The effect of vitamin D supplementation on the size of uterine leiomyoma in women with vitamin D deficiency

Abstract:
BACKGROUND: Uterine leiomyomas (fibroids) are the most common benign pelvic tumors in women of reproductive age with an incidence ranging from 5.4% to 77%, Also, there is a high prevalence of vit D deficiency in Iran and there are the numbers of in vivo and vitro biological studies on the relationship of vitamin D and uterine leiomyomas. The aim of this study was to evaluate the effect of vit D supplementation on the size of uterine leiomyoma in women with vit D deficiency.

METHODS: This double-blind prospective clinical trial was performed on 69 patients with uterine leiomyomas who had vit D deficiency. Group A (n=35) was treated with vit D 50,000 IU every 2 weeks for 10 weeks, while group B (n=34) received placebo with same color and shape. Finally, the leiomyoma size in both groups was compared (IRCT: 20160521027998N5).

RESULTS: After a 10-week intervention, 25-hydroxyvitamin D3 levels were significantly higher in group receiving vitamin D (36.08 vs 16.25 ng/ml). (P<0.001) Leiomyomas size in vit D group significantly decreased as compared to placebo group (52.58 vs 61.11 mm, respectively).

CONCLUSION: Our results showed that administration of vit D3 may reduce the size of leiomyoma. It seems that vitamin D administration is the effective way to treat leiomyoma.


Dmitry M. Kissin

Abstract: Assisted Reproductive Technology Surveillance - United States, 2016. Sunderam S(1), Kissin DM(1), Zhang Y(1), Folger SG(1), Boulet SL(2), Warner L(1), Callaghan WM(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. (2)Emory University School of Medicine, Atlanta, Georgia. PROBLEM/CONDITION: Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2016 and compares birth outcomes that occurred in 2016 (resulting from ART procedures performed in 2015 and 2016) with outcomes for all infants born in the United States in 2016. PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). RESULTS: In 2016, a total of 197,706 ART procedures (range: 162 in Wyoming to 24,030 in California) with the intent to transfer at least one embryo were performed in 463 U.S. fertility clinics and reported to CDC. These procedures resulted in 65,964 live-birth deliveries (range: 57 in Puerto Rico to 8,638 in California) and 76,892 infants born (range: 74 in Alaska to 9,885 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART use rate, was 3,075. ART use rates exceeded the national rate in 14 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Utah, and Virginia). ART use exceeded 1.5 times the national rate in nine states, including three (Illinois, Massachusetts, and New Jersey) that also had comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four oocyte retrievals). Nationally, among ART transfer procedures for patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age (1.5 among women aged <35 years, 1.7 among women aged 35-37 years, and 2.2 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 42.7% (range: 8.3% in North Dakota to 83.9% in Delaware). In 2016, ART contributed to 1.8% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.7% in Massachusetts). ART also contributed to 16.4% of all multiple-birth infants, including 16.2% of all twin infants and 19.4% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (21,455 of 22,233) of all ART-conceived infants born in multiple deliveries. The percentage of multiple-birth infants was higher among infants conceived with ART (31.5%) than among all infants born in the total birth population (3.4%). Approximately 30.4% of ART-conceived infants were twins and 1.1% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.0% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 23.6% had low birthweight compared with 8.2% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (29.9%) than among all infants born in the total birth population (9.9%). The percentage of ART-conceived infants who had low birthweight was 8.7% among singletons, 54.9% among twins, and 94.9% among triplets and higher-order multiples; the corresponding percentages among all infants born were 6.2% among singletons, 55.4% among twins, and 94.6% among triplets and higher-order multiples. The percentage of ART-conceived infants who were born preterm was 13.7% among singletons, 64.2% among twins, and 97.0% among triplets and higher-order infants; t

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


Autologous Platelet-Rich Plasma Treatment Enables Pregnancy for a Woman in  Premature Menopause

Konstantinos Sfakianoudis

Centre for Human Reproduction, Genesis Athens Clinic, 14-16, Papanikoli, 15232 Athens, Greece

Athanasios Pappas

Centre for Human Reproduction, Genesis Athens Clinic, Greece.

Nikolaos Nitsos

Microbiology-Biochemical Department, Genesis Athens Clinic, Greece

Anna Rapani

Department of Physiology, Medical School, National and Kapodistrian University of Athens, Greece

Abstract: This report presents the case of a woman aged 40 who has experienced premature menopause from the age of 35. Having rejected oocyte donation, she opted for intraovarian injection of autologous platelet-rich plasma with the aim to rejuvenate the ovarian tissue and enable the employment of her own gametes through in-vitro fertilization. Six weeks following the autologous platelet-rich plasma treatment, a significant reduction in the patient's follicle-stimulating hormone (FSH) levels were noted. A natural in-vitro fertilization cycle led to a biochemical pregnancy, resulting in a spontaneous abortion at the 5th week of pregnancy. This is the first report of a successful autologous platelet-rich plasma application leading to pregnancy in menopause. This report uniquely contributes to the medical knowledge and challenges current practice in the context of infertility. The efficiency and safety of this treatment with regard to the reproductive system merits further investigation.


The influence of different inositol stereoisomers supplementation in pregnancy on  maternal gestational diabetes mellitus and fetal outcomes in high-risk patients:  a randomized controlled trial

Barbara Matarrelli

Department of Obstetrics and Gynaecology, University of Chieti, Chieti, Italy;

Abstract:
Objective: To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.Design: A preliminary, prospective, randomized, placebo controlled clinical trial.

Participants: Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy.

Intervention: Supplementation with myo-inositol, d-chiro-inositol, combined myoand d-chiro-inositol or placebo.Main outcome measure: Development of GDM on a 75 grams oral glucose tolerance test at 24-28 weeks' gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia.

Results: The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups.

Conclusions: This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.

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


An inexpensive smartphone-based device for point-of-care ovulation testing

Abstract: The ability to accurately predict ovulation at-home using low-cost point-of-care diagnostics can be of significant help for couples who prefer natural family planning. Detecting ovulation-specific hormones in urine samples and monitoring basal body temperature are the current commonly home-based methods used for ovulation detection; however, these methods, relatively, are expensive for prolonged use and the results are difficult to comprehend. Here, we report a smartphone-based point-of-care device for automated ovulation testing using artificial intelligence (AI) by detecting fern patterns in a small volume (<100 μL) of saliva that is air-dried on a microfluidic device. We evaluated the performance of the device using artificial saliva and human saliva samples and observed that the device showed >99% accuracy in effectively predicting ovulation.


Fertility and infertility: Definition and epidemiology

Abstract: Infertility is a disease characterized by the failure to establish a clinical pregnancy after 12 months of regular and unprotected sexual intercourse. It is estimated to affect between 8 and 12% of reproductive-aged couples worldwide. Males are found to be solely responsible for 20-30% of infertility cases but contribute to 50% of cases overall. Secondary infertility is the most common form of female infertility around the globe, often due to reproductive tract infections. The three major factors influencing the spontaneous probability of conception are the time of unwanted non-conception, the age of the female partner and the disease-related infertility. The chance of becoming spontaneously pregnant declines with the duration before conception. The fertility decline in female already starts around 25-30 years of age and the median age at last birth is 40-41 years in most studied populations experiencing natural fertility. The disease-related infertility may affect both genders or be specific to one gender. The factors affecting both genders' fertility are hypogonadotrophic hypogonadism, hyperprolactinemia, disorders of ciliary function, cystic fibrosis, infections, systemic diseases and lifestyle related factors/diseases. Premature ovarian insufficiency, polycystic ovary syndrome, endometriosis, uterine fibroids and endometrial polyps may play a role in female infertility. Male infertility may be due to testicular and post-testicular deficiencies. Semen decline that has been observed over the years, endocrine disrupting chemicals and consanguinity are other factors that may be involved.


Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation

Abstract: OBJECTIVE: Alternative ovarian stimulation protocols for in vitro fertilisation  (IVF) have grown in popularity. Yet, patient populations best suited for these  protocols have not been defined. Our objective was, therefore, to determine  national IVF utilisation patterns and live birth rates of various ovarian  stimulation protocols. DESIGN: Retrospective cohort study. SETTING: Academic-affiliated private fertility centre. PARTICIPANTS: Aggregate data published by Society for Assisted Reproductive  Technology for autologous IVF cycles performed in the USA during 2014 and 2015  were analysed. IVF cycles were stratified based on ovarian stimulation protocol:  205 705 conventional stimulations, 4397 minimal stimulations, 2785 natural  cycles and 514 in vitro maturation (IVM) cycles. Repeat cycles could not be  determined in this analysis. OUTCOME MEASURES: Utilisation patterns and age-specific live birth rates for  various ovarian stimulation protocols. RESULTS: With advancing female age, utilisation of conventional stimulation  protocols decreased, while minimal stimulation and natural cycle IVF increased.  Diminished ovarian reserve diagnoses were in all age groups less prevalent in  patients undergoing conventional stimulation than with all other protocols. Live  birth rates were highest with conventional stimulation at 42.4%, 33.1%, 22.1%,  11.7% and 3.9% for <35, 35-37, 38-40, 41-42 and >42 female age groups,  respectively. The difference in live birth rates between conventional  stimulation and other protocols widened with advancing age from 1.6-fold to  3.9-fold among women <35 years of age, reaching 4.4-fold to 6.6-fold among women  >42 years of age. CONCLUSIONS: In comparison to conventional stimulation IVF-minimal stimulation,  natural cycle IVF and IVM protocols offer lower but still acceptable live birth  rates among young women. These alternative protocols are frequently used in  older women and those with diminished ovarian reserve, despite their lower live  birth rates. The reasons for this apparent incongruity warrant further careful  exploration.


Rejecting Humanae Vitae: The Social Costs of Denying the Obvious

Abstract:
Since contraceptives have been used to remove fertility from the conjugal act, the social consequences predicted in the encyclical Humanae vitae, such as the rise in cohabitation, decline of marriage, rise of divorce, and single parenthood, have exceeded expectations. The degradation of the sexual act from total mutual self-giving to momentary union has led to doubting the significance of the biological truth of the body and opened the door to gender fluidity. Promiscuity became normative, and the need for consent became eroded until women revolted with the #MeToo movement. Promiscuity, cohabitation, and divorce have resulted in 40 percent of children born to unmarried parents whose tenuous unions often leave the children in melded and dysfunctional families. Relation-free "hookups" have become the norm among young adults, leaving a flood of emotionally damaged women, an epidemic of sexually transmitted infections, and unplanned pregnancies, to which the healthcare industry has responded by doubling down on the means which caused the problem in the first place with near-coercive promotion of long-acting, reversible contraceptives (LARCs). LARCs must be inserted and removed professionally and make reproductive choice moot. Respecting the truth of the body is the precise counter measure. A woman's cyclic fertility is easily observed with reliable biomarkers-natural family planning-which requires the whole person. Fertility awareness-based methods of family planning have no side effects, are easy to learn, and can be used to achieve as well as delay conception. The self-discovery inherent in learning fertility literacy has empowered adolescent girls and boys to understand and value their sexuality and fertility and avoid choosing harmful behaviors. Why does society continue to treat fertility as if it were a disease?
Summary: Removing the idea of pregnancy from the sexual act as the result of readily available contraception has effectively limited choices about sexual behavior to the satisfaction of momentary desires. As Humanae vitae predicted, fewer marriages were contracted, divorce increased and now 40% of children are born out of wedlock despite extensive public education campaigns to promote contraception. Side effects of the hormonal pill have reduced their use so health care professionals have doubled down, providing long acting contraceptives which do not require the user to exercise choice before each act of intercourse, or of taking a pill. There is a much better way to regulate births-to learn to read the book of nature. Fertility is not a disease to be removed from the body. All that is needed is to understand the natural signs of fertility-natural family planning, now called FABM-Fertility Awareness-Based Methods. These have no side effects, enhance couple communication and offer effective choice for child spacing and demonstrably support premarital chastity for teens.


Dissociation between Cervical Mucus and Urinary Hormones during the Postpartum Return of Fertility in Breastfeeding Women

Abstract: Identifying the return of fertility with cervical mucus observations is challenging during the postpartum period. Use of urinary measurements of estrogen and progesterone can assist in understanding the return to fertility during this period. The purposes of this study were to describe the postpartum return of fertility by an analysis of total estrogen (TE) and pregnanediol glucuronide (PDG) profiles and to correlate these profiles with cervical mucus observations. Twenty-six participants collected urine samples during the postpartum period and recorded mucus scores. TE and PDG hormones were analyzed and compared with mucus scores. During amenorrhea, mucus reflected TE changes in only 35 percent of women; after amenorrhea, typical mucus patterns were seen in 33 percent of cycles. We concluded that postpartum mucus and hormone profiles are significantly dissociated but that monitoring urinary hormones may assist in identifying the return of fertility. We also identified different hormonal patterns in the return to fertility. The postpartum period is a challenging time for identifying the return of fertility. The purposes of this study were to describe the hormonal patterns during the return of fertility and to correlate these patterns with cervical mucus observations. Twenty-six postpartum women collected urine samples and recorded mucus scores. Urinary estrogen and progesterone hormones were analyzed and compared with mucus scores. Before the return of menses, mucus reflected hormonal changes in only 35 percent women and after first menses in 33 percent of cycles. We found that hormone profiles do not correlate well with mucus observations during the postpartum return of fertility.


Systematic Review of Hormonal Contraception and Risk of Venous Thrombosis

Abstract:
Background: Hormonal contraception (HC) is widely used throughout the world and has been associated with venous thrombosis (VT) such as deep vein thrombosis, pulmonary emboli, and cerebral VT.

Objectives: To provide a current comprehensive overview of the risk of objectively confirmed VT with HC in healthy women compared to nonusers. SEARCH

Methods: PubMed was searched from inception to April 2018 for eligible studies in the English language, with hand searching from past systematic reviews.
Selection Criteria: We selected original research evaluating risk of objectively confirmed VT in healthy women taking oral or nonoral HC compared with nonusers. DATA COLLECTION: The primary outcome of interest was a fatal or nonfatal VT in users of HC compared to nonusers or past users. Studies with at least twenty events were eligible. Adjusted relative risks with 95 percent confidence intervals were reported. Three independent reviewers extracted data from selected studies.

Results: 1,962 publications were retrieved through the search strategy, with 15 publications included. Users of oral contraception with levonorgesterol had increased risk of VT by a range of 2.79-4.07, while other oral hormonal preparations increased risk by 4.0-48.6. Levonorgestrel intrauterine devices did not increase risk. Etonogestrel/ethinyl estradiol vaginal rings increased the risk of VT by 6.5. Norelgestromin/ethinyl estradiol patches increased risk of VT by 7.9. Etonogestrel subcutaneous implants by 1.4 and depot-medroxyprogesterone by 3.6. The risk of fatal VT was increased in women aged fifteen to twenty-four by 18.8-fold.

Conclusion: Users of HC have a significant increased risk of VT compared to nonusers. Current risks would project at least 300-400 healthy young women dying yearly in the United States due to HC. Women should be informed of these risks and offered education in fertility-awareness-based methods with comparable efficacy for family planning.
Summary: HC is widely used throughout the world and has been associated with blood clots in the legs and lungs. We searched the literature and found the risks of currently used forms of birth control increased between threeand ninefold for blood clots for healthy women. The risks found would project 300-400 women dying from using HC each year in the United States.


The State of the Fertility Sector 2017/2018

Human Fertilisation and Embryology Authority


Systematic Review of Ovarian Activity and Potential for Embryo Formation and Loss during the Use of Hormonal Contraception

Cara Buskmiller

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

Donna Harrison

American Congress of Obstetricians and Gynecologists

Abstract: The purpose of this review was to determine whether there is evidence that ovulation can occur in women using hormonal contraceptives and whether these drugs might inhibit implantation. We performed a systematic review of the published English-language literature from 1990 to the present which included studies on the hormonal milieu following egg release in women using any hormonal contraceptive method. High circulating estrogens and progestins in the follicular phase appear to induce dysfunctional ovulation, where follicular rupture occurs but is followed by low or absent corpus luteum production of progesterone. Hoogland scoring of ovulatory activity may inadvertently obscure the reality of ovum release by limiting the term "ovulation" to those instances where follicular rupture is followed by production of a threshold level of luteal progesterone, sufficient to sustain fertilization, implantation, and the end point of a positive β-human chorionic gonadotropin. However, follicular ruptures and egg release with subsequent low progesterone output have been documented in women using hormonal contraception. In the absence of specific ovulation and fertilization markers, follicular rupture should be considered the best marker for egg release and potential fertilization. Women using hormonal contraceptives may produce more eggs than previously described by established criteria; moreover, suboptimal luteal progesterone production may be more likely than previously acknowledged, which may contribute to embryo loss. This information should be included in informed consent for women who are considering the use of hormonal contraception. SUMMARY: For this study, the authors looked at English-language research articles that focused on how hormonal birth control, such as the birth control pill, may affect very early human embryos. The authors found that abnormal ovulation, or release of an egg followed by abnormal hormone levels, may often occur in women using hormonal birth control. This may increase the number of very early human embryos who are lost before a pregnancy test becomes positive. For women who are thinking about using hormonal birth control, this is important information to consider.


Hormonal Contraception and the Informed Consent

Abstract: Since the 1960s, hormonal contraceptives have become the most commonly used method of pregnancy prevention in the United States and the world. Oral contraceptives are used by a large percentage of women, including Christian women. There are known health risks to women demonstrated in research published since Pope Paul VI's prophetic encyclical Humanae vitae in 1968. These risks include venous thrombosis, cardiovascular risks, and an increased risk of cancer. These risks are medically recognized with continued scientific debate on the degree. The risks are significantly increased with preexisting conditions and in certain demographic groups. Discussing known and potential treatment risks is a standard that is both accepted by the medical community and is increasingly expected by patients. This discussion can be accomplished by the mechanism and principle of informed consent. Depending on the circumstances, abstinence or fertility awareness-based methods (FABMs) should be presented to patients. FABMs are licit, safe, and effective methods of pregnancy prevention. Informed consent is the most effective means of providing patients with pertinent information on the significant risks of contraception. SUMMARY: This article discusses the use of the informed consent to provide patients with information on the medical and ethical risks of oral contraceptives. FABMs and abstinence are presented as effective, safe, and licit preferences to oral contraceptives. Discussing known and potential treatment risks is accepted by the medical community and expected by patients (shared decision making). The authors discuss the historical context of Pope Paul VI's encyclical Humanae vitae in relationship to the development and rapid adoption of oral contraceptives.


The State of the Science of Natural Family Planning Fifty Years after Humane  Vitae: A Report from NFP Scientists' Meeting Held at the US Conference of  Catholic Bishops, April 4, 2018

Abstract: A one-day meeting of physicians, professional nurses, and scientists actively involved in Natural Family Planning (NFP) research was held to review the state of the science of NFP and consider future priorities. The meeting had four objectives: (i) determine the gaps in research evidence for secure methods of NFP among women of all reproductive categories, (ii) determine the gaps in the research and development of new technology for providing NFP services, (iii) determine the gaps in the research that determine the benefits and challenges with use of NFP among married couples, and (iv) provide prioritized ideas for future research needs from the analysis of evidence gaps from objectives above. This article summarizes the discussion and conclusions drawn from topics reviewed. While much has been accomplished in the fifty years since Humane vitae, there are still many gaps to address. Five areas for future research in NFP were identified as high priority: (1) well-designed method effectiveness studies among various reproductive categories including important subpopulations (postpartum, perimenopause, posthormonal contraceptive), normally cycling women (especially US women), and comparative studies between NFP methods; (2) validation studies to establish the benefit of charting fertility signs (both currently known and potential new indicators) as a screening tool for women's health issues; (3) ongoing independent evaluation of fertility monitoring apps to provide users perspective on the relative merits of each and to identify those most worthy of further effectiveness testing; (4) studies evaluating the impact of new technologies on NFP adoption, use, and persistence; and (5) creation of a shared database across various NFP methods to collaborate on shared research interests, longitudinal studies, and so on. This summarizes a meeting to review the scientific and medical progress related to natural family planning made in the 50 years since Humane Vitae and to define priorities for future work. Areas reviewed included the evidence for avoiding pregnancy in normally cycling, postpartum, and perimenopausal women, the impact of new technology, including fertility charting apps, on NFP, and the impact on relationships and personal well-being from use of NFP. Five priority focus areas for future research were also identified.


Bioethical and Moral Perspectives in Human Reproductive Medicine

Abstract:
A reductive reading of Humanae vitae seeks to limit its appeal to a ban on contraception. In truth, however, it offers a vision of human sexuality and conjugal love with broad and enduring relevance. In setting forth the intrinsic complementarity and irreducibility of the unitive and procreative dimensions of the conjugal act, Paul VI has given us a hermeneutical key for assessing many contemporary ethical dilemmas in human reproductive medicine. From this perspective, this article seeks to apply the logic of Humanae vitae to several real-life scenarios confronted by medical practitioners, educators, and ethicists working in the field of fertility and reproductive health. These include a consideration of the ethics of prescribing hormonal contraceptives, the possibilities of investigating male infertility, issues of cooperation in counseling and assisting conception in same-sex relationships, the ethics pertaining to assisted reproductive technology (ART), the contested case of prenatal adoption, and the application of double-effect reasoning.
Summary: On the occasion of the fiftieth anniversary of the promulgation of Pope Paul VI's encyclical Humanae vitae, this article seeks to defend its enduring relevance to modern-day society, through application of its reasoning to contemporary dilemmas in reproductive medicine. It considers real cases of the ethics of prescribing hormonal contraceptives, of investigating male infertility, of cooperating in counseling and assisting conception in same-sex relationships, of ART, of prenatal adoption, and the application of double-effect reasoning.


Beyond fertility: polycystic ovary syndrome and long-term health

Abstract: Polycystic ovary syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder affecting millions of women worldwide. Women with PCOS are often identified in adolescence or early adulthood with symptoms of oligomenorrhea or hirsutism or when presenting for infertility care. The health risks associated out of PCOS, however, go far beyond management of these common presenting symptoms or fertility treatment and likely extend past the reproductive years through and beyond menopause. International surveys suggest that most patients are dissatisfied with long-term counseling related to medical and psychologic issues. We performed a review of comorbidities, including diabetes mellitus, dyslipidemia, obesity, hypertension, metabolic syndrome, depression, anxiety, obstructive sleep apnea, nonalcoholic fatty liver disease, endometrial cancer, and cardiovascular disease, in both reproductive-age and older women with PCOS. Most meta-analyses in reproductive-age women demonstrate increased risks independent from obesity. Longitudinal and cross-sectional studies including women with PCOS >40 years of age are limited in number and design, but many demonstrate that some of these comorbidities persist. All providers involved in the multidimensional care of women with PCOS should be aware of these long-term health risks to provide appropriate counseling, screening, and management options. We identify limitations that should be the focus of future studies designed to study health outcomes in postmenopausal women with PCOS.


Modifiable life style factors and risk for incident endometriosis

Jiyoung Byun

Division of Public Health Department of Family and Preventive Medicine University of Utah  Salt Lake City Utah

Kristina Allen-Brady

Genetic Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Background: Caffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone-dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis.

Methods: Four hundred and seventy three women, ages 18-44 years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007-2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors.

Results: There were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10 ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk.

Conclusions: This study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.


Letter to the Editor: "Long-Term Testosterone Administration on Insulin  Sensitivity in Older Men With Low or Low-Normal Testosterone Levels"

Pilar Vigil

Pontificia Universidad Católica de Chile

The Journal of Clinical Endocrinology and Metabolism


The Ethics of Interstitial and Cesarean Scar Ectopic Pregnancies: Four Case  Studies and a Review of the Literature

Abstract:
Catholic bioethicists have extensively addressed extrauterine tubal pregnancies, which represent the great majority of ectopic pregnancies. However, additional management options have been developed for the other 7-10 percent of ectopic pregnancies. Using two cases of interstitial pregnancy and two cases of cesarean scar pregnancy (CSP) seen at a Catholic tertiary care center, this article discusses options including expectant management, systemic methotrexate, intragestational methotrexate, intragestational potassium chloride, uterine artery embolization, dilation and curettage (D&C), vasopressin use, cornuostomy, cornual wedge resection, CSP evacuation, CSP scar excision, CSP salvage, and hysterectomy. Cornual wedge resection, vasopressin use, and CSP scar excision are morally acceptable; less clearly licit are aspiration of gestational sac contents, cornuostomy, gestational excision for CSPs, and methotrexate. Certainly illicit are any techniques leading to direct abortion such as D&Cs on live embryos or fetuses, double-balloon catheter placement, and use of potassium chloride.
Summary: An ectopic pregnancy is any pregnancy outside the uterus. These are dangerous because the pregnancy can burst out of its abnormal location and cause life-threatening internal bleeding. Most are in the part of the fallopian tube outside the uterus, but there are other types, including interstitial pregnancies (located in the part of the tube tunneling through the uterine wall) and cesarean scar pregnancies (buried in the uterine scar where the cut for a C-section was made). This article lists the ways that physicians prevent women from dying from interstitial and cesarean scar pregnancies and proposes which treatments are morally acceptable.


Vulvodynia: A disease commonly hidden in plain sight

Abstract: •Vulvodynia affects at least 6% of women, and can be found at any age and in all ethnic groups.•The diagnosis is one of exclusion but is very often missed.•Women with vulvodynia are frequently misdiagnosed as having vaginismus.•Failure to make the diagnosis often leads to irrelevant or deleterious examinations and treatments.


Sex-Gender Differences in Irritable Bowel Syndrome

Abstract: Because of the sex-gender differences that are shown in a diversity of physiological and psychological factors, it can be speculated that the clinical presentation of symptoms as well as treatment strategies in women and men with irritable bowel syndrome (IBS) may differ. Studies have revealed that IBS is more common in women than men. As for the IBS subtype, IBS with constipation is significantly more prevalent among women than men. Sex hormones and gender differences may play important roles in the pathophysiology of IBS. However, its pathophysiologic mechanisms still remain largely unknown, and therapeutic implications are limited. Moreover, women IBS patients have been reported to feel more fatigue, depression, anxiety, and lower quality of life than men IBS patients. Furthermore, there has been evidence of differences in the appropriate treatment efficacy to IBS in men and women, although relatively few men are enrolled in most relevant clinical trials. A more sex-gender-oriented approach in the medical care setting could improve understanding of heterogeneous patients suffering from IBS. An individualized and multicomponent approach including sex and gender issues might help improve the treatment of IBS.

Journal of Neurogastroenterology and Motility


Metabolic syndrome in women with polycystic ovary syndrome

Swaramya Chandrasekaran

Indira Gandhi Medical College and Research Institute

Haritha Sagili

Jawaharlal Institute of Post Graduate Medical Education and Research

Abstract: Key content The risk factors for metabolic syndrome include central obesity, hypertension, atherogenic dyslipidaemia and insulin resistance. Metabolic syndrome affects 33% of women with polycystic ovary syndrome (PCOS) and has been less well researched than other features such as infertility, anovulation and hirsutism. Consequences of metabolic syndrome include cardiovascular disease, type II diabetes, cancer, sleep apnoea and psychological problems. Cardiometabolic risk screening involves obtaining data on smoking history, weight, body mass index, waist circumference, blood pressure, lipid profile, and taking an oral glucose tolerance test. Management of metabolic syndrome should focus on risk factors and individual components. Lifestyle modification is the only recommended intervention at present. Learning objectives To know the pathogenesis and consequences of metabolic syndrome in women with PCOS. To understand the diagnostic criteria and screening procedures for metabolic syndrome. To learn how to manage metabolic syndrome in women with PCOS. Ethical issues Potential preventive long‐term medication raises two issues: duration of therapy and unwarranted adverse effects. Advocating bariatric surgery without availability of robust evidence in PCOS women.


Low-Dose Naltrexone (LDN)-Review of Therapeutic Utilization

Abstract: Naltrexone and naloxone are classical opioid antagonists. In substantially lower than standard doses, they exert different pharmacodynamics. Low-dose naltrexone (LDN), considered in a daily dose of 1 to 5 mg, has been shown to reduce glial inflammatory response by modulating Toll-like receptor 4 signaling in addition to systemically upregulating endogenous opioid signaling by transient opioid-receptor blockade. Clinical reports of LDN have demonstrated possible benefits in diseases such as fibromyalgia, Crohn's disease, multiple sclerosis, complex-regional pain syndrome, Hailey-Hailey disease, and cancer. In a dosing range at less than 1 μg per day, oral naltrexone or intravenous naloxone potentiate opioid analgesia by acting on filamin A, a scaffolding protein involved in μ-opioid receptor signaling. This dose is termed ultra low-dose naltrexone/naloxone (ULDN). It has been of use in postoperative control of analgesia by reducing the need for the total amount of opioids following surgery, as well as ameliorating certain side-effects of opioid-related treatment. A dosing range between 1 μg and 1 mg comprises very low-dose naltrexone (VLDN), which has primarily been used as an experimental adjunct treatment for boosting tolerability of opioid-weaning methadone taper. In general, all of the low-dose features regarding naltrexone and naloxone have been only recently and still scarcely scientifically evaluated. This review aims to present an overview of the current knowledge on these topics and summarize the key findings published in peer-review sources. The existing potential of LDN, VLDN, and ULDN for various areas of biomedicine has still not been thoroughly and comprehensively addressed.


Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study

Abstract:
OBJECTIVES: To investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer.

DESIGN: Prospective, nationwide cohort study.

SETTING: Denmark, 1995-2014.

PARTICIPANTS: All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives.

MAIN OUTCOME MEASURES: Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated.

RESULTS: During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%-that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population.

CONCLUSIONS: Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age-an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.


Association of oral contraceptive use with suicidal behavior among representative  Korean population: Results from Korea National Health and Nutrition Examination  Survey (2007-2016)

Abstract:
Introduction: The association of suicide with the use of oral contraceptives (OC) is unknown in the Asian population. We aimed to evaluate the association of OC use and suicidal behavior in a nationally representative population of Korean women. METHOD: Of the 44,501 women who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) (2007-2016), 27,067 women aged 20 years or older who had completed information on OC use and suicidal behavior were included. Women with a history of cancer were excluded. Compared to non-users of OC, odds ratios (ORs) for suicide attempt/ideation were calculated using a multivariable logistic regression among OC users, with testing of the interaction term of OC use and history of depression. We also conducted a stratified analysis by history of depression.

Results: A total of 4,067 women (14.0%) reported they had suicide ideations or had attempted suicide, respectively. OC use was associated with an increased prevalence of suicidality (OR = 1.13, 95% CI 1.00-1.24) after adjustments for age, demographic factors, age of menarche, and lifestyle behaviors. When stratified by history of depression diagnosis, ORs linearly increased as the total duration of OC use lengthened among women with a history of depression; however, women without a history of depression showed peaked OR at 4to 12-month use.

Conclusion: There is an increased association between OC use and suicidality and the pattern of the relationship differs depending on whether there is a history of depression.


The two FIGO systems for normal and abnormal uterine bleeding symptoms and  classification of causes of abnormal uterine bleeding in the reproductive years:  2018 revisions

Malcolm G Munro

Kaiser Permanente West Los Angeles Medical Center

Abstract:
Background: The International Federation of Gynecology and Obstetrics (FIGO) systems for nomenclature of symptoms of normal and abnormal uterine bleeding (AUB) in the reproductive years (FIGO AUB System 1) and for classification of causes of AUB (FIGO AUB System 2; PALM-COEIN) were first published together in 2011. The purpose was to harmonize the definitions of normal and abnormal bleeding symptoms and to classify and subclassify underlying potential causes of AUB in the reproductive years to facilitate research, education, and clinical care. The systems were designed to be flexible and to be periodically reviewed and modified as appropriate.

Objectives: To review, clarify, and, where appropriate, revise the previously published systems. METHODOLOGY AND OUTCOME: To a large extent, the process has been an iterative one involving the FIGO Menstrual Disorders Committee, as well as a number of invited contributions from epidemiologists, gynecologists, and other experts in the field from around the world between 2012 and 2017. Face-to-face meetings have been held in Rome, Vancouver, and Singapore, and have been augmented by a number of teleconferences and other communications designed to evaluate various aspects of the systems. Where substantial change was considered, anonymous voting, in some instances using a modified RAND Delphi technique, was utilized.

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


Innovations in Women's Bone Health-Appreciating Important "Bone Variables" Besides Estrogen

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre


Effectiveness of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain in the treatment of endometriosis-associated pelvic pain: LEAP study

Abstract:
OBJECTIVE: To assess the impact of an antioxidant preparation with N-acetyl cysteine, alpha lipoic acid and bromelain on endometriosis-associated pelvic pain.

STUDY DESIGN: Multicenter, open-label, non-comparative clinical trial in a representative sample of women with endometriosis-associated pelvic pain.

RESULTS: In total, 398 patients with a mean age of 34.6 ± 7.2 years were treated with a combination of N-acetyl cysteine, alpha lipoic acid and bromelain for 6 months. At baseline, 92.7% of the patients had pain intensity > 4 on the visual analogue scale (VAS); at 3 months of treatment, this percentage decreased to 87.2% (p = 0.074) and at 6 months the percentage was 82.7% (p < 0.05).

CONCLUSIONS: Women with endometriosis who wish to become pregnant and are treated with a preparation containing N-acetyl cysteine, alpha lipoic acid and bromelain experienced a significant improvement in endometriosis-associated pelvic pain and required lower intake of rescue analgesics.

European journal of obstetrics, gynecology, and reproductive biology


Goossens V; European IVF-monitoring Consortium (EIM); European Society of Human Reproduction and Embryology (ESHRE)

Abstract:
---
title: "ART in Europe, 2014: results generated from European registries by ESHRE"
source_file: "eshre-eim-2014-source.pdf"
doi: "10.1093/humrep/dey242"
journal: "Human Reproduction, pp. 1-16, 2018"
pages: 16
extracted_date: "2026-04-24"
figures_extracted: 3
tables_extracted: 5
review_flags: 3
authors: "Ch. De Geyter, C. Calhaz-Jorge, M.S. Kupka, C. Wyns, E. Mocanu, T. Motrenko, G. Scaravelli, J. Smeenk, S. Vidakovic, V. Goossens"
---


Abstract:
INTRODUCTION: Deep dyspareunia occurs in half of women with endometriosis, a condition present in 10% of reproductive-age women and associated with negative effects on sexual quality of life (SQoL). However, women with endometriosis can have other clinical factors (eg, superficial dyspareunia, other pelvic pains, and psychological or pain conditions) possibly affecting SQoL.

AIMS: To determine whether deep dyspareunia is associated with SQoL in women with endometriosis, independent of potential confounders.

METHODS: This study involved a prospective patient registry of women at a tertiary-level referral center for endometriosis and pelvic pain. Inclusion criteria were (i) referrals to the center recruited into the registry from January 2014 through December 2016 and (ii) subsequent surgery at the center with histologic confirmation of endometriosis. Exclusion criteria included menopausal status, age at least 50 years, never sexually active, or did not answer dyspareunia or SQoL questions. Bi-variable tests and multiple linear regression analysis were performed.

MAIN OUTCOME MEASURES: SQoL measured by the 5-item sexual intercourse subscale of the Endometriosis Health Profile-30 (EHP-30) modular questionnaire (0-100%, with higher scores indicating worse SQoL).

RESULTS: Consent rate for the prospective registry was 87%; 277 women met the study criteria (mean age = 34.2 ± 7.1 years). Most women had stage I to II endometriosis at time of surgery (64%), with the remaining having stage III to IV endometriosis. Through regression analysis, worse SQoL (higher EHP-30 sexual intercourse subscale score) was independently associated with: more severe deep dyspareunia (P < .0001), more severe superficial dyspareunia (P < .0001), increased depression (P < .001), higher pain catastrophizing (P = .04), bladder pain syndrome (P = .02), heterosexual orientation (P < .001), and new referral status (P = .02).

CONCLUSION: In women with endometriosis at a tertiary referral center, more severe deep dyspareunia was associated with worse SQoL, independent of superficial dyspareunia, psychological comorbidities, and other potential confounders. Shum LK, Bedaiwy MA, Allaire C, et al. Deep Dyspareunia and Sexual Quality of Life in Women With Endometriosis. Sex Med 2018;6:224-233.


Recognizing and Managing Postpartum Psychosis: A Clinical Guide for Obstetric Providers

Abstract: Postpartum psychosis is a psychiatric emergency that affects 1 to 2 per 1000 women. Key clinical features include mood fluctuation, abnormal thoughts or behaviors, and confusion. Women with a history of bipolar disorder are at heightened risk, as are first-time mothers; current research on the causes focuses on biological triggers, such as immune dysregulation. Women with postpartum psychosis require inpatient hospitalization and should be treated with lithium, antipsychotics, and benzodiazepines.

Obstetrics and gynecology clinics of North America


Long-term follow-up of ICSI-conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period

Abstract: BACKGROUND: A significant increase in the use of intracytoplasmic sperm injection (ICSI) since its introduction in 1992 has been observed worldwide, including beyond its original intended use for severe male factor infertility. Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility, and of the technique itself. The health and development of ICSI-conceived children beyond early infancy have not been comprehensively assessed. OBJECTIVE: A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to spontaneously conceived (SC) offspring. DESIGN: PubMed, OVID Medline/Embase, InformIT, Web of Science, and ProQuest databases were searched for studies reporting on health outcomes in ICSI-conceived offspring beyond 28 days after birth. MAIN OUTCOMES MEASURES: Physical and psychosocial health. RESULTS: The search strategy yielded 2826 articles. Of these, 2580 were not relevant or did not meet inclusion criteria and 138 were duplicates. One hundred and eight full-text papers were evaluated further, and 48 satisfied the inclusion criteria. Most studies reported on neurodevelopment during early infancy and childhood with reassuring results. Growth, vision, and hearing of ICSI and SC offspring also appear comparable, although important differences in general physical health, and particularly metabolic and reproductive health have been described, including recently poorer semen quality among ICSI-conceived young adult men compared to SC peers. CONCLUSION: Whilst neurodevelopment, growth, vision, and hearing appear similar between ICSI and SC children, evidence suggests differences in general physical health, and metabolic and reproductive endpoints. The clinical significance of many findings, however, remains unclear, and further prospective, large, and good quality studies with a focus on all these health outcomes in ICSI-conceived young adults are required.


Egg Freezing in Fertility Treatment: Trends and Figures 2010-2016

Human Fertilisation and Embryology Authority


Healthy Singleton Pregnancies From Restorative Reproductive Medicine (RRM) After Failed IVF

Karolina M Andralojc

Radboud Institute for Molecular Life Sciences

Phil C Boyle

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

Theun de Groot

International Institute for Restorative Reproductive Medicine, London, United Kingdom.

Abstract:
Objectives: To determine the live birth rate for patients who chose to undergo treatment with Restorative Reproductive Medicine (RRM) after previous IVF (includes ICSI). To look at birth outcomes with RRM after IVF, particularly rates of twin and higher order pregnancies, premature birth, low birth weight, and potential cost savings achieved with RRM.

Setting: Two outpatient clinics in Ireland providing advanced RRM treatment of infertility.

Materials and methods: All patients presenting between January 2004 and January 2010, with a history of infertility and previous IVF treatment were included if they proceeded beyond the initial consultation and began treatment. Main outcome is live birth per couple calculated using life table analysis.

Results: 403 patients met the study criteria, among which 74 had a subsequent live birth. These women had significant negative predictive characteristics for healthy live birth including: advanced reproductive age (average 37.2 years), an average of 5.8 years of infertility with 2.1 (range 1-9) previous IVF attempts, with only 5% having previously had a live birth from IVF. Despite these undesirable prognostic indicators, the overall RRM live birth rate was 32.1% (crude 18.4%). Women aged 35-38 had a live birth rate of 37.5% (crude 23.6%) and older women over 40 had a live birth rate of 27.4% (crude 16.0%). The average birth weight was 3374g (7lb 7oz) with 92% being born at 37+ weeks and no very low birth weight babies. There was only one twin pregnancy in the study population; the potential health care savings for avoidable multiple pregnancies in these patients was estimated at £205 672 (USD$284 915).

Conclusions: Patients who have already tried IVF can achieve comparable live birth outcomes with RRM compared to another cycle of IVF. RRM has a low risk of twin or multiple births, and very good neonatal outcomes with a potential cost savings to the health care system.


Effectiveness of Fertility Awareness-Based Methods for Pregnancy Prevention: A Systematic Review

Margaret E Greene

GreeneWorks, Washington DC, United States.

Emily Kennedy

The Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, United States.

Abstract:
OBJECTIVE: To summarize best available prospective data on typical and perfect use effectiveness of fertility awareness-based methods for avoiding pregnancy.

DATA SOURCES: We conducted a systematic review of studies published in English, Spanish, French, or German by June 2017 in MEDLINE, EMBASE, CINAHL, Web of Science, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We reviewed 8,755 unique citations and included 53 studies that contained 50 or greater women using a specific fertility awareness-based method to avoid pregnancy, calculated life table pregnancy probabilities or Pearl rates, and prospectively measured pregnancy intentions and outcomes. We systematically evaluated study quality. TABULATION, INTEGRATION, AND

RESULTS: Of 53 included studies, we ranked 0 high quality, 21 moderate quality, and 32 low quality for our question of interest. Among moderate-quality studies, first-year typical use pregnancy rates or probabilities per 100 woman-years varied widely: 11.2-14.1 for the Standard Days Method, 13.7 for the TwoDay Method, 10.5-33.6 for the Billings Ovulation Method, 4-18.5 for the Marquette Mucus-only Method, 9.0-9.8 for basal body temperature methods, 13.2 for single-check symptothermal methods, 11.2-33.0 for Thyma double-check symptothermal methods, 1.8 for Sensiplan, 25.6 for Persona, 2-6.8 for the Marquette Monitor-only Method, and 6-7 for the Marquette Monitor and Mucus Method. First-year perfect use pregnancy rates or probabilities among moderate-quality studies were 4.8 for the Standard Days Method, 3.5 for the TwoDay Method, 1.1-3.4 for the Billings Ovulation Method, 2.7 for the Marquette Mucus Method, 0.4 for Sensiplan, 12.1 for Persona, and 0 for the Marquette Monitor.

CONCLUSION: Studies on the effectiveness of each fertility awareness-based method are few and of low to moderate quality. Pregnancy rates or probabilities varied widely across different fertility awareness-based methods (and in some cases, within method types), even after excluding low-quality studies. Variability across populations studied precludes comparisons across methods.


Current Medical Research: Summer/Fall 2017

Abstract: This issue of Current Medical Research (CMR) includes studies that provide evidence that use of natural family planning (NFP) can be helpful for subfertile couples wishing to achieve a pregnancy, the effectiveness of a method of NFP during breastfeeding, and the effects of using NFP on marital relationships. This review also includes evidence on predicting the sex of a baby by timing intercourse, evidence that brain injuries can be reflected in changes in the menstrual cycle, and that women prefer methods of family planning that have no side effects. The issue ends with an in-depth review of new technologies that aid in the use of NFP. Topics covered include subfertile couples, breastfeeding, marriage, predicting the sex of a baby, brain injuries, and new technologies.


Special issue in Commemoration of the 50th Anniversary of Humanae vitae


Photobiomodulation: lasers vs. light emitting diodes?

Abstract: Photobiomodulation (PBM) is a treatment method based on research findings showing that irradiation with certain wavelengths of red or near-infrared light has been shown to produce a range of physiological effects in cells, tissues, animals and humans. Scientific research into PBM was initially started in the late 1960s by utilizing the newly invented (1960) lasers, and the therapy rapidly became known as "low-level laser therapy". It was mainly used for wound healing and reduction of pain and inflammation. Despite other light sources being available during the first 40 years of PBM research, lasers remained by far the most commonly employed device, and in fact, some authors insisted that lasers were essential to the therapeutic benefit. Collimated, coherent, highly monochromatic beams with the possibility of high power densities were considered preferable. However in recent years, non-coherent light sources such as light-emitting diodes (LEDs) and broad-band lamps have become common. Advantages of LEDs include no laser safety considerations, ease of home use, ability to irradiate a large area of tissue at once, possibility of wearable devices, and much lower cost per mW. LED photobiomodulation is here to stay.

Photochemical & Photobiological Sciences : Official Journal of the European  Photochemistry Association and the European Society for Photobiology


Non-steroidal anti-inflammatory drug induces luteinized unruptured follicle  syndrome in young female juvenile idiopathic arthritis patients

Renato Tomioka

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Abstract: To assess prospectively luteinized unruptured follicle (LUF) syndrome in juvenile idiopathic arthritis (JIA) patients with and without non-steroidal anti-inflammatory drugs (NSAIDs) and healthy controls. Twenty-three adolescent and young adult female JIA patients (ILAR criteria) and 11 female healthy subjects were studied by pelvic ultrasound monitoring for follicular development and ovulation in one menstrual cycle. LUF syndrome was prospectively investigated by pelvic ultrasound with a dominant ovarian follicle without signs of follicular rupture, with elevation of serum progesterone in the luteal phase of the menstrual cycle and luteinizing hormone (LH) detected in the urine. Comparison between JIA patients with (n = 8) vs. without NSAIDs (n = 15) and healthy controls (n = 11) revealed that LUF syndrome was significantly higher in the former group (2 (25%) vs. 0% vs. 0%, p = 0.049). These two patients with LUF syndrome had normal menstrual cycles without reduced ovarian reserve, and they were under naproxen 500 mg bid during the menstrual cycle. Disease duration was comparable in JIA with and without NSAIDs [19.8 (4.4-25) vs. 13 (3.1-33) years, p = 0.232]. Further comparison between JIA patients with and without NSAIDs and healthy controls showed similar mean anti-Müllerian hormone levels (p = 0.909), estradiol (p = 0.436), FSH (p = 0.662), LH (p = 0.686), and mean antral follicle count (p = 0.240) and ovarian volume (p = 0.363). No differences were evidenced in three groups regarding Caucasian race, body mass index, duration, and length of menstrual cycles (p > 0.05). This is the first study to identify that JIA patients have a high frequency of LUF without impaired ovarian reserve. Future prospective studies are necessary to determine if chronic/continuous use of NSAIDs in JIA will have an impact in these patients' fertility.


Insulin Sensitivity and Testicular Function in a Cohort of Adult Males Suspected  of Being Insulin-Resistant

Felipe Serrano

Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile

Ana M Salgado

Pontificia Universidad Católica de Chile

Abstract: A cohort of 141 males (18-80 yo, 42.9 ± 12.9) strongly suspected of being Insulin Resistant (IR) was prospectively studied by determining their insulin sensitivity (Pancreatic Suppression Test, PST) and testicular function (total testosterone and SHBG). The subjects were labeled as IR when the Steady State Plasma Glucose (SSPG) was ≥150 mg/dL and Non-Insulin Resistant (NIR) when SSPG was <150 mg/dl; similarly, the subjects were labeled as Hypogonadal (HYPOG) when total testosterone was ≤3.0 ng/mL and Eugonadal (EUG) when total testosterone was >3.0 ng/mL. Two out of three subjects turned out to be IR, while around one in four subjects were HYPOG. Contingency analysis indicated a significant interdependence between insulin resistance and hypogonadism (chi-square was 4.69, p = 0.0303). Age (>43 yo) predicted hypogonadism (AUROC 0.606, p = 0.0308). Twice as many HYPOG subjects were IR as compared with EUG subjects. Also, HYPOG subjects exhibited higher SSPG values as compared with EUG subjects. Statistically, neither Weight nor BMI predicted hypogonadism, while Waist Circumference (>110 cm) was only a mediocre predictor (AUROC 0.640, p = 0.009). SSPG (>224 mg/dL) on the other hand, was the best predictor of hypogonadism (AUROC 0.709, p = 0.002), outperforming Waist Circumference (half of the subjects with an SSPG >224 mg/dL were HYPOG). Age did not predict insulin resistance, while Weight (>99 kg), BMI (>29), and especially, Waist Circumference (>99 cm, AUROC 0.812, p < 0.0001) were all predictors of insulin resistance. Almost 90% of the subjects with a waist circumference >99 cm was IR. As a logical consequence of the selection criteria (various clues suggesting insulin resistance), most subjects with normal weight in this cohort were IR (53.3%) while 20% were HYPOG. On the other hand, 13.6% of the obese subjects were NIR, and 2 out of 3 of them were both NIR and EUG. In conclusion, Waist Circumference predicted both insulin resistance (>99 cm) and hypogonadism (>110 cm), suggesting that the first hit of abdominal obesity is insulin resistance and the second hit is male hypogonadism. Normal weight did not protect from IR, while a relevant proportion of obese subjects were NIR (with 2/3 being also EUG).


Current clinical applications of platelet-rich plasma in various gynecological  disorders: An appraisal of theory and practice

Abstract: The purpose of this paper is to review the current clinical uses of platelet-rich plasma (PRP) in the field of gynecology. All relevant articles published from January 2000 to December 2017 were reviewed and analyzed. The articles on PRP in the field of gynecology were mainly case series, pilot studies, or case reports. PRP is currently considered a new therapeutic modality for some disorders that are refractory to conventional drugs.

Clinical and Experimental Reproductive Medicine


Low Dose Naltrexone in the Treatment of Fibromyalgia

Abstract:
Background: ConclusionFibromyalgia is a chronic pain disorder characterized by diffuse musculoskeletal pain, fatigue, sleep disturbance and cognitive impairment.

Objective: A significant number of fibromyalgia patients do not respond adequately to the current drugs approved by the Food and Drug Administration (FDA) for fibromyalgia treatment including pregabalin, milnacipran, duloxetine. Thus, there is still a need for adjunctive therapies.

Method: Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia.

Results: Two small prospective pilot studies have previously shown that treatment with low dose naltrexone may be an effective, safe, and inexpensive treatment for fibromyalgia.

Conclusion: This prospective study lends further support to the preliminary body of evidence that naltrexone is a well tolerated and likely effective treatment option in the community setting. Further large prospective controlled trials are still needed.


Current Medical Research: Winter/Spring 2017


Self-Monitoring of Fertility Hormones: A New Era for Natural Family Planning?

Abstract:
Natural family planning (NFP) methods have served many generations well, and in particular, the symptothermal or symptohormonal methods. The comparison of daily mucus and temperature records for individual cycles with daily hormone measurements, which is now possible, shows that some of the assumptions underlying NFP may not be completely accurate. The various methods are inadvertently depending on an element of chance, which, of course, cannot be known by the NFP user. However, it is statistically inevitable that such errors will result eventually in an unexpected pregnancy, and these discrepancies are the likely reason for the method failures. Further research and integration of home hormone measurements with NFP symptoms are needed.
Summary: Traditional NFP methods, based on the observations of temperature, mucus, and luteinizing hormone, can work well. However, these data are sometimes difficult to interpret, and significant changes in the variables are sometimes "missing" from some cycles. Changes in these variables are elicited by the estrogen and progesterone released from the ovaries. It follows that the direct measures of events in the ovaries are the levels of estrogen and progesterone or their derivatives in blood or urine. Measurements of urinary derivatives of estrogen and progesterone can be used to monitor the ovaries directly and are clearer indicators than traditional NFP methods.


Progesterone for treatment of symptomatic menopausal women

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: This review's purpose is to highlight evidence that oral micronized progesterone (progesterone) is effective for hot flushes and night sweats (vasomotor symptoms, VMS), improves sleep and is likely safe in menopausal women (who are more than 1 year since last menstruation). Methods include randomized controlled clinical trials (RCT) supplemented with basic science, population and observational data as needed. The barrier to use of progesterone is lack of awareness that safety concerns with estrogen-including 'menopausal hormone therapy' (MHT) are not applicable to progesterone. In a single 3-month RCT, progesterone (300 mg at bedtime) was effective treatment of VMS in 133 healthy menopausal women. It caused an overall 55% VMS decrease, no withdrawal-related VMS rebound and a greater VMS decrease in 46 women with ≥50 moderate-intense VMS/week. Progesterone is equally or more effective than estradiol in improving cardiovascular endothelial function and caused no cardiovascular safety concerns in a 3-month RCT. An 8-year prospective cohort study (E3N) in more than 80 000 menopausal women showed progesterone prevented breast cancer in estrogen-treated women. Multiple RCTs confirm that progesterone (300 mg daily at bedtime) does not cause depression and improves deep sleep. In conclusion, progesterone effectively treats VMS, improves sleep and may be the only therapy that symptomatic women, who are menopausal at a normal age and without osteoporosis, need.

Climacteric : the Journal of the International Menopause Society


Progesterone for the prevention and treatment of osteoporosis in women

Abstract: Estradiol (E2) is women's dominant 'bone hormone' since it is essential for development of adolescent peak bone mineral density (BMD) and physiological levels prevent the rapid (3-week) bone resorption that causes most adult BMD loss. However, deceasing E2 levels trigger bone resorption/loss. Progesterone (P4) is E2's physiological partner, collaborating with E2 in every cell/tissue; its bone 'job' is to increase P4-receptor-mediated, slow (3-4 months) osteoblastic new bone formation. When menstrual cycles are normal length and normally ovulatory, E2 and P4 are balanced and BMD is stable. However, clinically normal cycles commonly have ovulatory disturbances (anovulation, short luteal phases) and low P4 levels; these are more frequent in teen and perimenopausal women and increased by everyday stressors: energy insufficiency, emotional/social/economic threats and illness. Meta-analysis shows that almost 1%/year spinal BMD loss occurs in those with greater than median (∼31%) of ovulatory disturbed cycles. Prevention of osteoporosis and fragility fractures requires the reversal of stressors, detection and treatment of teen-to-perimenopausal recurrent cycle/ovulatory disturbances with cyclic oral micronized progesterone. Low 'Peak Perimenopausal BMD' is likely the primary risk for fragility fractures in later life. Progesterone plus estradiol or other antiresorptive therapies adds 0.68%/year and may be a highly effective osteoporosis treatment. Randomized controlled trials are still needed to confirm progesterone's important role in women's bone formation.


Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles

Keewan Kim

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Jean Wactawski-Wende

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

Abstract: Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.


Update on male reproductive endocrinology

Abstract: Practitioners of male reproductive and sexual medicine must have an intimate understanding of the physiology of male reproductive endocrinology, as such a knowledge is the cornerstone on which hormonal treatments are based. In this review, we highlight what is known about male reproductive endocrine physiology and the various control mechanisms for the system. We also discuss the limitations of our current understanding of the reproductive physiology. We hope that this review is helpful for male reproductive medicine practitioners in understanding the principles on which hormonal treatments are based.


A prospective study of physical activity and fecundability in women with a history of pregnancy loss

Lindsey M Russo

Division of General Internal Medicine, Weill Cornell Medicine, 420 East 70th Street, New York, NY 10021, USA.

Daniel L Kuhr

Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 6710B Rockledge Dr. MSC 7004, Bethesda, MD, ...

Brian W Whitcomb

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

Abstract:
Study Question: Is physical activity (PA) associated with fecundability in women with a history of prior pregnancy loss?

Summary Answer: Higher fecundability was related to walking among overweight/obese women and to vigorous PA in women overall.

What Is Known Already: PA may influence fecundability through altered endocrine function. Studies evaluating this association have primarily utilized Internet-based recruitment and self-report for pregnancy assessment and have yielded conflicting results.

STUDY DESIGN, SIZE, Duration: This is a secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a multisite, randomized controlled trial of preconception-initiated low-dose aspirin. PARTICIPANTS/MATERIALS, SETTING,

Methods: Healthy women (n = 1214), aged 18-40 and with 1-2 prior pregnancy losses, were recruited from four US medical centers. Participants were followed for up to six menstrual cycles while attempting pregnancy and through pregnancy for those who became pregnant. Time to hCG detected pregnancy was assessed using discrete-time Cox proportional hazard models to estimate fecundability odds ratios (FOR) adjusted for covariates, accounting for left truncation and right censoring.

Main Results and the Role of Chance: The association of walking with fecundability varied significantly by BMI (P-interaction = 0.01). Among overweight/obese women, walking ≥10 min at a time was related to improved fecundability (FOR = 1.82, 95% CI: 1.19, 2.77). In adjusted models, women reporting >4 h/wk of vigorous activity had significantly higher fecundability (FOR = 1.69, 95% CI: 1.24, 2.31) compared to no vigorous activity. Associations of vigorous activity with fecundability were not significantly different by BMI (P-interaction = 0.9). Moderate activity, sitting, and International Physical Activity Questionnaire (IPAQ) categories were not associated with fecundability overall or in BMI-stratified analyses.

LIMITATIONS, Reasons for Caution: Some misclassification of PA levels as determined by the short form of the IPAQ is likely to have occurred, and may have led to non-differential misclassification of exposure in our study. Information on diet and change in BMI was not collected and may have contributed to some residual confounding in our results. The generalizability of our results may be limited as our population consisted of women with a history of one or two pregnancy losses. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide positive evidence for the benefits of PA in women attempting pregnancy, especially for walking among those with higher BMI. Further study is necessary to clarify possible mechanisms through which walking and vigorous activity might affect time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors report no conflicts of interest in this work.

Trial Registration Number: #NCT00467363.


Current and emerging treatment options for endometriosis

Abstract:
INTRODUCTION: Pharmacotherapy has a pivotal role in the management of endometriosis with long-term treatments balancing clinical efficacy (control of pain symptoms and prevention of recurrence of the disease after surgery) with an acceptable safety profile. Treatment choice is based on several factors including age and patient preference, reproductive plans, intensity of pain, severity of disease and incidence of adverse effects.

AREAS COVERED: The aim of this review is to provide the reader with a complete overview of drugs that are currently available or are under investigation for the treatment of endometriosis highlighting on-going clinical trials.

EXPERT OPINION: Almost all of the available treatment options for endometriosis suppress ovarian function and are not curative. Combined oral contraceptives and progestins are commonly administered to these patients in order to ameliorate pain symptoms. Gonadotropin-releasing hormone-agonists are prescribed when first-line therapies are ineffective, not tolerated or contraindicated. Aromatase inhibitors should be reserved only for women who are refractory to other treatments. Amongst the drugs under development, gonadotropin-releasing hormone antagonists have shown the most promising results. Presently, are a number of potential therapies currently in pre-clinical or early clinical studies which may alter treatment strategies in the future although further studies are necessary.


Vertebral Fractures and Morphometric Deformities

Fernando Rivadeneira

Departments of Internal Medicine and EpidemiologyErasmus MCRotterdamThe Netherlands

Ian Hammond

Ottawa Hospital-General Campus, Ottawa, Ontario, Canada.

Ling Oei

Departments of Internal Medicine and Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

Christopher S Kovacs

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

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Linda Probyn

Department of Medical ImagingUniversity of TorontoTorontoONCanada

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Angela M Cheung

Department of Medicine and Joint Department of Medical Imaging, Centre of Excellence in Skeletal Health Assessment, University Health NetworkUniversity of TorontoTorontoONCanada

Brian C Lentle

Department of RadiologyUniversity of British ColumbiaVancouverBCCanada

Abstract: To the Editor: We read with interest the editorial by Cummings and Eastell,1 A History of Pivotal Advances in Clinical Research in Bone and Mineral Diseases, published in a recent issue of the JBMR. In discussing such advances, they include spinal morphometry, and specifically refer to and illustrate the Genant semiquantitative (GSQ) paradigm,2 although also referring to the algorithm-based qualitative (ABQ) method3 of vertebral evaluation in the diagnosis of osteoporotic vertebral fractures (OVFs). Although in its day the GSQ method was a credible attempt at structured reporting, recent data suggest that GSQ grade 1 lesions, the most common, relate less well to bone density and fracture risk than comparable fractures diagnosed using the ABQ tool.4-6 Although morphometric methods may serve for understanding the epidemiology of osteoporotic fractures in large populations, it is much less certain that the GSQ method provides a basis for the care of individual patients. In a multidisciplinary context such as is served by this Journal, the endorsement of the GSQ method by the authors, without qualification, may well prove misleading. It is potentially invalid at the bedside and this should have been made explicit. We have observed a reluctance to give the presence of one or more vertebral fractures the importance they should be accorded because of confusion and ambiguity in the descriptive criteria and terminology used (eg, “wedging,” “deformity”) to define them. Perhaps the lack of a clear understanding of what might or might not constitute an OVF contributes to this disarray among radiologists and clinicians alike, again as noted recently by Szulc.7 Most of the many authors describing or reviewing “systems of morphometry,”8-12 such as in the current ASBMR primer,10 have cautioned that they are only to be used for epidemiological purposes. Moreover, most such reviews caution that positive findings should ideally be re-assessed by an “expert.” The danger, recognized by such constraints, is that of false-positive diagnoses from the clinical use of morphometry. In our experience, it is all too common for the iconic diagram provided by Dr. Genant to serve as a guide for the clinical evaluation of spinal images when that was not its intent. In the relevant article, Genant and colleagues2 were at pains to emphasize the importance of recognizing end-plate damage as evidence of OVF, but it has proved deceptively simple for readers to see only the diagram which Cummings and Eastell1 reproduce without noting these constraints. Historically the GSQ method was proposed as an attempt at structured diagnosis in fracture evaluation when such a concept was uncommon. Nevertheless it needs to be seen in perspective and it may have now outlived its usefulness. A great amount of admirable effort has gone into a structured understanding and diagnosis of atypical femoral fractures by the ASBMR.13 Those are, however, very rare events. Perhaps it is time to develop a comparable understanding of the much more common problem of OVF diagnosis to an extent the evidence allows. A taxonomy of such lesions is overdue. At present there are large differences in reported OVF incidence and prevalence for any given population. That fact probably reflects, at least in part, the method of diagnosis used, as much as any real insights into disease. None.


Hormonal Predictors of Abnormal Luteal Phases in Normally Cycling Women

Saman H Abdulla

Centre National de la Recherche Scientifique

Phil C Boyle

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

Abstract:
Objective: Explore potential relationships between preovulatory, periovulatory, and luteal-phase characteristics in normally cycling women.
Design: Observational study.
Setting: Eight European natural family planning clinics. Patient(s): Ninety-nine women contributing 266 menstrual cycles. Intervention(s): The participants collected first morning urine samples that were analyzed for estrone-3 glucuronide (E1G), pregnanediol-3alpha-glucuronide (PDG), follicle stimulating hormone (FSH), and luteinizing hormone (LH). The participants underwent serial ovarian ultrasound examinations. Main Outcome Measure(s): Four outcome measures were analyzed: short luteal phase, low mid-luteal phase PDG level (mPDG), normal then low luteal PDG level, low then normal luteal PDG level.

Results: A long preovulatory phase was a predictor of short luteal phase, with or without adjustment for other variables. A high periovulatory PDG level was a predictor for short luteal phase as well as normal then low luteal PDG level. A low periovulatory PDG level predicted low mPDG and low then normal luteal PDG level, with or without adjustment for other variables. A small maximum follicle predicted normal then low luteal PDG level, with or without adjustment for other variables. The relationship between small maximum follicle size and short luteal phase or small maximum follicle size and low mPDG was no longer present when the regression was adjusted for certain characteristics. A younger age at menarche and a high body mass index were both predictors of low mPDG.

Conclusion: Luteal phase abnormalities exist over a spectrum where some ovulation disorders may exist as deviations from the normal ovulatory process.This study confirms the negative impact of a small follicle size on the quality of the luteal phase. The occurrence of normal then low luteal PDG level is confirmed as a potential sign of luteal phase abnormality.


Steroid Hormones and Their Action in Women's Brains: The Importance of Hormonal  Balance

María I. Alliende

Reproductive Health Research Institute Santiago, Chile.

Felipe Serrano

Biomedical Division, Reproductive Health Research Institute (RHRI), Santiago, Chile

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: Sex hormones significantly impact women's lives. Throughout the different stages of life, from menarche to menopause and all stages in between, women experience dramatic fluctuations in the levels of progesterone and estradiol, among other hormones. These fluctuations affect the body as a whole, including the central nervous system (CNS). In the CNS, sex hormones act via steroid receptors. They also have an effect on different neurotransmitters such as GABA, serotonin, dopamine, and glutamate. Additionally, studies show that sex hormones and their metabolites influence brain areas that regulate mood, behavior, and cognitive abilities. This review emphasizes the benefits a proper hormonal balance during the different stages of life has in the CNS. To achieve this goal, it is essential that hormone levels are evaluated considering a woman's age and ovulatory status, so that a correct diagnosis and treatment can be made. Knowledge of steroid hormone activity in the brain will give women and health providers an important tool for improving their health and well-being.


Efficacy of acupuncture on pelvic pain in patients with endometriosis: study protocol for a randomized, single-blind, multi-center, placebo-controlled trial

Abstract:
BACKGROUND: Endometriosis is a chronic gynecological disease that is characterized by the presence of endometrial tissue outside the uterine cavity. The main symptoms include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. These symptoms impair the lives of most of the women suffering from the disease. Surgical resection of endometriotic lesions is an effective means of treating dysmenorrhea, but the risk of recurrence is high. Western medicine has limited use for treating it due to side effects and ineffectiveness. The purpose of this study is to verify the effectiveness and safety of acupuncture.

METHODS/DESIGN: This trial will be carried out in four parts. A total of 106 eligible patients with pelvic pain related to endometriosis will be randomly assigned into two groups, in a 1:1 ratio, as the treatment group or the control group. The participants assigned to the treatment group will be treated with acupuncture treatment at Guanyuan (CV4), Sanyinjiao (SP6), Taichong (LR3), Zhaohai (KI6) and Qichong (ST30) while the control group will receive acupuncture at non-acupoints. The trial will include three menstrual cycles of treatment and three menstrual cycles of follow-up. The primary outcome is pelvic pain that will be assessed by means of a 10-cm visual analog scale (VAS). At each stage, we will evaluate the safety of the acupuncture treatment.

DISCUSSION: The study will compare the effectiveness and safety of acupuncture with comfort needles on pelvic pain related to endometriosis in the hope of providing significant evidence for using acupuncture on pelvic pain related to endometriosis.

TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03125304 . Registered on 30 April 2017.


Women's Mid-Life Night Sweats and 2-Year Bone Mineral Density Changes: A  Prospective, Observational Population-Based Investigation from the Canadian  Multicentre Osteoporosis Study (CaMos)

Marsha M Pinto

Osteoporosis Program, University Health Network, Toronto, ON M5G 2C4, Canada. marshapinto@gmail.com.

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Women's hot flushes and night sweats, collectively called vasomotor symptoms (VMS), are maximal (79%) in late perimenopause. The evidence describing whether VMS are associated with loss of areal bone mineral density (BMD) is mixed. We examined baseline and 2-year data for 1570 randomly selected women aged 43⁻63 in the Canadian Multicentre Osteoporosis Study (CaMos), a prospective Canada-wide study; we used linear regression to assess the relationship of night sweats (VMSn) with BMD and its changes. Clinically important VMSn occurred for 12.2%. Women with VMSn were slightly younger (54.5 vs. 55.3 years, p = 0.02) and less likely to use sex steroid therapies (39.8% vs. 51.4%, p < 0.05). BMD at the lumbar spine (L1-4), femoral neck (FN) and total hip (TH) were similar between those with/without VMSn. In adjusted models, we did not find a significant association between VMSn and 2-year change in L1-4, FN and TH BMD. Age, reproductive status, weight, sex steroid therapy and smoking status were associated with 2-year change in BMD. Incident fractures over 2 years also did not differ by VMSn. Our analyses were restricted to VMSn and may not truly capture the relationship between VMS and BMD. Additional research involving VMS, bone loss and fracture incidence is needed.

International Journal of Environmental Research and Public Health


Combined hormonal contraceptives use and bone mineral density changes in  adolescent and young women in a prospective population-based Canada-wide  observational study

Tatjana S Brajic

Centre for Menstrual Cycle and Ovulation Research, Medicine/Endocrinology, University of British Columbia, Vancouver, B.C., Canada.

Christopher S Kovacs

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

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract:
Objectives: To assess combined hormonal contraceptives (CHC) use and adolescent women's peak areal bone mineral density (BMD) accrual.

Methods: We enrolled 527 randomly selected women across Canada (2004-6) divided by age into adolescents (16-19) and young adults (20-24) and by CHC use to ever (E-CHC)/never (N-CHC) users. At baseline and year 2 we measured height, weight, and BMD at lumbar spine (L1-4), femoral neck, and total hip sites. Interviewer-administered questionnaires addressed menarche age, cigarette and alcohol use, calcium/vitamin D intakes, physical activity and estrogen dose (≤30/>30 micrograms). Linear regression models examined associations of CHC use with 2-year BMD change adjusted for bone-related variables.

Results: Of 307 women with complete data, 229 (75%) used CHC. N-CHC adolescents gained significantly more unadjusted total hip BMD +0.012 g/cm(2)/2-y (95% C.I.: 0.001, 0.023) with similar trends at all sites. N-CHC adolescents tended to have greater adjusted femoral neck BMD gain: mean difference +0.009 g/cm(2) (95% CI: -0.002; 0.021). In young women N-CHC, however, adjusted femoral neck BMD decreased significantly more -0.021 g/cm(2) (95%CI: -0.006; -0.036) with similar trends at other sites. BMD changes were unrelated to estrogen dose and age at starting CHC.

Conclusions: Adolescent CHC users in a random population demonstrated less hip region peak BMD accrual than non-users. This requires randomized control trial confirmation.

Journal of Musculoskeletal & Neuronal Interactions


Progesterone and women's anxiety across the menstrual cycle

Abstract: Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three phases of the menstrual cycle: follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person association emerged: women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety.


Adult Premenopausal Bone Health Related to Reproductive  Characteristics-Population-Based Data from the Canadian Multicentre Osteoporosis  Study (CaMos)

Abstract: Amenorrhea is important for women's bone health. However, few have reported reproductive, anthropometric (body mass index [BMI], height) and bone health (areal bone mineral density [BMD], prevalent fractures) in a population-based study. The purposes of this cross-sectional study of women in the randomly-selected Canadian Multicentre Osteoporosis Study (CaMos) population were: (1) to describe reproductive, demographic, anthropometric and lifestyle variables; and (2) in menstruating women, to relate reproductive and other variables to BMD at the lumbar spine (L1-4, LS), femoral neck (FN) and total hip (TH) sites and to prevalent fragility fractures. This study describes the reproductive characteristics of 1532 women aged 30⁻60 years. BMD relationships with reproductive and other variables were described in the 499 menstruating women. Mean menarche age was 12.8 years, 96% of women were parous and 95% had used combined hormonal contraceptives (CHC). Infertility was reported by 9%, androgen excess by 13%, amenorrhea by 8% and nulliparity by 4%. LS BMD was negatively associated with amenorrhea and androgen excess and positively related to current BMI and height. A later age at menarche negatively related to FN BMD. BMI and height were strongly related to BMD at all sites. Prevalent fragility fractures were significantly associated with quartiles of both LS and TH BMD.