Use of menstruation and fertility app trackers: a scoping review of the evidence

Abstract:
Introduction: There has been a phenomenal worldwide increase in the development and use of mobile health applications (mHealth apps) that monitor menstruation and fertility. Critics argue that many of the apps are inaccurate and lack evidence from either clinical trials or user experience. The aim of this scoping review is to provide an overview of the research literature on mHealth apps that track menstruation and fertility.

Methods: This project followed the PRISMA Extension for Scoping Reviews. The ACM, CINAHL, Google Scholar, PubMed and Scopus databases were searched for material published between 1 January 2010 and 30 April 2019. Data summary and synthesis were used to chart and analyse the data.

Results: In total 654 records were reviewed. Subsequently, 135 duplicate records and 501 records that did not meet the inclusion criteria were removed. Eighteen records from 13 countries form the basis of this review. The papers reviewed cover a variety of disciplinary and methodological frameworks. Three main themes were identified: fertility and reproductive health tracking, pregnancy planning, and pregnancy prevention.

Conclusions: Motivations for fertility app use are varied, overlap and change over time, although women want apps that are accurate and evidence-based regardless of whether they are tracking their fertility, planning a pregnancy or using the app as a form of contraception. There is a lack of critical debate and engagement in the development, evaluation, usage and regulation of fertility and menstruation apps. The paucity of evidence-based research and absence of fertility, health professionals and users in studies is raised.


Increased risk of eating disorders in women with polycystic ovary syndrome: a case-control study

Nuray Bozkurt

Department of Obstetrics and Gynecology, Gazi University, Ankara, Turkey.

Abstract: Data on eating disorders in women with PCOS is insufficient. The objective of this case study was to examine the hypothesis that women with PCOS exhibit more impaired eating than healthy women. Women diagnosed with PCOS under the 2003 Rotterdam Diagnostic Criteria (n = 40) were compared with a healthy control group (n = 40). The groups also were divided into two as normal body weight and overweight/obese. The Eating Disorders Assessment Questionnaire (EDE-Q) and the Three Factor Eating Questionnaire (TFEQ-R21), were completed by all participants in order to evaluate eating behaviors in addition to eating disorders. Among the overweight/obese group, the average total and subscale scores of the EDE-Q as well as the total and sub-factor scores of the TFEQ-R21 were higher in women with PCOS compared to controls (p < .05). However, this statistically significant result was not shown among the women with normal weight (p > .05). In comparison to the controls, the PCOS women displayed higher values of the tool scores indicating abnormal restraint eating, body shape concern and weight concern subscale scores (p < .05). This result suggests that the evaluation of eating disorders should be added to routine screening and the monitoring of women with PCOS.


Vitamin D and Male Fertility: An Updated Review

Maria Elisabetta Coccia

Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy

Abstract: To date, the key role of vitamin D in male reproductive system has been suggested, since the expression of vitamin D receptors and metabolizing enzymes was demonstrated in the testis and spermatozoa. Nevertheless, a general consensus about the role of vitamin D in male fertility is still debated. The aim of this review is to provide an updated systematic revision of the current available literature, discussing the experimental and clinical evidence on the role of vitamin D in the regulation of testis hormone production, seminal parameters and male fertility. The consequences of vitamin D deficiency on serum levels of testicular hormones have been analysed by several observational and interventional studies, with controversial results. Equally, the experimental researches not were able to state a certain relationship between vitamin D status and testis hormone production. Possible bias, including age, body mass index, and baseline vitamin D status justified the differences among studies. As well as concerning the effect of vitamin D on semen parameters, most of the studies agreed in the possibility that vitamin D might have a positive effect on human male fertility potential, particularly through better sperm motility. Regarding pregnancy outcomes, normal level of vitamin D seems to be related to better pregnancies. However, all the previous studies displayed a wide heterogeneity in study design, population, methodology, and cut off values used for the evaluation of vitamin D status. Future studies are needed to better clarify the exact role of vitamin D on hormonal and seminal panel in both fertile and infertile men.


A Mixed-Methods Assessment of Health Care Providers' Knowledge, Attitudes, and Practices Around Fertility Awareness-Based Methods in Title X Clinics in the United States

Sandra Webb

Government of Western Australia Department of Health

Abstract: Objective: To understand how Title X providers currently engage with fertility awareness-based methods (FABMs) for pregnancy prevention in Title X clinics across the United States. Materials and Methods: We developed a survey to assess knowledge of fertility for purposes of pregnancy prevention, attitudes toward FABMs use for pregnancy prevention, and practices when patients request FABMs for pregnancy prevention. Results: In total, 329 participants who met all inclusion criteria completed the survey. Respondents were generally highly knowledgeable on fertility, felt neutrally toward FABMs or thought they were a nonviable option for most women, and were likely to respond to patient requests for FABMs for pregnancy prevention by providing information. Qualitative responses included several barriers to provision of FABMs for pregnancy prevention and few successes to provision. Conclusions: Fertility knowledge and discussion of specific methods increased with the number of methods included in the clinic's written materials or with the number of different FABMs someone at that clinic had been trained on. Significant clinician or administrative barriers may exist to offering FABMs to patients. Incorporating up-to-date information on a range of FABMs-rather than treating them as one method-into contraceptive counseling represents an opportunity to increase the contraceptive offering for clients who want them, leading to increased patient satisfaction and successful family planning outcomes.


The impact of disturbances in natural conception cycles

Abstract:
PURPOSE: Many physicians and other healthcare professionals are often asked questions on interfering factors for conception by couples with a desire for children. Such possible disturbances include, for example, the very common minor diseases, stress and also sexual intercourse during the suspected implantation period. Non-scientifically based statements about disturbances in conception cycles, as found in many layman publications and on the internet, can strongly unsettle couples with a desire for children and force them into corset of rules of conduct. Therefore, a systematic scientific evaluation of the impact of disturbances on conception is urgently needed.

METHODS: A search for possible disturbances in natural conception cycles together with up to three of the respective pre-cycles in a large cycle database from users of the symptothermal method of natural family planning in Germany was performed. Disturbances were qualified by scientific panel decision and analysed statistically with their effects on the chances of spontaneous conception. Mixed logistical regression models and survival time analyses were used.

RESULTS: A total of 237 women with a total of 747 cycles could be included in the analysis. In 61% of all 237 conception cycles, disturbances occurred. The statistical analysis shows that disturbances in natural conception cycles unexpectedly increase the likelihood of pregnancy by an overall factor of 1.32 (95% CI 1.04-1.70). Sexual intercourse in the window of implantation does not decrease the chances of conception. Relaxation states at the time of ovulation and/or during the implantation period have no representable effect and do not increase the chance of pregnancy.

CONCLUSIONS: Couples trying to conceive should at least be informed that disturbances in conception cycles, such as minor diseases, stress or sexual intercourse during the implantation period do not interfere with conception. Relaxation has no effect in favour of success. This takes away the guilty feeling of couples, fearing that they possibly did something wrong in cycles without the desired pregnancy.


Phthalates in preschool children’s clothing manufactured in seven Asian countries: Occurrence, profiles and potential health risks

Abstract: Phthalates could be introduced into clothing as chemical additives or impurities, becoming a potential source of human exposure. We measured the concentrations of 15 phthalates in new preschool children's clothing manufactured in seven Asian countries. Phthalates were prevalent in all samples, and total concentrations were 2.92-223 μg/g, indicating a moderate contamination level. Bis(2-ethylhexyl) phthalate, di(isobutyl) phthalate and di-n-butyl phthalate were the most abundant phthalates measured, representing a median of 48.5 %, 13.6 % and 13.4 % of the total concentrations, respectively. Total concentrations did not differ significantly by country of manufacture, while the concentrations of individual phthalates and their composition profiles varied widely. We also found differing phthalate levels by item type, fabric composition, and color. Under the assumed two exposure scenarios, the median of summed dermal exposure doses of six phthalate were 539 and 950 ng/kg of body weight per day, respectively. When children wore trousers, long-sleeved shirts, briefs and socks at the same time, the reproductive risks exceeded acceptable level, although the carcinogenic risk of DEHP was low. Our results suggested that new clothing is an important route of phthalate exposure to preschool children. More research is required to investigate the contaminations and associated with risks in child clothing.


Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case-Control Study in the Danish National Birth Cohort

Abstract:
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied.

METHODS: Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted.

RESULTS: We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women.

CONCLUSION: Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202.


Oxaloacetate reduces emotional symptoms in premenstrual syndrome (PMS): results  of a placebo-controlled, cross-over clinical trial

John Humiston

The Center for Health and Wellbeing, San Diego, CA, USA.

Lisa Tully

Nutritional Supplements Division, Energy Medicine Research Institute, Boulder, CO, USA.

Abstract:
Objective: Premenstrual syndrome (PMS) affects millions of women. While over-the-counter products have helped with the physical symptoms of PMS, emotional symptoms have been less well supported. The objective of this trial was to measure the effect of an oxaloacetate/vitamin C combination on the major emotional symptoms of PMS, including depression, anxiety, perceived stress, aggression, and suicidal ideation.

Methods: Forty-eight women experiencing PMS completed a baseline survey comprising the Beck's Depression Inventory, Cohen Perceived Stress Scale, Generalized Anxiety Disorder Test, and Buss-Perry Aggression Questionnaire. After baseline measurements, participants were randomly assigned to take either 2 capsules of 100 mg oxaloacetate/150 mg ascorbic acid, or 2 capsules of rice flour (placebo) for their entire menstrual cycle. At menstruation, the women completed the 4 surveys again. The women then switched capsules in a cross-over design and continued the study for an additional menstrual cycle. The final assessment was repeated at menstruation. Statistical analysis of the 4 surveys was performed to examine efficacy.

Results: Oxaloacetate/vitamin C supplementation during PMS significantly improved depression, perceived stress, anxiety, aggression, and suicidal ideation. The mean improvement in depression was 54.1%, 35.8% for perceived stress, 51.43% for generalized anxiety, and 17.8% for aggression. Suicidal ideation was reduced by 47.9%. All results were highly significant.

Conclusion: A combination of oxaloacetate and vitamin C supplementation helped to alleviate depression, anxiety, perceived stress, aggression, and suicidal ideation symptoms associated with PMS.

Trial Registration: ClinicalTrials.gov Identifier: NCT03509714.


Naltrexone

Naltrexone

Abstract: Naltrexone is a synthetic opioid antagonist used in prevention of relapse of opiate addiction and alcoholism. Naltrexone has been associated with low rates of serum enzyme elevations during therapy and with rare instances of clinically apparent liver injury.

LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]


Fertility awareness-based methods of family planning

Abstract: Fertility awareness-based methods (FABMs) of family planning involve monitoring various signs and symptoms of fertility during the menstrual cycle to identify the "fertile window," or the days of the cycle when unprotected intercourse is most likely to result in pregnancy. Signs and symptoms include menstrual cycle length, basal body temperature, urinary hormone measurements, and/or cervical fluid and may be used alone or in combination. Fertility signs reflect both physiological changes during the menstrual cycle and the life cycle of the ovum and sperm. Women learn to observe or measure and interpret these signs according to the instructions of their chosen FABM and avoid unprotected intercourse on fertile days. FABMs are appropriate for those who choose to use them, are able and willing to observe one or more fertility signs, and are in relationships that support the use of a coitus-related method such as a condom or abstaining from intercourse on fertile days.

Best Practice & Research. Clinical Obstetrics & Gynaecology


Genitourinary disease risks among ovarian cancer survivors in a population-based  cohort study

Chun-Pin Esther Chang

Department of Family and Preventive Medicine, Office of Cooperative Reproductive Health, Division of Public Health, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, United...

Chun-Pin Chang

Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, and Huntsman Cancer Institute, Salt Lake City, UT, United States of America.

Jennifer Doherty

Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT, United States of America; Department of Population Health Sciences, University of Utah School of ...

Abstract:
Objective: While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort.

Methods: We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis.

Results: Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis.

Conclusions: Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.


Physical activity and incidence of subclinical and clinical pregnancy loss: a secondary analysis in the effects of aspirin in gestation and reproduction randomized trial

Lindsey M Russo

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

Brian W Whitcomb

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

Sunni L Mumford

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Objective: To estimate the association between physical activity and risk of subclinical and clinical pregnancy loss among women with a history of pregnancy loss.
Design: Prospective cohort study as a secondary analysis of the Effects of Aspirin in Gestation and Reproduction randomized controlled trial of preconception-initiated low-dose aspirin among women with one or two prior pregnancy losses.
Setting: Four U.S. clinical centers, 2007-2011. PATIENT(S): Women with confirmed pregnancy (n = 785) as determined from hCG testing in longitudinally collected biospecimens. MAIN OUTCOME MEASURE(S): Subclinical loss of pregnancy detected only by hCG testing and clinically recognized loss. RESULT(S): Among 785 women (mean [SD] age, 28.7 [4.6] years) with an hCG-confirmed pregnancy, 188 (23.9%) experienced pregnancy loss. In multivariable models adjusted for confounders, compared with the first tertile of physical activity (median = 7.7 metabolic equivalent of task hours/week), there was a roughly twofold higher risk of subclinical loss in the second (risk ratio = 2.06; 95% confidence interval, 1.03-4.14) and third tertiles (risk ratio = 1.92; 95% confidence interval, 0.94-3.90), with median metabolic equivalent of task hours/week of 27.8 and 95.7, respectively. No relations were observed between physical activity and clinically recognized loss. CONCLUSION(S): Risk related to physical activity is different for pregnancy failure close to the time of implantation compared with that for later, clinical pregnancy loss. Higher physical activity levels were associated with an elevated risk of subclinical loss (i.e., pregnancies detected only by hCG, n = 55); however, no relationship was observed with clinically recognized loss. Further work is required to confirm these findings, assess generalizability to women without prior losses, and evaluate mechanisms. Ethical Approval: Each participating center's Institutional Review Board approved the study, and participants provided written informed consent. The trial was registered on ClinicalTrials.gov (NCT00467363), and a Data Safety and Monitoring Board provided oversight. OBJETIVO:: Estimar la asociación entre la actividad física y el riesgo de pèrdida gestacional subclínica y clínica entre mujeres con historia de pèrdida gestacional. DISEÑO:: Estudio prospectivo de cohortes como análisis secundario de un estudio aleatorizado de los efectos de aspirina en la gestación y la reproducción, utilizando bajas dosis de aspirina desde la preconcepción entre mujeres con una o dos pèrdidas gestacionales previas. LUGAR:: Cuatro clínicas en Estados Unidos, entre 2007–2011. PACIENTES:: Mujeres con embarazo confirmado (n= 785) determinado por pruebas de hCG en muestras biológicas recogidas longitudinalmente. PRINCIPALES MEDIDAS DE RESULTADO(S):: Pérdida gestacional subclínica detectada sólo por la prueba de hCG y la reconocida clínicamente. RESULTADOS:: Entre 785 mujeres (media de edad [Deviación standard], 28,7 [4,6] años) con una gestación confirmada con hCG, 188 (23.9%) que tuvieron pérdida gestacional. En un modelo multivariante ajustado para factores de confusión comparado con el primer tercil de actividad física (media= 7,7 equivalentes metabólicos de trabajo horas/semana) hubo un riesgo bruto dos veces mayor de pérdida subclínica en el segundo (relación de riesgo= 2,06; Intervalo de confianza 95%, 1,03–4,14) y el tercer tercil (Relación de riesgo = 1,92 Intervalo de confianza 95%, 0,94–3,9) con una media metabólica equivalente de trabajo horas/semana de 27,8 y 95,7 respectivamente. No hubo relación entre actividad física y pérdidas gestacionales clínicas. CONCLUSIONES:: El riesgo asociado a actividad física es diferente para fallo gestacional próximo al momento de la implantación comparado con el más tardío de pérdida gestacional clínica. Niveles mayores de actividad física estuvieron asociados con un riesgo elevado de pérdida subclínica (por ejemplo, embarazos detectados solo por hCG, n=55); sin embargo, no se observó relación con pérdida clínicamente reconocida. Se necesitan más trabajos para confirmar estos hallazgos, evaluando de forma general mujeres sin pérdidas gestacionales previas, y evaluar sus mecanismos. APROBACIÓN ÉTICA:: El comité de revisión institucional de cada centro participante aprobó el estudio y los participantes dieron por escrito su consentimiento informado. El ensayo fue registrado en ClinicalTrial.gov (NCT00467363), y el comité de seguridad y monitorización de los datos dio su aprobación


Menstrual bleeding, cycle length, and follicular and luteal phase lengths in women without known subfertility: A pooled analysis of three cohorts

Abstract:
BACKGROUND: There is variability between women for days of menstrual bleeding, cycle lengths, follicular phase lengths, and luteal phase lengths, related to age and parity.

OBJECTIVE: To describe total cycle length; anovulatory cycles; follicular and luteal phase lengths; and days and intensity of menstrual and non-menstrual bleeding in women without known subfertility over the course of 1 year.

METHODS: 581 women (3,324 cycles) with no known subfertility (18-40 years of age) were followed for up to 1 year. Women recorded vaginal bleeding and mucus discharge daily. We used the peak day of cervical mucus as the estimated day of ovulation and the last day of the follicular phase. We used generalised linear mixed models stratified by age and parity to describe menstrual cycle parameters.

RESULTS: The majority of women were <30 years of age (74.5%), non-Hispanic White (88.6%), and nulliparous (70.4%). The mean menses length was 6.2 (1.5) days, median 6; cycle length 30.3 (6.7) days, median 29; follicular phase length 18.5 (6.5) days, median 17; and luteal phase length 11.7 (2.8) days, median 12. Nulliparous women aged ≥30 years vs nulliparous women aged <30 had shorter cycles (29.2 days, 95% confidence interval (CI) 27.8, 30.7 vs 31.5 days, 95% CI 30.8, 32.2) and shorter follicular phases (17.6 days, 95% CI 16.2, 18.9 vs 19.6 days, 95% CI 18.9, 20.2). Among all women, within-woman differences between the longest and shortest menses length >3 days, total cycle length >7 days, follicular phase >7 days, and luteal phase >3 days were found in 11.6%, 43.0%, 41.7%, and 58.8% of women, respectively.

CONCLUSIONS: Our findings confirm variability between women of menstrual cycle parameters related to age and parity, and also highlight within-woman variability in the follicular and luteal phases.


Comparison of woman-picked, expert-picked, and computer-picked Peak Day of cervical mucus with blinded urine luteinising hormone surge for concurrent identification of ovulation

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.

Abstract:
BACKGROUND: Previous research has demonstrated that women instructed in fertility awareness methods can identify the Peak Day of cervical mucus discharge for each menstrual cycle, and the Peak Day has high agreement with other indicators of the day of ovulation. However, previous studies enrolled experienced users of fertility awareness methods or were not fully blinded.

OBJECTIVE: To assess the agreement between cervical mucus Peak Day identified by fertile women without prior experience on assessing cervical mucus discharge with the estimated day of ovulation (1 day after urine luteinising hormone surge).

METHODS: This study is a secondary analysis of data from a randomised trial of the Creighton Model FertilityCare(TM) System (CrM), conducted 2003-2006, for women trying to conceive. Women who had no prior experience tracking cervical mucus recorded vulvar observations daily using a standardised assessment of mucus characteristics for up to seven menstrual cycles. Four approaches were used to identify the Peak Day. The referent day was defined as one day after the first identified day of luteinising hormone (LH) surge in the urine, assessed blindly. The percentage of agreement between the Peak Day and the referent day of ovulation was calculated.

RESULTS: Fifty-seven women with 187 complete cycles were included. A Peak Day was identified in 117 (63%) cycles by women, 185 (99%) cycles by experts, and 187 (100%) by computer algorithm. The woman-picked Peak Day was the same as the referent day in 25% of 117 cycles, within ±1 day in 58% of cycles, ±2 days in 84%, ±3 days in 87%, and ±4 days in 92%. The ±1 day and ± 4 days' agreement was 50% and 90% for the expert-picked and 47% and 87% for the computer-picked Peak Day, respectively.

CONCLUSIONS: Women's daily tracking of cervical mucus is a low-cost alternative for identifying the estimated day of ovulation.


Experiences of health after dietary changes in endometriosis: a qualitative interview study

Abstract:
OBJECTIVES: Endometriosis is a chronic disease with no known cure. Persons affected by this disease often use complementary therapies such as dietary changes to reduce their symptoms, and so it is important to investigate whether and how these therapies affect endometriosis symptoms. The aim of this study was to explore how persons with endometriosis experienced their health after dietary changes.

DESIGN: Semi-structured qualitative interviews were conducted with 12 persons with endometriosis who had made individual dietary changes aimed at decreasing their endometriosis symptoms. The interviews were recorded and transcribed verbatim, and analysed using thematic analysis.

SETTING: Region Västra Götaland and the estern part of Central Sweden, Sweden.

PARTICIPANTS: Twelve persons with endometriosis aged 28 to 44 were recruited from two Swedish endometriosis support forums on the Internet.

RESULTS: Participants experienced an increase in well-being and a decrease in symptoms following their dietary and lifestyle changes. They also felt that the dietary changes led to increased energy levels and a deeper understanding of how they could affect their health by listening to their body's reactions. The participants understood that they could influence their symptoms through lifestyle changes. Support from family and friends was important in implementing and sustaining the dietary changes. However, the participants stressed the lack of support from healthcare professionals.

CONCLUSIONS: This study contributes to filling the knowledge gap about dietary strategies in endometriosis and lifestyle change as a method of alleviating suffering and increasing well-being. An important finding is that the participants experienced decreased symptoms and increased well-being after adopting an individually-adapted diet. Healthcare professionals should take their patients' knowledge and experience into consideration, and allow patients to participate in their own care. Further research is necessary to give evidenced-based dietary advices in endometriosis.


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

Abstract:
---
title: "ART in Europe, 2015: results generated from European registries by ESHRE"
source_file: "eshre-eim-2015-source.pdf"
pages: 17
extracted_date: "2026-04-24"
figures_extracted: 3
tables_extracted: 5
review_flags: 2
review_flags_resolved: 2
review_flags_corrected: 1
review_flags_confirmed: 0
review_flags_unreadable: 1
doi: "10.1093/hropen/hoz038"
journal: "Human Reproduction Open"
year: 2020
authors: "De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T, Scaravelli G, Smeenk J, Vidakovic S, Goossens V"
---

Human Reproduction Open, pp. 1–17, 2020
doi:10.1093/hropen/hoz038

**human reproduction open — ESHRE PAGES**


Mortality from infancy to adolescence in singleton children conceived from  assisted reproductive techniques versus naturally conceived singletons in Sweden

Frida E Lundberg

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Abstract:
Objective: To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons.
Design: Nationwide prospective study.
Setting: Sweden. PATIENT(S): All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including in vitro fertilization with and without intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Infant (<1 year) and childhood (1-18 years) mortality. RESULT(S): Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. CONCLUSION(S): Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.


Oral contraceptives use and risk of cervical cancer-A systematic review & meta-analysis

Satyanarayana Labani

National Institute of Cancer Prevention and Research

Abstract:
Background: Role of Oral Contraceptive (OC) as a risk factor for cervical cancer remained controversial and unclear.

Objective: To evaluate risk of cervical cancer in OC users and non-users through a comprehensive systematic review. Search Strategy: Literature search conducted in databases from January 1990 till August 2019 using various search terms. Selection Criteria: Primary research studies that evaluated and assessed the association of OC use with cervical cancer with study design of case control or cohort types published in English language. Data Collection and Analysis: PRISMA guided review was done by two independent researchers. Effect size estimated by pooled Odds ratio with 95 % Confidence Interval (CI) in random effect models on OC pill use for the risk of cervical cancer.

Results: Review included 19 studies. Overall risk of invasive cancer on OC use was found to be significant with unknown status of HPV OR (95 % CI) as 1.51 (1.35, 1.68) and for unknown HPV as 1.66 (1.24, 2.21). Adenocarcinoma, squamous cell carcinoma and carcinoma in situ had significant association with OR (95 % CI) of 1.77 (1.4, 2.24), 1.29 (1.18, 1.42) and 1.7 (1.18, 2.44) respectively.

Conclusion: OC pills use had a definite associated risk for developing cervical cancer specially for Adenocarcinoma and longer duration of OC pills use.


Combining Frailty and Trabecular Bone Score Did Not Improve Predictive Accuracy in Risk of Major Osteoporotic Fractures

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Mitchell Levine

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Jie Zeng

Guangdong Provincial Hospital of Traditional Chinese Medicine

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

for the Canadian Multicentre Osteoporosis Study (CaMos) Research Group

Christopher S Kovacs

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

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Abstract: It is recognized that the trabecular bone score (TBS) provides skeletal information, and frailty measurement is significantly associated with increased risks of adverse health outcomes. Given the suboptimal predictive power in fracture risk assessment tools, we aimed to evaluate the combination of frailty and TBS regarding predictive accuracy for risk of major osteoporotic fracture (MOF). Data from the prospective longitudinal study of CaMos (Canadian Multicentre Osteoporosis Study) were used for this study. TBS values were estimated using lumbar spine (L1 to L4 ) dual-energy X-ray absorptiometry (DXA) images; frailty was evaluated by a frailty index (FI) of deficit accumulation. Outcome was time to first incident MOF during the follow-up. We used the Harrell's C-index to compare the model predictive accuracy. The Akaike information criterion, likelihood ratio test, and net reclassification improvement (NRI) were used to compare model performances between the model combining frailty and TBS (subsequently called "FI + TBS"), FI-alone, and TBS-alone models. We included 2730 participants (mean age 69 years; 70% women) for analyses (mean follow-up 7.5 years). There were 243 (8.90%) MOFs observed during follow-up. Participants with MOF had significantly higher FI (0.24 versus 0.20) and lower TBS (1.231 versus 1.285) than those without MOF. FI and TBS were significantly related with MOF risk in the model adjusted for FRAX with bone mineral density (BMD) and other covariates: hazard ratio (HR) = 1.26 (95% confidence interval [CI] 1.11-1.43) for per-SD increase in FI; HR = 1.38 (95% CI 1.21-1.59) for per-SD decrease in TBS; and these associations showed negligible attenuation (HR = 1.24 for per-SD increase in FI, and 1.35 for per-SD decrease in TBS) when combined in the same model. Although the model FI + TBS was a better fit to the data than FI-alone and TBS-alone, only minimal and nonsignificant enhancement of discrimination and NRI were observed in FI + TBS. To conclude, frailty and TBS are significantly and independently related to MOF risk. Larger studies are warranted to determine whether combining frailty and TBS can yield improved predictive accuracy for MOF risk.


Inflammatory Markers in Dysmenorrhea and Therapeutic Options

Magdalena Emilia Grzybowska

Department of Gynecology, Gynecologic Oncology and Gynecologic Endocrinology, Medical University of Gdańsk, Smoluchowskiego 17, 80-214 Gdańsk, Poland

Abstract: Dysmenorrhea often significantly reduces the quality of women's life and is still an important public health problem. Despite numerous studies, the pathomechanism of dysmenorrhea is not fully understood. Previous research indicates the complexity of biochemical reactions between the endocrine, vascular, and immune systems. Prostaglandins play a major role in the pathomechanism of dysmenorrhea. In contrast, cytokines and other proinflammatory factors in primary dysmenorrhea are less studied. In addition to the applied pharmacotherapy, more and more studies proving the effectiveness of non-pharmacological methods appear. Therefore, the present work contains a review of the latest research concerning factors involved in dysmenorrhea, as well as therapeutic options. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual gynecology, physiotherapy journals and books.

International journal of environmental research and public health


Adjuvant treatment strategies in ovarian stimulation for poor responders  undergoing IVF: a systematic review and network meta-analysis

Hefeng Huang

International Peace Maternity & Child Health Hospital

Peter C K Leung

Department of Obstetrics and Gynaecology, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.

Abstract:
Background: Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. OBJECTIVE AND

Rationale: The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. SEARCH

Methods: Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217).

Outcomes: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). WIDER Implications: For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.


Laparoscopic ovarian drilling for ovulation induction in women with anovulatory polycystic ovary syndrome

Jacques Brown

Department of MedicineLaval UniversityQuebec CityQCCanada

Abstract:
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition affecting 8% to 13% of reproductive-aged women. In the past clomiphene citrate (CC) used to be the first-line treatment in women with PCOS. Ovulation induction with letrozole should be the first-line treatment according to new guidelines, but the use of letrozole is off-label. Consequently, CC is still commonly used. Approximately 20% of women on CC do not ovulate. Women who are CC-resistant can be treated with gonadotrophins or other medical ovulation-induction agents. These medications are not always successful, can be time-consuming and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Laparoscopic ovarian drilling (LOD) is a surgical alternative to medical treatment. There are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions.

OBJECTIVES: To evaluate the effectiveness and safety of LOD with or without medical ovulation induction compared with medical ovulation induction alone for women with anovulatory polycystic PCOS and CC-resistance.

SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 8 October 2019, together with reference checking and contact with study authors and experts in the field to identify additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with anovulatory PCOS and CC resistance who underwent LOD with or without medical ovulation induction versus medical ovulation induction alone, LOD with assisted reproductive technologies (ART) versus ART, LOD with second-look laparoscopy versus expectant management, or different techniques of LOD.

DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, extracted data and evaluated the quality of the evidence using the GRADE method. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS), ovulation, costs, and quality of life were secondary outcomes.

MAIN RESULTS: This updated review includes 38 trials (3326 women). The evidence was very low- to moderate-quality; the main limitations were due to poor reporting of study methods, with downgrading for risks of bias (randomisation and allocation concealment) and lack of blinding. Laparoscopic ovarian drilling with or without medical ovulation induction versus medical ovulation induction alone Pooled results suggest LOD may decrease live birth slightly when compared with medical ovulation induction alone (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.54 to 0.92; 9 studies, 1015 women; I2 = 0%; low-quality evidence). The evidence suggest that if the chance of live birth following medical ovulation induction alone is 42%, the chance following LOD would be between 28% and 40%. The sensitivity analysis restricted to only RCTs with low risk of selection bias suggested there is uncertainty whether there is a difference between the treatments (OR 0.90, 95% CI 0.59 to 1.36; 4 studies, 415 women; I2 = 0%, low-quality evidence). LOD probably reduces multiple pregnancy rates (Peto OR 0.34, 95% CI 0.18 to 0.66; 14 studies, 1161 women; I2 = 2%; moderate-quality evidence). This suggests that if we assume the risk of multiple pregnancy following medical ovulation induction is 5.0%, the risk following LOD would be between 0.9% and 3.4%. Restricting to RCTs that followed women for six months after LOD and six cycles of ovulation induction only, the results for live birth were consistent with the main analysis. There may be little or no difference between the treatments for the likelihood of a clinical pregnancy (OR 0.86, 95% CI 0.72 to 1.03; 21 studies, 2016 women; I2 = 19%; low-quality evidence). There is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage (OR 1.11, 95% CI 0.78 to 1.59; 19 studies, 1909 women; I2 = 0%; low-quality evidence). OHSS was a very rare event. LOD may reduce OHSS (Peto OR 0.25, 95% CI 0.07 to 0.91; 8 studies, 722 women; I2 = 0%; low-quality evidence). Unilateral LOD versus bilateral LOD Due to the small sample size, the quality of evidence is insufficient to justify a conclusion on live birth (OR 0.83, 95% CI 0.24 to 2.78; 1 study, 44 women; very low-quality evidence). There were no data available on multiple pregnancy. The likelihood of a clinical pregnancy is uncertain between the treatments, due to the quality of the evidence and the large heterogeneity between the studies (OR 0.57, 95% CI 0.39 to 0.84; 7 studies, 470 women; I2 = 60%, very low-quality evidence). Due to the small sample size, the quality of evidence is not sufficient to justify a conclusion on miscarriage (OR 1.02, 95% CI 0.31 to 3.33; 2 studies, 131 women; I2 = 0%; very low-quality evidence). Other comparisons Due to lack of evidence and very low-quality data there is uncertainty whether there is a difference for any of the following comparisons: LOD with IVF versus IVF, LOD with second-look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose.

AUTHORS' CONCLUSIONS: Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low-quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS. The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy.

The Cochrane database of systematic reviews


Testing a theoretical model of imminent fracture risk in elderly women: an observational cohort analysis of the Canadian Multicentre Osteoporosis Study

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health.
Introduction: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk.

Methods: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI).

Results: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001).

Conclusions: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.


Distinct Spontaneous Brain Activity Patterns in Different Biologically-Defined  Alzheimer's Disease Cognitive Stage: A Preliminary Study

Qi Zeng

School of Public Health and Management, Chongqing Medical University, Chongqing, China.

Xiao Luo

Second Affiliated Hospital of Zhejiang University

Ruiting Zhang

Women's Hospital, School of Medicine, Zhejiang University

Xiaojun Xu

Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA

Abstract:
Background: The National Institute on Aging-Alzheimer's Association (NIA-AA) has proposed a biological definition of Alzheimer's disease (AD): individuals with both abnormal amyloid and tau biomarkers (A+T+) would be defined as AD. It remains unclear why different cognitive status is present in subjects with biological AD. Resting-state functional magnetic resonance imaging (rsfMRI) has provided an opportunity to reveal the brain activity patterns in a biologically-defined AD cohort. Accordingly, we aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages. Method: We selected individuals with AD pathology (A+T+) and healthy controls (HC, A-T-) based on the cerebrospinal fluid (CSF) biomarkers. According to the cognitive stage, we divided the A+T+ cohort into three groups: (1) preclinical AD; (2) prodromal AD; and (3) AD with dementia (d-AD). We compared spontaneous brain activity measured by a fractional amplitude of low-frequency fluctuation (fALFF) approach among four groups.

Results: The analysis of covariance (ANCOVA) results showed significant differences in fALFF in the posterior cingulate cortex/precuneus (PCC/PCu). Further, compared to HC, we found increased fALFF values in the right inferior frontal gyrus (IFG) in the preclinical AD stage, whereas prodromal AD patients showed reduced fALFF in the bilateral precuneus, right middle frontal gyrus (MFG), right precentral gyrus, and postcentral gyrus. Within the d-AD group, both hyperactivity (right fusiform gyrus, right parahippocampal gyrus (PHG)/hippocampus, and inferior temporal gyrus) and hypoactivity (bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus) were detected.

Conclusion: We found the distinct brain activity patterns in different cognitive stages among the subjects defined as AD biologically. Our findings may be helpful in understanding mechanisms leading to cognitive changes in the AD pathophysiological process.


Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of  randomized evidence

Coomarasamy A, Devall AJ, Brosens JJ, Quenby S, Stephenson MD, Sierra S, Christiansen OB, Small R, Brewin J, Roberts TE, Dhillon-Smith R, Harb H, Noordali H, Papadopoulou A, Eapen A, Prior M, Di Renzo GC, Hinshaw K, Mol BW, Lumsden MA, Khalaf Y, Shennan A, Goddijn M, van Wely M, Al-Memar M, Bennett P, Bourne T, Rai R, Regan L, Gallos ID

Abstract: Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.

American Journal of Obstetrics and Gynecology


Human exposure to trace elements, aromatic amines and formaldehyde in swimsuits: Assessment of the health risks

Abstract: Nowadays, most of the swimsuits are mainly made of artificial fibres, which have interesting properties such as water repellence and fast drying. Swimsuits contain a wide range of additives, which can mean a hazard for the environment and/or human health. In this study, the concentrations of formaldehyde (free and water soluble), 24 aromatic amines, and 28 trace elements (Ag, Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sr, Sn, Tl, Ti, V and Zn) were analysed in 39 swimsuits covering a wide range of materials, colours and brands. Dermal exposure and health risks were assessed for adults (men and women) aged > 18 years old, babies between 2 and < 3 years old, children (boys and girls) between 3 and < 6 years old and 6 and < 11 years old, and teenagers (boys and girls) between 11 and < 16 years old, wearing swimsuits for 4 h or 8 h. Formaldehyde and aromatic amines were below their respective detection limits in all samples (<16 and < 1.5 mg/kg, respectively). Regarding trace elements, Ti showed the highest mean levels (1844 mg/kg), being significantly higher in polyamide (3759 mg/kg) than in polyester (24.1 mg/kg) swimsuits. These high Ti levels were confirmed by environmental scanning electron microscope in a single sample made of polyamide. Increased concentrations of Cr were also observed, but only in polyamide black fabrics, with values ranging from 624 to 932 mg/kg. Non-cancer risks (hazard quotients) derived from the exposure to trace elements were in a safe zone for all analysed trace elements. Furthermore, the carcinogenic risks were evaluated for As, Cr and Pb, exhibiting values below the 10-5 threshold, with the exception of Cr in babies and children-girls. For Ti, health risks could not be calculated due to the lack of information on toxicological data. However, because Ti was the element with the highest concentrations in swimsuits, and taking into account the potential toxicity of TiO2 nanoparticles, further research is needed to assess the migration of this element from fibres to skin.


Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood

Abstract:
IMPORTANCE: Prior studies have raised concern about maternal acetaminophen use during pregnancy and increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in their children; however, most studies have relied on maternal self-report.

OBJECTIVE: To examine the prospective associations between cord plasma acetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD, and developmental disabilities (DDs) in childhood.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study analyzed 996 mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled at birth and followed up prospectively at the Boston Medical Center from October 1, 1998, to June 30, 2018.

EXPOSURES: Three cord acetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samples collected at birth.

MAIN OUTCOMES AND MEASURES: Physician-diagnosed ADHD, ASD, and other DDs as documented in the child's medical records.

RESULTS: Of 996 participants (mean [SD] age, 9.8 [3.9] years; 548 [55.0%] male), the final sample included 257 children (25.8%) with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchanged acetaminophen levels were detectable in all cord plasma samples. Compared with being in the first tertile, being in the second and third tertiles of cord acetaminophen burden was associated with higher odds of ADHD diagnosis (odds ratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile, 2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95% CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivity analyses and subgroup analyses found consistent associations between acetaminophen buden and ADHD and acetaminophen burden and ASD across strata of potential confounders, including maternal indication, substance use, preterm birth, and child age and sex, for which point estimates for the ORs vary from 2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD.

CONCLUSIONS AND RELEVANCE: Cord biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood ADHD and ASD in a dose-response fashion. Our findings support previous studies regarding the association between prenatal and perinatal acetaminophen exposure and childhood neurodevelopmental risk and warrant additional investigations.


Relative Risk of Cervical Neoplasms Among Copper and Levonorgestrel-Releasing Intrauterine System Users

Patrick Ryan

Columbia University Irving Medical Center

Matthew E Spotnitz

Departments of Biomedical Informatics and Obstetrics and Gynecology, Columbia University Medical Center, Observational Health Data Sciences and Informatics, and Medical Informatics Services, New Yo...

Abstract:
Objective: To evaluate the relative risk of cervical neoplasms among copper intrauterine device (Cu IUD) and levonorgestrel-releasing intrauterine system (LNG-IUS) users.

Methods: We performed a retrospective cohort analysis of 10,674 patients who received IUDs at Columbia University Medical Center. Our data were transformed to a common data model and are part of the Observational Health Data Sciences and Informatics network. The cohort patients and outcomes were identified by a combination of procedure codes, condition codes, and medication exposures in billing and claims data. We adjusted for confounding with propensity score stratification and propensity score 1:1 matching.

Results: Before propensity score adjustment, the Cu IUD cohort included 8,274 patients and the LNG-IUS cohort included 2,400 patients. The median age for both cohorts was 29 years at IUD placement. More than 95% of the LNG-IUS cohort used a device with 52 mg LNG. Before propensity score adjustment, we identified 114 cervical neoplasm outcomes. Seventy-seven (0.9%) cervical neoplasms were in the Cu IUD cohort and 37 (1.5%) were in the LNG-IUS cohort. The propensity score matching analysis identified 7,114 Cu IUD and 2,174 LNG-IUS users, with covariate balance achieved over 16,827 covariates. The diagnosis of high-grade cervical neoplasia was 0.7% in the Cu IUD cohort and 1.8% in the LNG-IUS cohort (2.4 [95% CI 1.5-4.0] cases/1,000 person-years and 5.2 [95% CI 3.7-7.1] cases/1,000 person-years, respectively). The relative risk of high-grade cervical neoplasms among Cu IUD users was 0.38 (95% CI 0.16-0.78, P<.02) compared with LNG-IUS users. By inspection, the Kaplan-Meier curves for each cohort diverged over time.

Conclusion: Copper IUD users have a lower risk of high-grade cervical neoplasms compared with LNG-IUS users. The relative risk of cervical neoplasms of LNG-IUS users compared with the general population is unknown.


The effects of magnesium sulfate on cyclophosphamide-induced ovarian damage: Folliculogenesis

Abstract: Cyclophosphamide (CYP) is one of the alkylating chemotherapeutic agents and its adverse effects on folliculogenesis in the ovary are well-known due to the previous scientific research on this topic. Magnesium has various effects in organisms, including catalytic functions on the activation and inhibition of many enzymes, and regulatory functions on cell proliferation, cell cycle, and differentiation. In this study, the effects of magnesium sulfate (MgSO4) on CYP induced ovarian damage were investigated. Immature Wistar-Albino female rats of 28-days were treated with pregnant mare serum gonadotrophin (PMSG) to develop the first generation of preovulatory follicles. Rats of the experimental groups were then treated with either CYP (100 mg/kg, i.p) and MgSO4 (270 mg/kg loading dose; 27 mg/kg maintenance doseX12, i.p) solely or in combination. Following in-vivo 5-bromo-2-deoxyuridine (BrdU) labeling, animals were sacrificed and ovaries were embedded in paraffin and Epon. In the ovaries, added to the evaluation of general morphology and follicle count; BrdU and TUNEL-labeling, cleaved caspase-3 and p27 (cyclin-dependent kinase inhibitor) staining was also performed immunohistochemically and an ultrastructural evaluation was performed by transmission electron microscopy (TEM). The number of primordial follicles were decreased and multilaminar primary and atretic follicles were increased in CYP group. After MgSO4 treatment, while primordial follicle pool were elevated, the number of atretic follicles were decreased. Additionally, decreased BrdU-labeling, increased cleaved caspase 3 immunoreactivity and increased TUNEL labeling were observed in CYP group. In CYP treated animals, observations showed that while MgSO4 administration caused no alterations in BrdU proliferation index and caspase-3 immunoreactivity, it significantly reduced the TUNEL labeling. It was also observed that, while p27 immunoreactivity significantly increased in the nuclei of granulosa and theca cells in the CYP group; MgSO4 treatment significantly reduced these immunoreactivities. The ultrastructural observations showed frequent apoptotic profiles in granulosa and theca cells in both early and advanced stages of follicles in the CYP group and the MgSO4 treatment before the CYP application led to ultrastructural alleviation of the apoptotic process. In conclusion, our data suggest that MgSO4 may provide an option of pharmacologic treatment for fertility preservation owing to the beneficial effects of on chemotherapy-induced accelerated follicular apoptotic process, and the protection of the primordial follicle pool.


The influences of sleep duration, chronotype, and nightwork on the ovarian cycle

Pauline Mendola

University at Buffalo, State University of New York

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: Despite research indicating that sleep disorders influence reproductive health, the effects of sleep on reproductive hormone concentrations are poorly characterized. We prospectively followed 259 regularly menstruating women across one to two menstrual cycles (the BioCycle Study, 2005-2007), measuring fasting serum hormone concentrations up to eight times per cycle. Women provided information about daily sleep in diaries and chronotype and night/shift work on a baseline questionnaire. We evaluated percent differences in mean hormone concentrations, the magnitude of shifts in the timing and amplitude of hormone peaks, and the risk for sporadic anovulation associated with self-reported sleep patterns and night/shift work. We estimated chronotype scores - categorizing women below and above the interquartile range (IQR) as "morning" and "evening" chronotypes, respectively. For every hour increase in daily sleep duration, mean estradiol concentrations increased by 3.9% (95% confidence interval [CI] 2.0, 5.9%) and luteal phase progesterone by 9.4% (CI 4.0, 15.2%). Receiving less than 7 hours of sleep per day was associated with slightly earlier rises in peak levels for several hormones. Women reporting night/shift work (n = 77) had lower testosterone relative to women employed without night/shift work (percent difference: -9.9%, CI -18.4, -0.4%). Women with morning chronotypes (n = 47) had earlier rises in estradiol during their cycles and potentially an earlier rise in luteinizing hormone. Compared to those who had intermediate chronotypes, women with evening chronotypes (n = 42) had a later luteinizing hormone peak of borderline statistical significance. A reduced risk for sporadic anovulation was suggested, but imprecise, for increasing hours of daily sleep leading up to ovulation (risk ratio 0.79, CI 0.59, 1.06), while an imprecise increased risk was observed for women with morning chronotypes (risk ratio 2.50, CI 0.93, 6.77). Sleep-related hormonal changes may not greatly alter ovarian function in healthy women, but have the potential to influence gynecologic health.


Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic  review and meta-analysis

Luis Bahamondes

Universidade Estadual de Campinas (UNICAMP)

Bruna Salani Mota

Setor de Mastologia da Clinica Ginecológica do ICESP - Instituto do Câncer do estado de São Paulo, Hospital das Clínicas Faculdade de Medicina da Universidade de São Paulo - FMUSP Sao Paulo Brazil

Rachel Rieira

Universidade Federal de São Paulo - UNIFESP Center of Health Tecnology, Hospital Sírio Libanês Sao Paulo Brazil

Abstract:
Introduction: Epidemiological studies have shown that some hormonal contraceptive methods are associated with increased breast cancer risk, especially if used over long periods. Our objective was to conduct a systematic review and meta-analysis of the literature on the risk of breast cancer development in women using the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS).

MATERIAL AND Methods: We performed a thorough review of peer-reviewed publications from 10 January 1999, through 31 July 2019, using combinations of search terms for breast cancer risk and LNG-IUS in the Medline, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), and Scielo databases. This review was registered in PROSPERO (CRD42017059076). Studies reporting breast cancer risk estimates among healthy users of LNG-IUS were included according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) criteria. Two authors performed data extraction, and a third author resolved disagreements. The quality of evidence was evaluated using the Downs and Black instrument. A funnel plot was generated, and a linear regression test of funnel plot asymmetry was used to assess publication bias. Finally, we performed a random-effects model (owing to high study heterogeneity) meta-analysis of seven suitable studies, stratified by the age distribution of patients (<50 years, ≥50 years, and mixed).

Results: We identified 96 studies and manually cross-referenced and excluded duplicate articles. Seventy articles were excluded on the basis of the inclusion and exclusion criteria, resulting in the assessment of 26 full-text articles. Eight articles were considered adequate for inclusion in this systematic review, and seven studies were included in the meta-analysis. Three publications were case-control studies and five were cohort studies. According to the Downs and Black instrument, 5 studies were rated as "good" and 3 studies were deemed "fair". Our meta-analysis results indicated increased breast cancer risk in LNG-IUS users: for all women, odds ratio (OR) = 1.16 (95% CI 1.06-1.28, I(2) = 78%, P < .01); for women aged <50 years, OR = 1.12 (95% CI 1.02-1.22, I(2) = 66%, P = .02); and for women aged ≥50 years, OR = 1.52 (95% CI 1.34-1.72, I(2) = 0%, P = .84).

Conclusions: Current evidence suggests that LNG-IUS users have an increased breast cancer risk regardless of age and indication. The effect of LNG-IUS on breast cancer risk seems to be larger in older users. However, our systematic review detected methodological issues across the available studies, and confounding factors may be responsible for at least a fraction of the risk effects associated with LNG-IUS use. Nevertheless, users of LNG-IUS should be aware of these trends. We believe that caution is needed, and risks should be balanced against proven health benefits (eg effective treatment of heavy menstrual bleeding and avoidance of surgical interventions), when prescribing LNG-IUS for long periods of use, especially in women with other known breast cancer risk factors such as old age, obesity, and familial predisposition.

Acta Obstetricia Et Gynecologica Scandinavica


Knowledge about the impact of age on fertility: a brief review

Sarah Verbiest

University of North Carolina at Chapel Hill

Abstract: Delayed childbearing is currently a major challenge in reproductive medicine as increased age has an important impact on successful conception, both in natural and in assisted reproduction. There is a lack of knowledge about the impact of age on fertility, even in highly educated populations. A number of initiatives have been taken to increase fertility awareness. Health care providers have been encouraged to talk with patients about their reproductive life plan (RLP) for almost a decade based on recommendations from the Centres for Disease Control and Prevention. This concept has been explored successfully in Swedish contraception counselling. A growing number of online interventions aim to raise fertility awareness. These websites or interactive tools provide relevant information for individuals and couples as they consider whether they want children, when they should have them, and how many they may wish to have. These interventions are important, because research depicts that knowledge helps people in their decision-making process. With new fertility preservations such as egg freezing now available, additional education is needed to be sure that women and couples are well informed about the cost and low success rates of this intervention.


The effect of the copper intrauterine device (Cu-IUD) and the injectable depo-medroxyprogesterone acetate (DMPA) use on women’s sexual satisfaction and depression

Abstract:
Background: Health service utilization (HSU) is a significant health and political issue. Awareness of factors that affect HSU and the status of health service utilization can help health professionals improve their services. The aim of this study was to investigate the status of HSU and identify the factors affecting health service utilization among households residing in Tehran.

Methods: The present cross-sectional study included 1200 residing households from different regions of Tehran, the capital of Iran. They were selected by a multi-stage cluster sampling method in accordance with the zoning of Tehran concerning socio-economic development. Interviews were conducted by trained individuals using a health service utilization questionnaire introduced by the World Health Organization, Zimet's social support questionnaire, and demographic checklist during winter 2018 and spring 2019. Simple and multiple logistic regression models were applied to analyze the data. In order to include the factors related to the status of outpatient health service utilization, a set of bivariate analyses was conducted, and then the factors with a p-value of ≤0.20 were included in the multiple models. Data were analyzed using Stata 12 software.

Results: The results of the study indicated that the rate of outpatient HSU among households residing in Tehran was 63.61% (CI:60, 66.80). In addition, regarding the results of the study, asset index of family (OR=0.51, 95% CI: 0.28, 0.91), the level of awareness and knowledge of family members regarding health issues (OR=0.55, 95% CI: 0.34, 0.88) as well as the mother knowledge on health issues (OR=0.64, 95% CI: 0.45, 0.93), the level of social support (OR = 0.50, 95% CI: 0.37,0.68), family health expenditure (OR=1.20, 95% CI: 1.18, 4.06), having a member with a sort of disability in family (OR=1.66, 95% CI: 1.01, 2.77), and having an alcoholic member in family (OR=2.44, 95% CI: 1.27, 4.68) were factors associated with outpatient HSU among households. Considering the adjusted values of odds ratios, the prevalence of the HSU varied according to the area of residence. It should be noted that the variables included in the model explained 15% of the changes in the prevalence of HSU.

Conclusion: According to the results of the study and in order to increase HSU in different classes, the level of social support, especially among women in the family due to their role in the general health of family members, should be enhanced. Also, policies should be adopted to increase the awareness, knowledge, and information of family members about health issues, lifestyle changes, nutrition, and health behaviors through social media.


The Reproductive Microbiome: An Emerging Driver of Sexual Selection, Sexual Conflict, Mating Systems, and Reproductive Isolation

Abstract: All multicellular organisms host microbial communities in and on their bodies, and these microbiomes can have major influences on host biology. Most research has focussed on the oral, skin, and gut microbiomes, whereas relatively little is known about the reproductive microbiome. Here, we review empirical evidence to show that reproductive microbiomes can have significant effects on the reproductive function and performance of males and females. We then discuss the likely repercussions of these effects for evolutionary processes related to sexual selection and sexual conflict, as well as mating systems and reproductive isolation. We argue that knowledge of the reproductive microbiome is fundamental to our understanding of the evolutionary ecology of reproductive strategies and sexual dynamics of host organisms.


Adiposity and Endometriosis Severity and Typology

Kristina L. Allen-Brady

Department of Family and Preventive Medicine, Division of Public Health (Ms. Byun and Drs. Stanford, Allen-Brady, and Schliep); Department of Internal Medicine, Genetic Epidemiology (Dr. Allen-Brady).

Jiyoung Byun

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

Robert N Taylor

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

Abstract:
STUDY Objective: Prior research has collectively shown that endometriosis is inversely related to women's adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology.
Design: Cross-sectional study among women with no prior diagnosis of endometriosis.
Setting: Fourteen clinical centers in Salt Lake City, UT, and San Francisco, CA.

Patients: A total of 495 women (of which 473 were analyzed), aged 18-44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study.

Interventions: Gynecologic laparoscopy/laparotomy regardless of clinical indication. MEASUREMENTS AND

MAIN Results: Participants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I-IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I-IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators.

Conclusion: Our research highlights that the relationship between women's adiposity and endometriosis severity and typology may be more complicated than prior research indicates.

Journal of Minimally Invasive Gynecology


Hormone Therapy and Factors Affecting Fertility of Women Under 50-Year-Old with  Breast Cancer

Mehdi Moradinazar

Kermanshah University of Medical Sciences

Abstract:
Background: Although the use of contraceptive hormones is a risk factor for development of breast cancer, level of risk is unknown; thus the current research was conducted to investigate the effect of factors related to fertility and hormone use on risk of breast cancer in women aged under 50 years old in the west of Iran.

Methods: In this case-control study, all incidence cases of breast cancer aged between 25-49 years old (n=212) were selected. Twice as many as the case group, the individuals referred to other outpatient sections of the same hospital at the time of study and up to 2 years after the follow-up not diagnosed with breast or other cancers were selected as a control group. The data were collected using healthy fertility program and middle-aged periodical care forms developed by Iran's Ministry of Health (MOH).

Results: After controlling for confounding variables, history of hormonal use for contraception (OR=2.02, 95% CI=1.2-3.3) and hormone therapies (OR=1.9, 95% CI=1.2-3.04) were identified as factors increasing the risk of breast cancer. Dose-response relationships between breast cancer and the use of hormones for contraception and hormone therapy indicated that these factors increased the risk of breast cancer. The risk was found to be higher in women who had been under hormone therapy for more than 120 months. With an increase in the age of the first menstruation, risk of breast cancer increased linearly, but with an increase in the age of the first pregnancy, risk of breast cancer increased exponentially. After 20 years of age, the risk increased with a steeper slope.

Conclusion: Considering the effect of hormone therapy and fertility factors on breast cancer and changeability of listed risk factors, the researchers suggest planning for sensitizing, increasing the awareness, and educating women and professionals regarding the influence of fertility and hormonal factors including pregnancy at lower ages, minimizing the use of hormones for contraception, and hormone therapy.


The Effect of Berberine on Reproduction and Metabolism in Women with Polycystic  Ovary Syndrome: A Systematic Review and Meta-Analysis of Randomized Control  Trials

Liangzhen Xie

First Affiliated Hospital of Heilongjiang University of Chinese Medicine

Caixia Wang

Second Affiliated Hospital of Zhejiang University

Abstract:
Purpose: To assess the efficacy and safety of berberine on reproductive endocrine and metabolic outcomes in women with polycystic ovary syndrome (PCOS).

Methods: PubMed (from 1950), the Cochrane Library, the CNKI (from 1979), the VIP (from 1989), and the Wanfang Data (from 1990) and the reference lists of the retrieved articles were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome/PCOS" and "berberine/BBR/Huangliansu (in Chinese)/Xiao bojian (in Chinese)" till 30 May 2019. Relevant indicators were collected and the data were analyzed by using RevMan 5.3 software.

Results: Eventually, a total of 12 randomized controlled trials were included in this systematic review. Our study suggested that berberine had similar live birth rates compared with placebo or metformin and lower live birth rates (RR: 0.61, 95% CI: 0.44 to 0.82) compared with letrozole. There was a significant difference between berberine and placebo and between berberine and no treatment in terms of decreasing total testosterone and luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio (8 RCTs, 577 participants, MD: -0.34, 95% CI: -0.47 to -0.20; 3 RCTs, 179 participants, MD: -0.44, 95% CI: -0.68 to -0.21, respectively). Berberine was associated with decreasing total cholesterol (3 RCTs, 201 participants; MD: -0.44, 95% CI: -0.60 to -0.29), waist circumference (3 RCTs, 197 participants, MD: -2.74, 95% CI: -4.55 to -0.93), and waist-to-hip ratio (4 RCTs, 258 participants, MD: -0.04, 95% CI: -0.05 to -0.03) compared with metformin, but not with improved BMI (4 RCTs, 262 participants, MD: -0.03, 95% CI: -0.46 to 0.39). Berberine did not increase the incidence of gastrointestinal adverse events (3 RCTs, 567 participants, RR: 1.01, 95% CI: 0.76 to 1.35) or serious events during pregnancy (RR: 0.98, 95% CI: 0.70 to 1.37) compared with placebo.

Conclusion: This review found no solid evidence that berberine could improve live birth or other clinical outcomes in women with PCOS. However, berberine appeared to be more efficacious for improving insulin resistance and dyslipidemia and decreasing androgen levels and LH/FSH ratio in women with PCOS when compared with metformin.

Evidence-based Complementary and Alternative Medicine : eCAM


Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial

Enrique F Schisterman

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Pauline Mendola

University at Buffalo, State University of New York

Abstract:
Importance: Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.

Objective: To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.Design, setting, and participantsThe Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.

Interventions: Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.Main outcomes and measuresThe co-primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization.

Results: Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, -0.9% [95% CI, -4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).

Conclusions and relevanceAmong a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.

Trial registration: ClinicalTrials.gov Identifier: NCT01857310.


Perfluorooctanoic acid alters progesterone activity in human endometrial cells and induces reproductive alterations in young women

Abstract: Female fecundity is finely regulated by hormonal signaling, representing a potential target for endocrine-disrupting chemicals. Among the chemicals of most concern are the perfluoroalkyl substances (PFAS), widely used in consumer goods, that are associated with adverse effects on reproductive health. In this context, the endometrium clearly represents an important fertility determining factor. The aim of this study was to investigate PFAS interference on hormonal endometrial regulation. This study was performed within a screening protocol to evaluate reproductive health in high schools. We studied a cohort of 146 exposed females aged 18-21 from the Veneto region in Italy, one of the four areas worldwide heavily polluted with PFAS, and 1080 non-exposed controls. In experiments on Ishikawa cells included UV-Vis spectroscopy, microarray analysis and qPCR. We report a significant dysregulation of the genetic cascade leading to embryo implantation and endometrial receptivity. The most differentially-expressed genes upon PFOA coincubation were ITGB8, KLF5, WNT11, SULT1E1, ALPPL2 and G0S2 (all p < 0.01). By qPCR, we confirmed an antagonistic effect of PFOA on all these genes, which was reversed at higher progesterone levels. Molecular interference of PFOA on progesterone was confirmed by an increase in the intensity of absorption spectra at 250 nm in a dose-dependent manner, but not in the presence of β-estradiol. Age at menarche (+164 days, p = 0.006) and the frequency of girls with irregular periods (29.5% vs 21.5%, p = 0.022) were significantly higher in the exposed group. Our results are indicative of endocrine-disrupting activity of PFAS on progesterone-mediated endometrial function.


Transcutaneous Electrical Nerve Stimulation (TENS) for Primary Dysmenorrhea: An Overview

Abstract: Primary dysmenorrhea is a chronic health condition that affects primarily young women. Transcutaneous electrical nerve stimulation (TENS) has been suggested as an effective pain reduction modality in primary dysmenorrhea. TENS is a noninvasive, inexpensive, portable method with minimal risks and a few contraindications. When necessary, it can be self-administered on a daily basis during everyday activities. Several studies have investigated the effectiveness of TENS in reducing pain, decreasing the use of analgesics, and improving the quality of life in primary dysmenorrhea patients. These studies have some limitations in methodological quality and therapeutic validation. However, the overall positive effects of TENS in primary dysmenorrhea encountered in all prior studies indicated its potential value. This review presents the clinical recommendations for TENS parameters for treating primary dysmenorrhea symptoms based on previously published studies.


Endometriosis. Reply

Endometriosis. Reply


Pain and Quality of Life after Laparoscopic Excision of Endometriosis


Author Correction: Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christine L Hitchcock

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


Paradigm shift in pathophysiology of vasomotor symptoms: Effects of estradiol withdrawal and progesterone therapy


Levonorgestrel IUD: is there a long-lasting effect on return to fertility?

Abstract: Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.

Journal of assisted reproduction and genetics


Ethnic Diversity in Fertility Treatment 2018

Human Fertilisation and Embryology Authority

Abstract:
# Ethnic diversity in fertility treatment 2018
UK ethnicity statistics for IVF and DI fertility treatment
Published: March 2021
[**Download the underlying dataset as .xlsx (27kb)**](https://www.hfea.gov.uk/media/3348/2021-03-03-bame-report-suppl_mental-underlying-data-final.xlsx "download the underlying data as .xlsx").
## Table of contents
- [Main points](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#mainpoints)
- [Introduction](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#introduction)
- [Section 1. IVF birth rates lowest for patients of Black ethnicities](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section1)
- [Section 2. Multiple birth rate higher on average for Black patients](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section2)
- [Section 3. White egg donors most commonly used across all ethnic groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section3)
- [Section 4. Fewer Asian egg and sperm donors compared to UK Asian population](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section4)
- [Section 5. Asian patients represent a larger proportion of IVF users](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section5)
- [Section 6. Variation in NHS-funded IVF cycles between cycles in larger in younger age groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversity-in-fertility-treatment-2018/#Section6)
- [Section 7. Black patients start IVF later than other ethnic groups](https://www.hfea.gov.uk/about-us/publications/research-and-data/ethnic-diversit...


Chemical signals from eggs facilitate cryptic female choice in humans

Abstract: Mate choice can continue after mating via chemical communication between the female reproductive system and sperm. While there is a growing appreciation that females can bias sperm use and paternity by exerting cryptic female choice for preferred males, we know surprisingly little about the mechanisms underlying these post-mating choices. In particular, whether chemical signals released from eggs (chemoattractants) allow females to exert cryptic female choice to favour sperm from specific males remains an open question, particularly in species (including humans) where adults exercise pre-mating mate choice. Here, we adapt a classic dichotomous mate choice assay to the microscopic scale to assess gamete-mediated mate choice in humans. We examined how sperm respond to follicular fluid, a source of human sperm chemoattractants, from either their partner or a non-partner female when experiencing a simultaneous or non-simultaneous choice between follicular fluids. We report robust evidence under these two distinct experimental conditions that follicular fluid from different females consistently and differentially attracts sperm from specific males. This chemoattractant-moderated choice of sperm offers eggs an avenue to exercise independent mate preference. Indeed, gamete-mediated mate choice did not reinforce pre-mating human mate choice decisions. Our results demonstrate that chemoattractants facilitate gamete-mediated mate choice in humans, which offers females the opportunity to exert cryptic female choice for sperm from specific males.


Postpartum Lactational Amenorrhea and Recovery of Reproductive Function and Normal Ovulatory Menstruation

Maternal-Fetal and Neonatal Endocrinology