetal anomalies, previable PROM within 2 weeks of chorionic villus sampling or amniocentesis, and those with contraindications to expectant management (eg, chorioamnionitis) were excluded. Cases were women with the primary outcome of composite maternal morbidity (defined as having at one or more of the following: sepsis, intensive care unit admission, acute renal insufficiency, uterine curettage, hysterectomy, deep vein thrombosis, pulmonary embolus, blood transfusion, readmission, or maternal death). Controls were women without the primary composite morbidity. Bivariate analysis compared demographic, clinical, and management characteristics of women in the case group and those in the control group. Multivariable logistic regression models were developed to quantify the association between maternal characteristics and composite severe maternal morbidity.

RESULTS: During the study period, 174 women presented with by previable PROM and were candidates for expectant management. Sixty-five (37%) women opted for immediate delivery; 109 (63%) elected expectant management. Twenty-five of 174 (14%) experienced one or more components of the composite maternal morbidity (cases) and were compared with 149 (86%) women in the control group. Women in the case group were more not more likely to elect expectant management (68% compared with 59%, P=.40), but were more likely to be aged 35 years or older (40% compared with 14%, P=.002) or to be carrying twins (52% compared with 16%, P<.01). In the regression model, twin gestation and age 35 years or older were both significantly associated with increased odds of composite maternal morbidity (odds ratio [OR] 5.62, 95% confidence interval [CI] 2.21-14.3 and OR 4.00, 95% CI 1.48-10.8, respectively).

CONCLUSION: Antenatal counseling of women with previable PROM should include that one in seven women experience significant morbidity. Although expectant management was not associated with increased risk in this cohort, women with twins or those aged 35 years or older were at substantially increased risk.