The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

Marinus J C Eijkemans

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, CX Utrecht, Netherlands

Abstract:
BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.

METHODS: A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.

RESULTS: A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18-40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) -0.49 nmol/l (-0.55, -0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20-25 µg EE had similar effects on total and free T compared with COCs with 30-35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20-25 µg EE) were found to have less impact on SHBG concentrations.

CONCLUSIONS: The current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinical implications of suppressed androgen levels during COC use remain to be elucidated.


Congenital malformations among babies born following letrozole or clomiphene for infertility treatment

Abstract:
CONTEXT: Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations.

AIMS: To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment.

SETTINGS AND DESIGN: A retrospective cohort study done at a tertiary infertility centre.

METHODS AND MATERIAL: A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied.

RESULTS: Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%).

CONCLUSIONS: There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment.

KEY MESSAGES: Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.


Exposure to endocrine disrupting chemicals and male reproductive health

Abstract: Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs.


Xiyao Liu

First Affiliated Hospital of Chongqing Medical University

Paolo F. Rinaudo

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.

Abstract:
1. Endocrinology. 2014 May;155(5):1956-69. doi: 10.1210/en.2013-2081. Epub 2014
Mar 31.

Use of a mouse in vitro fertilization model to understand the developmental
origins of health and disease hypothesis.

Feuer SK(1), Liu X, Donjacour A, Lin W, Simbulan RK, Giritharan G, Piane LD,
Kolahi K, Ameri K, Maltepe E, Rinaudo PF.

Author information:
(1)Department of Obstetrics, Gynecology and Reproductive Sciences (S.K.F., X.L.,
A.D., W.L., R.K.S., G.G., L.D.P., K.K., P.F.R.), and Department of Pediatrics
(K.A., E.M.), University of California San Francisco, San Francisco, California
94143; Nevada Center for Reproductive Medicine (G.G.), Reno, Nevada 89511;
Obstetric and Gynecology Department (L.D.P.), University of Turin, Turin, Italy;
and Oregon Health & Science University (K.K.), Portland, Oregon 97239.

The Developmental Origins of Health and Disease hypothesis holds that
alterations to homeostasis during critical periods of development can predispose
individuals to adult-onset chronic diseases such as diabetes and metabolic
syndrome. It remains controversial whether preimplantation embryo manipulation,
clinically used to treat patients with infertility, disturbs homeostasis and
affects long-term growth and metabolism. To address this controversy, we have
assessed the effects of in vitro fertilization (IVF) on postnatal physiology in
mice. We demonstrate that IVF and embryo culture, even under conditions
considered optimal for mouse embryo culture, alter postnatal growth trajectory,
fat accumulation, and glucose metabolism in adult mice. Unbiased metabolic
profiling in serum and microarray analysis of pancreatic islets and insulin
sensitive tissues (liver, skeletal muscle, and adipose tissue) revealed broad
changes in metabolic homeostasis, characterized by systemic oxidative stress and
mitochondrial dysfunction. Adopting a candidate approach, we identify
thioredoxin-interacting protein (TXNIP), a key molecule involved in integrating
cellular nutritional and oxidative states with metabolic response, as a marker
for preimplantation stress and demonstrate tissue-specific epigenetic and
transcriptional TXNIP misregulation in selected adult tissues. Importantly,
dysregulation of TXNIP expression is associated with enrichment for H4
acetylation at the Txnip promoter that persists from the blastocyst stage
through adulthood in adipose tissue. Our data support the vulnerability of
preimplantation embryos to environmental disturbance and demonstrate that
conception by IVF can reprogram metabolic homeostasis through metabolic,
transcriptional, and epigenetic mechanisms with lasting effects for adult growth
and fitness. This study has wide clinical relevance and underscores the
importance of continued follow-up of IVF-conceived offspring.

DOI: 10.1210/en.2013-2081
PMCID: PMC3990843
PMID: 24684304 [Indexed for MEDLINE]


Adverse Incidents in Fertility Clinics: Lessons to Learn 2013

Human Fertilisation and Embryology Authority


Subcutaneous terbutaline pump

Subcutaneous terbutaline pump

Mohammed T. Ansari

Clinical Epidemiology Program, the Ottawa Hospital Research Institute, P.O. Box 201B, TOH-General Campus, 501 Smyth Rd, Ottawa, ON, Canada K1H 8L6


DIR Jahrbuch 2013 (Deutsches IVF-Register Annual Report 2013)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2013. 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).


CARTR Plus 2014 Annual Report (2013 Data) - Canadian Assisted Reproductive Technologies Register Plus

Canadian Fertility and Andrology Society; BORN Ontario

Abstract: CARTR Plus annual report covering Canadian ART cycle outcomes; presented at CFAS Annual Meeting October 2015 with 2013 birth outcomes and 2011-2014 cycle data. The Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus) is a voluntary professional society database operated by CFAS in collaboration with BORN Ontario.


Incarcerated Omentum With Tamponade Effect in the Uterine Perforation Scar After Dilation and Curettage: A Case Report

Abstract: Perforation of the uterus is the most common immediate complication at the time of dilatation and curettage (D&C). We experienced the case of a patient with intra-abdominal extrusion of fetal part and incarcerated omentum in the perforation site of uterine fundus after D&C. It resulted in massive bleeding after the reduction of the incarcerated omentum which had a tamponade effect. A 26-year-old gravida 2, para 1 woman was referred to our hospital because of uterine perforation during D&C. A laparoscopic exploration was performed. Bleeding started massively at the perforation scar after reduction of the incarcerated omentum which had a tamponade effect. Though bleeding from perforation site stopped after laparoscopic myometrial repair, vaginal bleeding persisted further. The placing of an intrauterine balloon tamponade stopped the vaginal bleeding. The patient recovered successfully and was discharged on the fifth postoperative day. J Med Cases. 2014;5(4):204-207 doi: http://dx.doi.org/10.14740/jmc1713w


Chronic Pelvic Pain: An Integrated Approach - APGO Educational Series on Women's Health Issues

Association of Professors in Gynecology and Obstetrics


Menstrual phase as predictor of outcome after mild traumatic brain injury in women

Abstract:
OBJECTIVE: To determine whether menstrual cycle phase in women at the time of mild traumatic brain injury (mTBI) predicts 1-month outcomes.

SETTING: Six emergency departments; 5 in Upstate New York, and 1 in Pennsylvania.

PARTICIPANTS: One hundred forty-four female participants (age, 16-60) who presented to participating emergency departments within 4 hours of mTBI.

DESIGN: Nested cohort study with neurologic and quality-of-life outcome assessment, 1 month after enrollment. Female subjects aged 16 to 60 enrolled in the parent cohort study, with 1-month neurological determination data available, were classified into menstrual cycle groups by serum progesterone concentration and self-reported contraceptive use.

MAIN MEASURES: Rivermead Post Concussion Questionnaire and EuroQoL/EQ5D.

RESULTS: Women injured during the luteal phase of their menstrual cycle, when progesterone concentration is high, had significantly lower EuroQoL General Health Ratings and Index Scores than women injured during the follicular phase of their cycle or women taking oral contraceptives. Multivariate analysis confirmed a significant independent effect of menstrual cycle phase on EuroQoL Index Score and the Rivermead Post Concussion Questionnaire Somatic Subscore.

CONCLUSION: Menstrual cycle phase and progesterone concentration at the time of mTBI affect 1-month quality-of-life and neurologic outcomes. This association has important implications for treatment and prognosis after mTBI.

The Journal of head trauma rehabilitation


The impact of consumer affordability on access to assisted reproductive technologies and embryo transfer practices: an international analysis

Abstract:
Comment in Fertil Steril. 2014 Jan;101(1):47-8. doi: 10.1016/j.fertnstert.2013.09.043.
 OBJECTIVE: To systematically quantify the impact of consumer cost on assisted reproduction technology (ART) utilization and numbers of embryos transferred. DESIGN: Ordinary least squared (OLS) regression models were constructed to measure the independent impact of ART affordability-measured as consumer cost relative to average disposable income-on ART utilization and embryo transfer practices. SETTING: Not applicable. PATIENT(S): Women undergoing ART treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): OLS regression coefficient for ART affordability, which estimates the independent effect of consumer cost relative to income on utilization and number of embryos transferred. RESULT(S): ART affordability was independently and positively associated with ART utilization with a mean OLS coefficient of 0.032. This indicates that, on average, a decrease in the cost of a cycle of 1 percentage point of disposable income predicts a 3.2% increase in utilization. ART affordability was independently and negatively associated with the number of embryos transferred, indicating that a decrease in the cost of a cycle of 10 percentage points of disposable income predicts a 5.1% increase in single-embryo transfer cycles. CONCLUSION(S): The relative cost that consumers pay for ART treatment predicts the level of access and number of embryos transferred. Policies that affect ART funding should be informed by these findings to ensure equitable access to treatment and clinically responsible embryo transfer practices.


A meta-analysis of the association of fracture risk and body mass index in women

Helena Johansson, John A Kanis, Anders Od\uen, Eugene McCloskey, Roland D Chapurlat, Claus Christiansen, Steve R Cummings, Adolfo Diez-Perez, John A Eisman, Saeko Fujiwara, Claus-C Gl\ufcer, David Goltzman, Didier Hans, Kay-Tee Khaw, Marc-Antoine Krieg, Heikki Kr\ufger, Andrea Z LaCroix, Edith Lau, William D Leslie, Dan Mellstr\ufm, L Joseph Melton, Terence W O'Neill, Julie A Pasco, Jerilynn C Prior, David M Reid, Fernando Rivadeneira, Tjerd van Staa, Noriko Yoshimura, M Carola Zillikens

Abstract: Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.


HFEA Fertility Trends and Figures 2012

HFEA Fertility Trends and Figures 2012


Binge eating and menstrual dysfunction

Binge eating and menstrual dysfunction

Li Huang

Guangdong Province Women and Children Hospital

Abstract:
OBJECTIVE: The relation between eating disorders and menstrual function has been widely studied, but it is unknown whether the behavior of binge eating itself is related to menstrual dysfunction.

METHODS: The 11,503 women included in this study were from the Swedish Twin study of Adults: Genes and Environment. The associations between menstrual dysfunction and binge eating were analyzed using logistic regression or multiple linear regression models with generalized estimation equations.

RESULTS: Women who reported lifetime binge eating were more likely to report either amenorrhea or oligomenorrhea than women who reported no binge eating. These results persisted when controlling for compensatory behaviors including self-induced vomiting, laxative use, and diuretic use. No differences between women with and without a history of binge eating were observed for age at menarche.

CONCLUSION: Even when controlling for the effect of compensatory behaviors, the behavior of binge eating is associated with menstrual dysfunction. Metabolic and endocrinological factors could underlie this association. Careful evaluation of menstrual status is warranted for women with all eating disorders, not just anorexia nervosa.


Veerle Goossens

European IVF-monitoring (EIM) Consortium

Abstract: Jul 27. Assisted reproductive technology in Europe, 2010: results generated from European registers by ESHRE†. Kupka MS(1), Ferraretti AP(2), de Mouzon J(2), Erb K(2), D'Hooghe T(2), Castilla JA(2), Calhaz-Jorge C(2), De Geyter C(2), Goossens V(2); European IVF-Monitoring Consortium, for the European Society of Human Reproduction and Embryology. Collaborators: Grunwald KM, Neulen J, Rösing B, Weisenborn U, Rau R, Schro B, Eid R, Hiller K-, Bauer T, Kraus H, Bayreuth K, Todorow S, Struller D, Etien C, Temme DH, Kentenich H, Siemann A, Stief G, Tandler-Schneider A, Remberg B, Tewordt S, Bloechle M, Marr S, Awwadeh H, Mutz A, Roth B, Kadgien C, Hannen R, Stoll CF, Jantke A, Spindeldreher S, Stegelmann A, Nowshari M, Sydow P, Peet DJ, Sydow C, Bergmann-Hensel U, Pfüller B, Bartley J, Scheiber I, Schmiady H, Ebert PA, Völklein K, Harms B, Baban N, Hilland U, Giesner Y, van der Ven H, van der Ven K, Bohlen U, Montag M, Prietl G, Drost O, Schmidt EH, Stutterheim Av, Finger T, Meyer-Ströh S, Jogschies P, Geistert D, Shugair L, Lahl A, Chemnitz S, Gabert A, Bauer K, Saager G, Leyendecker G, Bilgicyildirim A, Inacker M, Kroiss HJ, Bernhardt E, Braüker A, Vornehm H, Wilhelm E, Dieterle S, Neuer A, Greb R, Held HJ, Distler W, Keck G, Gouma E, Kru JS, Hess A, Mikat-Drozdzynski B, Schanz A, Hirchenhain J, Scholtes M, Marx K, Kisler S, Behler M, Pfeiffer S, Hubert P, Emde T, Yildirim-Assaf S, Frauena, Hamori M, Behrens R, Hammel A, Van Uem J, Beckmann MW, Müller A, Dittrich R, Katzorke T, Propping D, Wohlers S, Bielfeld P, Costea J, Wiegratz I, Merz E, Siebzehnru E, Weidner A, Weitzell, Thiemann, Wetzka, Geisthövel F, Friebel S, Hanjalic-Beck A, Zahradnik HP, Ina Walter-Göbel, Fiseler K, Hinney B, Michelmann HW, Moltrecht R, Hübner S, Welcker T, Sakin-Kaindl F, Mittmann S, Schulzeck P, Tobler M, Rostek J, Tigges J, Friol K, Gnoth C, Behre HM, Kaltwaser P, Seliger E, Horn, Michel u Partner, Bispink, Horn, Michel, Gohmann, Aytekin, Acar-Nosit, Kocak S, List P, Weidner U, Fischer R, Martina, Müseler-Albers, Arendt HP, Bühler K, Schill T, Schippert, Basler, Parta-Kehry W, Parta S, Tesarz F, Seehaus D, Tho C, Strowitzki T, Toth B, Algermissen, Justus, Wilke, Graf, Hildesheim, Fritzsche H, Reiher JP, Hoffmann A, Weiss J, Hoppe I, Wetzel V, Tetens F, Schlüter G, Willi MJ, Schmidt O, Hinrichsen M, Felberbaum R, Gerhard OA, Hiltensberger D, Kousehlar M, von Otte S, Schulz V, Völckers M, Eckel H, Schmutzler A, Salmassi A, Brandenburg K, Bonhoff A, Carstensen A, Merzenich M, Palm S, Pu I, Dannhof M, Keck C, Foth D, Ko U, Rahimi G, Moers C, Orth I, Leer K, von der Burg W, Alexander H, Weber W, Hmeidan FA, Jogschies P, Shugair L, Geistert D, Lahl A, Gabert A, Bauer K, Saager G, Griesinger G, Schultze-Mosgau A, Diedrich K, Schmidt T, Schmidt C, Motzkus N, Nickel I, Richter E, Kleinstein J, Brössner A, Sütterlin M, Schaffelder R, St Bussen, Schüttler J, Gentili, Sc RS, Passuello V, Kölbl H, Emig R, Mettlin S, Hadji P, Wagner U, Ziller V, Buurman O, Dumschat M, Menkhaus R, Heidecker B, Döhmen G, Schalk T, Bogenhausen AR, Berg D, Lesoine B, Kupka MS, Papadopoulos P, Thaler CJ, von Schönfeldt V, Friese K, Lacher H, Puchta J, Michna S, Pauer HU, Fiedler K, von Hertwig I, Würfel W, Laubert I, Santjohanser C, Völker S, Meri O, Krüsmann J, Bollmann W, Brückner T, Noss U, Belkien L, Niehoff C, Kiesel, Kreimer M, Kliesch, Sudik R, Kissing-Pahl K, Beran J, Müller B, Munzer-Neuwinger B, Neuwinger J, Licht P, Manolopoulos K, Oldenburg T, Hennefründ J, Boppert H, Heeder M, Jibril S, Pohlig G, Coordes I, Schneider M, Pforzheim K, Peuten V, Boehm S, Lehnert M, Recklinghausen K, Seifert B, Bals-Pratsch M, Luckhaus J, Müller H, Busecke A, Bossow A, Thaele M, Happel L, Giebel A, Nassar N, Otte M, Fuchs U, Maleika F, Harrer S, B D, Trier P, Satari M, Wissenschaftspark JP, Göhring, Göhring U, Göhring I, Lawrenz B, Neunhoeffer E, Gagsteiger, Sterzik K, Strehler E, Hancke K, Seemann B, Isachenko E, Rosenbusch B, Wetzlar V, Hajimohammad A, Oels B, Schorsch M, Hahn T, Adasz G, Schilberz K, Frambach T, Bernar T, Mai R, Schmitt W, Mulfinger L. (1)ESHRE Central Office, Meerstraat 60, Grimbergen B-1852, Belgium mail@prof-kupka.de. (2)ESHRE Central Office, Meerstraat 60, Grimbergen B-1852, Belgium. STUDY QUESTION: The 14th European IVF--monitoring (EIM) report presents the results of medically assisted reproduction treatments including assisted reproductive technology (ART) cycles and intrauterine insemination (IUI) cycles initiated in Europe during 2010: are there changes in the trends compared with previous years? SUMMARY ANSWER: Despite some fluctuations in the number of countries reporting, the overall number of ART cycles has continued to increase year by year, and while pregnancy rates in 2010 remained similar to those reported in 2009, the number of transfers with multiple embryos (three or more) further declined. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected and reported in 13 manuscripts, published in Human Reproduction. STUDY D


Assisted reproductive technology surveillance--United States, 2011

Dmitry M. Kissin

Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC

Abstract:
Sunderam S, Kissin DM, Crawford SB, Folger SG, Jamieson DJ, Barfield WD; Centers
for Disease Control and Prevention (CDC).

Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)


Abstract: Epub 2013 Nov 1. International Committee for Monitoring Assisted Reproductive Technology: world report on assisted reproductive technology, 2005. Zegers-Hochschild F(1), Mansour R(2), Ishihara O(3), Adamson GD(4), de Mouzon J(5), Nygren KG(6), Sullivan EA(7). (1)Clinica las Condes and Program of Ethics and Public Policies In Human Reproduction, University Diego Portales, Santiago, Chile. Electronic address: fzegers@clc.cl. (2)Egyptian IVF-ET Center, Cairo, Egypt. (3)Saitama Medical University Hospital, Moroyama, Japan. (4)Palo Alto Medical Foundation Fertility Physicians of Northern California, Palo Alto and San Jose, California. (5)IVF Unit, Institut National de la Santé et de la Recherche Médicale Service de Gynécologie Obstétrique II et de Médecine de la Reproduction, Groupe Hospitalier Cochin-Saint Vincet de Paul, Paris, France. (6)Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. (7)National Perinatal Epidemiology and Statistics Unit, School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia. OBJECTIVE: To analyze information on assisted reproductive technology (ART) performed worldwide and trends in outcomes over successive years. DESIGN: Cross-sectional survey on access, effectiveness, and safety of ART procedures performed in 53 countries during 2005. SETTING: A total of 2,973 clinics from national and regional ART registries. PATIENT(S): Infertile women and men undergoing ART globally. INTERVENTION(S): Collection and analysis of international ART data. MAIN OUTCOME MEASURE(S): Number of cycles performed by country and region, including pregnancies, single and multiple birth rates, and perinatal mortality. RESULT(S): Overall, 1,052,363 ART procedures resulted in an estimated 237,315 babies born. The availability of ART varied by country from 15 to 3,982 cycles per million of population. Of all initiated fresh cycles, 62.9% were intracytoplasmic sperm injection. The overall delivery rate per fresh aspiration was 19.6% and for frozen embryo transfer 17.4%, with a cumulative delivery rate of 23.9%. With wide regional variations, single embryo transfer represented 17.5% of cycles, and the proportion of deliveries with twins and triplets from fresh transfers was 23.6% and 1.5%, respectively. CONCLUSION(S): Systematic collection and dissemination of international ART data allows patients, health professionals, and policy makers to examine and compare the impact of reproductive strategies or lack of them as markers of reproductive health. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.


A pilot study to prevent a thin endometrium in patients undergoing clomiphene citrate treatment

Abstract:
BACKGROUND: Clomiphene citrate (CC) is most commonly used as a first-line treatment of infertility. However, a disturbance of endometrial growth by the adverse effects of the CC has been recognized. Since a thin endometrium is recognized as a critical factor of implantation failure, preventing CC-induced thinning of the endometrium is important. This study was undertaken to investigate whether the modified CC treatments are useful to prevent a thin endometrium in patients undergoing CC treatments.

METHODS: This study is a prospective, randomized controlled study. The study was performed at the Saiseikai Shimonoseki General Hospital during a 4-month period (May 2012 to September 2012). Sixty-six infertile women who had a thin endometrium (< 8 mm) during the standard CC treatment (50 mg/day on days 5-9 of the menstrual cycle) were enrolled. The patients were randomly divided into three groups: 22 patients were given 25 mg/day CC on days 5-9 (half-dose group), 22 patients were given 50 mg/day CC on days 1-5 (early administration group) and 22 patients received a standard CC treatment again (control group). Endometrial thickness at the induction of ovulation was assessed by ultrasonography. The primary endpoint of this study was an endometrial thickness.

RESULTS: Half dose administration and early administration improved the endometrial thickness (≥ 8 mm) in 14 patients (70%) and in 19 patients (90%) respectively, while only 3 patients (15%) improved in endometrial thickness in the control group. The mean endometrial thickness was also significantly higher in the half dose group (8.6 ± 1.5 mm) and early administration group (9.4 ± 1.5 mm) compared to the control group (6.7 ± 1.8 mm). No side effect was observed in this study.

CONCLUSIONS: The modified treatment with a half-dose or early administration of CC significantly increased endometrial thickness in patients with a history of thin endometrium caused by the standard CC regimen. The modified CC treatments in this study can be beneficial for patients with a thin endometrium as a result of standard CC treatment.

CLINICAL TRIAL REGISTRATION NUMBER: UMIN000007959.


Reproductive factors and breast cancer: a case-control study in tertiary care  hospital of North India

Abstract:
Background: Clinical, animal, and epidemiological studies have clearly demonstrated that cancer is a hormonally mediated disease and several factors that influence hormonal status or are markers of change in hormonal status have been shown to be associated with the risk of breast cancer.

Aims: To identify the association of various reproductive factors with breast cancer. SETTINGS AND Design: A hospital-based, matched, case-control study.

Materials and Methods: Three hundred and twenty newly diagnosed breast cancer cases and three hundred and twenty normal healthy individuals constituted the study population. The subjects in the control group were matched individually with the cases for their age ± 2 years and socioeconomic status. A pre-tested, semi-structured questionnaire was administered to each individual to collect information on identification data, socio-demographic profile, and reproductive factors. STATISTICAL ANALYSIS USED: The Chi-square test and unpaired t-test were used. The conditional univariate logistic regression analysis (unadjusted odds ratio and confidence intervals) was used to calculate the significance level of each variable followed by multivariate regression analysis. RESULTS AND

Conclusions: The cases had a lower mean age at menarche, higher age at marriage, higher mean age at last child birth, lower mean duration of breastfeeding, higher number of abortions, late age at menopause, history of oral contraceptive pills, and a family history of breast cancer as compared to the controls. The results of the present study revealed a strong association of reproductive factors with breast cancer in the Indian population.


The effect of oral contraceptive pills and the natural menstrual cYCLe on  arterial stiffness and hemodynamICs (CYCLIC)

Theodore G Papaioannou

National and Kapodistrian University of Athens

Abstract:
Background: Over 100 million women currently use oral contraceptive pills (OCPs) worldwide. However, little is known about the effects of OCPs on arterial stiffness and hemodynamics. Furthermore, whether arterial stiffness and hemodynamics vary throughout the natural menstrual cycle remains controversial. Herein, we estimated the effect of the natural menstrual cycle and OCP use on arterial stiffness and hemodynamics.

Methods: Healthy, nonsmoking women, aged 18-30 years, were recruited if they had regular menstrual cycles and never used OCPs (OCP nonuser group), or were using low-dose OCPs for at least 6 months (OCP user group). Using applanation tonometry, three assessments of arterial stiffness and central and peripheral hemodynamics were performed in a randomized order: during the early follicular (days 3-6), late follicular (days 14-16), and luteal (days 22-26) phases. Within group and between group comparisons were performed using general linear models.

Results: Sixty women (21.7 ± 2.8 years) were recruited. Compared with OCP nonusers, OCP users had significantly increased aortic and peripheral SBPs during the active OCP use, but not during the inert tablet phase. No differences in arterial stiffness were noted.

Conclusion: OCP use was associated with significant increases in aortic and peripheral blood pressures, but not with increased arterial stiffness. Given the widespread OCP use, future longitudinal studies are needed to confirm our findings and assess the long-term effect of OCPs on arterial stiffness and hemodynamics.


Efficacy of achieving pregnancy with fertility-focused intercourse

Abstract:
Purpose: To compare pregnancy rates when women have intercourse on self-estimated high and peak fertile days and when they only have intercourse on low fertile days during the fertile window (FW). STUDY DESIGN AND

Methods: We used a prospective observational cohort study design. Our convenience sample included 124 women who utilized our online charting Web sites to achieve pregnancy from January 2010 to November 2012. Participants used an electronic hormonal fertility monitor (EHFM) or self-observed cervical mucus or both to determine fertility during the estimated FW. Pregnancy rates were determined with Kaplan-Meier survival analysis. Chi square analysis was used to evaluate the efficacy of achieving pregnancy between two different intercourse patterns.

Results: The pregnancy rate was 87 per 100 women at 12 months when intercourse happened on high or peak days and 5 per 100 when intercourse occurred only on low days of the FW. Chi square analysis showed a greater proportion of pregnancies with intercourse on high and peak fertile days of the menstrual cycle (x2 = 40.2, p < .001, df = 1). NURSING Implications: Focusing intercourse on high or peak fertile days during the estimated FW enhances the probability of achieving a desired pregnancy. Fertility awareness-based online charting system is effective in helping women to determine their FW and target intercourse accordingly to achieve pregnancy.

MCN. The American Journal of Maternal Child Nursing


Longitudinal changes in calcium and vitamin D intakes and relationship to bone  mineral density in a prospective population-based study: the Canadian Multicentre  Osteoporosis Study (CaMos)

Susan I Barr

Vancouver Hospital and Health Sciences Centre

Christopher S Kovacs

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

Abstract:
Objectives: Our objective was to study changes in calcium and vitamin D intakes over time, and their cross-sectional and longitudinal associations with bone mineral density (BMD).

Methods: We followed 9382 women and men aged ≥25 and 899 aged 16-24, for 10 and 2 years respectively.

Results: Calcium and vitamin D intakes increased over time in adults, but decreased in women aged 16-18. The increased intakes in adults were largely attributable to the increased use of calcium and/or vitamin D supplements. Both the percentage of supplement users and average dose among users increased over time. There was nevertheless a high prevalence of calcium and vitamin D intake below the estimated average requirement. At baseline, higher calcium and vitamin D intakes were associated with higher total hip and femoral neck BMD in young men, and cumulatively high levels of calcium and vitamin D intakes over time contributed to better BMD maintenance at lumbar spine and hip sites in adult women.

Conclusions: Although total intakes, particularly of vitamin D, frequently fell below the Institute of Medicine recommendations despite an increase over time in supplement use, we found some positive associations between total calcium and vitamin D intake and bone health.

Journal of Musculoskeletal & Neuronal Interactions


Trace elements and endometriosis: the ENDO study

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Patrick J Parsons

University at Albany, State University of New York

Abstract: There has been limited study of trace elements and endometriosis. Using a matched cohort design, 473 women aged 18-44 years were recruited into an operative cohort, along with 131 similarly aged women recruited into a population cohort. Endometriosis was defined as surgically visualized disease in the operative cohort, and magnetic resonance imaging diagnosed disease in the population cohort. Twenty trace elements in urine and three in blood were quantified using inductively coupled plasma mass spectrometry. Logistic regression estimated the adjusted odds (aOR) of endometriosis diagnosis for each element by cohort. No association was observed between any element and endometriosis in the population cohort. In the operative cohort, blood cadmium was associated with a reduced odds of diagnosis (aOR=0.55; 95% CI: 0.31, 0.98), while urinary chromium and copper reflected an increased odds (aOR=1.97; 95% CI: 1.21, 3.19; aOR=2.66; 95% CI: 1.26, 5.64, respectively). The varied associations underscore the need for continued research.

Reproductive toxicology (Elmsford, N.Y.)


The immune modifying effects of amino acids on gut-associated lymphoid tissue

Abstract: The intestine and the gut-associated lymphoid tissue (GALT) are essential components of whole body immune defense, protecting the body from foreign antigens and pathogens, while allowing tolerance to commensal bacteria and dietary antigens. The requirement for protein to support the immune system is well established. Less is known regarding the immune modifying properties of individual amino acids, particularly on the GALT. Both oral and parenteral feeding studies have established convincing evidence that not only the total protein intake, but the availability of specific dietary amino acids (in particular glutamine, glutamate, and arginine, and perhaps methionine, cysteine and threonine) are essential to optimizing the immune functions of the intestine and the proximal resident immune cells. These amino acids each have unique properties that include, maintaining the integrity, growth and function of the intestine, as well as normalizing inflammatory cytokine secretion and improving T-lymphocyte numbers, specific T cell functions, and the secretion of IgA by lamina propria cells. Our understanding of this area has come from studies that have supplemented single amino acids to a mixed protein diet and measuring the effect on specific immune parameters. Future studies should be designed using amino acid mixtures that target a number of specific functions of GALT in order to optimize immune function in domestic animals and humans during critical periods of development and various disease states.

Journal of Animal Science and Biotechnology


Fallopian tube catheterization

Fallopian tube catheterization

Abstract: Fallopian tube catheterization is used for treatment of infertility caused by proximal tubal occlusion, and has replaced surgical treatment for this condition. More recently, fallopian tube catheterization has been used for tubal sterilization. Interventional radiologists tested numerous methods for tubal occlusion using the rabbit as an animal model. As a result, a tubal device has recently been Food and Drug Administration approved for permanent sterilization using hysteroscopic guidance; it can also be placed fluoroscopically by fallopian tube catheterization as an "off-label" procedure. This is a 5-year continuation and update on a procedure that has been done by interventional radiologists for 25 years; history of the development of fallopian tube catheterization in women has been published in detail in this journal. Highlighted in this article will be description of the basic components needed for fallopian tube catheterization.


Usual dietary isoflavone intake and reproductive function across the menstrual cycle

Jean Wactawski-Wende

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

Abstract:
Objective: To assess the association of total isoflavone intake with ovulatory function, including sporadic anovulation in healthy premenopausal women.
Design: Prospective cohort study.
Setting: University. PATIENT(S): Participants included 259 healthy regularly menstruating women aged 18-44 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum concentrations of E2, free E2, P, LH, FSH, and SHBG and sporadic anovulation in healthy premenopausal women. RESULT(S): Isoflavone intake was not associated with E2, free E2, P, LH, and FSH concentrations. Consumption in the highest quartile (Q4: 1.6-78.8 mg/d) was significantly associated with greater SHBG concentrations (β = 0.09; 95% confidence interval [CI] 0.02-0.16), compared with the first quartile (Q1: 0.0-0.3 mg/d). CONCLUSION(S): Isoflavone intake was not associated with sporadic anovulation (Q4 vs. Q1: odds ratio 0.87, 95% CI 0.32-1.66). Dietary isoflavone intake among young premenopausal women was not related to sex hormone concentrations or anovulation, but was associated with minimally increased SHBG concentrations. These results suggest potential endocrine effects with no subsequent effects on ovulation, easing concerns regarding their impacts on fertility.


Men perceive their female partners, and themselves, as more attractive around ovulation

Abstract: The purpose of this study was to test whether men perceive changes in their female partner's attractiveness as a function of her fertility status. We further tested how both male and female self-perception varies in relation to female fertility status. This study benefits from the use of transvaginal ultrasonography to detect fertility during the regular cycle and the use of a within-subjects design in which romantic couples were followed both across the cycle and during hormonal contraceptive use. We find that men rated their female partner as more attractive near to ovulation (when fertile) as compared to during the luteal cycle phase or during hormonal contraceptive use. Moreover, our results point to a presently unrecognized negative consequence of hormonal contraceptive use on male self-perception, with men rating themselves lower in attractiveness when their partner was using hormonal contraceptives than when she was regularly cycling. In contrast, there was no difference across measures in female self-reported attractiveness. Results are discussed in terms of their potential impact on within-couple social dynamics.


Negative spinal bone mineral density changes and subclinical ovulatory  disturbances--prospective data in healthy premenopausal women with regular  menstrual cycles

Christine L Hitchcock

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

Abstract: Subclinical ovulatory disturbances (anovulation or short luteal phases within normal-length menstrual cycles) indicate lower progesterone-to-estrogen levels. Given that progesterone plays a bone formation role, subclinical ovulatory disturbances may be associated with bone loss or less than expected bone gain. Our purpose was to perform a meta-analysis of prospective studies in healthy premenopausal women to determine the overall relationship of subclinical ovulatory disturbances to change in bone mineral density. Two reviewers independently identified from serial literature searches 6 studies meeting inclusion criteria: a 2-year study in 114 young adult women, 2006-2009, Vancouver, Canada; a 2-year study in 189 premenopausal women, 2000-2005, Toronto, Canada; a single-cycle study in 14 young women, 1996-1997, Melbourne, Australia; an 18-month study in 53 women, 1990-1995, Santa Clara, California; a 4-year study in 27 women, 1988-1995, Vancouver, Canada; and a 1-year study in 66 women, 1985-1988, Vancouver, Canada. This meta-analysis included a combined sample size of 473 observations in 436 premenopausal women studied over 1-4 years and aged 14-47 years. The percentage of women with ovulatory disturbances varied significantly from 13% to 82%. Women with more frequent ovulatory disturbances had more negative percentage changes in spine bone mineral density (weighted mean difference = -0.86; P = 0.040) for random-effects analysis. There was significant heterogeneity among these 6 studies (I(2) = 80%). In summary, these data show that regularly menstruating women with more frequent ovulatory disturbances experience more negative changes in bone (approximately -0.9% per year). These cycles with silent estrogen/progesterone imbalance may be clinically important.


Identification of TSG101 functional domains and p21 loci required for  TSG101-mediated p21 gene regulation

Tzu-Hao Cheng

Institute of Molecular Biology, Academia Sinica

Abstract: TSG101 (tumor susceptibility gene 101) is a multi-domain protein known to act in the cell nucleus, cytoplasm, and periplasmic membrane. Remarkably, TSG101, whose location within cells varies with the stage of the cell cycle, affects biological events as diverse as cell growth and proliferation, gene expression, cytokinesis, and endosomal trafficking. The functions of TSG101 additionally are recruited for viral and microvesicle budding and for intracellular survival of invading bacteria. Here we report that the TSG101 protein also interacts with and down-regulates the promoter of the p21 (CIP1/WAF1) tumor suppressor gene, and identify a p21 locus and TSG101 domains that mediate this interaction. TSG101 deficiency in Saos-2 human osteosarcoma cells was accompanied by an increased abundance of p21 mRNA and protein and the retardation of cell proliferation. A cis-acting element in the p21 promoter that interacts with TSG101 and is required for promoter repression was located using chromatin immunoprecipitation (ChIP) analysis and p21-driven luciferase reporter gene expression, respectively. Additional analysis of TSG101 deletion mutants lacking specific domains established the role of the central TSG101 domains in binding to the p21 promoter and demonstrated the additional essentiality of the TSG101 C-terminal steadiness box (SB) in the repression of p21 promoter activity. Neither binding of TSG101 to the p21 promoter nor repression of this promoter required the TSG101 N-terminal UEV domain, which mediates the ubiquitin-recognition functions of TSG101 and its actions as a member of ESCRT endocytic trafficking complexes, indicating that regulation of the p21 promoter by TSG101 is independent of its role in such trafficking.


Fracture risk prediction: importance of age, BMD and spine fracture status

John H Krege, Xiaohai Wan, Brian C Lentle, Claudie Berger, Lisa Langsetmo, Jonathan D Adachi, Jerilynn C Prior, Alan Tenenhouse, Jacques P Brown, Nancy Kreiger, Wojciech P Olszynski, Robert G Josse, David Goltzman

Abstract: Our purpose was to identify factors for a parsimonious fracture risk assessment model considering morphometric spine fracture status, femoral neck bone mineral density (BMD) and the World Health Organization (WHO) clinical risk factors. Using data from 2761 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, longitudinal cohort study of randomly selected community-dwelling men and women aged ⩾50 years, we previously reported that a logistic regression model considering age, BMD and spine fracture status provided as much predictive information as a model considering these factors plus the remaining WHO clinical risk factors. The current analysis assesses morphometric vertebral fracture and/or nonvertebral fragility fracture at 5 years using data from an additional 1964 CaMos subjects who have now completed 5 years of follow-up (total N=4725). Vertebral fractures were identified from lateral spine radiographs assessed using quantititative morphometry at baseline and end point. Nonvertebral fragility fractures were determined by questionnaire and confirmed using radiographs or medical records; fragility fracture was defined as occurring with minimal or no trauma. In this analysis, a model including age, BMD and spine fracture status provided a gradient of risk per s.d. (GR/s.d.) of 1.88 and captured most of the predictive information of a model including morphometric spine fracture status, BMD and all WHO clinical risk factors (GR/s.d. 1.92). For comparison, this model provided more information than a model considering BMD and the WHO clinical risk factors (GR/s.d. 1.74). These findings confirm the value of age, BMD and spine fracture status for predicting fracture risk.


The definition, aetiology, presentation, diagnosis and management of previous  caesarean scar defects

Abstract: Caesarean sections are the most commonly performed surgical procedures involving the uterus in fertile women. Typically, this surgery involves a transverse incision in the anterior lower uterine segment. The incidence of caesarean sections is on the increase worldwide, and consequently, the complications associated with them are becoming more common. One such complication that is gaining more attention is previous lower uterine segment caesarean scar defect (PCSD). In this review, we sought to explore the definition, aetiology, presentation, diagnosis and management of PCSD.

Journal of Obstetrics and Gynaecology : the Journal of the Institute of  Obstetrics and Gynaecology


Cancer risk among children born after assisted conception

A G Sutcliffe

Royal Free and University College Medical School, Department of Paediatrics and Child Health, Royal Free Campus, NW3 2PF, London, UK. icsi@rfc.ucl.ac.uk

Abstract:
BACKGROUND: Accurate population-based data are needed on the incidence of cancer in children born after assisted conception.

METHODS: We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility.

RESULTS: The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight.

CONCLUSIONS: There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).


Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment

Ettore Cicinelli

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

Ugo Indraccolo

L'organizzazione Ospedale di Civitanova M

Dominique De Ziegler

Université de Versailles Saint-Quentin-en-Yvelines

Abstract: Recurrent miscarriage (RM) is defined as 3 or more miscarriages before 20 weeks' pregnancy. In recent years, interest has been focused on chronic endometritis (CE), a subtle inflammation thought to be associated with RM. We aimed to evaluate the relationships between CE and RM. The records of 360 women with unexplained RM were retrospectively analyzed. Data from hysteroscopy, endometrial histology, endometrial culture, and polymerase chain reaction for chlamydia, performed before and after antibiotic treatment for CE, were analyzed. The occurrence of successful pregnancies within 1 year after treatment was also evaluated. Results showed that 208 (57.8%) women with RM showed CE at hysteroscopy; 190 (91.3%), positive at hysteroscopy, were also positive at histology, and 142 (68.3%) had positive cultures. Common bacteria were found in 110 (77.5%) patients. Mycoplasma and Ureaplasma were found in 36 (25.3%) patients and Chlamydia in 18 patients (12.7%). In 102 (71%) women, antibiogram-based antibiotic treatment normalized hysteroscopy, histology, and cultures (group 1); while in 40 (28.2%) patients, CE was still present at hysteroscopy (group 2). In 16 of the 66 patients positive at hysteroscopy, but not at cultures, the hysteroscopy becomes normal (group 3) after a Centers for Disease Control and Prevention-based therapy; while in 50 women, CE was still present (group 4). One year after treatment, group 1 showed a significantly higher number of pregnancies (78.4%) compared to group 2 (17.5%; P < .001) and group 4 (15.3%; P = .005). The CE is frequent in women with RM. Antibiotic treatment seems to be associated with an improved reproductive outcome.

Reproductive Sciences (Thousand Oaks, Calif.)


Neonatal uterine bleeding as antecedent of pelvic endometriosis

Abstract: We elaborate on a new theory to explain pelvic endometriosis, including endometriosis in premenarcheal girls, based on the finding that the neonatal endometrium can display secretory activity immediately after birth and, in some cases, changes analogous to those seen at menstruation in adults. The neonatal uterus is therefore capable of shedding its endometrium. Indeed, occult vaginal bleeding occurs in a majority of neonates, although overt bleeding is estimated to occur in only 5% of neonates. This may be due to functional plugging of the endocervical canal in the neonate, which in turn would promote retrograde flux of endometrial cells contained in menstrual debris. Ectopic endometrial implantation in a newborn with hydrometrocolpos has been documented. These data, coupled with the observation of a significantly increased risk of endometriosis in adolescents with cervical outflow obstruction and patent Fallopian tubes, indicate that endometriosis, especially in children and young adolescents, may originate from retrograde uterine bleeding soon after birth.


Early and late menarche are associated with oligomenorrhea and predict metabolic syndrome 26 years later

Jessica G Woo

Cincinnati Children's Hospital Medical Center

Abstract:
OBJECTIVE: We determined whether simple, clinical information on late and early menarche could help identify adult women with metabolic syndrome (MetS) and oligomenorrhea.

MATERIALS/METHODS: We carried out a 26-year prospective follow-up of 272 suburban schoolgirls from ages 5-22 to 30-46.

RESULTS: Early menarche (≤10 years, 5.2% of girls) and late menarche (≥16 years, 6.7% of girls) were both associated with oligomenorrhea (≥42 days) in adulthood, 29% and 11%, vs. 5% for normal menarche (11-15 years), p=.004. Early menarche was characterized by high childhood BMI (LS mean±SE: 21.2 ±1.0 kg/m2) and by high childhood and adult MetS (15%, 36%). Girls with late menarche had the lowest childhood BMI (18.1±1.0), no childhood MetS, and the highest adult MetS (47%). Increasing age at menarche was associated with uniformly decreasing childhood BMI and MetS, but with a U-shaped pattern of BMI (p = .05), MetS (p=.008), and oligomenorrhea (p=.02) in adulthood. Change to MetS from median ages 13 to 38 was associated with early-late menarche (OR=3.11, 95% CI 1.37-7.07, p=.007). MetS in adulthood was associated with childhood MetS (OR=8.03, 95% CI 2.57-25.08, p=.0003) and with early-late menarche (OR =3.43, 95% CI 1.44-8.15, p=.005).

CONCLUSIONS: Menarche age had a curvilinear ('U' shaped) relationship with MetS and oligomenorrhea in adulthood. Late menarche and early menarche are risk factors for adult oligomenorrhea, MetS, and cardiometabolic abnormalities. Girls with early (≤ age 10) and with late menarche (≥ 16) represent a group at high risk for adult cardiometabolic abnormalities and oligomenorrhea that is easily identifiable by physicians.


A randomised trial to evaluate the effects of low-dose aspirin in gestation and reproduction: design and baseline characteristics

Enrique F Schisterman

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Brian W Whitcomb

Department of Biostatistics & Epidemiology, University of Massachusetts Amherst, 715 N Pleasant Street, Amherst, MA, USA.

Laurie L Lesher

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

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:
Background: Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses.

Methods: We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period.

Results: There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >$100 000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced.

Conclusions: We describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.


Monitoring of ovarian activity by daily measurement of urinary excretion rates of  oestrone glucuronide and pregnanediol glucuronide using the Ovarian Monitor, Part  III: variability of normal menstrual cycle profiles

Pilar Vigil

Pontificia Universidad Católica de Chile

Catherine d'Arcangues

Special Programme of Research, Development, and Research Training in Human Reproduction, Geneva, Switzerland. darcanguesc@who.ch

Abstract:
STUDY Question: What are the characteristics of, and how variable are, individual normal menstrual cycle profiles of excretion rates for the urinary metabolites oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG)?

SUMMARY ANSWER: There is a continuum of menstrual cycle profiles that differ from standard textbook profiles but which can be understood simply in terms of growth, atresia and ovulation of ovarian follicles.

WHAT IS KNOWN ALREADY: Point-of-care assays with the Ovarian Monitor pre-coated assay tubes, using urine samples diluted to a constant volume per unit time, give laboratory accurate clinical data for individual menstrual cycles. Lay operators can perform the point-of-care assay system at home to achieve reliable and reproducible results, which can be used for natural family planning.

STUDY DESIGN, SIZE, DURATION: This prospective study involved 62 women, with normal menstrual cycles, recruited from three centres: Palmerston North, New Zealand, Sydney, Australia and Santiago, Chile. The study lasted 3 years.

PARTICIPANTS/MATERIALS, SETTING, Methods: Women collected daily urine samples and determined their E1G and PdG rates with a pre-coated enzyme assay system known as the Ovarian Monitor. For two cycles, the assays were repeated in a study centre and the results were averaged to give 113 individual menstrual cycles for analysis. The cycles were displayed individually in a proprietary database program.

MAIN RESULTS AND THE ROLE OF CHANCE: The individual normal hormonal profiles were more complex than the classic composite curves for 40% of the cycles. Of 113 ostensibly normal cycles, only 91 were potentially fertile and 22 had some luteal phase defect. The oestrone glucuronide and PdG excretion rates were reliable and informative in the non-invasive elucidation of ovulation and ovarian function for both simple and complex profiles. Daily monitoring revealed the variability of normal menstrual cycle profiles. The LH peaks were variable and ambiguous markers for ovulation.

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

WIDER IMPLICATIONS OF THE Findings: The principles established in this study should apply to cycles of any length. All peaks in oestrone glucuronide excretion should be tested by concurrent measurements of PdG, which gives a positive indication of the fate of the follicle it represents. The Ovarian Monitor provides a useful addition for practitioners of natural family planning. STUDY FUNDING/COMPETING INTEREST(S): Financial support for this study was obtained from the UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. is currently employed by and holds stock in Manawatu Diagnostics Ltd, a company in the development phase of a potentially competing product. The remaining authors have nothing to declare.


La conoscenza dei cicli sessuali femminili attraverso l’auto-osservazione per il trattamento della sterilità umana

Abstract: L’auto-osservazione e il follow-up grafico del ciclo mestruale in caso di presunta sterilita, aiutano a diagnosticare e trattare certe alterazioni ginecologiche, al fine di attuare il rapporto sessuale finalizzato ad ottimizzare concepimento. Attraverso queste procedure naturali (naprotecnologia), prive di aspetti negativi da un punto di vista etico, possiamo ottenere tassi di natalita che sono paragonabili, o addirittura superiori, a quelle ottenute con trattamenti invasivi. ---------- Self-observation and the graphic follow-up of the menstrual cycle in cases of supposed infertility, help to diagnose and treat certain gynaecological alterations in order to carry out the sexual intercourse focused on optimising conception. Through these natural procedures (Naprotechnology), with no ethical drawbacks, we can obtain birth rates that are comparable, or even higher, to those obtained with invasive treatments.


Angiotensin-converting enzymes play a dominant role in fertility

Fang Le

Department of Reproductive Endocrinology, Women's Hospital, School of Medicine,  Zhejiang University, 1 Xueshi Road, Hangzhou 310006, China

Abstract: According to the World Health Organization, infertility, associated with metabolic syndrome, has become a global issue with a 10%-20% incidence worldwide. An accumulating body of evidence has shown that the renin-angiotensin system is involved in the fertility problems observed in some populations. Moreover, alterations in the expression of angiotensin-converting enzyme-1, angiotensin-converting enzyme-2, and angiotensin-converting enzyme-3 might be one of the most important mechanisms underlying both female and male infertility. However, as a pseudogene in humans, further studies are needed to explore whether the abnormal angiotensin-converting enzyme-3 gene could result in the problems of human reproduction. In this review, the relationship between angiotensin-converting enzymes and fertile ability is summarized, and a new procedure for the treatment of infertility is discussed.

International Journal of Molecular Sciences


Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk  women: a systematic review and meta-analysis

Abstract:
Purpose: To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history.

Methods: We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer.

Results: From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned.

Conclusion: Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

Journal of Clinical Oncology : Official Journal of the American Society of  Clinical Oncology


Influence of motivation on the efficacy of natural family planning

Abstract:
Purpose: To determine the influence of mutual motivation on unintended pregnancy rates of couples who used natural family planning (NFP) methods to avoid pregnancy. STUDY DESIGN AND

Methods: Using an online taught NFP method, 358 women and (their male partners) indicated "how much" and "how hard" they wished to avoid pregnancy on a scale of 0 to 10 before each menstrual cycle charted over 12 month of use. This motivation scale is used in the National Survey of Family Growth as a measure of motivation. All pregnancies were verified with an online pregnancy evaluation and urine-based pregnancy test. A combined motivation score was used in analysis.

Results: There were 28 pregnancies among the low-motivation participants (N = 60) and 16 among the high-motivation participants (N = 298). At 12 months of use, there were 75 pregnancies per 100 users for the low-motivation group and only 8 for the high-motivation group. There was an 80% greater likelihood of a pregnancy with the low-motivation group (χ = 25.5, p < .001, odds ratio = 1.80; 95% confidence interval = 1.61-1.90).
Clinical Implications: High motivation to avoid pregnancy by both the female user of a behavioral method of family planning and her male partner is required for high efficacy. Assessing motivation of both the woman and her male partner before prescribing NFP methods is recommended.

MCN. The American Journal of Maternal Child Nursing


25-Hydroxyvitamin D in the range of 20 to 100 ng/mL and incidence of kidney stones

Leo Baggerly

Stacie Nguyen, Leo Baggerly, and Christine French are with GrassrootsHealth, Encinitas, CA. Robert P. Heaney is with Creighton University, Osteoporosis Research Center, Omaha, NE. Edward D. Gorham ...

Abstract:
OBJECTIVES: Increasing 25-hydroxyvitamin D serum levels can prevent a wide range of diseases. There is a concern about increasing kidney stone risk with vitamin D supplementation. We used GrassrootsHealth data to examine the relationship between vitamin D status and kidney stone incidence.

METHODS: The study included 2012 participants followed prospectively for a median of 19 months. Thirteen individuals self-reported kidney stones during the study period. Multivariate logistic regression was applied to assess the association between vitamin D status and kidney stones.

RESULTS: We found no statistically significant association between serum 25-hydroxyvitamin D and kidney stones (P = .42). Body mass index was significantly associated with kidney stone risk (odds ratio = 3.5; 95% confidence interval = 1.1, 11.3).

CONCLUSIONS: We concluded that a serum 25-hydroxyvitamin D level of 20 to 100 nanograms per milliliter has no significant association with kidney stone incidence.


Lateral temperature spread of monopolar, bipolar and ultrasonic instruments for  robot-assisted laparoscopic surgery

Abstract:
Objective: To assess critical heat spread of cautery instruments used in robot-assisted laparoscopic (RAL) surgery.

Materials and Methods: Thermal spread along bovine musculofascial tissues was examined by infrared camera, histology and enzyme assay. Currently used monopolar, bipolar and ultrasonic laparoscopic instruments were investigated at various power settings and application times. The efficacy of using an additional Maryland clamp as a heat sink was evaluated. A temperature of 45 °C was considered the threshold temperature for possible nerve damage.

Results: Monopolar instruments exhibited a mean (sem) critical thermal spread of 3.5 (2.3) mm when applied at 60 W for 1 s. After 2 s, the spread was >20 mm. For adjustable bipolar instruments the mean (sem) critical thermal spread was 2.2 (0.6) mm at 60 W and 1 s, and 3.6 (1.3) mm at 2 s. The PK and LigaSure forceps had mean (sem) critical thermal spreads of 3.9 (0.8) and 2.8 (0.6) mm respectively, whereas the ultrasonic instrument reached 2.9 (0.8) mm. Application of an additional Maryland clamp as a heat sink, significantly reduced the thermal spread. Histomorphometric analyses and enzyme assay supported these findings.

Conclusions: All coagulation devices used in RAL surgery have distinct thermal spreads depending on power setting and application time. Cautery may be of concern due to lateral temperature spread, causing potential damage to sensitive structures including nerves. Our results provide surgeons with a resource for educated decision-making when using coagulation devices during robotic procedures.


Use of urinary pregnanediol 3-glucuronide to confirm ovulation

A Direito

Laboratoire de Biométrie et Biologie Evolutive

Abstract:
Objective: Urinary hormonal markers may assist in increasing the efficacy of Fertility Awareness Based Methods (FABM). This study uses urinary pregnanediol-3a-glucuronide (PDG) testing to more accurately identify the infertile phase of the menstrual cycle in the setting of FABM.

Methods: Secondary analysis of an observational and simulation study, multicentre, European study. The study includes 107 women and tracks daily first morning urine (FMU), observed the changes in cervical mucus discharge, and ultrasonography to identify the day of ovulation over 326 menstrual cycles. The following three scenarios were tested: (A) use of the daily pregnandiol-3a-glucuronide (PDG) test alone; (B) use of the PDG test after the first positive urine luteinizing hormone (LH) kit result; (C) use of the PDG test after the disappearance of fertile type mucus. Two models were used: (1) one day of PDG positivity; or (2) waiting for three days of PDG positivity before declaring infertility.

Results: After the first positivity of a LH test or the end of fertile mucus, three consecutive days of PDG testing over a threshold of 5μg/mL resulted in a 100% specificity for ovulation confirmation. They were respectively associated an identification of an average of 6.1 and 7.6 recognized infertile days.

Conclusions: The results demonstrate a clinical scenario with 100% specificity for ovulation confirmation and provide the theoretical background for a future development of a competitive lateral flow assay for the detection of PDG in the urine.


DHEA supplementation positively affects spontaneous pregnancies in women with diminished ovarian function

Abstract: The aim of this article is to describe unexpected spontaneous pregnancies in poor responder patients with long-term infertility, when treated with dehydroepiandrosterone (DHEA) supplementation prior to in vitro fertilization (IVF). Our evaluation was carried out in two groups of women. The first group included 39 young women with <40 years, all treated with DHEA because of a previous poor response. The second group included 38 women over 40 years who received DHEA supplementation. Controls for latter group were 24 comparable women who had not been treated with DHEA before the first IVF cycle to evaluate the spontaneous pregnancy rate during preparation to IVF. Three tablets daily of 25 mg micronized DHEA were administered for at least 12 weeks before starting a long stimulation protocol for IVF. Surprisingly, spontaneous pregnancy rate significantly increased after DHEA treatment, allowing to achieve 10 spontaneous pregnancies and 9 spontaneous ongoing pregnancies among young poor responders. Pregnancy rate and ongoing pregnancy rate obtained before starting the IVF cycle were also significantly higher in older women treated with DHEA than in the control group: 21.05% and 13.15% and 4.1% and 0, respectively. Our results show that DHEA supplementation improves the ovarian function in poor responders and in women over 40 years, suggesting that this molecule alone can raise fecundity and fertility treatment success in women with poor prognosis for pregnancy.

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology


Potential role and therapeutic interests of myo-inositol in metabolic diseases

Abstract: Several inositol isomers and in particular myo-inositol (MI) and D-chiro-inositol (DCI), were shown to possess insulin-mimetic properties and to be efficient in lowering post-prandial blood glucose. In addition, abnormalities in inositol metabolism are associated with insulin resistance and with long term microvascular complications of diabetes, supporting a role of inositol or its derivatives in glucose metabolism. The aim of this review is to focus on the potential benefits of a dietary supplement of myo-inositol, by far the most common inositol isomer in foodstuffs, in human disorders associated with insulin resistance (polycystic ovary syndrome, gestational diabetes mellitus or metabolic syndrome) or in prevention or treatment of some diabetic complications (neuropathy, nephropathy, cataract). The relevance of such a nutritional strategy will be discussed for each context on the basis of the clinical and/or animal studies. The dietary sources of myo-inositol and its metabolism from its dietary uptake to its renal excretion will be also covered in this review. Finally, the actual insights into inositol insulin-sensitizing effects will be addressed and in particular the possible role of inositol glycans as insulin second messengers.


Comparison of Congenital Abnormalities of Infants Conceived by Assisted Reproductive Techniques versus Infants with Natural Conception in Tehran

Abstract:
BACKGROUND: In many countries, 1 to 3% of newborn infants are conceived by assisted reproductive techniques (ART). Despite the success of ART, there is concern about the risk of congenital malformations among these infants. We report our experience to determine whether use of ART is associated with an increase in major congenital malformations or adverse pregnancy outcomes.

MATERIALS AND METHODS: Historical cohort study of major congenital malformations (MCM) was performed in 978 births from January 2008 to December 2010. The data for this analysis were derived from a Tehran's ART linked data file by simple sampling method. In our study, the risk of congenital malformations was compared in 326 ART infants and 652 naturally conceived (NC) infants. We also performed multiple logistic regression analyses to calculate the odds ratio (OR) and 95% confidence intervals (CI) for the independent association of ART on each outcome.

RESULTS: We found 56 infants with major congenital malformations, these included 29 NC infants (4.4%) and 27 ART infants (8.3%). In comparison with NC infants, ART infants had a significant 1.94-fold increased risk of MCM.After adjustment for maternal age, infant's sex stillbirth, abortion and type of delivery, we found a relatively small difference in risk (OR=2.04). In this study the majority (94.3%) of all infants were normal but 5.7% of infants had at least one MCM. The prevalence rate for the intracytoplasmic sperm injection (ICSI) was 6.5% for the In vitro fertilisation (IVF) group was 15.9% or 2.73-fold higher than ICSI group (P=0.018). Also we ignore the possible role of genotype and other unknown factors in causing more malformations in ART infants.

CONCLUSION: Other studies have shown a slightly increased risk of major congenital malformations in pregnancies resulting from ART. Likewise, this study reports a greater risk of MCMs in ART infants than in naturally conceived infants. We also found evidence of a difference in risk of MCMs between IVF and ICSI. Musculoskeletal and urogenital malformations were the most reported MCMs in ART infants according to organs and systems classification.

International journal of fertility & sterility


Neural tube defects, folic acid and methylation

Abstract: Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

International journal of environmental research and public health


Association of hormonal contraceptive use with reduced levels of depressive symptoms: a national study of sexually active women in the United States

Abstract: An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.


Non-steroidal anti-inflammatory drug use and cervical cancer risk: a case-control study using the Clinical Practice Research Datalink

Abstract:
Purpose: Non-steroidal anti-inflammatory drugs (NSAIDs) have many anticarcinogenic properties via the inhibition of cyclooxygenase 2 (COX-2). Only one study, a cohort study examining risk of all cancers, investigated their role in cervical cancer with inconsistent findings between non-aspirin NSAIDs and aspirin. The aim of this study was to further investigate NSAID/aspirin use and cervical cancer risk.

Methods: Using the United Kingdom Clinical Practice Research Datalink, 724 women diagnosed with cervical cancer between 1 January, 1995 and December 2010 were compared to 3479 women (without cervical cancer) matched on year of birth and general practice. Conditional logistic regression analysis adjusted for smoking, sexually transmitted infections, HRT and contraceptive use, was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for cervical cancer risk among users of any oral NSAIDs, non-aspirin NSAIDs and aspirin, as assessed from primary care prescribing data.

Results: Excluding the year prior to diagnosis, there was no association in adjusted analyses between ever vs. never use of an NSAID (OR 0.92, 95% CI 0.77-1.09), non-aspirin NSAID (OR 0.95, 95% CI 0.80-1.13) or low-dose aspirin (OR 1.07, 0.80-1.44) and cervical cancer risk. In analysis of daily defined doses, there was no association with cervical cancer risk comparing the highest users to non-users of NSAIDs (OR 0.98, 95% CI 0.69-1.39) or non-aspirin NSAIDs (OR 1.00, 95% CI 0.70-1.43) or low-dose aspirin (OR 1.04, 95% CI 0.59-1.81).

Conclusion: This large historical cohort study found no evidence of an association between non-aspirin NSAID or aspirin use and cervical cancer risk.


Oral contraceptive use in women changes preferences for male facial masculinity and is associated with partner facial masculinity

Abstract: Millions of women use hormonal contraception and it has been suggested that such use may alter mate preferences. To examine the impact of oral contraceptive (pill) use on preferences, we tested for within-subject changes in preferences for masculine faces in women initiating pill use. Between two sessions, initiation of pill use significantly decreased women's preferences for male facial masculinity but did not influence preferences for same-sex faces. To test whether altered preference during pill use influences actual partner choice, we examined facial characteristics in 170 age-matched male partners of women who reported having either been using or not using the pill when the partnership was formed. Both facial measurements and perceptual judgements demonstrated that partners of women who used the pill during mate choice have less masculine faces than partners of women who did not use hormonal contraception at this time. Our data (A) provide the first experimental evidence that initiation of pill use in women causes changes in facial preferences and (B) documents downstream effects of these changes on real-life partner selection. Given that hormonal contraceptive use is widespread, effects of pill use on the processes of partner formation have important implications for relationship stability and may have other biologically relevant consequences.


Obesity leads to higher risk of sperm DNA damage in infertile patients

Abstract: There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index (BMI). A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling (TUNEL) assay, we observed an increased rate of sperm DNA damage in obese men (odds ratio (95% confidence interval): 2.5 (1.2-5.1)).


Is there a role for DHEA supplementation in women with diminished ovarian reserve?

Fady I Sharara

Virginia Center for Reproductive Medicine

Abstract:
PURPOSE: Poor ovarian reserve and poor ovarian response presents a challenge to IVF centers. Dehydroepiandrosterone (DHEA) supplementation is increasingly being used by many IVF centers around the world in poor responders despite the lack of convincing data. We therefore examined the rationale for the use of DHEA in poor responders, address the relevant studies, present new data, and address its potential mechanisms of action.

METHODS: All published articles on the role of DHEA in infertile women from 1990 to April 2013 were reviewed.

RESULTS: Several studies have suggested an improvement in pregnancy rates with the use of DHEA. Potential mechanisms include improved follicular steroidogenesis, increased IGF-1, acting as a pre-hormone for follicular testosterone, reducing aneuploidy, and increasing AMH and antral follicle count. While the role of DHEA is intriguing, evidence-based recommendations are lacking.

CONCLUSIONS: While nearly 25 % of IVF programs use DHEA currently, large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.

Journal of assisted reproduction and genetics


Disparities in Obstetrical Outcomes in ART Pregnancies Compared with Natural Conceptions

Torie Plowden

Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD.

Abstract: Health disparities are observed in all fields of medicine and reproductive health is not immune to this phenomenon. The incidence of women using infertility treatments to conceive is increasing. Women undergoing assisted reproduction appear to be at increased risk of adverse outcomes, and minority women tend to be at even greater risk. This article examines several adverse obstetrical outcomes including preterm birth, congenital malformations, and preeclampsia among women receiving infertility treatments compared with those who conceive spontaneously. It will further examine societal costs associated with these procedures.


Low AMH and Natural Conception

Low AMH and Natural Conception

Phil C Boyle

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

Abstract: AMH levels are commonly measured in fertility clinics to assess ovarian reserve and give an indication of female fertility potential. AMH levels are useful in deciding on stimulation protocols for IVF cycles. High AMH levels are useful to confirm a diagnosis of polycystic ovaries. Currently AMH levels cannot be used to predict a couple's ability to conceive naturally.


Low Dose Naltrexone: Novel Uses for a Licensed Medication

Abstract: Naltrexone hydrochloride is a licensed drug with a growing number of novel uses. Nothing has been published on low dose naltrexone for infertility, miscarriage, PMS, or pregnancy, but there is published literature on high dose naltrexone. First synthesised in the 1960s and licensed in the USA in 1985 and Ireland in 1991, naltrexone at 50-150mg per dose is used as adjunctive treatment of opioid dependence and now alcohol dependence (unlicensed). It works through competitive inhibition of opioid receptors in both the central and peripheral nervous system.


Spiritual Care of Couples Practicing Natural Family Planning

Abstract: There are few studies that have investigated the spiritual problems of couples practicing natural family planning (NFP). The purpose of this paper is to analyze the spiritual problems and interventions of couples who were taught NFP by means of a professional online Web-based support system. Responses from this online system and its forums were categorized according to spiritual responses, spiritual problems, and spiritual interventions to the practice of NFP. Themes addressed included spiritual care in regards to decisions about the transmission of new life, difficulties in dealing with chastity and abstinence, bioethical problems related to pregnancy and illness, end of the reproductive life decisions, ethical treatment of women's health problems, sacrifice, and personal and relational struggles. Online community support, help in building confidence in NFP methods, and bioethicist referral are key interventions. The complexity of these spiritual responses, problems, and appropriate interventions require the expertise of health professionals in cooperation with bioethicists. We concluded that NFP can be viewed as both a spiritual practice and a means of spiritual growth.


A study on risk factors of breast cancer among patients attending the tertiary  care hospital, in udupi district

Abstract:
Background: Cancer has become one of the ten leading causes of death in India. Breast cancer is the most common diagnosed malignancy in India, it ranks second to cervical cancer. An increasing trend in incidence is reported from various registries of national cancer registry project and now India is a country with largest estimated number of breast cancer deaths worldwide.

Aim: To study the factors associated with breast cancer.

Objectives: To study the association between breast cancer and selected exposure variables and to identify risk factors for breast cancer.

Materials and Methods: A hospital based Case control study was conducted at Shirdi Sai Baba Cancer Hospital and Research Center, Manipal, Udupi District.

Results: Total 188 participants were included in the study, 94 cases and 94 controls. All the study participants were between 25 to 69 years of age group. The cases and controls were matched by ± 2 years age range. Non vegetarian diet was one of the important risk factors (OR 2.80, CI 1.15-6.81). More than 7 to 12 years of education (OR 4.84 CI 1.51-15.46) had 4.84 times risk of breast cancer as compared with illiterate women.

Conclusion: The study suggests that non vegetarian diet is the important risk factor for Breast Cancer and the risk of Breast Cancer is more in educated women as compared with the illiterate women. LIMITATION: This is a Hospital based study so generalisability of the findings could be limited.

Indian Journal of Community Medicine : Official Publication of Indian Association  of Preventive & Social Medicine


Psychobehavioral effects of hormonal contraceptive use

Abstract: Although female use of hormonal contraceptives (HCs) has been associated with a variety of physical side effects, the psychological and behavioral side effects have received comparatively little attention until recently. Indeed, the long-term impact of HC use on human psychology has been vastly under-researched and has only recently become a focus for mainstream scholars. Women who use HCs report higher rates of depression, reduced sexual functioning, and higher interest in short-term sexual relationships compared to their naturally-cycling counterparts. Also, HC use may alter women's ability to attract a mate, as well as the mate retention behaviors in both users and their romantic partners. Some evidence even suggests that HC use alters mate choice and may negatively affect sexual satisfaction in parous women, with potential effects on future offspring. Interestingly, HCs have become a standard method of population control for captive nonhuman primates, opening up exciting avenues for potential comparative research. Here, the existing literature on the psychobehavioral effects of HCs in humans and nonhuman primates is reviewed and discussed. The potential resulting downstream consequences for the path of human evolution and recommendations for how future research could tease apart the underlying causes of these psychobehavioral effects of HC use are discussed, including suggestions for research involving nonhuman primates.

Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior


Cervical mucus monitoring prevalence and associated fecundability in women trying to conceive

Emily Evans-Hoeker

University of North Carolina at Chapel Hill

Abstract:
OBJECTIVE: To assess the use of cervical mucus monitoring (CMM) in women trying to conceive and determine whether monitoring is associated with increased cycle-specific probability of conception (fecundability).

DESIGN: Time-to-pregnancy cohort study.

SETTING: Population-based cohort.

PATIENT(S): Three hundred thirty-one women trying to conceive, ages 30 to 44 years, without known infertility.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): CMM prevalence and fecundability.

RESULT(S): During the first cycle of the study, CMM was performed consistently (checked on >66% of pertinent cycle days) by 20 women (6%), inconsistently (34% to 66% of days) by 60 women (18%), infrequently (≤33% of days) by 73 women (22%), and not performed by 178 women (54%). Cycles in which CMM was consistently performed were statistically significantly more likely to result in conception after adjusting for age, race, previous pregnancy, body mass index, intercourse frequency, and urinary luteinizing hormone (LH) monitoring. Fecundability also increased with increasing consistency of CMM.

CONCLUSION(S): Among women trying to conceive, CMM is uncommon, but our study suggests that CMM-a free, self-directed method to determine the fertile window-is associated with increased fecundability independent of intercourse frequency or use of urinary LH monitoring.


The effect of low-dose combined oral contraceptive pills on brachial artery  endothelial function and common carotid artery intima-media thickness

Abstract:
Background: Combined oral contraceptives (COCs) are considered for their thrombogenicity and the risk of premature atherosclerosis and the stroke caused by them. The aim of this study was to evaluate the relationship between chronic use of low-dose COCs (ethinyl estradiol 30 mcg + levonorgestrel 150 mcg) and endothelial dysfunction and intima-media thickness.

Methods: In a cross-sectional study, in 2011-2012, 60 healthy premenopausal women (30 cases of COC consumers and 30 controls as nonconsumers), aged between 25 and 45 years, participated in this study. They were current users for at least a 3-year period. Brachial artery flow-mediated dilatation (FMD) and common carotid artery intima-media thickness (CCA-IMT) were measured for the patients.

Results: The mean duration of COC consumption was 54.03 ± 27.27 months in the case group. There was a significant FMD% difference between 2 groups of cases and controls: 11 ± 3.53 versus 15.80 ± 9.22 (P = .01). In addition, a significant mean CCA-IMT thickness difference was detected: .53 ± .07 versus .44 ± .08 (P = .00). However, after multiple regression analysis and adjusting for body mass index (BMI), in COC users, no significant association between COC consumption duration and FMD% and mean CCA-IMT was observed.

Conclusions: Prolonged used of low-dose COCs may cause changes in both endothelial function (measured by FMD%) and endothelial structure (measured by CCA-IMT). There was a nonsignificant inverse relationship between the duration of COC ingestion and FMD% and a nonsignificant positive relationship with CCA-IMT. Our results are in favor of early atherosclerotic changes in prolonged users of COCs.

Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National  Stroke Association